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Furui Zhai, Shanshan Mu, Yinghui Song, Min Zhang, Cui Zhang, Ze Lv Gynecological Clinic, Cangzhou Central Hospital, Cangzhou, Hebei, People’s Republic of ChinaCorrespondence: Furui Zhai, Gynecological Clinic, Cangzhou Central Hospital, 16 Xinhua West Road, Cangzhou, Hebei, 061001, People’s Republic of China, Email zfr860708@126.comBackground: High-grade cervical intraepithelial neoplasia (CIN2/3) is a precursor to invasive cervical cancer, necessitating effective management. While the Loop Electrosurgical Excision Procedure (LEEP) is a successful treatment, recurrence remains a significant concern. This study evaluates the predictive value of preoperative immune-inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII), in assessing the risk of residual or recurrent CIN post-LEEP.Methods: A retrospective analysis was performed on 423 women who underwent LEEP for CIN2/3 at Cangzhou Central Hospital between 2016 and 2020. Cox proportional hazards regression models with restricted cubic splines were used to evaluate linear and non-linear associations between immune-inflammatory indices and recurrence risk. Multivariate models were adjusted for confounding factors, and subgroup analyses were conducted to test the robustness of the associations. Threshold non-linear fitting and saturation effect analyses were also performed to identify inflection points influencing residual or recurrent disease risk.Results: Significant differences in age, menopausal status, TCT results, HPV status, degrees of CIN and margin status were observed between recurrence and non-recurrence groups. NLR demonstrated a U-shaped relationship with recurrence risk, with a threshold effect. NLR values below 3.15 were associated with a reduced recurrence risk, while higher values increased the risk. PLR and SII showed a modest protective effect below their respective thresholds.Conclusion: Systemic inflammation plays a key role in CIN recurrence following LEEP. NLR serves as a valuable prognostic marker, highlighting the potential for personalised follow-up strategies. Further research is needed to confirm these findings and elucidate the underlying mechanisms.Keywords: cervical intraepithelial neoplasia, loop electrosurgical excision procedure, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, residual disease/recurrence

Zhenkang Liang,* Zehong Chen,* Chaowei Zhang, Cui Chen, Wende Yang, Yuxuan Zhang, Hongbo Wei Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongbo Wei, Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road 600, Guangzhou, 510630, People’s Republic of China, Tel +86-020-85253000, Email weihb@mail.sysu.edu.cnPurpose: Erectile dysfunction (ED) frequently arises as a complication of pelvic surgeries, including rectal and prostate surgery, and has no definitive cure. This study explored whether mitochondria-rich microvesicles (MVs) can be used to treat ED stemming from cavernous nerve injury (CNI) and investigated its potential mechanisms.Methods: We isolated MVs and mitochondria (MT) from PC12. The apoptosis rate, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial derived reactive oxygen species (mtROS), iron content, malondialdehyde (MDA) content and endogenous antioxidant system activity of corpus cavernosum smooth muscle cells (CCSMCs) cultured with MVs and MT were detected in vitro. In vivo, twenty-four male Sprague Dawley rats were randomly divided into four groups: sham operation group and CNI group were injected with PBS, MVs and MT respectively. After fourteen days of treatment, the erectile function was measured and penile tissues were collected for histological analysis. Subsequently, inhibition of mitochondria in MV was performed to explore the mechanism of the rescue experiment.Results: The CCSMCs, PC12-MVs and PC12-MT were successfully isolated and identified. After MVs culture, apoptosis rate, ROS, mtROS, iron content and MDA content of CCSMCs were significantly decreased, while MMP and the activities of endogenous antioxidant system were increased. MVs transplantation can significantly restore erectile function and smooth muscle content in CNIED rats. The rescue experiment suggested that MVs exerted the above therapeutic effect by transferring mitochondria within it.Conclusion: MVs transplantation significantly improve erectile function in CNI ED rats. MVs may play a role in anti-OS and anti-ferroptosis at the transplant site through efficient transfer of mitochondria, providing a potential treatment vehicle for CNI ED.Keywords: cavernous nerve injury, erectile dysfunction, microvesicles, oxidative stress, ferroptosis

Jun Zhou,1,2,&ast; Liu Shi,1,2,&ast; Chuwei Tian,1,2 Yucheng Gao,1,2 Jinyu Wang,2,3 Jin Mao,2,4 Yan Li,2,4 Wenbin Fan,1,2 Xiangxu Chen,1,2 Cheng Zhang,1,2 Tian Xie,1,2 Yunfeng Rui1,2,&ast; 1Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Multidisciplinary Team for Geriatric Hip Fracture Comprehensive Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Rehabilitation, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Emergency, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunfeng Rui, Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, People’s Republic of China, Tel +86 13705182577, Email ruiyunfeng@126.comIntroduction: This study aims to assess the impacts of the Fast Access to Surgery in Emergency (FASE) strategy on (1) the workflow of multidisciplinary team (MDT) during hospitalization; (2) the clinical outcomes of geriatric femoral neck fracture (FNF) patients.Methods: A retrospective study was conducted in a single trauma center to evaluate the clinical data of geriatric FNF patients admitted through emergency from July 2017 to June 2022. The FASE strategy was implemented since Jan 1st 2020, and patients were categorized into the FASE group or the control group according to the time of admission (before/after the initiation timepoint of FASE strategy). Propensity score matching (PSM) was utilized to limit confounding bias between the two groups.Results: Finally, 344 patients were included after a one-to-one matching. The FASE strategy resulted in a slightly prolonged duration in emergency (6.02± 5.99 h vs 2.72± 4.22 h, p< 0.001) but was meanwhile associated with significant decreases in time to surgery (61.16± 38.74 h vs 92.02± 82.80 h, p< 0.001), actual surgery delay (67.18± 39.04 h vs. 94.25± 84.41 h, p< 0.001) and total length of hospital stay (10.57± 4.93 h vs 12.50± 4.73 h, p < 0.001). Besides, despite the consistency of transfusion rate between the two groups, improved blood management was achieved in the FASE group, as evidenced by a smaller drop in hemoglobin levels (− 20.49± 17.02 g/L vs − 25.28± 16.33 g/L, p = 0.013) in patients without preoperative or intraoperative transfusion. However, no significant differences were observed regarding the overall clinical outcomes such as mortality or postoperative complications.Conclusion: The Fast Access to Surgery in Emergency (FASE) for geriatric FNF patients effectively optimized the preoperative evaluation workflow, which significantly shortened time to surgery and length of hospital stay, and reduced perioperative blood loss. FASE strategy improved the surgical workflows and turnover efficiency of geriatric FNF patients, therefore could play an important role in the optimal MDT co-management for geriatric FNF patients. Keywords: femoral neck fracture, geriatric, emergency optimization, multidisciplinary management, early surgery

Lihua Yu,1,2,&ast; Chunxia Zhang,3,&ast; Jie Yang,4 Lu Li3 1Department of Pediatric Dentistry, Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin, 300041, People’s Republic of China; 2Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, 300041, People’s Republic of China; 3Tianjin Baogang Rare Earth Research Institute Co., Ltd, Tianjin, 300300, People’s Republic of China; 4Department of Stomatology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunxia Zhang, Tianjin Baogang Rare Earth Research Institute Co., Ltd, Block B, Building 5, No. 6, Huafeng Street, Huaming High-Tech Industrial Zone, Dongli District, Tianjin, 300300, People’s Republic of China, Tel +86-022-58910562, Email zcx19941002@163.comPurpose: The primary goals of endodontic therapy are to eliminate microbes and prevent reinfection. Persistent root canal infections and failure of root canal therapy are primarily attributed to the presence of bacteria, particularly E. faecalis. Chemical irrigants play a crucial role in complementing mechanical instrumentation in ensuring adequate disinfection. However, current techniques and available irrigants are limited in their ability to achieve optimal sterilization of the root canal system. In this study, we developed a novel material called La@PCDs by combining CQD-PVA and lanthanum for root canal irrigation.Methods: A one-pot hydrothermal method was used to prepare composites of lanthanum and CQD-PVA (La@PCDs). Scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy and the particle size were employed to characterize La@PCDs. ROS generation was evaluated by measuring the fluorescence intensity emitted at 525 nm from 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA). In vitro experiments were conducted to assess the effectiveness of the nanoparticles in combating Enterococcus faecalis and eradicating in situ biofilm eradication in root canal. Furthermore, cytotoxicity assessments were carried out to demonstrate the safety of La@PCDs.Results: SEM and FTIR results showed that La@PCDs were successfully prepared and exhibiting a homogeneous size distribution and irregular morphology. ROS assessment demonstrated that La@PCDs have a synergistic effect, promoting the production of a large number of ROS. This effect only occurred under acidic PH conditions. The inherent acidity in the biofilm microenvironment can act as internal stimulus. In vitro experiments revealed superior antibacterial efficiency under acidic conditions without causing significant cytotoxicity compared to the commonly used NaClO irrigant. The biosafety of La@PCDs was confirmed.Conclusion: Compared to existing materials, these nanoparticles exhibit favorable antibacterial and anti-biofilm properties, along with improved biocompatibility. These findings emphasize the potential of the integrated La@PCDs as a promising option for enhancing root canal irrigation and disinfection.Keywords: lanthanum, La, reactive oxygen species, ROS, pH-response, antimicrobial, root canal irrigation

Furui Zhai, Shanshan Mu, Yinghui Song, Min Zhang, Cui Zhang, Ze Lv Gynecological Clinic, Cangzhou Central Hospital, Cangzhou, Hebei, People’s Republic of ChinaCorrespondence: Furui Zhai, Gynecological Clinic, Cangzhou Central Hospital, 16 Xinhua West Road, Cangzhou City, Hebei Province, People’s Republic of China, Tel +86-0317-2075783, Email zfr860708@126.comPurpose: Loop electrosurgical excision procedure (LEEP) for high-grade cervical intraepithelial neoplasia (CIN) carries significant risks of recurrence and persistence. This study compares the efficacy of a random survival forest (RSF) model with that of a conventional Cox regression model for predicting residual and recurrent high-grade CIN in premenopausal women after LEEP.Methods: Data from 458 premenopausal women treated for CIN2/3 at our hospital between 2016 and 2020 were analyzed. The RSF model incorporated demographic, pathological, and treatment-related variables. Feature selection utilizing LASSO and three other algorithms was performed to enhance the RSF model, which was further compared to a Cox regression model. Model performance was assessed using area under the curve (AUC), out-of-bag (OOB) error rates, and SHAP values to interpret predictor importance.Results: The RSF model showed superior performance compared to the Cox regression model, with AUC values of 0.767– 0.901 and peak predictive performance at 36 months post-LEEP. In contrast, the highest AUC achieved by Cox regression was 0.880. The RSF model also exhibited relatively lower OOB error rates, indicating better generalizability. Moreover, SHAP value analysis identified margin status and CIN severity as the most prominent predictors that directly affected risk predictions. Lastly, an online tool providing real-time predictions in clinical settings was successfully implemented using the RSF model.Conclusion: The RSF model outperformed the traditional Cox regression model in predicting residual and recurrent high-grade CIN risks post-LEEP. This model may be a more accurate clinical tool that facilitates improved personalized care and early interventions in gynecological oncology.Keywords: cervical intraepithelial neoplasia, residual/recurrent, random survival forest, Cox regression, premenopausal women

Chong Zhang, Jianqing Xu, Ming Wang, Yue He, Yumei Wu Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yumei Wu, Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, 17 Qihelou St, Dongcheng District, Beijing, 100006, People’s Republic of China, Email wym597118@ccmu.edu.cnPurpose: The aim of this study was to explore the immune subtypes of endometrial cancer (EC) and its characteristics by immunogenes from the perspective of multidimensional genomics (multi-omics).Patients and Methods: Immune subtypes were carried out using an unsupervised non-negative matrix factorization clustering (NMF) method and their characteristics were analysed. Key genes were identified using random forest analysis. A predictive model for immune subtypes and their clinical prognosis were constructed. The relationship between immune subtypes and molecular subtypes was investigated.Results: Two immune subtypes C1 and C2 were available. C2 patients were younger, less graded, had significantly higher immune cell infiltration, immune checkpoint expression, tumor neoantigens, tumor mutation load than C1 (P< 005). S100A9, CD3D, CD3E, HLA-DRB1 and IL2RB were the key genes with significant survival outcomes. S100A9 expression was lower in C2 than C1, and IL2RB, HLA-DRB1, CD3E and CD3D expression was higher than C1 (P< 0.05). The predictive accuracy of five key genes for immune subtypes was good, with a Receiver operating characteristic of 0.941. The incidence of TP53abn type in C2 was significantly lower than that of C1, and the incidence of POLE type was significantly higher than that of C1 (P< 0.0001).Conclusion: EC can be divided into two immune subtypes based on immunogenes. Low expression of S100A9 and high expression of IL2RB, HLA-DRB1, CD3E, and CD3D suggest sensitivity to immunotherapy and a good prognosis.Keywords: endometrial cancer, immune subtype, immunotherapy, multidimensional genomic, tumor immune microenvironment

Xiaoyu Liu, Pengyun Du, Jianing Xu, Wei Wang, Chenggang Zhang School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Chenggang Zhang, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email jxs@bucm.edu.cnPurpose: This study aims to assess the therapeutic potential of combining Shen-Ling-Bai-Zhu-San (SLBZS) or prebiotics with intermittent fasting (IF) in type 2 diabetes mellitus (T2DM) mice and to investigate the synergistic effects and underlying mechanisms.Methods: Type 2 diabetic mouse models were induced using high-fat diet (HFD) and streptozotocin (STZ), followed by IF treatment. Mice were then grouped for combined therapy with different doses of SLBZS and prebiotics. Fasting blood glucose (FBG) levels, body weight variations, and oral glucose tolerance tests were assessed to elucidate metabolic alterations. The hepatic and renal parameters were evaluated to determine systemic changes in T2DM mice, while the insulin levels were quantified by ELISA to assess glucose homeostasis. Gut microbiota alterations were examined via 16S rRNA sequencing. Alterations of the genes in relevant signaling pathways were analyzed using RT-qPCR.Results: IF improved FBG, body weight, insulin levels, and other diabetes indicators. Combined IF with SLBZS or prebiotics yielded similar effects. Furthermore, it ameliorated dyslipidemia and mitigated hepatic and renal parameters in T2DM mice. Pancreatic tissue histopathology showed islet cell restoration post-intervention. IF therapy reduced the abnormally elevated GSK-3β gene expression and increased the abnormally reduced GLUT2 genes. Further analysis indicated that the combination of IF with prebiotics and high doses of SLBZS upregulated the expression of the INSR and IRS1 genes. Gut microbiota analysis revealed restored diversity and structure, with notable changes in specific bacterial families. At the family level, the contents of Akkermansiaceae and Bifidobacteriaceae were restored. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) analysis suggested metabolic pathway alterations.Conclusion: IF improved type 2 diabetic symptoms, with combined SLBZS and prebiotics showing similar effects. IF with high concentration of SLBZS and prebiotics doses upregulated the INSR and IRS1 genes and had superior effects on gut microbiota compared to IF alone.Keywords: [type 2 diabetes mellitus, intermittent fasting, prebiotics, Shen-Ling-Bai-Zhu-San]

