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Ying Wang,1 Xiangzhuo Zhao,2 Jingxu Wang,2 Xiaoli Zhu3 1Department of Endocrine Nephrology, The First Affiliated Hospital of Xingtai Medical College (Xingtai First Hospital), Xingtai, Hebei Province, 054001, People’s Republic of China; 2Department of Rheumatic Immunology, Xingtai People’s Hospital, Xingtai, Hebei Province, 054000, People’s Republic of China; 3Department of Critical Care Medicine, Xingtai People’s Hospital, Xingtai, Hebei Province, 054000, People’s Republic of ChinaCorrespondence: Ying Wang, Department of Endocrine Nephrology, The First Affiliated Hospital of Xingtai Medical College (Xingtai First Hospital), Xingtai, Hebei Province, 054001, People’s Republic of China, Email wangying1990z@sina.comIntroduction: Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by persistent joint inflammation, pain, and tissue degradation. This study evaluates the therapeutic potential of Norisoboldine (NOR), an isoquinoline alkaloid from Lindera aggregata, in a rat model of RA.Methods: Rats were divided into five groups: normal control (G1), RA model (G2), NOR-treated groups at 15 mg/kg (G3) and 30 mg/kg (G4), and methotrexate-treated group (G5). NOR’s anti-arthritic effects were assessed by measuring clinical arthritis scores and inflammatory markers (RF, CRP, TNF-α, IL-6, IL-10). Oxidative stress markers (MDA, SOD, catalase, GPx) and pathways (NF-κB/IKKβ and Nrf2/Keap1) were also evaluated. Histopathology assessed synovial inflammation and tissue degradation.Results: NOR treatment significantly reduced arthritis severity, as evidenced by decreased clinical arthritis scores and inflammatory markers in RA rats. NOR also exhibited strong antioxidant effects, demonstrated by decreased MDA levels and enhanced SOD, catalase, and GPx activities. NOR further downregulated matrix metalloproteinases (Mmp-2, Mmp-3), aggrecanases (Adamts-4, Adamts-5), and PCNA expression. Histopathology confirmed marked reductions in synovial inflammation and tissue damage in NOR-treated groups.Discussion: These findings suggest that NOR’s anti-inflammatory and antioxidant properties contribute to reducing both inflammation and the overall severity of RA. NOR’s multifaceted actions support its potential as a novel therapeutic agent for RA.Conclusion: NOR demonstrates protective effects in RA rats by reducing inflammation, oxidative stress, and extracellular matrix degradation, offering promise as a therapeutic option to manage RA pathology comprehensively.Keywords: Norisoboldine, methotrexate, rheumatoid arthritis, inflammation, oxidative stress

Shaoli Shi,1 Guangyao Li,2 Xiaoli Zhu,2 Lingming Kong2 1Psychiatry Department, The 5th People’s Hospital of Luoyang, Luoyang, Henan Province, 471027, People’s Republic of China; 2Treatment & Prevention Center, No. 904th Hospital, Changzhou, Jiangsu Province, 213003, People’s Republic of ChinaCorrespondence: Lingming Kong, Treatment & Prevention Center, No. 904th Hospital, North Peace Road 55, No. 904th Hospital, Changzhou, Jiangsu, 213003, People’s Republic of China, Email lingmk123@163.comBackground: Adolescent group may be prone to a variety of behavioral disorders, one of which is nonsuicidal self-injury (NSSI), NSSI intervention is limited for its unknown mechanism, so this study aimed to explore the factors associated with and pathological mechanism underlying NSSI from the perspective of family dysfunction, alexithymia, circRNA_103636 in a sample of Chinese adolescents.Methods: A total of 200 MDD adolescents with NSSI and 200 healthy controls were enrolled via a convenient sampling method in clinical settings. The Family APGAR Index (APGAR), Toronto Alexithymia Scale (TAS-20), and Adolescent Nonsuicidal Self-injury Assessment Questionnaire (ANSSIAQ) were used for mental assessment of the study group and control group participants. Real-time quantitative reverse transcription PCR (qRT–PCR) was utilized to detect circRNA_103636 expression in peripheral blood mononuclear cells (PBMCs).Results: There were significant between-group differences of 134 patients (67%) in the study group and 42 patients in the control group (21%) with moderate or severe family dysfunction (P< 0.01). The APGAR score was lower, and the difficulty identifying feeling (DIF), difficulty describing feeling (DDF) and externally oriented thinking (EOT) scores of the TAS-20 and ΔCt value of circRNA_103636 were greater in the study group than in the control group. NSSI behavior and NSSI function were negatively correlated with the APGAR score and positively correlated with DIF, DDF, and the EOT of TAS-20 and the ΔCt value of circRNA_103636. Multiple regression analysis confirmed that EOT, circRNA_103636 expression, and APGAR were predictors of ANSSIAQ, which could explain 40.5% of the variance. Similarly, the alexithymia and circRNA_103636 expression mediated the correlation between family dysfunction and NSSI in the study group, and these mediating effects accounted for 27.25% and 23.33%, respectively, of the total effect. Taken together, family dysfunction, alexithymia, and circRNA_103636 expression have predictive effects on NSSI and alexithymia, circRNA_103636 expressions are mediators between family dysfunction and NSSI in Chinese adolescent.Conclusion: Here, we established a new model for NSSI in which exposure to family dysfunction could induce pathological process by modulating personality traits and epigenetic regulators.Keywords: nonsuicidal self-injury, family dysfunction, alexithymia, circRNA_103636, epigenetics

Xinqing Zhu,1,&ast; Abdullah Al-danakh,1,&ast; Yuli Jian,2,&ast; Mohammed Safi,3,&ast; Sijie Luo,1,&ast; Qiwei Chen,1 Shujing Wang,2 Deyong Yang1,4 1Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian, Liaoning People’s Republic of China; 3Thoracic/Head and Neck Medical Oncology Department, MD Anderson Cancer Center, Houston, TX, USA; 4Department of Surgery, Healinghands Clinic, Dalian, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Deyong Yang; Shujing Wang, Email yangdeyong@dmu.edu.cn; wangshujing@dmu.edu.cnBackground: Clear cell renal cell carcinoma (ccRCC), the predominant subtype of RCC, is distinguished by unique biological characteristics and heterogeneity, including eosinophilic and clear subtypes. Notwithstanding progress in therapy, immune checkpoint inhibitors (ICIs), and tyrosine kinase inhibitors (TKIs), the prognosis for individuals with metastatic ccRCC remains poor, presumably owing to metabolic alterations leading to mitochondrial dysfunction, which affects treatment response variability.Methods: We analyzed histological and immunohistochemical data from a cohort at Dalian Medical University’s First Affiliated Hospital alongside RNA-sequencing transcriptome data from the TCGA database. Histologically, eosinophilic and clear ccRCC subtypes were evaluated using Kaplan-Meier and Cox proportional hazards models for survival analysis and prognosis. Differential gene expression (DEG) analysis and Gene Set Enrichment Analysis were performed to explore transcriptomic differences and relevant pathways.Results: The study discovered substantial histological and molecular differences between the eosinophilic and clear cell subtypes of ccRCC. The eosinophilic subtype linked with frequent high-grade tumors (69.05% eosinophil vs 35.35% clear) and a poorer prognosis (HR=2.659, 95% CI:1.437– 4.919, P=0.002). DEG analysis revealed distinct expression patterns among subtypes and identified a risk score signature that remained significant even after adjusting for clinical variables (HR=3.967, 95% CI: 1.665– 9.449, P=0.002), showing less favorable survival in the high-risk group (P < 0.0001). RRM2 emerged as the most prognostic gene from this risk score, particularly in the eosinophilic subtype, alongside other clinical variables. By IHC, RRM2 shows high IHC score in eosinophilic compared to clear subtype (P=0.019). In addition, highly expressed RRM2 correlates with poor outcomes and is linked to mitochondrial genes, immunological pathways, and ICIs treatment.Conclusion: These findings show significant differences in prognosis between subtypes. RRM2 was the most prognostic gene from the discovered novel risk score signature associated with subtypes. Future research is essential to validate these insights and their therapeutic implications for ccRCC management.Keywords: clear cell renal cell carcinoma subtypes, metabolic reprogramming. mitochondria, tumor microenvironment, RRM2, immune checkpoint inhibitors

Sining Zeng,1,2,&ast; Min Wu,1,&ast; Ling Xu,1 Zining Guo,1 Shufan Chen,1 Keyu Ling,1 Haihan Li,1 Xiaoli Yu,1 Xiaoping Zhu1 1Department of Nursing, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China; 2School of Nursing, Soochow University, Suzhou, 215031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoping Zhu, Department of Nursing, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China, Tel +86-021-66300588, Fax +86-021-66307542, Email xiaopingzhu0424@163.comBackground and Objectives: While extensive research has examined the rehabilitation challenges faced by stroke survivors, there is limited literature addressing the difficulties encountered by older adult stroke survivors and their caregivers in accessing rehabilitation and long-term care within the Chinese community. This study aimed to investigate the specific challenges related to access, quality, and coordination of rehabilitation and long-term care experienced by older adult stroke survivors and their caregivers within the Chinese community.Methods: A qualitative phenomenological design was employed to explore the lived experiences of stroke survivors and their caregivers within the Chinese community. A purposive sampling method was used to recruit participants from June to August 2023. Participants engaged in face-to-face semi-structured interviews. The data were analyzed using an inductive thematic analysis approach to identify and understand key themes and sub-themes.Results: The study involved 38 participants, consisting of 21 older adult stroke survivors (13 males, 8 females) and 17 family caregivers (7 males, 10 females), recruited from five Chinese community health service stations. The analysis identified four distinct themes and 11 sub-themes that encapsulated the challenges faced by participants. These themes include (1) Difficulties in accessing medical services (insufficient medical resources, lack of rehabilitation resources, and time-consuming processes), (2) Challenges in daily life (inconvenience in daily mobility, inadequate financial support, and difficulties in applying for home care services), (3) Psychosocial stress (loneliness, powerlessness, and worry about burdening others), (4) Insufficient information (lack of awareness of available community services, and limited public health education activities).Conclusion: Older adult stroke survivors and their caregivers in Chinese communities face significant challenges. To improve their well-being and quality of life, it is crucial to address these challenges through enhanced access to healthcare, better support for daily living, and more effective information dissemination. Meeting these needs requires a coordinated effort from healthcare providers, community stakeholders, and policymakers to develop and implement effective, long-term care solutions.Keywords: stroke, survivors, caregivers, community, qualitative research

Chuxiao Zhang, Yuelan Qin, Yangguang Song, Yingying Liu, Xiaodong Zhu Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Xiaodong Zhu, Department of Radiation OncologyGuangxi Medical University Cancer Hospital, No. 71 hedi Road, Nanning, Guangxi, 530021, People’s Republic of China, Email xdzhu1466@hotmail.comPurpose: There are insufficient data about the optimal treatment for older patients with recurring medium or large hepatocellular carcinoma (HCC). The study intended to assess the effect of transcatheter arterial chemoembolization combined with microwave ablation (TACE-MWA) in an elderly cohort through a retrospective analysis.Methods: From 2011 to 2018, a cohort of individuals (age ≥ 70 years) with recurrent HCC tumors ranging from 3.1 cm to 7 cm underwent either a combination treatment of TACE and MWA (n = 43) or surgical intervention (n = 33). Using the Inverse Probability of Treatment Weighting (IPTW) technique, factors of disease-free survival (DFS), overall survival (OS), and rates of major adverse events were analyzed, retrospectively.Results: The group that underwent surgery had a greater history of alcohol use before treatment (P= 0.001), as well as a higher Barcelona Clinic Liver Cancer (BCLC) stage for the primary tumor before treatment (P= 0.014) and a higher primary tumor location before treatment (P= 0.045). The TACE-MWA group had DFS rates of 86.2%, 68.8%, and 60.4% at 1, 3, and 5 years, while the surgery group had rates of 53.0%, 42.2%, and 25.8% at the same time points. In the TACE-MWA treatment group, survival rates at 1 year, 3 years, and 5 years post-treatment were recorded as 93.0%, 80.8%, and 65.7%, respectively, while in the surgery group, they were 62.7%, 46.9%, and 42.6%. In the univariate analysis using IPTW, the type of treatment was found to have a significant correlation with disease progression (hazard ratio [HR] 0.41, 95% CI 0.20– 0.86, P=0.017). IPTW multivariate analysis showed that treatment modality (HR, 0.35; 95% CI, 0.17 to 0.79; P= 0.011) was the only significant prognostic factor for OS.Conclusion: In elderly patients with recurrent 3.1 cm≤ HCC ≤ 7 cm, TACE-WMA was superior to surgery in the respects of DFS and OS.Keywords: elderly patients, hepatocellular carcinoma, transcatheter arterial chemoembolization, microwave ablation, treatment modality

Haihong Cheng,1 Wei Zhou,1,&ast; Valeria Nahadi Nasuhi,2,&ast; Xiaoqiang Zhu,1 Chenyuan Yu,1 Hang Zhang,1 Hongwei Wang1 1Department of Anesthesiology, Tongde Hospital Affiliated to Zhejiang Chinese Medical University (Tongde Hospital of Zhejiang Province), Hangzhou, Zhejiang, People’s Republic of China; 2The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongwei Wang, Department of Anesthesiology, Tongde Hospital Affiliated to Zhejiang Chinese Medical University (Tongde Hospital of Zhejiang Province), Hangzhou, Zhejiang, 310012, People’s Republic of China, Tel +86 13857169356, Email wanghw1022@163.comPurpose: This study aims to investigate the impact of anesthetic methods on the occurrence of postoperative sleep disorders in elderly patients following their discharge from the hospital for 3 months.Patients and Methods: This retrospective observational cohort study included elderly patients aged > 60 years who had undergone general and regional anesthesia from 1 June 2023 to 31 December 2023. These patients were then assessed for sleep by telephone callback using the Athens Insomnia Scale after discharge from the hospital three months later. The duration of pain and sleep disturbance experienced by patients following discharge was also recorded.Results: Following propensity score matching, 308 individuals were included in the study (154 in the GA group and 154 in the RA group). Compared with general anesthesia (11.7%), regional anesthesia (5.2%) reduced the prevalence of sleep disorders in elderly patients after discharge from the hospital. However, the duration of sleep disturbance and pain exhibited no statistically significant difference between the two groups (p=0.818; p=0.211).Conclusion: Regional anesthesia was associated with a reduction in the incidence of sleep disorders in elderly patients after discharge from the hospital for 3 months.Keywords: sleep disturbance, regional anesthesia, general anesthesia, elderly patient

