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Man Zhang,1,2,* Siman Nie,3,* Ziwei Hai,2 Yixin Du,2 Menghan Jiang,4 Chunfeng Cai2 1Department of Oncology, The First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Wuhan University School of Nursing, Wuhan, Hubei, People’s Republic of China; 3Beijing Tsinghua Changgung Hospital, Beijing, People’s Republic of China; 4Shandong University of Traditional Chinese Medicine College of Health Sciences, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunfeng Cai, Faculty of Wuhan University School of Nursing, Wuhan, Hubei, People’s Republic of China, Email 1660433132@qq.comAim: Chronic disease self-management is critical to disease prognosis and patient quality of life. Several psychological factors influence this process of self-management. In this background, the present study investigated the impact of illness perceptions and coping style on self-management in people with peritoneal dialysis (PD).Methods: The study is a cross-sectional study. From May 2022 to January 2023, a convenience sampling method was used to recruit 246 peritoneal dialysis patients. General information questionnaire, brief illness perception questionnaire, medical coping style modes questionnaire and the self-management scale for peritoneal dialysis patients were used in this study. We used SPSS 24.0 to analyze the data, and the statistical methods included descriptive analysis, single factor analysis, Pearson correlation analysis and multiple linear regression analysis.Results: A total of 246 patients were included in this study (93.89% response rate). Cognitive representations and emotional representations were 30.40, 14.18, respectively. However, illness comprehensibility was 2.87. Illness perceptions were negative significantly correlated with self-management. With regard to coping style, our patients were more likely to adopt avoidance and resignation coping style. Confrontation and avoidance were positively related to self-management, while acceptance-resignation was negatively related.Conclusion: Self-management of peritoneal dialysis patients needs to be improved. Age, female sex, monthly income, illness perceptions and coping style were independently associated with self-management.Impact: These findings suggest that interventions that improve illness perceptions and coping style should be explored to ultimately improve their self-management. For example, patients can be provided with psychological counseling so that they can face the disease correctly, and we should pay attention to the positive role of social support.Keywords: peritoneal dialysis, illness perception, coping style, self-management

Yongkun Du, Shuai Wang, Ting Zhou, Zhongyan Zhao Department of Critical Care Medicine, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of ChinaCorrespondence: Zhongyan Zhao, Email zhongyan@jlu.edu.cnBackground: Recent evidence suggests that the gut microbiome and metabolites are intricately involved in Chronic Obstructive Pulmonary Disease (COPD) pathogenesis, yet the precise causal relationships remain unclear due to confounding factors and reverse causation. This study employs bidirectional two-sample Mendelian Randomization (MR) to clarify these connections.Methods: Summary data from publicly available Genome-Wide Association Studies (GWAS) concerning the gut microbiome, metabolites, and COPD were compiled. The selection of genetic instrumental variables (Single Nucleotide Polymorphisms, or SNPs) for MR analysis was conducted meticulously, primarily utilizing the Inverse Variance Weighting (IVW) method, supplemented by MR-Egger regression and the Weighted Median (WM) approach. The evaluation of heterogeneity and horizontal pleiotropy was performed using Cochran’s Q test, the MR-Egger intercept test, and the MR-PRESSO global test. Sensitivity analyses, including leave-one-out tests, were conducted to verify the robustness of our results. And the mediation effect of gut microbiota-mediated changes in metabolites on the causal relationship with COPD was analyzed.Results: Our study identified nine significant gut microbiota taxa and thirteen known metabolites implicated in COPD pathogenesis. Moreover, associations between the onset of COPD and the abundance of five bacterial taxa, as well as the concentration of three known metabolites, were established. These findings consistently withstood sensitivity analyses, reinforcing their credibility. Additionally, our results revealed that gut microbiota contribute to the development of COPD by mediating changes in metabolites.Conclusion: Our bidirectional Two-Sample Mendelian Randomization analysis has revealed reciprocal causal relationships between the abundance of gut microbiota and metabolite concentrations in the context of COPD. This research holds promise for identifying biomarkers for early COPD diagnosis and monitoring disease progression, thereby opening new pathways for prevention and treatment. Further investigation into the underlying mechanisms is essential to improve our understanding of COPD onset.Keywords: chronic obstructive pulmonary disease, gut microbiota, metabolites, Mendelian randomization, causal effect

Wei Guo,1 Jing Tian,1 Yajing Wang,1 Yajing Zhang,1 Jingjing Yan,2 Yutao Du,2 Yanbo Zhang,2,3 Qinghua Han1,4 1Department of Cardiology, the 1st Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, People’s Republic of China; 2Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi Province, People’s Republic of China; 3Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Taiyuan, Shanxi Province, People’s Republic of China; 4Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Taiyuan, Shanxi Province, People’s Republic of ChinaCorrespondence: Qinghua Han, Department of Cardiology, the 1st Hospital of Shanxi Medical University, No. 85 South JieFang Road, Yingze District, Taiyuan, Shanxi, People’s Republic of China, Email syhqh@sohu.com Yanbo Zhang, Department of Health Statistics, School of Public Health, Shanxi Medical University, No. 56 South XinJian Road, Yingze District, Taiyuan, Shanxi, People’s Republic of China, Email sxmuzyb@126.comPurpose: This study aimed to develop an integrative dynamic nomogram, including N-terminal pro-B type natural peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR), for predicting the risk of all-cause mortality in HFmrEF patients.Patients and Methods: 790 HFmrEF patients were prospectively enrolled in the development cohort for the model. The least absolute shrinkage and selection operator (LASSO) regression and Random Survival Forest (RSF) were employed to select predictors for all-cause mortality. Develop a nomogram based on the Cox proportional hazard model for predicting long-term mortality (1-, 3-, and 5-year) in HFmrEF. Internal validation was conducted using Bootstrap, and the final model was validated in an external cohort of 338 consecutive adult patients. Discrimination and predictive performance were evaluated by calculating the time-dependent concordance index (C-index), area under the ROC curve (AUC), and calibration curve, with clinical value assessed via decision curve analysis (DCA). Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were used to assess the contributions of NT-proBNP and eGFR to the nomogram. Finally, develop a dynamic nomogram using the “Dynnom” package.Results: The optimal independent predictors for all-cause mortality (APSELNH: A: angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitor (ACEI/ARB/ARNI), P: percutaneous coronary intervention/coronary artery bypass graft (PCI/CABG), S: stroke, E: eGFR, L: lg of NT-proBNP, N: NYHA, H: healthcare) were incorporated into the dynamic nomogram. The C-index in the development cohort and validation cohort were 0.858 and 0.826, respectively, with AUCs exceeding 0.8, indicating good discrimination and predictive ability. DCA curves and calibration curves demonstrated clinical applicability and good consistency of the nomogram. NT-proBNP and eGFR provided significant net benefits to the nomogram.Conclusion: In this study, the dynamic APSELNH nomogram developed serves as an accessible, functional, and effective clinical decision support calculator, offering accurate prognostic assessment for patients with HFmrEF.Keywords: heart failure with mildly reduced ejection fraction, all-cause mortality, risk prediction model, risk strategy, dynamic nomogram

Ningning Xue, Yue Du Emergency Department of Beijing Tiantan Hospital, Capital Medical University, Beijing, 100007, People’s Republic of ChinaCorrespondence: Yue Du, Emergency Department of Beijing Tiantan Hospital, Capital Medical University, No. 119, South Fourth Ring West Road, Fengtai District, Beijing, 100007, People’s Republic of China, Tel +8613718565030, Email 13718565030@sina.cnBackground: Community health education is essential in combating obesity and cardiovascular diseases by addressing nutritional knowledge gaps and promoting healthier dietary habits in China. The aim of this study was to investigate the nutritional knowledge, attitudes, and needs of residents at Beijing Fengtai District.Methods: This cross-sectional study was conducted between October 2021 and January 2022, residents from 31 communities of the Fengtai District were given an online questionnaire, which was designed to assess their nutritional knowledge, attitudes, and needs.Results: From 420 distributed surveys, a total of 416 participants were enrolled for an effective recovery rate of 99.05%. Among them, 317 participants (76.20%) scored 80% or higher on the nutritional knowledge questionnaire, participants with higher nutritional knowledge scores were more likely to be aged over 60 years (OR = 0.21, 95% CI 0.06– 0.76, p = 0.02), female (OR = 0.40, 95% CI 0.22– 0.73, p < 0.01) and employed (OR = 2.31, 95% CI 1.04– 5.12, p = 0.04). While many community residents expressed a desire to receive guidance on dietary guidance (n = 303, 72.84%) dietary matching (n = 303, 72.84%), and preventive health care (n = 286, 68.75%). Residents were familiar with nutritional care clinics (55.05%) and believed that the nutritional care clinics should be increased (59.86%). In addition, 345 residents (83.41%) wanted nutritional care clinics to provide consultation on nutritious meal planning.Conclusion: Beijing residents need additional access to clinical nutritional resources as their needs are not fulfilled despite a relatively strong knowledge of nutrition.Keywords: Beijing, community residents, nutrition knowledge, education, questionnaire

Lei Tan,1,2,&ast; Han She,1,2,&ast; Yi Wang,1,2,&ast; Yuanlin Du,1 Jun Zhang,1 Yunxia Du,1 Yinyu Wu,1 Wei Chen,1 Bingqiang Huang,1 Duanyang Long,1 Xiaoyong Peng,2 Qinghui Li,2 Qingxiang Mao,1 Tao Li,2 Yi Hu1 1Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Li; Yi Hu, Email lt200132@163.com; huyi921@sina.comBackground: Hemorrhagic shock was a leading cause of death worldwide, with myocardial injury being a primary affected organ. As commonly used solutions in fluid resuscitation, acetated Ringer’s (AR) and Lactate Ringer’s solution (LR) were far from perfect for their adverse reactions such as lactic acidosis and electrolyte imbalances. In previous studies, TPP@PAMAM-MR (TPP-MR), a novel nanocrystal resuscitation fluid has been found to protect against myocardial injury in septic rats. However, its role in myocardial injury in rats with hemorrhagic shock and underlying mechanism is unclear.Methods: The hemorrhagic shock rats and hypoxia-treated cardiomyocytes (H9C2) were utilized to investigate the impact of TPP-MR on cardiac function, mitochondrial function, and lipid peroxidation. The expressions of ferritin-related proteins glutathione peroxidase 4 (GPX4), Acyl CoA Synthase Long Chain Family Member 4 (ACSL4), and Cyclooxygenase-2(COX2) were analyzed through Western blotting to explore the mechanism of TPP-MR on hemorrhagic myocardial injury.Results: TPP-MR, a novel nanocrystalline resuscitation fluid, was synthesized using TPP@PAMAM@MA as a substitute for L-malic acid. We found that TPP-MR resuscitation significantly reduced myocardial injury reflected by enhancing cardiac output, elevating mean arterial pressure (MAP), and improving perfusion. Moreover, TPP-MR substantially prolonged hemorrhagic shock rats’ survival time and survival rate. Further investigations indicated that TPP-MR improved the mitochondrial function of myocardial cells, mitigated the production of oxidative stress agents (ROS) and increased the glutathione (GSH) content. Additionally, TPP-MR inhibited the expression of the ferroptosis-associated GPX4 protein, ACSL4 and COX2, thereby enhancing the antioxidant capacity.Conclusion: The results showed that TPP-MR had a protective effect on myocardial injury in rats with hemorrhagic shock, and its mechanism might be related to improving the mitochondrial function of myocardial cells and inhibiting the process of ferroptosis.Keywords: myocardial injury, hemorrhagic shock, mitochondria, ferroptosis

Jun Zhang,1,&ast; Yinyu Wu,1,&ast; Yuanlin Du,1,&ast; Yunxia Du,1 Daiqin Bao,1 Haibin Lu,2 Xiaoqiong Zhou,1 Rui Li,1 Haoyu Pei,1 Han She,1 Qingxiang Mao1 1Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2Department of Intensive Care Unit, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Han She; Qingxiang Mao, Email mazuishehan@163.com; qxmao@tmmu.edu.cnBackground: This study aimed to discover diagnostic and prognostic biomarkers for sepsis immunotherapy through analyzing the novel cellular death process, cuproptosis.Methods: We used transcriptome data from sepsis patients to identify key cuproptosis-related genes (CuRGs). We created a predictive model and used the CIBERSORT algorithm to observe the link between these genes and the septic immune microenvironment. We segregated sepsis patients into three subgroups, comparing immune function, immune cell infiltration, and differential analysis. Single-cell sequencing and real-time quantitative PCR were used to view the regulatory effect of CuRGs on the immune microenvironment and compare the mRNA levels of these genes in sepsis patients and healthy controls. We established a sepsis forecast model adapted to heart rate, body temperature, white blood cell count, and cuproptosis key genes. This was followed by a drug sensitivity analysis of cuproptosis key genes.Results: Our results filtered three key genes (LIAS, PDHB, PDHA1) that impact sepsis prognosis. We noticed that the high-risk group had poorer immune cell function and lesser immune cell infiltration. We also discovered a significant connection between CuRGs and immune cell infiltration in sepsis. Through consensus clustering, sepsis patients were classified into three subgroups. The best immune functionality and prognosis was observed in subgroup B. Single-cell sequencing exposed that the key genes manage the immune microenvironment by affecting T cell activation. The qPCR results highlighted substantial mRNA level reduction of the three key genes in the SP compared to the HC. The prediction model, which combines CuRGs and traditional diagnostic indicators, performed better in accuracy than the other markers. The drug sensitivity analysis listed bisphenol A as highly sensitive to all the key genes.Conclusion: Our study suggests these CuRGs may offer substantial potential for sepsis prognosis prediction and personalized immunotherapy.Keywords: sepsis, cuproptosis, prognosis, immune cell infiltration, nomogram

