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

Jianbao Zheng,1,2,* Zepeng Dong,1,* Xianzhen Jin,1 Jing Li,2 Yuanwu Zou,2 Guanghong Bai,2 Qianhong Wu,2 Shenghang Xu,3 Zifeng Wang,3 Xuejun Sun,1 Dingxin Liu,3 Li Guo3 1Department of General Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 2Tuberculosis Prevention and Treatment Hospital in Shaanxi Province, Xi’an, 710100, People’s Republic of China; 3Center for Plasma Biomedicine, State Key Laboratory of Electrical Insulation and Power Equipment, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qianhong Wu; Li Guo, Email 15902969531@126.com; guoli35@mail.xjtu.edu.cnPurpose: This study aimed to investigate the antibacterial effects of plasma-activated saline (PAS) on My-cobacterium tuberculosis (Mtb).Methods: We conducted a growth assay on 3 strains of Mtb and an antibiotic sensitivity test on 4 strains of Mtb. Both tests included groups treated with normal saline (NS), PAS, and hydrochloric acid (HCl). The test of antibiotic sensitivity consisted of parallel tests with two concentrations of bacteria suspension: 10− 2 and 10− 4. The selected antibiotics were rifampicin (RIF), isoniazid (INH), ethambutol (EMB), and streptomycin (SM). The number of bacteria was determined after one month of culture under different conditions. The Kruskal–Wallis test was used to analyze the differences in grouping factors at representative time points.Results: The growth assay indicated that PAS significantly inhibited the growth of 3 strains of Mtb compared with NS and HCl treatment groups. Furthermore, except for the initial observation time point, the remaining three observation time points consistently demonstrate no significant differences between the NS group and the HCl group. The antibiotic sensitivity test of INH, SM, and RIF indicated that PAS could inhibit the growth of antibiotic-resistant Mtb, and the antibiotic sensitivity test of INH and SM with bacterial suspension concentration of 10− 2 and SM with bacterial suspension concentration of 10− 4 showed statistically different results. The antibiotic sensitivity test of EMB indicated that the growth of Mtb in PAS was slower than that in NS and HCl in both antibiotic-resistant and sensitive Mtb, but there was no statistical difference.Conclusion: The study indicates that PAS contains a significant amount of active substances and exhibits high oxidizability and an acidic pH state. The unique physicochemical properties of PAS significantly delayed the growth of Mtb, compared to the NS and the HCl. PAS not only inhibited the growth of drug-sensitive strains but also significantly enhanced the sensitivity of drug-resistant strains to anti-tuberculosis drugs, which may provide a new therapeutic strategy for the treatment of tuberculosis.Keywords: plasma-activated saline, mycobacterium tuberculosis, antibacterial effect, antibiotic sensitivity

Huali Fei,1 Yixuan Yin,2 Xiaoyan Guo,3 Xuejing Jin1 1Department of Reproductive Endocrinology, Hangzhou Women’s Hospital, Hangzhou, People’s Republic of China; 2Department of Prenatal Diagnosis Center, Hangzhou Women’s Hospital, Hangzhou, People’s Republic of China; 3Department of Gynecology, Hangzhou Women’s Hospital, Hangzhou, People’s Republic of ChinaCorrespondence: Yixuan Yin, Department of Prenatal Diagnosis Center, Hangzhou Women’s Hospital, Hangzhou, People’s Republic of China, Email yinyixuan83@hotmail.comObjective: To report a rare case of spontaneous ectopic pregnancy (EP) after partial salpingectomy treated by laparoscopy.Case Report: A 30-year-old gravida 1 para 0 woman with a history of left adnexectomy, due to left ovarian torsion 13 years ago, was referred to our hospital. She had experienced lower abdominal pain for 1 day and amenorrhea for 1 week. Transvaginal ultrasonography did not reveal an intrauterine pregnancy, but showed a suspected extrauterine gestational sac on the left adnexal area. The patient was diagnosed with ectopic pregnancy, and laparoscopy was performed. During the operation, we found a gestational sac on the left fallopian tube stump.Conclusion: The most significant risk factors for ectopic pregnancy (EP) are previous procedures and conditions that cause tubal injury. Therefore, it is necessary to be alert to the occurrence of the disease even if there is a history of tubal resection and ensure no part of the fallopian tube is left behind during removal.Keywords: proximal tubal pregnancy, ectopic pregnancy, partial salpingectomy

Xiaofan Jin,1 Xiuzu Song2 1Zhejiang University School of Medicine, Department of Dermatology, Hangzhou Third People’s Hospital, Affiliated Hangzhou Dermatology Hospital, Hangzhou, People’s Republic of China; 2Department of Dermatology, Hangzhou Third People’s Hospital, Affiliated Hangzhou Dermatology Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Xiuzu Song, Department of Dermatology, Hangzhou Third People’s Hospital, Affiliated Hangzhou Dermatology Hospital, Zhejiang University School of Medicine, Westlake Ave 38, Hangzhou, 310009, People’s Republic of China, Email songxiuzu@sina.comAbstract: Autophagy is recognized as a crucial regulatory process, instrumental in the removal of senescent, dysfunctional, and damaged cells. Within the autophagic process, lysosomal digestion plays a critical role in the elimination of impaired organelles, thus preserving fundamental cellular metabolic functions and various biological processes. Mitophagy, a targeted autophagic process that specifically focuses on mitochondria, is essential for sustaining cellular health and energy balance. Therefore, a deep comprehension of the operational mechanisms and implications of autophagy and mitophagy is vital for disease prevention and treatment. In this context, we examine the role of autophagy and mitophagy during hair follicle cycles, closely scrutinizing their potential association with hair loss. We also conduct a thorough review of the regulatory mechanisms behind autophagy and mitophagy, highlighting their interaction with hair follicle stem cells and dermal papilla cells. In conclusion, we investigate the potential of manipulating autophagy and mitophagy pathways to develop innovative therapeutic strategies for hair loss.Keywords: hair follicle, mitophagy, dermal papilla cell, hair follicle stem cell, alopecia