Peiling Zhou,1 Shiyu Peng,2 Sizhe Wen,1 Qinghui Lan,1 Yingyin Zhuang,1 Xuyan Li,1 Mengliang Shi,1,3 Changzheng Zhang1 1Guangdong Provincial Key Laboratory of Development and Education for Special Needs Children & School of Educational Sciences, Lingnan Normal University, Zhanjiang, 524048, People’s Republic of China; 2Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3School of Education, South China Normal University, Guangzhou, 510631, People’s Republic of ChinaCorrespondence: Changzheng Zhang, School of Educational Sciences, Lingnan Normal University, 29 Cunjin Road, Zhanjiang, Guangdong Province, 524048, People’s Republic of China, Email neurozhang@163.com Mengliang Shi, School of Education, South China Normal University, 55 West Zhongshan Avenue, Shipai Street, Guangzhou, Guangdong Province, 510631, People’s Republic of China, Email 20240169@m.scnu.edu.cnAbstract: The cerebellum has long been implicated in the etiopathogenesis of autism spectrum disorder (ASD), and emerging evidence suggests a significant contribution by reciprocal neural circuits between the cerebellum and ventral tegmental area (VTA) in symptom expression. This review provides a concise overview of morphological and functional alterations in the cerebellum and VTA associated with ASD symptoms, primarily focusing on human studies while also integrating mechanistic insights from animal models. We propose that cerebello–VTA circuit dysfunctional is a major contributor to ASD symptoms and that these circuits are promising targets for drugs and therapeutic brain stimulation methods.Keywords: autism spectrum disorder, cerebellum, ventral tegmental area, neural circuit

Xiaoling Shang,1,&ast; Chenyue Zhang,2,&ast; Yuanyuan Lv,3,&ast; Xiaoxiao Zhang,3,&ast; Kaiyue Guo,4 Huijuan Li,3 Haiyong Wang5 1Shandong Cancer Hospital and Institute, Shandong University, Jinan, 250117, People’s Republic of China; 2Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai Medical College, Shanghai, People’s Republic of China; 3Department of Clinical Drug Research, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China; 4Department of Radiation Oncology, Qilu Hospital of Shandong University, Shandong University, Jinan, 250117, People’s Republic of China; 5Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huijuan Li, Department of Clinical Drug Research, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China, Email ywb234@126.com Haiyong Wang, Department of internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China, Tel +860531-87984777, Fax +86531-87984079, Email wanghaiyong6688@126.comBackground: Immune checkpoint inhibitors (ICIs) has prolonged survival in patients with extensive-stage small cell lung cancer (ES-SCLC) as first-line treatment. However, whether ICI rechallenge could bring survival benefit to patients with ES-SCLC following its failure as first-line treatment remains unknown. Therefore, we aim to address the issue and identify the cohort of patients that may derive such benefit.Methods: Patients with ES-SCLC from both the IMpower133 study and Shandong Cancer Hospital and Institute (shanzhong cohort) who failed first-line ICI were included. Kaplan Meier analysis was performed to compare overall survival (OS). Both univariate and multivariate Cox regression analyses were conducted to identify factors affecting survival. Tumor immune cell infiltration was evaluated by the CIBERSORT algorithm and detected by multiplex immunofluorescence (mIF).Results: A total of 125 ES-SCLC patients undergoing atezolizumab and 161 patients undergoing ICI as first-line treatment were recruited from IMpower133 and shanzhong cohort. Those receiving ICI rechallenge had a longer OS than those without in IMpower133 (P = 0.08) and shanzhong cohort (P = 0.013). In IMpower133 cohort, subgroup analyses found that patients with < 4 metastatic sites derived more survival benefit from atezolizumab (P = 0.008). For patients with ES-SCLC harboring < 4 metastatic sites, there was significant OS difference between atezolizumab versus non-atezolizumab as retreatment (P = 0.036). Moreover, for ES-SCLC patients with < 4 metastatic sites, atezolizumab improved survival compared with non-atezolizumab (hazard ratio [HR]: 0.457; 95% CI: 0.256– 0.817; P = 0.008). These findings were confirmed in shanzhong cohort. Those harboring < 4 metastatic sites had fewer M2 macrophage and more CD4 naïve T cells infiltration, which was further confirmed by mIF of ES-SCLC samples from shanzhong cohort.Conclusion: Our study provides rationale for ICI rechallenge among ES-SCLC patients with < 4 metastatic sites, suggesting beneficial outcome by reshaping TME.Keywords: extensive stage small cell lung cancer, ICI rechallenge, survival, metastatic sites, tumor microenvironment

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

Yali Liang,1,&ast; Yunxin Zhang,1,&ast; Yong Feng,2 Yuying Huang,2 Cuiling Zhang1 1Nursing Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2College of Nursing, Shanxi University of Chinese Medicine, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cuiling Zhang, Nursing Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, NO. 99, Longcheng Street, Xiaodian District, Taiyuan, 030032, People’s Republic of China, Tel +86-13753482546, Email sxbqezcl@163.comPurpose: To assess abusive supervision and organizational silence among nurses and investigate the mediating influence of psychological capital and fear.Background: Since the end of 2019, China’s National Development and Reform Commission (NDRC) department has decided to start the construction of regional medical centers in Shanxi, reducing cross-provincial and cross-regional medical care. In order to improve the overall standard of care in a hospital in a short period of time, health care leadership decision makers may adopt various effective leadership management practices to achieve the set goals and have high work pressure at the same time. In this case, abusive management may occur.Methods: A cross-sectional survey design was employed. In January -March 2024, a convenience sampling method was used to collect data from 470 nurses in a total of 5 hospitals in Shanxi province they were required to complete the questionnaires online anonymously. The chain mediation model was tested using the PROCESS macro program in the SPSS software and multiple linear regression model was used to verify the mediating effect.Results: Psychological capital and fear mediate the relationship between abusive supervision and nurses’ organizational silence, playing indirect mediating roles. Abusive supervision was positively associated with nurses’ organizational silence. Additionally, psychological capital plays a negative mediating role, accounting for 48.48% of the indirect effect, and fear plays a positive mediating role, accounting for 45.83% of the indirect effect. They form a chain intermediary, accounting for 5.69% of the indirect effect.Conclusion: Psychological capital and fear mediate the impact of abusive supervision on nurses’ organizational silence. Positive leadership training should be conducted to help reducing the level of head nurses’ abusive supervision behaviors, while also fostering actions that elevate nurses’ psychological capital levels.Keywords: Abusive supervision, Nurses’ organizational silence, psychological capital, fear, mediating effect

Yahui Yu,1,2 Buyun Dai,1 Lingkai Lin,1 Chao Zhang1,2 1School of Psychology, Jiangxi Normal University, Nanchang, Jiangxi, People’s Republic of China; 2School of Psychology, South China Normal University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Buyun Dai, School of Psychology, Jiangxi Normal University, 99 Ziyang Ave, Nanchang, Jiangxi, People’s Republic of China, Tel +86-13870055780, Email biweijianpsy@qq.comPurpose: The satisfaction of relational needs is an important indicator of the quality of interpersonal relationships, but few studies on this topic have been conducted in China. The Relational Needs Satisfaction Scale (RNSS) was developed and used in three countries.Patients and Methods: In this study, the scale was standardized. A total of 2136 Chinese adults aged 18– 30 years were recruited to complete the RNSS-Chinese (RNSS-C) and the Satisfaction with Life Scale (SWLS) online, and classical test theory and item response theory (IRT) were used to analyze the psychometric characteristics of the RNSS-C. The measurement invariance of the Chinese and Czech RNSSs was analyzed.Results: (1) The RNSS still has good reliability (Cronbach’s alpha = 0.935) and validity (CFI=0.948, TLI=0.940, RMSEA=0.049, and SRMR=0.032) in China. (2) The RNSS-C revealed differences in the perceptions of relational needs construct between the two groups (ΔCFI=0.014> 0.01).Conclusion: These findings contribute to a deeper understanding of the cultural factors that shape interpersonal relationships and satisfaction in China.Keywords: relational needs satisfaction scale, item response theory, cross culture, measurement invariance

Lili Wang,1 Le Cheng,1 Chenhui Lv,1 Jie Kou,1 Wenjuan Feng,1 Haoran Xie,1 Ruolin Yan,1 Xi Wang,1 Shuangzhi Chen,1 Xin Song,1 Lushan Xue,1 Cheng Zhang,1 Xuemin Li,2 Haifeng Zhao1,3 1Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Center for Disease Control and Prevention in Shanxi Province, Taiyuan, People’s Republic of China; 3MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education, Taiyuan, People’s Republic of ChinaCorrespondence: Haifeng Zhao, Department of Nutrition & Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China, Tel/Fax +86-351-4135046, Email haifengzao75@163.comBackground: The present study aimed to explore the association between the inflammatory potential of diet, assessed by energy-adjusted dietary inflammatory index (E-DII) and reduced rank regression (RRR)-derived inflammatory dietary pattern, and the risk for cognitive impairment (CI) in community-dwelling older adults, especially in older adults with chronic diseases and multimorbidity.Methods: A total of 549 older adults from Taiyuan city were included in the present cross-sectional study. The Chinese Version of the Mini-Mental State Examination (CMMSE) was used for the evaluation of cognitive function. E-DII score was calculated based on semi-quantitative food frequency questionnaire (FFQ). Blood samples, including interleukin (IL)-1β, interleukin (IL)-18, tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP), were tested for calculating RRR-derived inflammatory dietary pattern. Logistic regression was used to assess the association between inflammatory dietary pattern and risk of CI. In addition, patients with diabetes, hypertension, hyperlipidemia and multimorbidity were screened for further analysis among 549 older adults.Results: In those 549 older adults, adjusting for demographic characteristics and chronic disease status, there was no association between E-DII score tertile (ORT3VST1: 1.357, 95%CI:0.813~2.265, Ptrend = 0.267), RRR-derived inflammatory dietary pattern score tertile (ORT3VST1: 1.092, 95%CI:0.679~ 1.758, Ptrend = 0.737) and risk of CI. However, in older adults with diabetes and multimorbidity, the score tertile of E-DII and RRR-derived inflammatory dietary pattern were positively correlated with risk of CI in a dose-responsive manner (All Ptrend < 0.05). There is insufficient evidence to reach similar conclusion in patients with hypertension and hyperlipidemia (All Ptrend > 0.05).Conclusion: In the present study, pro-inflammatory diet contributed to the increased risk of CI in older adults with diabetes and multimorbidity. These results supplemented vital evidence for the prevention and treatment of CI in older adults with chronic diseases.Keywords: chronic diseases, multimorbidity, cognitive impairment, inflammatory dietary pattern, dietary inflammatory index, reduced rank regression

Qiang Shao,1,2,&ast; Ying Zhang,2,&ast; Zhiyuan Zhang,2 Wei Jiang,2 Yongcheng Yin,3 Yuepeng Fang,1 Ce Zhang,1 Qingfa Chen,2 Bin Ning1,2 1Cheeloo College of Medicine, Jinan Central Hospital, Shandong University, Jinan, People’s Republic of China; 2Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3School of Clinical Medicine, Shandong Second Medical University, Weifang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Ning; Qingfa Chen, Central Hospital Affiliated to Shandong First Medical University, No. 105, Jiefang Road, Jinan, Shandong, 250013, People’s Republic of China, Tel +86-18866510349, Email bning@sdfmu.edu.cn; tsingfachan@163.comBackground: Post-spinal cord injury (SCI) inflammation correlates with neurologic recovery. Through sequencing, we explored the roles of a differentially expressed circRNA in mice after SCI, circGla, on inflammation and recovery of SCI.Methods: The T8–T10 SCI model was established in C57BL6 mice. HE staining and RT-qPCR verified circGla upregulation results after injury obtained through sequencing. RNase R digestion and primer amplification experiments confirmed the circular properties of circGla. Nucleus and cytoplasm isolation experiments and FISH confirmed circGla expression in the astrocyte cytoplasm. AAV was used to establish a circGla knockdown mouse model. Behavioral tests were conducted to assess the recovery of the neurological function. The key inflammatory molecules after SCI were evaluated through MRI, RT-qPCR, and ELISA. For in vitro experiments, circGla was upregulated or knocked down in mouse astrocytes to detect its effect. The binding between miR-488 and circGla was confirmed through RIP and the dual luciferase experiment. RT-qPCR and ELISA confirmed the content correlation of the two molecules and the in vitro inflammatory function of miR-488. The binding experiment in astrocytes confirmed the binding between miR-488 and MEKK1 mRNA. Western blotting of MAPK pathway-related proteins confirmed that MEKK1 is a downstream effector for circGla and miR-488 in astrocytes.Results: Following SCI, the circular RNA circGla levels increased and it existed in the astrocyte cytoplasm. circGla knockdown reduced inflammation and improved neurological recovery in vivo. The correlation between circGla and proinflammatory factors was confirmed in vitro. circGla bound to miR-488, and the high miR-488 level was associated with the low astrocyte inflammatory state. miR-488 bound to MEKK1 mRNA, and upregulation or knockdown of circGla or miR-488 affected MAPK pathway-related protein expression.Conclusion: Following SCI, downregulation of circGla expression in astrocytes can reduce inflammatory manifestations and stimulate long-term functional recovery in mice through miR-488 and MEKK1. Keywords: non-coding RNAs, inflammation, competing endogenous RNAs, traumatic spinal cord injury, secondary injury

