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Jin Cheng,1,* Honglei Ju,1,* Guixiang Wang,2,* Chiyi He,1 Wei Wang1 1Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China; 2Department of Gastroenterology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Wang, Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, No. 2, Zheshan West Road, Wuhu, Anhui Prov, 241000, People’s Republic of China, Email wwwy@wnmc.edu.cnBackground: The Systemic Inflammation Response Index (SIRI) has demonstrated predictive capabilities for clinical outcomes in various diseases. However, its prognostic utility in decompensated liver cirrhosis (DLC) remains underexplored. This study aimed to investigate the association between SIRI and the risk of short-term (3 and 6 months) all-cause mortality in DLC patients.Methods: A total of 926 eligible patients with DLC from diverse etiologies was included in this study. In the initial cohort, the predictive accuracy of SIRI was evaluated using receiver operating characteristic (ROC) curve analysis. Patients were categorized into high- and low-SIRI groups based on the Youden index. Multivariable logistic regression analysis was employed to evaluate the independent association between SIRI and all-cause mortality. Restricted cubic spline (RCS) analysis was utilized to visualize the relationship between the continuous variable SIRI and mortality risk. These findings were validated in a validation cohort.Results: The initial cohort had mortality rates of 8.8% and 11.6% at 3 and 6 months, respectively. The SIRI level was significantly higher in the deceased group compared to the survival group. At both time points, SIRI was an independent indicator of all-cause mortality. RCS analysis demonstrated the risk of the risk of increased with an increase in SIRI value. The Validation cohort validated the independent association between higher SIRI levels and lower short-term all-cause mortality.Conclusion: This study’s findings underscore the prognostic value of SIRI in DLC patients, indicating that higher SIRI levels are significantly associated with short-term adverse outcomes.Keywords: decompensated liver cirrhosis, systemic inflammation response index, prognosis, all-cause mortality

Hui Lian,1,* Guangjian Wang,2,* Hongmin Zhang,2 Xiaoting Wang,2 Shuyang Zhang3 1Department of Health Care, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoting Wang, Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China, Email icuting@163.com Shuyang Zhang, Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China, Email shuyangzhang103@163.comBackground: The host response plays a critical role in the progression of all critical illnesses, especially in the aging population. With aging becoming a global phenomenon, understanding changes in the host response among elderly patients can provide valuable insights for diagnosis and treatment in the ICU.Methods: This study included all patients aged 65 and older admitted to our geriatric intensive care unit (GICU). Demographic, clinical, and medication data were extracted from electronic medical records. The primary outcome was in-hospital mortality, while secondary outcomes included hospital length of stay (LOS) and ICU stay duration. We employed the generalized additive mixed model for analysis and utilized nomogram analysis to build a predictive mortality model.Results: A total of 1204 patients, with a median age of 75 years and a maximum age of 110 years, were admitted to the GICU. Host response biomarkers were notably lower in patients over 85 years. White blood cell (WBC) count, lactate dehydrogenase (LDH), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) were positively associated with mortality, while a higher platelet-to-lymphocyte ratio (PLR) was inversely related to mortality. Lymphocyte count was identified as a significant risk factor for mortality (RR = 1.2181). Elevated host response biomarkers were inversely associated with both hospital and ICU LOS. The predictive model integrating these biomarkers exhibited strong predictive performance for mortality.Conclusion: Our findings underscore the significant impact of aging on host response in critically ill patients. Older patients, particularly those over 85, exhibited lower biomarker levels and higher mortality rates. The predictive model developed from inflammatory, immune, and coagulation markers demonstrated robust prognostic utility, aiding in the evaluation of critically ill elderly patients.Keywords: host response, critically ill, old patients, immune response, inflammatory response, procoagulant response

Qingqing Zhang,1,2,&ast; Jing Zheng,1,&ast; Guoyu Wang,1,3 Suyun Jiang,1 Peng Gao,1 Si Sun,1 Xiangwei Ding,3 Yucheng Wu3 1Department of Pan-Vascular Management Center, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, People’s Republic of China; 2Department of Endocrinology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, People’s Republic of China; 3Department of Cardiology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yucheng Wu; Xiangwei Ding, Email 2567181759@qq.com; dingxw1208@126.comObjective: To determine the prevalence of Cardiovascular-Kidney-Metabolic (CKM) Syndrome and identify risk factors, including occupational factors, lifestyle factors and clinical measurements, and female-specific risk enhancers among healthcare workers in China.Methods: A cross-sectional study was conducted among healthcare workers at Taizhou People’s Hospital between April and May 2024. We collected data through surveys and laboratory results. Univariate and multivariate logistic regression analyses were performed to identify predictors of CKM syndrome and female-specific risk enhancers.Results: A total of 1110 participants were recruited (197 male; 913 female; mean age 34.8± 7.9). Almost 90% of male healthcare workers and 60% of female healthcare workers met the criteria for CKM syndrome (stage 1 or higher). Additionally, most male CKM syndrome patients were in stages 2– 3 (53.81%), while most female CKM syndrome patients were in stage 1 (35.82%). Multivariate logistic regression analysis revealed that, compared to those with over 20 years of work duration, a work duration of less than 10 years was a protective factor for CKM Syndrome. Additionally, more than 8 hours of sedentary time was identified as a risk factor compared to less than 2 hours (OR = 1.376, 95% CI 1.027– 1.844, P < 0.05). Receiver operating characteristic analysis showed that body mass index (BMI) was superior to fasting plasma glucose, glycated hemoglobin, triglycerides, and the triglyceride glucose product index in predicting CKM Syndrome, with area under the curve values of 0.884 vs 0.638, 0.708, 0.745, and 0.761, respectively (P < 0.05 for all). BMI was identified as an independent risk factor for female-specific risk enhancers.Conclusion: CKM syndrome is prevalent among healthcare workers in Chinese tertiary hospitals, with males generally presenting at more advanced stages than females. BMI is a key predictor of CKM syndrome and female-specific risk enhancers.Keywords: cardiovascular-kidney-metabolic syndrome, BMI, healthcare workers, triglyceride glucose product index

Xiaofan Wu,1,2 Sheng Ding,1,2 Guizhi Wang,1,2 Wei Zhang,1 Keqiang He1 1Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China; 2Department of Anesthesiology, Bengbu Medical College Graduate School, Bengbu, Anhui, 233000, People’s Republic of ChinaCorrespondence: Keqiang He; Wei Zhang, Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China, Email doctorhector@ustc.edu.cn; doctor_zw97079@163.comBackground: The decrease expression of PGC-1α contributes to perioperative neurocognitive disorders (PND). This study aimed to investigate the effects of the PGC-1α agonist ZLN005 in preventing PND and to explore the potential mechanism.Methods: C57BL/6 mice were randomly divided into four groups: the control group (Group C), the surgery group (Group S), the surgery and ZLN005 (5 mg/(kg⋅d)) group (Group L), and the surgery and ZLN005 (7.5 mg/(kg⋅d)) group (Group H). Except for Group C, the other three groups received intraperitoneal injections of vehicle or ZLN005 once a day from 3 days before surgery to 3 days after surgery. The open field test, novel object recognition test and fear conditioning test were performed to measure anxiety behaviors, locomotor activity and memory. The levels of IL-6 and IL-1β were measured at 24 hours after surgery. ATP and ROS levels were measured at 3 days post-surgery. PGC-1α, NRF-1, Atp5d, Atp5k and Cox5a were measured at one day or three days post-surgery.Results: ZLN005 treatment improved the cognitive function of mice in Group L and Group H compared with Group S. The expression of IL-6 and IL-1β in the hippocampus of the S group was increased after surgery, and ZLN005 reduced the expression of IL-6 and IL-1β in the hippocampus of mice one day after surgery. There were parallel decreases in the expression of PGC-1α/NRF-1 and mitochondrial function in the hippocampus of the Group S mice compared with the Group C mice. The expression of PGC-1α/NRF-1 and mitochondrial function were upregulated after ZLN005 treatment.Conclusion: Neuroinflammation and mitochondrial damage are involved in the occurrence of PND. ZLN005 activates PGC-1α to increase the expression of mitochondrial proteins, improve mitochondrial function, and ultimately ameliorate the cognitive status of mice after surgery.Keywords: ZLN005, perioperative neurocognitive disorders, neuroinflammation, PGC-1α, mitochondrial respiratory chain complex, respiratory function

Guangjie Wang,1,&ast; Puhui Liu,2,&ast; Hui Xie,2 Chuanzhen Niu,2 Jie Lyu,1 Youzhong An,1 Huiying Zhao1 1Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Critical Care Medicine, Yantai Qishan Hospital, Yantai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiying Zhao, Department of Critical Care Medicine, Peking University People’s Hospital, No. 11, Southern Xizhimen Road, Beijing, 100044, People’s Republic of China, Tel +86 13811088270, Email zhaohuiying@pkuph.edu.cnPurpose: The high mortality rate associated with the critical stages of severe fever with thrombocytopenia syndrome (SFTS) does not have effective treatment. We aimed to evaluate the 28-day mortality and potential impact of glucocorticoid therapy in these patients.Patients and Methods: This retrospective observational study included participants from the intensive care unit between July 2019 and April 2023. The participants were categorized into glucocorticoid (GC) and non-GC groups. Propensity score matching (PSM) was employed to ensure comparability between groups. We used Cox proportional hazard models to examine mortality risk associated with GC use, Kaplan–Meier survival analyses for overall survival, stratified Cox proportional hazard models for subgroup analyses, and likelihood ratio tests to examine interactions between subgroups.Results: Of 218 patients with SFTS (median age, 71 years; male, 49.1%), 61.9% required mechanical ventilation, 58.3% received GC treatment, and the 28-day mortality rate was 61.5%. After PSM, there were 58 patients in each group; post-PSM analysis revealed improved 28-day mortality rates with GC treatment, particularly for patients with Glasgow coma scale (GCS) score < 13 (hazard ratio [HR], 95% confidence interval [CI] for GCS score: 9– 12: 0.39, 0.17– 0.88, p=0.024 and for GCS score: 3– 8: 0.09, 0.02– 0.35, p=0.001); lactate levels > 2 mmol/L (0.35, 0.15– 0.83, p=0.017); and norepinephrine usage (0.26, 0.13– 0.49, p< 0.001). Combining antiviral (0.41, 0.22– 0.78, p=0.006) or immunoglobulin therapy (0.22, 0.1– 0.51, p< 0.001) with GC treatment significantly decreased the 28-day mortality rates, compared with GC monotherapy.Conclusion: Using GCs reduced the high 28-day mortality rate in the patients, especially with low GCS score, high lactate levels, norepinephrine intake, and on antiviral or immunoglobulin therapy.Keywords: glucocorticoids, mortality, severe fever with thrombocytopenia syndrome, intensive care unit, virus infection

Jing Yang,1,&ast; Mei Liu,1,&ast; Lei Yang,1 Shujing Fang,2 Guangling Wang,2 Zejuan Gu1 1Nursing Department, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Orthopedics Department, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zejuan Gu, Nursing Department, Jiangsu province hospital and the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, People’s Republic of China, Tel +8602568305379, Email jassicagu@163.comObjective: To analyze the current utilisation of delirium risk assessment and screening for older patients after hip fracture surgery in tertiary hospitals in Jiangsu Province, China.Methods: This cross-sectional study was conducted from April 1 to April 30, 2023 among nurses working in orthopedics from Level III hospitals in Jiangsu Province, China. Data were collected using a self-designed questionnaire that focused on the utilisation of delirium risk assessment and prevention measures for older patients after hip fracture surgery. The questionnaire was administered through the online platform Questionnaire Star. Differences between data were analyzed using chi-square and rank-sum tests.Results: A total of 616 nurses from 48 hospitals in Jiangsu province responded to the survey. Among them, 50.17% reported having no training in delirium management, 66.88% did not assess patients for delirium risk, and 73.21% did not screen patients for delirium in their clinical practice. It was observed that nurses with longer tenure, nurses specialising in orthopaedics, and nurses with ICU experience were more attentive to delirium risk assessment and delirium screening of patients (P< 0.001).Conclusion: Medical institutions must focus on strengthening nurses’ training in delirium management for older patients after hip fracture surgery, improve their ability to undertake risk assessment and risk screening, unify delirium management norms, and ultimately improve nurses’ delirium management ability.Keywords: risk assessment and screening, delirium, older patients, postoperative Hip fracture

