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Yaping Shen,1,2,* Yijiu Wu,3,* Hai Zhuang,4 Zhumei Chen,5 Qiong Zhang,5 Peixin Li,5 Jing Wang,3 Zhi Huang,1 Qingfan Zeng3,5 1Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550002, People’s Republic of China; 2Department of Interventional Radiology, The Baiyun Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, 550014, People’s Republic of China; 3College of Anesthesiology, Guizhou Medical University, Guiyang, 550002, People’s Republic of China; 4Department of Infectious, The Baiyun Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, 550014, People’s Republic of China; 5Department of Anesthesiology, The Baiyun Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, 550014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhi Huang, Department of interventional radiology, the Affiliated Hospital of Guizhou Medical University, Guiyang, 550002, People’s Republic of China, Email huangzhi@gmc.edu.cn Qingfan Zeng, Department of Anesthesiology, The Baiyun Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, 550014, People’s Republic of China, Email 445483296@qq.comBackground: Isoflurane, as an anesthetic drug, has a neurotoxic effect on the developing brain tissue. Compound 21 (C21) has been reported to be neuroprotective and ameliorate stroke effects. However, the mechanism by which C21 protects against nerve damage remains unclear.Methods: Animal and cellular models of brain injury were constructed using isoflurane (ISO) in neonatal SD rats and primary rat neuronal cells (PRNCs). After treatment with C21, the ultrastructure and morphology of the hippocampus in the model rats were assessed using the transmission electron microscope and H&E staining. Methylation or apoptosis-related genes or proteins were examined using immunohistochemistry, RT-qPCR, and Western blot. The levels of inflammatory factors were monitored using the ELISA kits. m6A modification was analyzed by Dot blot and MeRIP-qPCR. Cell proliferation and apoptosis were also tested using Edu and TUNEL staining.Results: C21 suppresses apoptosis and inflammation and improves hippocampal morphology in ISO-induced neonatal rats. Mechanistically, C21 upregulates m6A modification, PPAR-a, BCL-2, and METTL3 in ISO-induced neonatal rats and ISO-treated PRNCs. C21 promotes cell proliferation, enhances BCL-2 m6A modification, and reduces inflammation by upregulating METTL3 by upregulating METTL3 in ISO-treated PRNCs.Conclusion: These findings suggest that C21 enhances neuronal cell survival and morphology and up-regulates methylation and Bc1-2 levels, potentially offering a therapeutic strategy for neuroprotection in clinical settings, particularly in cases of neurotoxic exposure. The mechanism may be related to the upregulation of METTL3. Keywords: compound 21, isoflurane, METTL3, anesthesia, neuron

Yi Xiao,1,2,* Shiyan Yang,2,3,* Yang Sun,2,* Robert L Sah,4,5 Jincheng Wang,2 Chunshan Han1 1Thoracic Surgery Department, The China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China; 2Orthopedic Medical Center, the Second Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China; 3Department of Head and Neck, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China; 4Department of Bioengineering, University of California–San Diego, La Jolla, CA, 92037, USA; 5Center for Musculoskeletal Research, Institute of Engineering in Medicine, University of California–San Diego, La Jolla, CA, 92037, USA*These authors contributed equally to this workCorrespondence: Chunshan Han, Thoracic Surgery Department, the China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China, Email hancs@jlu.edu.cnAbstract: Nanoscale morphologies on the surface of substrates/scaffolds have gained considerable attention in cartilage tissue engineering for their potential to improve chondrogenic differentiation and cartilage regeneration outcomes by mimicking the topographical and biophysical properties of the extracellular matrix (ECM). To evaluate the influence of nanoscale surface morphologies on chondrogenic differentiation of stem cells and discuss available strategies, we systematically searched evidence according to the PRISMA guidelines on PubMed, Embase, Web of Science, and Cochrane (until April 2024) and registered on the OSF (osf.io/3kvdb). The inclusion criteria were (in vitro) studies reporting the chondrogenic differentiation outcomes of nanoscale morphologies on the surface of substrates/scaffolds. The risk of bias (RoB) was assessed using the JBI-adapted quasi-experimental study assessment tool. Out of 1530 retrieved articles, 14 studies met the inclusion criteria. The evidence suggests that nanoholes, nanogrills, nanoparticles with a diameter of 10– 40nm, nanotubes with a diameter of 70– 100nm, nanopillars with a height of 127– 330nm, and hexagonal nanostructures with a periodicity of 302– 733nm on the surface of substrates/scaffolds result in better cell adhesion, growth, and chondrogenic differentiation of stem cells compared to the smooth/unpatterned ones through increasing integrin expression. Large nanoparticles with 300– 1200nm diameter promote pre-chondrogenic cellular aggregation. The synergistic effects of the surface nanoscale topography and other environmental physical characteristics, such as matrix stiffness, also play important in the chondrogenic differentiation of stem cells. The RoB was low in 86% (12/14) of studies and high in 14% (2/14). Our study demonstrates that nanomorphologies with specific controlled properties engineered on the surface of substrates/scaffolds enhance stem cells’ chondrogenic differentiation, which may benefit cartilage regeneration. However, given the variability in experimental designs and lack of reporting across studies, the results should be interpreted with caution.Keywords: nanomorphology, surface engineering, chondrogenesis, stem cell, cartilage regeneration

Xudong Wang,1– 3,* Zhiyong Li,1,* Jianhong Xu,1 Jun Wang,1 Ying Li,1 Qiang Li,4 Jianrong Niu,5 Rongya Yang2 1Outpatient Department of Yangfangdian, Southern Medical District of Chinese PLA General Hospital, Beijing, 100843, People’s Republic of China; 2Department of Dermatology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100010, People’s Republic of China; 3Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 4Medical Health Care Dept, Air Force Medical Center PLA, Beijing, 100142, People’s Republic of China; 5Department of Dermatology, Air Force Medical Center PLA, Beijing, 100142, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rongya Yang, Department of Dermatology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100010, People’s Republic of China, Email yangrya@sina.com Qiang Li, Medical Health Care Department, Air Force Medical Center PLA, Beijing, 100142, People’s Republic of China, Email 16585260@qq.comPurpose: Heat shock protein A4 (HSPA4) is associated with a variety of human diseases. However, its function in cutaneous malignant melanoma (CMM) remains uncertain.Patients and Methods: The gene and protein expression level of HSPA4 in CMM was investigated with public databases. Cell Counting Kit-8 (CCK8) assay was performed to assess the effect of HSPA4 on the proliferation of melanoma cells. Then, the diagnostic and prognostic value of HSPA4 in CMM were analyzed. Gene variations and methylation levels, and the correlation between HSPA4 expression and immune cell infiltration were evaluated, followed by the construction of HSPA4 related protein-protein interaction networks and functional enrichment analysis.Results: The mRNA and protein expression level of HSPA4 was significantly higher in CMM. Knocking down HSPA4 in A-375 cell line could inhibit tumor cell growth. The receiver operating characteristic (ROC) curve analysis confirmed the diagnostic value of HSPA4. Survival analysis showed that high expression of HSPA4 was associated with poor prognosis. HSPA4 gene alterations were observed in 3% of CMM patients. Five CpG sites are associated with the prognosis of CMM. HSPA4 is negatively correlated with most immune cells in CMM. The protein interaction network shows that HSPA4 is closely related to proteins such as DnaJ heat shock protein family (Hsp40) member B1 (DNAJB1) and DnaJ heat shock protein family (Hsp40) member B6 (DNAJB6), and the expression of DNAJB1 is positively correlated with HSPA4. Functional enrichment analysis indicated that HSPA4 may be associated with immune suppression and immune escape within the tumor microenvironment of CMM.Conclusion: HSPA4 may participate in the regulation of tumor development and microenvironment, which may be a potential diagnostic and prognostic marker of CMM.Keywords: heat shock protein, melanoma, HSPA4, TCGA, bioinformatics

Na Li,1,* Xinyao Zhang,1,* Yi Zheng,1 Qingchuan Liu,2 Sifang Niu,3 Yan Qin,4 Ying Zhang,5 Yan Liu,6 Jianli Wang7 1School of Mental Health, Jining Medical University, Jining, 272013, People’s Republic of China; 2School of Communication, East China Normal University, Shanghai, 200241, People’s Republic of China; 3School of Public Health, Binzhou Medical University, Yantai, 264003, People’s Republic of China; 4School of Public Health, Shandong First Medical University, Jinan, 250117, People’s Republic of China; 5School of Public Health, University of Sydney, Sydney, NSW, 2006, Australia; 6School of Public Health, Jining Medical University, Jining, 272013, People’s Republic of China; 7Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, B2N 5E3, Canada*These authors contributed equally to this workCorrespondence: Jianli Wang, Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, B2N 5E3, Canada, Email jianli.wang@dal.ca Yan Liu, School of Public Health, Jining Medical University, Jining, 272013, People’s Republic of China, Email hakunaly@163.comBackground: Perfectionism is a pivotal factor in the etiology and prognosis of major depression. Nevertheless, there is a scarcity of longitudinal research examining the association between perfectionism and major depressive disorder (MDD). The objective of this study was to explore the impact of perfectionism on MDD among a cohort of first-year Chinese university students.Methods: This study employed a longitudinal design to investigate the relationship between perfectionism and MDD in a sample of first-year Chinese university students (n=8079). Socially prescribed perfectionism and almost perfectionism were measured using the Multidimensional Perfectionism Scale (MPS) and the Almost Perfect Scale-Revised (APS-R), while MDD was assessed using the Composite International Diagnostic Interview (CIDI-3.0). Random effects logistic regression modeling was utilized to estimate the associations between the variables.Results: The findings revealed that the incidence of MDD was 0.6%. Lifetime exposure to severe traumatic events (≥ 10) (OR=2.619, 95% CI: 1.502– 4.565) and almost perfectionism (OR=1.015, 95% CI: 1.004– 1.026) were identified as significant risk factors for MDD.Conclusion: It is evident that perfectionism is linked to an increased susceptibility to MDD. However, additional longitudinal studies focusing on university students are imperative to delve deeper into the influence of perfectionism on the initial manifestation of MDD.Keywords: freshmen, major depressive disorder, perfectionism, lifetime severe traumatic events

Le Hu,1– 3 Jia Wang,1– 3 Ye Zhang,1– 3 Junyu Wang,1– 3 Bing Wei1– 3 1Emergency Medical Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing, People’s Republic of China; 3Clinical Center for Medicine in Acute Infection, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Bing Wei; Junyu Wang, Email dr_weibing@126.com; wangjunyu_cyyy@126.comObjective: To evaluate and predict adverse outcomes associated with serum Syndecan-1 (SYN-1) levels in patients with early sepsis, and to explore the prognostic risk factors in sepsis and septic shock.Methods: This retrospective single-center observational study included 168 sepsis patients admitted to the Emergency Department of Beijing Chao-Yang Hospital Shijingshan Branch, Capital Medical University, from October 2020 to October 2021. Patients were categorized into sepsis (n=114) and septic shock (n=54) groups based on Sepsis 3.0 criteria. They were further divided into survival (n=128) and death (n=40) groups. Comparative analyses included general demographics and laboratory findings (SYN-1, lactic acid [LAC], procalcitonin [PCT], C-reactive protein [CRP]) within 3 hours of admission, as well as Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores. Statistical methods included receiver operating characteristic (ROC) curve analysis, correlation analysis, and logistic regression.Results: Serum SYN-1 levels were significantly higher in the septic shock group (138.89± 9.26) compared to the sepsis group (102.89± 8.97) (P < 0.05). SYN-1 levels were also significantly higher in the death group (150.19± 7.65) compared to the survival group (103.301± 86.59) (P < 0.05). The area under the ROC curves for SYN-1, LAC, and APACHE II scores in predicting 28-day mortality were 0.668, 0.641, and 0.666, respectively. SYN-1 showed a positive correlation with SOFA scores (correlation coefficient=0.228). SYN-1, APACHE II score, and LAC were identified as independent risk factors for 28-day mortality in sepsis patients.Conclusion: SYN-1 demonstrates high sensitivity and specificity in early prediction of poor outcomes in sepsis patients. SYN-1, APACHE II score, and LAC serve as independent risk factors for 28-day mortality in sepsis patients.Keywords: Syndecan-1, sepsis, septic shock

Yang Chen,1,&ast; Lijie Sun,1,&ast; Minghui Chen,1,&ast; Hui Zhang,2 Bing Song,3 Hongxiao Wang,3 Aijun Jiang,1,4 Li Zhang,5 Sumei Li,1 Jumei Wang,1 Wei Wang,1 Haoqiang Zhang1 1Department of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 2Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, People’s Republic of China; 3Department of Endocrinology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, People’s Republic of China; 4University of Science and Technology of China, Hefei, People’s Republic of China; 5ShuCheng People’s Hospital, Luan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wang; Haoqiang Zhang, Email hfww2001@ustc.edu.cn; drhqzhang@ustc.edu.cnPurpose: Our objective is to investigate the potential involvement of free triiodothyronine (FT3), a key bioactive compound found in thyroid hormones (THs) in the pathogenesis of diabetic peripheral neuropathy (DPN) in patients diagnosed with type 2 diabetes mellitus (T2DM).Patients and Methods: A total of 121 T2DM patients were recruited. And then, they were divided into the control group and the DPN group. Clinical parameters were collected for each patient. Additionally, nerve conduction velocity was tested using neurophysiological methods. Correlation and regression analyses were employed to examine the relationship between the concentrations of FT3 and DPN.Results: Compared to 57 patients without DPN, 64 patients with DPN showed increased HbA1c and low-density lipoprotein cholesterol (LDL-C) levels (P=0.001 and 0.042), as well as decreased concentrations of FT3 (P=0.042). Additionally, FT3 levels are positively associated with the motor and sensory fibers conduction velocity of the Ulnar nerve, as well as the motor conduction velocity of the Tibial nerve, with (R=0.205, P=0.025; R=0.191, P=0.038; R=0.220, p=0.016) or without (R=0.257, P=0.004; R=0.227, P=0.012; R=0.227, p=0.012) adjustment for HbA1c and LDL-C. Furthermore, multiple linear regression analysis suggests that decreased FT3 levels may influence the motor and sensory fibers conduction velocity of the Ulnar nerve (β=0.795, P=0.025 and β=0.909, P=0.038), as well as the motor conduction velocity of the Tibial nerve (β=0.727, P=0.016). Moreover, our study demonstrated that decreased FT3 levels are one of the risk factors for DPN in T2DM patients, as determined by binary logistic regression analysis (OR=0.542, P=0.022).Conclusion: Lower concentrations of FT3 are one of the risk factors for DPN in patients with T2DM. Additionally, decreased FT3 levels may influence peripheral neuropathy, particularly affecting the motor and sensory fibers conduction velocity of the ulnar nerve, as well as the motor fiber conduction velocity of the tibial nerve.Keywords: free triiodothyronine, diabetic peripheral neuropathy, type 2 diabetes mellitus, thyroid hormone, conduction velocity of nerve