Zhidi Zhang, Qiang Zuo, Yali Du, Hailing Jiang, Furong Ma, Yinghong Zhang Department, Otolaryngology Head and Neck Surgery, Peking University Third Hospital, Beijing, 100191, People’s Republic of ChinaCorrespondence: Yinghong Zhang, Department, Otolaryngology Head and Neck Surgery, Peking University Third Hospital, Beijing, 100191, People’s Republic of China, Email yinghongzhang@bjmu.edu.cn Furong Ma, Department, Otolaryngology Head and Neck Surgery, Peking University Third Hospital, Beijing, 100191, People’s Republic of China, Email furongma@126.comObjective: Osteitis is more prevalent in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), making the disease refractory and prone to recurrence. However, the pathophysiologic mechanism of osteitis formation in CRS has not been fully elucidated, and this study aimed to further elucidate the association of eosinophils and type 2 inflammatory mediators with osteitis in patients with CRSwNP.Methods: This retrospective study collected clinical data on 125 cases of CRSwNP. The participants were categorized into two groups based on the presence or absence of osteitis in their sinus CT scan. The groups were classified as the osteitis group and the non-osteitis group. The clinical baseline data, type 2 inflammatory mediators, and eosinophils were compared between the two groups. The correlation between these factors and the Global Osteitis score scale (GOSS) was also evaluated.Results: There were 69 cases in the osteitis group and 56 cases in the non-osteitis group of CRSwNP patients. The prevalence of concomitant asthma (P=0.009), SNOT-22 score, LUND-MAKAY score, and LUND-KEDENY score were significantly higher in the osteitis group than in the non-osteitis group (All P values were < 0.001); the absolute values of IL-13 (P< 0.001), periosteal proteins (P< 0.001), and tissue eosinophils (P < 0.05) were significantly higher in the osteitis group as compared with the non-osteitis group. Logistic regression analysis showed that IL-13 and periosteal proteins were risk factors for CRSwNP osteitis (P< 0.001). ROC curve analysis revealed that IL-13 had the highest predictive value (AUC=0.786) with a cut-off value of 5.8059 pg/mL, the sensitivity of 58.0%, and a specificity of 89.3% respectively.Conclusion: Osteitis could indicate the more severe symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), and elevated IL-13, periosteal proteins, and tissue eosinophils are risk factors for osteitis formation in patients with CRSwNP.Keywords: chronic rhinosinusitis, osteitis, eosinophils, type 2 inflammatory mediators

Dan Qi,1– 9 Xi Zhang,1– 8 Fangli Li,10 Shengrui Zhao,2– 8 Qiumin Wang,1– 8 Wen Liu,2– 8 Lei Yan,1– 8 Yanbo Du1– 8 1State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, People’s Republic of China; 2National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, People’s Republic of China; 3Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, People’s Republic of China; 4Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, People’s Republic of China; 5Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, People’s Republic of China; 6Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 7Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No. 2021RU001), Jinan, Shandong, People’s Republic of China; 8Medical Integration and Practice Center, Shandong University, Jinan, Shandong, People’s Republic of China; 9Weifang People’s Hospital, Weifang, Shandong, People’s Republic of China; 10Department of Gynecology and Obstetrics, Public Health Clinical Center Affiliated to Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Yanbo Du, Center for Reproductive Medicine, Shandong University, Jinan, 250012, Shandong, People’s Republic of China, Tel +86 1 301 173 4515, Email duyanboivf@163.comPurpose: The objective of this study was to assess reproductive outcomes of D6 blastocysts transferred on day 6 in comparison to those transferred on day 7 of progesterone exposure in frozen-thawed embryo transfer cycles.Patients and Methods: This retrospective cohort study included 2029 D6 single blastocysts from the first frozen-thawed embryo transfer cycles of patients at the Hospital for Reproductive Medicine Affiliated to Shandong University from February 2017 to January 2020. Participants were divided into Group A (blastocyst transferred on the 6th day of progesterone exposure, n=1634) and Group B (blastocyst transferred on the 7th day of progesterone exposure, n=395).Results: The live birth rate was comparable between Group A and Group B (38.7% versus 38.7%, P=0.999). Subgroup analysis revealed a significantly higher preterm birth rate in D6 single blastocysts transferred on the 7th day than in those transferred on the 6th day of progesterone exposure for natural cycle frozen-thawed embryo transfer (5.2% versus 11.3%, P=0.020). After adjustment for potential confounders, the differences in the preterm birth rate in natural cycles persisted (adjusted odds ratio 2.347, 95% confidence interval 1.129– 4.877, P=0.022).Conclusion: In frozen-thawed embryo transfer cycles, transferring on the 6th or 7th day of progesterone exposure of D6 blastocysts did not affect the live birth rate; however, when a natural cycle protocol is adopted, the possible preterm risk of transferring D6 blastocysts on the 7th day of progesterone exposure should be noted.Keywords: frozen-thawed embryo transfer, blastocyst transfer, endometrium preparation, live birth rate

Wang Yi,1,2 Weikai Wang,3 Hua Zhang,2 Ying Wang,2 Yong Zhou,2 Zhangyan Guo,2 Jingmei Li,2 Le Ma,2 Dan Yao,2 Taining Zhang,3 Yanqiang Du,2 Li Liu1 1Department of Neonatology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Pediatric Intensive Care Unit, the Affiliated Children’s Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Pediatric intensive care unit, Gansu Provincial Maternity and Child Health Hospital, Gansu Provincial Central Hospital, Lanzhou, Gansu, People’s Republic of ChinaCorrespondence: Li Liu, Department of Neonatology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Yanta District, Xi’an, Shaanxi, 710003, People’s Republic of China, Email liuli918@sohu.com Yanqiang Du, Department of pediatric intensive care unit, the Affiliated Children’s Hospital of Xi’an Jiaotong University, No. 69, Xiju Lane, Lianhu District, Xi’an, Shaanxi, 710003, People’s Republic of China, Email duyanqiang_xaetyy@163.comBackground: In Asia, Hanta virus (HTNV) results in severe hemorrhagic fever with renal syndrome (HFRS). The efficacy of sivelestat in treating children with HTNV-induced HFRS remains unclear.Methods: An ambispective cohort study was performed on children diagnosed with HFRS and hospitalized at the Children’s Hospital Affiliated to Xi’an Jiaotong University from August 2018 to 2023. Patients who received neutrophil elastin-inhibitor infusion between August 2019 and August 2023 were assigned to the sivelestat group, while patients who did not were assigned to the control group. The independent sample t test was used for inter-group analysis. The Chi-square test and Fisher’s exact probability test were used for categorical variables. Spearman correlation test was used to evaluate the correlation between two sets of continuous variables. Kaplan-Meier survival curve and Log -Rank test was used to evaluate the difference in cumulative probability of survival between the two groups.Results: No significant differences were observed between the two groups in gender, age, contact history, body mass index, HFRS severity, clinical indexes at admission. Compared to the control group, the sivelestat group exhibited a significant decrease in the interleukin-8 level at 48 h (28.5± 3 vs 34.5± 3.5) and 72 h (21.3± 4.5 vs 31.5± 5.6) (P< 0.05), as well as the ICAM-1 level at 48 h (553± 122 vs 784± 187) and 72 h (452± 130 vs 623± 85) (P< 0.05). The concentration of VCAM-1 in the sivelestat group exhibited a consistent downward trend. Moreover, the level of VCAM-1 was significantly lower than that in the control group at 24 h (1760± 289 vs 2180± 445), 48 h (1450± 441 vs 1890± 267), and 72 h (1149± 338 vs 1500± 396) (P< 0.05). Kaplan-Meier curve analysis revealed a statistically significant difference in the cumulative probability of survival between two groups (P = 0.041). In the secondary outcomes, the sivelestat group demonstrated a decrease in the utilization rate of mechanical ventilation and continuous renal replacement therapy (CRRT).Conclusion: Sivelestat may suppress neutrophil-mediated inflammatory response to reduce endothelial and organ damage, and improve clinical outcomes in children with severe hemorrhagic fever and renal syndrome.Keywords: Sivelestat, hemorrhagic fever with renal syndrome, vascular endothelial injury, inflammatory response, cohort study, children

Ting Yang,1,2 Yanan Du,1 Mingzhen Sun,1 Jingjing Meng,1 Yiyi Li1 1School of Health Services Management, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 2Intelligent Interconnected Systems Laboratory of Anhui Province (Hefei University of Technology), Hefei, Anhui, 230009, People’s Republic of ChinaCorrespondence: Ting Yang, Email yangting@ahmu.edu.cnAbstract: Over the past decade, the global outbreaks of SARS, influenza A (H1N1), COVID-19, and other major infectious diseases have exposed the insufficient capacity for emergency disposal of medical waste in numerous countries and regions. Particularly during epidemics of major infectious diseases, medical waste exhibits new characteristics such as accelerated growth rate, heightened risk level, and more stringent disposal requirements. Consequently, there is an urgent need for advanced theoretical approaches that can perceive, predict, evaluate, and control risks associated with safe disposal throughout the entire process in a timely, accurate, efficient, and comprehensive manner. This article provides a systematic review of relevant research on collection, storage, transportation, and disposal of medical waste throughout its entirety to illustrate the current state of safe disposal practices. Building upon this foundation and leveraging emerging information technologies like Internet of Things (IoT), cloud computing, big data analytics, and artificial intelligence (AI), we deeply contemplate future research directions with an aim to minimize risks across all stages of medical waste disposal while offering valuable references and decision support to further advance safe disposal practices.Keywords: medical waste, safe disposal, major infectious diseases, progress and challenges

Zi-Guo Sun,1,2 Shi-Cheng Xu,2 Qin Yang,3 Yun Yao,2 Qi-Long Mao,2 Cheng-Feng He,2 Chang-Jiang Guan,2 Yan Du,2 Li Ma,2 Xie-Shan Huang,2 Xiao-Long Hou,2 Hong-Mei Yang,2 Xia Peng,2 Jun-Jie Jian4 1Department of Intensive Care and Emergency Center, Bazhong Hospital of Integrated Chinese and Western Medicine, Bazhong, Sichuan, 636600, People’s Republic of China; 2Department of Critical Care Medicine, Bazhong Central Hospital, Bazhong, Sichuan, 636600, People’s Republic of China; 3School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, 610000, People’s Republic of China; 4Department of Health Management, Bazhong Center for Health Education and Health Management, Bazhong, Sichuan, 636600, People’s Republic of ChinaCorrespondence: Xia Peng; Jun-Jie Jian, Email bzyszkzx@126.com; 2906194909@qq.comBackground: Fat overload syndrome is a rare and severe adverse reaction triggered by the infusion of a single source of lipid emulsion, resulting in elevated blood triacylglycerol (TG) levels. The majority of literature reports focus on cases of fat overload syndrome in patients with mild symptoms. This case is significant because it demonstrates the diagnostic and therapeutic experience and provide valuable insights for the management for severe fat overload syndrome.Case Presentation: We present a case report of a female patient who developed fat overload syndrome following prolonged and excessive infusion of lipid emulsion after colon resection surgery. In the setting of compromised immune function and malnutrition, the patient’s pulmonary infection and respiratory distress symptoms have further exacerbated. Hence, in addition to severe pancreatitis, the patient has also contracted severe pneumonia. Upon admission, tracheal intubation, plasma exchange and blood perfusion were performed. Subsequently, comprehensive treatment was provided, including anti-infection, antispasmodic, acid suppression, enzyme inhibition, as well as targeted supportive measures to stabilize electrolytes and nutritional status. After treatment, there was a progressive reduction in blood lipid levels. After assessing the relevant risks, it was deemed necessary to perform an emergency computed tomography (CT)-guided percutaneous drainage tube placement procedure targeting the necrotic area of the pancreas while the patient was still intubated. Finally, the patient was discharged from the hospital.Conclusion: The case highlights the association between fat overload syndrome and pancreatitis as well as the use of lipid emulsions and suggests the treatment strategies for severe fat overload syndrome.Keywords: lipid overload syndrome, plasma exchange, blood perfusion, pancreatitis, pneumonia

Yifan Liu,1 Yushan Liang,2 Jing Yuhong,3 Peng Xin,1 Jia Li Han,4 Yongle Du,5 Xinru Yu,3 Runhe Zhu,6 Mingxun Zhang,6 Wen Chen,7 Yingjie Ma7 1School of Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2School of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 3School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 4School of Health Sciences, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 5School of Ophthalmology and Optometry, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 6School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 7First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Yingjie Ma; Wen Chen, The First Clinical College, Shandong University of Traditional Chinese Medicine; Reproductive and Genetic Center of Integrative Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 42, Wenhua Road (W), Lixia District, Jinan, 250014, People’s Republic of China, Email 545914553@qq.com; wenchen0515@163.comAbstract: This manuscript offers a comprehensive overview of nanotechnology’s impact on the solubility and bioavailability of poorly soluble drugs, with a focus on BCS Class II and IV drugs. We explore various nanoscale drug delivery systems (NDDSs), including lipid-based, polymer-based, nanoemulsions, nanogels, and inorganic carriers. These systems offer improved drug efficacy, targeting, and reduced side effects. Emphasizing the crucial role of nanoparticle size and surface modifications, the review discusses the advancements in NDDSs for enhanced therapeutic outcomes. Challenges such as production cost and safety are acknowledged, yet the potential of NDDSs in transforming drug delivery methods is highlighted. This contribution underscores the importance of nanotechnology in pharmaceutical engineering, suggesting it as a significant advancement for medical applications and patient care.Keywords: nanotechnology, solubility and bioavailability, poorly soluble drugs, drug delivery systems, pharmaceutical engineering