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

Jiaxuan Zheng,1,&ast; Xiaolong Xiong,2,&ast; Ke Li,2,&ast; Guangji Wang,2 Huiyuan Cao,2 Hui Huang2 1Department of Pathology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou City, Hainan Province, 570311, People’s Republic of China; 2Department of Sports Medicine, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou City, Hainan Province, 570311, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Huang, Department of Sports Medicine, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), No. 19 Xiuhua Road, Haikou City, Hainan Province, 570311, People’s Republic of China, Tel +86-15108938272, Email 120653927@hainmc.edu.cnObjective: Synovial inflammation is vital for the progression of osteoarthritis (OA). The objective of this study was to explore the effects and potential molecular mechanisms of sphingosine kinase 2 (SPHK2) on the proliferation and migration of fibroblast-like synoviocytes (FLS).Methods: A TNF-α-stimulated FLS model and a papain-induced OA rat model were constructed. The functions of SPHK2 knockdown in OA were explored by a series of in vivo and in vitro assays. Downstream target genes of SPHK2 were investigated using transcriptome sequencing and validated by reverse transcription quantitative PCR (RT-qPCR). The effects of the SPHK2/IL-17 signaling pathway on inflammation, proliferation, and migration of OA-FLS were investigated using the IL-17 pathway inhibitor (secukinumab) and the activator (rhIL-17A).Results: TNF-α stimulation promoted SPHK2 expression at mRNA and protein levels in OA-FLS. SPHK2 knockdown reduced IL-1β, IL-6, MMP-2, MMP-9, cyclinD1, and PCNA levels and suppressed proliferation and migration of OA-FLS. SPHK2 knockdown alleviated cartilage damage and synovial inflammation in the OA rat model. LRRIQ3, H4C8, CXCL1, CABP4, COL23A1, and PROK2 expression levels were regulated by SPHK2. SPHK2 knockdown inhibited the protein levels of IL-17A, IL-17RA, and Act1. The IL-17 pathway inhibitor secukinumab enhanced the inhibitory effect of SPHK2 knockdown on the proliferation and migration of OA-FLS, while the IL-17 pathway activator rhIL-17A exerted the opposite effect.Conclusion: SPHK2 knockdown inhibits proliferation and migration of OA-FLS by blocking the IL-17 pathway, which provides a novel approach to the OA treatment.Keywords: sphingosine kinase 2, fibroblast-like synoviocyte, IL-17 signaling pathway, proliferation, migration

Baoliang Liu,1,&ast; Haotian Zheng,1,&ast; Guoyuan Ma,1,2 Hongchang Shen,3 Zhaofei Pang,3 Gemu Huang,4 Qingtao Song,4 Guanghui Wang,1,2 Jiajun Du1,2 1Department of Thoracic Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 3Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 4Research and Development Department, Amoy Diagnostics Co., LTD., Xiamen, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanghui Wang; Jiajun Du, Email wangguanghui66@email.sdu.edu.cn; dujiajun@sdu.edu.cnBackground: Lung cancer is the most common type of cancer in the world. In lung adenocarcinoma (LUAD), studies on receptor tyrosine kinase ROS proto-oncogene 1 (ROS1) have mainly focused on the oncogenic effects of its fusion mutations, whereas ROS1 has been reported to be aberrantly expressed in a variety of cancers and can extensively regulate the growth, survival, and proliferation of tumor cells through multiple signaling pathways. The comprehensive analysis of ROS1 expression has not been fully investigated regarding its predictive value for LUAD patients.Methods: Gene expression profiles collected from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were used to build and validate prognostic risk models. The association of ROS1 with overall survival and the immune landscape was obtained from the Tumor Immune Estimation Resource (TIMER) database. The following analyses were performed using the R package to determine the model’s validity: pathway dysregulation analysis, gene set enrichment analysis, Gene Oncology analysis, immune invasion analysis, chemotherapy, radiotherapy, and immunotherapy sensitivity analysis. Finally, we conducted a pan-cancer analysis and performed in vitro experiments to explore the regulatory role of intercellular adhesion molecule 5 (ICAM5) in the progression of LUAD.Results: We constructed a 17-gene model that categorized patients into two risk groups. The model had predictive accuracy for tumor prognosis and was specific for patients with high ROS1 expression. Comprehensive analysis showed that patients in the high-risk group were characterized by marked dysregulation of multiple pathways (eg, unfolded protein response), immune suppression of the tumor microenvironment, and poor benefit from immunotherapy and radiotherapy compared with patients in the low-risk group. PLX4720 may be a suitable treatment for the high-risk patient population. The ICAM5 gene has been demonstrated to inhibit the proliferation, cell cycle, invasion, and migration of LUAD cells.Conclusion: We constructed a 17-gene prognostic risk model and found differences in immune-related cells, biological processes, and prognosis among patients in different risk groups based on the correlation between ROS1 and immunity. Personalized therapy may play an essential role in treatment. We further investigated the role of ICAM5 in inhibiting the malignant bioactivity of LUAD cells.Keywords: ROS1, ICAM5, LUAD, immune, prognostic model

Linan Ren,1,2 Feng Ju,3 Siyuan Liu,1,2 Yunjia Cai,1,2 Xiaokun Gang,1 Guixia Wang1 1Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China; 2Institute of Translational Medicine, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China; 3Department of Orthopedics, Yuci District People’s Hospital, Yuci, Shanxi, 030600, People’s Republic of ChinaCorrespondence: Xiaokun Gang; Guixia Wang, Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, People’s Republic of China, Email gangxk@jlu.edu.cn; gwang168@jlu.edu.cnAbstract: Obesity represents a substantial risk factor for a multitude of metabolic disorders, which seriously threatens human life and health. As the global obesity epidemic intensifies, obesity-related nephropathy (ORN) has attracted great attention. ORN arises from both physical/mechanical and non-physical insults to the glomerular and tubular structures precipitated by obesity, culminating in structural impairments and functional aberrations within the kidneys. Physical injury factors include changes in renal hemodynamics, renal compression, and mechanical stretching of podocytes. Non-physical injury factors include overactivation of the RAAS system, insulin resistance, lipotoxicity, inflammation, and dysregulation of bile acid metabolism. Exploring molecules that target modulation of physical or nonphysical injury factors is a potential approach to ORN treatment. ORN is characterized clinically by microproteinuria and pathologically by glomerulomegaly, which is atypical and makes early diagnosis difficult. Investigating early diagnostic markers for ORN thus emerges as a critical direction for future research. Additionally, there is no specific drug for ORN in clinical treatment, which mainly focuses on weight reduction, mitigating proteinuria, and preserving renal function. In our review, we delineate a progressive therapeutic approach involving enhancements in lifestyle, pharmacotherapy, and bariatric surgery. Our emphasis underscores glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as poised to emerge as pivotal therapeutic modalities for ORN in forthcoming clinical avenues. Keywords: Obesity-related nephropathy, pathophysiology, diagnostics, therapeutics

Yuexiang Qin,1,2 Shanhu Yao,3,4 Gaoyuan Wang,5 Ziyuan Xu,6,7 Gangcai Zhu,8 Ying Li,1,2 Pingting Yang,1,2 Jiangang Wang,1,2 Chunbo Zou,5 Changhan Chen7,9 1Department of Health Management Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, 410013, People’s Republic of China; 2Hunan Chronic Disease Health Management Medical Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, 410013, People’s Republic of China; 3Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, 410013, People’s Republic of China; 4Key Laboratory of Medical Information Research, Central South University, Changsha, Hunan Province, 410013, People’s Republic of China; 5Department of Nephrology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 6Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, People’s Republic of China; 7National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 8Department of Otolaryngology, Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, People’s Republic of China; 9National Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, People’s Republic of ChinaCorrespondence: Changhan Chen, National Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China, Tel +86-13875974606, Email changhanchen@csu.edu.cnObjective: Inflammation plays a crucial role in the development of metabolic syndrome (MetS). However, the roles of pepsinogens (PGs) and gastrin, known biomarkers linked to gastric inflammation, in MetS and the transition of MetS status are unclear. This research aimed to explore the relationship between MetS, the transition of MetS status, and levels of gastric biomarkers.Methods: This large-scale cross-sectional study included 19162 participants aged 18– 80 years between August 2021 and March 2024. Serum levels of the gastric biomarkers PGI, PGII, and gastrin-17 were analyzed using enzyme-linked immunosorbent assay. In addition, the relationship between transitions of MetS status based on 1032 MetS-negative participants from baseline to the second health exam after 2 years was considered. The association between MetS and the transitions of MetS status and gastric biomarkers was analyzed using logistic regression models.Results: The prevalence of MetS in the study population was 31.4%, with higher rates in males (35.2%) than females (24.6%). Gastrin-17 levels were markedly elevated in participants with MetS, a trend observed in both genders. In the logistic regression analysis, after adjusting for confounding factors, gastrin-17 levels were strongly and positively correlated with MetS in the entire cohort and in males but not in females. Male participants with MetS had lower levels of PGI and PGII than those without MetS, whereas the opposite trend was observed in females. Logistic regression analysis indicated that PGI and PGII were not independently associated with MetS. During the follow-up of 2 years, 199 (19.28%) of the 1032 MetS-negative participants transitioned to MetS-positive status. As compared to the stable MetS-negative subjects, transition from MetS-negative to MetS-positive was associated with higher levels of gastrin-17, especially in males, but not in females.Conclusion: Gastrin-17 is a promising biomarker for MetS, exhibiting potential utility in monitoring the transition of MetS status and revealing gender difference.Keywords: gastric biomarkers, gastrin-17, metabolic syndrome, transition, gender difference

Rui Bai,1,2 Yuhang Sui,1,2 Tianqi Lu,1,2 Hua Chen,1,2 Gang Wang,1,2 Rui Kong,1,2 Hongtao Tan,1,2 Yongwei Wang,1,2 Guanqun Li,1,2 Bei Sun1,2 1Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China; 2Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of ChinaCorrespondence: Guanqun Li; Bei Sun, Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, 150001, People’s Republic of China, Email liguanqun@hrbmu.edu.cn; sunbei70@hrbmu.edu.cnPurpose: The effects of the step-jump approach on the survival and prognosis of infected pancreatic necrosis (IPN) patients have not yet been determined.Patients and Methods: Between November 2018 and June 2023, 188 patients were included in this study. There were 144 patients in the step-up group (the SU group) and 44 in the step-jump group (the SJ group). In the SU group, patients successfully treated with percutaneous catheter drainage (PCD) alone were classified into the SU-1 group (n=101), while those requiring additional surgery after PCD were categorized into the SU-2 group (n=43). In the SJ group, patients who underwent minimally invasive necrosectomy (MIN) without PCD were assigned to the SJ-1 group (n=34), whereas those who initially underwent PCD followed by immediate open surgery were placed in the SJ-2 group (n=10). Propensity score matching (PSM) was used to mitigate bias.Results: After PSM, a total of 34 pairs were successfully matched. A comparison of the SU group with the SJ-1 group (upfront MIN without PCD) revealed similar mortality rates (P=0.239); however, the incidences of multiple drug-resistant organisms (MDROs) (P=0.029) and surgical complications (P< 0.001) were significantly lower in the SJ-1 group. After comparing the SU-2 and SJ-2 groups (patients who underwent direct open necrosectomy without MIN after PCD failure), the incidences of surgical complications and MDRO in the SJ-2 group were significantly lower (P< 0.05).Conclusion: Compared with the step-up approach, the step-jump approach is safer and more effective and can significantly reduce the incidence of MDRO and surgical complications.Keywords: infected pancreatic necrosis, step-up approach, step-jump approach, propensity score match

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

Xuebing Zhang,1 Lianjie Wang,1 Ge Wang,1 Jiayue Li,1 Yiming Mu,2 Shidong Wang,1 Xiaoran Li1 1Department of Endocrinology, Dongzhimen Hospital Beijing University of Chinese Medicine, Beijing 100700, People’s Republic of China; 2Department of Endocrinology, First Medical Centre of Chinese PLA General Hospital, Beijing 100853, People’s Republic of ChinaCorrespondence: Shidong Wang; Xiaoran Li, Email A2082@bucm.edu.cn; 466187309@qq.comBackground: Nonalcoholic fatty liver disease (NAFLD) has become a major global health burden, which increases the risk of extra-hepatic complications such as type 2 diabetes mellitus (T2DM), dyslipidemia, metabolic syndrome (MetS), and cardiovascular disease (CVD). However, NAFLD remains underappreciated and underdiagnosed. Our study aimed to explore the prevalence of NAFLD and the association between NAFLD and CVD events among adults aged 40 and older in Northern China.Methods: This study was conducted in the Shijingshan district of Beijing, China from November 2011 to August 2012. A total of 18891 subjects were recruited in the study. The information including demographical information, lifestyle, previous history of diabetes, hypertension, dyslipidemia, CVD, and liver disease were gathered. Data on physical examination, blood lipid profile, fasting blood glucose, and 2-hour blood glucose were recorded. Determination of MetS was according to T2DM guideline of Chinese Diabetes Society (2020 edition). The association between CVD and NAFLD was evaluated by multivariate logistic regression.Results: The prevalence of NAFLD was 15.2%. After adjustment for age, smoking status, alcohol intake, WC, hypertension, dyslipidemia and hyperglycemia, the odds ratios (ORs) of CVD in men were 1.622 (95%CI: 1.345– 1.957) and 1.990 (95%CI: 1.709– 2.316) in women with NAFLD, compared with the subjects without NAFLD.Conclusions: NAFLD is independently associated with increased risk of CVD development.Keywords: nonalcoholic fatty liver disease, metabolic syndrome, cardiovascular disease, middle-aged and elderly, Chinese