Liuyi Huang,&ast; Xiaoxia Huang,&ast; Wei Zhou, Yanting Jiang, Haiqing Zhu, Yuehong Lao, Zhenjia Deng, Yuting Tang, Jian Wang, Xi Li Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Key Laboratory of Clinical Laboratory Medicine of Guangxi Department of Education, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xi Li; Jian Wang, Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Key Laboratory of Clinical Laboratory Medicine of Guangxi Department of Education, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Email cicicats@126.com; wangjian616161@163.comObjective: Idiopathic inflammatory myopathies (IIM) are classified into four subgroups: dermatomyositis (DM), anti-synthetase syndrome (ASS), immune-mediated necrotizing myopathy (IMNM), and sporadic inclusion body myositis (sIBM); however, the role of LGALS3BP in IIM remains unclear. Our study aimed to explore the ability of LGALS3BP to discriminate between the IIM subtypes. The correlation between serum LGALS3BP levels, clinical features, and inflammatory markers in patients with IIM was also assessed.Methods: Based on the Gene Expression Omnibus (GEO) database, we used bioinformatics analysis to screen for overlapping extracellular protein-differentially expressed genes between any two groups of DM, ASS, IMNM, and healthy controls (HCs). This study enrolled 84 patients with IIM and 36 HCs, and participant baseline data and laboratory parameters were recorded. Serum LGALS3BP levels were measured using an enzyme-linked immunosorbent assay (ELISA).Results: Through bioinformatics analysis, LGALS3BP was selected as a potential biomarker for the identification of DM, ASS, IMNM, and HC. LGALS3BP expression decreased sequentially in the DM, ASS, IMNM, and HC groups, with significant differences among the two groups. The ELISA results were similar to those of the bioinformatics analysis; however, the difference in serum LGALS3BP expression between DM and ASS was not statistically significant. According to the receiver operating characteristic (ROC) curve analysis, using HC as the control group, the area under the curve (AUC) values of serum LGALS3BP levels for the diagnosis of IIM, DM, and ASS were > 0.8. In addition, patients with elevated serum LGALS3BP levels had a higher prevalence of interstitial lung disease (ILD). Serum LGALS3BP levels correlated with inflammatory markers.Conclusion: LGALS3BP is differentially expressed in DM, ASS, IMNM, and HC and may assist in assessing the severity of IIM-ILD.Keywords: LGALS3BP, idiopathic inflammatory myopathies, dermatomyositis, anti-synthetase syndrome, immune-mediated necrotizing myopathy, interstitial lung disease

Xudong Hu,1,2 Sihui Zhu,1,2 Xiao Yang,1,2 Menglei Shan,1,2 Jiawei Wang,1,2 Xin Da,1,2 Yongkang Gui,1,2 Yang Liu,1,2 Rui Yang,1,2 Guanghong Xu1,2 1Department of Anesthesiology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Key Laboratory of Anesthesia and Perioperative Medicine of Anhui Higher Education Institutes, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Guanghong Xu, Department of Anesthesiology, the First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui, 230022, People’s Republic of China, Tel/Fax +86055162922344, Email xuguanghong2004@163.comPurpose: Postoperative cognitive dysfunction (POCD) is a common postoperative complication. Studies have reported that lymphocyte-to-monocyte ratio (LMR) was a predictor of many diseases associated with inflammation. However, further examination of the relationship between preoperative LMR and POCD is needed. We aimed to investigate the association between POCD and preoperative LMR levels to examine the potential of LMR to predict POCD.Patients and Methods: This was a prospective cohort study that included patients who underwent elective major abdominal surgery at our hospital between January 2019 and January 2022. Multivariate logistic regression analysis was used to analyze the effects of preoperative LMR on POCD development. The optimal threshold of preoperative LMR for predicting POCD was determined by receiver operating characteristic (ROC) approach. A subgroup analysis was performed according to age, sex, type of surgery and hypertension.Results: Of 964 patients, 362 (37.6%) developed POCD. The preoperative LMR level in the Non-POCD group was higher than that in the POCD group. According to the ROC curve, a cutoff value of 3.758 of the preoperative LMR level could be used to predict POCD occurrence and the area under the curve (AUC) was 0.747 (95% CI: 0.715– 0.779, P < 0.001). The results of the subgroup analyses were consistent with the primary ones, and no heterogeneity was observed in the subgroup analyses (P for interaction > 0.05).Conclusion: LMR was significantly associated with the occurrence of POCD after major abdominal surgery. Preoperative low LMR levels can be used to identify patients who may be at high risk of POCD.Keywords: postoperative cognitive dysfunction, lymphocyte-to-monocyte ratio, abdominal surgery, systemic inflammation

Jing Wang,1 Xintian Wang,1 Yuyang Li,1 Xin Yao,1 Yuanyuan Shen,1 Ziling Song,1 Peihua Zhang,2 Xiaoqiong Huang2 1School of Ophthalmology and Optometry, 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 ChinaCorrespondence: Xiaoqiong Huang, Email 13906632387@eye.ac.cnPurpose: Exploring the mechanisms of fear of negative evaluation (FNE) and self-esteem between family functioning and social avoidance and distress (SAD) to inform the promotion of social functioning in people with strabismus.Patients and Methods: Convenience sampling was used to select 249 strabismus patients attending a tertiary-level ophthalmology hospital in Wenzhou City from July 2023 to February 2024. The Social Avoidance and Distress Scale, Rosenberg Self-Esteem Scale, Brief Fear of Negative Evaluation Scale, and Family APGAR Index Questionnaire were utilized to assess levels of social avoidance and distress, self-esteem, fear of negative evaluation, and family functioning. Structural equation modeling (SEM) was employed to explore the sequential mediating role of FNE and self-esteem in the relationship between family functioning and SAD.Results: Family functioning negatively predicted SAD directly (β=− 0.14, P< 0.01). Additionally, family functioning predicted FNE (β=− 0.19, P< 0.01) and self-esteem (β=0.41, P< 0.01). FNE positively predicted SAD (β=− 0.38, P< 0.01) and negatively predicted self-esteem (β=− 0.22, P< 0.01). Moreover, self-esteem negatively predicted SAD (β=− 0.33, P< 0.01). FNE and self-esteem mediated the relationship between family functioning and SAD, with a combined mediating effect of − 0.249, explaining 63.52% of the total variance.Conclusion: This study examined how FNE and self-esteem affect the link between family functioning and SAD in patients with strabismus. These findings complement our understanding of SAD mechanisms in strabismus patients, encompassing familial, cognitive, and emotional perspectives, and offer theoretical insights for enhancing social functioning in this population.Keywords: strabismus, social avoidance and distress, family functioning, fear of negative evaluation, self-esteem, chain mediation

Fang An, Shiyan Wang, Lei Gao, Xiuli Sun, Jianliu Wang Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing, 100044, People’s Republic of ChinaCorrespondence: Fang An, Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China, Tel +86-13810267628, Email anfang_bjmu@hotmail.comPurpose: The purpose of this study is to examine the protective role of dietary vitamin B12 against depression, particularly as its prevalence is notably high among women experiencing urinary incontinence (UI). Nevertheless, the relationship between vitamin B12 intake, UI, and depression requires further clarification. This research aims to explore this association specifically among women.Methods: This cross-sectional study analyzed data from 14,154 women sourced from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2018. Depression was measured using the Personal Health Questionnaire (PHQ-9). Vitamin B12 intake was assessed through 24-h dietary recall interviews. Weighted univariate and multivariate logistic regression models assessed the relationships between UI, vitamin B12 intake, and depression in women, with additional analyses conducted across different age, body mass index (BMI), and vaginal delivery groups. Results are presented as odds ratios (ORs) with 95% confidence intervals (CIs).Results: The study included 14,154 women, averaging 48.18± 0.27 years in age, of whom 1609 (11.37%) exhibited depressive symptoms. Women with stress UI (OR=1.55, 95% CI: 1.26– 1.91), urgency UI (OR=1.92, 95% CI: 1.52– 2.44), and mixed UI (OR=2.60, 95% CI: 2.13– 3.19) showed significantly greater odds of depression compared to those without UI. Vitamin B12 intake of ≥ 2.4 mcg/day was associated with lower odds of depression (OR=0.95, 95% CI: 0.080– 1.14). In patients with UI, the odds of depression gradually decreased with a vitamin B12 intake of ≥ 2.4 mcg/day. A moderating role of vitamin B12 intake was observed among women with UI aged ≤ 64 years, with BMI ≥ 25 kg/m2, and those with or without vaginal deliveries.Conclusion: UI is linked to elevated depression odds, while vitamin B12 intake appears to moderate this relationship. It is essential for healthcare providers to prioritize early depression assessments in women with UI and to offer timely interventions to enhance their quality of life.Keywords: urinary incontinence, depression, vitamin B12 intake, NHANES

Jingyi Wang,1,&ast; Wei Zhang,1,&ast; Peige Song,2,&ast; Tingting Wang,3 Ye Yao,1 Yun Chen,4 Haijiang Lin,3 Xiaoqi Yang,1 Xiaoxiao Chen,1,3 Chaowei Fu1 1School of Public Health; NHC Key Laboratory of Health Technology Assessment, Fudan University, Shanghai, People’s Republic of China; 2School of Public Health and the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3Taizhou City Center for Disease Control and Prevention, Taizhou, Zhejiang Province, People’s Republic of China; 4Yale School of Nursing, Orange, CT, 06477, USA&ast;These authors contributed equally to this workCorrespondence: Chaowei Fu, School of Public Health, NHC Key Laboratory of Health Technology Assessment, Fudan University, Shanghai, 200032, People’s Republic of China, Email fcw@fudan.edu.cn Xiaoxiao Chen, Taizhou City Center for Disease Control and Prevention, Taizhou, Zhejiang Province, 318000, People’s Republic of China, Email tzcdccxx@126.comBackground: COVID-19 threatened global health, however little is known about the long-term courses of loneliness and their effect on mental health in adolescents. This study aimed to explore the trajectories of loneliness among adolescents in Taizhou, Zhejiang Province, China, during the last phase of the pandemic. We also aimed to identify risk factors in each loneliness course and the impact of loneliness on emotional problems, peer problems, hyperactivity and conduct problems.Methods: The study employed multistage cluster sampling to collect four waves of data from 2347 Chinese adolescents (average baseline age of 14.7 years) covering a period of 20 months (October 2021 – May 2023). The UCLA 3-Item Loneliness Scale and the Strengths and Difficulties Questionnaire were utilized to assess loneliness and mental health problems, respectively. Growth mixture modelling was employed to identify latent classes of loneliness trajectories. Associated risk factors were investigated using multinomial logistic regression model. Mixed-effects logistic regression models were constructed to examine the long-term impact of loneliness classes on mental health outcomes.Results: The overall percentage of loneliness increased from 22.9% at baseline to 32.2% at the fourth wave in our sample. Three classes of loneliness were identified: Decreasing Low Loneliness (58.71%), Increasing Medium Loneliness (36.52%), and Increasing High Loneliness (4.77%). Risk factors for poorer loneliness trajectories included lack of physical exercise habits, poorer mental health literacy, medium or low perceived social support, having study difficulties, being female, higher grades, and lower economic status. Loneliness classes were associated with the severity and variability of emotional problems, peer problems, hyperactivity and conduct problems (ORs for the highest loneliness class: 10.24, 4.21, 3.87, 2.68, respectively). Individuals in the higher loneliness classes experienced a significant increase in these mental health problems over time (p < 0.05 for interactions between loneliness classes and time).Conclusion: During the last phase of the pandemic, a large proportion of adolescents in our study endured medium to high levels of loneliness with no signs of improvement. Both unfavorable loneliness trajectories adversely affected internalizing and externalizing problems and displayed an upward trend in these difficulties. Results highlight the importance of tackling loneliness and improving mental health in adolescents.Keywords: adolescents, loneliness, risk factors, internalizing problems, externalizing problems, COVID-19

