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Xinbo Zhang, Bin Xu, Jiangwei Ni, Yucheng Xiang, Zhifeng He Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Zhifeng He, Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Email hezhifeng@wzhospital.cnPurpose: The chemotherapeutic agent doxorubicin (DOX) is limited by its cardiotoxicity, posing challenges in its application for non-small cell lung cancer (NSCLC). This study aims to explore the efficacy of polydopamine/Au nanoparticles loaded with DOX for chemotherapy and photothermal therapy in NSCLC to achieve enhanced efficacy and reduced toxicity.Methods: Hollow polydopamine (HPDA)/Au@DOX was synthesized via polydopamine chemical binding sacrificial template method. Morphology was characterized using transmission electron microscopy, particle size and potential were determined using dynamic light scattering, and photothermal conversion efficiency was assessed using near-infrared (NIR) thermal imaging. Drug loading rate and in vitro drug release were investigated. In vitro, anti-tumor experiments were conducted using CCK-8 assay, flow cytometry, and live/dead cell staining to evaluate the cytotoxicity of HPDA/Au@DOX on A549 cells. Uptake of HPDA/Au@DOX by A549 cells was detected using the intrinsic fluorescence of DOX. The in vivo anti-metastasis and anti-tumor effects of HPDA/Au@DOX were explored in mouse lung metastasis and subcutaneous tumor models, respectively.Results: HPDA/Au@DOX with a particle size of (164.26± 3.25) nm, a drug loading rate of 36.31%, and an encapsulation efficiency of 90.78% was successfully prepared. Under 808 nm laser irradiation, HPDA/Au@DOX accelerated DOX release and enhanced uptake by A549 cells. In vitro photothermal performance assessment showed excellent photothermal conversion capability and stability of HPDA/Au@DOX under NIR laser irradiation. Both in vitro and in vivo experiments demonstrated that the photothermal-chemotherapy combination group (HPDA/Au@DOX+NIR) exhibited stronger anti-metastatic and anti-tumor activities compared to the monotherapy group (DOX).Conclusion: HPDA/Au@DOX nanosystem demonstrated excellent photothermal effect, inhibiting the growth and metastasis of A549 cells. This nanosystem achieves the combined effect of chemotherapy and photothermal, making it promising for NSCLC treatment. Keywords: non-small cell lung cancer, chemotherapy, photothermal therapy, doxorubicin, Au nanoparticles

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

Jiaxin Zan,1,2 Xiaojing Dong,1,2 Hong Yang,1,2 Jingjing Yan,1,2 Zixuan He,3 Jing Tian,3 Yanbo Zhang1,2,4 1Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Taiyuan, People’s Republic of China; 3Department of Cardiology, The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4School of Health Services and Management, Shanxi University of Chinese Medicine, Taiyuan, People’s Republic of ChinaCorrespondence: Jing Tian; Yanbo Zhang, School of Public health, Shanxi Medical University, 56 Xinjian Road, Taiyuan, Shanxi Province, People’s Republic of China, Tel/Fax +86 15535406059, Email 1105551933@qq.com; sxmuzyb@126.comPurpose: This study sought to develop an unbalanced-ensemble model that could accurately predict death outcomes of patients with comorbid coronary heart disease (CHD) and hypertension and evaluate the factors contributing to death.Patients and Methods: Medical records of 1058 patients with coronary heart disease combined with hypertension and excluding those acute coronary syndrome were collected. Patients were followed-up at the first, third, sixth, and twelfth months after discharge to record death events. Follow-up ended two years after discharge. Patients were divided into survival and nonsurvival groups. According to medical records, gender, smoking, drinking, COPD, cerebral stroke, diabetes, hyperhomocysteinemia, heart failure and renal insufficiency of the two groups were sorted and compared and other influencing factors of the two groups, feature selection was carried out to construct models. Owing to data unbalance, we developed four unbalanced-ensemble prediction models based on Balanced Random Forest (BRF), EasyEnsemble, RUSBoost, SMOTEBoost and the two base classification algorithms based on AdaBoost and Logistic. Each model was optimised using hyperparameters based on GridSearchCV and evaluated using area under the curve (AUC), sensitivity, recall, Brier score, and geometric mean (G-mean). Additionally, to understand the influence of variables on model performance, we constructed a SHapley Additive explanation (SHAP) model based on the optimal model.Results: There were significant differences in age, heart rate, COPD, cerebral stroke, heart failure and renal insufficiency in the nonsurvival group compared with the survival group. Among all models, BRF yielded the highest AUC (0.810; 95% CI, 0.778– 0.839), sensitivity (0.990; 95% CI, 0.981– 1.000), recall (0.990; 95% CI, 0.981– 1.000), and G-mean (0.806; 95% CI, 0.778– 0.827), and the lowest Brier score (0.181; 95% CI, 0.178– 0.185). Therefore, we identified BRF as the optimal model. Furthermore, red blood cell count (RBC), body mass index (BMI), and lactate dehydrogenase were found to be important mortality-associated risk factors.Conclusion: BRF combined with advanced machine learning methods and SHAP is highly effective and accurately predicts mortality in patients with CHD comorbid with hypertension. This model has the potential to assist clinicians in modifying treatment strategies to improve patient outcomes. Keywords: coronary heart disease comorbid with hypertension, ensemble learning, balanced random forest, SHAP, Prognosis