Xingxing Zhu,1,&ast; Jialu Chen,2,&ast; Shengjie Wu,3 Jiling Zeng,4 Yahong Sun,1 Xiaohong Wu5 1Department of Pulmonary and Critical Care Medicine, Haining People’s Hospital, Haining, People’s Republic of China; 2Department of Gynaecology, Haining Maternal and Child Health Hospital, Haining, People’s Republic of China; 3Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohong Wu, Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Shangcheng District, Hangzhou, 310000, People’s Republic of China, Tel +86 13588706901, Email 3192018@zju.edu.cnBackground: The incidence of community-acquired empyema caused by the Streptococcus anginosus group (SAG) has been on the rise in the 2020s. To the best of our knowledge, while empyema caused individually by either strain has been reported, there are no reports on empyema caused by concurrent infection with these two strains. Here, we report for the first time empyema caused by concurrent infection with Streptococcus intermedius and Streptococcus constellatus (both SAG species) in a postoperative patient who had been treated for floor of the mouth carcinoma.Case Presentation: A 61-year-old male patient who had undergone surgical treatment for floor of the mouth carcinoma 2 year earlier suddenly presented with left-sided chest pain. Chest computed tomography (CT) revealed encapsulated pleural effusion on the left side, which was diagnosed as empyema. Metagenomic next-generation sequencing(mNGS) of the pleural fluid sample indicated mixed infection caused by Streptococcus intermedius and Streptococcus constellatus. The patient’s condition improved about 5 weeks after treatment with thoracic fluid drainage and cephalosporin antibiotics.Conclusion: This case highlights the possibility of concurrent infection with two SAG strains in patients with empyema. Currently, it is unclear whether there is a definitive relationship between a surgical history of carcinoma of the floor of the mouth and empyema caused by infection with SAG strains. This case could, perhaps, serve as a reference for future related research on the topic.Keywords: Streptococcus intermedius, Streptococcus constellatus, oral carcinoma, pleural effusion, carcinoma of the floor of the mouth, empyema

Bohao Dai,1,&ast; Xiaorong Peng,1,&ast; Jia Sun,1 Xueling Zhu,1 Xiang Liu,1 Ye Xiong,1 Zhikai Wan,1 Dairong Xiang,1 Jiangjin Hui,1 Chenxi Ying,2 Huiting Liu,1 Biao Zhu1,&ast; 1The Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Cardivascular Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Biao Zhu, The Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qing Chun Road, Hangzhou, 310006, People’s Republic of China, Email zhubiao1207@zju.edu.cnBackground: HIV-1 CRF01_AE is becoming the predominant HIV-1 subtype among patients in China. The distribution and characteristics of transmission clusters of HIV-1 CRF01_AE in Zhejiang, Eastern China remains unclear. This study analyzed the epidemiologic characteristics and transmission clusters of HIV-1 CRF01_AE in Zhejiang.Methods: Plasma samples obtained from 152 patients of HIV-1 CRF01_AE not undergoing ART were used to amplify HIV-1 pol and env gene. CRF01_AE drug resistance mutations (DRM) prevalence was analysed using Stanford University’s HIV Drug Resistance Database. A phylogenetic tree was constructed using FastTree (version 2.1.11) based on the GTR nucleotide substitution model and visualized using Figtree (version 1.4.4) and The Interactive Tree of Life; the Chinese HIV Gene Sequence Data Platform was used to construct genetic transmission networks.Results: Majority samples could be grouped into CRF01_AE transmission Clusters 1 (11.2%), 4 (64.5%), and 5 (7.2%). The CD4+ T-cell counts in Cluster 1, 4a, 4b are lower than 5 were 15, 38, 30, and 248 cells/mm3, respectively (P < 0.05). The high X4 tropism rates were 13.2%, 11.8%, 20.0%, and 0.0% in Clusters 1, 4a, 4b, and 5, respectively. DRM rates in Clusters 4a and 4b were 17.6%, and 25.45% respectively (P < 0.05), whereas they were 17.6% and 18.2% in Clusters 1 and 5, respectively. In total, 24 transmission genetic networks, comprising 72 sequences and 61 links, were discovered; of them, 61.2%, 11.7%, and 18.2% were from Clusters 4, 1, and 5, respectively (P < 0.05).Conclusion: In Zhejiang, different CRF01_AE clusters displayed unique clinic features. Cluster 4, particularly Cluster 4b, was considered a high-risk transmission cluster. The surveillance of epidemiology of HIV-1 should be enhanced to minimize its transmission.Keywords: HIV-1 CRF01_AE, drug resistance mutation, transmission cluster

Mu Yuan,1,2,&ast; Weijun Wan,1,2,&ast; Wei Xing,1,2 Chengxiu Pu,1,2 Xiaofeng Wu,1,2 Zhikang Liao,3 Xiyan Zhu,3 Xueting Hu,1,2 Zhan Li,1,2 Qing Zhao,1,2 Hui Zhao,3,&ast; Xiang Xu1,2,&ast; 1Department of Stem Cell and Regenerative Medicine, National Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2Central Laboratory, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 3Research Department Fourth Laboratory, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Xu, Stem Cell and Regenerative Medicine Department, Daping Hospital, Army Medical University, Chongqing, No. 10, Changjiang Road, Yuzhong District, Chongqing, 400042, People’s Republic of China, Email xiangxu@tmmu.edu.cn Hui Zhao, Research Department Fourth Laboratory, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China, Email Zhaohui@tmmu.edu.cnPurpose: We aimed to investigate whether peripheral blood biomarkers B2M related to immune response can serve as indicators of HAPE pathophysiological characteristics or disease progression.Patients and Methods: Bioinformatics technology was used to explore the peripheral blood pathophysiological mechanisms and immune hub genes related to the occurrence of HAPE. The hub gene was verified through animal experiments, and its function and correlation between its expression level and the diagnosis, treatment effect and prognosis of HAPE were explored.Results: The GSVA results showed that the occurrence of HAPE was related to the down-regulation of immune response pathways by RUNX3 and STING. WGCNA results showed that the peripheral blood immune gene module related to the development of HAPE was related to the decrease of immune function and the increase of immune checkpoint molecule PD-L1 gene expression, and the expression of immune checkpoint genes LILRB2 and SIGLEC15 increased. Cytoscape software, RT-qPCR and WB confirmed that the hub gene B2M is a specific peripheral blood biomarker of HAPE. ROC, DCA, RT-qPCR, HE and Masson results showed that the expression of peripheral blood B2M has the ability to indicate the diagnosis, treatment effect and prognosis of HAPE. The decreased expression of B2M protein in peripheral blood leukocytes may be a marker of HAPE. Single-gene GSEA confirmed that the reduced expression of B2M in peripheral blood may be involved in the down-regulation of the antigen presentation pathway mediated by MHC class I molecules, was positively correlated with the down-regulation of the TNF signaling pathway, and was negatively correlated with the expression of LILRB2 and SIGLEC15.Conclusion: The occurrence of HAPE may be related to decreased immune function and immune tolerance. Peripheral blood B2M may be involved in the related pathways, its expression level can prompt the diagnosis, treatment and prognosis of HAPE. Keywords: high altitude pulmonary edema, immune tolerance, biomarker, B2M, prognosis

Caixing Shi,1 Yueyao Li,2 Zhidong You,3 Yiran Tian,4 Xiaoyu Zhu,4 Hao Xu,4 Menghan Yang,4 Yutong Zhang,4 Rui Dong,4 Huirong Quan,4 Yongyi Shang,4 Xiaojin Li1 1School of Basic Medicine, Jining Medical University, Jining, 272067, People’s Republic of China; 2College of Integrated Chinese and Western Medicine, Jining Medical University, Jining, 272067, People’s Republic of China; 3School of Nursing, Jining Medical University, Jining, 272067, People’s Republic of China; 4School of Clinical Medicine, Jining Medical University, Jining, 272067, People’s Republic of ChinaCorrespondence: Xiaojin Li, School of Basic Medicine, Jining Medical University, No. 133 hehua Road, Taibai Lake New District, Jining, 272067, People’s Republic of China, Tel +8615265775150, Email jinli10221@163.comPurpose: Acute liver injury (ALI) is characterized by inflammation and oxidative stress (OS). Although mangiferin (MGF) has antioxidant and anti-inflammatory effects, its role in ALI remains unclear. Accordingly, we investigated the MGF molecular mechanism in carbon tetrachloride (CCl4)-induced ALI in vivo and in vitro.Materials and Methods: The CCl4 was utilized to induce ALI in mice. In vivo, the therapeutic effects of MGF on CCl4-induced liver injury were evaluated through biochemical assays and histomorphological analysis. Additionally, immunohistochemistry, immunofluorescence, ELISA and Western blotting were further applied to explore the mechanism. In vitro, The CCK-8 assay and flow cytometry were employed to investigate the protective effects of MGF against CCl4-induced toxicity in HepG2 cells, while mitochondrial reactive oxygen species levels and Western blotting were used to explore the biological effects and molecular mechanisms.Results: MGF treatment resulted in a reduction in serum levels of AST and ALT, diminished concentrations of TNF-α, IL-6, and IL-1β in liver tissue, and concurrently decreased cellular apoptosis. Furthermore, MGF pretreatment enhanced the activity of SOD and GSH while concurrently diminishing the MDA production. This study further demonstrated the upregulation of Nrf2, NQO1, and HO-1 protein expression levels, as well as the downregulation of p-p65 protein expression levels. In vitro investigations revealed that the mitigation of CCl4-induced inflammation and OS by MGF was mediated via the Nrf2- antioxidant response element (ARE) pathway, which was disrupted by ML385 in HepG2 cells.Conclusion: CCl4 can induce liver injury, while treatment with MGF mitigates ALI by inhibiting oxidative stress, inflammation, and apoptosis. The protective mechanism of MGF is mediated by the Nrf2-ARE pathway activation.Keywords: mangiferin, liver injury, oxidative stress, inflammation, Nrf2

Yanan Qi,1,2 Yuanyuan Yan,1,2 Dawei Tang,1,2 Jingjing Han,1,2 Xinyi Zhu,1,2 Mengting Cui,1,2 Hongyan Wu,3 Yu Tao,1,2 Fangtian Fan1,2 1School of Pharmacy, Bengbu Medical University, Bengbu, People’s Republic of China; 2Anhui Engineering Technology Research Center of Biochemical Pharmaceutical, Bengbu, People’s Republic of China; 3Institute of Biomedical Technology, Jiangsu Vocational College of Medicine, Yancheng, Jiangsu, 224005, People’s Republic of ChinaCorrespondence: Yu Tao; Fangtian Fan, Anhui Engineering Technology Research Center of Biochemical Pharmaceutical Bengbu Medical College, 2600 Donghai Avenue, Bengbu, Anhui, 233003, People’s Republic of China, Tel +86-15852921284 ; +86-16655258065, Email YuTao@bbmc.edu.cn; 2019050@bbmu.edu.cnBackground: Chronic obstructive pulmonary disease (COPD) currently ranks among the top three causes of mortality worldwide, presenting as a prevalent and complex respiratory ailment. Ongoing research has underscored the pivotal role of immune function in the onset and progression of COPD. The immune response in COPD patients exhibits abnormalities, characterized by diminished anti-infection capacity due to immune senescence, heightened activation of neutrophils and macrophages, T cell infiltration, and aberrant B cell activity, collectively contributing to airway inflammation and lung injury in COPD.Objective: This review aimed to explore the pivotal role of the immune system in COPD and its therapeutic potential.Methods: We conducted a review of immunity and COPD published within the past decade in the Web of Science and PubMed databases, sorting through and summarizing relevant literature.Results: This article examines the pivotal roles of the immune system in COPD. Understanding the specific functions and interactions of these immune cells could facilitate the development of novel therapeutic strategies and interventions aimed at controlling inflammation, enhancing immune function, and mitigating the impact of respiratory infections in COPD patients.Keywords: COPD, immune system, inflammation, immune regulation

Zuo Wang,1,2,&ast; Siqi Guo,3,&ast; Chong He,2,4,&ast; Lingling Chen,5 Jinxia Wang,2 Wenbo Xiu,2 Gao Zhang,2 Yang Chen,2 An Li,2 Xiong Zhu,6 Xiao Xiao,2 Ling Yu,3 Fang Lu2,4,7 1Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Department of Ophthalmology, Daping Hospital, Army Medical Center, Army Medical University, Chongqing, People’s Republic of China; 4Medico-Engineering Cooperation on Applied Medicine Research Center, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 5Department of Immunology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, People’s Republic of China; 6Department of Prenatal Diagnosis, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 7Health Management Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Yu; Fang Lu, Email oculistlingyu@hotmail.com; lufangfang@126.comObjective: Evidence suggests that dysbiosis of the gut microbiota plays a pivotal role in the development of glaucoma. This dysbiosis is commonly associated with chronic intestinal inflammation and increased intestinal permeability. However, the understanding of intestinal inflammation and permeability in glaucoma remains insufficient. This study aims to investigate the potential relationship between fecal inflammation and permeability markers and glaucoma.Methods: We recruited 114 glaucoma patients and 75 healthy controls. Levels of fecal lactoferrin (Lf) and alpha-1 antitrypsin (AAT) were quantified using enzyme linked immunosorbent assay (ELISA) to compare both biomarkers between groups and across different severity grades of glaucoma. Logistic regression analysis was used to assess the association between these fecal biomarkers and glaucoma. The severity of glaucoma was assessed based on the mean deviation (MD) in the visual field.Results: In this study, we observed elevated levels of fecal Lf and AAT in glaucoma patients. The proportion of glaucoma patients with abnormal fecal Lf levels (≥ 7.25 μg/g) was significantly higher than that of the controls (p = 0.012). A positive correlation was noted between fecal Lf and AAT (rho = 0.20, p = 0.006). After adjusting for age and sex, multivariable logistic regression analysis indicated that both fecal Lf (OR = 1.11, 95% CI: 1.01– 1.21, p = 0.026) and AAT (OR = 1.01, 95% CI: 1.01– 1.02, p < 0.001) positively correlated with glaucoma. These biomarkers might reflect glaucoma severity, with significant differences in fecal Lf levels observed between moderate and severe stages, but not in the early stage. Furthermore, increasing levels of fecal AAT correlated with greater severity of glaucomatous injury and a larger vertical cup-to-disc ratio (VCDR) (p < 0.05).Conclusion: This study suggests an increase in intestinal inflammation and permeability in glaucoma, further indicating the importance of the ‘gut-retina axis’ in the pathogenesis of the disease and potentially offering new therapeutic avenues.Keywords: fecal lactoferrin, fecal alpha-1 antitrypsin, glaucoma, intestinal inflammation, intestinal permeability, intestinal barrier