Xuan Li,1,2,&ast; Qiong Xiang,1,2,&ast; Haixin Cen,1,2 Zhaolin Zhai,1– 3 Tianhao Gao,1– 3 Chang Lu,1– 3 Yuke Dong,1– 3 Yujian Ye,1,2 Chenxi Zhang,4 Kaiming Zhuo,1,2 Yan Wang,5 Dengtang Liu1– 3,6,7,&ast; 1Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Clinical Center for Psychotic Disorders, National Center for Mental Disorders, Shanghai, People’s Republic of China; 3Department of Psychiatry, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 4Department of Psychiatry, Feng Xian Mental Health Center, Shanghai, People’s Republic of China; 5School of Psychology and Cognitive Science, East China Normal University, Shanghai, People’s Republic of China; 6Institute of Mental Health, Fudan University, Shanghai, People’s Republic of China; 7Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dengtang Liu, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Email liudengtang@smhc.org.cn Yan Wang, School of Psychology and Cognitive Science, East China Normal University, Shanghai, People’s Republic of China, Email wangyan@psy.ecnu.edu.cnObjective: The objective of our study was to evaluate whether intermittent theta burst stimulation(iTBS) applied to the regions with the strongest cortico-hippocampal connectivity within the lateral parietal cortical (LPC) or dorsolateral prefrontal cortical (DLPFC) areas in individuals with schizophrenia could enhance associative memory.Methods: We randomized 96 participants with schizophrenia to receive either active iTBS applied to the right DLPFC, left LPC or sham iTBS for 20 days. Clinical and cognitive assessments were performed at baseline and at the end of treatment. The primary outcome was change in associative memory. The secondary outcome was change in other cognitive functions and psychiatric symptoms.Results: In comparison to the sham group, iTBS targeting the right DLPFC or left LPC in schizophrenia did not yield significant improvements in auditory-auditory associative memory (F=1.27, p=0.294), auditory-visual associative memory (F=0.49, p=0.617), or visual-visual associative memory (F=1.094, p=0.347). Furthermore, after adjusting for variables such as education, disease duration, and negative symptoms, no significant changes were observed in any of these three memory domains.Conclusion: Although our study suggests that iTBS applied to the cortical-hippocampal did not lead to a significant change in associative memory. However, further investigation combining hippocampal-targeted iTBS with functional magnetic resonance imaging (fMRI) is warranted to elucidate the regulatory effects of iTBS on hippocampal function.Trial Registration: clinicaltrials.gov NCT03608462.Keywords: theta burst stimulation, associative memory, schizophrenia, cortical-hippocampal network

Man Huang,1,2,&ast; Yudi Jin,3,&ast; Mengyuan Wang,2 Qiang Song,4 Yanjia Fan,1 Yu Zhang,1 Cheng Tian,1 Chi Zhang,1 Shengchun Liu1 1Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Breast Center, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Central Laboratory, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengchun Liu, Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Email liushengchun1968@163.comBackground: HER2-low breast cancer represents a distinct subgroup with unique clinical characteristics and treatment challenges. Nevertheless, it remains uncertain whether there exists a distinction in δKi67 between patients with HER2-low and HER2-zero statuses, and whether the prognosis varies among patients with differing HER2 statuses and δKi67.Methods: We conducted a multi-center retrospective study to investigate the correlation between alterations in Ki67 index following NAC and the prognosis among patients with HER2-low or HER2-zero breast cancer. 3 distinct cohorts comprising patients with HER2-negative breast cancer who underwent NAC were included. Comprehensive clinicopathological data were documented, with particular emphasis on evaluating changes in Ki67 index from baseline to post-NAC. These changes were then correlated with disease-free survival (DFS) through rigorous analysis.Results: Three cohorts, comprising 403, 315, and 72 patients respectively, were finally included. The study found that δKi67 did not show significant associations with other variables and were not identified as independent risk factors for survival. Nevertheless, across the three cohorts, following NAC, HER2-low breast cancer patients with δKi67 below the cut-off value demonstrated a better prognosis compared to those with δKi67 above the cut-off value. Additionally, their prognosis was also superior to that of HER2-zero breast cancer patients with δKi67 below the cut-off value.Conclusion: Our study demonstrates that HER2-low breast cancer patients with δKi67 values below the cut-off point after NAC are associated with improved prognosis. Monitoring δKi67 index and HER2 status may help identify patients who are likely to benefit from NAC and guide personalized treatment strategies.Keywords: HER2-low breast cancer, neoadjuvant chemotherapy, Ki67 index, prognosis, survival

Chengshuai Zhang,1,2,&ast; Juan Xu,1,&ast; Tingting Dong,1 Xin Gai,1 Hongmei Zhang,1 Yuanyuan Li1 1Department of Neurorehabilitation, Sheng Li Oilfield Central Hospital, Dongying, People’s Republic of China; 2Binzhou Medical University, Binzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanyuan Li, Department of Neurorehabilitation, Shengli Oilfield Central Hospital, No. 31 Jinan Road, Dongying, 257000, People’s Republic of China, Tel +86-18562058575, Email 15754308875@163.comBackground: This study aimed to examine the blood concentrations of selected heavy metals, their corresponding pulmonary functions, and their interrelationship with university students.Methods: This prospective study, conducted from September 2019 to September 2020, encompassed 593 university students. Participants completed self-administered questionnaires regarding demographic factors and underwent lung function testing and blood mercury analysis at two distinct intervals: an initial assessment and a follow-up examination. Pulmonary function was assessed using Forced Vital Capacity, Forced Expiratory Volume in one second, and Peak Expiratory Flow. The blood concentrations of various heavy metals were determined through inductively coupled plasma mass spectrometry.Results: Notable disparities in pulmonary function emerged among university students when categorized by gender, Body Mass Index, physical activity, and seafood consumption frequency, all showing statistical significance (p< 0.05). Blood levels of Pb, Mn, Co, and Ni exhibited diverse patterns and extents of correlation with pulmonary function (p< 0.05 in each instance). Specifically, a positive correlation was observed with blood Pb levels, while Mn, Co, and Ni levels were inversely correlated with pulmonary function (p< 0.01 for both observations).Conclusion: This study uncovered significant and complex relationships between the blood concentrations of individual heavy metals and pulmonary function in university students. These findings highlight the need for further research to elucidate these associations in greater detail.Keywords: heavy metal, pulmonary function, students

Tuo Han,1,&ast; Ying Li,1,&ast; Jing Xiao,1,&ast; Hong Gong,2 Fuxue Deng,1 Wei Jiang,1 Congxia Wang,1 Fangyao Chen,3 Chunyan Zhang,1 Jie Deng,1 Yan Zhang1 1Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, People’s Republic of China; 2Department of Health Management, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, People’s Republic of China; 3Department of Epidemiology and Health Statistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Zhang; Jie Deng, Email zy1985525@126.com; jie.deng@xjtu.edu.cnBackground: Approximately 10– 20% of individuals with non-alcoholic fatty liver disease (NAFLD) are lean, and the underlying pathophysiology is not yet understood. This study aims to explore the characteristics and the diagnostic value of triglyceride-glucose index (TyG) in early diagnosis of lean NAFLD.Methods: 99 patients with lean NAFLD and 1891 healthy controls were included in the health examination. The characteristics were compared between groups. Restricted cubic spline was utilized to analyze the relationship between TyG index and the risk of lean NAFLD. Logistic regression and receiver operating curve (ROC) were applied to explore the diagnostic value of TyG index for lean NAFLD.Results: Overall, 99 (4.97%) patients had lean NAFLD. Patients with lean NAFLD have significant abnormal glycolipid metabolism and higher TyG index. Restriction cube spline analysis showed a significant dose-response relationship between the TyG index and risk of lean NAFLD. After adjusting for confounders, the relationship remained and the risk of developing lean NAFLD increased 2.99 times for per unit increase of TyG index (95% CI: 1.94, 4.67, P< 0.001). The areas under the ROC of the TyG index for lean NAFLD detection were 0.851 (0.815 to 0.886).Conclusion: The TyG index is positively associated with the risk of developing lean NAFLD and could be a useful marker for early diagnosis of lean NAFLD.Keywords: lean non-alcoholic fatty liver disease, triglyceride-glucose index, insulin resistance

Chan Zhang,1– 3,&ast; Yanhui Wang,1,3,4,&ast; Mengjie Li,1,4 Pengpeng Niu,1,2 Shuo Li,1,2 Zhuopeng Hu,5 Changhe Shi,1,2 Yusheng Li1– 3 1Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, 450000, People’s Republic of China; 2NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, Zhengzhou, Henan, People’s Republic of China; 3Henan Neurological Function Detection and Regulation Center, Zhengzhou, Henan, 450000, People’s Republic of China; 4The Academy of Medical Sciences of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 5The First Bethune Clinical Medical College of Ji Lin University, Changchun, Jilin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yusheng Li, Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, 450000, People’s Republic of China, Tel +86-18236145799, Fax +86-371-66862134, Email fccliyusheng@zzu.edu.cnBackground: Phase-amplitude coupling (PAC) between the phase of low-frequency signals and the amplitude of high-frequency activities plays many physiological roles and is involved in the pathological processed of various neurological disorders. However, how low-frequency and high-frequency neural oscillations or information synchronization activities change under chronic central hypoxia in OSA patients and whether these changes are closely associated with OSA remains largely unexplored. This study arm to elucidate the long-term consequences of OSA-related oxygen deprivation on central nervous system function.Methods: : We screened 521 patients who were clinically suspected of having OSA at our neurology and sleep centers. Through polysomnography (PSG) and other clinical examinations, 103 patients were ultimately included in the study and classified into mild, moderate, and severe OSA groups based on the severity of hypoxia determined by PSG. We utilized the phase-amplitude coupling (PAC) method to analyze the modulation index (MI) trends between different frequency bands during NREM (N1/N2/N3), REM, and wakefulness stages in OSA patients with varying severity levels. We also examined the correlation between the MI index and OSA hypoxia indices.Results: Apart from reduced N2 sleep duration and increased microarousal index, the sleep architecture remained largely unchanged among OSA patients with varying severity levels. Compared to the mild OSA group, patients with moderate and severe OSA exhibited higher MI values of PAC in the low-frequency theta phase and high-frequency beta amplitude in the frontal and occipital regions during N1 sleep and wakefulness. No significant differences in the MI of phase-amplitude coupling were observed during N2/3 and REM sleep. Moreover, the MI of phase-amplitude coupling in theta and beta bands positively correlated with hypoxia-related indices, including the apnea-hypopnea index (AHI) and oxygenation desaturation index (ODI), and the percentage of oxygen saturation below 90% (SaO2< 90%).Conclusion: OSA patients demonstrated increased MI values of theta phase and beta amplitude in the frontal and occipital regions during N1 sleep and wakefulness. This suggests that cortical coupling is prevalent and exhibits sleep-stage-specific patterns in OSA. Theta-beta PAC during N1 and wakefulness was positively correlated with hypoxia-related indices, suggesting a potential relationship between these neural oscillations and OSA severity. The present study provides new insights into the relationship between neural oscillations and respiratory hypoxia in OSA patients.Keywords: phase-amplitude coupling, PAC, modulation index, MI, obstructive sleep apnea, polysomnography, EEG

Yu Zhang,1 Hong-Hai Li,1 Min-Feng Ye,1 Wei-Wei Li,2 Chu Zhang,3 Hai-Feng Wang1 1Department of Gastrointestinal Surgery, Shaoxing People’s Hospital, Shaoxing, Zhejiang Province, 312000, People’s Republic of China; 2Department of Gastroenterology, Shaoxing People’s Hospital, Shaoxing, Zhejiang Province, 312000, People’s Republic of China; 3Department of Thoracic Surgery, Shaoxing People’s Hospital, Shaoxing, Zhejiang Province, 312000, People’s Republic of ChinaCorrespondence: Hai-Feng Wang, Department of Gastrointestinal Surgery, Shaoxing People’s Hospital, No. 568 Zhongxing North Road, Shaoxing, Zhejiang Province, 312000, People’s Republic of China, Email drwanghaifeng01@163.comBackground: Foreign body-induced cancer is a traditional way of understanding cancer development. The induction of cancers by exogenous foreign bodies has been identified in many organs. However, small bowel adenocarcinoma induced by foreign bodies has not been reported in the literature, although the incidence of small bowel adenocarcinoma is increasing globally.Case Presentation: A 70-year-old man was hospitalized for persistent right-sided abdominal pain for 3 months. Abdominal computed tomography revealed localized thickening and clustering of the small bowel wall in the right abdominal cavity. A comminuted fracture of the right 11th rib protruding into the abdominal cavity was observed, with a bone fragment located within the intestinal mass. Exploratory laparotomy was performed, and extensive adhesions were noted among the greater omentum, small bowel, mesentery, and right abdominal wall. Radical resection and lymph node dissection of the affected small bowel and appendix were performed. We also excised the rib end and repaired the abdominal wall to prevent further irritation. The patient was discharged 12 days post-surgery and follow-up assessments revealed no reported discomfort.Conclusion: We first report a case of small bowel adenocarcinoma induced by self-bone tissue, along with successful radical tumor excision and thorough foreign body removal. This case highlights the significant role of chronic inflammation in carcinogenesis.Keywords: foreign body, small bowel adenocarcinoma, chronic inflammation, rib fracture, case report