Xiaolong Wang,1,2,&ast; Guanyi Wang,2,&ast; Peibin Cen,1,&ast; Hongyu Lan,1 Linfa Guo,2 Zuhaer Yisha,2 Aodun Gu,2 Guiyong Liu,3 Zijian Wang,2 Tongzu Liu,2,4– 8 Qingfeng Yu1,9– 11 1Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Department of Urology, Qianjiang Central Hospital of Hubei Province, Qianjiang, People’s Republic of China; 4Hubei Key Laboratory of Urological Diseases, Wuhan University, Wuhan, People’s Republic of China; 5Hubei Clinical Research Center for Laparoscopic/Endoscopic Urologic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 6Institute of Urology, Wuhan University, Wuhan, People’s Republic of China; 7Hubei Medical Quality Control Center for Laparoscopic/Endoscopic Urologic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 8Wuhan Clinical Research Center for Urogenital Tumors, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 9Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou Medical University, Guangzhou, People’s Republic of China; 10Guangdong Engineering Research Center of Urinary Minimally Invasive Surgery Robot and Intelligent Equipment, Guangzhou Medical University, Guangzhou, People’s Republic of China; 11Guangzhou Institute of Urology, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tongzu Liu, Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China, Email liutongzu@163.com Qingfeng Yu, Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Email sunriseyu@yeah.netIntroduction: Overactive bladder (OAB) is a highly prevalent condition with limited treatment options due to poor efficacy, side effects, and patient compliance. Novel drug delivery systems that can target the bladder wall may improve OAB therapy.Methods: We explored a polydopamine (PDA)-coated lactobacillus platform as a potential carrier for localized OAB treatment. Urinary microbiome profiling was performed to identify the presence of lactobacillus in healthy and OAB groups. Lactobacillus-PDA nanoparticles were synthesized and characterized by electron microscopy and spectrophotometry. A rat bladder perfusion model and human bladder smooth muscle cell spheroids were used to assess the distribution and penetration of the nanoparticles. The efficacy of the Lactobacillus-PDA system (LPS) for delivering the antimuscarinic drug solifenacin was evaluated in an OAB rat model.Results: Urinary microbiome profiling revealed lactobacillus as a dominant genus in both healthy and OAB groups. The synthesized Lactobacillus-PDA nanoparticles exhibited uniform size and optical properties. In the rat bladder perfusion model, the nanoparticles distributed throughout the bladder wall and smooth muscle without toxicity. The nanoparticles also penetrated human bladder smooth muscle cell spheroids. In the OAB rat model, LPS facilitated the delivery of solifenacin and improved treatment efficacy.Discussion: The results highlight LPS as a promising drug carrier for targeted OAB therapy via penetration into bladder tissues. This bacteriotherapy approach may overcome limitations of current systemic OAB medications. Lactobacillus, a probiotic bacterium present in the urinary tract microbiome, was hypothesized to adhere to and penetrate the bladder wall when coated with PDA nanoparticles, making it a suitable candidate for localized drug delivery. Keywords: polydopamine, lactobacillus, nano material, drug delivery, overactive bladder

Xiao-Meng Xie,1 Sha Sha,1 Hong Cai,2 Xinyu Liu,1 Isadora Jiang,3 Ling Zhang,1 Gang Wang1 1The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders Beijing Anding Hospital & the Advanced Innovation Center for Human Brain Protection, Capital Medical University, School of Mental Health, Beijing, People’s Republic of China; 2Unit of Medical Psychology and Behavior Medicine, School of Public Health, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Bellarmine College of Liberal Arts, Loyola Marymount University, Los Angeles, CA, USACorrespondence: Gang Wang, Beijing Anding Hospital, Beijing, People’s Republic of China, Email gangwangdoc@gmail.comBackground: Major depressive disorder (MDD) becomes one of the psychiatric disorders characteristic of a combination of cognitive, emotional, and somatic symptoms. Additionally, cognitive impairment has the most significant impact on functional results. However, the evaluation of cognitive level is still based on various subjective questionnaires as there is no objective standard assessment yet. This research focuses on resting-state alpha activity to identify cognition in MDD patients using electroencephalography (EEG) signals.Methods: Ninety-two subjects were recruited: 44 patients with MDD and 48 healthy individuals as controls. Functional outcome and cognition were assessed using standardized instruments, and the EEG resting state signal of open and closed eyes was recorded. The comparison and correlation of cognitive levels with alpha power in the bilateral frontal region, bilateral central region, bilateral occipital region, and middle line was evaluated.Results: The relative alpha power in MDD group was significantly lower than that in the control group (P < 0.05). Through correlation analysis, it was shown that the bilateral frontal and occipital alpha power of MDD patients in the closed-eyes state was positively correlated with information processing rate, verbal learning, working memory, and attention retention. The alpha power of the bilateral frontal region in the open-eyes state was positively correlated with information processing rate, working memory, and attention retention (P < 0.05).Conclusion: The research indicates that the changes in frontal and occipital alpha activities may be a promising neurophysiological indicator of cognitive level to diagnose and treat response prediction.Keywords: major depressive disorder, MDD, EEG, alpha power, cognition impairment

Na Wang,1,2 Guofeng Wang,2 Xiuli Feng,2 Teng Yang2 1Department of Endocrinology, Lianyungang Clinical College of Nanjing Medical University, Lianyungang City, Jiangsu Province, 222000, People’s Republic of China; 2Department of Endocrinology, Jinzhou Medical University(The First People’s Hospital of Lianyungang), Lianyungang City, Jiangsu Province, 222000, People’s Republic of ChinaCorrespondence: Guofeng Wang, Department of Endocrinology, Lianyungang Clinical College of Nanjing Medical University (The First People’s hospital of Lianyungang), No. 6 Zhenhua East Road, Haizhou District, Lianyungang City, Jiangsu Province, 222000, People’s Republic of China, Email wangguofengo@21cn.comPurpose: This study aimed to investigate the abnormal infiltration of immune cells in type 1 diabetes mellitus (T1D) and elucidate their regulatory mechanisms.Methods: Public T1D-related gene expression data were obtained from the Gene Expression Omnibus database.The GSE123658 dataset analyzed whole blood RNA-seq data from type 1 diabetic patients and healthy volunteers. The GSE110914 dataset analyzed neutrophils purified from peripheral blood of patients with symptomatic and pre-symptomatic type 1 diabetes (T1D), at risk of T1D, and healthy controls. Immune cell infiltration analysis was performed to identify abnormally infiltrating immune cells. Differentially expressed immune genes (DEIGs) in T1D samples were identified, followed by the construction of an immune gene signature (IGS) using a protein-protein interaction (PPI) network and Least absolute shrinkage and selection operator Cox regression analyses (LASSO Cox regression analyses). The regulatory mechanisms underlying IGS were explored using gene set enrichment analysis. Furthermore, expression validation, diagnostic efficacy evaluation, and upstream miRNA prediction of hub signature genes were performed. We verified the miRNA expression of the key gene colony stimulating factor 1 (CSF1) and microRNA-326 (miR-326) by reverse transcription-quantitative PCR (RT‒qPCR).Results: The proportion of infiltrating T and natural killer (NK) cells differed between the T1D and control samples, and 207 immune genes (IGs) related to these immune cells were extracted. After differential expression, PPI, and LASSO Cox regression analyses, four signature DEIGs were identified for IGS construction: notch receptor 1 (NOTCH1), Janus kinase 3 (JAK3), tumor necrosis factor receptor superfamily member 4(TNFRSF4), and CSF1. Key pathways such as the Toll-like receptor signaling pathway were significantly activated in the high-risk group. Moreover, the upregulation of CSF1 in T1D samples was confirmed using a validation dataset, and CSF1 showed high diagnostic efficacy for T1D. Furthermore, CSF1 was targeted by miR-326.We used validated key genes in T1D patients, several of which were confirmed by RT‒qPCR.Conclusion: In conclusion, the identified key IGs may play an important role in T1D. CSF1 can be developed as a novel diagnostic biomarker for T1D.Keywords: Type 1 diabetes, immune cell infiltration, immune gene signature, diagnosis, CSF1

Xiaolu Chen,1– 3 Jian Liu,1,2 Guizhen Wang,1,2 Yanqiu Sun,1,2 Xiang Ding,1– 3 Xianheng Zhang1– 3 1Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, 230038, People’s Republic of China; 2Institute of Rheumatology, Anhui University of Chinese Medicine, Hefei, Anhui Province, 230012, People’s Republic of China; 3Anhui University of Traditional Chinese Medicine, Hefei, People’s Republic of ChinaCorrespondence: Jian Liu, Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, 230038, People’s Republic of China, Tel +86 551 62838582, Fax +86 551 62821605, Email liujianahzy@126.comObjective: Jianpi Qingre Tongluo Recipe (JQP) has been widely used in clinical practice, and its anti-Osteoarthritis (OA) effectiveness and specific mechanism have been concerned. This study aims to explore the clinical effect of JQP in reducing inflammation and dyslipidemia in OA and the molecular mechanism.Methods: The clinical efficacy of JQP in OA treatment was assessed through data mining. Through the network pharmacology technology, the interactive network of “active component-target-disease” was developed, the interaction relationship of the related proteins was analyzed, and enrichment analysis of gene pathway biological process was conducted. Molecular docking was carried out with PyMOL and AutodockTools-1.5.7. Finally, cell experiments were used to verify JQP’s delay of immune inflammation in OA.Results: We found that JQP could ameliorate the immune inflammatory and lipid metabolism indicators; reduce VAS and SAS score in OA. A total of 98 genes overlapped between target genes of JQP and OA. TNF, IL-6, IL-1β, and AKT1 shared the highest centrality among all target genes. KEGG analysis unveiled that 98 intersection genes were predominantly enriched in PI3K/AKT pathway in the anti-OA system. In vitro, after peripheral blood mononuclear cell (PBMC) stimulation, inflammatory cytokines imbalances and the expressions of adiponectin (APN) were decreased in osteoarthritis-chondrocytes (OA-CH). Furthermore, JQP-containing serum protected OA-CHs through down-regulating HOTAIR levels, thereby up-regulating APN and depressing PI3K/AKT pathway.Conclusion: This study suggests that JQP might reduce inflammation and improve lipid metabolism of OA by regulating HOTAIR/APN/PI3K/AKT. Our results bring a new solution for OA.Keywords: osteoarthritis, chondrocytes, inflammation, LncRNA HOTAIR/APN/PI3K/AKT

Guangjian Wang,1,&ast; Hui Lian,2,&ast; Qirui Guo,1 Hongmin Zhang,1 Xiaoting Wang1 1Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Health Care, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoting Wang, Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of China, Email wangxiaoting@pumch.cnPurpose: We previously proposed a new concept, the “critical unit”, which covers the structural integrity and function of mitochondria and endothelium. Injury of the critical unit plays a key role in the development of critical illnesses. High levels of inflammation may lead to abnormalities of the critical unit, which is an important mechanism for critical illnesses, and both inflammation and critical unit dysfunction may affect patient prognosis. Here we evaluated the correlation between interleukin-6 (IL6) and the critical unit biomarkers in critically ill patients and the impact of both on prognosis.Patients and Methods: This study included adult patients admitted to the intensive care unit for various reasons from January 1st to May 31st, 2023. Baseline characteristics, intensive care unit parameters, and laboratory test and outcome data were obtained from the electronic medical records system. Critical unit parameters were measured using polymerase chain reaction and enzyme-linked immunosorbent assay methods. Correlations were examined between IL6, critical unit parameters, and various outcomes.Results: In critically ill patients, IL6 was closely associated with all the critical unit biomarkers (activated partial thromboplastin time, sphingosine 1-phosphate, mitochondrial DNA, mitochondrial fission 1, and Parkin) and the prognoses of patients. A nomogram was constructed using the critical unit biomarkers to predict the in-hospital mortality of critically ill patients. The area under the curve for the mortality prediction model was 0.708. In sensitivity analyses, the predictive effect was better in the non-surgery and tumor groups compared with the surgery and non-tumor groups, with area under the curve values of 0.885 and 0.891, respectively.Conclusion: Our study innovatively integrated mitochondrial and endothelial markers in the critical unit to comprehensively evaluate patient prognosis, which may be a trend in the future assessment of critically ill patients. There are few such studies, and ours may promote the progress of related research.Keywords: critical unit, IL6, critically ill patients, pro-inflammatory response, prognosis