Huishang Feng,1,2 Yeping Qin,3 Yuanwen Li,4 Shuo Li,5 Yuyi Zheng,6 Juntang Yan,6 Rongting Xu,6 Shulin Yu,7 Ru Liang,7 Jiayu Wang,7 Huiqin Zou6,7 1Department of Dermatology, Dongzhimen Hospital Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Second Clinical Medical School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, People’s Republic of China; 4Department of Dermatology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Department of Basic Products, China Mobile Communications Group Co., Ltd. Government and Enterprise Customer Branch in Beijing, Beijing, People’s Republic of China; 6Ministry of Education Science and Technology Inspection Department, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 7School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Yuanwen Li, Department of Dermatology, Dongfang Hospital Beijing University of Chinese Medicine, No. 6 Fangxingyuan Fengtai District, Beijing, 100078, People’s Republic of China, Tel/Fax +86-1067689620, Email 15810104902@163.com Huiqin Zou, Ministry of Education Science and Technology Inspection Department, Beijing University of Chinese Medicine, No. 11 Beisanhuan Donglu Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86-1064287526, Fax +86-1064287502, Email huiqin.zou@bucm.edu.cnAim: The application of bibliometric analysis gives insights into research trend and future perspectives. This paper aims to understand the current status of studies on traditional Chinese medicine (TCM) in the treatment of atopic dermatitis (AD), and to investigate the cooperation network, hotspots and trends in the field.Methods: The original data were retrieved from the Web of Science Core Collection by searching for the topic “atopic dermatitis” and “traditional Chinese medicine” with the time span of 2004– 2023. Microsoft Excel was used to create statistical tables and charts, whereas CiteSpace and VOSViewer were applied for knowledge mapping.Results: In total, 252 publications were identified and downloaded. Current research on TCM treating AD is in the steady growth period. China has the largest number of publications, whereas the USA has the greatest international influence. Notably, the Arab Emirates, Malaysia, India and Bangladesh all have a high research impact but with a low amount of publications. Universities in Hong Kong China have the largest number of publications, but their interaction with other institutions is very poor. The top three most productive authors are all from Hong Kong, having a strong collaboration network with each other. The popular research topics in this field are “children” “cell” “activation” “nf kappa b” “inflammation” “asthma” “extract” “management” and “cytokine”. According to the analysis of leading co-cited journals and authors, “J ETHNOPHARMACOL” has the largest amount of citations whilst “AM J CHINESE MED” the strongest academic influence. The largest number of co-cited authors comes from “Hon Karn-Lun Ellis”, a well-known scholar from Hong Kong.Conclusion: TCM has been widely used in AD treatment, honored for its individualized therapeutic concepts of evidence-based treatment. The academic community must form a continuous and deep-going pattern to achieve higher international influence and a stronger research degree in this field.Keywords: atopic dermatitis, traditional Chinese medicine, bibliometrics, knowledge mapping, visual analysis

Juan Wang,1,&ast; Hua Cheng,2,&ast; Xinyue Zhao,1 Xiuwen Zhang,3 Xiaolei Ding,1 Taomin Huang3 1Department of Pharmacy, School of Medicine, Shanghai University, Shanghai, 200444, People’s Republic of China; 2Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA; 3Department of Pharmacy, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaolei Ding; Taomin Huang, Email xlding@shu.edu.cn; taominhuang@fudan.edu.cnBackground: Hyperactive Hedgehog (Hh) signaling initiates and drives the progression of various tumors. Despite the clinical success of Hh inhibitors targeting Smoothened (SMO), drug resistance, often stemming from SMO mutations, remains a formidable obstacle in cancer therapy. Here, we investigated the potential of imperatorin (IMP), a Chinese herbal medicine, to overcome drug resistance and revealed the potential mechanisms.Methods: The effect of IMP on Hh signaling pathway was evaluated via Quantitative reverse transcription-polymerase chain reaction, Dual-luciferase reporter assay and Western blot. Meanwhile, we tested its ani-proliferative potential on Hh-driven tumor cells. Loss/gain-of-function, network pharmacology analysis, RNA-sequence analysis and molecular docking were performed to investigate the potential mechanisms of IMP-mediated functions. Furthermore, we established a subcutaneous Hh-driven medulloblastoma xenograft model using the DAOY cell line and examined the in vivo therapeutic efficacy of IMP.Results: We identified IMP as a novel Hh inhibitor capable of overcoming drug-resistance caused by SMO mutants by inhibiting downstream transcription factor GLI1. IMP suppressed the proliferation of Hh-dependent cancer cells along with Hh activity inhibition. Mechanistically, IMP attenuated the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and its interaction with GLI1 promoter, consequently blocking GLI1 transcription and the target gene expressions. Molecular docking analysis revealed the favorable binding affinity between IMP and STAT3. Importantly, IMP application effectively inhibited the growth of medulloblastoma in vivo, accompanied by the downregulation of GLI1 and phosphorylated STAT3.Conclusion: Our findings revealed IMP as an innovative approach to combat the drug resistance of SMO inhibitors in Hh-driven tumors, highlighting the crucial role of STAT3 as a transcriptional regulator in Hh signaling.Keywords: Hedgehog, resistance, GLI1, imperatorin, STAT3, medulloblastoma

Hang Yi,1 Ruiping Ye,2 Jinfeng Wang,3 Lin Gao,4 Weiwei Zhang,4 Chao Liu4 1Department of Intensive Care Medicine, Qianjiang Central Hospital, Qianjiang City, Hubei Province, 433100, People’s Republic of China; 2Department of Intensive Care Medicine, The First People’s Hospital of Dingnan County, Ganzhou City, Jiangxi Province, 341900, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, People’s Republic of China; 4Department of Intensive Care Medicine, Ganzhou People’s Hospital, Ganzhou City, Jiangxi Province, 341000, People’s Republic of ChinaCorrespondence: Chao Liu, Department of Intensive Care Medicine, Ganzhou People’s Hospital, No. 16, Meiguan Avenue, Zhanggong District, Ganzhou City, Jiangxi Province, People’s Republic of China, Email a15116461784@126.comObjective: To investigate the diagnostic value of serum fibrinogen domain-containing lectin-3 (Ficolin-3) and galectin-3 (Gal-3) in sepsis-associated acute kidney injury (SA-AKI).Methods: This study retrospectively analyzed 126 SA-AKI patients with SA-AKI and 103 septic patients without AKI as controls. Based on the severity of renal injury, the SA-AKI patients were divided into three groups: mild (41 cases), moderate (53 cases), and severe (32 cases). Serum levels of Ficolin-3 and Gal-3 were measured using ELISA, and their correlation was determined through Pearson analysis. Multivariate logistic regression was used to identify factors associated with the occurrence of SA-AKI.Results: The serum creatinine (SCr), blood urea nitrogen (BUN), as well as the expression levels of serum Ficolin-3 and Gal-3 in the SA-AKI group were higher than those in the non SA-AKI group (P< 0.05). The expression levels of Ficolin-3 and Gal-3 in the serum of the SA-AKI group were also higher than those of the non SA-AKI group (P< 0.05). The expression levels of Ficolin-3 and Gal-3 in serum gradually increased with the severity of renal injury in SA-AKI patients (P< 0.05). The expression levels of Ficolin-3 and Gal-3 in serum were greatly positively correlated (P< 0.001). Elevated levels of BUN, Ficolin-3, and Gal-3 were risk factors affecting the occurrence of SA-AKI (P< 0.05). The area under the curve (AUC) of serum Ficolin-3 and Gal-3 for individual diagnosis of SA-AKI was 0.877 and 0.867, respectively, the AUC of their combined diagnosis was 0.953, and the diagnostic sensitivity was higher than that of their individual diagnosis (P< 0.001).Conclusion: The expression levels of serum Ficolin-3 and Gal-3 are closely related to associated with the onset and progression of SA-AKI and hold diagnostic value for its detection. Furthermore, the combined use of both markers provides a more accurate diagnosis than either marker alone.Keywords: Sepsis complicated with acute kidney injury, Fibrinogen domain-containing lectin-3, Galectin-3

Qingpeng Xie,1,2,&ast; Jiawen Gu,1,2,&ast; Yujia Sun,3 Jinjia Hong,1,2 Jia Wang,1,2 Na Li,1,2 Yuan Zhang,1,2 Meixian Liu,1,2 Xiaoxuan Zhang,1,2 Xiangyu Zhao,1,2 Xiaohang Chen,1,2 Xing Wang1,2 1Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People’s Republic of China; 2Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, People’s Republic of China; 3Nursing College of Shanxi Medical University, Taiyuan, 030001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohang Chen; Xing Wang, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People’s Republic of China, Tel +8618834896163 ; +8613934224604, Email kqyx__cxh@163.com; wangxing@sxmu.edu.cnPurpose: Periodontitis is a chronic inflammatory oral disease that causes defects in periodontal tissue. Conventional therapies are limited, and often lead to high recurrence rates. The emerging concept of medicinal food homology has shed light on the potential of ginger as a therapeutic adjuvant for periodontitis, given its antioxidant and anti-inflammatory properties. However, fresh ginger exhibits poor stability and bioavailability. Ginger exosome-like nanoparticles (GELNs), a derivative of ginger, have not been reported to exert therapeutic effects in periodontitis. This study aimed to explore the therapeutic effects of GELNs on tissue damage caused by periodontitis and their underlying mechanisms of action.Methods: The GELNs composition was analyzed using a widely targeted metabolome. Stability was assessed using nanoparticle tracking analysis (NTA) and zeta potential measurements, flavor was evaluated using an electronic nose, and membrane penetration was studied using confocal microscopy. A periodontitis model was established in SD rats, periodontal clinical indicators were monitored, and histological changes were assessed using H&E and TRAP staining. Co-culture experiments investigate the antioxidant and reparative abilities of GELNs on periodontal ligament fibroblasts (PDLFs) in inflammatory environment. NF-κB protein expression was examined by immunofluorescence and immunohistochemistry.Results: The findings revealed that GELNs demonstrated good stability in different environments and mitigated the pungent taste of the raw ginger. In vivo experiments showed that GELNs improved periodontal clinical parameters and pathology compared with ginger juice. In vitro data suggested that GELNs enhanced the proliferation and migration of PDLFs while reducing the reactive oxygen species (ROS) levels by inhibiting the NF-κB signaling pathway in an inflammatory setting.Conclusion: This study is the first to demonstrate that GELNs have a potential therapeutic effect on periodontitis. GELNs can alleviate oxidative stress (OS) and inflammatory reactions by inhibiting the NF-κB signaling pathway. These findings provide a promising method for the treatment of periodontitis by regulating an unbalanced OS state. Keywords: ginger exosome-like nanoparticles, periodontitis, tissue repair, oxidative stress, periodontal ligament fibroblasts

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

Xingmei Xu, Libin Zhao, Yue Li, Li Zhan, Lidong Zheng, Jingxian Wang Department of Anesthesiology, Lu’an Hospital of Anhui Medical University, Luan, 237000, People’s Republic of ChinaCorrespondence: Li Zhan, Department of Anesthesiology, Lu’an Hospital of Anhui Medical University, Luan, 237000, People’s Republic of China, Email 1784158909@qq.comBackground: The objective of this study is to investigate the impact of cheek acupuncture on perioperative pain in patients with hip fracture.Methods: A random number table was utilized to allocate the patients into three distinct cohorts: Only spinal anesthesia was performed (group S), cheek acupuncture was performed before spinal anesthesia (group C), and ultrasound-guided fascia iliaca block was performed before spinal anesthesia (group F). The primary outcome measure was the Visual Analogue Scale (VAS) score within 24 hours post-surgery, as well as the level of beta-endorphin. The secondary outcome measures included intraoperative mean arterial pressure (MAP), heart rate (HR), length of hospital stay, postoperative complications, levels of interleukin-6 (IL-6), and degree of motor block.Results: Compared to Group S, patients in group C and group F exhibited significantly lower Visual Analog Scale (VAS) scores at the following endpoints: when the patient is positioned in the spinal anesthesia position (T2); 12 hours post-surgery (T5); and 24 hours post-surgery (T6). And patients in group C and group F demonstrated a decreased beta-endorphin level at the T6. Compared to Group S, patients in group C and group F displayed reduced Mean Arterial Pressure (MAP) levels at T2.Conclusion: The application of cheek acupuncture therapy in hip fracture surgery can effectively reduce the Visual Analog Scale (VAS) score, enhance perioperative safety, facilitate postoperative recovery, and optimize the overall medical experience for patients.Clinical Trial: ChiCTR2100043194.Keywords: cheek acupuncture, hip fracture, VAS score

Gengyu Cen,1,&ast; Jun Wang,1,&ast; Xue Wang,1 Yiting Song,1 Shijian Chen,1 Jing Li,2 Qiuhui Huang,1 Zhijian Liang1 1Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Neurology, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Liang, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email lzj200415@126.comObjective: To investigate the pathogenesis of cancer-related ischemic stroke (CRIS) and to search for reliable biomarkers of CRIS.Methods: Patients with CRIS, only-cancer and only-ischemic stroke who were hospitalized in the First Affiliated Hospital of Guangxi Medical University from May 2022 to January 2024 were recruited, and laboratory and clinical data of the three groups were collected. Peripheral venous blood was collected and enzyme-linked immunosorbent assay (ELISA) was used to detect markers of coagulation (D-dimer) and endothelial integrity (intercellular adhesion molecule-1 (ICAM-1)).Results: The study included 16 patients with CRIS, as well as 16 patients with only-cancer and 16 patients with only-ischemic stroke. Among patients with CRIS, the most common cancer was lung cancer, and the most common pathological type was adenocarcinoma. It was found that compared with patients with only-cancer and only-ischemic stroke, the hemoglobin and lymphocyte percentage in patients with CRIS were decreased (P< 0.05), while the neutrophil percentage and neutrophil to lymphocyte ratio (NLR) were increased (P< 0.05). Compared with only-ischemic stroke group, the lymphocyte absolute value in patients with CRIS was decreased (P< 0.05), and platelet to lymphocyte ratio (PLR), globulin, prothrombin time (PT), international normalized ratio (INR) and ICAM-1 were increased (P< 0.05). D-dimer level was higher in patients with CRIS than in only-cancer group (P< 0.05).Conclusions: In the present study, the increased NLR, PLR, ICAM-1 and D-dimer were expected to be biomarkers of CRIS, indicating that hypercoagulability mediated by cancer inflammation and endothelial damage may be the pathogenesis of CRIS. The novel findings in the present study will facilitate clinicians to identify the patients at high risk of CRIS. Because of the small sample size, the findings need to be validated by prospective large-sample studies in the future.Keywords: cancer-related ischemic stroke, hypercoagulability, pathogenesis, biomarkers