XiaoLang Miao,1 Yanxia Han,1 Zhenyun Wu,1 Xiaoliang Jin,1 Mei’e Niu,1 Qian Zhao,1 Xiangmin Lu2 1Department of Respiratory Medicine, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2School of Nursing, Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Mei’e Niu, Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, 899th, Pinghai Road, Suzhou, 215006, People’s Republic of China, Tel +86 13812671786, Email meniu_123@163.comPurpose: To translate a disease-specific anxiety questionnaire on chronic obstructive pulmonary disease (COPD) and test its reliability and validity in China.Patients and Methods: The German version of the revised COPD Anxiety Questionnaire (CAF-R) was initially validated using step-by-step translation, back-translation, and cross-cultural adaptation. The reliability and validity of the Chinese version of the CAF-R (CAF-R-CN) were tested among 448 patients with COPD (mean age =71.42± 9.33 years, 17.2% female) from four medical institutions in Suzhou, Jiangsu Province, using convenience sampling, from April 2022 to June 2023.Results: The CAF-R-CN included six dimensions with a total of 25 items. The item-level content validity index was 0.860– 1.000; the scale-level content validity index was 0.920. The structural validity χ2/df was 2.326, the root mean square error of approximation was 0.077, the comparative fit index was 0.924, and the Tucker–Lewis index was 0.912. The six-dimensional internal consistency index Cronbach’s α coefficient was 0.696– 0.910, and the test–retest reliability was 0.949. An optimal cut-off score of 50.5 was selected with a sensitivity of 0.786 and specificity of 0.870.Conclusion: The CAF-R-CN had satisfactory reliability and validity and can be used to identify and assess anxiety in COPD patients with a Chinese cultural background.Keywords: fear, scale, specificity, chronic respiratory disease, Chinese translation, assessment

Chaoqun Tang,1 Lei Li,2 Xin Jin,2 Jinfeng Wang,2 Debao Zou,2 Yan Hou,2 Xin Yu,2 Zhizhou Wang,2 Hongjiang Jiang1,2 1The First Clinical Medical School, Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China; 2Department of Orthopedics, Shandong Wendeng Osteopathic Hospital, Wendeng, Weihai, Shandong, People’s Republic of ChinaCorrespondence: Hongjiang Jiang, Department of Orthopedics, Shandong Wendeng Osteopathic Hospital, Wendeng, Weihai, Shandong, People’s Republic of China, Tel +86-19819687688, Email boneman@163.comBackground: The relationship between gout and gut microbiota has attracted significant attention in current research. However, due to the diverse range of gut microbiota, the specific causal effect on gout remains unclear. This study utilizes Mendelian randomization (MR) to investigate the causal relationship between gut microbiota and gout, aiming to elucidate the underlying mechanism of microbiome-mediated gout and provide valuable guidance for clinical prevention and treatment.Materials and Methods: The largest genome-wide association study meta-analysis conducted by the MiBioGen Consortium (n=18,340) was utilized to perform a two-sample Mendelian randomization investigation on aggregate statistics of intestinal microbiota. Summary statistics for gout were utilized from the data released by EBI. Various methods, including inverse variance weighted, weighted median, weighted model, MR-Egger, and Simple-mode, were employed to assess the causal relationship between gut microbiota and gout. Reverse Mendelian randomization analysis revealed a causal association between bacteria and gout in forward Mendelian randomization analysis. Cochran’s Q statistic was used to quantify instrumental variable heterogeneity.Results: The inverse variance weighted estimation revealed that Rikenellaceae exhibited a slight protective effect on gout, while the presence of Ruminococcaceae UCG_011 is associated with a marginal increase in the risk of gout. According to the reverse Mendelian Randomization results, no significant causal relationship between gout and gut microbiota was observed. No significant heterogeneity of instrumental variables or level pleiotropy was detected.Conclusion: Our MR analysis revealed a potential causal relationship between the development of gout and specific gut microbiota; however, the causal effect was not robust, and further research is warranted to elucidate its underlying mechanism in gout development. Considering the significant association between diet, gut microbiota, and gout, these findings undoubtedly shed light on the mechanisms of microbiota-mediated gout and provide new insights for translational research on managing and standardizing treatment for this condition.Keywords: Gout, Gut Microbiota, Mendelian Randomization, Diet

Jing-Fan Gao,* Yue-Yan Dong,* Xin Jin, Li-Jun Dai, Jing-Rao Wang, Hong Zhang Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Zhang, Department of Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China, Email zhanghong@hrbmu.edu.cnObjective: Keratoconus is a commonly progressive and blinding corneal disorder. Iron metabolism and oxidative stress play crucial roles in both keratoconus and ferroptosis. However, the association between keratoconus and ferroptosis is currently unclear. This study aimed to analyze and verify the role of ferroptosis-related genes (FRGs) in the pathogenesis of keratoconus through bioinformatics.Methods: We first obtained keratoconus-related datasets and FRGs. Then, the differentially expressed FRGs (DE-FRGs) associated with keratoconus were screened through analysis, followed by analysis of their biological functions. Subsequently, the LASSO and SVM-RFE algorithms were used to screen for diagnostic biomarkers. GSEA was performed to explore the potential functions of the marker genes. Finally, the associations between these biomarkers and immune cells were analyzed. qRT‒PCR was used to detect the expression of these biomarkers in corneal tissues.Results: A total of 39 DE-FRGs were screened, and functional enrichment analysis revealed that the DE-FRGs were closely related to apoptosis, oxidative stress, and the immune response. Then, using multiple algorithms, 6 diagnostic biomarkers were selected, and the ROC curve was used to verify their risk prediction ability. In addition, based on CIBERSORT analysis, alterations in the immune microenvironment of keratoconus patients might be associated with H19, GCH1, CHAC1, and CDKN1A. Finally, qRT‒PCR confirmed that the expression of H19 and CHAC1 was elevated in the keratoconus group.Conclusion: This study identified 6 DE-FRGs, 4 of which were associated with immune infiltrating cells, and established a diagnostic model with predictive value for keratoconus.Keywords: keratoconus, ferroptosis, immune infiltration, machine learning