Yijun Du,1,2,&ast; Yue Wang,1,2,&ast; Ping Zhang,1,2 Xing Zhong,1,2 Tianrong Pan1,2 1Department of Endocrinology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianrong Pan, Department of Endocrinology, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Jingkai District, Hefei, 230601, People’s Republic of China, Email PanTR1968@163.comBackground: Previous studies have shown that the prevalence of sarcopenia in patients with type 2 diabetes mellitus (T2DM) has increased significantly over the years. However, the risk factors for the association of sarcopenia in patients with T2DM are unknown. Therefore, we attempted to investigate the risk factors through measurement and analysis of the patients’ data from April 2020 to April 2022.Methods: A total of 334 hospitalized patients with T2DM were divided into sarcopenia group (n=101) and non-sarcopenia group (n=233). Clinical factors were compared between the two groups and also between the two genders. Receiver operating characteristic curve (ROC) was used to analyze the ROC diagnostic ability of related factors in sarcopenia.Results: (1) Among the 334 patients, the overall prevalence of sarcopenia was 30.2%; 41.3% in men and 20.1% in women. (2) The multifactorial logistic regression analysis showed that gender (specifically for men; OR=4.997, 95% CI: 2.611– 9.564), low body mass index (BMI) (OR=1.525, 95% CI: 1.353– 1.718), lower 25(OH)D levels (OR=1.076, 95% CI:1.036– 1.117), and lower IGF-1 (OR=1.013, 95% CI:1.006– 1.020) were independent risk factors (P < 0.05). (3) ROC curve analysis results showed that BMI, 25 (OH) D, IGF-1, and testosterone (for men) had predictive significance for sarcopenia with T2DM (P < 0.05). However, the AUC of 25 (OH) D, IGF-1 and testosterone (for men) were all < 0.7, while the AUC of BMI and the combined factors were all > 0.7, has great predictive significance.Conclusion: The prevalence of sarcopenia in hospitalized patients with T2DM is higher in men than in women. Low BMI and lower serum levels of 25 (OH) D and IGF-1 are risk factors of sarcopenia in patients with T2DM. Low BMI, 25(OH)D, IGF-1, and testosterone (for men) all contributed to the prediction of sarcopenia, among which BMI and combined factors were more significant.Keywords: risk factors, sarcopenia, T2DM, body mass index, 25 (OH) D, IGF-1

Lingling Zhu,1,2 Qiang Zhou,1,2 Ziyue Huang,3 Yuan Yang,4,5 Ying Yang,6 Yao Du,6 Yuqian Zhao,2 Xiaoping Yu,7 Tingyuan Li,2 Wen Chen5 1College of Public Health, Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of China; 2Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People’s Republic of China; 3Mianyang Maternal and Child Health Care Hospital, Mianyang, Sichuan, 621000, People’s Republic of China; 4School of Public Health, Xiamen University, Xiamen, Fujian, 361102, People’s Republic of China; 5Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 6Yanting County Maternal and Child Health Hospital, Mianyang, Sichuan, 621600, People’s Republic of China; 7School of Preclinical Medicine, Chengdu University, Chengdu, Sichuan, 610106, People’s Republic of ChinaCorrespondence: Xiaoping Yu, School of Preclinical Medicine, Chengdu University, Chengdu, Sichuan, 610106, People’s Republic of China, Tel +86 13981909673, Email yuxiaoping@cdu.edu.cn Tingyuan Li, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86 28 85420667, Email ltyuan008@126.comBackground: This study aimed to explore the current knowledge level of breast cancer among rural women in Southwest China and analyze the influencing factors of breast cancer cognition.Methods: From May to November 2022, 1468 rural women were invited to participate in this study. Demographic information and the Chinese version of the Breast Cancer Awareness Measure (C-BCAM) were collected through one-on-one investigations. The data were analyzed using descriptive statistics, chi-square tests, and multiple regression analysis in SPSS 26.0.Results: The study included a total of 1468 rural women with a median age of 54.0 (IQR, 47.0, 60.0).The average score of breast cancer in the study population was 73.0 (IQR, 66.0, 82.0). Among women in Southwest China, the awareness rates of knowledge on breast cancer symptoms, barriers to seeking medical help, and risk factors were 68.8%, 98.4%, and 62.1%, respectively. The awareness rate was found to increase with higher education levels (P< 0.001) and decrease with increasing age (P< 0.001). Multivariate logistic regression analysis identified three variables that might influence breast cancer awareness: education level, contraceptive measures, and history of breast disease (all P< 0.05). Specifically, history of breast disease (Odds ratio (OR) = 1.907, 95% CI = 1.128 ~ 3.223), middle school education (OR = 2.155, 95% CI = 1.585 ~ 2.928), and junior college education and above (OR = 5.536, 95% CI = 1.898 ~ 16.148) were positive factors for women’s breast cancer awareness. Conversely, the use of intrauterine devices (OR = 0.523, 95% CI = 0.384 ~ 0.712) was found to be a negative factor for women’s breast cancer awareness.Conclusion: This study highlights the insufficient awareness of breast cancer among women in rural area of Southwest China. It emphasizes the necessity of health education to improve female breast cancer awareness.Keywords: China, breast cancer, awareness, screening, rural women

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

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

Jinni Hong,1,2 Tingting Fu,1,2 Weizhen Liu,1,2 Yu Du,1,2 Junmin Bu,1,2 Guojian Wei,1,2 Miao Yu,1,2 Yanshan Lin,1,2 Cunyun Min,1,2 Datao Lin3 1Department of Traditional Chinese Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China; 2Guangdong Provincial Institute of Geriatric, Guangzhou, Guangdong, 510080, People’s Republic of China; 3Department of Parasitology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of ChinaCorrespondence: Jinni Hong, Department of Traditional Chinese Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel/Fax +86 02083827812, Email hongjinni@gdph.org.cn Datao Lin, Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel/Fax +86 02087330118, Email lindt5@mail.sysu.edu.cnAbstract: Ruminococcus gnavus (R. gnavus) is a gram-positive anaerobe commonly resides in the human gut microbiota. The advent of metagenomics has linked R. gnavus with various diseases, including inflammatory bowel disease (IBD), obesity, and diabetes mellitus (DM), which has become a growing area of investigation. The initial focus of research primarily centered on assessing the abundance of R. gnavus and its potential association with disease presentation, taking into account variations in sample size, sequencing and analysis methods. However, recent investigations have shifted towards elucidating the underlying mechanistic pathways through which R. gnavus may contribute to disease manifestation. In this comprehensive review, we aim to provide an updated synthesis of the current literature on R. gnavus in the context of IBD, obesity, and DM. We critically analyze relevant studies and summarize the potential molecular mediators implicated in the association between R. gnavus and these diseases. Across numerous studies, various molecules such as methylation-controlled J (MCJ), glucopolysaccharides, ursodeoxycholic acid (UDCA), interleukin(IL)-10, IL-17, and capric acid have been proposed as potential contributors to the link between R. gnavus and IBD. Similarly, in the realm of obesity, molecules such as hydrogen peroxide, butyrate, and UDCA have been suggested as potential mediators, while glycine ursodeoxycholic acid (GUDCA) has been implicated in the connection between R. gnavus and DM. Furthermore, it is imperative to emphasize the necessity for additional studies to evaluate the potential efficacy of targeting pathways associated with R. gnavus as a viable strategy for managing these diseases. These findings have significantly expanded our understanding of the functional role of R. gnavus in the context of IBD, obesity, and DM. This review aims to offer updated insights into the role and potential mechanisms of R. gnavus, as well as potential strategies for the treatment of these diseases. Keywords: Ruminococcus gnavus, inflammatory bowel disease, obesity, diabetes mellitus

Yinci Zhu,1,2 Zhong Zheng,1,2 Bihong Fan,1,2 Yun Sun,1,2 Junyu Zhai,1,2 Yanzhi Du1,2 1Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200135, People’s Republic of China; 2Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, 200135, People’s Republic of ChinaCorrespondence: Junyu Zhai; Yanzhi Du, Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200135, People’s Republic of China, Tel +86-21-20284525; +86-21-20284518, Email zhaijy2007@foxmail.com; duyz@sjtu.edu.cnPurpose: Together with ultrasound measurement of follicle size, serum estradiol (E2) provides guidance for controlled ovarian hyperstimulation (COH). However, during the COH process, some patients experience decreased serum E2 level, especially before human chorionic gonadotropin (hCG) trigger. In order to elucidate the effect of E2 reduction as well as the role of oral contraceptive pretreatment, a retrospective study was performed in our center from 2013 to 2019.Patients and Methods: In total, 333 patients who experienced an E2 decrease prior to hCG administration were recruited as E2 decline group, while 333 patients with continuously E2 increase during COH were considered as control group. Based on pretreatment strategy, the two groups were further categorized into oral contraceptive (OC) and non-OC sub-groups, and IVF and clinical outcomes were compared between paired groups.Results: Number of dominant follicles on hCG day and normally fertilized zygotes were significantly decreased in E2 decline group, and the significantly reduced live birth rate in E2 decline group indicated the close relationship between E2 decline and clinical outcomes. To analyse further, we found that in patients without OC pretreatment, the pregnancy rate and live birth rate of E2 decline group (n = 141) were significantly lower than control group (n = 136) (56.3% versus 68.0%, 50.8% versus 63.5%, respectively). However, for patients with OC pretreatment, no difference was detected between two groups, suggesting a potential effect of OC pretreatment on clinical outcomes.Conclusion: E2 decline prior to hCG-triggering day adversely affects IVF and clinical outcomes in patients without OC pretreatment, especially fertilization rate and live birth rate.Keywords: estradiol decline, controlled ovarian hyperstimulation, oral contraceptive, in vitro fertilization, fertilization rate, live birth rate

Yong Du,1 Jens Baumert,1 Stefan Damerow,1 Alexander Rommel,1 Hannelore Neuhauser,1,2 Christin Heidemann1 1Department of Epidemiology and Health Monitoring, Robert Koch Institute, Berlin, Germany; 2German Centre for Cardiovascular Research (DZHK), Berlin, GermanyCorrespondence: Yong Du, Department of Epidemiology and Health Monitoring, Robert Koch Institute, General-Pape-Str. 62-66, Berlin, D-12101, Germany, Tel +49-30-18754 3199, Fax +49 − 30-18754 3211, Email duy@rki.dePurpose: Fear of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and lockdown measures may have an impact on health care utilization particularly for people with chronic diseases. We investigated changes in outpatient utilization behavior in pandemic phases among people with selected chronic diseases in Germany.Methods: The nationwide population-based telephone surveys German Health Update (GEDA) 2019/2020 (April 2019 to September 2020) and GEDA 2021 (July to December 2021) covered 4 out of 7 pandemic phases from the pre-pandemic to the 4th pandemic wave. Data on hypertension, diabetes and major cardiovascular diseases (CVD) in the past 12 months and visiting a general practitioner (GP) or a specialist (excluding dentist) in the past 4 weeks was collected using a standardized questionnaire. Proportions and odds ratios were derived from logistic regression models adjusted for age, sex, education and federal states.Results: Among 27,967 participants aged ≥ 16 years, 8,449, 2,497 and 1,136 individuals had hypertension, diabetes and major CVD. Participants with these chronic diseases visited a GP or specialist significantly more often than the overall study population, irrespective of pandemic phases. Compared to the pre-pandemic phase, a significant reduction in specialist-visiting was found in the first pandemic wave among people with hypertension (34.3% vs 24.1%), diabetes (39.5% vs 25.5%) and major CVD (41.9% vs 25.6%). GP-visiting was lower only among people with hypertension (53.0% vs 46.0%). No difference in GP or specialist visiting was found in the 4th pandemic wave compared to the pre-pandemic phase.Conclusion: The observed decrease particularly in specialist utilization among people with the selected chronic diseases at the beginning of the pandemic was not observed for the second half of 2021 despite the ongoing pandemic. Further studies are required to examine whether the temporary changes in the utilization of ambulatory health care have affected the disease management of people with chronic diseases.Keywords: health service utilization, outpatients, SARS-CoV-2, chronic disease, cardiometabolic diseases, diabetes, Germany