Pan Gao,1,&ast; Xinyu Li,1,&ast; Ziqiu He,1 Yifan Xu,2 Zhi Zhang1 1Department of Urology, Second People’s Hospital of Yichang, Second People’s Hospital of China Three Gorges University, Yichang, Hubei Province, People’s Republic of China; 2Department of Pathology, Second People’s Hospital of Yichang, Second People’s Hospital of China Three Gorges University, Yichang, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi Zhang, Department of Urology, Second People’s Hospital of Yichang, Second People’s Hospital of China Three Gorges University, 21 Xiling One Road, Yichang, Hubei Province, 443000, People’s Republic of China, Email 702032715@qq.comAbstract: Primary bladder large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive neoplasm with high recurrence rates and poor prognosis. Traditional management has heavily relied on radical cystectomy, which, despite its aggressiveness, often results in unsatisfactory outcomes. Emerging evidence suggests the potential for less invasive, bladder-sparing approaches, yet detailed reports and long-term outcomes remain scarce. We report a groundbreaking case of a 59-year-old male diagnosed with primary bladder LCNEC, managed through a pioneering bladder-sparing multimodal treatment. This novel strategy included transurethral resection followed by a tailored chemoradiation protocol, resulting in exceptional disease control and preservation of bladder function over a 20-month follow-up period, without evidence of recurrence. This case underscores the viability of bladder conservation strategies as a legitimate alternative to radical cystectomy for managing LCNEC, presenting a beacon of hope for patients wishing to preserve bladder functionality. It prompts a reevaluation of traditional treatment paradigms and advocates for further research into multimodal, organ-sparing approaches for this challenging malignancy.Keywords: LCNEC, bladder conservation, TURBT, secondary transurethral resection, EP regimen, radiotherapy

Christian S Chan,1,2 Tammy Smith,3 Zemiao He,4 Carrie Garter3 1Department of Psychology, The University of Hong Kong, Hong Kong SAR, People’s Republic of China; 2Department of Psychology and Linguistics, International Christian University, Tokyo, Japan; 3P&G Beauty, Cincinnati, OH, USA; 4P&G Beauty, SingaporeCorrespondence: Tammy Smith, P&G Beauty, Cincinnati, OH, USA, Email smith.tj.2@pg.comIntroduction: The psychological impact of dandruff has been largely understudied.Methods: In this cross-sectional study (N = 2116), we examined the consequences of self-perception of dandruff severity on mental health, quality of life, and sleep quality among Chinese adults. Additionally, we examined the moderating factors that influence these associations.Results: Bivariate analyses revealed that greater self-perceived dandruff severity was associated with poorer mental health, lower quality of life, and reduced sleep quality. Furthermore, dandruff severity was positively correlated with appearance anxiety, feelings of helplessness, and perceived stigma. Individuals with more severe dandruff experienced increased teasing and ostracism and, subsequently, heightened psychological distress. Moderation analyses demonstrated that females were more adversely affected by dandruff than males, and those with comorbid skin conditions or a history of being teased and ostracized during adolescence due to dandruff experienced exacerbated negative outcomes.Discussion: This study highlights the need for further research on the psychological consequences of self-perceived severity of dandruff and potential interventions to mitigate its impact.Keywords: dandruff, quality of life, psychological distress, sleep quality