Panpan Fan,1,&ast; Pan Fu,2,3,&ast; Jing Liu,1,&ast; Chuanqing Wang,2,3 Xiaolei Zhang,1 Yixue Wang,1 Yingying Zhang,1 Ting Zhu,1 Caiyan Zhang,1 Guoping Lu,1 Gangfeng Yan,1 Members and affiliations of China Paediatric Intensive care Unit Pathogen Surveillance Network (CHIPS)Panpan Fan,1 Pan Fu,2 Jing Liu,1 Xiaolei Zhang,1 Yixue Wang,1 Yingying Zhang,1 Ting Zhu,1 Caiyan Zhang,1 Chuanqing Wang,2 Guoping Lu,1 Gangfeng Yan,1 Hong Ren,3 Juanzhen Li,3 Yucai Zhang,4 Yiping Zhou,4 Chengmei Zhang,5 Zhenjie Chen,5 Mingming Zhou,5 Zhengjiang Bai,6 Saihu Hang,6 Lili Hang,6 Hehe Chen,7 Yao Zheng,7 Qunying Chen,7 Pengwei Zhu,8 Yong Li,8 Yan Xu,8 BiZhen Zhu,9 Huixuan Shi,9 Shaoxian Hong,10 Yukun Huang,10 Meilian Huang,10 Danqun Jing,11 Wenjia Tong,11 ChengYu Zhang,11 Weiguo Yang,12 Weike Mang,12 Qing meng,12 Yibing Cheng,13 Qunqun Zhang,13 Kaijie Gao,13 Huiming Xu,14 Yuxia Li,14 Hanghai Ding,14 Xiulan Lu,15 Jiaotian Huang,15 Jianlong Liu,15 Yourong Zhu,16 Yuanyuan Chen,16 Shufang Xiao,17 Juan He,17 Li Jiang,17 Jianli Chen,18 Yi Lin,18 Jia Lei18 1Department of Pediatric Intensive Care Unit, Children’s Hospital of Fudan University, National Center for Children’s Health, Shanghai, People’s Republic of China; 2Lab of Microbiology, Department of Clinical Laboratory, Children’s Hospital of Fudan University, National Center for Children’s Health, Shanghai, People’s Republic of China; 3Nosocomial Infection Control Department, Children’s Hospital of Fudan University, National Center for Children’s Health, Shanghai, People’s Republic of China; 1Department of Pediatric Intensive Care Unit, Children’s Hospital of Fudan University, National Center for Children’s Health, Shanghai, People’s Republic of China; 2Clinical Microbiology Laboratory, Department of Nosocomial Infection Control, Children’s Hospital of Fudan University, National Center for Children’s Health, Shanghai, People’s Republic of China; 3Department of Pediatric Intensive Care Unit, Shanghai Children’s Medical Center affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Pediatric Intensive Care Unit, Shanghai Children’s Hospital affiliated to Shanghai Jiaotong University, Shanghai, People’s Republic of China; 5Department of Pediatric Intensive Care Unit, Children’s Hospital Affiliated to Zhejiang University Medical School, Hangzhou, People’s Republic of China; 6Department of Pediatric Intensive Care Unit, Children’s Hospital of Soochow University, Suzhou, People’s Republic of China; 7Department of Pediatric Intensive Care Unit, Ningbo Women and Children’s Hospital, Ningbo, People’s Republic of China; 8Department of Pediatric Intensive Care Unit, Wuxi Children’s Hospital, Wuxi, People’s Republic of China; 9Department of Pediatric Intensive Care Unit, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China; 10Department of Pediatric Intensive Care Unit, Xiamen Children’s Hospital, Xiamen, People’s Republic of China; 11Department of Pediatric Intensive Care Unit, Anhui Children’s Hospital, Hefei, People’s Republic of China; 12Department of Pediatric Intensive Care Unit, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 13Department of Pediatric Intensive Care Unit, Henan Children’s Hospital, Zhengzhou, People’s Republic of China; 14Department of Pediatric Intensive Care Unit, Kaifeng Children’s Hospital, Kaifeng, People’s Republic of China; 15Department of Pediatric Intensive Care Unit, Hunan Children’s Hospital, Changsha, People’s Republic of China; 16Department of Pediatric Intensive Care Unit, Jiangxi Provincial Children’s Hospital, Nanchang, Kunming, People’s Republic of China; 17Department of Pediatric Intensive Care Unit, Kunming Children’s Hospital, People’s Republic of China; 18Department of Pediatric Intensive Care Unit, Guiyang Children’s Hospital, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoping Lu; Gangfeng Yan, Email 13788904150@163.com; gangfeng_yan@fudan.edu.cnObjective: To investigate the characteristics and drug resistance patterns of Klebsiella pneumoniae (K. pneumoniae) infection in pediatric intensive care unit (PICU).Methods: K. pneumoniae strains from 17 domestic PICUs were analyzed for overall condition and drug resistance using WHO-NET software.Results: From 2016 to 2022, there was a linear increase in the detection rate of K. pneumoniae (P< 0.05), with a total of 2591 (9.7%) strains detected. The primary sites of K. pneumoniae detection were the respiratory tract (71.1%), blood (8.6%), and urinary tract (7.1%). K. pneumoniae’s resistance to penicillin drugs exceeded 90%, and are over 50% to cephalosporins. Resistance to cefoperazone-sulbactam decreased from 51.7% to 25.7%, and ranged from 9.1% to 20.8% for ceftolozane-tazobactam. Carbapenem-resistant K. pneumoniae strains constituted 32.3%. Resistance to imipenem and meropenem have decreased to 33.8% and 40.2%, while increased to 35.2% for ertapenem. Levofloxacin and amikacin resistance rates have decreased to 25.7% and 9.1%, but remain high at 63.8% for moxifloxacin and 44.6% for ciprofloxacin. K. pneumoniae demonstrated the lowest resistance rates to polymyxin B (0.9%), tigecycline (2.2%), and polymyxin E (3.1%). No strain of K. pneumoniae was resistant to both polymyxin B and meropenem. However, some strains showed co-resistance to meropenem with other antibiotics, including tigecycline (2%), imipenem (16%), amikacin (27%), colistin (37%), and levofloxacin (41%).Conclusion: The rates of isolation and drug resistance of K. pneumoniae in PICU have significantly increased over 7 years. Careful antibiotic use, infection control strategies, and appropriate antibiotic combinations are crucial in addressing this problem.Keywords: pediatric intensive care unit, Klebsiella pneumoniae, bacterial drug resistance

Jing Yu,1,2 Yanzi Ding,1,2 Xue Zhang,1,2 Shuhong Tai,1,2 Chengwen Zhang,1,2 Cailin Liu,3 Enwu Yuan,1,2 Yitao Duan1,2 1Department of Laboratory Medicine, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China; 2Zhengzhou Key Laboratory for in vitro Diagnosis of Hypertensive Disorders of Pregnancy, Zhengzhou, Henan, 450052, People’s Republic of China; 3Department of Laboratory Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Yitao Duan; Enwu Yuan, Department of Laboratory Medicine, the Third Affiliated Hospital of Zhengzhou University, No. 7 Front Kangfu Street, Zhengzhou, Henan, 450052, People’s Republic of China, Email duanyitao@zzu.edu.cn; yuanenwu@126.comPurpose: Understanding the horizontal transfer of resistance genes, such as blaNDM-5, is pivotal in developing strategies to control the spread of resistance. In this study, we isolated two bacterial strains, Escherichia coli (designated GYB01) and Klebsiella pneumoniae (designated GYB02), from a single patient. The aim of our research is to explore the biological characteristics of these strains and to investigate the interspecies horizontal transfer of blaNDM-5.Materials and Methods: Strain identification and antimicrobial susceptibility testing were conducted using the Vitek 2 system. Both GYB01 and GYB02 were sequenced with the Illumina HiSeq platform. Bioinformatics analysis tools, including multilocus sequence typing, PlasmidFinder, ResFinder, and others, were utilized to analyze the strains. Additionally, conjugation assays and Galleria mellonella infection assays were employed to assess the strains.Results: The isolates exhibited similar antimicrobial resistance profiles and both harbored the blaNDM-5 gene within the IncFIA plasmids (pGYB01-2, 165.8 kb and pGYB02-2, 211.6 kb, respectively). These plasmids (pGYB01-2 and pGYB02-2) shared over 99% homology, suggesting a common ancestral origin. Conjugation experiments confirmed the transferability of the blaNDM-5 carrying IncFIA plasmids among Enterobacteriaceae. GYB02 possessed an iucACD-iutA gene cluster, exhibited high virulence, and tested positive in the string test.Conclusion: Our findings provide direct evidence of potential in vivo interspecies transfer of a multidrug-resistant plasmid, thus enriching our understanding of the mechanisms driving multidrug resistance (MDR) and aiding in the formulation of containment and treatment strategies.Keywords: CRE, NDM-5 carbapenemase, IncFIA plasmid, interspecies horizontal transfer

Jingyi Lu,1,&ast; Caiping Zhang,1,&ast; Suren Rao Sooranna,2,3 Zhiyan He,1 Guangzi Qi,1,4– 6 Yaqin Pang1,4– 6 1College of Public Health and Management, Youjiang Medical University for Nationalities, Baise, Guangxi, People’s Republic of China; 2Life Science and Clinical Research Center, Youjiang Medical University for Nationalities, Baise, Guangxi, People’s Republic of China; 3Department of Metabolism, Digestion and Reproduction, Imperial College London, Chelsea & Westminster Hospital, London, SW10 9NH, UK; 4Modern Industrial College of Biomedicine and Great Health, Youjiang Medical University for Nationalities, Baise, Guangxi, People’s Republic of China; 5Key Laboratory of Research on Environment and Population Health in Aluminium Mining Areas (Youjiang Medical University for Nationalities), Education Department of Guangxi Zhuang Autonomous Region, Baise, Guangxi, People’s Republic of China; 6Key Laboratory of Research on Environmental Pollution and health Risk Assessment, Youjiang Medical University for Nationalities, Baise, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangzi Qi; Yaqin Pang, College of Public Health and Management, Youjiang Medical University for Nationalities, No. 98, Chengxiang Road, Baise, Guangxi, People’s Republic of China, Tel +86-0776-2846550, Fax +86-0776-2846565, Email qiguangzi@ymun.edu.com; pangyaqin@126.comObjective: To understand the current situation for social support and HPV vaccination behavior of female sex workers (FSWs) in entertainment venues and to explore the association between the support and HPV vaccination behavior.Methods: 923 FSWs in entertainment venues in a region of Guangxi were selected as survey respondents by using intentional sampling and employing a self-developed basic information questionnaire. The social support rating and the HPV vaccination behavior scales were analyzed to determine the current status of support and HPV vaccination behavior of FSWs in entertainment venues. In addition, the correlations between these parameters were analyzed.Results: The total score of social support of FSWs in entertainment venues was 35.13± 8.10, and the score for HPV vaccination behavior was 30.08± 5.73. There were significant differences between these two parameters for FSWs of different ages, monthly incomes and working hours (P < 0.05). Objective, subjective and social support were positively correlated with all dimensions of HPV vaccination behavior (r = 0.212~0.236, 0.245~0.334 and 0.113~0.152, respectively; P < 0.01 in all cases). Typical correlation analysis yielded a correlation between these three dimensions of social support as well as with two dimensions of HPV vaccination behavior (self-decision-making and self-efficacy) (r = 0.373; P < 0.01).Conclusion: Social support and HPV vaccination behavior of FSWs in entertainment venues initially low. However, as social support for FSWs was increased, their behavior towards HPV vaccination was elevated. Both subjective and objective support helped FSWs in entertainment venues their behavior to HPV vaccination and to maintain their physical and mental health.Keywords: female sex workers, social support, HPV vaccination, inoculation behavior, knowledge of HPV

Furui Zhai, Shanshan Mu, Yinghui Song, Min Zhang, Cui Zhang, Ze Lv Gynecological Clinic, Cangzhou Central Hospital, Cangzhou City, Hebei Province, People’s Republic of ChinaCorrespondence: Furui Zhai, Department of Gynecological Clinic, Cangzhou Central Hospital, 16 Xinhua West Road, Cangzhou City, Hebei Province, People’s Republic of China, Tel +86-0317-2075783, Email zfr860708@126.comPurpose: This study aims to develop a machine learning (ML) model to predict the risk of residual or recurrent high-grade cervical intraepithelial neoplasia (CIN) after loop electrosurgical excision procedure (LEEP), addressing a critical gap in personalized follow-up care.Methods: A retrospective analysis of 532 patients who underwent LEEP for high-grade CIN at Cangzhou Central Hospital (2016– 2020) was conducted. In the final analysis, 99 women (18.6%) were found to have residual or recurrent high-grade CIN (CIN2 or worse) within five years of follow-up. Four feature selection methods identified significant predictors of residual or recurrent CIN. Eight ML algorithms were evaluated using performance metrics such as AUROC, accuracy, sensitivity, specificity, PPV, NPV, F1 score, calibration curve, and decision curve analysis. Fivefold cross-validation optimized and validated the model, and SHAP analysis assessed feature importance.Results: The XGBoost algorithm demonstrated the highest predictive performance with the best AUROC. The optimized model included six key predictors: age, ThinPrep cytologic test (TCT) results, HPV classification, CIN severity, glandular involvement, and margin status. SHAP analysis identified CIN severity and margin status as the most influential predictors. An online prediction tool was developed for real-time risk assessment.Conclusion: This ML-based predictive model for post-LEEP high-grade CIN provides a significant advancement in gynecologic oncology, enhancing personalized patient care and facilitating early intervention and informed clinical decision-making.Keywords: cervical intraepithelial neoplasia, loop electrosurgical excision procedure, residual or recurrent, machine learning, predictive modeling

Hongwei Xiang,&ast; Bin Shen,&ast; Chunmei Zhang, Rui Li Department of Ultrasound, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rui Li, Email raylee7991@hospital.cqmu.edu.cnIntroduction: Cell death regulation holds a unique value in the field of cancer therapy. Recently, disulfidptosis has garnered substantial scientific attention. Previous studies have reported that sonodynamic therapy (SDT) based on reactive oxygen species (ROS) can regulate cancer cell death, achieving an limited anti-cancer effect. However, the integration of SDT with disulfidptosis as an anti-cancer strategy has not been extensively developed. In this study, we constructed an artificial membrane disulfidptosis sonosensitizer, specifically, a nanoliposome (SC@lip) coated with a combination of the chemotherapy medicine Sorafenib (Sora) and sonosensitizer Chlorin e6 (Ce6), to realize a one-stop enhanced SDT effect that induces disulfidptosis-like cancer cell death.Methods: Sorafenib and Ce6 were co-encapsulated into PEG-modified liposomes, and SC@Lip was constructed using a simple rotary evaporation phacoemulsification method. The cell phagocytosis, ROS generation ability, glutathione (GSH) depletion ability, lipid peroxidation (LPO), and disulfidptosis-like death mediated by SC@Lip under ultrasound (US) irradiation were evaluated. Based on a 4T1 subcutaneous tumor model, both the in vivo biological safety assessment and the efficacy of SDT were assessed.Results: SC@Lip exhibits high efficiency in cellular phagocytosis. After being endocytosed by 4T1 cells, abundant ROS were produced under SDT activation, and the cell survival rates were below 5%. When applied to a 4T1 subcutaneous tumor model, the enhanced SDT mediated by SC@Lip inhibited tumor growth and prolonged the survival time of mice. In vitro and in vivo experiments show that SC@Lip can enhance the SDT effect and trigger disulfidptosis-like cancer cell death, thus achieving anti-tumor efficacy both in vitro and in vivo.Conclusion: SC@Lip is a multifunctional nanoplatform with an artificial membrane, which can integrate the functions of sonosensitization and GSH depletion into a biocompatible nanoplatform, and can be used to enhance the SDT effect and promote disulfidptosis-like cancer cell death.Keywords: disulfidptosis, sonodynamic therapy, reactive oxygen species, liposomes, lipid peroxidation