Hua Qiang Wang,1 Xin Jiang,1 Dan Li,2 Xin Jin,3 Jie Zhang1 1School of Economics and Management, Yangtze University, Jingzhou, Hubei Province, People’s Republic of China; 2School of Business Administration, Zhongnan University of Economics and Law, WuHan, Hubei Province, People’s Republic of China; 3Wuchang Shouyi University, Wuhan, Hubei Province, People’s Republic of ChinaCorrespondence: Xin Jin, Email 47532103@qq.comPurpose: Despite growing evidence of significant role of leader perfectionism in the workplace, few theoretical accounts have delved into intricate dynamics of interpersonal relationships impacted by leader perfectionism, nor have they explored the extent to which these interactions might stimulate employee unethical behavior. From an interpersonal relationship perspective, based on interpersonal complementarity theory, this study proposes a link between leader perfectionism and employee deviant behavior while assessing the mediating impact of supervisor-subordinate relationship conflict, and the moderating influence of employee narcissism.Methods: This study employed three-wave surveys, with 335 employees (female 55.8%, 26– 35 years old 67.4%, bachelor’s degree 61.5%, worked 3– 10 years 67.4%, worked with their current leader 1– 5 years 66.3%) across 11 enterprises in Chinato reduce the risk of common method bias. On this basis, MPLUS 7.4 was used to test the confirmatory factor analysis of data, and SPSS 24.0 was used to test the hypotheses.Results: (1) Leader perfectionism has a positive effect on supervisor-subordinate relationship conflict. (2) Leader perfectionism has a significantly positive effect on employee deviant behavior via supervisor-subordinate relationship conflict. (3) Employee narcissism positively moderates the relationship between leader perfectionism and supervisor-subordinate relationship conflict, and further positively moderates the indirect effect of leader perfectionism on employee deviant behavior via supervisor-subordinate relationship conflict.Conclusion: This study reveals the mechanism of how employee through deviant behavior as a opposition to leader perfectionism from an interpersonal relationship perspective, which provides theoretical and practical implications for reducing the negative impact of leader perfectionism and employee deviant behavior.Keywords: leader perfectionism, employee narcissism, supervisor-subordinate relationship conflict, employee deviant behavior, an interpersonal relationship perspective

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

Kang Yang,1,* Chengye Liu,1,* Jun Shao,2 Lingxiang Guo,2 Qing Wang,3 Zhaoxiang Meng,1,* Xing Jin,1,* Xianghe Chen4,* 1Rehabilitation Medicine Department, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou city, Jiangsu Province, People’s Republic of China; 2Cardiovascular Disease Center, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou city, Jiangsu Province, People’s Republic of China; 3Respiratory Department, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou city, Jiangsu Province, People’s Republic of China; 4College of Physical Education, Yangzhou University, Yangzhou city, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xianghe Chen, College of Physical Education, Yangzhou University, Huayang West Road 196, Yangzhou city, Jiangsu Province, People’s Republic of China, Email huashixh@163.com Xing Jin, Rehabilitation Medicine Department, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Nantong West Road 98, Yangzhou city, Jiangsu Province, People’s Republic of China, Email yzjinxing@qq.comBackground: Swimming and intermittent fasting can both improve obesity-induced NAFLD, but which of the two is more effective and whether the combination of the two has a superimposed effect is inconclusive.Methods: The model of NAFLD in obese rats was established by a high-fat diet and performed swimming, intermittent fasting, and a combination of both interventions for 8 weeks. Serum lipids and enzyme activity were measured by an automatic biochemical analyzer. Liver morphostructural analysis was observed by transmission electron microscopy, and morphology was observed by HE staining. RT‒PCR was used to detect the mRNA level.Results: Morphology and microstructure of the liver of model rats were impaired, with the upregulation of miR-122-5p, SREBP-1c, FASN and ACC1. Eight weeks of swimming exercise, intermittent fasting and the combination of both attenuate these effects, manifested by the downregulation of miR-122-5p and upregulation of CPT1A mRNA levels. There was no significant stacking effect of the combination of the swimming and intermittent fasting interventions.Conclusion: NAFLD leads to pathology in model rats. Eight weeks of swimming exercise, intermittent fasting and the combination of both can inhibit miR-122-5p and improve hepatic lipid metabolism, while no significant additive effects of combining the interventions were found.Keywords: obesity, NAFLD, swimming, intermittent fasting, miR-122-5p

Jing Wang,1,&ast; Lisha He,2,&ast; Zhiyan Jin,1,&ast; Guoguang Lu,1 Sufei Yu,1 Lingling Hu,1 Meidan Fang,1 Xiaxia Jin1 1Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Taizhou, Zhejiang Province, People’s Republic of China; 2Department of Ultrasound, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Taizhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meidan Fang; Xiaxia Jin, Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Taizhou, Zhejiang Province, People’s Republic of China, Tel +86 13586102337; +86 15967063239, Email fangmd@enzemed.com; jinxiax@enzemed.comObjective: To explore the early predictors and their predicting value of 28-day mortality in sepsis patients and to investigate the possible causes of death.Methods: 127 sepsis patients were included, including 79 cases in the survival group and 48 cases in the death group. The results of all patients on admission were recorded. After screening the risk factors of 28-day mortality, the receiver operating characteristic curve (ROC) was used to determine their predictive value for the 28-day mortality rate on admission, and the Kaplan-Meier curve was drawn to compare the 28-day mortality rate between groups. Finally, patients with cytokine and lymphocyte subsets results were included for investigating the possible causes of death through correlation analysis.Results: APACHE II (acute physiology and chronic health evaluation II), SOFA (Sequential Organ Failure Assessment) and red blood cell distribution width (RDW) were the risk factors for 28-day mortality in sepsis patients (OR: 1.130 vs.1.160 vs.1.530, P < 0.05). The area under the curve (AUC), sensitivity and specificity of APACHE II, SOFA and RDW in predicting the mortality rate at 28 days after admission in sepsis patients were 0.763 vs 0.806 vs 0.723, 79.2% vs 68.8% vs 75.0%, 65.8% vs 89.9% vs 68.4%. The combined predicted AUC was 0.873, the sensitivity was 89.6%, and the specificity was 82.3%. The Kaplan-Meier survival curve showed that the 28-day mortality rates of sepsis patients with APACHE II≥ 18.5, SOFA≥ 11.5 and RDW≥ 13.8 were 58.5%, 80.5% and 59.0%, respectively. In the death group, APACHE II was positively correlated with SOFA, IL-2, and IL-10, and RDW was positively correlated with PLT, TNF-α, CD3+ lymphocyte count, and CD8+ lymphocyte count.Conclusion: Sepsis patients with high APACHE II, SOFA and RDW levels at admission have an increased 28-day mortality rate. The elevation of these indicators in dead patients are related to immune dysfunction.Keywords: sepsis, APACHE II, SOFA, red blood cell distribution width, mortality, immune dysfunction