Lingbo Bi,&ast; Chaofan Wang,&ast; Yimei Du,&ast; Changpei Lu, Min Zhao, Yunbu Ding, Weiling Sun, Weixin Fan Department of Dermatology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weixin Fan; Weiling Sun, Department of Dermatology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, 210029, People’s Republic of China, Tel +86-13327805737 ; +86-13813955963, Email swl0560@sina.com; hairmanfwx@163.comPurpose: To investigate whether increased levels of lipids-related metabolites (LRMs) result in androgenic alopecia (AGA).Patients and Methods: A two-sample Mendelian randomization (MR) study was designed, and single nucleotide polymorphisms (SNPs) respectively related to nine LRMs were selected from the genome-wide association study (GWAS) dataset. An MR analysis was performed to assess the causal association between LRMs and AGA.Results: Through the fixed-effect inverse variance weighting (IVW) method, MR analysis indicated that Apolipoprotein B (ApoB), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) had a causal relationship with AGA. No obvious heterogeneity or pleiotropy was observed.Conclusion: The risk of AGA increases significantly when the serum levels of ApoB, LDL, and VLDL increase. This causal relationship is solid and free of interference from confounding factors.Keywords: androgenic alopecia, apolipoprotein B, VLDL, LDL

Huajun Sun,1 Fangshi Li,1 Yaxuan Xu,2 Qi Qi,3 Yue Du1 1School of Public Health, Tianjin Medical University, Tianjin, People’s Republic of China; 2School of Nursing, Tianjin Medical University, Tianjin, People’s Republic of China; 3School of Optometry, Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Yue Du, School of Public Health, Tianjin Medical University, 22&num; Qixiangtai Road, Heping District, Tianjin, 300070, People’s Republic of China, Tel +86 18920015698, Fax +86 02283336597, Email duyue@tmu.edu.cnObjective: Physical examination services play a crucial role in the early detection of diseases, improving the effectiveness of treatment. However, the current physical examination services provided by community health service centers are limited. The objective of this study was to investigate the aspects of physical examination services that are most valued by residents.Methods: Identify and develop attributes and levels through literature research and expert group interviews. A discrete choice experiment was designed. The main effects design gives rise to 16 choice sets. The 16 choice sets were grouped into 2 blocks, and respondents were randomly assigned to one of the blocks. In each choice set, respondents were asked to choose from two alternatives with an opt-out option. In 2023, the discrete choice experiment was administered in several community health service centers within a China population sample. A mixed logit and a latent class analysis were conducted.Results: Participants (n = 399) preferred to receive health advice service. The services provided by the basic team with clinical experts are preferred over those provided solely by the basic team. The results indicated a preference for a participant to be serviced by face-to-face or telephone compared with WeChat. Low cost is also preferred. As participants grow older, their preference for face-to-face or telephone-based services increased. As participants’ service demand increase, participants more preferred to receive interpretation of physical examination report and follow-up of important abnormal results, participants more preferred to be serviced by basic team with clinical experts or basic team with health manager etc.Conclusion: We should improve the construction of the service team, optimize the service mode, expand the scope of examination services, reduce the cost of examination services, and meet the needs of residents for physical examination services. More attention should be paid to the needs of elderly and rural residents.Keywords: discrete choice experiment, physical examination, community health service, preference

Jingcheng Ding,1,&ast; Qian Shi,1,&ast; Ling Dong,2 Hong Su,3 Yijun Du,1 Tianrong Pan,1 Xing Zhong1 1Department of Endocrinology, The Second Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, 230601, People’s Republic of China; 2Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, 230601, People’s Republic of China; 3Department of Epidemiology and Health Statistics, Anhui Medical University, Hefei City, Anhui Province, 230601, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xing Zhong, Department of Endocrinology, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei City, Anhui province, People’s Republic of China, Tel +86 18905692292, Email zhongxing761@163.comPurpose: To investigate the relationship between HbA1c variability and vibrating perception threshold (VPT) in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM).Patients and Methods: A total of 367 middle-aged and elderly patients with T2DM were enrolled. All patients were categorized into the control and vibration sensation deficiency group (VSD) based on VPT. Clinical data were collected. The coefficient of variation of glycated hemoglobin A1c (HbA1c-CV) and the mean glycated hemoglobin A1c(HbA1c-Mean) are considered as indexes of HbA1c variability. Multivariate logistic regression analysis, the generalized linear model and ROC curve correlation analysis were used to analyze the correlation of various factors and VPT.Results: The multivariate logistic regression analysis revealed that age, systolic blood pressure (SBP), and HbA1c-CV were identified as risk factors for vibration sensation deficiency in middle-aged and elderly patients with T2DM, while estimated glomerular filtration rate (eGFR), triiodothyronine (T3), and alanine aminotransferase (ALT) were considered as protective factors. In the unadjusted generalized linear model, a significant association was observed between HbA1c-CV and VPT values. After adjusting for age, diabetic duration, SBP, homeostatic model assessment for beta-cell function (HOMA-β), ALT, eGFR, T3, 24-hour urinary protein excretion levels, and HbA1c-Mean, HbA1c-CV remained significantly correlated with VPT values on both sides. (left side, B=2.560, 95% CI 1.298~3.823; P< 0.001; right side, B=2.608, 95% CI 1.498~3.718, P< 0.001). The area under the curve (AUC) for HbA1c-CV and VSD prevalence was 0.723, with a sensitivity of 79.85%, specificity of 56.22%.Conclusion: The risk of developing VSD increases proportionally with higher HbA1c-CV levels in middle-aged and elderly patients with T2DM. Reaching and maintaining blood glucose stability is essential to the mitigation of diabetes peripheral neuropathy occurrence.Keywords: type 2 diabetes mellitus, HbA1c variability, vibrating perception threshold, diabetic peripheral neuropathy

Guang Chen,1,&ast; Caohua Lv,2,&ast; Qing Nie,3 Xin Li,1 Yinyi Lv,1 Guoyan Liao,1 Shuangchun Liu,4 Weiwei Ge,2 Jinguang Chen,1 Yunting Du5 1Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, 318000, People’s Republic of China; 2Department of Dermatology, Taizhou Second People’s Hospital, Taizhou, 317200, People’s Republic of China; 3Weifang Centers for Disease Control and Prevention, Weifang, 261061, People’s Republic of China; 4Municipal Hospital Affiliated to Medical School of Taizhou University, Taizhou, 318000, People’s Republic of China; 5Department of Laboratory Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, 110042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinguang Chen; Yunting Du, Tel/Fax +86 576 88661988, Email tongly0422@126.com; m15840557769@163.comBackground: The traditional Matricaria chamomilla L. has been used to treat dermatitis for thousands of years. Due to emerging trends in alternative medicine, patients prefer natural remedies to relieve their symptoms. Therefore, finding safe and effective plant medicines for topical applications on the skin is an important treatment strategy for dermatologists. German chamomile (Matricaria chamomilla L.) from the Compositae family is a famous medicinal plant, often known as the “star of medicinal species.”However, the function of Matricaria chamomilla essential oil on skin inflammation has not been thoroughly examined in earlier research.Methods: GC-MS analyzed the components of MCEO, and this study explored the anti-inflammation effects of MCEO on psoriasis with network pharmacological pathway prediction. Following this, we used clinical samples of psoriasis patients to confirm the secretory characteristic of relative inflammatory markers. The therapeutic effect of MCEO on skin inflammation was detected by examination of human keratinocytes HaCaT. At the same time, we prepared imiquimod-induced psoriatic-like skin inflammation in mice to investigate thoroughly the potential inhibition functions of MCEO on psoriatic skin injury and inflammation.Results: MCEO significantly reduced interleukin-22/tumor necrosis factor α/lipopolysaccharide-stimulated elevation of HaCaT cell inflammation, which was correlated with downregulating PI3K/Akt/mTOR and p38MAPK pathways activation mediated by MCEO in HaCaT cells treated with IL-22/TNF-α/LPS. Skin inflammation was evaluated based on the PASI score, HE staining, and relative inflammatory cytokine levels. The results showed that MCEO could significantly contribute to inflammatory skin disease treatment.Conclusion: MCEO inhibited inflammation in HaCaT keratinocytes induced by IL-22/TNF-α/LPS, the potential mechanisms associated with inhibiting excessive activation and crosstalk between PI3K/Akt/mTOR and p38MAPK pathways. MCEO ameliorated skin injury in IMQ-induced psoriatic-like skin inflammation of mice by downregulating the levels of inflammatory cytokines but not IL-17A. Thus, anti-inflammatory plant drugs with different targets with combined applications were a potential therapeutic strategy in psoriasis.Keywords: Matricaria chamomilla, essential oil, psoriasis, HaCaT, IMQ, mouse

Yushen Jin,1 Zhongquan Cheng,2 Zhu Yuan,2 Yang Du,3 Jie Tian,3 Bing Shao1,4 1Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Centre for Disease Prevention and Control, Beijing, 100013, People’s Republic of China; 2Department of General Surgery, Capital Medical University, Beijing Friendship Hospital, Beijing, 100050, People’s Republic of China; 3CAS Key Laboratory of Molecular Imaging, Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, People’s Republic of China; 4College of Veterinary Medicine, China Agricultural University, Beijing, 100193, People’s Republic of ChinaCorrespondence: Bing Shao; Jie Tian, Email shaobingch@sina.com; jietian@ia.ac.cnPurpose: Liver cancer is considered as the third leading cause of cancer-related deaths, with hepatocellular carcinoma (HCC) accounting for approximately 90% of liver cancers. Improving the treatment of HCC is a serious challenge today. The primary objective of this study was to construct SP94-Fe3O4@ICG&DOX nanoparticles and investigate their potential diagnosis and treatment effect benefits on HCC.Methods: Firstly, we synthesized and characterized SP94-Fe3O4@ICG&DOX nanoparticles and confirmed their in vitro release behavior, photothermal and photodynamic performance. Moreover, the in vivo imaging capability was also observed. Finally, the inhibitory effects on Hepa1-6 in vitro and in vivo were observed as well as biosafety.Results: SP94-Fe3O4@ICG&DOX nanoparticles have a size of ~22.1 nm, with an encapsulation efficiency of 45.2% for ICG and 42.7% for DOX, showing excellent in vivo MPI and fluorescence imaging capabilities for precise tumor localization, and synergistic photo-chemotherapy (pH- and thermal-sensitive drug release) against tumors under irradiation. With the assistance of a fluorescence molecular imaging system or MPI scanner, the location and contours of the tumor were clearly visible. Under a constant laser irradiation (808 nm, 0.6 W/cm2) and a set concentration (50 μg/mL), the temperature of the solution could rapidly increase to ~45 °C, which could effectively kill the tumor cells. It could be effectively uptaken by HCC cells and significantly inhibit their proliferation under the laser irradiation (100% inhibition rate for HCC tumors). And most importantly, our nanoparticles exhibited favorable biocompatibility with normal tissues and cells.Conclusion: This versatile agent can serve as an intelligent and promising nanoplatform that integrates multiple accurate diagnoses, precise positioning of cancer tissue, and effective coordination with synergistic tumor photodynamic therapy. Keywords: porous hollow structure, magnetic particle imaging, fluorescence imaging, synergistic treatment, theranostics

Min Yang,1,2 Mengyao Xie,1,2 Jiajun Guo,1,2 Yuqing Zhang,1,2 Yan Qiu,1,2 Zhibiao Wang,1,2 Yonghong Du1,2 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Zhibiao Wang; Yonghong Du, State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Tel/Fax +86-23-68485000 ; +86-23-68485021, Email wangzb@cqmu.edu.cn; duyonghong@cqmu.edu.cnBackground: Candida albicans (C. albicans) forms pathogenic biofilms, and the dense mucus layer secreted by the epithelium is a major barrier to the traditional antibiotic treatment of mucosa-associated C. albicans infections. Herein, we report a novel anti-biofilm strategy of mucus-permeable sonodynamic therapy (mp-SDT) based on ultrasound (US)-mediated amphotericin B-loaded PEGylated PLGA nanoparticles (AmB-NPs) to overcome mucus barrier and enable the eradication of C. albicans biofilm.Methods: AmB-NPs were fabricated using ultrasonic double emulsion method, and their physicochemical and sonodynamic properties were determined. The mucus and biofilm permeability of US-mediated AmB-NPs were further investigated. Moreover, the anti-biofilm effect of US-mediated AmB-NPs treatment was thoroughly evaluated on mucus barrier abiotic biofilm, epithelium-associated biotic biofilm, and C. albicans-induced rabbit vaginal biofilms model. In addition, the ultrastructure and secreted cytokines of epithelial cells and the polarization of macrophages were analyzed to investigate the regulation of local cellular immune function by US-mediated AmB-NPs treatment.Results: Polymeric AmB-NPs display excellent sonodynamic performance with massive singlet oxygen (1O2) generation. US-mediated AmB-NPs could rapidly transport through mucus and promote permeability in biofilms, which exhibited excellent eradicating ability to C. albicans biofilms. Furthermore, in the vaginal epithelial cells (VECs)-associated C. albicans biofilm model, the mp-SDT scheme showed the strongest biofilm eradication effect, with up to 98% biofilm re-formation inhibition rate, improved the ultrastructural damage, promoted local immune defense enhancement of VECs, and regulated the polarization of macrophages to the M1 phenotype to enhance macrophage-associated antifungal immune responses. In addition, mp-SDT treatment exhibited excellent therapeutic efficacy against C. albicans-induced rabbit vaginitis, promoted the recovery of mucosal epithelial ultrastructure, and contributed to the reshaping of a healthier vaginal microbiome.Conclusion: The synergistic anti-biofilm strategies of mp-SDT effectively eradicated C. albicans biofilm and simultaneously regulated local antifungal immunity enhancement, which may provide a new approach to treat refractory drug-resistant biofilm-associated mucosal candidiasis.Keywords: C. albicans biofilm, PEGylated nanoparticles, mucus penetration, sonodynamic therapy