Xinyong Lu,1,&ast; Zixuan Li,2,&ast; XianFeng Zhu,3 Dong Li,4 Jiahui Wei1 1College of Economy and Trade, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong, People’s Republic of China; 2Peking University, School of Psychological and Cognitive Sciences, Beijing, People’s Republic of China; 3University of Macau, Faculty of Education, Macau, People’s Republic of China; 4Department of International Culture Education, Chodang University, Muan, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Jiahui Wei, College of Economy and Trade, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong, People’s Republic of China, Email weijiahui@zhku.edu.cnPurpose: There is robust evidence indicating the adverse association between childhood abuse and depressive symptoms. However, the ways in which childhood physical abuse is indirectly associated with adulthood depressive symptoms by alexithymia and moral disengagement remain poorly understood, particularly in the context of China. The present study aims to investigate how childhood physical abuse may be associated with depressive symptoms via the serial mediation effects of alexithymia and moral disengagement among college students in China.Methods: A total of 686 college students (female: 53.2%) aged from 17 to 28 years old (M = 21.33; SD = 2.53) were recruited from mainland China to participate in an online survey assessing the variables of interest. Structural equation modeling and multiple group analysis were performed using Mplus 7.0 to investigate the hypothesized model.Results: College students’ experiences with childhood physical abuse was significantly associated with their depressive symptoms. This relationship was partially mediated by alexithymia and then by moral disengagement. Meanwhile, alexithymia and moral disengagement had a chain mediating effect on childhood physical abuse and depressive symptoms. Furthermore, multigroup analysis revealed that the association between alexithymia and depressive symptoms was stronger among rural students compared to urban students. Furthermore, the mediation model involving moral disengagement applies exclusively to rural students.Conclusion: Alexithymia and moral disengagement exerted serial mediating effect on the association between childhood physical abuse and depressive symptoms. This pattern was particularly pronounced among rural students. These findings underscore the importance of addressing both childhood adversity and maladaptive cognitive processes in the prevention and treatment of depression.Keywords: childhood physical abuse, depressive symptoms, alexithymia, moral disengagement, urban-rural areas

Xiaohui Zhu,1,2 Dongmei Jiang,1 Hongjie Zhang,3 Ruyuan Cai,3 Yuying Wang,1 Fei Hua2 1Department of Endocrinology, Affiliated Hospital 6 of Nantong University, Yancheng, 224000, People’s Republic of China; 2Department of Endocrinology, The Third Affiliated Hospital of Soochow University, Changzhou, 213000, People’s Republic of China; 3Department of Ophthalmology, Affiliated Hospital 6 of Nantong University, Yancheng, 224000, People’s Republic of ChinaCorrespondence: Fei Hua, Email huafeihf@21cn.comObjective: The study aimed to explore the correlation between retinal nerve fiber layer thickness (RNFLT) with blood biochemical indicators and cognitive dysfunction in patients with type 2 diabetes mellitus (T2DM) and the possible mechanism, thereby providing more theoretical basis for the occurrence and prevention of diabetes related complications.Methods: Eighty T2DM patients treated in our hospital from March 2022 to September 2022 were selected as the study subjects, and the clinical data of the patients were retrospectively analyzed. All patients underwent fundus fluorescein angiography (FFA) to analyze the changes in retinal blood vessels. Patients who met the inclusion criteria were divided as the diabetic retinopathy (DR) group (n=46) and simple diabetes group (n=34). The RNFLT, blood biochemical indexes and changes in cognitive functions of the patients were detected. The correlation between RNFLT with blood biochemical indexes and cognitive dysfunction was analyzed.Results: Compared with the simple diabetes group, patients in the DR group had much lower mean, nasal, inferior and superior thicknesses (P< 0.01). There existed no significant difference in blood pressure, body mass index (BMI), blood lipids (triglycerides, cholesterol, low-density lipoprotein, high-density lipoprotein) between the two groups (P> 0.05). Compared with the simple diabetes group, patients in the DR group had much higher fasting blood glucose (FBG), hemoglobin A1c (HbA1c), fasting insulin (FINS), insulin resistance (HOMA-IR) index, apolipoprotein B (ApoB)/apolipoprotein A1 (ApoA1) (P< 0.001). Besides, the DR group had sharply lower scores on the Mini-Mental State Examination (MMSE) scale and higher levels of the Trail Making Test-A (TMT-A) and TMT-B (P< 0.001). Spearman correlation analysis confirmed that the mean RNFLT was negatively correlated with the levels of FBG, HbA1c, HOMA-IR index, TMT-A and TMT-B (P< 0.05), positively correlated with the score of mini-mental state examination (MMSE) (P< 0.05), and was no significant correlation with FINS and ApoB/ApoA1 (P> 0.05).Conclusion: DR patients had significantly reduced RNFLT, elevated levels of blood glucose related indicators, and cognitive dysfunction. There existed a correlation between RNFLT and FBG, HbA1c, HOMA-IR index, TMT-A, TMT-B and MMSE.Keywords: type 2 diabetes mellitus, retinal nerve fiber thickness, blood biochemical indicators, cognitive dysfunction, correlation

Jingjing Wei,1,&ast; Zhaoyang Liu,1,2,&ast; Mingming Li,1 Lingyun Du,1 Xia Zhu,1 Yi Leng,1 Changyu Han,1 Qingqing Xu,1 Chunhong Zhang1 1Department of Dermato-Venereology, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Dermato-Venereology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunhong Zhang, Department of Dermato-Venereology, the Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Dajie Street, Jinan, People’s Republic of China, Tel +86-531-85875027, Fax +86-531-88962544, Email aliu133@163.comBackground: Psoriasis is an immune-mediated chronic inflammatory disease. Qingre Lishi Decoction (QRLSD) has achieved great clinical effect in the treatment of psoriasis. However, the potential bioactive components and the mechanisms are yet unclear.Aim: To analyze the serum parameters of rats fed with QRLSD, screen out the active components of QRLSD, and explore the potential targets and pathway of QRLSD in the treatment of psoriasis.Materials and Methods: The active components of serum containing QRLSD were analyzed using ultra-high performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS). The targets of QRLSD in the treatment of psoriasis were predicted by network pharmacology and molecular docking. In vitro experiments verified the underlying mechanism.Results: By UPLC-Q-TOF/MS, 15 prototype components and 22 metabolites were identified in serum containing QRLSD. Subsequently, 260 chemical composition targets and 218 psoriasis targets were overlapped to obtain 23 intersection targets, including LGALS3, TNF, F10, DPP4, EGFR, MAPK14, STAT3 and others. TNF, IL-10, GAPDH, STAT3, EGFR, ITGB1, LGALS3 genes were identified as potential drug targets in the PPI network analyzed by CytoHubba. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that QRLSD may improve psoriasis by regulating immune and inflammatory pathways, the cytokine mediated signal transduction pathways and other signaling pathways. Molecular docking results showed that the main active components of the serum containing QRLSD had higher affinities for TNF and LGALS3. In vitro experiments confirmed that QRLSD may decrease levels of inflammatory cytokines by suppressing the NF-κB signaling pathway activated by TNF-α in human keratinocytes.Conclusion: This study explores the potential compounds, targets and signaling pathways of QRLSD in the treatment of psoriasis, which will help clarify the efficacy and mechanism of QRLSD.Keywords: qingre lishi decoction, psoriasis, UPLC-Q-TOF/MS, network pharmacology, molecular docking, NF-κB signaling pathway

Tong Guo,1,2 Yuan Feng,1,2 Jingjing Zhou,1,2 Linghui Meng,1,2 Xuequan Zhu,1,2 Xu Chen,1,2 Le Xiao,1,2 Lei Feng,1,2 Ling Zhang,1,2 Yu-Tao Xiang,3,4 Yan-Jie Zhao,1,2 Gang Wang1,2 1Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 3Unit of Psychiatry, Department of Public Health and Medicinal Administration, Faculty of Health Sciences, Institute of Translational Medicine, University of Macau, Taipa, Macao SAR, People’s Republic of China; 4Centre for Cognitive and Brain Sciences, University of Macau, Taipa Macao SAR, People’s Republic of ChinaCorrespondence: Yan-Jie Zhao; Gang Wang, Email yzhao118@126.com; gangwangdoc@ccmu.edu.cnBackground: Understanding the dynamic relationship between depressive symptoms and quality of life (QOL) is essential in improving long-term outcomes for patients with Major Depressive Disorder (MDD). While previous studies often relied on cross-sectional data, there is a pressing need for stronger evidence based on longitudinal data to better inform the development of effective clinical interventions. By focusing on key depressive symptoms, such interventions have the potential to ultimately enhance QOL in individuals with MDD.Methods: This multi-center prospective study, conducted between 2016 and 2020, enrolled outpatients and inpatients diagnosed with MDD across twelve psychiatric hospitals in China. Longitudinal data on Patient Health Questionnaire – 9 (PHQ-9) and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) was analyzed using an Extended Bayesian Information Criterion (EBIC) graphical least absolute shrinkage and selection operator (gLASSO) network model to explore the connections between depressive symptom changes and QOL changes. Flow network was applied to investigate relationships between individual symptom changes and overall QOL score change, as well as daily functional independence.Results: This study included 818 participants with complete data after 8-week antidepressant treatment. Apart from the overlapping items from PHQ-9 and Q-LES-Q-SF, the three edges between “mood” (delta-QLES2) and “anhedonia” (delta-DEP1), between “physical health” (delta-QLES1) and “sleep problems” (delta-DEP3), and between “physical health” (delta-QLES1) and “sad mood” (delta-DEP2) were the most strong bridges between the cluster of depressive symptoms alleviation and the cluster of QOL change. “Anhedonia” (delta-DEP1), “sad mood” (delta-DEP2) and “loss of energy” (delta-DEP4) had the highest bridge strength between the alleviations of depressive symptoms and the total score change of Q-LES-Q-SF. Anhedonia had the greatest connection with participants’ satisfaction with function in daily life.Conclusion: This study highlighted the potential for developing highly effective interventions by targeting on central symptoms, thereby to ultimately improve QOL for patients with MDD.Keywords: network analysis, patients with MDD, acute phase treatment, depressive symptoms, quality of life

Qiming Gan,1,&ast; Quanzhen Liu,1,2,&ast; Yanjuan Wu,1,&ast; Xiaofeng Zhu,1,2 Jingcun Wang,1 Xiaofen Su,1 Dongxing Zhao,1 Nuofu Zhang,1 Kang Wu1 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Disease, Department of Sleep Medicine Center, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510160, People’s Republic of China; 2Nanshan School, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kang Wu; Nuofu Zhang, Department of Pulmonary and Critical Care Medicine, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, No. 28 Qiaozhong Mid Road, Guangzhou, Guangdong, 510160, People’s Republic of China, Email d102_wk@126.com; nfzhanggird@163.comPurpose: Obstructive sleep apnea (OSA) had been associated with asthma in observational studies, but the effect of OSA on the onset of asthma in childhood or adulthood remains unclear, and the causal inferences have not been confirmed. This study aims to investigate the potential causal association between OSA with asthma, including different age-of-onset subtypes, providing reliable basis for the clinical treatment of OSA and asthma.Patients and Methods: Causality between OSA and asthma was assessed using a two-sample bi-directional Mendelian randomization (MR) analysis. OSA data were obtained from the FinnGen consortium R9, while asthma and its subtypes (adult-onset asthma, child-onset asthma, and moderate-to-severe asthma) were sourced from the IEU OpenGWAS project. The inverse-variance weighted (IVW) method was chosen as the primary analysis and was complemented by various sensitivity analyses. The MR-PRESSO outlier test was employed to systematically identify and remove outlier variants, mitigating heterogeneity and potential effects of horizontal pleiotropy.Results: The MR analyses provided evidence of genetically predicted OSA having a promoting effect on child-onset asthma (OR,1.49; 95% CI, 1.05– 2.11; P=0.025) and moderate-to-severe asthma (OR,1.03; 95% CI, 1.00– 1.06; P=0.046). However, no causal association between OSA with asthma and adult-onset asthma was observed.Conclusion: Our study revealed a causal association between OSA and child asthma, but not in adults. Moderate-to-severe asthma may have a potential promoting effect on OSA. These findings underscore the importance of age-specific considerations in managing asthma and suggests the need for personalized approaches in clinical practice.Keywords: asthma, obstructive sleep apnea, Mendelian randomization, genetic

Wenwu Zhang,1,2,&ast; Yuhan Xiao,3,&ast; Xin Zhu,1 Yanxia Zhang,1 Qin Xiang,1 Shunhong Wu,1 Xiaoyu Song,1 Junxiu Zhao,3 Ruanfei Yuan,1 Qiguang Li,1 Bin Xiao,1 Linhai Li1 1Department of Laboratory Medicine, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University, Qingyuan, Guangdong, 511518, People’s Republic of China; 2Department of Laboratory Medicine, Suzhou Municipal Hospital, Affiliated to Nanjing Medical University, Suzhou, 21500, People’s Republic of China; 3School of Public Health, Dali University, Dali, 671000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linhai Li; Bin Xiao, Email mature303@126.com; xiaobin2518@163.comPurpose: Meiotic nuclear division 1 (MND1) is a meiosis-specific protein that promotes lung adenocarcinoma progression. However, its expression and biological function across cancers remain largely unexplored.Patients and Methods: The expression, prognostic significance, mutation status, and methylation profile of MND1 in various cancers were comprehensively analyzed using the TIMER, GTEX, Kaplan-Meier plotter, cBioPortal, and GSCA databases. Additionally, we constructed a PPI network, enrichment analysis and single-cell transcriptomic sequencing to elucidate the underlying mechanism of MND1. Furthermore, we investigated the association between MND1 expression and drug sensitivity using CellMiner. Moreover, we also explored the correlation between MND1 expression and immune infiltration. Finally, we validated the functional role of MND1 in breast cancer through IHC staining, CCK8, EdU, colony formation, and flow cytometry assays.Results: MND1 has been reported to be highly expressed in Pan-cancer, High MND1 expression was significantly associated with poor prognosis in cancers. Additionally, MND1 mutation frequency is high in most cancers, and its expression correlates with methylation. Furthermore, MND1 expression significantly correlates with immune checkpoint blockade (ICB) markers, including PD-L1, PD-1, and CTLA-4. The PPI network reveals interactions between MND1 and PSMC3IP, BRCA1, and BRCA2. Enrichment analysis and single-cell sequencing indicate that MND1 positively correlates with cell cycle. ROC curve reveals favorable diagnostic efficacy of MND1 in breast cancer. In vitro, MND1 overexpression promotes breast cancer cell proliferation and increases the expression of key cell cycle regulators (CDK4, CDK6, and cyclin D3), accelerating the G1/S phase transition and leading to abnormal breast cancer cell proliferation. The immunohistochemical analysis revealed a robust expression of MND1 in breast cancer tissues, exhibiting a significant positive correlation with PD-L1 and FOXP3.Conclusion: MND1 is an oncogene and may serve as a biomarker for cancer prognosis and immunotherapy. Targeting MND1 may be a potential tumor treatment strategy.Keywords: meiosis-specific protein, pan-cancer, prognosis biomarker, immune infiltration, cell cycle