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

He Ma,1,2 Juan Perez,2 Julia Bertsch,2 Marissa L Albanese,2 Elizabeth G Korn,2 Ariel Mueller,2 Timothy Houle,2 Briana June Burris,3 Joseph McCain,3 Jingping Wang2 1Department of Anesthesiology, the Second Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 3Department of Oral & Maxillofacial Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USACorrespondence: Jingping Wang, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, GRJ 420, Boston, MA, 02214, USA, Tel +1 (617) 643 2729, Email jwang23@MGH.Harvard.eduBackground: Pain intensity after temporomandibular joint (TMJ) surgery is often underestimated, and inadequate pain control may relate to poor recovery quality, increased opioid consumption, and longer hospital stay. This trial aims to evaluate whether non-opiate anesthesia provides a promising option of pain management for patients undergoing TMJ surgery.Methods: Sixty patients receiving TMJ surgery were randomly assigned to either the control group or the non-opiate group. Non-opiate anesthesia used lidocaine, dexmedetomidine, and ketamine infusion therapy for pain management. The primary outcome was the highest documented pain score while in the post-anesthesia care unit (PACU). Secondary outcomes included perioperative opioid consumption, utilization, dosage, and timing of rescue analgesia in the PACU, incidence of postoperative nausea and vomiting in the PACU and at home, pain satisfaction levels, occurrence of opioid-related adverse effects, duration of PACU and hospital stays, and total consumption of oxycodone-acetaminophen tablets at 24 and 48 hours post-surgery.Results: Patients were predominantly female (88.3%) and had a median age of 37.5 [IQR 26.0, 52.5] years. There were no significant differences observed in the highest documented pain scores (mean difference [MD] − 0.36 points, 95% CI: − 1.84, 1.12, p = 0.63), postoperative oxycodone-acetaminophen consumption (MD 6.68 mg, 95% CI: − 2.48, 15.84, p = 0.15), pain satisfaction (odds ratio [OR] 0.81, 95% CI: 0.23, 2.81, p = 0.74), time to PACU discharge (hazard ratio [HR] 1.24, 95% CI: 0.67, 2.30, p = 0.49) or time to hospital discharge (HR 1.48, 95% CI: 0.80, 2.75, p = 0.21) between the two groups. Similarly, no significant difference was observed in time to rescue analgesia, calculated in minutes from the end of surgery (HR 1.69, 95% CI: 0.79, 3.61, p = 0.18).Conclusion: Non-opiate anesthesia for pain management shows a similar postoperative analgesia effect, compared to opioid-based anesthesia, in patients undergoing arthroscopic TMJ surgery.Keywords: non-opiate, anesthesia, temporomandibular joint disorders, temporomandibular joint, surgery

Jiyang Li,1,&ast; Xinxing Fei,2,&ast; Shiqi Wang,3,4,&ast; Zhangyu Xu,5,6 Fangyuan Xu,5,6 Jianxiong Wang,5,6 Yaqian Gao,7 Yue Hu5,6 1Department of Rehabilitation Medicine, Sichuan Tianfu New Area People’s Hospital, Chengdu, People’s Republic of China; 2Department of Psychiatry, Chengdu Eighth People’s Hospital (Geriatric Hospital of Chengdu Medical College), Chengdu, People’s Republic of China; 3Department of Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Key Laboratory of Rehabilitation Medicine in Sichuan Province, Chengdu, Sichuan, People’s Republic of China; 5Department of Rehabilitation Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 6Rehabilitation Medicine and Engineering Key Laboratory of Luzhou, Luzhou, People’s Republic of China; 7Department of Rehabilitation Medicine, the First Affiliated Hospital of Chengdu Medical College, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaqian Gao; Yue Hu, Email 673509366@qq.com; huyue@swmu.edu.cnBackground: Many studies have been conducted on the use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression. However, the overall trends in research publications in this field remain elusive. There is still little quantitative analysis of the literature in this field. Therefore, we conducted a bibliometric analysis to explore the research patterns surrounding SSRIs for depression, aiming to gain a deeper understanding of their development and impact.Methods: Publications about the use of SSRIs for the treatment of depression were identified in the Web of Science Core Collection. Visualization analysis was performed with Bibliometrix, VOSviewer, and CiteSpace.Results: A total of 1149 publications published from 1990 to 2024 were included in the bibliometric analysis. Since 1990, the annual number of published papers has increased annually, reaching the maximum value of output in 2004. Fitted curve showed that after 2004, the number of publications per year was essentially stable The United States dominates the field. Among these institutions, University of Pittsburgh excels in this field. Fava M has the highest scientific productivity and extensive academic influence. European Neuropsychopharmacology is the most active journal in this field. The three most relevant keywords were “fluoxetine”, “double-blind”, and “major depression”. The trend topics in recent years were “connectivity”, “c-reactive protein”, and “anhedonia”.Conclusion: Research on the use of SSRIs for the treatment of depression continues to receive increased attention but still requiraes further exploration and innovation. We further analyze the current research hotspots and frontiers in this field.Keywords: selective serotonin reuptake inhibitors, depression, bibliometrics, double-blind, fluoxetine, major depression

Xiaoqin Ji,1,&ast; Xuebing Shi,2,&ast; Jun Hu,3 Wanrong Jiang,3 Bin Zhou,3 Houlong Zhou,3 Xi Yuan,3 Yikun Li,3 Hua Huang,3 Jiasheng Wang,3 Wei Ding,3 Yong Wang,4 Xiangdong Sun3 1Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Radiation Oncology, Nanjing Jiangbei Hospital, Nanjing, People’s Republic of China; 3Department of Radiation Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 4Department of Outpatient Clinic, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Wang; Xiangdong Sun, Email 292917354@qq.com; sunxd_81@126.comPurpose: The objective of this study was to compare the clinical outcomes of stereotactic body radiation therapy (SBRT) in elderly patients aged 65 or older with clinical stage I–II non-small-cell lung cancer (NSCLC), specifically examining the differences between centrally located lung tumors and peripherally located lung tumors.Methods: From April 2009 to January 2020, a total of 136 patients with 136 tumors (65 central, 71 peripheral; NSCLC) at an early stage (T1-3N0M0) were treated with SBRT at a single institution. Central/peripheral location was assessed retrospectively on planning CT scans. A propensity score matching analysis was utilized to compare the two groups. In addition, the prognosis and related toxicity were compared between the two study arms.Results: A total of 33 central tumors and 33 peripheral tumors were matched and analyzed. The results showed no significant differences in overall survival (OS) and progression-free survival (PFS) between the two groups. The 2-year OS was 71.88% (95% CI, 57.87%-89.27%) in the central lung cancer group, while it was 93.94% (95% CI, 86.14%-100.00%) in the peripheral lung cancer group (P=0.462). The 2-year PFS was 43.75% in the central lung cancer group, while it was 78.79% in the peripheral lung cancer group (P=0.279). Further subgroup analysis indicated that the location of peripheral tumor have a positive impact on OS in patients with adenocarcinoma. The occurrence of local failure, regional failure, or distant failure was comparable between central and peripheral tumors. There was no statistically significant difference in toxicity between the central and the peripheral tumor groups.Conclusion: The outcomes of SBRT for central tumors versus peripheral lung tumors in elderly patients with early-stage NSCLC were similar. SBRT demonstrated a similar level of safety in terms of toxicity for both central and peripheral lung tumors.Keywords: Non-small cell lung cancer, stereotactic body radiation therapy, central lung cancer, elderly patients, propensity score matching

Yihong Tian,1,2,&ast; Yanyue Tan,3,&ast; Ming Yang,1 Xiayang Lv,3 Yunhao Zheng,1 Qiang Zhang,4 Yanyu Sun,1 Jun Wang,1,2 Xin Xiong1,2 1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chengdu, Sichuan, People’s Republic of China; 2Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Nursing, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Orthodontics, Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Wang; Xin Xiong, West China Hospital of Stomatology, Sichuan University, No. 14 section 3, Renmin South Road, Chengdu, 610041, People’s Republic of China, Email wangjunv@scu.edu.cn; drxiongxin@scu.edu.cnObjective: This study aimed to thoroughly explore the relationship between individual oral behavior and the differing numbers of temporomandibular disorder (TMD) symptom in the general population.Methods: A total of 565 participants were recruited and completed a questionnaire containing demographic characteristics, eight specific oral behaviors, and five major TMD symptoms (5Ts) checklist. Multivariate linear regression analysis was performed to assess the relationship between individual oral behavior and the number of TMD symptoms, after controlling for confounders.Results: The prevalence of TMD symptoms was up to 38.2% in the general population, with 64.6% of the participants engaging in one or more oral behaviors. Female participants showed a stronger positive association with most oral behaviors than males. Moreover, wake oral behaviors exhibited a higher correlation coefficient value with TMD symptom number than sleep oral behaviors. Among the eight oral behaviors, bruxism in sleep exhibited no significant correlation with the of TMD symptom number (P> 0.05). Seven other specific oral behaviors were significantly correlated with the number of TMD symptoms by multivariate linear regression analysis (P< 0.01). The associations between the seven oral behaviors and TMD symptom number remained significant in sleep posture pressuring jaw (β: 0.165, 95% CI: 0.080– 0.250), bruxism in awake (β: 0.341, 95% CI: 0.132– 0.550), teeth clenching (β: 0.422, 95% CI: 0.264– 0.580), pressing, holding, or touching teeth together (β: 0.282, 95% CI: 0.169– 0.395), holding or tightening muscles without clenching (β: 0.447, 95% CI0.304– 0.589), holding jaw forward or to the side (β: 0.694, 95% CI0.526– 0.861), and holding jaw in rigid or tense position (β: 0.571, 95% CI0.418, 0.724) after adjustment for demographic factors (P< 0.01).Conclusion: There was a positive association between seven specific oral behaviors and TMD symptom number. Individuals with higher frequency of specific oral behaviors are more likely to suffer from more TMD symptoms. Sleep bruxism exhibited no association with TMD symptoms and symptom number.Keywords: oral behaviors, temporomandibular disorders, TMD symptom number, cross-sectional study

Yan Chu,1,&ast; Xiaomin Wang,2,&ast; Min Dou,1 Jin Wang,2 Baoqian Wang,1 Hairong Wang,1 Shasha Lv,1 Shuihua Lu,2,&ast; Tongxia Li1,&ast; 1Qingdao Chest Hospital, Qingdao, Shandong, People’s Republic of China; 2National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tongxia Li; Shuihua Lu, Email qdlitx@163.com; lushuihua66@126.comObjective: To analyze the clinical characteristics, species distribution and drug resistance of patients with non-tuberculous mycobacteria (NTM) lung disease in Qingdao, China.Methods: Clinical data of patients with NTM lung disease and pulmonary tuberculosis (TB) treated at Qingdao Chest Hospital from July 2021 to July 2023 were retrospectively analyzed.Results: The prevalence of NTM lung disease was 8.03%, with a high rate of drug resistance during the study period. Patients with NTM lung disease had higher rates of older age, bronchiectasis, malignancy, HIV infection and bronchial dilatation shadow and lower rates of hollow shadow compared to patients with pulmonary TB.Conclusion: Comprehensive understanding of NTM lung disease, improved laboratory testing techniques and appropriate treatment regimens are essential for the management of NTM lung disease.Keywords: non-tuberculous mycobacteria, pulmonary tuberculosis, clinical characteristics, drug resistance

Yujuan Mao,1,&ast; Tianjiao Hao,2,&ast; Hongxiu Zhang,2,&ast; Xiaofei Gu,2 Jing Wang,1 Feifei Shi,1 Xiaolan Chen,1 Liuna Guo,1 Jie Gao,1 Yan Shen,2 JinLin Zhang,3 Shenglan Yu4 1Jiangsu Agri-Animal Husbandry Vocational College, Taizhou, Jiangsu, 225300, People’s Republic of China; 2Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China; 3Jiangsu Institute for Food and Drug Control, Nanjing, Jiangsu Province, 210019, People’s Republic of China; 4College of Animal Medicine, Jiangsu Agri-Animal Husbandry Vocational College, Taizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shenglan Yu; JinLin Zhang, Email slyu70@126.com; zjluser@126.comIntroduction: Eprinomectin offers promise against parasitic infections. This study develops Eprinomectin (EPR) mixed micelles for transdermal delivery, aiming to enhance efficacy and convenience against endoparasites and ectoparasites. Physicochemical characterization and pharmacokinetic studies were conducted to assess its potential as an effective treatment for parasitic infections.Methods: Blank and EPR mixed micelles were prepared using PEG-40 Hydrogenated castor oil (RH-40) and Nonyl phenol polyoxyethylene ether 40 (NP-40). Critical micelle concentrations (CMC) determined using the pyrene fluorescence probe method. Particle size, EE, DL, in vitro release, permeation, and skin irritation were evaluated. In vivo pharmacokinetic studies were conducted in male Sprague-Dawley rats.Results: Results show that EPR mixed micelles present suitable stability, physicochemical properties, and safety. Moreover, the rapid release and high bioavailability of EPR mixed micelles have also been verified in the study. Pharmacokinetic experiments in vivo showed that an improvement in the transdermal absorption and bioavailability of EPR after encapsulation in mixed micelles formulations.Conclusion: The results proved that the novel mixed micelles are safe and effective and are expected to become a promising veterinary nano-delivery system.Keywords: eprinomectin, mixed micelles, transdermal delivery, pharmacokinetics