Mindy Hong,1 Jeffrey Krauss,1 Grace Wang,2 Ken Cohen,3 Christine E Chaisson,4 Amitabh Gulati5 1Hinge Health, San Francisco, CA, USA; 2Weitzman Institute, Middletown, CT, USA; 3Optum Care Center for Research and Innovation, Eden Prairie, MN, USA; 4Yale University Center for Clinical Investigation, New Haven, CT, USA; 5Memorial Sloan Kettering Cancer Center, New York, NY, USACorrespondence: Mindy Hong, Email mindy.hong@hingehealth.comPurpose: Physical therapy (PT) and conservative care are recommended first-line treatments for musculoskeletal (MSK) pain. While essential to high-quality care, these solutions often do not provide immediate or sufficient pain relief. Traditional transcutaneous electronic nerve stimulation (TENS) devices are often recommended; however, there is mixed evidence behind their effectiveness. A novel approach called hybrid form impulse therapy (HFIT) incorporates a priming pulse with a traditional TENS pulse width and frequency. This randomized controlled trial (RCT) aimed to compare the effectiveness of HFIT versus traditional TENS versus usual care among members of a digital MSK program.Patients and Methods: A three-arm RCT comparing HFIT versus TENS versus usual care was conducted. A total of 325 people with chronic back or knee pain who were members of a digital MSK program consisting of PT-guided exercise therapy, education, and coaching were randomized. Outcomes including pain, function, anxiety, and depression were examined at 1, 2, and 4 weeks (primary endpoint). Engagement was measured through exercise therapy (ET) sessions completed. Unadjusted and adjusted logistic generalized estimating equations were conducted.Results: Adjusted per-protocol results at 4 weeks showed significantly lower odds of achieving pain improvement for both TENS (OR: 0.42, 95% CI: [0.19, 0.92]) and usual care (OR: 0.35, 95% CI: [0.17, 0.72]) groups, compared to HFIT group. Both HFIT and usual care users had significantly higher engagement than the TENS users (p=0.026 and p=0.002, respectively). No adverse events were reported throughout the study.Conclusion: More participants of a digital MSK program who were randomized to the HFIT group experienced meaningful pain improvement at 4 weeks than participants who used TENS and usual care. HFIT can be an effective, non-pharmaceutical solution for relief as a complement to first-line treatments for patients with chronic back and knee pain.Keywords: HFIT, pain, chronic pain, neuromodulation, noninvasive treatment

Hong Xu,1 Zuoli Sun,1 Gang Wang,1,2 Rena Li1 1Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Gang Wang; Rena Li, Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, People’s Republic of China, Email gangwangdoc@ccmu.edu.cn; renali@ccmu.edu.cnBackground: Several clinical studies have examined the connection between depression and bone loss, but the cause-and-effect relationship between the two conditions, especially in animal models, is not well-studied.Methods: A total of 32 female mice were, randomly divided into control group (CON, n=19) and depression group (DEP, n=13). The mice in the DEP group were subjected to 21 consecutive days of restraint stress, following depressive-like behaviors were assessment. The femurs were collected using Micro-Computed Tomography (μCT) and histochemical staining. In parallel, levels of serotonin-related proteins in the brain were measured using Western blot analysis, and sex hormone profiles were determined through liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS).Results: The mice in the DEP group exhibited clear signs of depressive-like behaviors and an increase in serotonin transporter levels (t=-2.435, P< 0.05). In comparison to the CON mice, the DEP mice showed a decrease in bone mineral density (t =3.741, P< 0.05), bone surface area density (t =8.009, P< 0.01), percent bone volume (t =4.293, P< 0.05), trabecular number (t =5.844, P< 0.01), and connected density (t =11.000, P< 0.05). Additionally, there was an increase in trabecular separation (t =-7.436, P< 0.01) in DEP mice. Furthermore, the DEP mice displayed a significant reduction in serum estrogen levels (t =4.340, P< 0.05) and changes in its metabolite (t =-3.325, P< 0.05), while the levels of androgens remained unchanged.Conclusion: The restraint stress not only led to the development of depressive-like behaviors but also disrupted the estrogen metabolism pathway, resulting in damage to bone mass and microstructure in female mice. These findings suggest that stress-induced depression may pose a risk for bone loss in female mice by altering estrogen metabolism pathways.Keywords: depression, bone mineral density, bone structure, estrogen, female

Yannan Pan,1,2,&ast; Jiandan Qian,1,&ast; Guiqiang Wang,1 Hong Zhao1 1Department of Infectious Diseases, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guiqiang Wang; Hong Zhao, Department of Infectious Diseases, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of China, Email john131212@126.com; zhaohong_pufh@bjmu.edu.cnBackground: Infective endocarditis caused by Streptococcus sinensis is exceedingly rare, with only limited cases reported. Here, we present the first documented case of prosthetic valve endocarditis attributed to Streptococcus sinensis.Case Presentation: A 40-year-old Chinese female was admitted with a 45-day history of intermittent fever. The presumed diagnosis was a pulmonary infection and antibiotic therapies failed to alleviate her symptoms. On admission, infective endocarditis was suspected, considering the history of aortic valve replacement and recent dental procedure without prophylactic antibiotics. Transesophageal echocardiography disclosed a 3-millimeter vegetation in the prosthetic aortic valve, and metagenomic next-generation sequencing and mass spectrometry identified Streptococcus sinensis. The patient was diagnosed with infective endocarditis. Antibiotic treatments resulted in temporary clinical improvements, although fluctuations in temperature and inflammatory markers led to multiple attempts at antibiotic therapies. At last, the patient underwent an elective aortic valve replacement with a favorable prognosis.Conclusion: In this case, we demonstrated prosthetic valve endocarditis caused by Streptococcus sinensis, which is an extremely rare pathogen. All reported endocarditis cases caused by Streptococcus sinensis were reviewed and summarized. Most of these patients had rheumatic heart diseases or congenital heart diseases. Antibiotic prophylaxis is important for high-risk procedures. Timely identification of the bacterium is crucial for diagnosis and treatment. Overall, infective endocarditis caused by this bacterium had a good prognosis.Keywords: infective endocarditis, prosthetic valve, Streptococcus sinensis, metagenomic next-generation sequencing, case report

Guoqin Wang,1,&ast; Xiaoying Hu,1,&ast; Nan Ye,1 Xiaoyi Xu,1 Weiyi Guo,1 Lijun Sun,1 Hongrui Dong,1 Xiaoyi Zhao,2 Hong Cheng1 1Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Division of Nephrology, Affiliated Hospital of Chifeng University, Neimenggu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Cheng, Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Beijing, 100029, People’s Republic of China, Email drchengh@163.comPurpose: In recent years, the incidence of malignancy patients with membranous nephropathy (MN) has gradually increased, but the clinical and pathological characteristics of these patients are still unclear. Our study aims at elucidating the clinical and pathological characteristics of malignancy patients with MN, especially the expression patterns of MN-specific antigens in both kidney and tumor tissue.Patients and Methods: A retrospective analysis was performed to summarize the clinical and pathological data of MN patients with malignancy at Beijing Anzhen Hospital from January 1, 2012, to December 31, 2022, followed by a thorough review of relevant literature published between May 1, 2000 to May 1, 2023 and case aggregation.Results: 19 patients in our center’s MN cohort and 21 patients from literature review were diagnosed with malignancy either before or after being diagnosed with MN. Among them, 16 (40.0%) and 17 (42.5%) patients tested PLA2R-only and THSD7A-only positive in renal tissue, respectively. And 16 of 26 patients showed similar staining in tumor and kidney tissues. Compared to the idiopathic membranous nephropathy (IMN) patients at our center, patients with malignancy were older, had a lower estimated glomerular filtration rate, and had a lower rate of partial or complete response to treatment. Renal tissue from MN patients with concomitant malignancy was less frequently PLA2R-positive, more frequently THSD7A-positive, and more often glomerular IgG subclass IgG2 (P = 0.033) but less frequently IgG4 (P < 0.001).Conclusion: The clinical and pathological characteristics of MN patients with concomitant malignancy are different from those of IMN patients. Active screening for malignancy should be performed in non-PLA2R-positive elderly MN patients with a poor therapeutic response. Staining for MN target antigens in kidney and tumor tissues may be inconsistent, and the role of MN target antigens needs to be further explored.Keywords: malignancy, membranous nephropathy, PLA2R, THSD7A, NELL-1

Gang Wang,1,&ast; Tianmei Si,2,&ast; Andreas Rieckmann,3 Jingdong Ma,4 Michael Cronquist Christensen3 1The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital & The Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 2Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, People’s Republic of China; 3Global Medical Affairs, H. Lundbeck A/S, Valby, Denmark; 4Medical Affairs, Lundbeck China, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Michael Cronquist Christensen, Global Medical Affairs, H. Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark, Tel +45 3083 5168, Email MCRC@lundbeck.comBackground: Major depressive disorder (MDD) causes significant functional impairments that impact on all aspects of patients’ daily lives, including their ability to work, work productivity, and social life.Purpose: To assess the real-world effectiveness of the multimodal antidepressant vortioxetine in working patients with MDD in China.Patients and methods: RELIEVE China was an observational, prospective cohort study. Patients (aged ≥ 18 years) with MDD initiating treatment with vortioxetine in routine clinical practice settings were followed for 24 weeks. In this subgroup analysis, functioning was assessed using the Sheehan Disability Scale (SDS) in patients in full- or part-time work or education at baseline who remained on treatment at all follow-up visits (n=424). Depressive, cognitive, and anxiety symptoms were also assessed. For all endpoints, mean change from baseline at weeks 8 and 24 was analyzed using mixed models for repeated measures.Results: Clinically relevant and sustained improvements in patient functioning and measures of work productivity were observed over the 24 weeks of vortioxetine treatment. The adjusted mean (standard error) reduction in SDS total score from baseline was 5.4 (0.3) points at week 8 and 8.7 (0.3) points at week 24 (both P< 0.001 vs baseline). Significant improvements were observed across all SDS domains and in levels of absenteeism and presenteeism (P< 0.001 vs baseline for all endpoints at both time points). Significant improvements in depressive, cognitive, and anxiety symptoms were also observed over the study period (all P< 0.001 vs baseline). The proportion of patients in remission (ie, 17-item Hamilton Depression Rating Scale score ≤ 7) after 24 weeks of vortioxetine treatment was 65.4%. Vortioxetine was well tolerated; nausea was the most common adverse event, reported by 18.6% of patients.Conclusion: These findings support the effectiveness and tolerability of vortioxetine in working patients with MDD receiving treatment in routine clinical practice settings in China.Keywords: China, cognitive symptoms, major depressive disorder, patient functioning, vortioxetine, work productivity

Xixia Chen,1 Sang Lin,2 Qiwen Jin,1 Lu Zhang,3 Wei Jiang,3 Xin Lu,3 Guochun Wang,1,3 Yongpeng Ge3 1Peking University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of China; 2Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Rheumatology, Key Myositis Laboratories, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yongpeng Ge, Department of Rheumatology, China-Japan Friendship Hospital, Yinghua East Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86 13716106183, Email gyp2016@163.comObjective: To investigate the prevalence, risk factors and prognosis of invasive pulmonary aspergillosis (IPA) in patients with anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+ DM).Methods: A retrospective analysis was conducted in anti-MDA5+ DM patients diagnosed between January 2016 and March 2023. Patients with lower respiratory tract specimens were categorized into IPA+ and IPA- groups based on the presence of IPA and their clinical characteristics and prognoses then compared.Results: Of the 415 patients diagnosed with anti-MDA5+ DM, 28 cases had IPA (prevalence rate of 6.7%) with Aspergillus fumigatus being the most common species. The patients were categorized into IPA+ (n=28) and IPA- (n=98) groups, with no significant age or gender-related differences (P> 0.05). The IPA+ group had a lower lymphocyte count, particularly the CD4+ T-cell count, and reduced serum albumin and higher serum ferritin levels (P all< 0.05). An elevated bronchoalveolar lavage fluid (BALF) galactomannan level was found to be the sole independent risk factor for the occurrence of IPA (adjusted OR=2.191, P=0.029) with a cut-off value of 0.585 and area under the curve of 0.779. The mortality rate in the IPA+ group was 25%. Compared to survivors, non-survivors in this group exhibited a higher incidence of rapidly progressive interstitial lung disease, lower lymphocyte counts, and increased co-infection with Pneumocystis jirovecii (P all< 0.05).Conclusion: IPA was not rare in patients with anti-MDA5+ DM, with elevated BALF galactomannan levels being an independent risk factor for IPA occurrence. Clinicians must exercise vigilance to identify patients exhibiting the aforementioned risk factors.Keywords: invasive pulmonary aspergillosis, opportunistic infection, anti-MDA5+ dermatomyositis, prevalence, risk factors, prognosis