Bo Jiang,1 Dong Lu,2 Jiaying Dai,3 Kunfeng Li,4 Qianqian Du,1 Bo Xie,5 Jun Xie,6 Xianhai Zhu,2 Xiang Xie1 1Department of Interventional Ultrasound, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 2Department of Interventional Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences & Medicine, University of Science & Technology of China, Hefei, 230001, People’s Republic of China; 3Department of Interventional Radiology, Anqing Municipal Hospital, Anqing, Anhui, 246000, People’s Republic of China; 4Department of Radiology, Tongling People’s Hospital, Tongling, Anhui, 244300, People’s Republic of China; 5Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, People’s Republic of China; 6Department of Radiology, Fuyang People’s Hospital, Fuyang, Anhui, 236600, People’s Republic of ChinaCorrespondence: Xiang Xie, Department of Interventional Ultrasound, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Email 15956922618@163.comObjective: To develop a simple and effective prognostic scoring system to predict the efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in the treatment of hepatocellular carcinoma (HCC).Methods: Data were retrospectively collected from 230 patients with HCC who received DEB-TACE treatment at six medical centers between January 2019 and December 2022. We developed a predictive score based on independent risk factors for overall survival (OS), validated the model using a validation cohort, and compared its prognostic accuracy with commonly used HCC staging systems.Results: The number of tumors, albumin-bilirubin levels, alpha-fetoprotein levels, and portal vein thrombus grade were identified as independent factors influencing OS. Based on these factors, we established the DEB-TACE treatment of HCC (DTH) scoring system. The DTH score correlated well with OS, which decreased as the DTH score increased. According to the DTH score, patients were categorized into three risk groups: low-risk (DTH-A, 0– 4 points), medium-risk (DTH-B, 5– 6 points), and high-risk (DTH-A, 7 points). The OS of each risk group was 18.73± 0.62 months, 12.73± 0.10 months, and 6.93± 0.19 months, respectively (p< 0.001). The external cohort validation confirmed the accuracy of the DTH score, demonstrating superior predictive performance compared to other commonly used HCC scoring systems.Conclusion: The DTH-HCC scoring system effectively predicts the outcomes of HCC patients undergoing DEB-TACE as initial treatment. This model can aid in the initial planning and decision-making process for DEB-TACE treatment in HCC patients.Keywords: hepatocellular carcinoma, transcatheter arterial chemoembolization, prognosis prediction model

Haijie Tan,1,&ast; Yi Chen,2,&ast; Yan Jiang,1 Xiaojing Sun,1 Wei Ye,1 Xuefang Zhu,1 Xiangsheng Xiong1 1Department of Anesthesiology, The Fifth People’s Hospital of Huaian, Huaian, People’s Republic of China; 2Department of Anesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangsheng Xiong, Department of Anesthesiology, The Fifth People’s Hospital of Huaian, Huaian, People’s Republic of China, Email 158193942@qq.comBackground: Vasopressors remain an important strategy for managing spinal anesthesia-induced hypotension in women with preeclampsia. The aim of this study was to investigate the ED90s and efficacy ratio of phenylephrine and norepinephrine in managing spinal anesthesia-induced hypotension in women with preeclampsia during cesarean delivery.Methods: 60 women with preeclampsia, who underwent cesarean delivery, were randomly assigned to receive either a continuous intravenous infusion of phenylephrine or norepinephrine following spinal anesthesia. The initial dosage of phenylephrine or norepinephrine for the first women was 0.5 or 0.05 μg/kg/min, respectively, and subsequent infusion dosages were adjusted based on their efficacy in preventing spinal anesthesia-induced hypotension (defined as a systolic blood pressure less than 80% of the baseline level). The incremental or decremental doses of phenylephrine or norepinephrine were set at 0.1 or 0.01 μg/kg/min. The primary outcomes were the ED90s and efficacy ratio of phenylephrine and norepinephrine infusions for preventing spinal anesthesia-induced hypotension prior to delivery.Results: The results obtained from isotonic regression analysis revealed that the ED90 values of the phenylephrine and norepinephrine group for preventing spinal anesthesia-induced hypotension were 0.597 (95% CI: 0.582– 0.628) and 0.054 (95% CI: 0.053– 0.056) μg/kg/min, respectively, with an efficacy ratio of 11.1:1. The results of Probit regression analysis revealed that the ED90 values were determined to be 0.665 (95% CI: 0.576– 1.226) and 0.055 (95% CI: 0.047– 0.109) μg/kg/min, respectively, with an efficacy ratio of 12.1:1.Conclusion: The administration of 0.6 μg/kg/min phenylephrine and 0.05 μg/kg/min norepinephrine has been found to effectively manage a 90% incidence of spinal anesthesia-induced hypotension in women with preeclampsia.Keywords: ED90, phenylephrine, norepinephrine, spinal anesthesia-induced hypotension, preeclampsia, cesarean delivery

Runzhi Wang,1 Rong Zhao,2 Zhongguo Liang,1 Kaihua Chen,1 Xiaodong Zhu1,3– 6 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Radiation, Inner Mongolia Autonomous Region People’s Hospital, Hohhot, Inner Mongolia autonomous Region, 010020, People’s Republic of China; 3Department of Oncology, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of China; 4Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of China; 5Guangxi Clinical Medicine Research Center of Nasopharyngeal Carcinoma, Nanning, Guangxi, 530021, People’s Republic of China; 6Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Xiaodong Zhu, Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, 71 He-Di Road, Nanning, 530021, People’s Republic of China, Tel +86 15778028340, Email zhuxdonggxmu@126.comPurpose: To evaluate the prognostic significance of platelet distribution width-to-lymphocyte ratio (PDWLR) in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Moreover, a nomogram based on PDWLR was built and validated to predict the overall survival (OS) of this population.Patients and Methods: All LA-NPC patients who were diagnosed and treated between January 2015 and December 2017 at Guangxi Medical University Cancer Hospital were included. Cox regression analyses were performed to assess PDWLR and clinical features that might affect OS to screen for independent predictors. The independent predictors and important clinical variables were used to build and validate a nomogram for predicting OS. Then, the capability of the model was estimated by discrimination, calibration and clinical usefulness. Risk stratification was conducted using the nomogram-calculated risk score, and the comparison of survival in the high-risk group and the low-risk group was through Kaplan–Meier method.Results: This study included 746 LA-NPC patients. Multivariate Cox analysis suggested that age (hazard ratio [HR]: 1.81, 95% confidence interval [CI]: 1.18– 2.78, P = 0.007), gender (HR: 2.03, 95% CI: 1.12– 3.68, P = 0.019), pre-treatment plasma Epstein–Barr virus (EBV) DNA (HR: 1.55, 95% CI: 1.01– 2.39, P = 0.047), PDWLR (HR: 2.61, 95% CI: 1.67– 4.09, P < 0.001) were independent predictors of OS. Compared to the 8th edition TNM staging system, the nomogram based on the above four factors and important clinical variables (T stage and N stage) demonstrated better predictive performance. Moreover, the model had the ability to identify individuals at high risk.Conclusion: PDWLR was a promising negative predictor for patients with LA-NPC. The nomogram based on PDWLR demonstrated better predictive performance than the current staging system.Keywords: nomogram, platelet distribution width-to-lymphocyte ratio, inflammatory biomarker, locoregionally advanced nasopharyngeal carcinoma, overall survival

Wennuo Huang,1,&ast; Yuanzhe Li,2,&ast; Zhuqing Bao,3,&ast; Jing Ye,1 Wei Xia,1 Yan Lv,1 Jiahui Lu,4 Chao Wang,1 Xi Zhu1 1Department of Radiology, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, 225002, People’s Republic of China; 2Department of CT/MRI, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, 362000, People’s Republic of China; 3Department of Emergency, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, 225002, People’s Republic of China; 4School of Medical Imaging, Hangzhou Medical College, Hangzhou, Zhejiang, 310053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xi Zhu, Department of Radiology, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, 225002, Jiangsu, People’s Republic of China, Tel +8618051062318, Email yzdxlcyxyzhuxi@qq.comPurpose: This study aimed to investigate the knowledge, attitudes, and practice (KAP) of radiologists regarding artificial intelligence (AI) in medical imaging in the southeast of China.Methods: This cross-sectional study was conducted among radiologists in the Jiangsu, Zhejiang, and Fujian regions from October to December 2022. A self-administered questionnaire was used to collect demographic data and assess the KAP of participants towards AI in medical imaging. A structural equation model (SEM) was used to analyze the relationships between KAP.Results: The study included 452 valid questionnaires. The mean knowledge score was 9.01± 4.87, the attitude score was 48.96± 4.90, and 75.22% of participants actively engaged in AI-related practices. Having a master’s degree or above (OR=1.877, P=0.024), 5– 10 years of radiology experience (OR=3.481, P=0.010), AI diagnosis-related training (OR=2.915, P< 0.001), and engaging in AI diagnosis-related research (OR=3.178, P< 0.001) were associated with sufficient knowledge. Participants with a junior college degree (OR=2.139, P=0.028), 5– 10 years of radiology experience (OR=2.462, P=0.047), and AI diagnosis-related training (OR=2.264, P< 0.001) were associated with a positive attitude. Higher knowledge scores (OR=5.240, P< 0.001), an associate senior professional title (OR=4.267, P=0.026), 5– 10 years of radiology experience (OR=0.344, P=0.044), utilizing AI diagnosis (OR=3.643, P=0.001), and engaging in AI diagnosis-related research (OR=6.382, P< 0.001) were associated with proactive practice. The SEM showed that knowledge had a direct effect on attitude (β=0.481, P< 0.001) and practice (β=0.412, P< 0.001), and attitude had a direct effect on practice (β=0.135, P< 0.001).Conclusion: Radiologists in southeastern China hold a favorable outlook on AI-assisted medical imaging, showing solid understanding and enthusiasm for its adoption, despite half lacking relevant training. There is a need for more AI diagnosis-related training, an efficient standardized AI database for medical imaging, and active promotion of AI-assisted imaging in clinical practice. Further research with larger sample sizes and more regions is necessary.Keywords: artificial intelligence, medical imaging, knowledge, attitude, practice, radiologists, cross-sectional study

Xiaodong Zhu,1 Ya Huang,2 Jia Ding,1 Jianguo Liu,1 Changmeng Cui,1 Guangkui Han1 1Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China; 2College of Traditional Chinese Medicine, Shandong Polytechnic College, Jining, 272000, People’s Republic of ChinaCorrespondence: Guangkui Han, Department of Neurosurgery, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, Shandong, 272000, People’s Republic of China, Tel +8618266808351, Email hanguangkui1997@163.comPurpose: SN-38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan, has been extensively studied in drug delivery systems. However, its impact on neural metabolism remains unclear. This study aims to investigate the toxic effects of SN-38 on mouse brain metabolism.Methods: Male mice were divided into an SN-38 group and a control group. The SN-38 group received SN-38 (20 mg/kg/day) via intraperitoneal injection, while the control group was given an equal volume of a blank solvent mixture (DMSO and saline, ratio 1:9). Gas chromatography-mass spectrometry (GC-MS) was employed to analyze differential metabolites in the cortical and hippocampal regions of the SN-38-treated mice.Results: SN-38 induced metabolic disturbances in the central nervous system. Eighteen differential metabolites were identified in the hippocampus and twenty-four in the cortex, with six common to both regions. KEGG pathway enrichment analysis revealed statistically significant alterations in six metabolic pathways in the hippocampus and ten in the cortex (P< 0.05).Conclusion: This study is the first to demonstrate the neurotoxicity of SN-38 in male mice through metabolomics. Differential metabolites in the hippocampal and cortical regions were closely linked to purine metabolism, pyrimidine metabolism, amino acid metabolism, and glyceride metabolism, indicating disruptions in the blood-brain barrier, energy metabolism, and central signaling pathways.Keywords: SN-38 (7-ethyl-10-hydroxycamptothecin), biomarker, gas chromatography mass spectrometry, metabolomics, toxicity mechanism

Shuang Xiao,1 Anthony Androulakis,2 William D Skelton,3 Irene L Quan,4 Jinlian Cheng,1 Yan Wang,1 Xueqi Zhu,1 Haiqun Zhang5 1Office of Drug Clinical Trial Institution, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2School of Public Health, University of South Carolina, Columbia, SC, USA; 3D.AC, The Acupuncture Clinic, Columbia, SC, USA; 4Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 5Trauma Orthopaedics, Beijing Fengsheng Special Hospital of Traditional Medical Traumatology and Orthopaedics, Beijing, People’s Republic of ChinaCorrespondence: Jinlian Cheng, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Art Museum Back Street, Dongcheng District, Beijing, People’s Republic of China, Tel +86-010-87906813, Email cjltitan@126.comAim: The aim of this study is to assess the willingness, motivation, satisfaction levels, and expectations of participants engaged in clinical trials, while also exploring factors that influence compliance from the participants’ standpoint. Furthermore, this research aims to enhance the understanding of all stakeholders involved in clinical trials about the needs of participants and to offer evidence-based and pragmatic recommendations for effectively managing clinical trial participants.Methods: An electronic questionnaire covers various aspects of Traditional Chinese Medicine (TCM) clinical trials. The distribution of the electronic questionnaire was facilitated through WeChat groups, WeChat Moments, and individual interactions. Count data was expressed in terms of frequency (or rate), and subsequent analysis was conducted utilizing the standard chi-squared test. A p value≤ 0.05 was considered significant. By drawing a Pareto chart, the priority of factors influencing participants’ willingness to participate in clinical trials was systematically assessed.Results: 88 participants answered the questionnaire. A decline in education level corresponded to a decreasing comprehension of participants’ grasp of “clinical trial” and “clinical trial participant” (p< 0.05). The primary reason for participants’ reservations about joining clinical trials stems from their inadequate comprehension of clinical trial details. The key factors contributing to participants’ reluctance to engage in clinical trials encompass aspects of trial design, the operational procedures, insufficient understanding of clinical trial particulars, concerns about potential harm to their bodies and opposition from family members. Importantly, these areas of participants’ hesitation and unwillingness to partake in clinical trials mirror the factors participants’ dissatisfaction contributing to.Conclusion: We found four factors significantly influencing participants’ willingness to engage and their overall satisfaction: the participant’s profile, trial design, trial institution setup, and the qualifications of the researchers. Derived from these critical factors, this paper presents a series of constructive measures.Keywords: clinical trial, traditional Chinese medicine, compliance, satisfaction, participants