Qian Shi,1,&ast; Jingcheng Ding,1,&ast; Hong Su,2 Yijun Du,1 Tianrong Pan,1 Xing Zhong1 1Department of Endocrinology, the Second Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, 230601, People’s Republic of China; 2Department of Epidemiology and Health Statistics, Anhui Medical University, Hefei City, Anhui Province, 230601, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xing Zhong, No. 678 Furong Road, Hefei City, Anhui Province, 230601, People’s Republic of China, Tel +86 18905692292, Email zhongxing761@163.comPurpose: To explore the relationship between long-term glycemic variability and anxiety and depression in patients with type 2 diabetes.Participants and Methods: A cohort comprising 214 individuals diagnosed with type 2 diabetes participated in this study. Comprehensive demographic and laboratory information was gathered for them. The evaluation of anxiety relied on the 7-item Generalized Anxiety Disorder Scale (GAD-7), while depression was assessed utilizing the 9-item Health Questionnaire (PHQ-9). Based on the presence or absence of anxiety and depression, participants were categorized into either the mood disorder or control groups. Subsequently, univariate and stepwise multiple binary logistic regression analyses were conducted to investigate the potential correlations between factors and the presence of anxiety and depression.Results: The prevalence of anxiety disorders is 23%, and depression is 32%. The prevalence of smoking, diabetic autonomic neuropathy, stroke, and osteoporosis in the mood disorder group was significantly higher than that in the control group (P < 0.05), the glycated hemoglobin A1c variability score (HVS), mean hemoglobin A1c value, total cholesterol, urinary albumin/creatinine and systemic immune-inflammatory index (SII) were significantly higher in the control group (P < 0.05). The level of high-density lipoprotein in the mood disorder group was significantly lower than the control group (P < 0.05). In stepwise multiple binary logistic regression analyses, the main factors associated with anxiety were depression (P < 0.001, OR=117.581) and gender (P < 0.001, OR=9.466), and the main factors related to depression included anxiety (P < 0.001, OR=49.424), smoking (P=0.042, OR=2.728), HVS (P=0.004, OR=8.664), and SII (P=0.014, OR=1.002).Conclusion: Persistent fluctuations in blood glucose levels have been linked to anxiety and depression. Consequently, maintaining an optimal level of glycemic control and minimizing fluctuations becomes imperative in the comprehensive management of diabetes.Keywords: type 2 diabetes, anxiety, depression, long-term glycemic variability

Yang M, Xie M, Guo J, et al. Int J Nanomedicine. 2023;18:7941-7963. We, the Editor and Publisher of the journal International Journal of Nanomedicine are retracting the published article. Following publication of the article, the authors raised concerns about the duplication of images from Figures 2, 6, 9, 11 and 12. Specifically, The image for Figure 2A, SEM image of AmB-NPs, has been duplicated with the image for Figure 3B, SEM image of BM2-LVFX-NPs, from Li G, Li J, Hou Y, et al. Levofloxacin-Loaded Nanosonosensitizer as a Highly Efficient Therapy for Bacillus Calmette-Guérin Infections Based on Bacteria-Specific Labeling and Sonotheranostic Strategy. Int J Nanomedicine. 2021;16:6553-6573. https://doi.org/10.2147/IJN.S321631. Images for Figure 6C, AmB-NPs and US+AmB have been duplicated but show a different colour intensity. Images for Figure 9C, Control and US, have been duplicated. Images for Figure 11C, C. albicans CD86, AmB and IL-4 CD206, AmB-NPs, have been duplicated. Images for Figure 11C, C. albicans CD86, US+AmB-NPs and IL-4 CD206, US, have been duplicated but show a different immunofluorescene staining intensity. Images for Figure 12C, AmB and US+AmB, have been duplicated but one of the images has been flipped. Images for Figure 12D, US+AmB and US+AmB-NPs, have been duplicated. The authors were cooperative and responded to our queries but were unable to provide a satisfactory explanation for the duplicated images but did provide some original data for the study. However, as verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the authors agree with this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Hanxiao Liu,1– 3 Hui Lv,2,3 Xuehui Duan,3 Yan Du,3 Yixuan Tang,3 Wei Xu1– 3 1School of Pharmacy, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 2Department of Pharmacy, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, 250014, People’s Republic of China; 3School of Pharmaceutical Sciences & Institute of Materia Medica, National Key Laboratory of Advanced Drug Delivery System, Medical Science and Technology Innovation Center, Key Laboratory for Biotechnology Drugs of National Health Commission, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of ChinaCorrespondence: Yixuan Tang; Wei Xu, Email tangyixuan@sdfmu.edu; xuwei6420@126.comAbstract: Macrophages play a crucial role in tissue homeostasis and the innate immune system. They perform essential functions such as presenting antigens, regulating cytokines, and responding to inflammation. However, in diseases like cancer, cardiovascular disorders, and autoimmune conditions, macrophages undergo aberrant polarization, which disrupts tissue regulation and impairs their normal behavior. To address these challenges, there has been growing interest in developing customized targeted drug delivery systems specifically designed for macrophage-related functions in different anatomical locations. Nanomedicine, utilizing nanoscale drug systems, offers numerous advantages including improved stability, enhanced pharmacokinetics, controlled release kinetics, and precise temporal drug delivery. These advantages hold significant promise in achieving heightened therapeutic efficacy, specificity, and reduced side effects in drug delivery and treatment approaches. This review aims to explore the roles of macrophages in major diseases and present an overview of current strategies employed in targeted drug delivery to macrophages. Additionally, this article critically evaluates the design of macrophage-targeted delivery systems, highlighting limitations and discussing prospects in this rapidly evolving field. By assessing the strengths and weaknesses of existing approaches, we can identify areas for improvement and refinement in macrophage-targeted drug delivery.Keywords: macrophages, nanomedicine, drug delivery, tumors, autoimmune disease

Jinni Hong,1,2 Tingting Fu,1,2 Weizhen Liu,1,2 Yu Du,1,2 Junmin Bu,1,2 Guojian Wei,1,2 Miao Yu,1,2 Yanshan Lin,1,2 Cunyun Min,1,2 Datao Lin3 1Department of Traditional Chinese Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China; 2Guangdong Provincial Institute of Geriatric, Guangzhou, Guangdong, 510080, People’s Republic of China; 3Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of ChinaCorrespondence: Jinni HongDepartment of Traditional Chinese Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel +86 2083827812, Fax +86 2083827812, Email hongjinni@gdph.org.cnDatao LinDepartment of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel +86 2087330118, Fax +86 2087330118, Email lindt5@mail.sysu.edu.cnPurpose: This study aimed to elucidate the impact of Jiangtang decoction (JTD) on diabetic kidney disease (DKD) and its association with alterations in the gut microbiota.Methods: Using a diabetic mouse model (KK-Ay mice), daily administration of JTD for eight weeks was undertaken. Weekly measurements of body weight and blood glucose were performed, while kidney function, uremic toxins, inflammation factors, and fecal microbiota composition were assessed upon sacrifice. Ultra-structural analysis of kidney tissue was conducted to observe the pathological changes.Results: The study findings demonstrated that JTD improve metabolism, kidney function, uremic toxins and inflammation, while also exerting a modulatory effect on the gut microbiota. Specifically, the genera Rikenella, Lachnoclostridium, and unclassified_c_Bacilli exhibited significantly increased abundance following JTD treatment, accompanied by reduced abundance of norank_f_Lachnospiraceae compared to the model group. Importantly, Rikenella and unclassified_c_Bacilli demonstrated negative correlations with urine protein levels. Lachnoclostridium and norank_f_Lachnospiraceae were positively associated with creatinine (Cr), indoxyl sulfate (IS) and interleukin (IL)-6. Moreover, norank_f_Lachnospiraceae exhibited positive associations with various indicators of DKD severity, including weight, blood glucose, urea nitrogen (UN), kidney injury molecule-1 (KIM-1) levels, trimethylamine-N-oxide (TMAO), p-cresyl sulfate (pCS), nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (NLRP3) and IL-17A production.Conclusion: These findings suggested that JTD possess the ability to modulate the abundance of Rikenella, Lachnoclostridium, unclassified_c_Bacilli and norank_f_Lachnospiraceae within the gut microbiota. This modulation, in turn, influenced metabolic processes, kidney function, uremic toxin accumulation, and inflammation, ultimately contributing to the amelioration of DKD.Graphical Abstract: Keywords: Chinese herbal medicine, gut microbiota, diabetic kidney disease, inflammation, uremic toxins

Lin Xia,1,&ast; Yu Liu,1,&ast; Zhonglu Yang,1 Yuguang Ge,1 Lu Wang,1 Yejun Du,1 Yinan Dong,2 Hui Jiang1 1Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, 110016, People’s Republic of China; 2Department of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning Province, 110016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Jiang, Department of Cardiovascular Surgery, General Hospital of Northern Theater, Command, 83 Wenhua Road, Shenyang, Liaoning Province, 110016, People’s Republic of China, Tel +86-024-2889-7390, Fax +86-024-2889-7391, Email jianghsyzy@163.comPurpose: Upper hemisternotomy (UHS) has benefits over conventional full sternotomy because it ameliorates trauma during cardiac surgery. Owing to its challenging and technically demanding nature, this incision in acute type A aortic dissection (ATAAD) has rarely been reported. This study aimed to analyze the learning curve of total arch replacement (TAR) with moderate hypothermic circulatory arrest via a single UHS approach, which is necessary to guide the training of surgeons in adopting minimally invasive procedures.Patients and Methods: A total of 202 consecutive patients who were definitively diagnosed with ATAAD between July 2016 and June 2021 were enrolled in this retrospective analysis. Patients were divided into three groups based on cumulative sum plots for circulatory arrest time in chronological order. Perioperative characteristics were compared between the groups.Results: There was significant difference in the circulatory arrest time and cross-clamp time respectively among three groups (39.0 min vs 28.0 min vs 15.0 min, P < 0.001; 104.5 min vs 106.2 min vs 84.1 min, P < 0.001). The ventilation time and first 24-h chest tube drainage were statistically different among groups (35.5 h vs 24.0 h vs 19.0 h, P = 0.031; 220.0 mL vs 192.5 mL vs 125.5 mL, P = 0.043). No other clinical outcome was observed as significant difference.Conclusion: A cardiac surgeon can convert a conventional full sternotomy to a single UHS for TAR after experiencing a learning curve, to ensure patient safety. The mastery of this minimally invasive surgical technique may be beneficial for the prognosis of patients with ATAAD.Keywords: aneurysm, dissecting, cardiac surgical procedures, sternotomy, circulatory arrest, deep hypothermia induced, learning curve

Can Hu,1,2,&ast; Yan Qiu,1,2,&ast; Jiajun Guo,1,2 Yuchao Cao,1,2 Dairong Li,3 Yonghong Du1,2 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dairong Li, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-23-89012745, Fax +86-23-68485021, Email lidairong@hospital.cqmu.edu.cn Yonghong Du, State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, No. 1, Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel/Fax +86-23-68485021, Email duyonghong@cqmu.edu.cnPurpose: Tuberculosis (TB) is a chronic disease caused by Mycobacterium tuberculosis (MTB) that remains a major global health challenge. One of the main obstacles to effective treatment is the heterogeneous microenvironment of TB granulomas. This study aimed to investigate the potential of a hypoxic remission-based strategy to enhance the outcome of tuberculosis treatment when implemented in combination with ultrasound.Methods: A PLGA nanoparticle (LEV@CAT-NPs) loaded with levofloxacin (LEV) and catalase (CAT) was fabricated by a double emulsification method, and its physical characteristics, oxygen production capacity, drug release capacity, and biosafety were thoroughly investigated. The synergistic therapeutic effects of ultrasound (US)-mediated LEV@CAT-NPs were evaluated using an experimental mouse model of subcutaneous tuberculosis granuloma induced by Bacille Calmette-Guérin (BCG) as a substitute for MTB.Results: LEV@CAT-NPs exhibited excellent oxygen production capacity, biosafety, and biocompatibility. Histological analysis revealed that ultrasound-mediated LEV@CAT-NPs could effectively remove bacteria from tuberculous granulomas, significantly alleviate the hypoxia state, reduce the necrotic area and inflammatory cells within the granuloma, and increase the penetration of dyes in granuloma tissues. The combined treatment also reduced the serum levels of inflammatory cytokines (eg, TNF-α, IL-6, and IL-8), and significantly downregulated the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF). These results suggested that the synergistic treatment of ultrasound-mediated LEV@CAT-NPs effectively eradicated the bacterial infection and reversed the hypoxic microenvironment of tuberculous granulomas, further promoting tissue repair.Conclusion: This study provides a non-invasive and new avenue for treating refractory tuberculosis infections. The potential role of regulating hypoxia within infected lesions as a therapeutic target for infection deserves further exploration in future studies.Keywords: tuberculosis granulomatous, hypoxia, catalase, sonodynamic therapy, Bacille Calmette-Guérin