Xu Su,1,&ast; Yimei Zhang,1,&ast; Huilin Zhou,1 Fang Ma,1 Xiaorong Jin,1 Yangjuan Bai,2 Wei Wei,3 Xiong Zhang,1 Min Zhou1 1Department of Nursing, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2Cardiology Department, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Digestive Surgery Department, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Ma, Department of Nursing, The First Affiliated Hospital of Kunming Medical University, No. 295, Xichang Road, Kunming, 650032, People’s Republic of China, Email rebeccamalei@126.comPurpose: Studies had reported some influencing factors of health behavior among patients with coronary heart disease(CHD) after percutaneous coronary intervention(PCI). However, considering that human perceptions are complex, unrestricted and dynamically changing. A longitudinal qualitative study was conducted to explore the determinants of health-related behaviors of patients after PCI and dynamic changes of these determinants at the 1st, 3rd, and 6th months.Patients and Methods: Using purposive sampling, 18 patients undergoing PCI were interviewed. The conventional content analysis method was used to identify categories and subcategories. Semi-structured, face-to-face or telephone in-depth interviews were conducted at the cardiology unit of a tertiary referral hospital in Yunnan Province, China from March 2022 to January 2023.Results: Seven categories with some subcategories were constructed from the data, categorized into three domains. Firstly, individual factors include (i) Personal coping with healthy lifestyle requirements (tried but failed; I can do it), (ii) individual perception and feeling toward disease (knowing about the disease; belief of cure; fears of relapse), and (iii) personal benefits (improved health; meaning of life). Secondly, social factors include (i) social facilitators (family resources; healthcare support), (ii) social barriers (inconvenient medical care service; conflicting information). Finally, cultural factors include (i) way of living (dietary habits; key roles of yan (cigarette) and jiu (alcohol) in Chinese society), (ii) way of thinking (fatalism and Confucian familism).Conclusion: The determinants of health-related behaviors of patients after PCI are multifaceted and dynamic. Different interventions should be formulated to promote patients’ adherence to health behaviors. Moreover, priority should be given to the impact of traditional Chinese philosophy on the health behaviors of patients after PCI, and the health promotion program for these patients should be culturally sensitive. In addition, future research should further explore the determinants of health behaviors among diverse ethnic minorities after PCI, which has not been fully inquired in this study.Keywords: coronary heart disease, percutaneous coronary intervention, health behavior adherence, qualitative research, Chinese traditional culture

Anping Lu,1,2,&ast; Fangyi Yu,2,&ast; Xiaohan Tan,2 Xiaohong Jin,1 Xiaohua Wang,3 Wenya Wu1 1Nursing Department, The First People’s Hospital of Changshu, Changshu, 215500, People’s Republic of China; 2School of Nursing, Medical College, Soochow University, Suzhou, 215006, People’s Republic of China; 3Division of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenya Wu, Nursing Department, The First People’s Hospital of Changshu, Changshu, 215500, People’s Republic of China, Tel +86-1386236425, Fax +86-512-52223921, Email 106313851@qq.comPurpose: Previous research has consistently shown that self-perception of aging (SPA) is an important predictor of health and longevity, while Chinese rural elderly patients with hypertension had poorer SPA. Whether it was associated with their mortality kept unknown. The objective of this study was to investigate the long-term mortality and analyze the association between SPA and this mortality in the specific context of rural elderly patients with hypertension.Patients and Methods: This study is a longitudinal investigation of the mortality in elderly patients with hypertension in rural Suzhou, China. Sociodemographic and clinical data, SPA, and six-year mortality were investigated. We used binary logistic regression and subgroup analyses to assess the effect of SPA at baseline on six-year mortality.Results: A total of 280 hypertensive patients aged 60 years and older participated in the study, of whom 21 died, with a six-year mortality rate of 7.5%. After controlling for covariates, the “Emotional representation” dimension (OR=2.824, 95% CI:1.034– 7.712) in SPA remained a risk factor for death. In subgroup analyses of the group aged 75 years and older, high scores on the “Timeline cyclical” (OR=14.125, 95% CI: 1.258– 158.593) and “Emotional representations” (OR=2.567, 95% CI:1.066– 6.182) dimensions were associated with a higher risk of death, while weekly nut intake may have mitigated the negative SPA effect on mortality.Conclusion: Poorer self-perception of aging was associated with a high risk of mortality in rural elderly patients with hypertension, while the habit of weekly nut intake might help reduce this risk in the group aged 75 years or older.Keywords: China, hypertension, mortality, rural population, self-perception