Meng Xiang,1,&ast; Chengzhi Chen,2,&ast; Yuting Chen,1,&ast; Yuhan Zhang,1 Lei Shi,1 Yan Chen,1 Jie Li,2 Bowen Li,1 Bin Zeng,2 H Rosie Xing,1 Jianyu Wang,2 Zhen Zou2 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Molecular Biology Laboratory of Respiratory Disease, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen Zou; Jianyu Wang, Email zouzhen@cqmu.edu.cn; 102758@cqmu.edu.cnIntroduction: Inhalation exposure to silica nanoparticles (SiNPs) is frequently inevitable in modern times. Although the impact of SiNPs on the ecological niche of the lungs has been extensively explored, the role and mechanism of SiNPs in the microenvironment of lung tumors remain elusive.Methods: In this investigation, Lewis lung carcinoma (LLC) was implanted into the left lung in situ after 28 days of intratracheal SiNPs injection into the lungs of mice. This study evaluates the effects of SiNPs on the tumor immune microenvironment both in vitro and in vivo. Our findings indicate that SiNPs can suppress lung cancer by modulating the immune microenvironment of tumors.Results: SiNPs treatment promotes macrophage M1 polarization by activating both NF-κB pathway and glycolytic mechanisms. This phenomenon may be associated with lung inflammation and fluctuation in the pre-metastatic and metastatic microenvironments induced by SiNPs exposure in mice. Additionally, we have shown for the first time that SiNPs have an inhibitory effect on lung carcinogenesis and its progression.Conclusion: This study uniquely demonstrates that SiNPs suppress lung cancer by promoting M1 polarization of macrophages in the immune microenvironment of lung tumors. Our findings are critical in exploring the interaction between SiNPs and lung cancer. Keywords: silicon nanoparticles, lung cancer, macrophage polarization, NF-κB, glycolysis

Tielong Chen,1,&ast; Jianwu Zheng,1,&ast; Cheng Bao,1 Yu Wang,1 Shiwang Wang,1 Lu Liang,1 Li Zhang,2 Hui Zhang,2 Chaoxia Ji,2 Jian Wang,2 Xudong Zhang,1 Guangli Zhu,1 Houyong Zhu1 1Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tielong Chen; Houyong Zhu, Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453 Stadium Road, Hangzhou, Zhejiang, 310007, People’s Republic of China, Email ctlppp@foxmail.com, ctlppp@163.com; houyongzhu@foxmail.comBackground: Despite statins and other medications central to atherosclerotic cardiovascular disease (ASCVD) secondary prevention, stable coronary artery disease (SCAD) patients remain at significant cardiovascular risk, partly due to residual inflammation risk (RIR). This study aims to assess if adding Guanxinning to standard ASCVD therapy further mitigates RIR in SCAD patients.Methods: In a prospective, randomized, single-blind endpoint design, 50 patients with SCAD who received ASCVD standardized treatment strategy were randomly assigned to either take Guanxinning tablets (4 tablets, thrice daily) or no Guanxinning tablets and were followed up for an average of 12 weeks. The primary outcomes were changes in inflammation-related indicators, including interleukin-2 (IL-2), IL-4, IL-6, tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hs-CRP).Results: Compared with the control group, the intervention group showed significantly greater decreases in the levels of IL-2, IL-6, TNF-α, and hs-CRP (all P < 0.05). However, there was no significant difference in the IL-4 level between the two groups (P > 0.05). Compared with the control group, there were also significant improvements in endothelial function-related indicators (vascular endothelial growth factor (VEGF), nitric oxide (NO), and peroxisome proliferator-activated receptor-γ (PPAR-γ)), blood lipid profile (total cholesterol (Tch), low-density lipoprotein cholesterol (LDL-C)), and chest pain related scores (angina and Traditional Chinese medicine syndrome scores) in the intervention group (all P< 0.05). There was no significant difference in the triglyceride (TG) and carotid intima-media thickness between the two groups (P< 0.05). Compared to the control group, there was no significant difference in the white blood cell line, liver and kidney function, anemia, and bleeding in the intervention group (all P< 0.05).Conclusion: The addition of Guanxinning tablets (4 tablets, thrice daily) to the standard treatment strategy for ASCVD was associated with a reduction in the RIR in patients with SCAD and demonstrated good safety.Plain Language Summary: In the quest for a heart-healthy life, even with statins at our side, some folks with stable heart troubles still face a sneaky foe: lingering inflammation. Our study explored whether adding Guanxinning, a traditional Chinese medicine, to the standard treatment might help. Over 12 weeks, patients who took Guanxinning along with their usual heart meds showed promising signs of reduced inflammation and improved heart health markers. These preliminary positive signs hint at the potential benefits of Guanxinning, which, however, need further studies to confirm. Fortunately, it appears to be safe to use Guanxinning alongside conventional treatments for now. As we delve deeper into the mysteries of heart health, every promising discovery brings us one step closer to developing better therapeutic strategies.Keywords: Guanxinning, stable coronary artery disease, risk of residual inflammation, secondary prevention

Jaina Razbek,1 Yanggui Chen,2 Jiandong Yang,2 Yaying Zhang,1 Baofeng Wen,1 Junan Wang,1 Xiaomin Wang,1 Guliziba Kuerbanjiang,1 Abulikemu Aili,1 Mingqin Cao1 1Department of Epidemiology and Health Statistics, College of Public Health, Xinjiang Medical University, Urumqi, 830011, People’s Republic of China; 2Department of Prevention and Control of Tuberculosis, Urumqi Centre for Disease Control and Prevention, Urumqi, 830011, People’s Republic of ChinaCorrespondence: Mingqin Cao, Email cmq66@126.comPurpose: Latent tuberculosis infection (LTBI) is a critical stage in tuberculosis (TB)control, and few studies have addressed the role of vitamin D receptor(VDR) gene polymorphisms in differentiating between TB and late-onset TB from an immunogenetic perspective.Patients and Methods: Recruitment of tuberculosis patients and latently infected population in Urumqi, Xinjiang, and use of propensity score matching(PSM) to match the two groups and control confounding to further construct a Bayesian network to analyze causal associations between VDR polymorphisms and tuberculosis disease status.Results: 137 LTBI and 237 TB were obtained through PSM. Logistic regression showed that the VDR gene BsmI locus, TaqI locus, and ApaI locus were associated with a higher risk of TB in a codominant model (P< 0.05). Further Bayesian network construction showed that occupation and being a VDR gene BsmI locus were direct influences on TB disease status, and the VDR gene TaqI locus played an indirect role through the BsmI locus, and the probability of TB risk was highest in individuals with manual labour and BsmI locus of the C/T type, which was 84.15%.Conclusion: Bayesian network modelling intuitively revealed that individuals with a C/T type of BsmI locus and physical labour are at high risk of TB compared with TB infection, and they are key factors between with TB disease, providing reference evidence for controlling TB progression.Keywords: tuberculosis, disease state, vitamin D receptor, propensity score matching, Bayesian network

Yang Liu,1,&ast; Chunan Wang,1,&ast; Sitong Liu,1,&ast; Hangzhan - Ma,2 Jiayun Xu,3 Kai Jiang,1 Ruitao Lu,4 Xintao Shuai,5 Jinming Wang,3 Zhong Cao1 1School of Biomedical Engineering, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Orthopedics, Panyu Hospital of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Oral Implantology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, People’s Republic of China; 4Shenzhen International Institute for Biomedical Research, Shenzhen, Guangdong, People’s Republic of China; 5Nanomedicine Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhong Cao; Jinming Wang, Email caozhong@mail.sysu.edu.cn; wjinm@mail.sysu.edu.cnBackground: As a burgeoning cancer treatment modality, photothermal therapy (PTT) has shown robust anti-tumor effects. However, it still faces numerous challenges, such as triggering an inflammatory response and potentially increasing the risk of cancer recurrence. To address these concerns, integration of PTT with anti-inflammatory therapies presents a promising approach to enhance the efficacy of cancer treatment and meanwhile reduce the risk of recurrence.Methods: In this study, Gd3+ was first chelated with dopamine to create Gd-DA chelates, and then the mesoporous dopamine nanoparticles MX@Arg-Gd-MPDA (MAGM NPs) were synthesized by combining arginine (Arg) and the anti-inflammatory medication meloxicam (MX). The photothermal properties of MAGM NPs were then defined and examined; the in vivo MRI imaging effect, as well as MAGM NPs’ anti-cancer and anti-inflammatory efficiency, were tested in a mouse model of breast cancer.Results: The incorporation of Arg doping into MAGM NPs was intended to boost its photothermal conversion efficiency and reactive oxygen species (ROS) scavenging ability. Additionally, synergizing with the anti-inflammatory agent meloxicam (MX) within the nanoparticles aimed to enhance the anti-inflammatory effect following photothermal therapy. Furthermore, gadolinium ions (Gd3+) were chelated into the nanostructure to enable precise T1-T2 dual-mode magnetic resonance imaging (MRI) of the intratumor accumulation profile. This imaging capability was leveraged to guide the implementation of photothermal therapy. Animal experiments demonstrated that MAGM NPs exerted a notable anticancer effect in a 4T1 breast cancer mouse model, under the precise guidance of MRI.Keywords: magnetic resonance imaging, photothermal therapy, anti-inflammatory therapy, mesoporous polydopamine, cancer therapy

Dandan Wang,1– 3,&ast; Jingguo Wang,3,&ast; Zequn Yin,4 Ke Gong,3 Shuang Zhang,3 Zhengbao Zha,3 Yajun Duan4 1School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, 230011, People’s Republic of China; 2State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, People’s Republic of China; 3School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, 230601, People’s Republic of China; 4Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengbao Zha, School of Food and Biological Engineering, Hefei University of Technology, No. 420 Feicui Road, Hefei, Anhui, 230601, People’s Republic of China, Email zbzha@hfut.edu.cn Yajun Duan, Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 96 Jinzhai Road, Hefei, Anhui, 230031, People’s Republic of China, Email yajunduan@ustc.edu.cnIntroduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver disorder, has garnered increasing attention globally owing to its associated health complications. However, the lack of available therapeutic medications and inadequate management of complications in metabolic dysfunction-associated steatohepatitis (MASH) present significant challenges. There are little studies evaluating the effectiveness of POM in treating MASLD. In this study, we synthesized polyoxometalates (POM) for potential treatment of MASLD.Methods: We induced liver disease in mice using two approaches: feeding a high-fat diet (HFD) to establish MASLD or feeding a methionine–choline deficient (MCD) diet to induce hepatic lipotoxicity and MASH. Various metabolic parameters were detected, and biochemical and histological evaluations were conducted on MASLD. Western blotting, qRT-PCR and immunofluorescence assays were used to elucidate the molecular mechanism of POM in the treatment of MASLD.Results: POM therapy resulted in significant improvements in weight gain, dyslipidemia, liver injury, and hepatic steatosis in mice fed a HFD. Notably, in a more severe dietary-induced MASH model with MCD diet, POM significantly attenuated hepatic lipid accumulation, inflammation, and fibrosis. POM treatment effectively attenuated palmitic acid and oleic acid-induced lipid accumulation in HepG2 and Huh7 cells by targeting the AMPK pathway to regulate lipid metabolism, which was confirmed by AMPK inhibitor. Additionally, the activation of AMPK signaling by POM suppressed the expression of lipid synthesis genes, including sterol regulatory element-binding protein 1c (SREBP1c) and SREBP2, while concurrently upregulating the expression of sirtuin 1 (SIRT1) to promote fatty acid oxidation.Conclusion: These findings suggest that POM is a promising therapeutic strategy with high efficacy in multiple MASLD models. Keywords: polyoxometalates, MASLD, MASH, AMPK, lipotoxicity

Fenfen Guo,1 Hong Li,1 Jingjing Wang,1 Jiangfeng Wang,1 Jinling Zhang,1 Fanfang Kong,1 Zemin Zhang,2 Jinbao Zong1 1Departments of Clinical Laboratory, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao, People’s Republic of China; 2Departments of Infectious Disease, Qingdao Women and Children’s Hospital, Qingdao, People’s Republic of ChinaCorrespondence: Jinbao Zong, Email sdjinbaozong@163.comAbstract: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Tumor immune microenvironment (TIME), angiogenesis, epithelial-mesenchymal transformation (EMT), invasion, metastasis, metabolism, and drug resistance are the main factors affecting the development and treatment of tumors. MiRNAs play crucial roles in almost all major cellular biological processes. Studies have been carried out on miRNAs as biomarkers and therapeutic targets. Their dysregulation contributes to the progression and prognosis of HCC. This review aims to explore the molecular cascades and corresponding phenotypic changes caused by aberrant miRNA expression and their regulatory mechanisms, summarize and analyze novel biomarkers from somatic fluids (plasma/serum/urine), and highlight the latent capacity of miRNAs as therapeutic targets.Keywords: hepatocellular carcinoma, microRNAs, regulatory mechanisms, biomarker, targeted therapy

Jiali Wang,1,2 Yiqing Liu,3 Chengkui Xiu,1 Xue Wang,1 Yinan Liu,1 Yanhong Hu,1 Jing Yang,1 Yan Lei1 1Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, People’s Republic of China; 3National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Yan Lei; Jing Yang, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China, Tel +13651217893 ; +15901070286, Email 13651217893@163.com; yangjingdr@163.comObjective: To explore the mechanism of the traditional Chinese medicine (TCM), Zhizhu granule (ZZG), in treating metabolic syndrome (MS) based on network pharmacology and pharmacodynamic experiment.Materials and Methods: Network pharmacology combined with a pharmacodynamic experiment was used to elucidate the therapeutic mechanism of ZZG in MS. Serum samples were collected from rats with MS, induced by a high-sugar-fat-salt diet (HSFSD) combined with streptozotocin (STZ), to measure the levels of biochemical markers. The glucose (GLU), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were detected. The liver tissue of rats was used for histological examination and Western blot analysis.Results: Network pharmacology analysis generated 69 drug-disease common targets and 10 hub genes closely related to ZZG against MS. KEGG pathway analysis revealed that the PI3K/AKT signaling pathway was the most potential pathway, which took part in the therapeutic mechanisms. In the animal experiments section, the therapeutic effect of ZZG on MS and the therapeutic pathway of ZZG on MS were verified. ZZG could significantly decrease the body weight, TC, TG, LDL-C and GLU levels in MS rats (all p< 0.01), alleviate hepatocyte steatosis and decrease liver lipid droplet deposition. Western blot analysis indicated that compared with the model group, the expression levels of PI3K, AKT, and IRS-1 protein were significantly increased (all p< 0.05), and the FOXO-1 was significantly decreased (all p< 0.05) in the ZZG group.Conclusion: ZZG can improve glucose-lipid metabolism disorder in rats with metabolic syndrome. The reported results provide experimental evidence for ZZG in the treatment of MS.Keywords: metabolic syndrome, network pharmacology, Zhizhu granule, pharmacodynamic experiment, PI3K/AKT pathway