Xuan Wei,1,2,&ast; Yu Zhong,3,&ast; Xiaofei Yi,1 Tingting Li,1 Zhougui Ling,2 Moyu Ming,2 Shuang Zhang,1 Zhiyi He1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, People’s Republic of China; 3Department of Emergency Medicine, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiyi He, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, NO. 6 Shuangyong Road, Qingxiu District, Nanning City, Guangxi Zhuang Autonomous Region, People’s Republic of China, 530000, Tel +86 187 7801 7698, Email zhiyi-river@163.comObjective: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence, morbidity, and mortality. Chuankezhi (CKZ) injection, a Chinese patent medicine, has been commonly used for treating COPD. This study evaluated the clinical efficacy of CKZ injections in COPD patients and explored potential underlying mechanisms by integrating meta-analysis and network pharmacology.Research Methods: Randomized controlled trials (RCTs) were search in database by Web of Science, Cochrane Library and PubMed as of November 2022 for literature collection, and the Review Manager 5.4 was used to analyze the data. Through the network pharmacology method, the chemical components and their targets, as well as the disease targets were further analyzed.Results: A total of 15 RCTs including 1212 patients were included. The results of meta-analysis showed that CKZ injection can significantly improve the clinical effective rate (RR = 1.25, 95% CI: 1.14 to 1.36), and the clinical advantage was that it can significantly reduced acute exacerbation rate (RR = 0.29, 95% CI: 0.12 to 0.70) and COPD assessment test (CAT) scores (MD =− 4.62, 95% CI:-8.966 to-0.28). A total of 31 chemical compounds and 178 potential targets for CKZ injection were obtained from the online databases. Molecular docking revealed that most key components and targets could form stable structure.Conclusion: This systematic review with meta-analysis and network pharmacology demonstrates that CKZ could effectively improve the clinical efficacy and safety in the treatment of COPD. Such efficacy may be related to an anti-inflammatory effect and immunoregulation of CKZ via multiple components, multiple targets and multiple pathways. Keywords: meta-analysis, network pharmacology, chronic obstructive pulmonary disease, Chuankezhi injection

Yuwei Ma,1,2,&ast; Tao Jiang,1,2,&ast; Rong Zhang,1 Fei Liu,3 Shilong Song,1,2 Huijun Zhang,4 Jingwen Huang,1 Zelai He1,2 1The First Affiliated Hospital of Bengbu Medical University & Tumor Hospital Affiliated to Bengbu Medical University, Bengbu, 233004, People’s Republic of China; 2Department of Radiation Oncology, the First Affiliated Hospital of Bengbu Medical University & Tumor Hospital Affiliated to Bengbu Medical University, Bengbu, 233004, People’s Republic of China; 3Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, Molecular Diagnosis Center, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, People’s Republic of China; 4Department of Cardiothoracic Surgery, Huashan Hospital of Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zelai He; Jingwen Huang, Email hezelai@alumni.sjtu.edu.cn; he.ze.lai@163.com; byyfyhjw@163.comIntroduction: Lung cancer’s high incidence and dismal prognosis with traditional treatments like surgery and radiotherapy necessitate innovative approaches. Despite advancements in nanotherapy, the limitations of single-treatment modalities and significant side effects persist. To tackle lung cancer effectively, we devised a temperature-sensitive hydrogel-based local injection system with near-infrared triggered drug release. Utilizing 2D MXene nanosheets as carriers loaded with R837 and cisplatin (DDP), encapsulated within a temperature-sensitive hydrogel-forming PEG-MXene@DDP@R837@SHDS (MDR@SHDS), we administered in situ injections of MDR@SHDS into tumor tissues combined with photothermal therapy (PTT). The immune adjuvant R837 enhances dendritic cell (DC) maturation and tumor cell phagocytosis, while PTT induces tumor cell apoptosis and necrosis by converting light energy into heat energy.Methods: Material characterization employed transmission electron microscopy, X-ray photoelectron spectroscopy, phase transition temperature, and near-infrared thermography. In vitro experiments assessed Lewis cell proliferation and apoptosis using CCK-8, Edu, and TUNEL assays. In vivo experiments on C57 mouse Lewis transplant tumors evaluated the photothermal effect via near-infrared thermography and assessed DC maturation and CD4+/CD8+ T cell ratios using flow cytometry. The in vivo anti-tumor efficacy of MDR@SHDS was confirmed by tumor growth curve recording and HE and TUNEL staining of tumor sections.Results: The hydrogel exhibited excellent temperature sensitivity, controlled release properties, and high biocompatibility. In vitro experiments revealed that MDR@SHDS combined with PTT had a greater inhibitory effect on tumor cell proliferation compared to MDR@SHD alone. Combining local immunotherapy, chemotherapy, and PTT yielded superior anti-tumor effects than individual treatments.Conclusion: MDR@SHDS, with its simplicity, biocompatibility, and enhanced anti-tumor effects in combination with PTT, presents a promising therapeutic approach for lung cancer treatment, offering potential clinical utility.Keywords: 2D Mxene, drug delivery system, hydrogel, lung cancer