Sandip Patil,1,2,&ast; Xinye Li,3,&ast; Pai Liu,1 Yan Dai,3 Xiyi Zhu,3 Junjun Li,3 Sixi Liu,1 Feiqiu Wen1,2 1Department of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 2Paediatric Research Institute, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Paediatrics, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning City, Guangxi Zhuang Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feiqiu Wen, Department of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, Guangdong, People’s Republic of China, Tel +86-755-83009888, Email fwen62@163.comBackground: Syphilis, a prevalent sexually transmitted infection, poses severe risks, especially during pregnancy. This study aimed to elucidate the trends and impacts of syphilis in Guangxi, China, focusing on prevalence, clinical manifestations, and treatment outcomes in pregnant women and newborns. The objectives included understanding the demographic characteristics of affected pregnant women, analysing the clinical manifestations in newborns, and assessing the effectiveness of the treatment protocol.Methods: Conducted in adherence to ethical guidelines, a retrospective cohort study from January 2013 to December 2023 included 54,048 pregnant women tested for T. pallidum. Diagnosis involved a comprehensive approach, utilizing tests like the Toluidine Red Unheated Serum Test (TRUST) and the Treponema pallidum Particle Agglutination (TPPA) assay. Infant diagnosis and clinical manifestations were evaluated through a decade-long follow-up. Treatment protocols, including Benzathine penicillin, were implemented. Statistical analyses were conducted using SAS version 9.4.Results: Among 54,048 pregnant women, 0.10% were syphilis positive, correlating with a rise in hospitalizations. Newborns exhibited varied clinical manifestations, with neonatal pneumonia and jaundice being prevalent. The treatment protocol, especially with Benzathine penicillin, achieved a remarkable 100% cure success rate. The study noted a significant reduction in mother-to-child transmission. Syphilis in mothers and babies was diagnosed at different clinical stages, including primary, secondary, latent, and tertiary.Conclusion: This study underscores the escalating impact of syphilis on pregnant women and newborns in Guangxi, China. The findings highlight the necessity for robust preventive measures, early diagnosis, and effective treatment strategies. The observed 100% cure success rate with Benzathine penicillin emphasizes the importance of strict treatment protocols in mitigating the adverse effects of congenital syphilis and reducing its transmission.Keywords: congenital syphilis, mother-to-child transmission, diagnosis, antibiotic treatment

Chenxi Li,1,&ast; Xiaolei Chen,2,&ast; Xiaowen Zhu,1 Mengjiao Cao,3 Qunfeng Tang,3 Wenjun Wu1,4 1Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 2Department of Neurology, Jiangnan University Medical Center, Wuxi No. 2 People’s Hospital, Wuxi, People’s Republic of China; 3Department of Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 4Jinshan Branch of Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjun Wu, Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People’s Republic of China, Tel +86-15358008856, Fax +86-510-85737592, Email wuwenjung@163.comPurpose: Arterial stiffness is often increased in overweight or obese individuals before the development of hypertension (HT). This study aimed to determine the connection between pancreatic fat and atherosclerosis in overweight and obese people without HT.Patients and methods: We included 128 patients who were non-hypertensive and overweight or obese in a study between December 2019 and November 2022. Medical history was collected, and all participants underwent a physical examination and blood tests. Pancreatic fat content was measured by magnetic resonance imaging (MRI) and was grouped into quartiles based on pancreatic fat fraction (PFF). The upper three quartiles (PFF≥ 10.33%) were defined as non-alcoholic fatty pancreas disease (NAFPD) and the first quartile (PFF< 10.33%) as non-NAFPD. High baPWV (H-baPWV) and low baPWV (L-baPWV) were classified according to the median baPWV (1159 cm/s). The effect of NAFPD on baPWV was examined using binary logistic regression. The study population consisted of 96 NAFPD and 32 non-NAFPD cases.Results: Participants with NAFPD had significantly higher levels of baPWV than people without. The rates of NAFPD and the PFF values varied significantly in the L-baPWV and H-baPWV groups. Logistic regression analysis suggested that the presence of NAFPD was independently correlated with increased baPWV after adjusting for age, smoking, body mass index, blood pressure, lipid profiles, and glycemic index.Conclusion: NAFPD is an independent risk factor for increased baPWV in individuals with overweight and obesity but no HT, suggesting that the presence of NAFPD may be a warning signal of early atherosclerosis.Keywords: obesity, non-alcoholic fatty pancreas disease, overweight, arterial stiffness, brachial-ankle pulse wave velocity

Juanjuan Lei,1,2 Huijing Lai,1,3 Siting Zhong,4 Xiaoli Zhu,5 Dianyu Lu6 1School of Nursing, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Department of Pneumology, Foshan Hospital of TCM, Foshan, People’s Republic of China; 4Department of Radiotherapy, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, People’s Republic of China; 5Department of Nursing, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, People’s Republic of China; 6Department of Anaesthesiology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Dianyu Lu, Department of Anaesthesiology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, 78 Hengzhigang Road, Yuexiu District, Guangzhou, 510095, People’s Republic of China, Tel +86-020-66673666, Email ldy020505@163.com Xiaoli Zhu, Department of Nursing, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, 78 Hengzhigang Road, Yuexiu District, Guangzhou, 510095, People’s Republic of China, Tel +86-15902037400, Email zhuxseven@163.comObjective: The primary objective of this cross-sectional study was to examine the prevalence of different types of intimate partner violence (IPV) among female nurses employed in public hospitals across China. Additionally, the study sought to investigate the relationship between nurses’ psychological resilience and their experiences of work thriving and work alienation in the aftermath of IPV.Methods: This cross-sectional study utilized an online self-report survey to collect data from a sample of 522 female nurses working in public healthcare facilities across several major cities in China. The survey instrument collected information on participants’ sociodemographic characteristics, experiences of intimate partner violence (IPV), psychological resilience, work thriving, and work alienation. The Kruskal–Wallis one-way ANOVA test was used to compare outcome variables across IPV exposure groups, and multiple linear regression modeling was subsequently performed to examine the associations between the dependent variables (work thriving and work alienation) and the independent variables, including IPV exposure and resilience.Results: The overall prevalence of IPV reported by the female nurse participants was 74.26%. Specifically, the rates of emotional IPV, physical IPV, and sexual IPV were 74.06%, 24.27%, and 7.53%, respectively. The results indicated that total IPV exposure, the three IPV subtypes, psychological resilience, work thriving, and work alienation were all significantly and positively interrelated. IPV scores demonstrated a negative association with psychological resilience and work thriving, but a positive association with work alienation. Importantly, psychological resilience was found to be positively correlated with work thriving and negatively correlated with work alienation.Conclusion: The findings suggest that psychological resilience plays a pivotal role, both directly and indirectly, in influencing the work-related outcomes of female nurses who have experienced IPV. Specifically, resilience was positively associated with thriving at work and directly negatively associated with work alienation, though a partial mediating effect of resilience was also observed.Keywords: resilience, Chinese female nurses, intimate partner violence, thriving at work, work alienation

Xianmin Zhu,1 Shuang Dong,1 Jing Tang,1 Rong Xie,1 Huijing Wu,1 Jun Guan,2 Sheng Hu1 1Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Hematology, Wuhan NO.1 Hospital, Wuhan, People’s Republic of ChinaCorrespondence: Sheng Hu, Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, 116 South Road, Wuhan, 430079, People’s Republic of China, Email ehusmn@163.comAbstract: In recent years, there have been limited reports on the efficacy of later-line anti-programmed cell death − 1 (PD-1) therapy in achieving prolonged and complete remission in patients with hepatocellular carcinoma (HCC). Tislelizumab, a humanized anti-PD-1 monoclonal IgG4 antibody, has shown promising results in the treatment of HCC. This report highlights the case of a patient with HCC who experienced the development of lung metastatic lesions following HCC resection and chemotherapy, but achieved a prolonged complete response (CR) after receiving tislelizumab treatment. In April 2017, a 56-year-old male diagnosed with primary HCC underwent hepatectomy and hepatic arterial infusion pump placement. Following the surgery, the patient received adjuvant hepatic arterial infusion chemotherapy (HAIC) with 4 cycles of cisplatin+5-fluorouracil (PF) regimen starting in June 2017. In May 2018, lung metastatic lesions were detected, and the patient underwent 4 cycles of oxaliplatin+leucovorin+5-fluorouracil (FOLFOX) chemotherapy. However, the disease progressed in August 2018, leading to the administration of arsenic trioxide treatment. Despite this, further progression was observed in October 2018, prompting the patient’s enrollment in a clinical trial for tislelizumab therapy. Initially, the patient achieved a partial response (PR) to tislelizumab, which was followed by a CR that lasted for almost 4 years. Unfortunately, tislelizumab treatment had to be discontinued due to immune-related adverse events (AE). Subsequently, the patient received lenvatinib and maintained a CR until July 2023. Tislelizumab monotherapy, when used as a third-line treatment, has demonstrated remarkable efficacy in facilitating patients with advanced HCC to attain a durable CR.Keywords: hepatocellular carcinoma, complete response, immune checkpoint inhibitor, tislelizumab, chemotherapy failure, metastasis

Jingjing Wei,1 Chunhong Zhang,1 Yi Leng,1 Mingming Li,1 Lingyun Du,1 Zhiqiang Cao,2 Xia Zhu,1 Changyu Han,1 Liya Meng1 1Department of Dermato-Venereology, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Dermatology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Liya Meng, Department of Dermato-venereology, The Second Hospital of Shandong University, 247 Beiyuan Dajie Street, Jinan, 250033, People’s Republic of China, Tel +86-531-85875027, Fax +86-531-88962544, Email mly0706@sina.comObjective and Design: The treatment of recurrent rosacea has always been a problem. Oral minocycline has been widely used in the treatment of rosacea. However, the efficacy and safety of ozonated hydrotherapy combined with LED yellow light irradiation and oral minocycline for mild to moderate papulopustular rosacea (PPR) has not been thoroughly studied.Methods: Patients with rosacea who met the criteria and had complete clinical statistic admitted to our hospital from April 2021 to September 2022 were retrospectively collected and divided into combined therapy group and oral only group. The patients in the two groups were treated with minocycline for 8 weeks. In addition, the patients in combined therapy group were treated with ozone hydrotherapy once a week, followed by LED yellow light irradiation for a total of 4 weeks. The Investigator’ s global assessment (IGA) score was used to assess the condition. The efficacy was evaluated using the patients’ subjective symptom scores. Skin lesion images and adverse reactions were recorded. The recurrence rate was observed after 24 weeks of follow-up.Results: A total of 39 patients included in the study. After 4 weeks of treatment, the effective rate was 90% in combined therapy group and 52.63% in oral only group (p< 0.05). After 8 weeks of treatment, the total score of the patients’ subjective symptom scores and the scores of itching and burning sensation in combined therapy group were lower than those in oral only group (p< 0.05). After 24 weeks of follow-up, the recurrence rate of combined therapy group was 5%, and that of oral only group was 26.32%. The mild adverse reactions experienced by both groups disappeared during follow-up.Conclusion: This combination therapy has a significant, rapid and safe therapeutic effect, especially in relieving itching and burning sensations, and may reduce the recurrence rate.Keywords: papulopustular rosacea, ozonated hydrotherapy, LED yellow light, minocycline, combined therapy

Jia Li,1,2 Wenjing Guo,1,2 Jieru Wang,1,2 Xiaomeng Feng,1,2 Qingsong Lin,1,2,&ast; Yizhou Zheng,1,2 Fengkui Zhang,1,2 Yingchang Mi,1,2 Xiaofan Zhu,1,2 Erlie Jiang,1,2 Zhijian Xiao,1,2 Jianxiang Wang,1,2 Sizhou Feng1,2,&ast; 1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, People’s Republic of China; 2Tianjin Institutes of Health Science, Tianjin, 301600, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sizhou Feng, Hematopoietic Stem Cell Transplantation Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 288 Nanjing Road, Tianjin, 300020, People’s Republic of China, Tel +86-022-23909162, Fax +022-23909047, Email doctor_szhfeng@163.com; szfeng@ihcams.ac.cnObjective: This study aimed to assess the impact of colonization status on the outcomes of Acinetobacter spp. bloodstream infection (BSI) and investigate the homology and within-host evolution between colonizing and bloodstream carbapenem-resistant Acinetobacter spp. (CRA) to inform antibiotic therapeutic decisions.Methods: We analyzed clinical outcomes of 46 hematological patients with Acinetobacter spp. BSI and performed whole-genome sequencing on the remaining CRA isolates.Results: Among the patients, 39.1% (n=18) had prior Acinetobacter spp. colonization. Colonized patients had higher rates of polymicrobial BSI (50.0% vs 21.4%, P=0.044) and CRA BSI (72.2% vs 17.9%, P< 0.001), resulting in elevated inflammatory markers and increased 30-day mortality. Each of the eight pairs of the remaining respiratory colonizing and bloodstream CRA strains belonged to the same genomospecies. Each pair exhibited definitive agreement in at least 21 of the 22 most representative antibiotic susceptibility tests. The minimum spanning tree based on multilocus sequence typing (MLST) and phylogenetic trees based on MLST and single nucleotide polymorphism (SNP) all indicated that each pair shared the same minimum branch. Very few non-synonymous SNPs in genic regions were identified during the transition from respiratory colonization to bloodstream infection, with minimal changes in virulence genes. Homology analysis suggested that CRA BSI originated from colonizing isolates in the respiratory tract.Conclusion: Strict infection control measures are needed to manage Acinetobacter spp. colonisation in hematological patients. Appropriate empirical therapy can be administered for suspected CRA BSI based on the antimicrobial minimum inhibitory concentration of CRA colonising the respiratory tract.Keywords: Acinetobacter, colonization, bloodstream infections, homology, therapy, carbapenem-resistant

Ling Lv,1 Xin Zhang,1 Yajun Liu,1 Xutong Zhu,2 Ruihan Pan,1 Lifa Huang1 1Department of Neurosurgery, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 2The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Lifa Huang, Department of Neurosurgery, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), No. 54 Youdian Road, Hangzhou, 310006, People’s Republic of China, Tel/Fax +86-57186620251, Email jazzle@163.comPurpose: Dysregulated liquid-liquid phase separation (LLPS) instigates tumorigenesis through biomolecular condensate dysfunction. However, the association between LLPS-associated genes and glioma remains underexplored.Patients and Methods: Differentially expressed genes (DEGs) of glioma were obtained from the GSE50161 dataset, including 34 glioma and 13 normal samples. We analyzed differentially expressed LLPS-related genes in glioma from public databases. These genes informed refined molecular subtyping on the TCGA-glioma dataset. CIBERSORT assessed immune cell infiltration across three subclusters. A prognostic model was devised using univariate and lasso Cox regressions on intersecting genes. Prognostic gene expression was validated in glioma cells via RT-qPCR.Results: A total of 673 differentially expressed LLPS-associated genes were identified in glioma. Three distinct molecular subtypes (C1, C2, and C3) of glioma were obtained with a marked variance in the expression of immune checkpoint genes PD1 and PDL1. Differences in immune cell infiltration were observed across subtypes. In addition, a tri-gene prognostic signature (TAGLN2, NTNG2, and IGF2BP2) was derived with significant survival differences between high and low-risk groups. The prognostic model displayed impressive AUC values for 1, 3, and 5-year survival in both training and validation sets. Further analysis highlighted a notable correlation between the three prognostic genes and immune cells in glioma samples. Furthermore, we found the upregulation of TAGLN2 and IGF2BP2 and the downregulation of NTNG2 in glioma tumors and cells.Conclusion: This study innovatively uncovers the significant role of LLPS-related genes in glioma tumor grading and prognosis. The constructed tri-gene prognostic model holds promise for enhancing personalized prognosis assessments and optimizing immunotherapy strategies for glioma patients.Keywords: liquid-liquid phase separation, glioma, prognostic model, molecular subtype, immune cell infiltration