Li Li,&ast; Run Guo,&ast; Yingxue Zou, Xu Wang, Yifan Wang, Shiying Zhang, Huihua Wang, Xingnan Jin, Ning Zhang Department of Pulmonology, Tianjin Children’s Hospital (Children’s Hospital, Tianjin University) Machang Compus, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingxue Zou, Department of Pulmonology, Tianjin Children’s Hospital (Children’s Hospital, Tianjin University) Machang Compus, Tianjin, People’s Republic of China, Email zouyingxue2015@126.comBackground: This study aimed to develop a nomogram model for early prediction of the severe Mycoplasma pneumoniae pneumonia (MPP) in children.Methods: A retrospective analysis was conducted on children with MPP, classifying them into severe and general MPP groups. The risk factors for severe MPP were identified using Logistic Stepwise Regression Analysis, followed by Multivariate Regression Analysis to construct the nomogram model. The model’s discrimination was evaluated using a receiver operating characteristic curve, its calibration with a calibration curve, and the results were visualized using the Hosmer–Lemeshow goodness-of-fit test.Results: Univariate analysis revealed that age, duration of fever, length of hospital-stay, decreased sounds of breathing, respiratory rate, hypokalemia, and incidence of co-infection were significantly different between severe and general MPP. Significant differences (p < 0.05) were also observed in C-reactive protein, procalcitonin, peripheral blood lymphocyte count, neutrophil-to-lymphocyte ratio, ferritin, lactate dehydrogenase, alanine aminotransferase, interleukin-6, immunoglobulin A, and CD4+ T cells between the two groups. Logistic Stepwise Regression Analysis showed that age, decreased sounds of breathing, respiratory rate, duration of fever (OR = 1.131; 95% CI: 1.060– 1.207), length of hospital-stay (OR = 1.415; 95% CI: 1.287– 1.555), incidence of co-infection (OR = 1.480; 95% CI: 1.001– 2.189), ferritin level (OR = 1.003; 95% CI: 1.001– 1.006), and LDH level (OR = 1.003; 95% CI: 1.001– 1.005) were identified as risk factors for the development of severe MPP (p < 0.05 in all). The above factors were applied in constructing a nomogram model that was subsequently tested with 0.862 of the area under the ROC curve.Conclusion: Age, decreased sound of breathing, respiratory rate, duration of fever, length of hospital-stay, co-infection with other pathogen(s), ferritin level, and LDH level were the significant contributors for the establishment of a nomogram model to predict the severity of MPP in children.Keywords: Mycoplasma pneumoniae pneumonia, nomogram, severity prediction

Zhijian Wu,1– 3 Xiaotian Jin,1 Ilyas Tudahun,1 Shangjie Wu,2,3 Mingxian Chen,1 Jianjun Tang1 1Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, 410011, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Hunan Centre for Evidence-Based Medicine, Changsha, 410011, People’s Republic of ChinaCorrespondence: Jianjun Tang; Mingxian Chen, Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, No. 139 Middle Renmin Road, Furong District, Changsha, Hunan, 410011, People’s Republic of China, Fax + 86 731 85533525, Email tom200210@csu.edu.cn; xymingxianchen@csu.edu.cnBackground and Aims: Whether IMH can directly cause persistent myocardial necrosis after reperfusion therapy in STEMI patients is still unclear. We conducted a prospective study to compare the cardiovascular parameters in patients with STEMI with and without IMH to explore the potential correlations between IMH and poor outcomes.Methods and Results: We prospectively enrolled 65 consecutive patients with newly diagnosed STEMI admitted to the CCU of the Second Xiangya Hospital of Central South University between April 2019 and November 2021, all of whom underwent primary PCI. Of these, 38 (58.5%) and 27 (41.5%) patients were in the IMH-absent and IMH-present groups, respectively. At a mean time of 5– 7 days after reperfusion therapy, the volume of MI measured using LGE sequence was larger in STEMI patients with IMH than in patients without IMH (34.2 ± 12.7 cm3 vs 21.1 ± 13.1 cm3, P< 0.001). HsTNT levels were significantly higher in the IMH-present group than in the IMH-absent [2500.0 (1681.5– 4307.0) pg/mL vs 1710.0 (203.0– 3363.5) pg/mL, P=0.021] group during hospitalization. The LVEF measured using CMR in the IMH-present group was lower than that in the IMH-absent group (30.7 ± 9.8% vs 42.3 ± 11.0%, P < 0.001). The rate of MACE at 12 months in IMH-present group was significantly higher than in the IMH-absent group (9/27 VS 2/38, P = 0.012).Conclusion: IMH can lead to further expansion of MI volumes in patients with STEMI, resulting in lower LVEF and higher MACE rate in the post-discharge follow-up.Keywords: myocardial infarction, cardiac magnetic resonance, intramyocardial hemorrhage, infarction volume, outcome

Boyi Yu,1– 4 Xuanyi Lu,5 Xianglong Feng,1– 4 Ting Zhao,1– 4 Jiaxin Li,1– 4 Yudie Lu,5 Fei Ye,1– 4 Xiongxiong Liu,1– 4 Xiaogang Zheng,1– 4 Zheyu Shen,5 Xiaodong Jin,1– 4 Weiqiang Chen,1– 4 Qiang Li1– 4 1Biomedical Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, People’s Republic of China; 2Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, People’s Republic of China; 3Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou, Gansu Province, People’s Republic of China; 4College of Life Sciences, University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 5School of Biomedical Engineering, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Xiaodong Jin; Weiqiang Chen, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Lanzhou, Gansu Province, 730000, People’s Republic of China, Tel +86-931-4969316, Fax +86-931-8272100, Email jinxd@impcas.ac.cn; chenwq7315@impcas.ac.cnIntroduction: Radiotherapy is a widely recognized first-line clinical treatment for cancer, but its efficacy may be impeded by the radioresistance of advanced tumors. It is urgent to improve the sensitivity of radioresistant tumors to radiotherapy. In this work, gadolinium oxide nanocrystals (GONs) were utilized as radiosensitizers to enhance the killing effect and reinforce the immune activation of X-ray irradiation on 4T1 breast cancer cells in vitro and in vivo.Methods: 1.0 T small animal MR imaging (MRI) system was employed to trace GONs in vivo, while 225 kVp X-ray irradiation equipment was utilized for investigating the radiosensitization of GONs in 4T1 breast cancer cells in vitro and in vivo. Western blot, quantitative real-time PCR (RT-qPCR), immunohistochemistry, immunofluorescence, clonal survival assay, flow cytometry and reactive oxygen species assay were used to explore the biological mechanism of GON sensitization.Results: GONs exhibited exceptional utility as contrast agents for both in vivo and in vitro MRI imaging. Interestingly, a single dose of 8.0 Gy X-rays together with GONs failed to confer superior therapeutic effects in tumor-bearing mice, while only 3.0 Gy × 3 fractions X-rays combined with GONs exhibited effective tumor growth inhibition. Moreover, fractionated X-ray irradiation with GONs demonstrated a superior capacity to activate the cGAS-STING pathway.Discussion: Fractionated X-ray irradiation in the presence of GONs has demonstrated the most significant activation of the anti-tumor immune response by boosting the cGAS-STING pathway. Keywords: gadolinium oxide nanoparticles, magnetic resonance imaging, radiosensitization, cGAS-STING pathway, 4T1 breast cancer cells