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

Xiangzhi Xu,1,&ast; Yafeng Zheng,2,&ast; Xiaojing Zhang,2,&ast; Chenmei Zhang,1 Wei Gai,2 Zihao Yang1 1Department of Pediatric Intensive Care Unit, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2WillingMed Technology (Beijing) Co., Ltd, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zihao Yang, Department of Pediatric Intensive Care Unit, Children’s Hospital, Zhejiang University School of Medicine, No. 3333 Binsheng Road, Binjiang District, Hangzhou, Zhejiang, People’s Republic of China, Email 6200038@zju.edu.cn Wei Gai, Willing Med Technology (Beijing) Co., Ltd, No.156 Jinghai 4th Road, Beijing Economic and Technological Development Zone, Beijing, People’s Republic of China, Email weigai@willingmed.comPurpose: Infections cause high rates of illness and death in children worldwide. However, studies on the clinical value of metagenomic next-generation sequencing (mNGS) for immunocompromised children are still limited.Patients and Methods: From June 2021 to December 2023, 119 samples were collected at Pediatric Intensive Care Unit (PICU) of a single-center pediatric hospital and classified into two groups based on their immune states. We compared the diagnostic performance of mNGS and conventional microbiological test (CMT) for pathogen identification, and assessed the clinical impacts of mNGS.Results: Among the 119 samples, 48 (40.34%) belonged to the immunocompromised children. mNGS had a higher positivity rate than CMT (76.47% vs 55.46%, P = 0.0006). The positive percent agreement (PPA) of mNGS for immunocompromised children was higher compared to immunocompetent children (95.24% vs 77.78%). The most common pathogens for immunocompromised patients were gram-negative bacteria and herpesvirus. However, immunocompetent children showed a higher detection rate for gram-positive bacteria and respiratory viruses. Furthermore, the proportions of the positive impact of mNGS results were significantly higher in immunocompromised patients compared to immunocompetent patients for both diagnosis (91.67% vs 57.75%) and treatment (95.83% vs 64.79%) (P < 0.0001). Immunocompromised state, length of hospital stays, times stay in ICU, Pediatric Risk of Mortality (PRISM) score, neutrophil percentage (NEUT%) and the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) were considered independent factors for poor prognosis in critically ill pediatric patients.Conclusion: In patients from PICU, mNGS had a greater clinical significance in immunocompromised children compared to immunocompetent children. mNGS technology is an important auxiliary method for achieving accurate diagnosis and treatment of critically ill pediatric patients.Keywords: infectious diseases, immunocompromised, pediatrics, mNGS, clinical impact

Beibei Luo, Wenbo Xu, Dan Ye, Xuejing Bai, Mengna Wu, Chunting Zhang, Rui Shi Clinical Laboratory, People’s Hospital of Yuxi City, the Sixth Affiliated Hospital of Kunming Medical University, Yuxi City, Yunnan Province, 653100, People’s Republic of ChinaCorrespondence: Wenbo Xu, Clinical Laboratory, People’s Hospital of Yuxi City, the Sixth Affiliated Hospital of Kunming Medical University, 21 Nieer Road, Yuxi City, Yunnan Province, 653100, People’s Republic of China, Email xwb103196@sina.comIntroduction: Dyslipidemia commonly complicates type 2 diabetes mellitus, yet the relationship between glycosylated hemoglobin and blood lipid levels remains uncertain.Methods: This retrospective cross-sectional study included 27,158 participants from the People’s Hospital of Yuxi. Statistical comparisons for continuous variables utilized analysis of variance (ANOVA), while chi-square analysis was employed for categorical variables. Boxplots assessed the concentration, dispersion, and deviation of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) distribution. A linear regression analysis examined the association between HbA1c and lipid profile, complemented by a fitting curve to visualize trends.Results: Participants who developed diabetes exhibited higher age and elevated Body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, TG, LDL-C, and FPG levels compared to those without diabetes (p < 0.001). Linear regression analysis demonstrated significant associations between HbA1c values and TC, TG, LDL-C, and HDL-C (p < 0.001). The plotted curve indicated that as TC, TG, and LDL levels increased, HbA1c levels rose, while HDL levels decreased.Conclusion: HbA1c was positively correlated with TC, TG, LDL-C, and negatively correlated with HDL-C in the population in the central Yunnan Plateau.Keywords: dyslipidemia, HbA1c, lipid profile

Daniel Zhu,1,2,&ast; Paras P Shah,1,2,&ast; Charles Zhang,3 Amanda Wong,4 Michael Bouaziz,1,2 Daniel Barmas-Alamdari,1,2 Joseph Mootz,1,2 Austin Yu,5 Andrew Tirsi,1,2 Celso Tello1,2 1Department of Ophthalmology, Northwell Health Eye Institute, Great Neck, New York, 11021, USA; 2Manhattan Eye, Ear, & Throat Hospital, New York, New York, 10065, USA; 3Department of Ophthalmology, Ross Eye Institute, Jacobs School of Medicine and Biomedical Sciences, State University of New York, University at Buffalo, Buffalo, NY, 14203, USA; 4Department of Ophthalmology, New York Eye and Ear Infirmary, New York, New York, 10003, USA; 5Department of Ophthalmology, Drexel University College of Medicine, Philadelphia, PA, 19129, USA&ast;These authors contributed equally to this workCorrespondence: Daniel Zhu, Department of Ophthalmology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 600 Northern Blvd., Suite 214, Great Neck, NY, 11021, USA, Email dzhu@northwell.eduPurpose: To perform a meta-analysis and systematic review to compare the efficacy and complications of micropulse laser trabeculoplasty (MLT) and selective laser trabeculoplasty (SLT) in adult patients with open-angle glaucoma (OAG) and ocular hypertension (OHT).Methods: We performed a systematic review utilizing PubMed, Embase, and Scopus, on April 8, 2024. Meta-analyses were performed for the mean change in intraocular pressure (IOP) at one-month, six-month, and one-year follow-up visits, rate of IOP spikes (> 5 mmHg increase from the pre-procedure baseline IOP), rate of treatment failure (< 20% or < 3 mmHg reduction in IOP or requiring additional medications or procedures), and mean change in number of medications.Results: Six studies, with a total of 593 eyes, were included: 283 underwent MLT, while 310 underwent SLT. A statistically significant difference in the efficacy of MLT versus SLT at one-month and six-month follow-ups was present, with SLT reducing IOP by 0.83 mmHg (95% CI: 0.20, 1.47; P = 0.01) more and 0.55 mmHg (95% CI: 0.02, 1.08; P = 0.04) more than MLT, respectively. At the one-year follow-up, there was no significant disparity in IOP reduction between SLT and MLT (WMD = 0.16; 95% CI: − 0.40, 0.71; P = 0.58). There was a significantly lower rate of IOP spikes in the MLT treatment group (RR = 0.37; 95% CI: 0.16, 0.89; P = 0.03). There was no statistically significant difference in the rate of treatment failures (RR = 1.05; 95% CI: 0.68, 1.62; P = 0.84) or number of topical medications reduced (WMD = 0.06; 95% CI: − 0.13, 0.26; P = 0.53).Conclusion: While SLT may offer greater short-term reductions in IOP, it may be associated with more postoperative IOP spikes when compared to MLT. At one-year follow-up, there were no significant differences in IOP reduction or failure rates between the MLT and SLT groups.Keywords: trabeculoplasty, micropulse, SLT, selective laser trabeculoplasty, glaucoma

Yong-Yao Wu,1,&ast; Jun-Yuan Li,1,&ast; Qiao-Jing Xia,1 Yi-Yi Gao,1 Chao Zhang,1 Peng-Jie Xu,1 Jiang Liu,1 Hao-Jie Zhang,1 Ri-Zhen Yu2 1Department of Nephrology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang Province, 315099, People’s Republic of China; 2Urology & Nephrology Center, Department of Nephrology, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang Province, 310014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao-Jie Zhang, Department of Nephrology, Ningbo Medical Center Lihuili Hospital, No. 1111 Jiangnan Road, Yinzhou District, Ningbo City, Zhejiang Province, 315099, People’s Republic of China, Email zhang_haojie843@outlook.com Ri-Zhen Yu, Urology & Nephrology Center, Department of Nephrology, Affiliated People’s Hospital, Hangzhou Medical College, No. 158 Shangtang Road, Gongshu District, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86 571-85893889, Fax +86 571-85131448, Email rizhen_3180yu83@126.comObjective: Sarcopenia is more common in maintenance hemodialysis (MHD) patients, and the aim of this study is to analyze the risk factors associated with sarcopenia in MHD patients, along with its correlation to emotional status and quality of life.Methods: This is a cross-sectional cohort study. A total of 111 MHD patients who were treated in the Department of Nephrology of our hospital were selected as the study subjects by convenience sampling. The quality of life and emotional status were evaluated by health survey scale (SF-36), self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Regression analysis was used to explore the influencing factors of sarcopenia. Correlation analysis was used to investigate the correlation between sarcopenia and quality of life and emotional status.Results: The prevalence of sarcopenia was 59.8%. The results showed that age, gender, body mass index (BMI), dialysis time, economic status, marital status and pre-dialysis creatinine were significant factors affecting the development of sarcopenia in hemodialysis patients (p< 0.05). The SF-36 total score was significantly lower in the sarcopenia group (72.05± 12.28 vs 78.03± 10.55) than in the non-sarcopenia group, but the anxiety scale score (52.97± 4.67 vs 36.2± 3.36) and depression scale score (57.67± 4.58 vs 38.71± 3.77) were significantly higher than those in the non-sarcopenia group (p< 0.001). Correlation analysis showed that sarcopenia was positively correlated with SAS and SDS scores and negatively correlated with SF-36 total score (p < 0.05).Conclusion: The risk of sarcopenia was higher among MHD patients who were older, male, single, with a longer MHD duration, lower economic status, lower BMI, comorbid diabetes and lower levels of creatinine.Keywords: maintenance hemodialysis, sarcopenia, quality of life, risk factors, cross-sectional studies

Longyi Zheng,1,&ast; Chengjing Zhang,2,&ast; Shichang Bu,1,&ast; Wencheng Guo,3,&ast; Tongtong Li,4 Ying Xu,5 Yunan Liu,4 Caimei Yuan,4 Chengwu Feng,4 Geng Zong,4 Jingwen Zhu,4 Maoying Xing,5 Xin Geng5 1Department of Endocrinology, Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Nutrition, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, People’s Republic of China; 3Department of General Surgery and Vascular Surgery, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 4CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China; 5National Center for Liver Cancer, Naval Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Maoying Xing; Xin Geng, Email xmyxing@sina.com; gxouc@hotmail.comBackground: Neuregulin 4 (NRG4) was known to be associated with serum lipid levels and atherosclerosis. However, it is unknown whether the role of NRG4 in lipid homeostasis is causal to atherosclerosis and whether the effect is beneficial across different atherosclerosis subtypes.Methods: We investigated the causal role of the levels of serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides regulated by NRG4 in subtypes of atherosclerosis through two sample Mendelian randomization. Aggregated genome-wide association study (GWAS) summary data for serum lipid level of 1.32 million individuals with European ancestry were obtained from the Global Lipids Genetics Consortium. GWAS summary data for four atherosclerosis subtypes (peripheral, coronary, cerebral and the other atherosclerosis) were obtained from FinnGen Consortium. Generalized inverse-variance–weighted Mendelian randomization and several sensitivity analyses were used to obtain the causal estimates.Results: A 1-SD genetically elevated LDL-C level mediated by NRG4 was validated to be nominally associated with the risk of peripheral atherosclerosis (log (odds ratio)= 4.14, 95% confidence interval 0.11 to 8.17, P = 0.04), and the other associations were not significant or could not be validated by sensitivity analyses.Conclusion: LDL-C lowering mediated by NRG4 is likely to prevent peripheral atherosclerosis.Keywords: Mendelian randomization analysis, NRG4, atherosclerosis, lipid