Jing Wang,1,&ast; Yan Zhao,2,&ast; Cunming Lv,3,&ast; Feng Li1 1Department of Neurology, Lu’an Municipal People’s Hospital, Lu’an, People’s Republic of China; 2Department of Neurology, Jiangsu Provincial Medical Key Discipline (Laboratory), Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, People’s Republic of China; 3Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College, China Three Gorges University, Yichang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Li, Department of Neurology, Lu’an Municipal People’s Hospital, No.21 Wanxi West Road, Jin’an District, Lu’an, Anhui Province, People’s Republic of China, Email lif0616@163.comBackground: Neutrophil-to-lymphocyte ratio (NLR) and Lymphocyte-to-monocyte ratio (LMR) have been reported to be associated with outcomes in acute ischemic stroke. However, research on elderly populations remains relatively scarce. We investigated the prognosis of NLR and LMR in elderly with acute ischemic stroke(AIS).Methods: Based on the modified Rankin Score (mRS) on the 90th day after stroke, patients were divided into group and bad prognosis groups. Multivariate logistic regression analysis and receiver operating curves were used to identify prognostic factors and their predictive powers.Results: In total, 824 elderly patients with AIS were enrolled between November 2021 and December 2023. Significant differences emerged in the NLR, LMR, and lymphocyte count between the two groups (P< 0.05). Binary logistic regression identified NLR, LMR and neutrophil count as independent risk factors for an unfavorable prognosis in elderly patients with AIS. The areas under the curve (AUCs) of NLR, LMR, and the combination of NLR and LMR to discriminate poor function prognosis were 0.703, 0.672, and 0.706, respectively. ROC analysis also showed that combination of NLR and LMR was superior to NLR and LMR alone for predicting AIS.Conclusion: NLR and LMR independently contribute to an unfavorable prognosis in elderly patients with AIS. The area under the ROC curve (AUC) for the combined NLR and LMR was higher than that for NLR and LMR individually, suggesting that combining these two indicators can improve the predictive ability for clinical outcomes in elderly patients with AIS.Keywords: neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio, acute ischemic stroke, elderly patients

Jingwen Zhang,1,2,&ast; Guoqiang Zhang,1,2,&ast; JiaJia Wang,1,2,&ast; Yun Xiao,1,2 Xinxin Lu,1,2 Xunhong Lan,1,2 Yan Zhang,1,2 Zhang Dai1,2 1Centre of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 2Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Zhang; Zhang Dai, Centre of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China, Tel +86-0592-2293046, Email zy1983@xmu.edu.cn; 180219034@qq.comBackground: Nosocomial candidemia is a life-threatening condition, and the incidence has increased in recent years. Thorough epidemiological data is still lacking in China.Methods: A retrospective cohort study was conducted to investigate the patients admitted to Zhongshan Hospital Xiamen University from 1 January 2004 to 31 December 2022. This study included 205 individuals who were diagnosed with candidemia as subjects. Additionally, 303 cases with blood cultures were negative during the same period and were from the same department as a control group. We randomly assigned them to the training and validation groups in a 7:3 ratio. The least absolute shrinkage and selection operator regression, univariate and multivariate logistic regression analyses were used to filtrate independent factors associated with nosocomial candidemia. A nomogram model was established based on the selected variables. Receiver operating characteristic (ROC) curve, calibration plots and decision curve analysis (DCA) were used to evaluate clinical utility.Results: Two hundred and five nosocomial candidemia patients were reported, containing a high proportion of Candida albicans (n = 91,44.39%), followed by Candida parapsilosis (n = 40, 19.51%), Candida tropicalis (n = 37,18.05%), Candida glabrata (n = 23, 11.22%) and Candida guilliermondii (n = 9,4.39%). Multiple organ dysfunction syndrome (OR = 10.372, 95% CI: 4.745– 24.14 P < 0.001), increased urea nitrogen of serum (OR=1.088,95% CI: 1.039– 1.144 P< 0.001), decreased albumin of serum (OR = 0.922 95% CI: 0.850– 0.997 P=0.045), mechanical ventilation (OR=4.074,95% CI: 1.397– 12.77 P=0.012), central venous indwelling catheter (OR=7.422,95% CI: 3.189– 18.41 P< 0.001) and solid tumor (OR = 3.036 95% CI: 1.276– 7.359 P=0.012) were identified as independent risk factors of candidemia. The area under the curve (AUC) of the nomogram model was 0.925 (95% CI: 0.898– 0.952) in the training group and 0.946 (95% CI: 0.881– 0.963) in the validation group. The calibration curve revealed good agreement between the probability and the observed values. DCA indicated that this nomogram might be clinically beneficial.Conclusion: The nomogram including multiple organ dysfunction syndrome, elevated blood urea nitrogen, decreased albumin, mechanical ventilation, central venous indwelling catheter and solid tumor could provide reference value to clinicians for identifying nosocomial candidemia.Keywords: candidemia, risk factors, nomogram model, ROC curve

Maoye Shen,1 Wenxue Jiang,1 Ping Qian,1 Gaorui Cai,1 Xiaona Wu,1 Jinghua Wang,2 Xianjia Ning,2 Lixia Song1 1Department of Orthopedics, Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China; 2Center of Clinical Epidemiology, Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Lixia Song, Department of Orthopedics, Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, 29 Bulan Road, Longgang District, Shenzhen, Guangdong Province, 518112, People’s Republic of China, Tel + 86-755-61222333, Fax + 86-755-61238928, Email songlixia525529@163.com Xianjia Ning, Center of Clinical Epidemiology, Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, 29 Bulan Road, Longgang District, Shenzhen, Guangdong Province, 518112, People’s Republic of China, Tel +86-755-61222333, Fax +86-755-61238928, Email xjn0906@163.comBackground: Bilateral hip arthroplasty is a common surgical intervention for patients with bilateral hip disease. The decision between simultaneous versus staged procedures remains debated, primarily due to concerns over cost, postoperative recovery, and complication rates. This study aimed to evaluate the economic burden and clinical outcomes of simultaneous versus staged bilateral hip arthroplasty.Methods: In this single-center, prospective study, patients who underwent bilateral hip replacement at XXX between 2021 and 2022 were included. Participants were divided into groups based on the surgical approach: simultaneous bilateral hip arthroplasty or staged bilateral hip arthroplasty. Data on costs, operation times, hospital stay lengths, and postoperative outcomes were collected and analyzed.Results: A total of 57 patients were studied, with 45 undergoing simultaneous and 12 staged surgeries. The total cost for staged procedures was significantly higher, with a mean difference of 63,967.54 yuan compared to simultaneous procedures. No significant difference was found in prosthesis costs between the groups. Operation times and hospital stays did not significantly differ, with averages closely aligned between the simultaneous (operation time: 3.2 hours, hospital stay: 5 days) and staged groups (operation time: 3.4 hours, hospital stay: 5.2 days). The obesity rate was higher in the simultaneous group (P < 0.05).Conclusion: Simultaneous bilateral hip arthroplasty appears to be an economically favorable option, with comparable perioperative and immediate postoperative outcomes to staged procedures. These insights have significant implications for clinical practice and policy-making, suggesting that simultaneous procedures can be safely implemented for appropriate patients, potentially optimizing healthcare resources.Keywords: Bilateral Hip Arthroplasty, Simultaneous, Staged, Economic Burden, Clinical Outcomes

Junmei Fan,1,&ast; Jinghui Zhao,2,&ast; Junkun Zhang,3 Yanhua Chen,1 Xingyu Bi,1 Huiping Liu,1 Junfen Liu,1 Jinbao Wang,1 Xueqing Wu1 1Department of Reproductive Medicine Center, Children’s Hospital of Shanxi and Women Health Center of Shanxi, Taiyuan, Shanxi, 030013, People’s Republic of China; 2Department of Pediatric and Adolescent Gynecology, Shenzhen Children’s Hospital, Shenzhen, Guangdong, 518000, People’s Republic of China; 3Department of Intensive Care Unit, Shanxi Bethune Hospital, The Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xueqing Wu, Department of Reproductive Medicine Center, Children’s Hospital of Shanxi and Women Health Center of Shanxi, 13th Xinmin North Street, Xinghualing District, Taiyuan, Shanxi, 030013, People’s Republic of China, Tel +86 351 3360725, Email xueqingw_wu95@163.comBackground: This study aimed to explore the effect of vitamin D supplementation on lymphocyte subsets in infertile women.Methods: The study involved a total of 247 patients who suffered recurrent embryo implantation failure (RIF) or recurrent spontaneous abortion (RSA) between January and December 2019 in the Reproductive Medicine Center of Children’s Hospital of Shanxi and Women Health Center of Shanxi. The differences in the vitamin D and lymphocyte subsets of the two diseases, the correlation between the 25-hydroxy vitamin D and lymphocyte subsets, the changes in the lymphocyte subsets after vitamin D supplementation and the impact on pregnancy outcome were analysed.Results: The prevalence of vitamin D deficiency was 77.33% (191/247). After vitamin D supplementation, there were no significant differences in helper T cells (Th), cytotoxic T cells (Tc), Th/Tc and natural killer cells (NK) (p > 0.05), but there were significant differences in leukocyte differentiation antigens 3+ (CD3+), natural killer T cells (NKT), B lymphocytes and vitamin D (p < 0.05). Before vitamin D supplementation, the difference in the composition ratio of different vitamin D levels between the RIF and RSA groups was not statistically significant. At different vitamin D levels, there were no significant differences in CD3+, Th, Tc, Th/Tc, NK or B lymphocyte (p > 0.05), but there was a significant difference in NKT (p < 0.05).Conclusion: Vitamin D supplementation can reduce the level of NKT in infertile women, which may be of benefit to the pregnancy outcome of couples who experience RIF.Keywords: recurrent embryo implantation failure, infertility, lymphocyte subsets, recurrent spontaneous abortion, vitamin D

Yanping Wu,1 Yueqin Zheng,1 Sumei Sha,1 Yu Wang,2 Junyan Wang,3 Wei Zhang,4 Yixuan Lu,1 Yan Cheng,1 Jie Wu,5 Bin Qin,1 Yuan Gao6 1Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 2Department of Gastroenterology, Xi’an Central Hospital, College of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 3Department of Gastroenterology, the Second Affiliated Hospital of Xi ‘an Medical University, Xi’an, Shaanxi Province, People’s Republic of China; 4Department of General Internal Medicine, Staff Hospital of Changqing Oilfield, Xi’an, Shaanxi Province, People’s Republic of China; 5Department of Pathology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 6Department of Gastroenterology, Ankang Central Hospital, Ankang, Shaanxi Province, People’s Republic of ChinaCorrespondence: Bin Qin, Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an City, Shaanxi Province, 710004, People’s Republic of China, Email qinbin@xjtu.edu.cn Yuan Gao, Department of Gastroenterology, Ankang Central Hospital, Ankang City, Shaanxi Province, 725000, People’s Republic of China, Email gaoyuan015@163.comPurpose: Ischemic colitis appears to be a rare but serious complication of COVID-19. About 33.3% hospitalized COVID-19 patients who underwent endoscopy showed features resembling ischemic colitis. The aim of this prospective study was to describe the symptoms, treatment, and outcomes of these patients, particularly their colonoscopy and histologic findings.Patients and methods: We conducted a prospective study on ischemic bowel disease associated with COVID-19 across four centers from December 2022 to January 2023. All cases were identified through a comprehensive search of electronic medical records for procedure-related data. The initial diagnosis of ischemic bowel disease was confirmed using colonoscopy and biopsy findings. After the patients were discharged, a 12-month follow-up was conducted through regular phone interviews to assess their clinical outcomes.Results: Overall, the study included 3 male patients and 9 female patients (age range, 33– 76 years). Abdominal pain and hematochezia always occurred within 2 weeks after COVID-19 infection (average 5.5 days). Gastrointestinal manifestations did not parallel the severity of COVID-19 infection. The descending colon was the most susceptible segment, which was involved in 10 patients (83.33%). Colonoscopy revealed diffuse redness, edema, bleeding, erosion, and ulceration of the intestinal mucosa, similar to the findings of ischemic colitis, and biopsy revealed crypt atrophy, reduction, and interstitial bleeding. All patients were self-limited without converting to chronic changes in the next 12 months.Conclusion: SARS-CoV-2 infection may induce transient acute colon ischemia within 2 weeks, accompanied by severe clinical symptoms such as acute abdominal pain and hematochezia, which are self-limiting and do not lead to chronic symptoms.Keywords: SARS-CoV-2, lower gastrointestinal bleeding, ischemic colitis, colonoscopy