Wen-Bin Duan,1 Xiao-Hui Wang,2 Guo-Can Zhang,2 Zhuo He,1 Shao-Qiang Li,3 Jie Zhou1 1Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, 410005, People’s Republic of China; 3Hepatic Pancreatobiliary Surgery Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of ChinaCorrespondence: Xiao-Hui Wang, Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, 410005, People’s Republic of China, Tel +86-0731-83928052, Email xiaohuiwang21@163.com Jie Zhou, Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China, Tel +86-020-61641701, Email jacky_nfyy@163.comBackground: Lenvatinib or Sorafenib combined with programmed cell death protein-1 (PD-1) inhibitor as recommend treatment of advanced hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM). We aimed to compared the prognosis of Lenvatinib plus PD-1 inhibitor (Len+PD-1) versus Sorafenib plus PD-1 (Sora+PD-1) as an initial therapy for HCC with EHM.Methods: Incorporating a sum of 229 HCC patients with EHM were encompassed within this study, with 127 in the Sora+PD-1 group and 102 in the Len+PD-1 group. Through propensity score matching (PSM), we compared overall survival (OS), progression-free survival (PFS), and patient safety between these two groups.Results: The median OS were 13.0 months and 14.2 months in the Sora+PD-1 group and Len+PD-1 group. The 6-, 12-, and 24-month OS rates were 92.9%, 58.9% and 5.6% in Sora+PD-1 group and 93.1%, 61.8% and 22.6% in Len+PD-1 group, respectively. The Len+PD-1 group had obviously better OS than the Sora+PD-1 group (P = 0.002). The 3-, 6-, and 12-month PFS rates were 76.4%, 27.6% and 1.6% in Sora+PD-1 group and 86.2%, 50.5% and 12.2% in Len+PD-1 group, respectively. Compared with Sora+PD-1 group, the Len+PD-1 group had obviously better PFS (P < 0.001). Analysis within subgroups showed that OS was significant in patients receiving TACE in Len+PD-1 group than Sora+PD-1 group (p = 0.003).Conclusion: Len+PD-1 group had longer OS and PFS than Sora+PD-1 group for patient with EHM. In addition, OS in patients received TACE was improved with Len+PD-1 treatment. For patients without TACE, there was no significance between Sora+PD-1 and Len+PD-1 groups.Keywords: hepatocellular carcinoma, extrahepatic metastasis, lenvatinib, sorafenib, PD-1 inhibitor

Fang Liu,1,&ast; XuYong Yang,2,&ast; Zhaohui He,1 Chenghong OuYang,1 Xiaogang Yang,1 Chunli Yang1 1Department of Intensive Care Unit, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, People’s Republic of China; 2Department of Pediatrics, Gaoxin Hospital of The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaogang Yang; Chunli Yang, Department of intensive care unit, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, People’s Republic of China, Email JXSRMICU@163.com; 434533590@qq.comBackground: In addition to the well-known Whipple’s disease (WD), Tropheryma Whipplei (TW) can also lead to acute pneumonia. There is no unified consensus on the susceptible population, pathogenesis, clinical manifestations, diagnostic criteria, and treatment options for TW pneumonia.Clinical Presentation and Intervention: This is an elderly patient with multiple injuries caused by falling from a building, and was transferred to intensive care unit (ICU) for mechanical ventilation and empirical anti-infection treatment due to severe pneumonia, and then the results of targeted next-generation sequencing (tNGS) in patient’s bronchoalveolar lavage fluid (BALF) suggested TW and human metapneumovirus (HMPV) infection, and after switching to anti-infective therapy for TW, the patient was successfully extubated and transferred out of the ICU.Conclusion: This is the first case of using tNGS to diagnose severe pneumonia caused by TW and HMPV. We hope that our study can serve as a reference for the diagnosis and treatment of related cases in the future.Keywords: Tropheryma Whipplei, bronchoalveolar lavage fluid, targeted next-generation sequencing, human metapneumovirus