Jinlu Huang,1,&ast; Jiugeng Chen,2,&ast; Le Ma,3,&ast; Xieyi Zhu,4 Lili Wan,1 Xinyan Li,4 Cheng Guo1 1Department of Pharmacy, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Instrumental Analysis Center, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai Mental Health Center, Shanghai, People’s Republic of China; 4College of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinyan Li; Cheng Guo, Email lixy@sjtu.edu.cn; guopharm@126.comBackground: Ionomics is used to study levels of ionome in different states of organisms and their correlations. Bone cancer pain (BCP) severely reduces quality of life of patients or their lifespan. However, the relationship between BCP and ionome remains unclear.Methods: The BCP rat model was constructed through inoculation of Walker 256 cells into the left tibia. Von Frey test, whole-cell patch-clamp recording and inductively coupled plasma mass spectrometry (ICP-MS) technologies were conducted for measuring tactile hypersensitivity, the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) of neurons of spinal slices, and ionome of spinal cord samples, respectively. Principal component analysis (PCA) was used to explore ionomic patterns of the spinal cord.Results: The BCP rat model was successfully constructed through implantation of Walker 256 cells into the left tibia. The frequency and amplitude of mEPSCs of neurons in the spinal cord slices from the BCP model rats were notably greater than those in the sham control. In terms of ionomics, the spinal cord levels of two macroelements (Ca and S), four microelements (Fe, Mn, Li and Sr) and the toxic element Ti in the BCP group of rats were significantly increased by inoculation of Walker 256 cancer cells, compared to the sham control. In addition, the correlation patterns between the elements were greatly changed between the sham control and BCP groups. PCA showed that inoculation of Walker 256 cells into the tibia altered the overall ionomic profiles of the spinal cord. There was a significant separation trend between the two groups.Conclusion: Taken together, inoculation of Walker 256 cells into the left tibia contributes to BCP, which could be closely correlated by some elements. The findings provided novel information on the relationship between the ionome and BCP.Keywords: bone cancer pain, spinal cord, micronutrient, ionomic profile

Min Wu,1,2,&ast; Sining Zeng,3,&ast; Yi Zhang,1,2,&ast; Yanru Liu,1,2 Bingbing Li,1,2 Xuemei Yi,1,2 Yuling Shi,1,2 Xiaoping Zhu3 1Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, People’s Republic of China; 2Institute of Psoriasis, Tongji University School of Medicine, Shanghai, 200443, People’s Republic of China; 3Nursing Department, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoping Zhu, Nursing Department, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Yanchang Middle Road, Jing’an District, Shanghai, People’s Republic of China, Tel +86-021-66300588, Fax +86-021-66307542, Email xiaopingzhu0424@163.com Yuling Shi, Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, 1278 Baode Road, Jing’an District, Shanghai, People’s Republic of China, Tel +86-021-36803020, Fax +86-021-36803021, Email shiyuling1973@tongji.edu.cnBackground: Psoriasis is a chronic autoimmune inflammatory skin condition characterized by erythema, papules, and scales. It imposes a heavy psychological and social strain on both patients and their families. Surprisingly, there’s limited research delving into the disease burden and coping strategies of spouses contending with psoriasis.Objective: The objective is to explore the disease burden faced and coping strategies utilized by spouses of individuals living with psoriasis. This exploration aims to offer insights crucial for devising mental health support and intervention strategies.Methods: The research methodology employed in this study was phenomenological, a qualitative approach. A total of fifteen spouses of patients with psoriasis were selected using an objective sampling method for in-depth, semi-structured interviews. Thematic analysis was then applied to the recorded interview data to derive meaningful themes.Results: This study has identified and analyzed three core themes concerning the disease burden and coping strategies of spouses of patients with psoriasis: Overwhelming disease burden; Lack of support system; Coping strategies (Problem - centered coping strategies: Proactive acquisition of disease knowledge; Active confrontation of illness - related issues; Behavioral habit alteration; and Emotional - centered coping strategies: Active acceptance and normalization; Passive acceptance and internalized stigma; Avoidance of disease - related problems).Conclusion: This study adds valuable insights into comprehending the disease burden encountered by spouses of patients with psoriasis and sheds light on the coping strategies they employ. Healthcare providers should proactively recognize and address the burden experienced by spouses early on. Establishing a robust support network is crucial, and promoting adaptive coping strategies can significantly aid spouses in effectively navigating and managing the complexities associated with psoriasis.Keywords: psoriasis, spouse, disease burden, coping strategies, qualitative research

Cheng Ma,1 Minnan Yue,2 Xiaoling Zhu1 1Department of Physical Education, University of Shanghai for Science and Technology, Shanghai, 200093, People’s Republic of China; 2School of Energy and Power Engineering, University of Shanghai for science and technology, Shanghai, 200093, People’s Republic of ChinaCorrespondence: Cheng Ma, Department of Physical education, University of Shanghai for science and technology, Shanghai, 200093, People’s Republic of China, Tel +86-13795365789, Email macheng@usst.edu.cnPurpose: To investigate the knowledge, attitudes and practices (KAP) among college students toward physical literacy during COVID-19 school closure.Patients and Methods: This web-based cross-sectional study was conducted between December 9th, 2022 and December 24th, 2022 among college students during COVID-19 school closure. A self-designed questionnaire was developed to collect demographic information of the college students, and assess their KAP toward physical literacy.Results: A total of 969 students were recruited, with mean age of 18.73± 0.97 years. The majority were male (54.70%), urban residents (78.02%), majoring in engineering (58.00%), and having exercise habits (61.09%). The mean KAP scores were 6.57± 0.95, 32.63± 4.07, and 27.06± 7.23, respectively. Positive associations were identified between knowledge and attitude (OR = 2.01, 95% CI: 1.52– 2.66, P < 0.001), and between attitude and practice (OR = 1.17, 95% CI: 1.12– 1.22, P < 0.001). A bachelor’s degree and being in the sophomore year were positively associated with knowledge (OR = 1.51– 4.05, all P < 0.05). Urban residence and being in the sophomore year were negatively associated with attitude (OR = 0.43– 0.59, all P < 0.05), while having daily exercise habits showed the opposite trend (OR = 1.85, 95% CI: 1.33– 2.57, P < 0.001). Father’s education level of high school and technical secondary school (OR = 0.58, 95% CI: 0.37– 0.93, P = 0.023) and having daily exercise habits (OR = 3.88, 95% CI: 2.72– 5.55, P < 0.001) were associated with practice.Conclusion: College students had sufficient knowledge, moderate attitudes and negative practices towards physical literacy during COVID-19 school closure. The findings hold significant potential for developing educational programs, fostering healthier lifestyles and promoting mental well-being among college students during public health outbreaks.Keywords: knowledge, attitude, practice, cross-sectional study, physical literacy

Junwei Pu,1 Xiong Gan,1 Zaiming Pu,2 Xin Jin,1 Xiaowei Zhu,1 Chunxia Wei3 1College of Education and Sports Sciences, Yangtze University, Jingzhou City, Hubei Province, People’s Republic of China; 2College of Marxism, ENSHI POLYTECHNIC, Enshi City, Hubei Province, People’s Republic of China; 3Foreign languages college, Jingzhou University, Jingzhou City, Hubei Province, People’s Republic of ChinaCorrespondence: Xiong Gan, Department of Psychology, College of Education and Sports Sciences, Yangtze University, Jingzhou, 434023, People’s Republic of China, Tel +86 7168062663, Email 307180052@qq.com Chunxia Wei, Foreign languages college, Jingzhou University, Jingzhou, 434023, Hubei, People’s Republic of China, Email msvivien2023@126.comIntroduction: Bullying is a significant concern for young people, with studies consistently showing a link between bullying and negative emotional consequences. However, the mechanisms that underlie this association remain unclear, particularly in terms of the classroom environment. This study aimed to explore the paradoxical phenomenon between bullying victimization and emotional adaptation among junior high school students in China, using the hypothesis of the healthy context paradox.Methods: The study involved 880 students (565 girls; Mage=14.69; SD=1.407 years), and data were collected using self-reported surveys. The findings of the study, utilizing multilevel structural equation modeling (MSEM) techniques, demonstrated a cross-level moderated effect of classroom-level bullying victimization on the relationship between individual bullying victimization and emotional adaptation.Results: Specifically, the results indicated that in classrooms with higher levels of victimization, the association between individual bullying victimization and increased depressive symptoms and State&Trait anxiety was more pronounced. These findings support the “Healthy context paradox” hypothesis in the Chinese context and provide insight into the mechanisms underlying this phenomenon.Discussion: The results suggest that the classroom environment plays a crucial role in shaping the emotional consequences of bullying and that addressing classroom victimization is crucial for promoting emotional health among young people. By understanding the mechanisms that underlie the association between bullying and emotional consequences, interventions can be developed to target the underlying factors that contribute to this paradoxical phenomenon. Overall, the study provides new insights into the complex relationship between bullying and emotional health among young people, highlighting the importance of considering the classroom environment in addressing this issue.Keywords: the healthy context paradox, bullying victimization, emotional adaptation, the level of classroom victimization

Qilin Han,1,2 Yifan Li,3 Yao Liu,1 Xuehan Zhu,1 Qiqi An,4 Yameng Li,5 Tingting Wang,5 Yuzhen Zhang,1,2 Yingying Li,5 Weiwei Fang,1,2 Ningning Tao,1,&ast; Huaichen Li1,2,&ast; 1Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 2Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Shandong First Medical University (Affiliated Hospital of Shandong Academy of Medical Sciences), Jinan, Shandong, 250031, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Xingyi People’s Hospital, Qianxinan, Guizhou, 561499, People’s Republic of China; 5Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ningning Tao, Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China, Email 826794467@qq.com Huaichen Li, Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Huaiyin District, Jinan, Shandong, 250021, People’s Republic of China, Email lihuaichen@163.comPurpose: To analyze the time trends in the notification rates of registered tuberculosis (TB) and bacteriologically confirmed TB in Shandong Province. And analyze the changes in TB treatment outcomes during 2005– 2021.Patients and Methods: The information of TB patients registered in the Shandong Information Center for Disease Control and Prevention (CDC) was collected during 2005– 2021. We calculated the notification rates of registered TB and bacteriologically confirmed TB. Moreover, we calculated the year-to-year change rate of TB in treatment outcomes before and after COVID-19. The time trends were analyzed using the joinpoint regression method and illustrated as the annual percentage change (APC) of notification rates.Results: A total of 236,898 cases of TB were diagnosed during 2005– 2021, of which 51.11% were bacteriologically confirmed cases. Since 2008, the notification rates of registered TB have declined. The notification rates of bacteriologically confirmed TB had been declining during 2005– 2016, then remained stable after 2016. In subgroup, the notification rates of both registered TB and bacteriologically confirmed TB were higher among men, rural residents, and people aged ≥ 60 years. Compared with clinically confirmed TB, bacteriologically confirmed TB has shown higher rates of poor outcomes since 2008 and higher case fatality rate since 2005. The rate of poor outcomes remained stable during 2008– 2019. However, after the COVID-19 outbreak, the rate of poor outcomes and case fatality rate of TB has risen significantly.Conclusion: After unremitting efforts to fight against TB, the notification rates of registered TB and bacteriologically confirmed TB declined in Shandong Province. The rate of poor outcomes remained stable during 2008– 2019, then rise significantly after the COVID-19 outbreak. In the context of the long-term existence of COVID-19, further efforts should be made in TB diagnosis and treatment among high-risk population, especially with regard to males, rural residents and older adults.Keywords: tuberculosis, joinpoint regression, time trends, COVID-19

Lei Yuan,&ast; Lan Min Lai,&ast; Xinyu Zhu, Zhao Rui, Yang Liu, Qiang Chen Department of Clinical laboratory, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Chen, Email 674389899@qq.comBackground: The HACEK group comprises Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae, are Gram-negative bacteria that are slow-growing and fastidious. These organisms are common causes of culture-negative endocarditis. However, brain abscesses caused by Haemophilus aphrophilus and E. corrodens have been rarely reported. The case we describe, which was promptly identified and successfully treated, will be meaningful for the diagnosis and treatment of such infectious diseases.Case Presentation: Herein, we report a case of brain abscess in a young man who was infected with Haemophilus aphrophilus and E. corrodens. The patient was admitted to the hospital with sudden onset of vomiting, coma, and fever. Magnetic resonance imaging (MRI) of the brain and cerebrospinal fluid cell counts suggested cerebral abscess, he underwent drainage of the abscess and empirical antimicrobial therapy of meropenem (2 g every 8 hours) and linezolid (0.6 g every 12 hours) for more than 10 days without significant improvement. Metagenomic next-generation sequencing (mNGS) of drainage fluid and matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF MS) detection for isolated bacteria from samples suggested the presence of H. aphrophilus and E. corrodens. After 7 weeks of ceftriaxone (2 g every 12 hours) and meropenem (2 g every 8 hours) intravenously, the patient was discharged with a normal temperature and brain MRI showed improvement of the lesion.Conclusion: Similar cases reported in previous studies were always associated with bacterial blood dissemination after dental surgery or myocarditis; however, the patient in our case had no any associated risk factors. As far as we know, this is the only case of central nervous system infection caused by H. aphrophilus and E. corrodens that has utilized combined mNGS and MALDI-TOF MS in the diagnosis.Keywords: Haemophilus aphrophilus, Eikenella corrodens, HACEK, brain abscess