Guangtian Wang,1,2,&ast; Zhihui Li,3,&ast; Gongchen Wang,4,&ast; Qixu Sun,5 Peng Lin,1 Qian Wang,2 Huishu Zhang,6 Yanyan Wang,7 Tongshuai Zhang,8 Feiyun Cui,9 Zhaohua Zhong1,2 1Teaching Center of Pathogenic Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Microbiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 3Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China; 4Department of Vascular Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China; 5Department of Gastroenterology, Penglai People’s Hospital, Yantai, Shandong, 265600, People’s Republic of China; 6Teaching Center of Biotechnology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 7Teaching Center of Morphology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 8Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 9Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaohua Zhong; Feiyun Cui, Email zhongzh@hrbmu.edu.cn; feiyun@hrbmu.edu.cnAbstract: Angiogenesis, or the formation of new blood vessels, is a natural defensive mechanism that aids in the restoration of oxygen and nutrition delivery to injured brain tissue after an ischemic stroke. Angiogenesis, by increasing vessel development, may maintain brain perfusion, enabling neuronal survival, brain plasticity, and neurologic recovery. Induction of angiogenesis and the formation of new vessels aid in neurorepair processes such as neurogenesis and synaptogenesis. Advanced nano drug delivery systems hold promise for treatment stroke by facilitating efficient transportation across the the blood-brain barrier and maintaining optimal drug concentrations. Nanoparticle has recently been shown to greatly boost angiogenesis and decrease vascular permeability, as well as improve neuroplasticity and neurological recovery after ischemic stroke. We describe current breakthroughs in the development of nanoparticle-based treatments for better angiogenesis therapy for ischemic stroke employing polymeric nanoparticles, liposomes, inorganic nanoparticles, and biomimetic nanoparticles in this study. We outline new nanoparticles in detail, review the hurdles and strategies for conveying nanoparticle to lesions, and demonstrate the most recent advances in nanoparticle in angiogenesis for stroke treatment. Keywords: angiogenesis, ischemic stroke, nanoparticles, blood brain barrier, neurogenesis, neuroprotection therapy

Weiwei Xie,1,&ast; Junqi Luo,1,&ast; Ruowei Tang,2,&ast; Xuan Zhou,3 Xiaohong Wang,4,5 Guojie Wang,1,5 Yaqin Zhang1 1Department of Radiology, the Fifth Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, People’s Republic of China; 2Department of Radiology, Beijing Friendship Hospital, Beijing, People’s Republic of China; 3Departments of Pathology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong Province, People’s Republic of China; 4Department of Radiology, the Third Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 5Department of Radiology, The First People’s Hospital of Kashi Prefecture, Kashi Prefecture, Xinjiang Uygur Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaqin Zhang; Guojie Wang, Department of Radiology, the Fifth Hospital of Sun Yat-sen University, 52 East Meihua Road, Xiangzhou District, Zhuhai, Guangdong Province, People’s Republic of China, Email zhyaqin@mail.sysu.edu.cn; wanggj5@mail.sysu.edu.cnPurpose: To explore the clinical and imaging features of rare site Kimura’s disease (KD).Methods: Retrospective analysis was conducted on the clinical manifestations, laboratory examinations, and imaging features of five patients with rare site KD. All imaging data, including the location, quantity, size, uniformity, boundary, and enhanced appearance of the lesion were evaluated by two independent radiologists.Results: Of the five patients, four were asymptomatic, and one experienced localized skin itching. Four cases involved subcutaneous nodules in the upper arm, while one was in the inguinal region. The main manifestations were single (three cases) or multiple (two cases) subcutaneous nodules/masses, with three patients accompanied by local lymph node enlargement. Four patients exhibited elevated eosinophil counts in their peripheral blood. Four patients had lesions with vascular flow voids; in three of these, the lesions also showed prominent enhancement. Notably, the lesion in a 5-year-old did not show vascular flow voids but displayed significant enhancement. Additionally, two patients showed edema around the lesions.Conclusion: The presence of solitary or multiple subcutaneous nodules/masses in the upper arm or inguinal area, accompanied by lymph node enlargement, elevated eosinophils in the peripheral blood, and the observation of internal vascular within the lesion, can aid in the diagnosis of KD occurring in uncommon anatomical locations.Keywords: Kimura disease, increased eosinophils, image, uncommon anatomical locations

Gen Wang, Ning Lin Department of Neurosurgery, The Affiliated Chuzhou Hospital of Anhui Medical University (The First People’s Hospital of Chuzhou), Chuzhou, Anhui Province, People’s Republic of ChinaCorrespondence: Ning Lin, Email lin_neurosurgery@163.comBackground: This study focuses on the role of SIRT1 in neuroinflammation caused by early brain injury (EBI) after subarachnoid hemorrhage (SAH), and explores its mechanism in mitophagy after SAH.Methods: C57BL/6J mice and primary microglia SAH in vivo and in vitro models were constructed to explore the expression level of SIRT1 in neuroinflammation after SAH. Subsequently, the brain edema content, blood–brain barrier (BBB) damage and neurological function scores of the mice were observed after using the SIRT1 inhibitor EX-527. q-PCR and Western blot were used to detect relevant genes and proteins, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of IL-6, IL-1β, and TNF-α inflammatory factors. Immunofluorescence staining was used to observe the positive level of SIRT1 and the degree of mitochondria-lysosome fusion, and transmission electron microscopy was used to observe mitochondrial damage and autophagosome levels.Results: In in vivo and in vitro experiments, we found that SIRT1 expression increased after SAH, and neurological deficits, brain edema, and blood–brain barrier damage after SAH were aggravated. Inhibiting SIRT1 further aggravates the aforementioned damage. In addition, EX-527 can also inhibit the level of mitophagy and aggravate neuroinflammation after SAH.Conclusion: Our results indicated that SIRT1 promotes mitophagy and alleviates neuroinflammation after SAH.Keywords: subarachnoid hemorrhage, SIRT1, mitophagy, early brain injury

Jinchun Liu,1 Zhijun Yu,2,3 Guohua Wang2 1Department of Medicine, Henan Vocational College of Nursing, Anyang, Henan Province, 455000, People’s Republic of China; 2Department of Neurophysiology and Neuropharmacology, Institute of Special Environmental Medicine and Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226019, People’s Republic of China; 3Department of Thoracic Surgery, Nantong Second People’s Hospital, Nantong, Jiangsu, 226001, People’s Republic of ChinaCorrespondence: Guohua Wang, Email wgh036@hotmail.comAbstract: Coronary artery fistulae (CAF) are a rare anomaly characterized by abnormal connections between a coronary artery and a cardiac chamber or a great vessel, with most patients remaining asymptomatic. Despite being predisposed to severe complications like heart failure, patients with CAF infrequently experience severe stenosis in the coronary artery. This study delineates a case involving a 46-year-old male presenting with a fistula bridging the right coronary artery (RCA) and right atrium (RA), manifesting a pronounced 99% stenosis at the right extremity of the coronary artery proximal to the fistula. Concurrently, the individual exhibits six conventional risk factors: age over 40, male gender, hypertension, diabetes, smoking, and hypertriglyceridemia. Following pharmaceutical intervention, the patient was discharged and subjected to extended follow-up. This case highlights the dual processes of “accelerating damage” and “retarding renewal” in the progression of atherosclerosis. Factors such as shear stress, smoking, and hypertension are posited to expedite endothelial cell damage, while aging and diabetes may impede the renewal and repair of these cells. Together with the concept of secondary atherosclerotic plaque healing, this case prompts the introduction of a “Double Endothelial Healings” hypothesis, proposing a potential pathogenetic mechanism for coronary artery atherosclerosis.Keywords: coronary artery fistulae, atherosclerosis, pathogenesis, plaque healing, endothelial injury

Yue Wang,&ast; Liyan Chu,&ast; He Li, Yingjie Du, Shanshan Wang, Ying Liu, Guyan Wang Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guyan Wang, Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaominxiang, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-13910985139, Email guyanwang2006@163.comPurpose: The aim of this study was to determine whether preoperative video distraction reduces the incidence of emergence delirium in preschool children under general anesthesia with sevoflurane.Patients and Methods: In this prospective randomized controlled study, children aged 3– 6 years were randomized to receive either video distraction (Group V) or common clinical practice (Group C) from arrival at the holding area to induction of anesthesia. The primary outcome was the incidence of emergence delirium. Preoperative anxiety scores, assessed by the simple modified Yale Perioperative Anxiety Scale, were also collected.Results: A total of 160 patients were included in our study. The children in Group V (n=80) exhibited a significantly lower incidence of emergence delirium than did those in Group C (n=80) (12.5% vs 35.0%; RR 0.36, 95% CI 0.19, 0.69; P =0.0008). The maximum Pediatric Anesthesia Emergence Delirium score in Group V was significantly lower than that in Group C (3.0 vs 5.0; mean difference − 2.64, 95% CI: − 4.12, − 1.16; P=0.0003). The simple modified Yale Perioperative Anxiety Scale scores at separation from parents and the onset of inhalation induction in Group V were significantly lower than those in Group C (36.4 ± 9.9 vs 48.2 ± 16.7; mean difference 11.92, 95% CI 7.25, 16.59; P< 0.0001 and 41.5 ± 15.9 vs 59.7 ± 21.5; mean difference 18.11, 95% CI 11.76, 24.47; P< 0.0001).Conclusion: Preoperative video distraction reduces the incidence of emergence delirium in preschool children who undergo strabismus surgery under general anesthesia with sevoflurane.Keywords: emergence delirium, anxiety, children, preschool

Dong Hu,1 Ruyue Yang,1 Guidan Wang,2 Hao Li,1 Xulong Fan,1 Gaofeng Liang1 1School of Basic Medicine and Forensic Medicine, Henan University of Science & Technology, Luoyang, 471023, People’s Republic of China; 2School of Medical Technology and Engineering, Henan University of Science & Technology, Luoyang, 471023, People’s Republic of ChinaCorrespondence: Gaofeng Liang, School of Basic Medicine and Forensic Medicine, Henan University of Science & Technology, Luoyang, 471023, People’s Republic of China, Email lgfeng990448@163.comAbstract: Adoptive T cells immunotherapy, specifically chimeric antigen receptor T cells (CAR-T), has shown promising therapeutic efficacy in the treatment of hematologic malignancies. As extensive research on CAR-T therapies has been conducted, various challenges have emerged that significantly hampered their clinical application, including tumor recurrence, CAR-T cell exhaustion, and cytokine release syndrome (CRS). To overcome the hurdles of CAR-T therapy in clinical treatment, cell-free emerging therapies based on exosomes derived from CAR-T cells have been developed as an effective and promising alternative approach. In this review, we present CAR-T cell-based therapies for the treatment of tumors, including the features and benefits of CAR-T therapies, the limitations that exist in this field, and the measures taken to overcome them. Furthermore, we discuss the notable benefits of utilizing exosomes released from CAR-T cells in tumor treatment and anticipate potential issues in clinical trials. Lastly, drawing from previous research on exosomes from CAR-T cells and the characteristics of exosomes, we propose strategies to overcome these restrictions. Additionally, the review discusses the plight in large-scale preparation of exosome and provides potential solutions for future clinical applications.Keywords: tumor, CAR-T cells, immune escape, exosome

Yue Zhang,&ast; Yafan Bai,&ast; Yi Zhang, Yingjie Du, Min Liu, Jiayu Zhu, Guyan Wang Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guyan Wang, Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaomingxiang, Beijing, 100730, People’s Republic of China, Tel +86-13910985139, Fax +86-10-58268017, Email guyanwang2006@163.comPurpose: Despite the implementation of various insulation measures, the incidence of hypothermia during thyroid surgery remains high. This randomized controlled study aimed to evaluate the effects of aggressive thermal management combined with resistive heating mattresses to prevent perioperative hypothermia in patients undergoing thyroid surgery.Patients and Methods: 142 consecutive patients scheduled for elective thyroid surgery were enrolled in the study. They were randomly and equally allocated to the aggressive warming or routine care groups (n = 71). The patients’ body temperature was monitored before the induction of anesthesia until they returned to the ward. The primary outcome was the incidence of perioperative hypothermia. Secondary outcomes included postoperative complications, such as mortality, cardiovascular complications, wound infection, shivering, postoperative nausea and vomiting (PONV), visual analog scale (VAS) pain scores, fever, headache and hospital length of stay (LOS).Results: In our study, the results showed that a significantly higher rate of hypothermia was observed in the routine care group compared with the aggressive warming group. The incidence of perioperative hypothermia was 19.72% (14/71) in the aggressive warming group and 35.21% (25/71) in the routine care group (P < 0.05). The incidence of shivering in the aggressive warming group (1.41%) was significantly lower than that in the routine care group (11.27%) (P < 0.05), and a one-day reduction in hospital length of stay was observed in the aggressive warming group (P < 0.05). There was no significant difference in mortality or other postoperative complications, such as cardiovascular complications, wound infection, PONV, pain, fever or headache, between the two groups (P > 0.05).Conclusion: Our results suggest that aggressive thermal management combined with resistive heating mattresses provided improved perioperative body temperature and reduced the incidence of perioperative hypothermia and shivering compared to routine thermal management.Plain Language Summary: ●The incidence of perioperative hypothermia during thyroid surgery was high.●The use of resistive heating mattresses during thyroid surgery can effectively reduce the occurrence of perioperative hypothermia.●It is recommended to take aggressive thermal protection during the operation of minor and medium surgeries, and to continuously monitor the temperature.Keywords: hypothermia, thyroid surgery, resistive heating mattresses, perioperative period