Ning Li,1 Jia Zhang,1,2 Si-Jia Li,1 Yang Du,1,2 Qi Zhou,2 Hong-Qiu Gu,2 Xing-Quan Zhao1– 3 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China; 3Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Xing-Quan Zhao, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +86-13501031486, Email zxq@vip.163.comBackground: The presence of mild deficit is the most common reason for nonuse of intravenous alteplase in ischemic stroke. We analyzed within a national prospective cohort on whether patients with minor stroke can benefit from intravenous alteplase.Methods: This observational study included patients with acute ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score 0 to 5 at admission. The short-term outcomes at discharge and 3-month were analyzed including the modified Rankin Scale score, gait speed, Montreal Cognitive Assessment, Patient Health Questionnaire-9, General Anxiety Disorder-7 and Stroke Impact Scale-16. Multivariate regression models were performed to evaluate the association between intravenous thrombolysis and clinical outcomes.Results: A total of 1876 consecutive patients were included in the current analyses with 102 patients (5.4%) received alteplase and 1774 patients (94.5%) were in non-alteplase group. We found that 10.9% patients presented unfavorable functional outcome with a mRS ≥ 2 at 3-month. Patients with alteplase treatment had a more favorable outcome in SIS-16 at discharge (OR, 5.45; 95% CI, 2.22– 8.68) and 3-month after stroke (OR, 2.34; 95% CI, 0.17– 4.50). There was an association of alteplase with better gait speed in the restricted sample of age > 60 (OR,0.14; 95% CI, 0.02– 0.25), while an unfavorable effect was found in anxiety (OR, 2.23; 95% CI, 2.23, 0.91– 3.55) and depression (OR, 1.54; 95% CI, 0.17– 2.91) in female.Conclusion: Alteplase showed a suggestive benefit in function and motor outcomes in patients with low NIHSS score of 0– 5. Meanwhile, female seemed more inclined to post-stroke emotional problems after alteplase treatment, which should be further explored in the future.Keywords: alteplase, minor stroke, ischemic, outcomes

Jiajia Zhai,1 Junyan Zhang,2,3 Jingfang He,3 Minzhi Lv,4,5 Bozheng Zhang,6 Guanqun Li,7 Yuanjie Du,1 Guimin Hao1 1Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Shanxi Bethune Hospital, Shanxi Academy Of Medical Sciences, Department of Clinical Epidemiology and Evidence-Based Medicine, Taiyuan, People’s Republic of China; 3Bothwin Clinical Study Consultant, Shanghai, People’s Republic of China; 4Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 5Center of Evidence-Based Medicine, Fudan University, Shanghai, People’s Republic of China; 6Department of Psychology, College of Arts and Sciences, University of Washington, Seattle, WA, 98053, USA; 7Technoderma Medicines Inc, Shanghai, People’s Republic of ChinaCorrespondence: Guimin Hao, Email haoguimin@163.comObjective: For patients with polycystic ovary syndrome (PCOS) to undergo in vitro fertilization (IVF) and embryo transfer (ET), there has been no consensus regarding which protocol is the most optimal for live birth rate in fresh cycles. We sought to evaluate depot gonadotropin-releasing hormone (GnRH) agonist protocol versus GnRH antagonist protocol in IVF outcomes for PCOS patients in a single fertility center.Methods: In this retrospective cohort, PCOS patients who visited the Second Hospital of Hebei Medical University reproductive center between February 2012 and December 2019 were screened, and 533 PCOS infertility patients were included undergoing their first IVF cycle, with 470 in the depot GnRH agonist group and 63 in the GnRH antagonist group. The primary of this study outcome was the fresh live birth rate (LBR).Results: PCOS women in the depot GnRH agonist group had a higher LBR (49.79%) than those in the GnRH antagonist group (34.92%, p = 0.027). The multivariable logistic regression also confirmed that women in the depot GnRH agonist group had a higher LBR than those in the GnRH antagonist group (OR = 1.83, 95% CI 1.05~3.18, p = 0.032). After propensity score matching (PSM), the LBR in the depot GnRH agonist group was higher (50.32%) than that of the GnRH antagonist group (35.48%), p = 0.033. The ovarian hyperstimulation syndrome (OHSS) rates were similar between the two groups, with 35 in the depot GnRH group and 6 in the GnRH antagonist group (p = 0.561).Conclusions: For PCOS patients in fresh embryo transfer cycles, the depot GnRH agonist protocol may lead to a higher LBR than the antagonist protocol with satisfied lower OHSS rates.Keywords: PCOS, depot gonadotropin-releasing hormone agonist protocol, gonadotropin-releasing hormone antagonist protocol, cumulative live birth rate, live birth rate

Yujiao Du,1 Jing Li,1 Pengfei Qu,2 Shaonong Dang1 1Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, People’s Republic of China; 2Assisted Reproduction Center, Northwest Women’s and Children’s Hospital, Xi’an Jiaotong University Health Science Center, Xi’an, 710003, People’s Republic of ChinaCorrespondence: Shaonong Dang, Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, People’s Republic of China, Tel +86-13468779736, Fax +86-2982655730, Email tjdshn@mail.xjtu.edu.cnPurpose: There remains a data gap on vitamin B12 and folate level in maternal and child populations. This study aimed to assess the status of vitamin B12 and folate in maternal serum (MS) and umbilical cord serum (UCS).Materials and Methods: This was a planned secondary analysis of a case-control study. A total of 858 pregnant women during late pregnancy and their newborns in the hospitals of China were included. Maternal peripheral venous blood and neonatal umbilical cord blood were collected to determine serum vitamin B12 and folate concentration. Relationship of vitamin B12 or folate concentration between MS and UCS was assessed by a quantile regression model and the non-linear relationship between them was examined.Results: Nutritional status of serum folate was better than that of vitamin B12. Prevalence of deficiency in MS vitamin B12 and folate was 73.4% and 14.2%, respectively and these figures were about 17.8% and 0.1% in UCS. Both vitamin B12 and folate levels in UCS were significantly higher than those in MS (vitamin B12: 321.0 pg/mL vs 158.3 pg/mL, folate: 16.5 ng/mL vs 7.0 ng/mL, P < 0.001). The median UCS-MS ratio of vitamin B12 and folate was 2.0 (95% CI: 1.94– 2.06) and 2.4 (95% CI: 2.30– 2.53), respectively. The levels of folate and vitamin B12 in UCS increased nonlinearly with their increase in MS which presented an inverted U-shaped curve.Conclusion: Deficiency in vitamin B12 and folate in the women during late pregnancy in China is prevalent. Nutritional status of the two vitamins in umbilical cord serum is correlated nonlinearly with that in maternal serum. Folic acid supplementation may be accompanied with vitamin B12 to improve status of vitamin B12 and folate during pregnancy.Keywords: vitamin B12, folate, umbilical cord serum, maternal serum, pregnancy

Yingwu Guo,1,2,&ast; Jun Liu,1,&ast; Yingrong Du,1,&ast; Virasakdi Chongsuvivatwong2,&ast; 1Department of Infectious Diseases, Third People’s Hospital of Kunming City, Kunming, People’s Republic of China; 2Department of Epidemiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand&ast;These authors contributed equally to this workCorrespondence: Virasakdi Chongsuvivatwong, Department of Epidemiology, Faculty of Medicine, Prince of Songkla University, 15 Kanjanavanich Road, Hat Yai, Songkhla, 90110, Thailand, Tel +66897350098, Email cvirasak@medicine.psu.ac.thBackground: Fertility decision-making plays a negligible role in completing fertility goals among couples living with HIV (CLWH). Being commonly matched concerning fertility motivation seems essential for fertility desire/intention. Few studies report on intra-couple congruences or incongruences in fertility motivation on desire/intention. This study aims to assess the effects of (in)congruency in fertility motivation on fertility desire and intention among couples living with HIV.Methods: This study uses the actor-partner interdependence model (APIM) to assess the independent direct and indirect effect of fertility motivation on intention, and dyadic response surface analysis with congruency/incongruent effect (DRSA) of fertility motivation on intention using fertility desire as mediator variable among CLWH. CLWH were selected from a clinic in Kunming, China, between October and December 2020. Cross-sectional research included 314 CLWH.Results: APIM revealed that the wife’s fertility motivation had an indirect influence on fertility intention of couples mediated by her fertility desire (R2 = 0.42). There was a significant effect on fertility intention by interaction of (in)congruency in fertility motivation among couples. DRSA shows that linear congruency in fertility motivation of both husband and wife increased fertility desire and intention of couples. However, if there was an incongruent in fertility motivation among husband and wife, husband’s domination in fertility motivation was common and negatively affect the wife’s fertility desire to have a child. Overall, couples who were matched on fertility motivation reported a significant greater relationship with fertility intention than couples who were mismatched.Conclusion: Counseling could help both the husband and wife achieve a greater positive fertility intention by addressing comparable fertility goals.Keywords: (in)congruency, dyadic data analysis, Traits-Desires-Intentions-Behavior model, couples living with HIV

Honghao Hu,1,2 Yuechao Du,1,2 Zhongming Wang1,2 1School of Management, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 2Global Entrepreneurship Research Center, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Yuechao Du, Email ycdu@zju.edu.cnIntroduction: In the aftermath of the COVID-19 pandemic, innovation has become a crucial factor for the success of entrepreneurial ventures in China. However, the mechanisms underlying the promotion of innovation by entrepreneurs are not yet fully understood. Drawing on self-determination theory, this study develops a comprehensive “motivation-behaviors-performance” model to examine the relationship between entrepreneurs’ felt responsibility for constructive change and ventures’ innovation performance.Methods: Two waves of questionnaire surveys with a sample of 376 entrepreneurs in East China were conducted. Hierarchical regression analysis was performed to test the hypotheses.Results: The empirical findings demonstrate that entrepreneurs’ felt responsibility for constructive change is a key driver of innovation performance in ventures. Furthermore, external learning, encompassing technological and market learning, serves as a mediator for the positive link between entrepreneurs’ felt responsibility and innovation performance. The study also reveals that entrepreneurs’ perception of shared vision moderates the relationships between entrepreneurs’ felt responsibility and both technological and market learning, such that the relationships are stronger when the perception of shared vision is higher.Discussion: These results yield important contributions to the entrepreneurial psychology research and self-determination theory. The study also has managerial implications for entrepreneurs aiming to enhance ventures’ innovation performance.Keywords: entrepreneur, felt responsibility for constructive change, innovation performance, technological learning, market learning, shared vision

Yikuan Du,1,&ast; Xiaolin Cai,2,3,&ast; Bijun Xu,2,3 Yuqing Wu,2,3 Mianhai Chen,2,3 Jinjin Wang,2,3 Bing Yuan,2,3 Weichui Zhang,2,3 Jinfeng Zhu,2,3 Chun Yang2,3 1Central Laboratory, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, 523059, People’s Republic of China; 2Dongguan Key Laboratory of Chronic Inflammatory Diseases, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523808, People’s Republic of China; 3Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, Guangdong Medical University, Dongguan, 523808, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun Yang, Dongguan Key Laboratory of Chronic Inflammatory Diseases, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, People’s Republic of China, Tel +86 150 1915 9295, Email yangchunangel@163.comBackground: Fascial pathological pain is the main type of chronic pain in older adults today, and studying the relationship between fascia and pain can help in the clinical search for effective treatments. However, in the face of the vast amount of research findings, there is no systematic assessment of the relationship between fascia and pain in a bibliometric analysis. Therefore, the purpose of this study is to analyze studies on fascia and pain using CiteSpace and VOSviewer to identify research hotspots and future directions.Materials and Methods: A total of 744 papers related to fascia and pain from 2013 to 2022 were collected from the core collection database of Web of Science, and the authors, countries, institutions, keyword co-occurrence, keyword clustering, and keyword emergence were analyzed by CiteSpace and VOSviewer to construct a knowledge map.Results: Literature publication has shown an overall upward trend over the past decade, but there have been some fluctuations. Carmelo Pirri, Caterina Fede, and Raffaele De Caro are the top three authors with the most articles. The United States, China, and Spain are major contributors to fascial and pain research. The University of Padua, Universidad Complutense and Harvard Medical School are leading institutions in this field. However, it is noteworthy that the collaboration between authors, countries and institutions is not active. Keyword analysis showed that hot spots and trends in research on fascia and pain focused on hot diseases, major interventions, and mechanism exploration.Conclusion: This analysis identifies the most influential authors, institutions, and countries in the field of fascial and pain research and provides a reference for assessing their academic impact. The analysis of keywords and co-cited literature is useful for analyzing research hotspots and their evolution, as well as for predicting future trends.Keywords: fascia, pain, bibliometrics analysis, knowledge graph, research progress