Zhaoyong Li,1,&ast; Yanping Lin,1,&ast; Ting Qiu,2,&ast; Junsheng Liang,1 Yintao Lan,3 Fan Meng,4 Chaohao Liang,4 Yiqing Zhang,4 Qingyun Wang,1 Da Shi,1 Changli Zhang,1 Yanan Shi,1 Liujun Liu,1 Yanlan Yang,1 Jian Zhang4,5 1Department of Radiology, DongGuan Tungwah Hospital, Dongguan Key Laboratory of Radiology and Molecular Imaging, DongGuan, Guangdong, 523000, People’s Republic of China; 2Department of Radiology, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, 519000, People’s Republic of China; 3Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, 510030, People’s Republic of China; 4School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China; 5Department of Oncology, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, Guangdong, 511500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Zhang; Zhaoyong Li, Email jianzhang@gzhmu.edu.cn; lizhaoyong2003@163.comBackground: Photothermal therapy (PTT) guided by photoacoustic imaging (PAI) using nanoplatforms has emerged as a promising strategy for cancer treatment due to its efficiency and accuracy. This study aimed to develop and synthesize novel second near-infrared region (NIR-II) absorption-conjugated polymer acceptor acrylate-substituted thiadiazoloquinoxaline-diketopyrrolopyrrole polymers (PATQ-DPP) designed specifically as photothermal and imaging contrast agents for nasopharyngeal carcinoma (NPC).Methods: The PATQ-DPP nanoparticles were synthesized and characterized for their optical properties, including low optical band gaps. Their potential as PTT agents and imaging contrast agents for NPC was evaluated both in vitro and in vivo. The accumulation of nanoparticles at tumor sites was assessed post-injection, and the efficacy of PTT under near-infrared laser irradiation was investigated in a mouse model of NPC.Results: Experimental results indicated that the PATQ-DPP nanoparticles exhibited significant photoacoustic contrast enhancement and favorable PTT performance. Safety and non-toxicity evaluations confirmed the biocompatibility of these nanoparticles. In vivo studies showed that PATQ-DPP nanoparticles effectively accumulated at NPC tumor sites and demonstrated excellent tumor growth inhibition upon exposure to near-infrared laser irradiation. Notably, complete elimination of nasopharyngeal tumors was observed within 18 days following PTT.Discussion: The findings suggest that PATQ-DPP nanoparticles are a promising theranostic agent for NIR-II PAI and PTT of tumors. This innovative approach utilizing PATQ-DPP nanoparticles provides a powerful tool for the early diagnosis and precise treatment of NPC, offering a new avenue in the management of this challenging malignancy.Keywords: nasopharyngeal carcinoma, photoacoustic imaging, photothermal therapy, PATQ-DPP nanoparticles

Bohai Du,1 Tianlan Li,1 Haoqi He,1 Xun Xu,2 Chunmei Zhang,1 Xianzhu Lu,1 Yuhan Wang,1 Jingyi Cao,1 Yinghan Lu,1 Yiwa Liu,1 Shanshan Hu,1 Juxiao Li,1 Li Li,1 Ming Shi1 1Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, Guangdong Province, 523808, People’s Republic of China; 2Experimental Animal Center, Guangdong Medical University, Dongguan, Guangdong Province, 523808, People’s Republic of ChinaCorrespondence: Li Li; Ming Shi, School of Public Health, Guangdong Medical University, Dongguan, Guangdong Province, 523808, People’s Republic of China, Tel +86-15889530426 ; +86-769-22896568, Email lily2017@gdmu.edu.cn; shiming@gdmu.edu.cnIntroduction: Studies have shown that microplastics (MPs) and nanoplastics (NPs) could accumulate in the human body and pose a potential threat to human health. The purpose of this study is to evaluate the biodistribution and toxicity of MPs/NPs with different particle sizes comprehensively and thoroughly.Methods: The purpose of this study was to investigate the biodistribution and in vivo toxicity of polystyrene (PS) MPs/NPs with different sizes (50 nm, 100 nm, and 500 nm). The BALB/c mice were given 100 μL of PS50, PS100 and PS500 at the dosage of 1 mg/kg BW or 10 mg/kg BW, respectively, by gavage once a day. After 28 consecutive days of treatment, the biodistribution of differently sized PS MPs/NPs was determined through cryosection fluorescence microscopy and fluorescent microplate reader analysis, and the subsequent effects of differently sized PS MPs/NPs on histopathology, hematology and blood biochemistry were also evaluated.Results: The results showed that the three different sizes of PS MPs/NPs were distributed in the organs of mice, mainly in the liver, spleen, and intestine. At the same time, the smaller the particle size, the more they accumulate in the body and more easily penetrate the tissue. During the whole observation period, no abnormal behavior and weight change were observed. The results of H&E staining showed that no severe histopathological abnormalities were observed in the main organs in the low-dose exposure group, while. Exposure of three sizes of PS MPs/NPs could cause some changes in hematological parameters or biochemical parameters related to heart, liver, and kidney function; meanwhile, there were size- and dose-dependencies.Conclusion: The biological distribution and toxicity of plastic particles in mice were more obvious with the decrease of particle size and the increase of concentration of plastic particles. Compared with MPs, NPs were easier to enter the tissues and produce changes in liver, kidney, and heart functions. Therefore, more attention should be paid to the toxicity of NPs.Keywords: microplastics, nanoplastics, polystyrene, size, biodistribution, nanotoxicology

Yantao Yu,1– 3,&ast; Chenkai Zhang,2,3,&ast; Qiannan Sun,2– 4 Shantanu Baral,2,3 Jianyue Ding,2,3 Fanyu Zhao,2,3 Qing Yao,2,3 Shuyang Gao,2,3 Bin Liu,2– 4 Daorong Wang1– 4 1The Yangzhou School of Clinical Medicine of Dalian Medical University, Yangzhou, 225001, People’s Republic of China; 2General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou, 225001, People’s Republic of China; 3Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, 225001, People’s Republic of China; 4Northern Jiangsu People’s Hospital, Yangzhou, 225001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daorong Wang; Bin Liu, Email 18051062590@yzu.edu.cn; liubin2006cool@126.comBackground: Gastric cancer (GC) is a highly phenotypically heterogeneous disease and is caused by a combination of factors. Retinol binding protein 4 (RBP4) is a member of a family of lipid transport proteins that are involved in the transport of substances between cells and play a crucial role in a variety of cancers. However, the expression and role of RBP4 in GC remain unknown.Methods: In this study, we explored the expression, prognostic significance, immune microenvironment, drug responsiveness and function of associated signaling pathways of RBP4 in GC using web-based bioinformatics tools. Immunohistochemistry and real-time quantitative PCR were utilized to analyze the tissue and cell expression levels of RBP4. CCK-8, colony formation, EDU incorporation, wound healing and transwell assays were applied to demonstrate the effect of RBP4 on GC cell function. Flow cytometric detection of apoptosis after RBP4 knockdown. Nude mice xenograft model elucidates the role of RBP4 for GC in vivo. Related proteins of the RAS signaling pathway were analyzed by employing Western blot assays.Results: RBP4 is highly expressed in GC. RBP4 is closely associated with patient survival and sensitivity to a wide range of antitumor agents. Knockdown of RBP4 promoted apoptosis and inhibited cell proliferation, invasion and migration. RBP4 promotes GC tumorigenesis in vivo. Finally, RBP4 modulates the RAS/RAF/ERK axis.Conclusion: RBP4 may promote gastric carcinogenesis and development through the RAS/RAF/ERK axis and is expected to be a novel target for GC treatment.Keywords: RBP4, gastric cancer, invasion, migration, RAS/RAF/ERK axis

Panpan Xu,1– 3 Yu Cao,1– 3 Ruiqing Ren,1– 3 Shuai Zhang,1– 3 Cheng Zhang,1– 3 Panpan Hao,1– 3 Meng Zhang1– 3 1State Key Laboratory for Innovation and Transformation of Luobing Theory, Jinan, People’s Republic of China; 2Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Jinan, People’s Republic of China; 3Department of Cardiology, Qilu Hospital of Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Meng Zhang; Panpan Hao, Department of Cardiology, Qilu Hospital of Shandong University, No. 107, Wenhuaxi Road, Jinan, Shandong, 250012, People’s Republic of China, Email zhangmeng@sdu.edu.cn; panda.how@sdu.edu.cnPurpose: The systemic inflammation response index (SIRI) and the systemic immune inflammation index (SII) are indicators that reflect the body’s overall systemic inflammatory response. Inflammation plays an important role in the pathogenesis of in-stent restenosis (ISR). The aim of this study was to investigate the predictive value of preoperative SIRI and SII for the occurrence of ISR in patients undergoing coronary stent implantation.Materials and Methods: We retrospectively analyzed the clinical, hematological, and angiographic data of 387 patients who underwent coronary angiography for recurrent angina after coronary stent implantation at Qilu Hospital of Shandong University. Receiver operating characteristic curve (ROC) analysis was used to determine the optimal cutoff values for SIRI and SII to predict ISR. Based on the optimal cutoff values for SIRI and SII, patients were categorized into high-SIRI, low-SIRI, high-SII, and low-SII groups. Multivariate logistic regression models were constructed to assess the predictive value of SIRI and SII for ISR > 50% and ISR > 70%.Results: This study included a total of 387 patients who underwent coronary angiography and follow-up at Qilu Hospital of Shandong University. Patients in the high-SIRI group had a higher incidence of ISR than those in the low-SIRI group (ISR > 50%: 44.8% vs 30.7%, p = 0.018; ISR > 70%: 41.5% vs 4.5%, p < 0.001). In addition, ISR occurred more frequently in patients with a higher SII than in patients with a lower SII (ISR > 50%: 52.6% vs 35.7%, p = 0.001; ISR > 70%: 51.9% vs 23%, p < 0.001). In multivariate logistic regression analysis, SIRI and SII were found to be independent predictive factors for ISR, both as continuous and categorical variables. In the ROC analysis, the optimal cutoff value for SIRI was set at 0.54 (sensitivity: 84.5%, specificity: 27%), and the optimal cutoff value for SII was set at 545.29 (sensitivity: 44.1%, specificity: 71.7%).Conclusion: Elevated preoperative SIRI and SII values help predict ISR and may serve as a useful screening tool to perform interventional procedures based on the patient’s risk of ISR after stent implantation.Keywords: SIRI, SII, in-stent restenosis, percutaneous coronary intervention

Yanmeng Sun,1,2,&ast; Zheng Li,1,2,&ast; Yanfang Li,3 Chunyan Zhang,1,2 Mengyuan Wang,1,2 Wenwen Yu,1,2 Guohua Liu,2,3 Shifu Wang1,2 1Department of Microbiology Laboratory, Children’s Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Microbiology Laboratory, Shandong Provincial Clinical Research Center for Children’s Health and Disease, Jinan, Shandong, People’s Republic of China; 3Department of Neonatology, Children’s Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shifu Wang, Email wshfu709@163.comAbstract: Anaerobic bacterial meningitis is a serious infection of the central nervous system (CNS) that leads to severe neurological complications, resulting in high levels of disability and mortality worldwide. However, accurately diagnosing and isolating the responsible pathogens remains challenging due to the difficulty in culturing anaerobic bacteria, as they require harsh anaerobic culture conditions. Anaerobic bacteria have rarely been reported in meningitis, especially in children. This report details the first infant with anaerobic meningitis caused by Prevotella bivia. Additionally, we present a case of infant anaerobic meningitis caused by P. bivia, detected using metagenomics next-generation sequencing (mNGS). Our clinical experience highlights the importance of early identification of Prevotella spp. through mNGS and anaerobic culture, the effectiveness of antimicrobial medications, and the timely implementation of carefully planned precision therapeutic regimens. Furthermore, we have conducted a comprehensive review of 10 cases of Prevotella spp. infection, summarized their clinical and laboratory examination characteristics, and identified their commonalities.Keywords: Prevotella bivia, anaerobic meningitis, infant

Boye Zhang,1,2 Jianliang Man,3,4 Lingyun Guo,1 Xiaoxia Ru,1 Chengwu Zhang,1,2 Wen Liu,1,2,5 Lihong Li,1,2,5 Sufang Ma,1,2 Lixia Guo,2,4 Haojiang Wang,1,2 Bin Wang,1,2 Haipeng Diao,1,5 Renchao Che,6,7 Lili Yan1,2,5 1School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 2Shanxi Province Brain Degenerative Diseases Precision Diagnosis and Treatment Engineering Research Center, Shanxi Medical University, Jinzhong, 030606, People’s Republic of China; 3Academy of Medical Sciences, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 4College of Pharmacy, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 5Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 6Laboratory of Advanced Materials, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Academy for Engineering &Technology, Fudan University, Shanghai, 200438, People’s Republic of China; 7Zhejiang Laboratory, Hangzhou, 311100, People’s Republic of ChinaCorrespondence: Lili Yan; Renchao Che, Email yanlili@sxmu.edu.cn; rcche@fudan.edu.cnBackground: Challenges such as poor drug selectivity, non-target reactivity, and the development of drug resistance continue to pose significant obstacles in the clinical application of cancer therapeutic drugs. To overcome the limitations of drug resistance in chemotherapy, a viable treatment strategy involves designing multifunctional nano-platforms that exploit the unique physicochemical properties of tumor microenvironment (TME).Methods: Herein, layer-by-layer nanoparticles with polyporous CuS as delivery vehicles, loaded with a sonosensitizer (tetra-(4-aminophenyl) porphyrin, TAPP) and sequentially functionalized with pH‐responsive CaCO3, targeting group hyaluronic acid (HA) were designed and synthesized for synergistic treatment involving chemodynamic therapy (CDT), sonodynamic therapy (SDT), photothermal therapy (PTT), and calcium overload. Upon cleavage in an acidic environment, CaCO3 nanoparticles released TAPP and Ca2+, with TAPP generating 1O2 under ultrasound trigger. Exposed CuS produced highly cytotoxic ·OH in response to H2O2 and also exhibited a strong PTT effect.Results: CuS@TAPP-CaCO3/HA (CTCH) delivered an enhanced ability to release more Ca2+ under acidic conditions with a pH value of 6.5, which in situ causes damage to HeLa mitochondria. In vitro and in vivo experiments both demonstrated that mitochondrial dysfunction greatly amplified the damage caused by reactive oxygen species (ROS) to tumor, which strongly confirms the synergistic effect between calcium overload and reactive oxygen therapy.Conclusion: Collectively, the development of CTCH presents a novel therapeutic strategy for tumor treatment by effectively responding to the acidic TME, thus holding significant clinical implications.Keywords: mitochondria damage, calcium overload, reactive oxygen oncotherapy, pH-responsive, synergistic treatment