Fengting Wang,1,&ast; Limin Rong,1,&ast; Linlin Luo,2 Fuqin Mu,1 Liju Qian,3 Yandan Qian,4 Xinyao Zhang,1 Yuying Lang,1 Weijia Wang,1 Yan Liu,5,6 Ying Zhang,7 Jianli Wang1,8 1School of Mental Health, Jining Medical University, Jining, Shandong, People’s Republic of China; 2Department of Hematology, Tai’an Central Hospital, Tai’an, Shandong, People’s Republic of China; 3Shandong Daizhuang Hospital, Jining, Shandong, People’s Republic of China; 4The Third People’s Hospital of Jiashan County, Jiashan, Zhejiang, People’s Republic of China; 5School of Public Health, Jining Medical University, Jining, Shandong, People’s Republic of China; 6Center of Evidence-Based Medicine, Jining Medical University, Jining, Shandong, People’s Republic of China; 7School of Public Health, University of Sydney, Sydney, NSW, Australia; 8Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada&ast;These authors contributed equally to this workCorrespondence: Fengting Wang, School of Mental Health, Jining Medical University, Jining, Shandong, 272013, People’s Republic of China, Email wft.0810@163.com Yan Liu, School of Public Health, Jining Medical University, Jining, Shandong, 272013, People’s Republic of China, Email hakunaly@163.comBackground: Youth and young adults have a high prevalence of major depressive disorder (MDD). Limited longitudinal research has explored the relationship between different dimensions of psychological stress and MDD. This study aimed to estimate the effect of psychological stress on the risk of first onset MDD in a sample of Chinese freshmen.Methods: Using a longitudinal design, 8079 Chinese first-year students were recruited at baseline, and 6985 were followed up one year later. The Psychological Stress Scale for College Students was utilized to evaluate the levels of psychological stress. MDD was evaluated using the Chinese version of the Composite International Diagnostic Interview (CIDI-3.0). Logistic regression modeling was utilized to estimate the associations between dimensions of psychological stress and the risk of MDD.Results: Two dimensions of psychological stress, namely learning stress (OR=1.05, 95% CI:1.01– 1.09, P=0.017) and economic stress (OR=1.11, 95% CI:1.04– 1.19, P=0.001), were significantly associated with the risk of MDD. Other dimensions of psychological stress (specify family stress, interpersonal stress, intimate relationship stress, employment stress and appearance stress) were not associated with MDD.Conclusion: Psychological stress, especially learning and economic stresses, could increase the risk of MDD in university students. These factors should be incorporated into mental health prevention and intervention programs at universities to reduce the risks of MDD.Keywords: major depressive disorder, psychological stress, longitudinal study, freshmen

Nanxin Chen,1 Xuejie Si,2 Jun Wang,2 Wenjing Chen2 1First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250014, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250001, People’s Republic of ChinaCorrespondence: Wenjing Chen, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250000, People’s Republic of China, Email c13969155126@163.comBackground: The existence of an association between physical activity (PA) and asthma and chronic obstructive pulmonary disease (COPD) has been confirmed in observational studies. Therefore, it is necessary to reveal whether there is a risk-effect relationship between physical activity and asthma and COPD through Mendelian randomization (MR) analysis.Materials and Methods: Univariate Mendelian randomization (UVMR) analyses were performed to examine the associations between moderate to vigorous physical activity (MVPA), vigorous physical activity (VPA), accelerometer-assessed physical activity (AA), and strenuous exercise or other exercise (SSOE) with asthma and COPD. The methods of analysis were dominated by Inverse Variance-Weighted (IVW), Weighted median (WM), and MR-Egger methods. In addition, multivariate Mendelian randomization (MVMR) analyses were performed to correct the effects of four types of physical activity on asthma and COPD. Finally, potential mediating effect relationships were identified through mediation analyses.Results: The results of Univariate Mendelian randomization analysis showed that SSOE could reduce the risk of asthma and COPD(asthma: OR=0.15,95% CI=0.04– 0.58, P=0.006; COPD: OR=0.05, 95% CI=0.01– 0.33, P=0.002). The results of the Multivariate Mendelian randomization analysis showed that SSOE was still able to reduce the risk of asthma and COPD after adjusting for the effects of different types of physical activity(asthma: 95% CI=− 2.77–− 0.31, P=0.014; COPD: 95% CI=− 4.00–− 0.50, P=0.012). Mediation analyses showed that frailty intervened in the causal relationship between physical activity and asthma and chronic obstructive pulmonary disease.Conclusion: SSOE is a protective factor for asthma and COPD in the European population, while frailty plays a mediating role.Keywords: asthma, chronic obstructive pulmonary disease, multivariate Mendelian randomization, mediation analyses, physical activity, univariate Mendelian randomization

Luwei Xiang,1,&ast; Jing Wang,1,&ast; Wen Li,1,2 Hongfang Ye1,2 1School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 2Nursing Department, Nanjing Drum Tower Hospital, Nanjing, 210008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongfang Ye, School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Email 13915969627@163.comPurpose: To explore the status quo and influencing factors of personal mastery in Chinese patients with chronic heart failure, based on the analysis of patient characteristics.Methods: The sample of the study comprised 249 chronic heart failure patients who visited a university hospital in China. We collected the data using general demographic Information, personal mastery scale, the Simple Coping Style Questionnaire and Minnesota Living With Heart Failure Quality of Life Questionnaire (MLHFQ). SPSS26.0 was used to describe the survey results statistically, and univariate analysis, Pearson correlation analysis and multiple linear regression were used to analyze the influencing factors of personal sense of control.Results: Chronic heart failure patients’ total personal mastery scores were (20.63± 4.486), which is in the medium level. Multiple linear regression analysis shows that Age group (β=− 1.627, p=0.036), NYHA functional classification (β=− 1.563, P< 0.001), Positive coping style (β= 0.088, P=0.004) and MLHFQ (β= − 0.121 P< 0.001) significantly influenced patients’ personal mastery (P< 0.001).Conclusion: Our study suggests that the personal mastery of patients with chronic heart failure is at a moderate level in China. Additionally, age group, NYHA functional classification, Positive coping style and MLHFQ emerged as significant influencing factors. Clinical staff should dynamically observe the changes in the level of personal mastery of patients with chronic heart failure, pay more attention to the elderly and patients with poor heart function according to the influencing factors, and encourage active responses to improve the level of personal mastery of patients with heart failure.Keywords: chronic heart failure, the personal mastery, positive coping style, negative coping style, quality of life

Shouye Sun,1 Qian Wang,2 Bin Zhang,3 Yutao Cui,1 Xinghui Si,4 Gan Wang,1 Jingwei Wang,1 Hang Xu,1 Baoming Yuan,1 Chuangang Peng1 1Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Otolaryngology, The First Hospital of Jilin University, Changchun, People’s Republic of China; 3Department of Spinal Surgery, The 964th Hospital of PLA Joint Logistic Support Force, Changchun, People’s Republic of China; 4Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, People’s Republic of ChinaCorrespondence: Baoming Yuan, Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China, Email yuanbm@jlu.edu.cnPurpose: During treatment of infected bone defects, control of infection is necessary for effective bone repair, and hence controlled topical application of antibiotics is required in clinical practice. In this study, a biodegradable drug delivery system with in situ gelation at the site of infection was prepared by integrating vancomycin into a polyethylene glycol/oxidized dextran (PEG/ODEX) hydrogel matrix.Methods: In this work, PEG/ODEX hydrogels were prepared by Schiff base reaction, and vancomycin was loaded into them to construct a drug delivery system with controllable release and degradability. We first examined the microstructure, degradation time and drug release of the hydrogels. Then we verified the biocompatibility and in vitro ability of the release system. Finally, we used a rat infected bone defect model for further experiments.Results: The results showed that this antibacterial system could be completely biodegradable in vivo for 56 days, and its degradation products did not cause specific inflammatory response. The cumulative release of vancomycin from the antibacterial system was 58.3% ± 3.8% at 14 days and 78.4% ± 3.2% at 35 days. The concentration of vancomycin in the surrounding environment was about 1.2 mg/mL, which can effectively remove bacteria. Further studies in vivo showed that the antibacterial system cleared the infection and accelerated repair of infected bone defects in the femur of rats. There was no infection in rats after 8 weeks of treatment. The 3D image analysis of the experimental group showed that the bone volume fraction (BV/TV) was 1.39-fold higher (p < 0.001), the trabecular number (Tb.N) was 1.31-fold higher (p < 0.05), and the trabecular separation (Tb.Sp) was 0.58-fold higher than those of the control group (p < 0.01).Conclusion: In summary, this study clearly demonstrates that a clinical strategy based on biological materials can provide an innovative and effective approach to treatment of infected bone defects.Keywords: infected bone defects, drug delivery system, hydrogel, vancomycin

Jinglei Wang,1 Dehong Qiao,2 Yunzhu Wang,3 Rui Xiong,1 Xinyi Ding,1 Wei Zhang,3 Tingting Wang,1 Kai Tang1 1Department of Gastroenterology, Zhejiang Rongjun Hospital, Jiaxing, People’s Republic of China; 2Minimally Invasive Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, Jiaxing, People’s Republic of China; 3Endoscopy Center, Zhejiang Rongjun Hospital, Jiaxing, People’s Republic of ChinaCorrespondence: Kai Tang, Department of Gastroenterology, Zhejiang Rongjun Hospital, Jiaxing, People’s Republic of China, +86 15858363565, Email 15858363565@sohu.comPurpose: Helicobacter pylori (Hp)-related gastropathies are accompanied by alterations in gastric secretion function, but the effects of infection of different Hp strains on gastric function are not yet well-elucidated. Our cross-sectional clinical study aim to research the effects of infection with different Hp types on gastric function.Patients and Methods: We analyzed 525 patients’ serum cytotoxin-associated protein gene A (CagA), vacuolating cytotoxin-associated protein gene A (VacA), urease (Ure), Gastrin-17 (G-17), Pepsinogen I (PGI), Pepsinogen II (PGII) and PGI/PGII ratio (PGR).Results: The PGII levels (8.19 ± 5.44 vs 5.98 ± 10.75, P = 0.013) were higher in the Hp infected group than in the uninfected, while the PGR levels (16.81 ± 8.22 vs 23.23 ± 8.36, P < 0.001) were lower. The PGR levels were higher in the uninfected group (23.23 ± 8.36, P < 0.001) than in Hp-I (16.47 ± 7.45) and Hp-II infected groups (17.39 ± 8.98). In the uninfected group, the G-17 level was positively correlated with the levels of PGI (Pearson coefficient = 0.177, P = 0.001), PGII (Pearson coefficient = 0.140, P = 0.008) and age (Pearson coefficient = 0.121, P = 0.022), negatively with the PGR levels (Pearson coefficient = − 0.201, P < 0.001). In the Hp-I (Pearson coefficient = − 0.003, P = 0.975) and Hp-II (Pearson coefficient = 0.018, P = 0.161) infected groups, the G-17 levels were not correlated with age.Conclusion: Hp-I with CagA and/or VacA positive and Hp-II without cytotoxicity can reduce gastric secretion function regardless of age and sex. Gastric function in patients with Hp eradication was similar to that in those without Hp infection. G-17 rises physiologically with age, but infection with Hp will affect it.Keywords: Helicobacter pylori, Pepsinogen I, Pepsinogen II, Gastrin-17, cytotoxin-associated protein gene A, vacuolating cytotoxin-associated protein gene A

Zhengdong Yang, Xinyang Wang, Huiying Zhou, Minghan Jiang, Jinghui Wang, Bowen Sui The First Department of Oncology, Heilongjiang University of Chinese Medicine, Heilongjiang, 150040, People’s Republic of ChinaCorrespondence: Bowen Sui, The First Department of Oncology, Heilongjiang University of Chinese Medicine, Heilongjiang, 150001, People’s Republic of China, Email suibowen79@sina.comAbstract: Colorectal cancer (CRC) is a diverse disease entity and a leading cause of cancer-related mortality worldwide. CRC results from the accumulation of multiple genetic and epigenetic alterations. This heterogeneity of CRC underscores the significance of understanding its molecular landscape, as variations in tumor genetics can greatly influence both patient prognosis and therapeutic response. The molecular complexity of CRC is defined by three major carcinogenesis pathways: chromosomal instability (CIN), microsatellite instability (MSI), and the CpG island methylator phenotype (CIMP). These pathways contribute to the onset and progression of CRC through mutations, epigenetic modifications, and dysregulated cellular signalling networks. The heterogeneous nature of CRC continues to pose challenges in identifying universally effective treatments, highlighting the need for personalized approaches. Hence, the present review aims at unravelling the molecular complexity of CRC that is essential for improving diagnosis, prognostication, and treatment. We detail on the current understanding of the molecular framework of CRC, central signalling pathways of CRC associated with its initiation to a malignant phenotype, further invasion, progression, metastases, and response to therapy. Continued research into CRC’s pathways and biomarkers will pave the way for the development of more precise and effective therapeutic strategies, ultimately improving patient outcomes.Keywords: colorectal cancer, molecular mechanisms, pathways, chromosomal instability, adenomatous polyposis coli, biomarkers