Ailong Huang,&ast; Yuchao Wang,&ast; Haiyan Xu, Xiuxiu Jin, Bingqing Yan, Wei Zhang Department of Microbiology, Nantong Center for Disease Control and Prevention, Nantong, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Zhang, Department of Microbiology, Nantong Center for Disease Control and Prevention, No. 189, Gongnong South Road, Chongchuan District, Nantong City, Jiangsu Province, People’s Republic of China, Email zhangwei_1886@sina.comPurpose: The objective of this study was to investigate the prevalence and molecular characteristics of Vibrio parahaemolyticus isolates from fecal samples of patients in Nantong, China.Methods: From 2018 to 2021, a total of 106 clinical cases and samples of V. parahaemolyticus infection were collected. The virulence genes, serotypes and antibiotic resistance of these isolates were analyzed. Additionally, pulsed-field gel electrophoresis (PFGE) was used to analyze the homogeneity of the isolates.Results: Outbreaks of V. parahaemolyticus infection were concentrated in the summer, with seafood consumption being the primary contributing factor, followed by meat and meat products. tlh+tdh+trh- was confirmed as the most frequently detected virulence genotype among the clinical isolates. 16 serotypes were identified, and O3:K6 was the dominant serotype in Nantong. The antimicrobial susceptibility testing revealed the highest resistance rate to cefazolin (99.1%, 104/106), followed by ampicillin (64.2%, 68/106) and tetracycline (29.2%, 31/106). Fourteen resistant phenotypes were identified, with ampicillin-cefazolin being the most prevalent. The multiple antibiotic resistance (MAR) index ranged from 0.07 to 0.36. PFGE typing clustered isolates with similarity greater than 85% into ten genetic clusters (A-J).Conclusion: Clinical isolates generally exhibited pathogenicity and drug resistance, with some isolates displaying high homology. Clusters C, E, and G were the predominant circulating clusters in this area, posing a potential risk of recurrent outbreaks, which demanded our vigilance.Keywords: Vibrio parahaemolyticus, clinical isolates, antibiotic resistance, PFGE

Sun L, Yang S, Chi G, Jin X. Onco Targets Ther. 2018;11:1583–1593. We, the Editor and Publisher of the journal OncoTargets and Therapy have retracted the published article. Following publication of the article, concerns were raised about the duplication of images from Figure 6 with images from an unrelated article. Specifically, Images for Figure 6E, TUNEL, U87, Untreated and NMS-E973, have been duplicated with images for Figure 6C, TUNEL, WT, Control and 17-DMAG, respectively, from He K, Zheng X, Zhang L, Yu J. Hsp90 Inhibitors Promote p53-Dependent Apoptosis through PUMA and Bax. Mol Cancer Ther. 2013;12(11):2559–2568. https://doi.org/10.1158/1535-7163.MCT-13-0284. The corresponding author did not respond to our queries and was unable to provide a satisfactory explanation for how the images came to be duplicated or provide satisfactory original data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Psychological science is at an inflection point: The COVID-19 pandemic has exacerbated inequalities that stem from our historically closed and exclusive culture. Meanwhile, reform efforts to change the future of our science are too narrow in focus to fully succeed. In this article, we call on psychological scientists-focusing specifically on those who use quantitative methods in the United States as one context for such conversations-to begin reimagining our discipline as fundamentally open and inclusive. First, we discuss whom our discipline was designed to serve and how this history produced the inequitable reward and support systems we see today. Second, we highlight how current institutional responses to address worsening inequalities are inadequate, as well as how our disciplinary perspective may both help and hinder our ability to craft effective solutions. Third, we take a hard look in the mirror at the disconnect between what we ostensibly value as a field and what we actually practice. Fourth and finally, we lead readers through a roadmap for reimagining psychological science in whatever roles and spaces they occupy, from an informal discussion group in a department to a formal strategic planning retreat at a scientific society.

Jingbo Li,1,&ast; Kun Zhou,2,3,&ast; Meng Wu,3,&ast; Rongzheng Zhang,3 Xi Jin,3 Han Qiao,3 Jiaqi Li,3 Xinyang Cao,3 Shuyun Zhang,3 Guanglu Dong4 1Department of Anesthesiology Research Institute, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Department of Clinical Laboratory, Beidahuang Industry Group General Hospital, Harbin, People’s Republic of China; 3Scientific Research Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Tumor Radiotherapy, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanglu Dong, Department of Tumor Radiotherapy, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Tel +1 380 450 3001, Email DGL64@163.com Shuyun Zhang, Scientific Research Center, the Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Tel +1 321 450 1198, Email 13214501198@163.comPurpose: Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related deaths, posing a significant threat to people in diverse regions. T-cell exhaustion (Tex) can hinder the efficacy of immunotherapy in patients with HCC, and the transcription factors that regulate Tex in HCC have not yet been fully elucidated.Patients and Methods: We used the single sample gene set enrichment analysis (ssGSEA) method to define the transcription factor pathway that regulates Tex and employed LASSO regression analysis to establish Tex related genes (TEXRS). To predict differences in immunotherapy efficacy between the two groups, we used the immunophenotype score and submap algorithm. RT-qPCR was used to detect the expression levels of the model genes in 21 pairs of HCC tissues. Finally, we assessed the cell communication strength and identified ligand receptors using the “CellChat” R package.Results: Nine Tex transcription factors were identified as regulators of the HCC immune microenvironment, with Tex scores affecting patient survival. Patients with a high Tex Risk Score (TEXRS) had significantly worse overall survival compared to patients with low TEXRS. After adjusting for confounding factors, TEXRS remained an independent prognostic factor. Importantly, TEXRS performed well in multiple independent external validation cohorts. Various algorithms have shown that patients in the low-TEXRS group might benefit more from immunotherapy. Finally, RT-qPCR analysis of 21 HCC samples showed that C7, CD5L, and SDS were significantly downregulated in HCC tissues, consistent with the bioinformatics analysis results.Conclusion: TEXRS proved to be a valuable predictor of immunotherapy and transcatheter arterial chemoembolization efficacy in patients with HCC. This holds promise for enhancing the prognosis and treatment outcomes of patients with HCC.Keywords: T-cell exhaustion, transcription factors, single-cell RNA sequencing, immune microenvironment, immunotherapy