Xiaoyan He,1 Guozhen Zai,1 Lidan Zhou,2 Shengyang Chen,3 Guizhi Wang1 1Department of Pathology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Radiology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Guizhi Wang, Email wgz2019@126.comBackground: Research has indicated that VRK1 is essential for the tumor cell cycle. However, its prognostic and immunotherapeutic predictive significance has not been documented in hepatocellular carcinoma (HCC).Methods: The TCGA, ICGC, and GSE14520 datasets were used to investigate VRK1 expression and its predictive significance of survival outcomes. The qRT-PCR and immunohistochemistry (IHC) were used to confirm the findings. The immunotherapeutic response of VRK1 was anticipated by the IMvigor210 cohort. Lastly, the association between immune infiltration, m6A modification, and functional enrichment of differentially expressed genes (DEGs) was investigated in connection to VRK1 expression.Results: VRK1 expression was markedly elevated on both the mRNA and protein levels in HCC. In HCC patients, a high expression of VRK1 was linked to a poor prognosis. Furthermore, there was a substantial positive correlation seen between increased VRK1 expression and the response rate to anti-PD-L1 immunotherapy. Relationships between VRK1 and m6A-related genes as well as different immune cells were shown by correlation studies. Lastly, enrichment analysis revealed a tight relationship between VRK1 and important biological functions, including DNA replication, cell cycle control, and fatty acid metabolism.Conclusion: Our research reveals the potential of VRK1 as a novel biomarker for prognosis and immunotherapy response in HCC patients.Keywords: VRK1, immune infiltration, immunotherapy, m6A, HCC

Geng Wang, Jian Xu School of Media & Communication, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaCorrespondence: Jian Xu, School of Media & Communication, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang District, Shanghai, 200240, People’s Republic of China, Tel +86 13817505128, Email xujian@sjtu.edu.cnPurpose: In the intersection of the aging and information era, the development of digital aging significantly influences the well-being of older individuals. Given the divergent findings in various studies exploring the effects of social media use on mental health, this study specifically examined the impact of forwarding, a prevalent social media behavior among older individuals, focusing on the effects of use intensity on their subjective well-being (SWB) and the specific mechanisms involved.Materials and Methods: A total of 323 Chinese older adults completed the questionnaire. SPSS along with Hayes Process Models 4 and 7 was employed to test the hypotheses.Results: The results indicated that social media forwarding intensity significantly and positively predicted SWB of older adults. This association was partially mediated by perceived social support (PSS) and self-esteem. Gender served as a moderator, highlighting that the positive predictive effects of forwarding intensity on PSS and self-esteem were more pronounced for older men than for older women. Further, the findings confirmed the existence of the moderated mediating effect such that the impact of forwarding on SWB was mediated through both PSS and self-esteem for older men, while, for older women, it was solely mediated by PSS.Conclusion: This study revealed the positive impact of forwarding, a user-friendly social media function, on the well-being of older adults and elucidated the specific mechanisms through a moderated mediation model. In light of these findings, we propose customizing the development of age-friendly social media functions to address the diverse psychological needs of older adults, taking into account gender differences. These findings may offer valuable insights for constructing digital age-friendly platforms and fostering active aging development.Keywords: social media forwarding, Chinese older adults, well-being, perceived social support, self-esteem, gender

Yuanli Ai,1,&ast; Kun Peng,2,&ast; Chunli Li,1,&ast; Jun Zhang,1 Gang Wang,3,4 Bin Wang,1 Enyi Huang3,4 1Institute of Life Sciences, College of Basic Medicine, Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Medical and Pharmaceutical College, Chongqing, People’s Republic of China; 3Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education College of Stomatology, College of Stomatology, Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Wang; Enyi Huang, Email bwang@cqmu.edu.cn; enyihuang@hospital.cqmu.edu.cnIntroduction: Bone, a pivotal structural organ, is susceptible to disorders with profound health implications. The investigation of gene expression in bone tissue is imperative, particularly within the context of metabolic diseases such as obesity and diabetes that augment the susceptibility to bone fractures. The objective of this study is to identify a set of internal control genes for the analysis of gene expression.Methods: This study employs reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) to assess gene expression in bone tissue. We selected fourteen housekeeping genes and assessed their stability in the cortical bone of mouse models for obesity and diabetes using four well-established algorithms (GeNorm, BestKeeper, NormFinder, and the comparative Delta Ct method).Results and Conclusion: We identified Rpl13a as the mostly stably expressed reference gene in cortical bone tissue from mouse models of obesity and diabetes (db/db), while Gapdh was found to be the most stable reference gene in another diabetes model, KKAy mice. Additionally, Ef1a, Ppia, Rplp0, and Rpl22 were identified as alternative genes suitable for normalizing gene expression in cortical bone from obesity and diabetes mouse models. These findings enhance RT-qPCR accuracy and reliability, offering a strategic guide to select reference gene for studying bone tissue gene expression in metabolic disorders.Keywords: reference genes, Rpl13a, Gapdh, cortical bone, metabolic disorders

Yunzhi Xiang,&ast; Guanghui Wang,&ast; Baoliang Liu, Haotian Zheng, Qiang Liu, Guoyuan Ma, Jiajun Du Institute of Oncology, Shandong Provincial Hospital, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiajun Du, Shandong Provincial Hospital, No. 324 Jingwu Road, Huaiyin District, Jinan, 250000, People’s Republic of China, Email dujiajun@sdu.edu.cnBackground: In recent years, the immunotherapy of lung adenocarcinoma has developed rapidly, but the good therapeutic effect only exists in some patients, and most of the current predictors cannot predict it very well. Tumor-infiltrating macrophages have been reported to play a crucial role in lung adenocarcinoma (LUAD). Thus, we want to build novel molecular markers based on macrophages.Methods: By non-negative matrix factorization (NMF) algorithm and Cox regression analysis, we constructed macrophage-related subtypes of LUAD patients and built a novel gene signature consisting of 12 differentially expressed genes between two subtypes. The gene signature was further validated in Gene-Expression Omnibus (GEO) datasets. Its predictive effect on prognosis and immunotherapy outcome was further evaluated with rounded analyses. We finally explore the role of TRIM28 in LUAD with a series of in vitro experiments.Results: Our research indicated that a higher LMS score was significantly correlated with tumor staging, pathological grade, tumor node metastasis stage, and survival. LMS was identified as an independent risk factor for OS in LUAD patients and verified in GEO datasets. Clinical response to immunotherapy was better in patients with low LMS score compared to those with high LMS score. TRIM28, a key gene in the gene signature, was shown to promote the proliferation, invasion and migration of LUAD cell.Conclusion: Our study highlights the significant role of gene signature in predicting the prognosis and immunotherapy efficacy of LUAD patients, and identifies TRIM28 as a potential biomarker for the treatment of LUAD.Keywords: lung adenocarcinoma, macrophage, TRIM28, prognosis, immunotherapy

Yuping Ding,1,2 Guiqiang Wang,3,4 Quanjun Deng,1,2 Mei Yang,1,2 Jinghua Li,5 Zuoyu Wang,1,2 Haiyan Niu,1,2 Shihai Xia1,2 1Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China; 2Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China; 3Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, People’s Republic of China; 4Department of Infectious Diseases, Peking University International Hospital, Beijing, People’s Republic of China; 5Department of Endocrinology and Hematology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of ChinaCorrespondence: Shihai Xia, Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, 220, Chenglin Road, Dongli, Tianjin, 300162, People’s Republic of China, Email xshhcx@sina.comBackground: Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are closely related conditions.Aim: This study investigated a group of individuals with NAFLD to evaluate if liver fibrosis, identified by FibroScan, correlated with T2DM.Methods: 154 NAFLD patients obtained FibroScan, liver ultrasonography (US), and a thorough assessment of clinical implications and chemical biomarkers.Results: In comparison to the NAFLD without T2DM group, the hemoglobin A1c(HBA1c)(mmol/mol%), homeostasis model of assessment for insulin resistance index (HOMA-IR), gamma-glutamyl transferase (GGT), fibrosis indices, and liver stiffness measurement (LSM) values were all considerably higher in the NAFLD with T2DM group. Patients with NAFLD and T2DM had considerably lower serum uric acid(SUA) levels than those with NAFLD alone.Those with severe fibrosis (79.3%, 23/29) in the NAFLD group showed a greater frequency of T2DM than those with mild fibrosis (45.6%, 21/46) or no fibrosis (27.85%, 22/79) (P=0.000). LSM value and elements of the metabolic syndrome (MetS) were independent risk factors for incident T2DM among NAFLD patients (OR=1.466, 95% CI [1.139-1.888], P=0.003; and OR=0.273, 95% CI [0.081-0.916], P=0.036).Conclusion: FibroScan can identify significant fibrosis, which is independently linked to a higher prevalence of T2DM. As a result, it is crucial to make use of this technology to predict T2DM in NAFLD patients.Keywords: liver stiffness measurement, NAFLD, T2DM, risk factors, early warning

Lanwei Xu,1,2 Zheng Wang,3 Gang Wang1 1Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Department of Hand and Foot Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China; 3Department of Neurosurgery, Liaocheng Traditional Chinese Medicine Hospital, Liaocheng, 252000, People’s Republic of ChinaCorrespondence: Zheng Wang, Department of Neurosurgery, Liaocheng Traditional Chinese Medicine Hospital, Liaocheng, 252000, People’s Republic of China, Tel +86 18063560328, Email zhengyimingdao@gmail.com Gang Wang, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Tel +86 13791006108, Email wanggangnfmed@gmail.comPurpose: Osteoarthritis (OA) is a joint disease with a long and slow course, which is one of the major causes of disability in middle and old-aged people. This study was dedicated to excavating the cellular senescence-associated biomarkers of OA.Methods: The Gene Expression Omnibus (GEO) database was searched and five datasets pertaining to OA were obtained. After removing the batch effect, the GSE55235, GSE55457, GSE82107, and GSE12021 datasets were integrated together for screening of the candidate genes by differential analysis and weighted gene co-expression network analysis (WGCNA). Next, those genes were further filtered by machine learning algorithms to obtain cellular senescence-associated biomarkers of OA. Subsequently, enrichment analyses based on those biomarkers were conducted, and we profiled the infiltration levels of 22 types immune cells with the ERSORT algorithm. A lncRNA-miRNA-mRNA regulatory and drug-gene network were constructed. Finally, we validated the senescence-associated biomarkers at both in vivo and in vitro levels.Results: Five genes (BCL6, MCL1, SLC16A7, PIM1, and EPHA3) were authenticated as cellular senescence-associated biomarkers in OA. ROC curves demonstrated the reliable capacity of the five genes as a whole to discriminate OA samples from normal samples. The nomogram diagnostic model based on 5 genes proved to be a reliable predictor of OA. Single-gene GSEA results pointed to the involvement of the five biomarkers in immune-related pathways and oxidative phosphorylation in the development of OA. Immune infiltration analysis manifested that the five genes were significantly correlated with differential immune cells. Subsequently, a lncRNA-miRNA-mRNA network and gene-drug network containing were generated based on five cellular senescence-associated biomarkers in OA.Conclusion: A foundation for understanding the pathophysiology of OA and new insights into OA diagnosis and treatment were provided by the identification of five genes, namely BCL6, MCL1, SLC16A7, PIM1, and EPHA3, as biomarkers associated with cellular senescence in OA.Keywords: osteoarthritis, cellular senescence-related genes, biomarkers, drugs, PIM1