Ente Li,1,2,&ast; Qingfeng Zhu,3,&ast; Ziman Lv,1,2,&ast; Songsong Xie,3 Chunju Zhang,4 Wei Li,5 Ligu Mi,1,2 Quan Liu,6 Yuanzhi Wang,1,2 Xiaobo Lu2 1Department of Basic Medicine, School of Medicine, Shihezi University, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 2Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, the Xinjiang Production and Construction Corps, Shihezi University, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 3The First Affiliated Hospital of Shihezi University Medical College, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 4Tumxuk Center for Disease Prevention and Control, Tumxuk City, Xinjiang Uygur Autonomous Region, 843806, People’s Republic of China; 5Department of Basic Medicine, School of Medicine, Tarim University, Alaer City, Xinjiang Uygur Autonomous Region, 843300, People’s Republic of China; 6Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, Key Laboratory of Zoonotic Diseases, The First Hospital of Jilin University, Changchun City, Jilin Province, 30061, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanzhi Wang; Xiaobo Lu, Email wangyuanzhi621@126.com; xjykdluxiaobo@126.comAbstract: Visceral leishmaniasis (VL), also known as kala-azar. It is characterized by prolonged intermittent fever, anemia, splenomegaly, hepatomegaly, and skin darkening. VL is primarily endemic in regions, such as Brazil, East Africa, and India. However, Northern Xinjiang, which is located in northwestern China, is considered a low-incidence area for VL, contributing to its status as a neglected infectious disease. In this report, we present a case of VL caused by Leishmania donovani that was diagnosed using metagenomic next-generation sequencing (mNGS). This case underscores the diagnostic value of mNGS, particularly in regions with low incidence of VL. Keywords: Visceral leishmaniasis, Leishmania donovani, metagenomic next-generation sequencing, northwestern China

Xiaojun Chen,1,&ast; Shushu Zuo,1,&ast; Chunhua Zhang,1 Bing Sun,1 Mengyue Zhang,1 Dandan Jiang,2 Yanyan Chen2 1School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 2National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanyan Chen; Dandan Jiang, National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, No. 270, Xueyuan West Road, Lucheng District, Wenzhou, Zhejiang, 325027, People’s Republic of China, Tel +86 13858855689 ; +86 13506649289, Email cyy@eye.ac.cn; jiangdandan@eye.ac.cnObjective: This study aims to explore the effects of eye exercises on the accommodative ability of Chinese school-aged children.Methods: This study used a convenience cluster sampling and selected 149 students from grades 2– 5 in a Wenzhou primary school to participate in the intervention in June 2022. This study involved a one-month intervention teaching eye exercises using a composite feedback model. Assessments were made at 3 and 9 months post-intervention. Data collection occurred thrice, including a baseline and two follow-ups, measuring monocular and binocular accommodative facility, monocular and binocular accommodative amplitude, CISS scale, spherical equivalent refraction, and uncorrected visual acuity. Analysis used chi-square tests and generalized estimating equations to evaluate the exercises’ effectiveness, with a significance threshold of P < 0.05.Results: 134 students completed the follow-up, including 61 females (45.52%). After teaching intervention, students showed significant improvements in the accuracy of manipulation, rhythm, acupoint location, strength effectiveness and rhythm of acupressure eye exercises (all P < 0.05), with increases of 10.37%, 13.03%, 16.96%, and 25.17%, respectively. Follow-up assessments revealed both monocular and binocular accommodative amplitude at T3 were significantly higher than at T1 and T2. Moreover, the binocular accommodative amplitude in the high-quality eye exercise group remained significantly higher than that in the low-quality group even(B=1.39,1.46, P < 0.01). Eye exercises could improve monocular and binocular accommodative amplitude in the short term(P < 0.05). High-quality eye exercises could alleviate visual fatigue (B=− 2.00--3.49, both P < 0.05). However, eye exercises did not demonstrate any advantages in affecting spherical equivalent refraction or uncorrected visual acuity (P > 0.05).Conclusion: Eye exercises can alleviate myopia-related symptoms in Chinese children aged 7 to 11 years. However, this study did not find that eye exercises effectively reduce the degree of myopia in children.Trial Registration: The original trial (Registration site: https://www.chictr.org.cn/ Registration number: ChiCTR2300070903) was retrospectively registered on 26/04/2023.Keywords: Eye exercises, myopia, accommodative facility, accommodative amplitude, visual fatigue

Jilei Li,1,&ast; Wenchao Dan,2,&ast; Chenchen Zhang,3 Nian Liu,3 Yichong Wang,1 Jixiang Liu,3 Shengsheng Zhang1 1Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China; 2Department of Dermatology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China; 3Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengsheng Zhang, Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, Tel +8613801088329, Email zhangshengsheng@bjzhongyi.comPurpose: This study aimed to delineate the molecular processes underlying the therapeutic effects of berberine on UC by employing network pharmacology tactics, molecular docking, and dynamic simulations supported by empirical validations both in vivo and in vitro.Patients and Methods: We systematically screened potential targets and relevant pathways affected by berberine for UC treatment from comprehensive databases, including GeneCards, DisGeNET, and GEO. Molecular docking and simulation protocols were used to assess the interaction stability between berberine and its principal targets. The predictions were validated using both a DSS-induced UC mouse model and a lipopolysaccharide (LPS)-stimulated NCM460 cellular inflammation model.Results: Network pharmacology analysis revealed the regulatory effect of the TLR4/NF-κB/HIF-1α pathway in the ameliorative action of berberine in UC. Docking and simulation studies predicted the high-affinity interactions of berberine with pivotal targets: TLR4, NF-κB, HIF-1α, and the HIF inhibitor KC7F2. Moreover, in vivo analyses demonstrated that berberine attenuates clinical severity, as reflected by decreased disease activity index (DAI) scores, reduced weight loss, and mitigated intestinal inflammation in DSS-challenged mice. These outcomes include suppression of the proinflammatory cytokines IL-6 and TNF-α and downregulation of TLR4/NF-κB/HIF-1α mRNA and protein levels. Correspondingly, in vitro findings indicate that berberine decreases cellular inflammatory injury and suppresses TLR4/NF-κB/HIF-1α signaling, with notable effectiveness similar to that of the HIF-1α inhibitor KC7F2.Conclusion: Through network pharmacology analysis and experimental substantiation, this study confirmed that berberine enhances UC treatment outcomes by inhibiting the TLR4/NF-κB/HIF-1α axis, thereby mitigating inflammatory reactions and improving colonic pathology. Keywords: berberine, ulcerative colitis, TLR4/NF-κB/HIF-1α, network pharmacology, molecular docking, experimental validation, inhibitor

Weiwei Guan,1,2 Congyue Zhang,1 Tongguo Miao,1 Chen Dong,1 Lu Li,1 Xiwei Yuan,1 Dandan Zhao,1 Rong Ai,1 Xiaoxiao Zhang,1 Mengjiao Sun,1 Haiyan Kang,2,&ast; Yuemin Nan1,&ast; 1Department of Traditional and Western Medical Hepatology, Hebei Medical University Third Hospital & Hebei International Joint Research Center for Liver Cancer Molecular Diagnosis, Hebei International Science and Technology Cooperation Base, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 2Department of Liver Disease, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, Hebei, 050023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuemin Nan, Department of Traditional and Western Medical Hepatology, Hebei Medical University Third Hospital & Hebei International Joint Research Center for Liver Cancer Molecular Diagnosis, Hebei International Science and Technology Cooperation Base, No. 139, Ziqiang Road, Shijiazhuang, Hebei Province, 050051, People’s Republic of China, Tel +86 18533112266, Email nanyuemin@163.com Haiyan Kang, Department of Liver Disease, The Fifth Hospital of Shijiazhuang, Hebei Medical University, No. 42, Tanan Road, Shijiazhuang, Hebei Province, 050023, People’s Republic of China, Tel +86 13315952782, Email kanghaiyan1976@126.comPurpose: Long noncoding RNAs (lncRNAs) might be closely associated with hepatocellular carcinoma (HCC) progression and could serve as diagnostic and prognostic markers. This study aimed to investigate lncRNA-based diagnostic biomarkers for hepatitis B virus (HBV)-associated HCC.Materials and Methods: High‐throughput transcriptome sequencing was conducted on the liver tissues of 15 patients with HBV-associated liver diseases (5 with chronic hepatitis B [CHB], 5 with liver cirrhosis [LC], and 5 with HCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze lncRNA expressions. Potential diagnostic performance for HBV-associated HCC screening was evaluated.Results: Through trend analysis and functional analysis, we found that 8 lncRNAs were gradually upregulated and 1 lncRNA was progressively downregulated by regulation of target mRNAs and downstream HCC-associated signaling pathways. The validation of dysregulated lncRNAs in peripheral blood mononuclear cells (PBMCs) and HCC tissues by qRT-PCR revealed that ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were significantly increased in HCC compared with CHB and cirrhosis. Moreover, differentially expressed lncRNAs were aberrantly elevated in Huh7, Hep3B, HepG2, and HepG2.215 cells compared with LX2 cells. Furthermore, ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were identified as novel biomarkers for HBV-associated HCC. For distinguishing HCC from CHB, ADAMTSL4-AS1, AC067931, and SOCS2-AS1 combined with alpha-fetoprotein (AFP) had an area under the curve (AUC) of 0.945 (sensitivity, 83.9%; specificity, 89.8%). Similarly, for distinguishing HCC from LC, this combination had an AUC of 0.871 (sensitivity, 91.1%; specificity, 68.2%). Furthermore, this combination showed the highest diagnostic ability to distinguish HCC from CHB and LC (AUC, 0.905; sensitivity, 91.1%; specificity, 75.3%). In particular, this combination identified AFP-negative (AFP < 20 ng/mL) (AUC = 0.814), small (AUC = 0.909), and early stage (AUC = 0.863) tumors.Conclusion: ADAMTSL4-AS1, SOCS2-AS1, and AC067931 combined with AFP in PBMCs may serve as a noninvasive diagnostic biomarker for HBV-associated HCC, especially AFP-negative, small, and early stage HCC.Keywords: ADAMTSL4-AS1, AC067931, SOCS2-AS1, HBV-associated HCC, diagnostic biomarkers

Chenyu Zhang,1,2,&ast; Yalan Li,1,&ast; Wo Wang,1 Zhenghao Jiang,1 Chuan Liu,1 Yiting Kong,2 Daqi Li,1 Liuyi Ran,1 Li Kuang1,2 1Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, People’s Republic of China; 2Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liuyi Ran; Li Kuang, Mental Health Center, University-Town Hospital of Chongqing Medical University, Shapingba District, Chongqing, 401331, People’s Republic of China, Tel/Fax +86-023-65714061, Email ranliuyi@163.com; kuangli0308@163.comPurpose: The aim of our study was to explore the relation between serum levels of non-enzymatic antioxidants, thyroid function with the risk of non-suicidal self-injury (NSSI) in depressed adolescents.Patients and Methods: We retrospected the electronic records of 454 hospitalized patients aged 13– 17 years old with a diagnosis of major depressive disorder (239 patients with NSSI and 215 subjects without NSSI), and collected their demographic and clinical information, including serum levels of total bilirubin (Tbil), uric acid (UA), free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH).Results: The incidence of NSSI was 52.6% among depressed adolescents aged 13– 17, 57.1% in female and 38.5% in male. After using the propensity scoring method to exclude the influence of age between the two groups, it was found that patients with NSSI showed lower levels of Tbil (P=0.046) and UA (P=0.015) compared with those without NSSI. Logistic regression results showed that serum UA was associated with NSSI behavior in female patients (OR=0.995, 95% CI: 0.991– 0.999, P=0.014), and TSH was associated with NSSI in male participants (OR=0.499, 95% CI: 0.267– 0.932, P=0.029).Conclusion: Female and male may have different pathological mechanisms of NSSI. NSSI is more likely to be related to antioxidant reaction in female adolescent patients, while more likely to be related to thyroid function in male depressed adolescent patients.Keywords: antioxidant system, depressed adolescents, incidence, non-suicidal self-injury, thyroid function

Liwei Sun,1,&ast; Hailong Bing,1,&ast; Chenxi Zhang,1,&ast; Lin Lin,2 Hongkai Lian,2 Qinjun Chu,1 Xiaogao Jin1,3 1Department of Anesthesiology and Perioperative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, People’s Republic of China; 2Research of Trauma Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450007, People’s Republic of China; 3Department of Anesthesiology, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaogao Jin; Liwei Sun, Email jinxiaoagao@zzu.edu.cn; sunliwei2972@163.comObjective: Insulin attaches insulin receptor to activate the PI3-kinase/Akt signaling to maintain glucose homeostasis and inhibit apoptosis. This study determined whether preconditioning with insulin and glucose protects the kidney against ischemia-reperfusion injury (IRI).Methods: Kidney IRI was performed in C57BL/6 mice by clamping the renal vessels for 30 min, followed by reperfusion for 24 h. A total subcutaneous 0.1 unit of insulin along with 10% glucose in drinking water was treated on the mice for 24 h before kidney IRI. The kidney function and injuries were investigated through the determination of BUN and Cr in blood plasma, as well as the apoptosis and the expression of P-AKT, BAX, and caspase-3 in the kidneys. The role of P-AKT in insulin-treated IRI kidneys was tested using an AKT inhibitor. The effects of the preconditional duration of insulin and glucose on IRI kidneys were investigated by expanding the treatment duration to 1, 3, and 6 days.Results: Preconditioning with insulin and glucose protected the kidney against IRI as manifested by a decrease in creatinine and BUN and a reduction of kidney tubular injury. The protection effect was mediated by P-AKT-BAX-caspase-3 signaling pathway resulting in suppression of apoptotic cell death. An AKT inhibitor partially reversed the protective effects of preconditional insulin. The preconditional duration for 1, 3, and 6 days had no differences in improving kidney functions and pathology.Conclusion: A short-term preconditioning with insulin and glucose protected the kidney from IRI through the activation of p-AKT and subsequent reduction of BAX-caspase-3-induced apoptosis. The short-term precondition provides a practicable strategy for protecting the kidney against predictable IRI, such as kidney transplant and major surgical operations with high risk of hypotension.Keywords: kidney, insulin, ischemia-reperfusion injury, AKT, Bax, caspase-3