Ting Lan,1,&ast; Yang Zhao,1,2,&ast; Yu Du,1,3,&ast; Chunyi Ma,1 Rui Wang,1 Qianlei Zhang,1 Shanshan Wang,1 Wenxian Wei,4 Honghua Yuan,2 Qingli Huang1,2 1Medical Technology School of Xuzhou Medical University, Xuzhou City, Jiangsu, 221000, People’s Republic of China; 2Public Experimental Research Center of Xuzhou Medical University, Xuzhou City, Jiangsu, 221004, People’s Republic of China; 3Xuzhou Center for Disease Control and Prevention, Xuzhou City, Jiangsu, 221006, People’s Republic of China; 4Testing Center, Yangzhou University, Yangzhou City, Jiangsu, 225009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Honghua Yuan, Public Experimental Research Center of Xuzhou Medical University, Tong Shan No. 209, Xuzhou, 221004, People’s Republic of China, Tel/Fax +86-516-83262091, Email XUYIyhh@xzhmu.edu.cn Qingli Huang, Medical Technology School, Public Experimental Research Center of Xuzhou Medical University, Tong Shan No. 209, Xuzhou, 221004, People’s Republic of China, Tel/Fax +86-516-83262091, Email qlhuang@xzhmu.edu.cnPurpose: A novel CYPA-targeted, SiO2 encapsulated Au star@AgAu yolk-shell nanostructure (YSNS) was synthesized and used for ovarian cancer early diagnosis and therapy.Methods: Diverse spectroscopic and microscopic methods were utilized to investigate the pattern of the yolk-shell nanostructure. In addition, in vitro and in vivo experiments were carried out.Results: It can be found that the ratio of HAuCl4 and AgNO3 played a critical role in the constitution of the yolk-shell nanostructure. The as-prepared yolk-shell nanostructure showed excellent SERS performance, which could be utilized as SERS substrate for specific sensitivity analysis of ovarian cancer markers cyclophilin A (CYPA) with detectable limit of 7.76&ast;10− 10 μg/mL. In addition, the as-prepared yolk-shell nanostructure possessed outstanding photothermal performance, which could be used as photothermal agent for ovarian cancer therapy. Experiments in vitro and in vivo proved that the as-prepared yolk-shell nanostructures are ideal candidate for early diagnosis and therapy for ovarian cancer in one platform.Conclusion: This work holds promise to offer a new method for the detection and therapy of ovarian cancer in the early stage.Graphical Abstract: Keywords: yolk-shell nanostructure, surface-enhanced Raman scattering, early diagnosis, cancer targeted therapy

Zhaohua Yang,1,&ast; Jinying Wei,1,&ast; Yashu Wang,1 Yunxia Du,1 Shan Song,1 Jiawei Li,2 Ziyuan Su,2 Yonghong Shi,1 Haijiang Wu1 1Department of Pathology, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China; 2Basic Medical College, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haijiang Wu, Email haijianglaoqi@163.comBackground: The primary pathophysiology of diabetic kidney disease (DKD) is tubulointerstitial fibrosis (TIF), and an essential contributing element is excessive extracellular matrix deposition. Irisin is a polypeptide formed by splitting fibronectin type III domain containing 5 (FNDC5), which participates in a number of physiological and pathological processes.Methods: The purpose of this article is to examine irisin’s function in DKD and analyze both its in vitro and in vivo effects. The Gene Expression Omnibus (GEO) database was used to download GSE30122, GSE104954, and GSE99325. Analysis of renal tubule samples from nondiabetic and diabetic mice identified 94 differentially expressed genes (DEGs). The transforming growth factor beta receptor 2 (TGFBR2), irisin, and TGF-β 1 were utilized as DEGs to examine the impact of irisin on TIF in diabetic kidney tissue, according to the datasets retrieved from the GEO database and Nephroseq database. Additionally, the therapeutic impact of irisin was also examined using Western blot, RT-qPCR, immunofluorescence, immunohistochemistry, and kits for detecting mouse biochemical indices.Results: In vitro, the findings demonstrated that irisin not only down-regulated the expression of Smad4 and β-catenin but also reduced the expression of proteins linked to fibrosis, the epithelial-mesenchymal transition (EMT), and mitochondrial dysfunction in HK-2 cells maintained in high glucose (HG) environment. In vivo, overexpressed FNDC5 plasmid was injected into diabetic mice to enhance its expression. Our studies found that overexpressed FNDC5 plasmid not only reversed the biochemical parameters and renal morphological characteristics of diabetic mice but also alleviated EMT and TIF by inhibiting Smad4/β-catenin signaling pathway.Conclusion: The above experimental results revealed that irisin could reduce TIF in diabetic mice via regulating the Smad4/β-catenin pathway.Keywords: irisin, diabetic kidney disease, tubulointerstitial fibrosis, Smad4, β-catenin

Xiaojing Yin,1,&ast; Yongkang Lai,1,2,&ast; Yiqi Du,1,&ast; Tinglin Zhang,3,&ast; Jie Gao,3 Zhaoshen Li1 1Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China; 2Department of Gastroenterology, Ganzhou People’s Hospital Affiliated to Nanchang University, Ganzhou, Jiangxi, 341000, People’s Republic of China; 3Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaoshen Li; Jie Gao, Email zhsl@vip.163.com; gaojiehighclea@smmu.edu.cnAbstract: Helicobacter pylori (H. pylori) is an infectious pathogen and the leading cause of gastrointestinal diseases, including gastric adenocarcinoma. Currently, bismuth quadruple therapy is the recommended first-line treatment, and it is reported to be highly effective, with > 90% eradication rates on a consistent basis. However, the overuse of antibiotics causes H. pylori to become increasingly resistant to antibiotics, making its eradication unlikely in the foreseeable future. Besides, the effect of antibiotic treatments on the gut microbiota also needs to be considered. Therefore, effective, selective, antibiotic-free antibacterial strategies are urgently required. Due to their unique physiochemical properties, such as the release of metal ions, the generation of reactive oxygen species, and photothermal/photodynamic effects, metal-based nanoparticles have attracted a great deal of interest. In this article, we review recent advances in the design, antimicrobial mechanisms and applications of metal-based nanoparticles for the eradication of H. pylori. Additionally, we discuss current challenges in this field and future perspectives that may be used in anti-H. pylori strategies.Keywords: H. pylori, antimicrobial applications, metal based nanoparticles, antibiotic-free, antimicrobial mechanisms

Xuemei Wang,1 Chenxi Liu,2 Yaling Du,3 Dan Wang,4 Xinping Zhang2 1Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, People’s Republic of China; 2School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 3First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, People’s Republic of China; 4School of Management, Hubei University of Chinese Medicine, Wuhan, Hubei Province, People’s Republic of ChinaCorrespondence: Dan Wang, School of Management, Hubei University of Chinese Medicine, Wuhan, Hubei Province, People’s Republic of China, Email 815310016@qq.com Xinping Zhang, school of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China, Email xpzhang602@hust.edu.cnPurpose: Healthcare-associated infections (HCAIs) have become a global public health problem, resulting in high mortality, serious morbidity, and heavy healthcare costs. Infection prevention and control (IPC) is a significant priority for healthcare workers (HCWs) to eliminate HCAIs. However, barriers exist in the IPC implementation in daily clinical work. This study aimed to explore the relationship between HCWs’ knowledge, attitudes, barrier perception, as well as their effects on IPC practice.Patients and Methods: A structured questionnaire survey was conducted among HCWs who were responsible for IPC in a large tertiary hospital in China. Cronbach’s alpha, average variance extracted (AVE), composite reliability (CR), as well as confirmatory factor analyses (CFA) were performed for reliability and validity. Structural equation modelling (SEM) was applied to establish the relationship between knowledge, attitudes, barrier perception and IPC practice. A Multiple Indicators Multiple Causes (MIMIC) model was conducted to detect the effects of covariates on factor structure.Results: In total, 232 valid questionnaires were eventually collected. The average score of knowledge, attitudes, barrier perception and IPC practice were 2.95± 0.75, 4.06± 0.70, 3.14± 0.86, and 4.38± 0.45, respectively. The instrument demonstrated good reliability and validity. The SEM results showed that knowledge was positively associated with attitudes (β=0.151, p=0.039), and attitudes had positive effects on IPC practice (β=0.204, p=0.001), whereas barrier perception was negatively associated with attitudes and IPC practice (β=− 0.234, p< 0.001; β=− 0.288, p< 0.001, respectively). Additionally, time proportion spent on IPC was significantly associated with attitudes and practice (β=0.180, p=0.015; β=0.287, p< 0.001, respectively), and training on HCAIs was a predicator for barrier perception and practice (β=0.192, p=0.039; β=− 0.169, p=0.038, respectively).Conclusion: IPC practice was indirectly affected by knowledge through the mediation of attitudes, whereas barrier perception had a negative impact. Designing deficiency-based training programs, developing sustained IPC habits, and strengthening management support are recommended to optimize IPC practice.Keywords: healthcare-associated infections, infection prevention and control, knowledge, attitudes, barrier perception, structural equation modelling

Zeli Xun,1,&ast; Pengfei Gao,2,3,&ast; Yanan Du,1 Xue Yan,3 Jingmin Yang,2– 4 Zhihua Wang1 1Department of Endocrinology, Xi’an Children’s Hospital, Shanxi, People’s Republic of China; 2State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People’s Republic of China; 3Shanghai WeHealth Biomedical Technology Co, Ltd, Shanghai, People’s Republic of China; 4Key Laboratory of Birth Defects and Reproductive Health of National Health and Family Planning Commission (Chongqing Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning, Science and Technology Research Institute), Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihua Wang, Xi’an Children’s Hospital, Shanxi, 710002, People’s Republic of China, Email xasetyy@126.comAim: Mutations in the SLC12A3 gene have been reported to cause Gitelman syndrome (GS), characterized by hypokalemic metabolic alkalosis. The aim of this research is to investigate the genetic mutations and clinical features of patients with clinical suspicion of GS.Methods: Six families were enrolled. The symptoms, clinical examination, laboratory results, genotypes, and effect of mutations on mRNA splicing were analyzed. Genomic DNA was screened for gene variations using whole exome sequence and Sanger sequencing. DNA sequences were compared with reference sequences.Results: Genetic analysis revealed nine genetic variants of SLC12A3, including three novel heterozygous mutations (c.1096– 2A>G, c.1862A>G, and c.2747+4del) and six previously characterized mutations (c.965– 1_976delinsACCGAAAATTTT, c.506– 1G>A, c.602– 16G>A, c.533C >T, c.1456 G>A, and c.1108 G>C). Probands presented with the clinical syndrome of hypokalemia, increased plasma renin, hypocalciuria and hypokalemic alkalosis.Conclusion: These clinical manifestations and genotypes were consistent with the diagnostic criteria of GS. The study described the phenotypes and genotypes of six pedigrees involving GS patients, demonstrating the importance of SLC12A3 gene screening for GS. This study expands the mutation spectrum of SLC12A3 gene in GS.Keywords: SLC12A3, Gitelman syndrome, gene mutation, mRNA splicing, clinical characteristics

Ruobing Jiang,1,&ast; Xin Ta,1,&ast; Min Xu,2 Zhihua Luo,3 Yijun Du,4 Xing Zhong,4 Tianrong Pan,4 Xiujing Cao1 1Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Endocrinology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Department of Pediatrics, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 4Department of Endocrinology, Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiujing Cao, Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China, Email xiujing.cao@ahmu.edu.cn Tianrong Pan, Department of Endocrinology, Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People’s Republic of China, Email ptr1968@163.comObjective: To investigate the current status of diabetes self-care behavior and the association between depression, self-efficacy and self-care in a sample of Chinese elderly type 2 diabetes mellitus (T2DM) patients.Methods: A cross-sectional study with a convenient sample including 240 elderly T2DM patients collected the data of demographic characteristics, diabetes self-care behavior, self-efficacy and depression status. The difference of self-care behavior in different sample characteristics was compared by independent t-test. The Personal correlation analysis was employed to examine the correlation of study variables. The method of bootstrap was used to analyze mediating role of depression.Results: Only 22.5% of patients reported better diabetes self-care behavior and depression partly mediated the association between self-efficacy and self-care behavior. The significant coefficient of path a (B = − 0.052, p < 0.001) and path b (B = − 0.423, p < 0.05) indicated negative associations of self-efficacy on depression, and depression on self-care behavior. The indirect effect (Path a × b) between self-efficacy and self-care behavior through depression was significant (B = 0.022, p < 0.05), the 95% bias-corrected bootstrap confidence interval was 0.004 to 0.006. Meanwhile, the mediating role of depression was not found significant among the participants reported 60– 74 years old (B = 0.104, p < 0.001). But depression completely mediated this association among the participants reported 75– 89 years old (B = 0.034, p > 0.05).Conclusion: The level of diabetes self-care behavior among the elderly T2DM patients in Dahu community of Anqing city was hardly optimistic. The self-efficacy focused intervention could be encouraged for community and clinicians to improve diabetes self-care behavior. Moreover, the prevalence of depression and T2DM is increasing in younger population. More work is needed to confirm these findings, especially conducting cohort studies on different populations.Keywords: diabetes self-care behavior, the elderly, type 2 diabetes mellitus, diabetes management self-efficacy, depression

Yuetong Du,1 Jian Raymond Rui,1 Nan Yu2 1Department of New Media and Communication, South China University of Technology, Guangzhou, Guangdong Province, People’s Republic of China; 2Nicolson School of Communication and Media, University of Central Florida, Orlando, FL, USACorrespondence: Jian Raymond Rui, Tel +86 178 1972 0631, Email ruijian@scut.edu.cnIntroduction: Social media enable advertisers to promote products by placing ads into videos posted by social media influencers. However, according to psychological reactance theory, any persuasive attempt may evoke reactance. Therefore, how to minimize the audience’s potential resistance to product placements is important. This study investigated how the parasocial relationship (PSR) between audiences and influencers as well as the extent to which the influencer’s expertise matched the product (termed as influencer-product congruence) shaped audience attitude towards the product placement and their purchase intention through reactance.Methods: The study conducted a 2 (PSR: high vs low) × 2 (influencer-product congruence: congruent vs incongruent) between-subjects online experiment (N = 210) to test hypotheses. SPSS 24 and PROCESS macro by Hayes were used to analyze the data.Results: The results demonstrate that PSR and influencer-product congruence enhanced the audience’s attitude and purchase intention. Moreover, these positive effects were mediated by lowering levels of the audience’s reactance. Additionally, we found preliminary evidence suggesting that PSR moderated the effect of perceived expertise of the influencer on reactance. Specifically, this effect was stronger among those reporting a low level of PSR compared to a high level.Conclusion: Our findings reveal how PSR and influencer-product congruence are intertwined to shape audience evaluation of product placement via social media and highlight the central role of reactance in this process. This study also provides advice on the selection of influencer when promoting product placement on social media.Keywords: product placement, psychological reactance, parasocial relationship, match-up hypothesis, influencer marketing