Qian Fan,1,&ast; Ling Gao,1,&ast; Zhiquan Wang,2,&ast; Fabrice Yves Ndjana Lessomo,2 Gang Wang1 1Department of Cardiology, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of China; 2Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gang Wang, Email cardio9090@sina.comAim: To determine the predictive significance of the platelet-to-lymphocyte ratio (PLR) combined with the CHA2DS2-VASc score for cardiogenic cerebral embolism (CCE) in patients with nonvalvular atrial fibrillation (NVAF).Methods: A total of 553 patients with NVAF were included in this retrospective study. The general data, PLR, CHA2DS2-VASc score and echocardiography indicators were compared. The risk factors for CCE and the predictive value of PLR and CHA2DS2-VASc were analyzed. Stratified analysis was performed based on the cut-off value. Least absolute shrinkage and selection operator (LASSO) regression analysis was utilized to build a model. The relationship between risk score and different anticoagulants was evaluated.Results: Multiple regression analysis showed hypertension (OR=3.95, 95% CI=2.12– 7.35, p=1.40× 10− 5), diabetes mellitus (OR=2.95, 95% CI=1.57– 5.58, p=7.65× 10− 4), PLR (OR=1.01, 95% CI=1.00– 1.01, p< 10− 6), creatinine level (OR=1.01, 95% CI=1.00– 1.02, p=7.44× 10− 3), left atrial diameter (LAD) (OR=1.90, 95% CI=1.13– 3.19, p=1.51× 10− 2), ejection fraction (EF) (OR=0.93, 95% CI=0.87– 0.98, p=8.06× 10− 3) and CHA2DS2-VASc score (OR=3.79, 95% CI=2.95– 4.85, p< 10− 6) were independent risk factors for CCE. A one-way linear analysis also showed the above seven indexes were significantly correlated with CCE (F=56.4, p< 10− 6). The area under the receiver operating characteristic (ROC) curve of PLR and CHA2DS2-VASc score was 0.760 (95% CI:0.721– 0.800), and 0.855 (95% CI: 0.824– 0.886), respectively. Pearson correlation analysis showed that PLR was correlated with CHA2DS2-VASc score (r=0.331, p< 10− 6). Stratified analysis indicated there was a positive correlation between different risk group (p< 10− 6). Using the LASSO model, a composite indicator displayed differential power for distinguishing CCE with an AUC value of 0.884 (95% CI: 0.857– 0.911). Patients with dabigatran and rivaroxaban exhibited higher risk score than those with warfarin (warfarin vs dabigatran, p=1.40× 10− 2; warfarin vs rivaroxaban p=3.00× 10− 3).Conclusion: PLR and CHA2DS2-VASc score are independent risk factors for CCE with NVAF, and the combination of the two indices can improve the prediction of CCE.Keywords: NVAF, CCE, PLR, CHA2DS2-VASc score, LASSO model

Jian Yang,1,&ast; Xuanhao Zhang,1,2,&ast; Guanyu Wang,1,2 Shixing Ma,1,2 Yejia Yu,1 Chengcheng Liao,1 Zhuo Wang,1,2 Cheng Liang,1 Maojiao Li,1,2 Weidong Tian,1,2 Li Liao1,2 1State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Liao; Weidong Tian, State Key Laboratory of Oral Disease, West China School of Stomatology, Sichuan University, No. 14, 3Rd Section of Ren Min Nan Road, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85503499 ; +86-28-85501256, Email lliao@scu.edu.cn; drtwd@sina.comBackground: Diabetic chronic wounds present a formidable challenge in clinical management, lacking effective treatment options. Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapy for tissue repair and regeneration. However, transplanted MSCs often undergo rapid apoptosis, giving rise to heterogeneous extracellular vesicles (EVs), including apoptotic bodies (apoBDs) and apoptotic small extracellular vesicles (apoSEVs). The potential stimulatory role of these EVs in diabetic wound healing remains unknown.Methods: In this study, we investigated the effects of apoSEVs derived from adipose-derived mesenchymal/stromal cells (ADSCs) on the recovery of diabetic wounds by modulating the function of versatile target cells. First, we characterized the apoSEVs and apoBDs derived from apoptotic ADSCs. Subsequently, we evaluated the effects of apoSEVs and apoBDs on macrophages, endothelial cells, and fibroblasts, three essential cell types in wound healing, under high-glucose conditions. Furthermore, we developed a gelatin methacryloyl (GelMA) hydrogel for the sustained release of apoSEVs and investigated its therapeutic effects on wound healing in type 2 diabetic mice in vivo.Results: apoSEVs facilitated the polarization of M1 phenotype macrophages to M2 phenotype, promoted proliferation, migration, and tube formation of endothelial cells, and enhanced fibroblast proliferation and migration. However, apoBDs failed to improve the function of endothelial cells and fibroblasts. In vivo, the apoSEVs-loaded GelMA effectively promoted wound healing by facilitating collagen fiber deposition, angiogenesis, and immune regulation.Conclusion: Our study elucidates the beneficial effects of apoSEVs on wound recovery in diabetes and introduces a novel strategy for diabetic wound treatment based on apoSEVs. Keywords: apoptotic small extracellular vesicles, wound healing, diabetes, stem cells, GelMA

Ning Zhang, Guang Wang Department of Endocrinology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Guang Wang, Email drwg6688@126.comPurpose: A bone turnover marker reflects bone bioactivity. The effects of metabolically healthy compared with metabolically unhealthy obesity phenotypes on bone metabolism are not well understood. The aim of the study was to evaluate differences of bone transformation indexes in these two obesity phenotypes.Patients and Methods: A total of 419 obese subjects were recruited, 64 with metabolically healthy obesity (MHO) and 351 with metabolically unhealthy obesity (MuHO). BTMs and clinical parameters were measured.Results: Bone metabolism indexes, including tartrate resistant acid phosphatase (TRACP, p < 0.05), β carboxyl terminal peptide of collagen (β-CTX, p < 0.01), and bone alkaline phosphatase (BAP, p < 0.01), were higher in subjects with MHO than MuHO, but parathyroid hormone (PTH) was lower (p < 0.05). The between-group difference in serum calcium was not significant. Low bone turnover activity was associated with significant hyperglycemia, insulin resistance, and body fat index (p < 0.05). Multivariate logistic regression found that TRACP, β-CTX, and BAP were independently associated with the presence of MHO. Receiver operating characteristic curve analysis found that the maximum area under the curve value for the definition of MHO was (0.8221) and was obtained when sex, age, body mass index (BMI), TRACP, β-CTX and BAP were included simultaneously, resulting in a sensitivity of 81.25% and specificity: 72.3%.Conclusion: The MHO group had significantly increased circulating TRACP and β-CTX compared with the MuHO group and BAP levels were within the physiological range. Obesity with the metabolically healthy phenotype had slightly increased bone turnover activity that may be an early compensatory response of skeletal metabolism to the increased BMI.Keywords: bone turnover bioactivity, metabolically healthy obesity, obesity phenotype

Xinjie Wang,1 Zhongren Zheng,1 Jialiang Wang,1 Hui Ma,2 Guodong Wang,2 Xiaowei Zhao2 1Department of Clinic Medicine, Jining Medical University, Jining, Shandong, 272067, People’s Republic of China; 2Department of Joint and Sports Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272029, People’s Republic of ChinaCorrespondence: Xiaowei Zhao, Department of Joint and Sports Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272029, People’s Republic of China, Tel +86 18678766708, Email 18678766708@163.comBackground: Currently, there is no single test indicator for diagnosing periprosthetic joint infection (PJI) with an acceptable level of sensitivity. Therefore, ratio indicators have been introduced to improve the accuracy of diagnostic algorithms. Platelet count /mean platelet volume (PMR) is reported to be a potential PJI diagnostic biomarker, but its clinical value for diagnosing PJI is still uncertain. This study aims to provide additional evidence to support the effectiveness of PMR in accurately diagnosing PJI.Methods: This study recruited 116 patients with PJI and 137 patients with aseptic loosening, divided them into PJI group and AL group. Collect subjects’ preoperative laboratory indicators such as ESR, CRP, PLT, MPV, etc. The area under the curve (AUC) was calculated by plotting the receiver operating characteristic (ROC) curve to determine the diagnostic efficacy of PMR.Results: ESR, CRP, PLT, and PLT/MPV were significantly increased in the PJI group, while MPV levels were decreased (both P< 0.001). The AUC of the PMR was 0.752, and the optimal cut-off value for diagnosing chronic PJI was determined to be 27.8 based on the Youden index. The sensitivity and specificity for diagnosing PJI were 79.3% and 47.9%, respectively, with a positive predictive value of 68.27%, a negative predictive value of 69.80%, and a diagnostic odds ratio of 4.97. The AUC (0.752) of the ratio biomarker was lower than that of ESR (0.825) and CRP (0.900). After predictive model calculation, the combination of PMR, CRP, and ESR had an AUC value of 0.910, with a sensitivity of 84.5% and a specificity of 84.7%, showing good discriminative ability.Conclusion: Compared with traditional biomarkers ESR and CRP, the value of the PMR for diagnosing PJI is not significant, but it can be used as an auxiliary indicator for PJI diagnosis in combination with other indicators (P< 0.001).Keywords: periprosthetic joint infection, biomarkers, C-reactive protein, erythrocyte sedimentation rate, platelet count/mean platelet volume, diagnosis

Xi Zhang, Ruzhe Li, Guonian Wang Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, People’s Republic of ChinaCorrespondence: Guonian Wang, Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China, Email guonianwang609cn@aliyun.comPurpose: Programmed cell death ligand 1 (PDL1) has the predictive and prognostic value in a great deal of cancers. This study aims to explore the expression of PDL1 in stage III breast cancer (BC) and its correlation with clinical outcome.Methods: The protein expression of PDL1 in tumor tissues was determined by immunohistochemistry (IHC). The correlations between PDL1 and clinicopathological variables were performed by χ²-tests or Fisher’s exact tests. The Cox proportional hazards model was used for univariate and multivariate analysis of the potential prognostic factors. Survival curves were estimated based on Kaplan–Meier analyses, and Log Rank test was used to contrast factors influencing the survival outcome.Results: On the basis of the semiquantitative scoring method for PDL1 expression, the patients were divided into low PDL1 expression group (109 cases) and high PDL1 expression group (107 cases). PDL1 expression was correlated with positive lymph nodes, positive axillary lymph nodes, postoperative radiotherapy, and CK5/6 expression (P < 0.05). The PDL1 expression in tumor tissues was discovered to be a potential prognostic risk factor with the disease-free survival (DFS) and overall survival (OS) for stage III BC. Moreover, patients with high PDL1 expression showed longer lifetime (DFS and OS) compared to those with low PDL1 expression in total patient population (P < 0.05). Moreover, the nomogram showed that the prediction line is in good agreement with the reference line for postoperative 1-, 3-, and 5-year lifetime. The DCA curve showed that the 3- and 5-year lifetime by nomogram had so much better divination of the clinical application than only by PDL1.Conclusion: PDL1 is a latent prognostic factor in stage III BC and is closely related to some clinicopathological features. PDL1 expression in tumor tissues is significantly associated with better lifetime rate in stage III BC.Keywords: breast cancer, programmed death ligand-1, improved individual outcomes, patient stratification, tumor cell

Dandan Zhang,1– 3,&ast; Xiaoxuan Yu,4,&ast; Qian Lin,1,3 Ying Xia,2 Guyi Wang,2 Jianhua Zhang,3 Yanyi Yang2 1Office of Pediatrics, Pediatric College, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Music Education, Shanghai Conservatory of Music, Shanghai, People’s Republic of China; 3Shanghai Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4College of Basic Medical Sciences, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanyi Yang; Jianhua Zhang, Email proyyy666@163.com; zjh12195@126.comAbstract: Music therapy (MT) is a common modality that performs a complementary and integrative role along with standard treatments for many pediatric diseases. This article briefly reviewed the effects of MT on children aged 5– 11 years old and adolescents with asthma from previous studies, specified its functional target towards asthma symptoms, and sorted out the design and investigation of selected research. Medline/PubMed, Embase, SportDis-cus, Cochrane Library, Teacher Reference Centre, Web of Science, Academic Search Complete, PsycARTICLES, and Scopus were queried for experimental and observational studies published between 1990 and 2021. Then, researchers showed that MT lessened patients’ asthma symptoms, improved medication compliance, pulmonary function, and quality of life, and helped children and their parents manage anxiety and depression. This article may serve as a reference for clinical research for pediatric asthma therapies and lay the foundation for future research on MT and its clinical practice.Keywords: pediatric asthma, music therapy, breath exercise, sing and play the wind instruments

Jie Li,1,2 Yuchen Jia,1,2 Feng Cao,1,2 Gang Wang,3 Fei Li1,2 1Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Clinical Center for Acute Pancreatitis, Capital Medical University, Beijing, People’s Republic of China; 3Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of ChinaCorrespondence: Fei Li; Gang Wang, Email feili36@ccmu.edu.cn; wgilu79@163.comBackground: Ferroptosis plays an important role in a variety of disease processes and is equally important in pancreatic diseases. However, the role of ferroptosis-related genes (FRGs) in acute pancreatitis (AP) remains unknown, and their specific potential mechanisms still need to be explored extensively.Methods: AP-related gene microarray data were obtained from the GEO database, while FRGs were obtained from the ferroptosis database (FerrDb). Differentially expressed genes (DEGs) were screened by the “limma” package, and GSEA was performed. The corresponding ferroptosis-related differentially expressed genes (FRDEGs) were screened, and GO and KEGG pathway analyses were performed. A PPI network was constructed to identify hub FRDEGs by CytoHubba, MCODE and CTD scores. Transcription factors and miRNAs predicted using the NetworkAnalyst database were used to establish the regulatory network. Immune cell infiltration analysis was performed by the R package “ssGSEA” algorithm. The hub genes were validated by transcriptome sequencing of AP model mice and immunohistochemistry in rats and mice.Results: A total of 82 FRDEGs were screened, and these genes were mainly associated with ferroptosis, hypoxic response, autophagy, mitophagy and immune inflammation. However, we also found that these genes are also jointly involved in other cell death modalities, such as apoptosis and necroptosis. Further analysis obtained 7 hub genes from 82 genes, and single-sample gene set enrichment analysis (ssGSEA) showed that the hub genes are closely associated with the infiltration of specific immune cells and the activation of immune pathways.Conclusion: This study reveals the complex functions and important roles of ferroptosis-related genes in AP and provides gene targets for further studies of AP.Keywords: acute pancreatitis, ferroptosis, mitophagy, autophagy, inflammation