Xiaoli Zhu,1 Yijun Chen,1 Mingan Zhu,2 Jinxi Hu3 1Department of Laboratory Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China; 2Department of Medical Laboratory, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 3Department of Oncological Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of ChinaCorrespondence: Mingan Zhu, Department of Medical Laboratory, Renmin Hospital, Hubei University of Medicine, No. 39 Chaoyang Middle Road, Shiyan, Hubei Province, 442000, People’s Republic of China, Tel +86 13872767288, Email 839239972@qq.com Jinxi Hu, Department of Oncological Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No. 150 Ximen Road of Linhai, Taizhou, Zhejiang Province, 317000, People’s Republic of China, Tel +86 18257689350, Email hujinxi6886@163.comBackground: Prior research has established an association between small dense low-density lipoprotein cholesterol (sdLDL-C) and dyslipidemia, serving as a significant marker for predicting cardiovascular diseases. Nevertheless, the connection between sdLDL-C and metabolic syndrome (MetS) remains unclear.Methods: This study retrospectively analyzed 23,187 individuals who underwent health checkups at Taizhou Hospital’s health management center. Here, we investigated the relationship between sdLDL-C and MetS, along with its components, utilizing Spearman correlation analysis, receiver operating characteristic (ROC) curve analysis, logistic regression, and mediation analysis.Results: The MetS group exhibited significantly higher level of sdLDL-C compared to the non-MetS group (P< 0.001). We observed a strong correlation between sdLDL-C and several key factors: TG (r = 0.711), TC (r = 0.672), LDL-C (r = 0.781), GGT (r = 0.420), and HDL-C (r = − 0.417). After adjusting for age and gender, the odds ratio (OR) (95% confidence interval [CI]) for MetS incidence in the second, third, and fourth quartiles versus the first quartile of sdLDL-C concentration were 2.264 (95% CI: 1.851, 2.770), 4.053 (95% CI: 3.350, 4.903), and 9.034 (95% CI: 7.531, 10.837). The optimal cut-off value for diagnosing MetS using sdLDL-C was determined to be 0.98 mmol/L, with an area under the ROC curve (AUC) of 0.716 (95% CI: 0.705, 0.726). Additionally, mediation analysis revealed that sdLDL-C mediated a 12.8% correlation between GGT and TG concentration.Conclusion: The sdLDL-C is correlated with MetS and it can successfully mediate the relationship between GGT and TG. Our data suggests that sdLDL-c and GGT are suitable parameters for preventing and monitoring MetS.Keywords: metabolic syndrome, small dense low-density lipoprotein cholesterol, mediation analysis, GGT

Zetan Chen,1,2 Gang Wu,2 Xiangying Lin,2 Xiaopeng Huang,2 Shuai Zhang,2 Kaihua Chen,1 Zhongguo Liang,1 Xiaodong Zhu1,3,4 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China; 3Department of Oncology, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of China; 4Key Laboratory of Early Prevention and Treatment for Regional High-Incidence-Tumor, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Xiaodong Zhu, Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-13978873616, Email zhuxdonggxmu@126.comPurpose: Elevated serum sialic acid (SA) is one of the indicators of poor prognosis in various malignant tumors. This study intends to determine the relationship between serum SA levels and survival prognosis in nasopharyngeal carcinoma (NPC).Patients and Methods: From 2014 to 2016, NPC patients with no distance metastasis undergoing intensity-modulated radiotherapy (IMRT) were retrospectively analyzed. The serum SA levels before initial treatment were measured, and an optimal cut-off level was determined by X-tile software. A propensity score matching (PSM) technique was applied to reduce intergroup differences between the low serum SA level group and the high serum SA level group. Chi-square tests were utilized for comparing intergroup differences, Kaplan-Meier approach was utilized for plotting survival curves, and univariate and multivariate Cox proportional hazards regression models were employed for analyzing prognostic factors.Results: Overall, 293 NPC patients with no distance metastasis were included. The optimal cut-off level of serum SA was 65.10 mg/dl. The baseline levels after PSM were more balanced compared to those before PSM. Survival analysis showed that the locoregional relapse-free survival (LRRFS, p=0.010), distant metastasis–free survival (DMFS, p=0.014), progression-free survival (PFS, p=0.009), and overall survival (OS, p=0.015) survival curves of the low serum SA level group and high serum SA level group were statistically significant differences. Univariate analysis showed that American Joint Committee on Cancer (AJCC) stage, T stage, N stage, neoadjuvant chemotherapy (NC), and serum SA expression level were factors influencing the prognosis of NPC patients. Multivariate analysis showed that high serum SA expression level was related to worse PFS and OS in NPC patients with no distance metastasis.Conclusion: High serum SA level (SA > 65.10 mg/dl) before treatment is associated to poor survival outcomes in NPC and is an independent adverse prognostic factor in NPC patients with no distance metastasis.Keywords: serum sialic acid, nasopharyngeal carcinoma, prognosis, propensity score matching

Ci Lu,1,&ast; Panpan Lv,2,&ast; Xiaoying Zhu,1 Yongmei Han1 1Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Ultrasound, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoying Zhu; Yongmei Han, Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3&num; Qingchun East Road, Hangzhou, 310016, People’s Republic of China, Email 3202091@zju.edu.cn; 3408235@zju.edu.cnAbstract: Cogan’s syndrome (CS) is a rare chronic inflammatory disease, characterized by interstitial keratitis and vestibular auditory dysfunction. Hypertrophic pachymeningitis (HP) is a rare chronic aseptic inflammatory disease of the central nervous system. This article reports a patient with CS coexisting with HP. The patient was a 66-year-old male with fever, headache, red eyes, hearing loss, and significantly elevated inflammatory markers. Cerebrospinal fluid examination, blood culture, and tests for autoantibodies such as antinuclear antibodies were negative. Pure tone audiology (PTA) indicated bilateral sensorineural deafness. Both Positron emission tomography–computed tomography (PET/CT) and vascular color Doppler ultrasound suggest the presence of vasculitis. Considering Cogan’s syndrome, the patient received 40 mg of methylprednisolone intravenously once daily. The brain’s magnetic resonance imaging (MRI) revealed slightly thickened and enhanced dura mater, suggesting HP. The dose of methylprednisolone was increased to 40 mg intravenously every 8 hours, leading to the patient’s improved symptoms and decreased inflammatory markers. Both CS and HP are rare chronic inflammatory diseases, and their coexistence is even rarer, with only two reported cases in literature up to date. The coexistence of CS and HP should be considered when the CS patients with headaches do not respond well to treatment.Keywords: Cogan’s syndrome, hypertrophic pachymeningitis, vasculitis

Gehang Ju,1– 3 Xin Liu,1– 3 Wenyu Yang,4 Nuo Xu,4 Lulu Chen,3,5 Chenchen Zhang,6 Qingfeng He,4 Xiao Zhu,4,&ast; Dongsheng Ouyang1– 3,5,&ast; 1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Institute of Clinical Pharmacology, Central South University, Changsha, People’s Republic of China; 3Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd, Changsha, People’s Republic of China; 4Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China; 5Changsha Duxact Biotech Co., Ltd, Changsha, People’s Republic of China; 6School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongsheng Ouyang; Xiao Zhu, Email 801940@csu.edu.cn; xiaozhu@fudan.edu.cnIntroduction: Isoniazid (INH) is a crucial first-line anti tuberculosis (TB) drug used in adults and children. However, various factors can alter its pharmacokinetics (PK). This article aims to establish a population pharmacokinetic (popPK) models repository of INH to facilitate clinical use.Methods: A literature search was conducted until August 23, 2022, using PubMed, Embase, and Web of Science databases. We excluded published popPK studies that did not provide full model parameters or used a non-parametric method. Monte Carlo simulation works was based on RxODE. The popPK models repository was established using R. Non-compartment analysis was based on IQnca.Results: Fourteen studies included in the repository, with eleven studies conducted in adults, three studies in children, one in pregnant women. Two-compartment with allometric scaling models were commonly used as structural models. NAT2 acetylator phenotype significantly affecting the apparent clearance (CL). Moreover, postmenstrual age (PMA) influenced the CL in pediatric patients. Monte Carlo simulation results showed that the geometric mean ratio (95% Confidence Interval, CI) of PK parameters in most studies were within the acceptable range (50.00– 200.00%), pregnant patients showed a lower exposure. After a standard treatment strategy, there was a notable exposure reduction in the patients with the NAT2 RA or nonSA (IA/RA) phenotype, resulting in a 59.5% decrease in AUC0-24 and 83.2% decrease in Cmax (Infants), and a 49.3% reduction in AUC0-24 and 73.5% reduction in Cmax (Adults).Discussion: Body weight and NAT2 acetylator phenotype are the most significant factors affecting the exposure of INH. PMA is a crucial factor in the pediatric population. Clinicians should consider these factors when implementing model-informed precision dosing of INH. The popPK model repository for INH will aid in optimizing treatment and enhancing patient outcomes.Keywords: Isoniazid, model-informed precision dosing, population pharmacokinetics, nonlinear mixed-effects model

Sheng Yin,1 YingRui Lin,1 Bingqi Wang,1 Yizhi Peng,2 Zeyou Wang,1 Xiaolin Zhu,1 Hao Liang,1 Xianping Li,1 Min Wang1 1Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Department of Laboratory Medicine, Hunan Cancer Hospital, Central South University, Changsha, Hunan, 410031, People’s Republic of ChinaCorrespondence: Min Wang, Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Tel +86 13298697558, Email wangmin0000@csu.edu.cnPurpose: Bloodstream infection(BSI) is linked with high mortality, underscoring the significance of prompt etiological diagnosis for timely and precise treatment. This study aims to investigate the diagnostic value of droplet digital polymerase chain reaction(ddPCR) in combination with conventional inflammatory markers [interleukin-6(IL-6) and procalcitonin(PCT)] concerning disease progression and treatment prognosis in BSI patients. Furthermore, the study aims to explore a more efficient clinical application strategy.Patients and Methods: This prospective case seried study centers on 176 patients suspected of or confirmed with BSI. Blood samples were collected to extract nucleic acids for identifying pathogens (bacteria, fungi, and viruses) and determining copy loads via ddPCR.Results: The sensitivity of ddPCR was markedly higher compared to the culture method (74.71% vs 31.03%). A positive correlation existed between bacterial load and levels of inflammatory markers [IL-6 (P= 0.0182), PCT (P= 0.0029), and CRP (P= 0.0005)]. In suspected BSI cases, the combination of ddPCR and inflammatory markers could predict sepsis risk [ROC: Area under the curve(AUC)=0.6071, P= 0.0383]. Within confirmed BSI patients, the ddPCR bacterial load of those with SOFA< 7 was lower than that of the SOFA≥ 7 (P= 0.0334). ddPCR (OR: 1.789, P= 0.035) monitoring combined with PCT (OR: 1.787, P= 0.035) holded predictive value for SOFA progression (AUC=0.7913, P= 0.0003). Similarly, BSI survivors displayed a lower burden than non-survivors (P= 0.0170). Additionally, ddPCR combinated with IL-6 provided a more accurate and expedited insight into clinical outcomes prediction for BSI confirmed patients (AUC=0.7352, P= 0.0030). Serial monitoring of bacterial load by ddPCR effectively mirrored the clinical course of BSI in patients. Notably, patients with positive ddPCR virus infection exhibited significantly reduced lymphocyte counts (P= 0.0003).Conclusion: In a clinical context, qualitative ddPCR results and quantitative continuous monitoring can more precisely assess sepsis progression and treatment prognosis in BSI patients. Furthermore, ddPCR results offer quicker and more accurate reference points for clinical antibacterial and antiviral interventions.Keywords: bloodstream infection, droplet digital polymerase chain reaction, interleukin-6, procalcitonin, prognosis

Yunhao Zhang,1 Xuejiao Zhu,1 Fuer Gao,1 Shulan Yang2 1College of Nursing, Hangzhou Normal University, Hangzhou, People’s Republic of China; 2Department of Nursing, Zhejiang Hospital, Hangzhou, People’s Republic of ChinaCorrespondence: Xuejiao Zhu, College of Nursing, Hangzhou Normal University, Hangzhou, 311121, People’s Republic of China, Email jj_ice@163.comPurpose: Coronary artery disease (CAD) patients frequently face readmissions due to suboptimal disease management. Prediction models are pivotal for detecting early unplanned readmissions. This review offers a unified assessment, aiming to lay the groundwork for enhancing prediction models and informing prevention strategies.Methods: A search through five databases (PubMed, Web of Science, EBSCOhost, Embase, China National Knowledge Infrastructure) up to September 2023 identified studies on prediction models for coronary artery disease patient readmissions for this review. Two independent reviewers used the CHARMS checklist for data extraction and the PROBAST tool for bias assessment.Results: From 12,457 records, 15 studies were selected, contributing 30 models targeting various CAD patient groups (AMI, CABG, ACS) from primarily China, the USA, and Canada. Models utilized varied methods such as logistic regression and machine learning, with performance predominantly measured by the c-index. Key predictors included age, gender, and hospital stay duration. Readmission rates in the studies varied from 4.8% to 45.1%. Despite high bias risk across models, several showed notable accuracy and calibration.Conclusion: The study highlights the need for thorough external validation and the use of the PROBAST tool to reduce bias in models predicting readmission for CAD patients.Keywords: coronary artery disease, readmission, prediction model, systematic review

Xiaoqun Xu,1,&ast; Xinyu Zhu,2,&ast; Hanxin Wang,3 Xiao Liu,3 Chao Yang,3 Libin Liu,1 Tielong Chen,4 Long Cai,1 Houyong Zhu4 1Centre of Laboratory Medicine, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Houyong Zhu, Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453 Stadium Road, Hangzhou, 310007, People’s Republic of China, Email houyongzhu@foxmail.com Long Cai, Department of Clinical Laboratory, Hangzhou Red Cross Hospital, NO. 208 East Huancheng Road, Hangzhou, 310003, People’s Republic of China, Email cailong317@hotmail.comAim: The purpose of this study was to investigate the role of neutrophil-lymphocyte ratio (NLR), C-reactive protein-albumin ratio (CAR), and platelet-lymphocyte ratio (PLR) in the prognosis of patients with coronary artery disease (CAD) complicated with coronavirus disease 2019 (COVID-19).Methods: This study included 265 patients. A receiver operating characteristic (ROC) curve analysis was performed to preliminarily evaluate the predictive ability of NLR, CAR, and PLR for all-cause death. The primary outcome was all-cause death during hospitalization, while the secondary outcomes were cardiovascular death and respiratory failure death. The Cox proportional hazard model with adjusted covariates was used to analyze the cumulative risk of outcomes. We also conducted subgroup analyses based on the acute and chronic characteristics of CAD. Propensity score matching (PSM) was used to further evaluate the robustness of the primary outcome.Results: The ROC curve analysis results showed that the area under curve (AUC) values were 0.686 (95% CI 0.592– 0.781, P< 0.001) for NLR, 0.749 (95% CI 0.667– 0.832, P< 0.001) for CAR, and 0.571 (95% CI 0.455– 0.687, P=0.232) for PLR. The Cox proportional hazard model showed that trends in NLR and PLR did not affect the risk of all-cause death (P=0.096 and P=0.544 for trend, respectively), but a higher CAR level corresponded to a higher risk of all-cause death (P< 0.001 for trend). Similarly, The trends of NLR and PLR did not affect the risk of cardiovascular death and respiratory failure death, while a higher CAR level corresponded to a higher risk of cardiovascular death and respiratory failure death. The results of subgroup analyses and PSM were consistent with the total cohort.Conclusion: In patients with CAD complicated with COVID-19, a higher CAR level corresponded to a higher risk of all-cause death, cardiovascular death, and respiratory failure death, while trends in NLR and PLR did not.Keywords: coronary artery disease, coronavirus disease 2019, neutrophil-lymphocyte ratio, C-reactive protein-albumin ratio, platelet-lymphocyte ratio