Yiting Du,1,2 Limin Zuo,2 Ying Xiong,1 Xuedong Wang,3 Jun Zou,2 Hong Xu1 1Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 3Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Ying Xiong, Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Sec. 3 No. 17, South Renmin Road, Chengdu, 610041, People’s Republic of China, Email xiongying20006@163.comBackground: Bronchopulmonary dysplasia (BPD) refers to a chronic lung disease which is commonly observed in preterm infants. It can usually be caused by several pathological processes that endanger the long-term lung development, such as inflammation and immune dysfunction.Methods: In this study, a bioinformatics approach was applied to identify the differentially expressed immune-related genes (DEIRGs). We downloaded the transcriptional profiles (GSE32472 dataset) from the Gene Expression Omnibus (GEO) database and performed gene set enrichment analysis (GSEA). Cell type Identification By Estimating Relative Subsets of RNA Transcripts (CIBERSORT), microenvironment cell populations counter (MCPcounter), and Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) were used for the analysis of the immune cell infiltration landscape of BPD. A weighted co-expression network was subsequently constructed using weighted gene co-expression network analysis (WGCNA) to screen candidate differentially expressed immune related genes (DEIRGs).Results: GSEA results indicated that immune-related pathways were mainly involved in BPD. Ten significantly different immune cell types were observed between BPD and normal groups. A total of 228 DEGs in the turquoise module were identified, and 31 DEIRGs were further identified. Cluster of the differentiation 8 alpha (CD8A) expression was down-regulated in BPD, and its expression was validated by the GSE25286, GSE25293, GSE99633 datasets and qRT-PCR. In addition, CD8A expression was closely associated with immune cells infiltration, especially T cells CD8 and neutrophil.Conclusion: A distinct immune cell infiltration landscape was found between BPD and normal group. CD8A can be a novel candidate biomarker for BPD, which plays an essential role in the onset and progress of hyperoxia-related BPD via the disruption of immune cell functions.Keywords: bronchopulmonary dysplasia, CD8A, preterm infants, immunocytes infiltrate, hyperoxia

Meina Feng,&ast; Wenxian Tu,&ast; Qin Zhou, Yuanmin Du, Kang Xu, Yunfeng Wang Department of Neurology, Wuhan Brain Hospital, General Hospital of the YANGTZE River Shipping, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunfeng Wang, Email wyf4get@aliyun.comPurpose: The objective of this paper is to explore the role of circHECTD1 in vascular smooth muscle cells (VSMCs) and atherosclerosis (AS).Methods: VSMCs were treated with platelet-derived growth factor-BB (PDGF-BB) in vitro, and the level of circHECTD1 was determined using qRT-PCR. Cell proliferation, migration, and invasion were analyzed using CCK8 and transwell assays. Cell apoptosis and cell cycle were analyzed using flow cytometry. The binding interaction between circHECTD1 and KHDRBS3 or EZH2 was investigated using the RIP, RNA pull-down.Results: CircHECTD1 was upregulated in PDGF-BB-induced VSMCs with a dose-dependent and time-dependent manner. Knockdown of circHECTD1 suppressed VSMCsproliferation and migration and enhanced cell apoptosis in VSMCs, while circHECTD1 overexpression yielded opposite effects. Mechanistically, circHECTD1 could interact with KHDRBS3, thus enhanced the stability of EZH2 mRNA and increased EZH2 protein level. In addition, silencing EZH2 in VSMCs reversed the proliferation-enhancing effect of circHECTD1 overexpression.Conclusion: Our findings provided providing a potential prognostic and therapy biomarker for AS.Keywords: circHECTD1, KHDRBS3, EZH2, VSMCs, atherosclerosis

He Li,1,&ast; Yingjie Du,1,&ast; Wenjing Yang,1 Yue Wang,1 Shaofei Su,2 Xiaoyan Zhao,1 Guyan Wang1 1Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Central Laboratory, Beijing Obstetrics and Gynecology 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 Dongjiaominxiang, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-13910985139, Fax +86-10-58268017, Email guyanwang2006@163.comPurpose: Regarding the quality of surgical field visibility, previous studies and meta-analyses comparing total intravenous anesthesia (TIVA) and inhalational anesthesia (IA) in endoscopic sinus surgery (ESS) have presented inconsistent findings. Considering that IA has some advantages over TIVA, we aimed to test the hypothesis that IA with sevoflurane-remifentanil is noninferior to TIVA with propofol-remifentanil in terms of surgical field visibility quality during ESS.Patients and Methods: In this randomized, double-blind, noninferiority clinical trial, 110 adult patients were recruited and randomly assigned to the IA (n = 55) or TIVA (n = 55) group. The primary outcome was the quality of surgical field visibility, as measured by the intraoperative mean Boezaart score (BS). Additionally, post hoc analysis was performed for patients with Lund-Mackay scores of ≤ 12 or > 12. Other secondary outcomes included total blood loss, bleeding rate, total fluid, mean arterial pressure, heart rate, dose of remifentanil for anesthesia maintenance, end-tidal CO2, length of stay in the post anesthesia care unit, postoperative hypoxemia, sore throat, and nausea.Results: The intraoperative mean BS of the IA group was noninferior to that of the TIVA group [medians with interquartile ranges (IQRs), 2.0 (1.7– 2.2) vs 2.0 (1.8– 2.1), P = 0.923]. Moreover, post hoc analysis confirmed no difference between IA and TIVA for patients with Lund-Mackay scores ≤ 12 (P = 0.403) or > 12 (P = 0.226). No differences in total blood loss, bleeding rate, or other intraoperative indicators or complications were observed between groups.Conclusion: Regarding surgical field visibility during ESS, IA with sevoflurane-remifentanil is noninferior to TIVA with propofol-remifentanil anesthesia maintenance.Keywords: sevoflurane, remifentanil, propofol, blood loss, bleeding rate, Boezaart score

Chaofan Wang, Yimei Du, Lingbo Bi, Xuewen Lin, Min Zhao, Weixin Fan Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Weixin Fan, Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Gulou District, Nanjing, Jiangsu Province, People’s Republic of China, Tel +86 13327805737, Email hairmanfwx@163.comIntroduction: Androgenetic alopecia (AGA) has negative impacts on both men and women in terms of appearance and mental stress. Spironolactone is a synthetic aldosterone receptor antagonist known to stimulate hair growth and has been widely used by dermatologists to treat AGA.Objective: To conduct a systematic review evaluating the efficacy and safety of topical and oral spironolactone in AGA treatment.Methods: We searched PubMed, Embase, the Cochrane Library, and the Web of Science until October 23rd, 2022, for human studies evaluating the efficacy of spironolactone for the treatment of AGA, regardless of doses and routes.Results: We retrieved 784 papers and ultimately 7 articles matched our inclusion criteria and comprised 618 AGA patients (65 men, 553 women), 414 of them received spironolactone treatment. Oral spironolactone doses ranged from 25mg to 200mg daily, with the vast majority between 80mg and 110 mg. Dosage forms for topical spironolactone use include gels of 1% and solutions of 5% twice daily. Both oral and topical spironolactone have been shown efficacy for alopecia recovery, but topical use has significantly fewer side effects and is suitable for any gender. It showed better efficacy in combination with other therapies such as oral or topical minoxidil compared with monotherapy.Conclusion: Spironolactone is an effective and safe treatment of androgenic alopecia which can enhance the efficacy when combined with other conventional treatments such as minoxidil. Topical spironolactone is safer than oral administration and is suitable for both male and female patients, and is expected to become a common drug for those who do not have a good response to minoxidil. Furthermore, more high-quality clinical randomized controlled studies should be performed.Keywords: androgenetic alopecia, spironolactone, dosage, combine therapy, efficacy, adverse effects

Zhiwei Zhang,1,&ast; Jiawei Zhuang,2,&ast; Daohan Sun,3,&ast; Qingwei Ding,1 Hui Zheng,1 Haixiang Li,1 Xiaoyu Zhang,1 Yaming Du,3 Teng Ma,1 Qingyou Meng1 1Department of Vascular Surgery, General Surgery Clinical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Cardiovascular Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 3Department of Vascular Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingyou Meng; Teng Ma, Email mengqy@163.com; m_aeolus@163.comBackground: Abdominal aortic aneurysms (AAAs) are a global health and economic burden. Therapeutic strategies to inhibit the progression of AAAs are currently lacking. Recently, the therapeutic effect of metformin on aneurysms has attracted considerable interest. However, the unfavorable pharmacokinetic properties of metformin limit its feasibility for AAA treatment.Methods and Results: We constructed a metformin-loaded netrin-1-responsive AAA-targeted nanoparticle (Tgt-NP-Met) for AAA management. Evaluation of the therapeutic effect of Tgt-NP-Met was performed by in vitro and in vivo experiments. Our results showed that the binding of netrin-1 monoclonal antibodies enhanced the AAA-targeting capability of nanoparticles (NPs). Moreover, Tgt-NP-Met administration prevented AAA development and reduced the aneurysm diameter in apolipoprotein E (ApoE)-deficient (ApoE−/−) mice that received continuous infusion of angiotensin II. Furthermore, metformin prevented AAA progression by inhibiting the transformation of vascular smooth muscle cells (VSMCs) from a contractile phenotype to a synthetic phenotype, which is mediated by macrophage infiltration and activation.Conclusion: Our findings identify metformin as a functional suppressor for macrophage-mediated phenotypic transformation of VSMCs and Tgt-NP-Met as an efficient therapeutic strategy for AAA management.Graphical Abstract: Keywords: abdominal aortic aneurysm, nanoparticle, metformin, macrophage

Jianyi Li,1,&ast; Keke Li,2,&ast; Yukun Du,1,&ast; Xiaojie Tang,3,&ast; Chenjing Liu,1 Shannan Cao,3 Baomeng Zhao,2 Hai Huang,3 Hongri Zhao,3 Weiqing Kong,1 Tongshuai Xu,3 Cheng Shao,1 Jiale Shao,1 Guodong Zhang,4 Hongbo Lan,5 Yongming Xi1 1Department of Orthopaedic Surgery, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Yantai Campus of Binzhou Medical University, Yantai, People’s Republic of China; 3Yantai Affiliated Hospital of Binzhou Medical University, Yantai, People’s Republic of China; 4Tengzhou Central People’s Hospital, Tengzhou, People’s Republic of China; 5Shandong Engineering Research Center for Additive Manufacturing Qingdao University of Technology, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongming Xi, Department of Orthopaedic Surgery, the Affiliated Hospital of Qingdao University, Qingdao, 266071, People’s Republic of China, Email xym700118@163.com Hongbo Lan, Shandong Engineering Research Center for Additive Manufacturing Qingdao University of Technology, Qingdao, 266520, People’s Republic of China, Email hblan99@126.comBackground: Successful treatment of infectious bone defect remains a major challenge in the orthopaedic field. At present, the conventional treatment for infectious bone defects is surgical debridement and long-term systemic antibiotic use. It is necessary to develop a new strategy to achieve effective bone regeneration and local anti-infection for infectious bone defects.Methods: Firstly, vancomycin / poly (lactic acid-glycolic acid) sustained release microspheres (VAN/PLGA-MS) were prepared. Then, through the dual-nozzle 3D printing technology, VAN/PLGA-MS was uniformly loaded into the pores of nano-hydroxyapatite (n-HA) and polylactic acid (PLA) scaffolds printed in a certain proportion, and a composite scaffold (VAN/MS-PLA/n-HA) was designed, which can not only promote bone repair but also resist local infection. Finally, the performance of the composite scaffold was evaluated by in vivo and in vitro biological evaluation.Results: The in vitro release test of microspheres showed that the release of VAN/PLGA-MS was relatively stable from the second day, and the average daily release concentration was about 15.75 μg/mL, which was higher than the minimum concentration specified in the guidelines. The bacteriostatic test in vitro showed that VAN/PLGA-MS had obvious inhibitory effect on Staphylococcus aureus ATCC-29213. Biological evaluation of VAN/MS-PLA/n-HA scaffolds in vitro showed that it can promote the proliferation of adipose stem cells. In vivo biological evaluation showed that VAN/MS-PLA/n-HA scaffold could significantly promote bone regeneration.Conclusion: Our research shows that VAN/MS-PLA/n-HA scaffolds have satisfying biomechanical properties, effectively inhibit the growth of Staphylococcus aureus, with good biocompatibility, and effectiveness on repairing bone defects. The VAN/MS-PLA/n-HA scaffold provide the clinic with an application prospect in bone tissue engineering.Graphical Abstract: Keywords: osteogenesis, dual-nozzle 3D printing technology, drug-loaded microspheres, vancomycin, nano-hydroxyapatite