Ling Chen,1 Zujian Wu,1 Chi Guo,1 Guoping Wang,1 Kui Tu,2 Jichang Jiang2 1General Surgery, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang Province, 310012, People’s Republic of China; 2General Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, 563000, People’s Republic of ChinaCorrespondence: Jichang Jiang, Email 719182702@qq.comObjective: This study aimed to assess the efficacy of Endoscopic Retrograde Cholangiopancreatography (ERCP), common bile duct exploration, and percutaneous transhepatic cholangiography combined with common bile duct exploration for treating choledocholithiasis with acute cholangitis, to guide management strategies.Methods: A retrospective evaluation was conducted on a cohort of 283 inpatients diagnosed with choledocholithiasis and acute cholangitis at the affiliated hospital. Patients were categorized into three groups: Group A (ERCP group), Group B(common bile duct exploration group), and Group C(PTCD combine common bile duct exploration group.) Parameters such as hepatic function recovery, inflammation level control, blood loss, postoperative hospital duration, and postoperative complications were compared.Results: All groups exhibited notable reductions in postoperative biochemical parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TBIL), and WBC (P < 0.05). Group A had the least blood loss(P < 0.05), and shortest hospital stay(P < 0.05), but a higher incidence of pancreatitis(P < 0.05), with a total of 8 cases occurred(7.3%). Group C had a shorter hospital stay compared to Group B(P < 0.05).Conclusion: For patients with fewer and smaller common bile duct stones and milder symptoms, it is recommended to primarily choose endoscopic retrograde cholangiopancreatography (ERCP), endoscopic sphincterotomy (EST), and endoscopic nasobiliary drainage (ENBD), it procedures offer quicker recovery and cause minimal trauma. For patients with numerous, larger common bile duct stones but stable conditions, bile duct exploration is recommended. For those with severe conditions and significant inflammation, PTCD and common bile duct exploration are advised.Keywords: choledocholithiasis, acute cholangitis, ERCP, PTCD

Xiaoting Fang,1,&ast; Haijuan Liu,1,&ast; Mina Wang,1 Guohua Wang2 1Graduate School, Beijing University of Chinese Medicine, Beijing, China; 2Gynecology, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China&ast;These authors contributed equally to this workCorrespondence: Guohua Wang; Mina Wang, Email wgh1188@163.com; WMNmmm@126.comPurpose: This study aims to help researchers master the most active hotspots and trends quickly through bibliometric analysis in the field of dysmenorrhea.Methods: We retrieved literature on Web of Science from 2001 to 2021, and bibliometric analysis software CiteSpace was used in combination with VOSviewer.Results: We finally acquired 944 papers and an upward trend in articles continued in this field overall. Through the map, China contributed the most, followed by the USA and Turkey. For institutions, Beijing University of Chinese Medicine in China contributed the most, followed by National Yang-Ming University in Taiwan, China. Hsieh JC and Hellman KM were both the most prolific authors with 14 articles. Five major research groups, respectively, with Hsieh JC, Hellman KM, Zhu J, Liang F and Dun W were the key group. Dawood MY was the most dominant author and most frequently cited author. The Cochrane Database of Systematic Reviews Journal was the most productive, and the Fertility and Sterility Journal was the most cited. Advances in pathogenesis and management for primary dysmenorrhea written by Dawood MY was most cited and influential. Pathophysiology, the potential central mechanism, syndrome, evaluation index, diagnosis of adenomyosis-associated dysmenorrhea, treatment, etc., were the main trends and hotspots.Conclusion: Dysmenorrhea research has received a lot of attention from scholars. Strengthening international cooperation may promote the development of this field. The pathophysiology of dysmenorrhea, its impact on public health and its treatment are current research hotspots and are likely to be the focus of future study.Keywords: scientific knowledge graph, dysmenorrhea, bibliometric analysis, trends, hotspots

Xiangjie Fu,1 Yaqiong Ni,2 Guanchen Wang,3 Runda Nie,3 Yang Wang,4 Run Yao,1 Danyang Yan,1 Mingming Guo,3 Ning Li1 1Department of Blood Transfusion, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 2Hunan Provincial Key Laboratory of Micro&Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, People’s Republic of China; 3School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, People’s Republic of China; 4Institute of Integrative Medicine, Key Laboratory of Hunan Province for Liver Manifestation of Traditional Chinese Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of ChinaCorrespondence: Ning Li, Tel +86 731 84327436, Email liningxy@csu.edu.cnBackground: Multidrug-resistant staphylococcus aureus infected wounds can lead to nonhealing, systemic infections, and even death. Although advanced dressings are effective in protecting, disinfecting, and maintaining moist microenvironments, they often have limitations such as single functionality, inadequate drug release, poor biosafety, or high rates of drug resistance.Methods: Here, a novel wound dressing comprising glycyrrhizic acid (GA) and tryptophan-sorbitol carbon quantum dots (WS-CQDs) was developed, which exhibit synergistic and long-lasting antibacterial and anti-inflammatory effects. We investigated the characterization, mechanical properties, synergistic antibacterial effects, sustained-release properties, and cytotoxicity of GA/WS-CQDs hydrogels in vitro. Additionally, we performed transcriptome sequence analysis to elucidate the antibacterial mechanism. Furthermore, we evaluated the biosafety, anti-inflammatory effects, and wound healing ability of GA/WS-CQDs dressings using an in vivo mouse model of methicillin-resistant staphylococcus aureus (MRSA)-infected wounds.Results: The prepared GA/WS-CQDs hydrogels demonstrated superior anti-MRSA effects compared to common antibiotics in vitro. Furthermore, the sustained release of WS-CQDs from GA/WS-CQDs hydrogels lasted for up to 60 h, with a cumulative release of exceeding 90%. The sustained-released WS-CQDs exhibited excellent anti-MRSA effects, with low drug resistance attributed to DNA damage and inhibition of bacterial biofilm formation. Notably, in vivo experiments showed that GA/WS-CQDs dressings reduced the expression of inflammatory factors (TNF-α, IL-1β, and IL-6) and significantly promoted the healing of MRSA-infected wounds with almost no systemic toxicity. Importantly, the dressings did not require replacement during the treatment process.Conclusion: These findings emphasize the high suitability of GA/WS-CQDs dressings for MRSA-infected wound healing and their potential for clinical translation.Graphical Abstract: Keywords: tryptophan-sorbitol CQDs, glycyrrhizic acid, wound dressings, synergistic synergism, sustained release, methicillin-resistant staphylococcus aureus-infected wounds healing

Jianquan Li, Yongyang He, Xi Lei, Zhongqiang Cao, Yuwei Liao, Guoqiang Wang, Zebin Chen, Xuejuan Li, Xiaoya Liu Department of Pharmacy, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of ChinaCorrespondence: Xiaoya Liu, Department of Pharmacy, Shenzhen Children’s Hospital, Shenzhen, 518026, Guangdong Province, People’s Republic of China, Tel +86 075583008256, Email liuxy2949@163.comBackground: Antimicrobial agents’ wastage is a huge problem, especially for pediatric patients, resulting in excessive drug expenditure and increasing the economic burden on patients’ families. Moreover, the cost of disposing of antimicrobial agents’ waste and the risk of environmental and occupational exposure also increased. This study aimed to explore the cost-effectiveness of the vial-sharing strategy combined with the daily-rate charge mode for pediatric inpatients to provide a strategy for reducing patients’ expenditures, saving medical costs, and reducing drug proportion.Methods: This retrospective study was conducted at Pharmacy Intravenous Admixture Service (PIVAS), Shenzhen Children’s Hospital, Guangdong Province, China, in 2022. Data on prescription drugs were collected from the PIVAS system. Ten antimicrobial drugs with a frequency of prescriptions no less than twice once daily were selected, and the drug costs, drug weight, and drug saved were further analyzed according to the combination of real-time vial sharing strategy and daily-rate charge mode. Traditional single vial charge mode without vial sharing was set as a control strategy. The actual expenditure of the hospital was also calculated and analyzed.Results: During 2022, ¥ 4,122,099 (34.4%) was saved for inpatients by applying a vial-sharing strategy on ten antibacterial agents, and more than 46,343,750 mg (24.6%) of drugs were totally saved. The top 5 drugs saved by the real-time vial-sharing strategy were cefoperazone-sulbactam, vancomycin, amoxicillin-sulbactam, ceftazidime, and meropenem. Taken the price into consideration, the top five payment-saved drugs were vancomycin (¥ 1,522,385), meropenem (¥ 1,311,475), cefoperazone-sulbactam (¥ 736,697), imipenem-cilastatin (¥ 406,092), and amoxicillin-sulbactam (¥ 51,394). Moreover, the account balance of the hospital was up to ¥ 426,499.Conclusion: The real-time vial sharing strategy combined with the daily-rate charge mode greatly reduces drug wastage and patients’ payments. It may be useful for hospitals with PIVAS to achieve vial-sharing while protecting the best interest of inpatients.Keywords: real-time vial sharing strategy, daily-charge mode, antimicrobial drugs, inpatients, PIVAS

Liyu Yang,1,&ast; Long Zhou,1,&ast; Guanqi Wang,2 Min Qiu,1 Feng Liang,1 Changqing Jia,1 Weibing Xu,3 Qin Fu,1 Liqing Yang,1 Gen Ba1 1Department of Orthopedic, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Rehabilitation Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Spinal Surgery, Dalian Central Hospital Affiliated to Dalian Medical University, Dalian, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gen Ba, Department of Orthopedic, Shengjing Hospital of China Medical University, Sanhao Street 36, He Ping District, Shenyang, Liaoning Province, People’s Republic of China, 110004, Tel +86 18940259116, Email bagen1983@163.comObjective: This article aims to discuss a novel surgical strategy, referred to as unilateral bi/multi-portal endoscopy (UME), which used a uniaxial spinal endoscope instead of an arthroscope in the traditional unilateral biportal endoscopy (UBE) surgical procedure in our study of the treatment of complicated lumbar degenerative diseases.Methods: This retrospective study included 42 patients diagnosed with high-migrated lumbar disc herniation and bilateral spinal stenosis who underwent UME surgery from January 2021 to December 2021. Patients included 20 men and 22 women, with an average age of 55.97± 14.92 years. The average follow-up period was 13.19 months. The demographic data, operation time (min), and complications were recorded and analyzed. The visual analogue scale (VAS), Oswestry Disability Index (ODI) scores were used to evaluate the surgical outcomes. Three-dimensional CT scans and MRI were conducted to evaluate the radiographic improvement.Results: A total of 26 patients were diagnosed with lumbar disc herniation and 16 with lumbar spinal stenosis. All 42 patients underwent UME surgery and achieved satisfactory outcomes. The operation time was 154.46± 46.09 min. The average follow-up time was 13.19± 1.33 months. The preoperative back pain (VAS-Back) and the last follow-up VAS-Back were 3.84± 1.00 and 0.70± 0.46, respectively (P < 0.05). The preoperative leg pain (VAS-Leg) and the last follow-up VAS-Leg were 6.46± 1.08 and 1.03± 0.64, respectively (P < 0.05). Significant differences existed between preoperative ODI scores (58.70± 11.22%) and the last follow-up ODI scores (9.24± 3.04%; P< 0.05). All patients achieved significant pain relief and functional improvement after the surgery. No severe complications occurred, except for two cases of postoperative dysesthesia and one case suffered from vertebral compression fractures induced by a postoperative accidental injury. Symptoms of numbness disappeared within one week with treatment using dexamethasone and neurotrophic drugs. The vertebral fracture case recovered with percutaneous kyphoplasty treatment.Conclusion: This study suggests that UME is a promising treatment strategy for high-migrated disc herniation and bilateral spinal stenosis.Keywords: unilateral bi/multi-portal endoscopy, lumbar degenerative diseases, high-migrated disc herniation, bilateral spinal stenosis, ligamentum flavum, spinal endoscope