Xiaoming Jin,&ast; Riming He,&ast; Yunxin Lin, Jiahui Liu, Yuzhi Wang, Zhongtang Li, Yijiao Liao, Shudong Yang Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518033, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shudong Yang, Email shudong_yang@126.comBackground: Acute kidney injury (AKI) is a common clinical condition resulting in a rapid decline in renal function, and requires improvement in effective preventive measures. Ferroptosis, a novel form of cell death, is closely related to AKI. Shenshuaifu granule (SSF) has been demonstrated to prevent AKI through suppressing inflammation and apoptosis.Objective: This study aimed to explore whether SSF can inhibit ferroptosis in AKI.Methods: Active ingredients in SSF were detected through HPLC-MS/MS, and their binding abilities with ferroptosis were evaluated by molecular docking. Then, male C57/BL/6J mice were randomly divided into control, cisplatin, and cisplatin+SSF groups. In the latter two groups, mice were intraperitoneally injected with 20 mg/kg of cisplatin. For five consecutive days prior to cisplatin injection, mice in the cisplatin+SSF group were gavaged with 5.2 g/kg of SSF per day. 72 h after cisplatin injection, the mice were sacrificed. Serum creatinine (SCr) and blood urea nitrogen (BUN) were measured to evaluate renal function. H&E and PAS staining were used to observe pathological damage of kidney. Cell death was observed by TUNEL staining, and iron accumulation in kidneys of mice was detected by Prussian blue staining. Western blotting, immunohistochemistry, and immunofluorescence were used to investigate the presence of inflammation, oxidative stress, mitochondrial dysfunction, iron deposition, and lipid peroxidation in mouse kidneys.Results: Active ingredients in SSF had strong affinities with ferroptosis. SSF reduced SCr (p< 0.01) and BUN (p< 0.0001) levels, pathological damage (p< 0.0001), dead cells in the tubular epithelium (p< 0.0001) and iron deposition (p< 0.01) in mice with cisplatin induced AKI. And SSF downregulated macrophage infiltration (p< 0.01), the expressions of high mobility group box 1 (HMGB1, p< 0.05) and interleukin (IL)-17 (p< 0.05), upregulated superoxide dismutase (SOD) 1 and 2 (p< 0.01), and catalase (CAT, p

Xiaolin Jin,1 Haiyan Sun,2 Lina Yang1,3 1Department of International Physical Examination Center, The First Hospital of China Medical University, Shengyang, People’s Republic of China; 2Department of Endodontics, School of Stomatology, China Medical University, Shenyang, People’s Republic of China; 3Department of Geriatrics, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Haiyan Sun; Lina Yang, Email 13066784163@163.com; yanglina1984@163.comAbstract: Sepsis is a systemic inflammatory reaction caused by infection. Severe sepsis can lead to multiple organ dysfunction, with a high incidence rate and mortality. The molecular pathogenesis of sepsis is complex and diverse. In recent years, with further study of the role of extracellular vesicles (EVs) in inflammatory diseases, it has been found that EVs play a dual role in the imbalance of inflammatory response in sepsis. Due to the great advantages such as lower toxicity, lower immunogenicity compared with stem cells and better circulation stability, EVs are increasingly used for the diagnosis and treatment of sepsis. The roles of EVs in the pathogenesis, diagnosis and treatment of sepsis were summarized to guide further clinical studies.Keywords: extracellular vesicles, sepsis, inflammatory response, exosome, microvesicle

Jun Ma,1,&ast; Deep K Vaishnani,2,&ast; Mansi,2 Jing Zeng,3 Zhenwen Xie,3 Xuanchen Jin,3 Haixia Zhang,3 Khaing Wut Yi Hla,2 Furong Ying4 1Department of Pathology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 2School of International Studies, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325035, People’s Republic of China; 3School of Clinical Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325035, People’s Republic of China; 4Department of Clinical Laboratory, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Furong Ying, Department of Clinical Laboratory, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China, Tel/Fax +86 57755579738, Email 764741293@qq.comPurpose: The objective of this study was to evaluate the therapeutic efficacy of the curcumin analogue L6H4 in attenuating liver fibrosis and alleviating insulin resistance in streptozotocin-induced diabetic rats.Methods: Male Sprague-Dawley rats were fed a high-fat diet to induce insulin resistance, followed by streptozotocin injection to induce diabetes. The rats were then treated with L6H4 for eight weeks. Body weight, metabolic parameters, liver function, and liver histopathology were evaluated. Immunohistochemistry was performed to assess the expression of TGF-β 1, TIMP-2, and MMP-2 in liver tissues. Statistical analysis was conducted using one-way ANOVA and Spearman rank correlation test.Results: L6H4 treatment effectively reversed the weight gain associated with a high-fat diet and improved metabolic parameters in diabetic rats. Liver function markers, such as ALT and AST, were reduced after L6H4 treatment. Histological analysis showed improved liver morphology and reduced fibrosis in L6H4-treated rats. Electron microscopy revealed improved ultrastructural features of hepatocytes. Immunohistochemistry demonstrated downregulation of TGF-β 1 and TIMP-2 expression and restoration of MMP-2 expression in the liver tissue of L6H4-treated rats. Correlation analysis showed a significant positive correlation between TGF-β 1 and TIMP-2 expression.Conclusion: The findings suggest that L6H4 has therapeutic potential in attenuating liver fibrosis and alleviating insulin resistance in streptozotocin-induced diabetic rats. The hepatoprotective effect of L6H4 may be attributed to its anti-inflammatory properties and its ability to target molecules involved in fibrosis. Further research is warranted to explore the potential of L6H4 as a treatment option for nonalcoholic fatty liver disease and type 2 diabetes.Plain Language Summary: The versatile curcumin, derived from turmeric, has shown potential in treating type 2 diabetes (T2D) and its complications. However, its bioavailability is limited. This study evaluated the efficacy of L6H4, a curcumin analogue, in treating T2D-induced hepatic fibrosis in rats. The rats were fed a high-fat diet and injected with streptozotocin to induce T2D. L6H4 treatment for eight weeks reversed weight gain, abnormal liver function, and histological changes. The analogue reduced markers of T2D severity, including blood glucose, insulin levels, and insulin resistance. L6H4 also decreased liver fibrosis by reducing the expression of TGF-β 1 and TIMP-2 and increasing MMP-2 expression. These changes in protein expression were consistent with previous studies on liver fibrosis. The effects of L6H4 on MMP-2 and TIMP-2 expression in the liver of diabetic rats had not been observed before. Additionally, L6H4 exhibited anti-inflammatory properties and regulated the expression of key fibrosis-related proteins. The study suggests that L6H4 has the potential as a therapeutic candidate for treating diabetic hepatopathy. Further research is needed to elucidate the molecular mechanisms of action of L6H4 and other curcumin analogues in T2D and liver fibrosis. In conclusion, L6H4 shows promise as a curcumin analogue with hepatoprotective effects and the ability to modulate protein expression involved in liver fibrosis in T2D.Keywords: type 2 diabetic rats, curcumin analogue, L6H4, TIMP– 2, MMP– 2, TGF-β 1