Jie Wang,1 Yuanbo Wu,2 Meng Mao,3 Hailong Bing,1 Liwei Sun,1 Wei Xu,1 Wangli Tian,1 Zhengyuan Xia,4,5 Xiaogao Jin,1,6 Qinjun Chu1 1Department of Anesthesiology and Perioperative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Anesthesiology, Hubei Cancer Hospital, Wuhan, Hubei, People’s Republic of China; 3Center for Advanced Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450007, People’s Republic of China; 4Department of Anesthesiology, The First Affiliated Hospital, Jinan University, Guangzhou, People’s Republic of China; 5Department of Anesthesiology, The University of Hong Kong, Hong Kong; 6Department of Anesthesiology, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of ChinaCorrespondence: Xiaogao Jin; Qinjun Chu, Email jinxiaoagao@zzu.edu.cn; jimmynetchu@163.comPurpose: We aim to detect the effects of sivelestat on renal ischemia-reperfusion associated with AKI and also explore the underlying mechanism.Materials and Methods: Mice, aged between 8 and 12 weeks, were randomly allocated among four distinct groups, respectively normal saline sham group(C), normal saline surgery group(I), sivelestat (50 mg/kg) sham group(S), sivelestat (50 mg/kg) surgery group(SI) (n=6, each group). In the surgical groups, the renal pedicles of mice were clamped with non-traumatic micro-aneurysm clamps, resulting in ischemia of the kidneys for 45 minutes. This was followed by a period of reperfusion lasting 24 hours. Sham group mice underwent the identical surgery produced without clamping renal pedicles. Mice blood was obtained from eyeballs, and Serum creatinine and blood urea nitrogen levels were measured. After a 24-hour period of reperfusion, the mice were euthanized, and their kidneys were gathered for various analyses, including Western Blot (WB) analysis, RT-PCR, immunofluorescence (IF), hematoxylin and eosin (H&E) staining, and Tunel assay.Results: Pretreatments with sivelestat decreased renal Neutrophil elastase (NE), serum creatinine, and blood urea nitrogen levels after renal ischemia-reperfusion. Sivelestat also reduced histological damage and cell apoptosis in kidneys following ischemia-reperfusion injury (IRI). In addition, the sivelestat administration diminished the levels of mRNA expression of interleukin 6 (IL-6), Macrophage inflammatory protein-2 (MIP-2), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-α in the kidneys during IRI. The kidney tissues of the SI group had significantly mitigated TLR4, Myd88, and NF-κB p-p65 protein expression levels compared to the I group (all P< 0.05).Conclusion: We demonstrated a previously unidentified mechanism that sivelestat effectively attenuates AKI-induced renal dysfunction, possibly through suppressing the TLR4/Myd88/ NF-κB pathway.Keywords: neutrophil elastase, ischemia reperfusion injury, renal dysfunction, inflammation

Yong Huang,&ast; Chunmei Yin,&ast; Jue Wang, Maijian Wang, Xingbin Zheng, Ming Xie, Jiwei Wang Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiwei Wang, Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, Guizhou, People’s Republic of China, Tel +86-13017410630, Email wjw@smail.nju.edu.cnPurpose: This study investigated the effects of parenteral glutamine (Gln) supplement immunonutrition versus conventional nutritional support on postoperative Clavien–Dindo classification complications and recovery, perioperative nutritional status, and immune, inflammation, and safety indicators in patients with colorectal cancer (CRC).Patients and Methods: Clinical data were collected for a retrospective cohort study of 178 patients (58 and 120 patients in the observation and control groups, respectively) who underwent radical resection of CRC from January 2019 to December 2021. The incidence of postoperative complications was calculated. Postoperative recovery, nutritional indicators, inflammatory factors indicator, and the safety indicators before operation and at 1, 3, and 7 days after operation were compared. SPSS 29.0 statistical software was used for statistical analysis.Results: The incidence of postoperative overall complications in the control group and the observation group was 22.50% (27/120) and 17.24% (10/58), respectively, and there was no significant difference between the two groups (P=0.42). The incidence of postoperative complications of Clavien-Dindo grade ≥III in the control group and the observation group was 14.17% (17/120) and 3.45% (2/58), respectively, and the difference between the two groups was statistically significant (P=0.03). Secondary outcomes (first exhaust, defecation, and liquid diet intake times) were significantly recovered earlier in the observation group than those in the control group (P< 0.05), while the postoperative hospital stay was significantly shorter(P=0.04). The perioperative nutritional status did not significantly differ between the groups before and after surgery(P> 0.05), although significant differences were observed in several inflammatory and safety indicators(P< 0.05).Conclusion: Unlike conventional nutritional support, postoperative parenteral Gln supplementation reduced the incidence of postoperative Clavien–Dindo complications grade ≥III in patients with CRC while increasing intestinal and immune functions, decreasing inflammation, and reducing the length of hospital stay.Keywords: glutamine, parenteral nutrition, colorectal cancer, clavien–dindo complication

Na Yu,1,&ast; Mingqin Su,1,&ast; Juan Wang,2 Yakun Liu,1 Jingya Yang,1 Jingyi Zhang,1 Meimei Wang1 1Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2Department of Public Health Inspection and Quarantine, School of Public Health, Anhui Medical University, Hefei, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meimei Wang, Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, No. 81, Mei-Shan Road, Hefei, 230032, People’s Republic of China, Email wangmm@ustc.edu.cnBackground: Tumor development and progression is a long and complex process influenced by a combination of intrinsic (eg, gene mutation) and extrinsic (eg, environmental pollution) factors. As a detoxification organ, the liver plays an important role in human exposure and response to various environmental pollutants including nanomaterials (NMs). Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and remains a serious threat to human health. Whether NMs promote liver cancer progression remains elusive and assessing long-term exposure to subtoxic doses of nanoparticles (NPs) remains a challenge. In this study, we focused on the promotional effects of nano zinc oxide (nZnO) on the malignant progression of human HCC cells HepG2, especially aged nZnO that has undergone physicochemical transformation.Methods: In in vitro experiments, we performed colony forming efficiency, soft agar colony formation, and cell migration/invasion assays on HepG2 cells that had been exposed to a low dose of nZnO (1.5 μg/mL) for 3 or 4 months. In in vivo experiments, we subcutaneously inoculated HepG2 cells that had undergone long-term exposure to nZnO for 4 months into BALB/c athymic nude mice and observed tumor formation. ZnCl2 was administered to determine the role of zinc ions.Results: Chronic low-dose exposure to nZnO significantly intensified the malignant progression of HCC cells, whereas aged nZnO may exacerbate the severity of malignant progression. Furthermore, through transcriptome sequencing analysis and in vitro cellular rescue experiments, we demonstrated that the mechanism of nZnO-induced malignant progression of HCC could be linked to the activation of Claudin-2 (CLDN2), one of the components of cellular tight junctions, and the dysregulation of its downstream signaling pathways.Conclusion: Long-term exposure of fresh and aged nZnO promotes hepatocellular carcinoma malignancy by up-regulating CLDN2. The implications of this work can be profound for cancer patients, as the use of various nanoproducts and unintentional exposure to environmentally transformed NMs may unknowingly hasten the progression of their cancers. Keywords: nano zinc oxide, environmental transformation of NPs, long-term exposure, malignant progression of tumors, CLDN2

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

Xiwen Yin,1,&ast; Qiang Zhang,1,&ast; Yuting Wang,1 Bilin Tao,1 Xiaolong Zhang,2 Jinyan Shi,3 Xiaowei Deng,1 Jianming Wang1,4,5 1Department of Epidemiology, Key Laboratory of Public Health Safety and Emergency Prevention and Control Technology of Higher Education Institutions in Jiangsu Province, Center for Global Health, School of Public Health, Nanjing, 211166, People’s Republic of China; 2Department of Tuberculosis Control, Center for Disease Control and Prevention, Suzhou, 215000, People’s Republic of China; 3Department of Clinical Laboratory, The Fourth People’s Hospital of Lianyungang, Lianyungang, 222000, People’s Republic of China; 4Department of Tuberculosis, The Third People’s Hospital of Changzhou, Changzhou, 215000, People’s Republic of China; 5National Vaccine Innovation Platform, Nanjing Medical University, Nanjing, 211166, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianming Wang, Department of Epidemiology, Key Laboratory of Public Health Safety and Emergency Prevention and Control Technology of Higher Education Institutions in Jiangsu Province, Center for Global Health, School of Public Health, Nanjing, 211166, People’s Republic of China, Tel +86-25-86868414, Email jmwang@njmu.edu.cnPurpose: Understanding the mode of Mycobacterium tuberculosis (M. tuberculosis) transmission is crucial for disease prevention and control. Compared to traditional genotyping methods, whole genome sequencing (WGS) provides higher resolution and comprehensive genetic information, enabling the tracing of infection sources and determining of transmission routes to resolve extensive tuberculosis (TB) outbreaks. We conducted a ten-year study on the transmission of M. tuberculosis in a population in eastern China.Patients and Methods: We selected Lianyungang, an eastern city in China, as the study site. Patients diagnosed with active pulmonary TB from 2011 to 2020 were enrolled as the study subjects. We isolated and sequenced 2252 M. tuberculosis. Strains with pairwise genetic distances of less than 12 single nucleotide polymorphisms were defined as genomic clusters and which were considered recent transmissions. Kernel density estimation and K-function analysis were applied to explore the spatial distribution of recently transmitted strains.Results: After excluding non-tuberculous mycobacteria and duplicated samples, 2114 strains were included in the final analysis. These strains comprised lineage 2 (1593, 75.35%) and 4 (521, 24.65%). There were 672 clustered strains, with a recent transmission rate of 31.79%. The logistic regression model showed that the risk of recent transmission was high in students [adjusted odds ratio (aOR): 2.68, 95% confidence interval (CI): 1.63– 4.49, P< 0.001] and people infected with L2.2.1 strains (aOR: 1.59, 95% CI: 1.20– 2.12). Higher spatial aggregation of TB transmission has been concentrated in Haizhou, Donghai, and Guanyun for the past 10 years. Three outbreaks affecting 46 patients were spatially spaced, with 11 to 23 persons each. Different groups exhibited varying geographic distances between the initial and later cases.Conclusion: There are areas with a high risk of transmission for M. tuberculosis in the research site, and the risk varies among different populations. Accurate prevention strategies targeted at specific regions and key populations can help curb the prevalence of TB.Keywords: tuberculosis, transmission, cluster, whole genome sequencing, spatial analysis

Wenbin Guo,1,&ast; Lin Sun,1,&ast; Huijun Yue,1,&ast; Xueqin Guo,1 Lin Chen,1 Jinhong Zhang,1 Zhuqi Chen,1 Yiming Wang,1 Jiao Wang,2 Wenbin Lei1 1Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of China; 2School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiao Wang, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong, People’s Republic of China, Email wangj836@mail.sysu.edu.cn Wenbin Lei, Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, People’s Republic of China, Email leiwb@mail.sysu.edu.cnPurpose: Clinical studies focusing on the association between the gut microbiota and obstructive sleep apnea (OSA) are limited. This study aimed to explore the relationship between intermittent hypoxia and the composition of gut microbiota in adults by analyzing the differences in the characteristics and functional distribution of gut microbiota between patients with different severities of OSA and healthy individuals.Patients and Methods: A cohort of 113 individuals from the First Affiliated Hospital of Sun Yat-sen University underwent overnight polysomnography from July 2019 to August 2021. The individuals included 16 healthy controls and 97 patients with OSA, categorized by the apnea-hypopnea index into mild, moderate, and severe groups. Fecal samples were analyzed using high-throughput sequencing of the 16S rRNA V3–V4 region to assess gut microbiota composition and function. Correlation analysis was used to evaluate the association between clinical indicators and microbiota markers.Results: In patients with OSA, the gut microbiota diversity and the abundance of specific microbes that produce short-chain fatty acids decreased (P< 0.05). The phyla Verrucomicrobia and Candidatus Saccharibacteria, genera Gemmiger and Faecalibacterium, and the species Gemmiger formicilis exhibited decreasing abundance with increasing OSA severity. Correlation analysis revealed a robust association between the proportion of total sleep time, characterized by nighttime blood oxygen saturation below 90%, and the alterations in the gut microbiota, demonstrating that elevated levels of desaturation are correlated with pronounced microbiota dysbiosis (P< 0.05).Conclusion: Compared to the control group, the intermittent hypoxia exhibited by patients with OSA may be related to alterations in the composition and structure of the gut microbiota. Our results demonstrate the importance of monitoring hypoxia indicators in future clinical practice.Keywords: obstructive sleep apnea, gut microbiota, 16S rRNA, intermittent hypoxia

Mingtao Liu,1,&ast; Zhangkai J Cheng,1,&ast; Jiaxi Chen,2,&ast; Haiyang Li,1,3 Mingshan Xue,4,5 Xing Fu,1 Yanjun Li,2 Jiaxin Wang,2 Chenwei You,2 Haisheng Hu,1 Haojie Wu,1 Huimin Huang,1 Baoqing Sun1,4 1Department of Clinical Laboratory of the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, 510120, People’s Republic of China; 2KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, 511495, People’s Republic of China; 3MRC Biostatistics Unit, University of Cambridge, Cambridge, CB2 0SR, UK; 4Guangzhou Laboratory, Guangzhou, 510005, People’s Republic of China; 5Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, 510440, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoqing Sun; Huimin Huang, Department of Clinical Laboratory of the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, 510120, People’s Republic of China, Tel +86 13824124015 ; +86 13631496651, Email sunbaoqing@vip.163.com; huanghuimin311@126.comBackground: While serum periostin and Krebs von den Lungen-6 (KL-6) have been acknowledged as independent markers in idiopathic pulmonary fibrosis (IPF) diagnosis, the clinical combinatory potential of these biomarkers combined with high-resolution computed tomography (HRCT) has yet to be fully explored.Methods: This retrospective study involved 78 participants, comprising 51 UIP-IPF patients and 27 healthy controls. All subjects underwent clinical and laboratory examinations, particularly the detection of periostin and KL-6 using ELISA with innovative HRCT fibrosis score evaluations at admission and discharge during hospitalization in UIP-IPF patients.Results: In our cohort of patients with IPF, predominantly male, over an average follow-up period of 195.27 days. Serum levels of periostin and KL-6 were significantly elevated in IPF patients compared to healthy controls (&ast;p < 0.05). Post-treatment, KL-6 levels decreased significantly, while periostin levels increased. Notably, periostin exhibited superior prognostic accuracy over KL-6, with a higher AUC of 0.875 than 0.639 in ROC analysis. An increase in periostin levels correlated with disease progression, as evidenced by worsened HRCT fibrotic scores and decreased survival probability. These findings underscore periostin’s potential as a reliable biomarker for assessing IPF severity and therapeutic response.Conclusion: Our findings underscore the preeminence of serum periostin over KL-6 in UIP-IPF diagnosis, particularly when conjoined with HRCT fibrosis score.Keywords: periostin, Krebs von den Lungen-6, idiopathic pulmonary fibrosis, HRCT fibrosis score, diagnostic hematology