Qinzheng Chen,1 Zhen He,1 Yaxin Wang,2 Xuanjin Yang,2 Nana Liu,2 Suhan Zhang,2 Liangkun Ma,2 Xuezhong Shi,1 Xiaocan Jia,1 Yongli Yang,1 Yin Sun,2 Yuan He3 1Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences (CAMS) and PUMC, Beijing, People’s Republic of China; 3National Human Genetic Resources Center, National Research Institute for Family Planning, Beijing, People’s Republic of ChinaCorrespondence: Yin Sun, Department of Obstetrics and Gynecology, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences (CAMS) and PUMC, Beijing, 100730, People’s Republic of China, Email yinsun_pumch@163.com Yongli Yang, Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China, Email ylyang377@zzu.edu.cnPurpose: To assess the impact of maternal pre-pregnancy body mass index (BMI) on longitudinal fetal growth, and the potential mediation effect of the maternal fasting plasma glucose in first trimester.Methods: In this retrospective cohort study, we collected pre-pregnancy BMI data and ultrasound measurements during pregnancy of 3879 singleton pregnant women who underwent antenatal examinations and delivered at Peking Union Medical College Hospital. Generalized estimation equations, linear regression, and logistic regression were used to examine the association between pre-pregnancy BMI with fetal growth and adverse neonatal outcomes. Mediation analyses were also used to examine the mediating role of maternal fasting plasma glucose (FPG) in first trimester.Results: A per 1 Kg/m² increase in pre-pregnancy BMI was associated with increase fetal body length Z-score (β 0.010, 95% CI 0.001, 0.019) and fetal body weight (β 0.017, 95% CI 0.008, 0.027). In mid pregnancy, pre-pregnancy BMI also correlated with an increase Z-score of fetal abdominal circumference, femur length (FL). Pre-pregnancy BMI was associated with an increased risk of large for gestational age and macrosomia. Mediation analysis indicated that the associations between pre-pregnancy BMI and fetal weight in mid and late pregnancy, and at birth were partially mediated by maternal FPG in first trimester (mediation proportion: 5.0%, 8.3%, 1.6%, respectively).Conclusion: Maternal pre-pregnancy BMI was associated with the longitudinal fetal growth, and the association was partly driven by maternal FPG in first trimester. The study emphasized the importance of identifying and managing mothers with higher pre-pregnancy BMI to prevent fetal overgrowth.Keywords: body mass index, fetal growth, adverse neonatal outcomes, fasting plasma glucose, mediation analysis, cohort study

Tongxin Zhang,1,2 Zilong He,1,2 Yankui Liu,3 Linfang Jin,4 Teng Wang1,2 1Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214122, People’s Republic of China; 2Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, 214122, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214122, People’s Republic of China; 4Department of Pathology, Wuxi No. 9 People’s Hospital, Wuxi, Jiangsu, 214062, People’s Republic of ChinaCorrespondence: Teng Wang, Department of Oncology, Affiliated Hospital of Jiangnan University, 1000 Hefeng Road, Binhu District, Wuxi, Jiangsu Province, 214000, People’s Republic of China, Tel +8618861530279, Email 9862016033@jiangnan.edu.cnBackground: Anti-claudin (CLDN) 18.2 therapy has been proven to be effective in treating advanced gastric cancer with negative human epidermal growth factor receptor 2 (HER-2). This study purposed to investigate the relationship of CLDN 18.2 expression with prognosis of HER-2-positive gastric cancer patients.Objective: To investigate the expression of claudin (CLDN) 18.2 in Human epidermal growth factor receptor 2 (HER-2) positive gastric cancer patients after radical resection and its relationship with gastric cancer prognosis.Methods: A total of 55 postoperative HER-2-positive gastric cancer patients were included in this study. CLDN 18.2 protein was detected by immunohistochemistry, and detailed clinical and pathological information was collected. Factors considered potentially important in the univariate analysis were included in the multivariate analysis, which involved COX regression to find the independent prognostic factors affecting disease-free survival (DFS).Results: Immunohistochemistry showed that different levels of CLDN 18.2 protein were expressed in HER-2 positive gastric cancer tissues, and the Chi-square analysis showed that the expression level of CLDN 18.2 was significantly correlated with the lymph node stage. Higher expression levels of CLDN 18.2 were found in patients with lymph node positivity and were associated with poor prognosis in HER-2-positive gastric cancer patients. Gastric cancer patients with low and high expressions of CLDN 18.2 had postoperative median DFS of 38.5 months (95% confidence interval (CI) 28.8– 48.2 months) and 12.1 months (95% CI, 11.7– 41.0 months), respectively.Conclusion: High expression of CLDN 18.2 in HER-2 positive gastric cancer is associated with poor prognosis, and the optimal treatment mode for this population is worth exploring after the approval of anti-CLDN 18.2 drugs.Keywords: gastric cancer, HER2, claudin 18.2, prognosis