Baojiang Liu,&ast; Song Gao,&ast; Jianhai Guo, Fuxin Kou, Shaoxing Liu, Xin Zhang, Aiwei Feng, Xiaodong Wang, Guang Cao, Hui Chen, Peng Liu, Haifeng Xu, Qinzong Gao, Renjie Yang, Liang Xu, Xu Zhu Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xu Zhu, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China, Tel + 86-10-8819-6059, Email drzhuxu@163.comPurpose: Recently, hepatic arterial infusion chemotherapy (HAIC) has also gained popularity for hepatocellular carcinoma (HCC). Several studies have compared HAIC and Transarterial chemoembolization (TACE). However, comparisons between TACE plus HAIC and HAIC are rarely reported. Here, we evaluated the performance of HepaSphere DEB-TACE combined with HAIC (Hepa-HAIC) compared to HAIC in patients with advanced HCC.Patients and Methods: In this retrospective study, we enrolled 167 patients diagnosed with advanced HCC and treated at Peking University Cancer Hospital from May 2018 to May 2022. The cohort comprised 74 patients who received HepaSphere DEB-TACE combined with HAIC-FOLFOX (Hepa-HAIC) and 93 patients who received HAIC-FOLFOX. Over 60% of patients received prior treatments. To avoid selection bias, propensity score matching was applied to the efficacy and safety analyses. The primary endpoints are progression-free survival (PFS) and overall survival (OS); the secondary endpoints include objective response rate (ORR), disease control rate (DCR), and safety.Results: Propensity-matching yielded 48 pairs, and group baselines were almost equal after matching. Median PFS and median OS were both higher in the matched Hepa-HAIC cohort (median PFS: 8.9 vs 5.8 months, p = 0.035; median OS: 22.4 vs 9.5 months, p = 0.027), which was consistent with pre-matching analysis. The ORR in the Hepa-HAIC and HAIC cohorts was 75.0% and 37.5%, respectively; the DCR was 93.8% after Hepa-HAIC and 81.3% after HAIC. There was no treatment-related death. Grade 3– 4 ALT elevation was more frequent in the Hepa-HAIC group (33.3% vs 8.3%, p = 0.003), while vomiting was more frequent in the HAIC group (29.2% vs 12.5%, p = 0.084).Conclusion: The Hepa-HAIC group is superior to the HAIC group in metrics of PFS, OS, ORR, and DCR, which indicates the combination of HepaSphere DEB-TACE and HAIC may lead to improved outcomes with a comparable safety profile in advanced HCC.Keywords: transarterial chemoembolization, advanced hepatocellular carcinoma, hepatic arterial infusion chemotherapy, propensity score matching

Zongwei Xue,1,&ast; Xiaoyan Zhu,2– 4,&ast; Wenqi Wu,1 Yan Zhu,5 Yuhao Xu,1 Ming Yu1 1Department of Neurology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of China; 2Department of Neurology, People’s Hospital of Yangzhong City, Yangzhong, Jiangsu, 212299, People’s Republic of China; 3School of Clinical Medicine, Medical College of Yangzhou University, Yangzhou, Jiangsu, 225000, People’s Republic of China; 4Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, Jiangsu, 225000, People’s Republic of China; 5Department of Radiology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuhao Xu; Ming Yu, Department of Neurology, The Affiliated Hospital of Jiangsu University, No. 438 Jiefang Road, Zhenjiang, 212001, People’s Republic of China, Tel +86 187 9601 7221, Email xuyuh0217@163.com; yuming7251@163.comBackground: Cognitive impairment is one of the common concomitant symptoms of depression. The aims of the present study were to predict the occurrence of mild cognitive impairment (MCI) in patients with depression.Methods: In this study, 217 patients with depression were recruited. Demographic data, serum indices and ERP indices from all participants were collected in the baseline period. The participants were followed for one year, and data from 200 patients were included in final analysis. Patients with depression were divided into those with MCI group (DWM group; n=145) and those without MCI (DWOM group; n=55). Data from the DWM group and the DWOM group were used to construct a logistic regression model, and a receiver operating characteristic (ROC) curve was drawn. Another 72 patients were used to validate the accuracy of our model.Results: Compared with DWOM individuals, DWM individuals were more likely to live alone (P< 0.05), had lower baseline serum levels of brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and fibroblast growth factor 22 (FGF22) (P< 0.05), and exhibited higher baseline latencies of P300, mismatch negativity (MMN), and N200 (P< 0.05). Baseline serum BDNF and FGF22 levels, along with the P300 latency, were selected to construct the regression model using logistic regression. The regression equation was , and the combination of the 3 indices yielded an area under the ROC curve (AUC) of 0.790 and a predictive accuracy of 0.806.Conclusion: The logistic regression model and ROC curves based on serum BDNF and FGF22 levels and the P300 latency could provide a more effective means to predict the occurrence of MCI in patients with depression.Keywords: depression, mild cognitive impairment, brain-derived neurotrophic factor, fibroblast growth factor 22, P300, prediction

Yinfeng Chen,&ast; Xiaying Wang,&ast; Jie Min, Jie Zheng, Xuanli Tang, Xiaoling Zhu, Dongrong Yu, De Jin Department of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310007, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongrong Yu; De Jin, Department of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310007, People’s Republic of China, Email yudr68@163.com; 826901274@qq.comPurpose: This study investigated the mechanism of TSF in treating DN through network pharmacology, molecular docking, and experimental validation.Methods: To identify critical active ingredients, targets, and DN genes in TSF, multiple databases were utilized for screening purposes. The drug-compound-target network was constructed using Cytoscape 3.9.1 software for network topological analysis. The protein interaction relationship was analyzed using the String database platform. Metascape database conducted enrichment analysis on the key targets using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. The renoprotective effect was evaluated using a mouse model of diabetic nephropathy (db/db mice) that occurred spontaneously. Validation of the associated targets and pathways was performed using Western Blot (WB), Polymerase Chain Reaction (PCR), and Immunohistochemical methods (IHC).Results: The network analysis showed that the TSF pathway network targeted 24 important targets and 149 significant pathways. TSF might have an impact by focusing on essential objectives such as TP53, PTEN, AKT1, BCL2, BCL2L1, PINK-1, PARKIN, LC3B, and NFE2L2, along with various growth-inducing routes. Our findings demonstrated that TSF effectively repaired the structure of mitochondria in db/db mice. TSF greatly enhanced the mRNA levels of PINK-1. WB and IHC findings indicated that TSF had a notable impact on activating the PINK-1/PARKIN signaling pathway in db/db mice, significantly increasing LC3 and NRF2 expression.Conclusion: Our results indicate that TSF effectively addresses DN by activating the PINK-1/PARKIN signaling pathway and enhancing Mitochondrion structure in experimental diabetic nephropathy.Keywords: tangshen formula, diabetes nephropathy, network pharmacology, mitophagy, PINK1/Parkin pathway

Wei Li,1,&ast; Mingrui Lin,1,&ast; Jiapeng Li,2,&ast; Qihang Ding,2 Xiaoling Chen,3 Huaiyu Chen,1 Zhiqing Shen,1 Xueli Zhu1 1The People’s Hospital of Fujian Traditional Medical University, Fuzhou, Fujian, People’s Republic of China; 2Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 3Department of Infectious Disease, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiqing Shen; Xueli Zhu, Email 1191863753@qq.com; zhuxueli19840205@163.comBackground: Xijiao Dihuang decoction (XJDHT), a traditional Chinese medicine, is widely used to treat patients with sepsis. However, the mechanisms underlying the effects of XJDHT on cardiac dysfunction have yet to be fully elucidated. The present study evaluated the potential utility of XJDHT in protecting against sepsis-induced cardiac dysfunction and myocardial injury.Methods: The mice were randomly divided into 3 groups and administered Lipopolysaccharide (LPS,10 mg/kg) or equivalent saline solution (control) and treated with XJDHT (10 g/kg/day) or saline by gavage for 72 hours. XJDHT was dissolved in 0.9% sodium chloride and administered at 200 μL per mouse. Transthoracic echocardiography, RNA-seq, TUNEL assays and hematoxylin and eosin (H&E) staining of cardiac tissues were performed.Results: Treatment with XJDHT significantly enhanced myocardial function and attenuated pathological change, infiltration of inflammatory cells, levels of TNF-α, IL-1β and expression of TLR4 and NF-κB in mice with sepsis. RNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway analyses identified 531 differentially expressed genes and multiple enriched signaling pathways including the PI3K/AKT pathway. Further, XJDHT attenuated cardiac apoptosis and decreased Bax protein expression while increasing protein levels of Bcl-2, PI3K, and p-AKT in cardiac tissues of mice with sepsis.Conclusion: In summary, XJDHT improves cardiac function in a murine model of sepsis by attenuating cardiac inflammation and apoptosis via suppressing the TLR4/NF-κB pathway and activating the PI3K/AKT pathway. Keywords: XJDHT, sepsis, inflammation, apoptosis, TLR4/NF-κB, PI3K/AKT pathway

Ye Ren,1,&ast; Xiaochuan Cui,2,&ast; Xiaowen Zhu,1 Hua Guo,2 Qunyan Zhou,3 Peng Yuan,4 Haiyan Cheng,1 Wenjun Wu1 1Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 2Department of Sleep Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 3Department of Nutrition Department, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 4Department of Rehabilitation, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjun Wu, Department of Endocrinology, Wuxi People’s Hospital, No. 299, Qingyang Road, Wuxi, 214023, People’s Republic of China, Tel +86-15358008856, Email wuwenjung@163.comPurpose: The present study aimed to evaluate the efficiency of traditional anthropometric and body composition parameters in predicting apnea hypopnea index (AHI) change after weight loss.Patients and Methods: Chinese adults with overweight and obesity were included into this study containing two parts. A cross-sectional study was conducted in 137 individuals using the baseline data from two weight loss intervention trials. The second part was the weight-loss intervention study conducted in 60 overweight and obese patients with obstructive sleep apnea (OSA). All participants underwent physical examination, bioelectrical impedance analysis and overnight polysomnography. Multivariate linear regression models were used to identify the most accurate parameters to predict AHI and the mediation analysis to evaluate the mediators between weight loss and AHI reduction.Results: Waist circumference (WC), body mass index and fat mass were positively associated with AHI after adjusting multiple collinearities in the cross-sectional study. After weight-loss intervention, body weight decreased from 94.6 ± 15.3 to 88.0 ± 13.9 kg, and AHI decreased from 41.9 (13.0,66.9) to 20.7 (8.7,51.2) events/h. Among these parameters, only percentage changes in WC and AHI across the intervention were positively intercorrelated after controlling for covariates (adjusted r = 0.271, P = 0.041). The mediation analysis supported WC as a mediator between weight loss and AHI reduction (standardized indirect effect [95% CI] = 4.272[0.936,7.999]).Conclusion: Both general and abdominal obesity are of high prognostic value for OSA. WC as an easily accessible parameter mediates the effects of weight loss in decreasing OSA severity.Plain Language Summary: Current Knowledge: Obesity is a well-recognized risk factor for the development of obstructive sleep apnea (OSA), whereas weight loss has been written into the treatment guidelines for overweight and obese patients with OSA. However, the anthropometric parameters more related to OSA have not been fully clarified, and an easily acquired index is needed to predict the effect of weight loss on apnea hypopnea index (AHI) improvement.Study Impact: This study found that both general obesity and abdominal obesity were positively associated with AHI, and waist circumference mediated the effect of weight loss in improving AHI. These results provide an easily acquired index to monitor the effect of weight loss on OSA.Keywords: obesity, obstructive sleep apnea, weight loss, waist circumference, body composition

Xian Ding,1,&ast; Wenqi Liang,2,&ast; Hongjuan Xia,1,&ast; Yuee Liu,2 Shuxiong Liu,1 Xinyu Xia,1 Xiaoli Zhu,1 Yongyan Pei,3 Dewen Zhang4 1Department of Emergency, Third Affiliated Hospital of Naval Medical University, Shanghai, People’s Republic of China; 2Department of Emergency, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 3School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan, People’s Republic of China; 4Longhua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongyan Pei, School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, No. 9-13, Zhongshan Campus, No. 13, Changmingshui Avenue, Wuguishan, Zhongshan City, Guangdong Province, People’s Republic of China, Email peiyongyan@gdpu.edu.cn Dewen Zhang, Longhua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New Area, Shanghai, People’s Republic of China, Email zhangdewen120@hotmail.comBackground: Sepsis was a high mortality and great harm systemic inflammatory response syndrome caused by infection. lncRNAs were potential prognostic marker and therapeutic target. Therefore, we expect to screen and analyze lncRNAs with potential prognostic markers in sepsis.Methods: Transcriptome sequencing and limma was used to screen dysregulated RNAs. Key RNAs were screened by correlation analysis, lncRNA-mRNA co-expression and weighted gene co-expression network analysis. Immune infiltration, gene set enrichment analysis and gene set variation analysis were used to analyze the immune correlation. Kaplan–Meier curve, receiver operator characteristic curve, Cox regression analysis and nomogram were used to analyze the correlation between key RNAs and prognosis. Sepsis model was established by lipopolysaccharide-induced HUVECs injury, and then cell viability and migration ability were detected by cell counting kit-8 and wound healing assay. The levels of apoptosis-related proteins and inflammatory cytokines were detected by RT-qPCR and Western blot. Reactive Oxygen Species and superoxide dismutase were detected by commercial kit.Results: Fourteen key differentially expressed lncRNAs and 663 key differentially expressed genes were obtained. And these lncRNAs were closely related to immune cells, especially T cell activation, immune response and inflammation. Subsequently, Subsequently, lncRNA PRKCQ-AS1 was identified as the regulator for further investigation in sepsis. RT-qPCR results showed that PRKCQ-AS1 expression was up-regulated in clinical samples and sepsis model cells, which was an independent prognostic factor in sepsis patients. Immune correlation analysis showed that PRKCQ-AS1 was involved in the immune response and inflammatory process of sepsis. Cell function tests confirmed that PRKCQ-AS1 could inhibit sepsis model cells viability and promote cell apoptosis, inflammatory damage and oxidative stress.Conclusion: We constructed immune-related lncRNA-mRNA regulatory networks in the progression of sepsis and confirmed that PRKCQ-AS1 is an important prognostic factor affecting the progression of sepsis and is involved in immune response.Keywords: sepsis, immune-related lncRNA, lncRNA-mRNA, PRKCQ-AS1, prognosis and progress