Jiawen Zhang,1,&ast; Duoduo Gu,2,&ast; Yang Yan,3,&ast; Ruoxin Pan,2 Hui Zhong,4,5 Chengfeng Zhang,1 Yang Xu2 1Department of Dermatology, Huashan Hospital of Fudan University, Shanghai, People’s Republic of China; 2Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Cardiology, Ren Ji Hospital of Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People’s Republic of China; 5School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengfeng Zhang; Yang Xu, Email e3dangdang@hotmail.com; yangxu@njmu.edu.cnAbstract: Rosacea is a chronic inflammatory skin disease that affects a patient’s appearance and quality of life. It mainly affects the midface region and presents as erythema, flushing, telangiectasia, papules, pustules, and rhinophyma. Despite its prevalence, the precise pathophysiology of rosacea remains unknown, and novel pharmacological therapies are currently under investigation. Tranexamic acid (TA) is a synthetic, lysine-like compound that competitively inhibits fibrinogen production by synthesizing fibrinolytic enzymes. In addition to its popular application in hemorrhage treatment, TA has been used to manage a number of skin conditions, including melasma, chronic urticaria, and angioedema. TA is a better option for melasma treatment. However, the role of TA in treating rosacea has not yet been systematically elucidated. In this study, we reviewed all available literature on the use of TA for rosacea treatment. The included articles examined the therapeutic effects of TA in patients with rosacea, including traditional methods such as oral and topical administration and more novel approaches such as intradermal injections, microneedling, and laser-assisted delivery. Several recent clinical studies demonstrated that TA alleviates rosacea symptoms by restoring the permeability barrier, ameliorating the immune reaction, and inhibiting angiogenesis. In this review, we summarized the function and potential application of TA in rosacea treatment, aiming to facilitate the implementation of clinical applications.Keywords: rosacea, tranexamic acid, topical, oral, microinjection

Cunxin Zhang,1,&ast; Qian Wang,1,&ast; Kang Li,1 Maoqing Fu,1 Kai Gao,2 Chaoliang Lv1 1Department of Spine Surgery, Jining No. 1 People’s Hospital, Jining, 272011, People’s Republic of China; 2Department of Orthopaedics, Jining No. 1 People’s Hospital, Jining, 272011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaoliang Lv, Department of Spine Surgery, Jining No. 1 People’s Hospital, No. 6 Healthy Road, Rencheng District, Jining, 272011, People’s Republic of China, Tel +86 15265775628, Fax +86-0537- 2253252, Email lvchaolianggk@163.com Kai Gao, Department of Orthopaedics, Jining No. 1 People’s Hospital, Jining, No. 6 Healthy Road, Rencheng District, Jining, 272011, People’s Republic of China, Tel +86 15853760330, Fax +86-0537- 2253252, Email gaohaikai88@126.comBackground: Intervertebral disc degeneration (IDD) underlies the pathogenesis of degenerative diseases of the spine; however, its exact molecular mechanism is unclear.Purpose: To explore the molecular mechanism of mechanical pressure (MP)-induced IDD and to assess the role and mechanism of Rosuvastatin (RSV) inhibits MP-induced IDD.Methods: SD rat nucleus pulposus cells (NPCs) were cultured in vitro and an apoptosis model of NPCs was constructed using MP. Proliferative activity, reactive oxygen species content, apoptosis, and wound healing were detected in each group of NPCs, respectively. The expression of relevant proteins was detected by qPCR and Western Blot techniques. 18 SD rats were randomly divided into control, pressure and RSV groups. Elisa, qPCR, Western Blot and immunohistochemical staining techniques were used to detect changes in the content of related proteins in the intervertebral discs of each group. HE staining and Modified Saffron-O and Fast Green Stain Kit were used to assess IDD in each group.Results: MP treatment at 1.0 MPa could significantly induce apoptosis of NPCs after 24 h. MP could significantly inhibit the proliferative activity and wound healing ability of NPCs, and increase the intracellular reactive oxygen species content and apoptosis rate; pretreatment with RSV could significantly activate the Nrf2/HO-1 signaling pathway and reverse the cellular damage caused by MP; when inhibit the Nrf2/HO-1 signaling pathway activation, the protective effect of RSV was reversed. In vivo MP could significantly increase the content of inflammatory factors within the IVD and promote the degradation of extracellular matrix, leading to IDD. When the intervention of RSV was employed, it could significantly activate the Nrf2/HO-1 signaling pathway and improve the above results.Conclusion: RSV may inhibit MP-induced NPCs damage and IDD by activating the Nrf2/HO-1 signaling pathway.Keywords: rosuvastatin, intervertebral disc, nucleus pulposus cells, oxidative stress, nuclear factor E2-related factor 2, heme oxygenase-1, quinone oxidoreductase 1

Mingyue Xu,&ast; Chunlin Zhang,&ast; Linlin Zhang, Hua Qu, Yuren Wang Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Second Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Qu; Yuren Wang, Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, the Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China, Tel +86 2368763255, Fax +86 2368755707, Email quhuahua120@163.com; 346577395@qq.comPurpose: To explore the expression of asprosin in subjects with pre-DKD and DKD and to analyze its relationship with kidney injury, inflammation, and glucose and lipid metabolism.Methods: Based on urine albumin:creatinine ratio (UACr), participants were divided into DM, pre-DKD, and DKD groups. Relevant human physiological and biochemical parameters were detected in the three groups.Results: We found relatively higher levels of asprosin in both pre-DKD and DKD groups than the DM group. Moreover, data from the Nephroseq database support increased gene expression of asprosin in kidney tissue from DKD patients. Further correlation analysis revealed that the plasma asprosin level was positively correlated with age, waist circumference, waist:hip ratio, systolic blood pressure, creatinine, UACr, triglycerides, HDL-c, fasting insulin, HOMA-IR, and the inflammatory marker G3P and negatively associated with eGFR. Multiple logistical regression analysis showed that asprosin concentration was significantly associated with pre-DKD and DKD after adjusting for sex, age, BMI, WHR, and HOMA-IR, while this correlation was lost after controlling for G3P.Conclusion: Plasma asprosin is associated with kidney injury in diabetic conditions, and this association might be connected through inflammatory response. Further studies are needed to assess the role and mechanism of asprosin in DKD.Keywords: asprosin, diabetes, diabetic kidney disease, kidney injury

Shuxiu Xiao,1,&ast; Lili Lu,1,&ast; Zhiyuan Lin,2,&ast; Xinming Ye,3 Sheng Su,3 Chenlu Zhang,4 Yang You,4 Wei Li,4 Xiaowu Huang,3 Weizhong Wu,5 Yuhong Zhou1,4 1Clinical Center for Biotherapy, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of Liver Surgery and Transplantation, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 4Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 5Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuhong Zhou; Weizhong Wu, Email zhou.yuhong@zs-hospital.sh.cn; wu.weizhong@zs-hospital.sh.cnBackground: Layilin (LAYN) represents a valuable prognostic biomarker across various tumor types, while also serving as an innovative indicator of dysfunctional or exhausted CD8+ T cells and exhibiting correlation with immune context. However, the immune function and prognostic significance of LAYN in hepatocellular carcinoma (HCC) remain unexplored. Therefore, our objective is to investigate the role of LAYN in CD8+ T cell exhaustion, clinical prognosis, and the tumor microenvironment within HCC.Methods: TIMER or GEPIA databases were used to analyze LAYN expression level and its correlation with immune infiltration in HCC. Bioinformatics analysis was conducted on TCGA and scRNA-seq cohorts. The evaluation of LAYN expression level in fresh specimens was performed through IF, IHC, and ELISA assays. Flow cytometry and mRNA-seq were employed to investigate co-expressed genes of LAYN, the LAYN+CD8+ T cell exhaustion signature and immune function. Cell proliferation ability and killing activity were assessed using CCK8 and CFSE/PI.Results: The expression level of LAYN in HCC tumors was significantly higher compared to peri-tumors. Patients with high levels of LAYN exhibited poorer OS. GO or KEGG analysis confirmed that LAYN was involved in immune response and was positively associated with CD8+ T cell immune infiltration levels. Furthermore, LAYN negatively regulated the immune function of CD8+ T cells, leading to dysfunctional phenotypes characterized by elevated levels of CD39, TIM3 and reduced levels of perforin, TNF-α, Ki-67. CFSE/PI assays demonstrated that LAYN+CD8+ T cells displayed decreased cytotoxic activity. Additionally, there was a positive correlation between LAYN and CD146 levels, which are involved in adhesion and localization processes of CD8+ T cells. Interestingly, blocking LAYN partially restored the exhaustion properties of CD8+ T cells.Conclusion: LAYN exhibits a strong correlation with immune infiltration in the TME and represents a novel biomarker for predicting clinical prognosis in HCC. Moreover, targeting LAYN may hold promise as an effective strategy for HCC immunotherapy. Keywords: hepatocellular carcinoma, layilin, CD8+ T cell exhaustion, prognosis

Wenjin Zhang,1 Qiang Song,1 Xiaofei Bi,1 Wei Cui,1 Chengmei Fang,1 Jianya Gao,1 Jinan Li,1 Xiang Wang,1 Kai Qu,1 Xian Qin,1 Xuan An,2,3 Cheng Zhang,1,3 Xianxiang Zhang,1,3 Fang Yan,4 Guicheng Wu1– 3 1Chongqing Municipality Clinical Research Center for Endocrinology and Metabolic Diseases, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China; 2Department of Hepatology, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China; 3School of Medicine, Chongqing University, Chongqing, People’s Republic of China; 4Geriatric Diseases Institute of Chengdu, Department of Geriatrics, Chengdu Fifth People’s Hospital, Chengdu, People’s Republic of ChinaCorrespondence: Guicheng Wu, Chongqing University Three Gorges Hospital, Xincheng Road 165&num;, Wanzhou District, Chongqing, 404000, People’s Republic of China, Tel +(86) 58103079, Fax +86 23 581045783, Email wuguicheng@cqu.edu.cn Fang Yan, Geriatric Diseases Institute of Chengdu, Department of Geriatrics, Chengdu Fifth People’s Hospital, Mashi Street 33&num;, Wenjiang District, Chengdu, 611130, People’s Republic of China, Tel/Fax +86 28 82661127, Email fangyan@cdutcm.edu.cnPurpose: Pueraria lobata (P. lobata), a dual-purpose food and medicine, displays limited efficacy in alcohol detoxification and liver protection, with previous research primarily focused on puerarin in its dried roots. In this study, we investigated the potential effects and mechanisms of fresh P. lobata root-derived exosome-like nanovesicles (P-ELNs) for mitigating alcoholic intoxication, promoting alcohol metabolism effects and protecting the liver in C57BL/6J mice.Methods: We isolated P-ELNs from fresh P. lobata root using differential centrifugation and characterized them via transmission electron microscopy, nanoscale particle sizing, ζ potential analysis, and biochemical assays. In Acute Alcoholism (AAI) mice pre-treated with P-ELNs, we evaluated their effects on the timing and duration of the loss of the righting reflex (LORR), liver alcohol metabolism enzymes activity, liver and serum alcohol content, and ferroptosis-related markers.Results: P-ELNs, enriched in proteins, lipids, and small RNAs, exhibited an ideal size (150.7 ± 82.8 nm) and negative surface charge (− 31 mV). Pre-treatment with 10 mg/(kg.bw) P-ELNs in both male and female mice significantly prolonged ebriety time, shortened sobriety time, enhanced acetaldehyde dehydrogenase (ALDH) activity while concurrently inhibited alcohol dehydrogenase (ADH) activity, and reduced alcohol content in the liver and serum. Notably, P-ELNs demonstrated more efficacy compared to P-ELNs supernatant fluid (abundant puerarin content), suggesting alternative active components beyond puerarin. Additionally, P-ELNs prevented ferroptosis by inhibiting the reduction of glutathione peroxidase 4 (GPX4) and reduced glutathione (GSH), and suppressing acyl-CoA synthetase long-chain family member 4 (ACSL4) elevation, thereby mitigating pathological liver lipid accumulation.Conclusion: P-ELNs exhibit distinct exosomal characteristics and effectively alleviate alcoholic intoxication, improve alcohol metabolism, suppress ferroptosis, and protect the liver from alcoholic injury. Consequently, P-ELNs hold promise as a therapeutic agent for detoxification, sobriety promotion, and prevention of alcoholic liver injury.Keywords: Pueraria lobata root-derived exosome-like nanovesicles, acute alcoholism, loss of the righting reflex, ethanol metabolism, ferroptosis

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

Tingting Shao,1 Chengwei Zhu,2 Hanning Lei,2 Yiru Jiang,3 Haitao Wang,4 Cai Zhang2 1Institute of Early Childhood Education, Faculty of Education, Beijing Normal University, Beijing, People’s Republic of China; 2Collaborative Innovation Center of Assessment for Basic Education Quality, Beijing Normal University, Beijing, People’s Republic of China; 3School of Education Science, Shangrao Normal University, Shangrao, People’s Republic of China; 4Department of education, Ocean University of China, Qingdao, People’s Republic of ChinaCorrespondence: Cai Zhang, Collaborative Innovation Center of Assessment for Basic Education Quality, Beijing Normal University, No. 19 Xinjiekouwai Street, Beijing, 100875, People’s Republic of China, Email caizhangbj@163.comPurpose: With the increasing ubiquity of smartphones in our daily lives, technoference has emerged as a novel threat to family relationships and child development. This study explored the impact of parent-child technoference on child problematic smartphone use and its underlying mechanism and potential gender difference among children.Participants and Methods: The participants were 3032 fourth-grade students (42.6% female; 80.6% one-child families; 32.9% lower income level families, 33.3% middle income level families; Mage = 10.59 years, SD=0.32) from 535 primary schools. Students in the target classes were invited to participate anonymously in the questionnaire survey in classrooms. Then, SPSS, AMOS and other software were used to analyze the data.Results: 1) Parent-child technoference, negative parenting styles and child problematic smartphone use were positively correlated with each other, while they were negatively correlated with parent-child relationship; 2) Parent-child technoference can not only directly and positively predict child problematic smartphone use, but also indirectly and positively predict child problematic smartphone use through parent-child relationship and negative parenting styles respectively; 3) Parent-child relationship and negative parenting styles play a chain mediating role between parent-child technoference and child problematic smartphone use; 4) There are significant gender differences in the chain mediation model.Conclusion: The results showed that parent-child technoference significantly affected child problematic smartphone use through a chain mediation of parent-child relationship and negative parenting styles. Gender differences were observed, with girls experiencing a more pronounced disruption in the parent-child relationship, while boys were more likely to develop problematic smartphone use. In cases of strained parent-child relationships due to technoference, girls also tended to perceive more negative parenting styles. These findings promote parents’ understanding of the influencing factors and mechanisms of child problematic smartphone use, especially helpful for follow-up measures to prevent and intervene child problematic smartphone use from the perspective of families and parents.Keywords: parent-child technoference, parent-child relationship, negative parenting styles, child problematic smartphone use, gender difference