Xiaxia Jin,1,&ast; Haideng Yang,2,&ast; Weiwei Ma,1,&ast; Yuan Yuan,1 Tao Li3 1Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People’s Republic of China; 2Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People’s Republic of China; 3Department of Cardiovascular Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuan Yuan, Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province, 150 Ximen Road, Linhai, Zhejiang Province, People’s Republic of China, Email yuany@enzemed.com Tao Li, Department of Cardiovascular Medicine, Taizhou Hospital of Zhejiang Province, 150 Ximen Road, Linhai, Zhejiang Province, People’s Republic of China, Email litao@enzemed.comObjective: To evaluate the relationship between high-sensitivity cardiac troponin T (hs-cTnT) and prognosis in elderly patients with coronavirus disease 2019 (COVID-19).Methods: This study recruited 1399 COVID-19 patients aged 65 years or older admitted to Taizhou Hospital or Enze Hospital in Zhejiang Province from December 15, 2022, to January 4, 2023. The Cox regression model was used to evaluate the relationship between hs-cTnT level and in-hospital death. The logistic regression model was used to evaluate the relationship between hs-cTnT level and major adverse events. The restricted cubic spline (RCS) model is used for nonlinear analysis.Results: The increase of peak hs-cTnT was associated with the increased risk of death (HR 9.49; 95% CI 1.19– 75.48; trend p = 0.012) and major adverse events (OR 20.59; 95% CI 10.41– 40.71; trend p < 0.001). RCS model showed the association between peak hs-cTnT and death and major adverse events were nonlinear (P for non-line < 0.001). Starting from the limit of quantification of hs-cTnT (3ng/L), the risk of death and major adverse events had a steep S-shaped increase until hs-cTnT reached the 90th percentile point (hs-cTnT = 131 ng/L), followed by a plateau period. Peak hs-cTnT has good predictive value for death and major adverse events, with AUC of 0.834 and 0.804, respectively.Conclusion: Peak hs-cTnT has high predictive value for the risk of in-hospital death and major adverse events in elderly patients with COVID-19. The association between peak hs-cTnT and death and major adverse events were nonlinear.Keywords: high-sensitivity cardiac troponin T, elderly, COVID-19, nonlinearly, prognosis

Xiaochong Li,1,&ast; Bowen Hu,1,&ast; Jiachen Zheng,2,3 Zhiyong Pan,1 Yuxiang Cai,4 Mingjuan Zhao,1 Xiaoqing Jin,2 Zhi-Qiang Li1 1Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 2Emergency Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 3The Second Clinical School, Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 4Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoqing Jin; Zhi-Qiang Li, Email redjin@whu.edu.cn; lizhiqiang@whu.edu.cnIntroduction: Temozolomide (TMZ) induces intestinal mucosa injury that cannot be fully counteracted by supportive treatment. Probiotics regulate gut microbial composition and the host immune system and may alleviate this side effect. We aimed to investigate the potential and mechanism of Lactobacillus rhamnosus GG (LGG) in relieving intestinal mucosal injury induced by TMZ.Methods: Glioblastoma mice were divided into four groups: CON (control), LGG (109 CFU/mL, treated for 7 days), TMZ (50 mg/kg·d, treated for 5 days), LGG+TMZ (LGG for 7 days and TMZ subsequently for 5 days). Body weight, food intake, and fecal pH were recorded. Intestinal tissue samples were collected 1 day after the end of TMZ treatment. Degree of damage to intestine, expression of IL1β, IL6, TNFα, and IL10 in jejunum were determined. Levels of tight-junction proteins (ZO1, occludin), TLR4, IKKβ, IκBα, and P65 with their phosphorylation in jejunum were measured.Results: Decreases in body weight, food intake, spleen index in the TMZ group were mitigated in the LGG+TMZ group, and the degree of intestinal shortening and damage to jejunum villus were also alleviated. The expression of tight-junction proteins in the LGG+TMZ group was significantly greater than that in the TMZ group. IκBα in intestinal tissue significantly decreased in the TMZ group, phos–IKKβ and phos-P65 increased compared to the CON group, and LGG reversed such changes in IκBα and phos-P65 in the LGG+TMZ group. Intestinal inflammatory cytokines were significantly increased in the TMZ group, but lower in the LGG+TMZ group. Moreover, expression of TLR4 in LGG group was significantly lower than that in the CON group. LGG inhibited the rise of TLR4 after TMZ in the LGG+TMZ group compared to the TMZ group.Conclusion: LGG inhibits the activation of the TLR4–NFκB pathway and alleviates intestinal mucosal inflammation induced by TMZ, thereby protect the jejunum villi and mucosal physical barrier.Keywords: Lactobacillus rhamnosus GG, temozolomide, intestinal mucosal injury, TLR4, NFκB