Pan Gao,1,2 Xinyu Li,1,2 Ziqiu He,1,2 Hongbo Zhang,1,2 Zhi Zhang,1,2 Zonglai Liu1,2 1Department of Urology, Second People’s Hospital of Yichang, Yichang, Hubei Province, People’s Republic of China; 2Department of Urology, Second People’s Hospital of China Three Gorges University, Yichang, Hubei Province, People’s Republic of ChinaCorrespondence: Zonglai Liu, Department of Urology, Second People’s Hospital of Yichang, Second People’s Hospital of China Three Gorges University, 21 Xiling One Road, Yichang, 443000, Hubei Province, People’s Republic of China, Email 85538230@qq.comAbstract: Immune checkpoint inhibitors (ICI) have become a new hope for many patients with advanced cancer by blocking tumor immune escape. Bladder cancer is a common malignant tumor of the urinary tract epithelium that often relapses and metastasizes after surgery, chemotherapy, and radiotherapy. Immunotherapy has dramatically improved patient survival rates and clinical benefits as a new, potentially effective therapy. However, avoidance of various immune-related adverse events (irAEs) remains an implausible idea. ICI-induced myocarditis is different from viral myocarditis, and mortality is still high with the current treatment. We report the case of an 82-year-old female patient with ICI-induced fulminant myocarditis and myasthenia gravis. Although she actively accepted the current mainstream treatment for immune-related myocarditis and myasthenia, she died of heart and respiratory failure. Analyzing and reporting the patient’s disease development process and the changes in related indicators may help peers gain a deeper understanding of immune-related adverse events and reduce the mortality of immune-related myocarditis.Keywords: immune checkpoint inhibitors, immunotherapy, heart failure, multiple organs failure

Xiaoguang Xiao,1 Jianhai Sun,2 Dongsheng Zhang,3 Linjun Li,4 Haibo Zhou,5 Yongjun Li,6 Quan Li,7 Zhongshi He,8 Yang Fu,9 Qiwen Duan,10 Guping Zheng,11 Ze Tang,12 Qian Chu,1,&ast; Yuan Chen1,&ast; 1Department of Oncology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Oncology, Hubei Zhongshan Hospital, Wuhan, Hubei, People’s Republic of China; 3Department of Oncology, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei, People’s Republic of China; 4Department of Oncology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, Hubei, People’s Republic of China; 5Department of Oncology, Yichang Central People’s Hospital, Yichang, Hubei, People’s Republic of China; 6Department of Oncology, Yichang Second People’s Hospital, Yichang, Hubei, People’s Republic of China; 7Department of Oncology, Xiangyang Central Hospital, Xiangyang, Hubei, People’s Republic of China; 8Department of Oncology, Xiangyang No 1 People’s Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei, People’s Republic of China; 9Department of Oncology, Xiangyang Hospital of Traditional Chinese Medicine, Xiangyang, Hubei, People’s Republic of China; 10Department of Oncology, Taihe Hospital, Shiyan, Hubei, People’s Republic of China; 11Department of Oncology, Xiaogan Central Hospital, Xiaogan, Hubei, People’s Republic of China; 12Department of Oncology, Huangshi Central Hospital, Huangshi, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian Chu; Yuan Chen, Email qianchu@tjh.tjmu.edu.cn; chenyuantj2023@126.comBackground: Studies have shown that oral oxycontin tablets can be used for opioid titration. The European Society for Medical Oncology (ESMO) guidelines for adult cancer pain recommend opioid titration through the parenteral route, usually the intravenous or subcutaneous route. Patient-controlled subcutaneous analgesia (PCSA) with hydromorphone needs further evaluation for opioid titration. This prospective multicenter study was designed to compare the efficacy and safety of hydromorphone PCSA with oral oxycontin tablets for opioid titration of cancer pain.Patients and Methods: Eligible patients with cancer pain were randomly assigned in a 1:1 ratio to the PCSA group or the oxycontin group for dose titration. Different titration methods were given in both groups depending on whether the patient had an opioid tolerance. The primary endpoint of this study was time to successful titration (TST).Results: A total of 256 patients completed this study. The PCSA group had a significantly lower TST compared with the oxycontin group (median [95% confidence interval (CI)], 5.5[95% CI:2.5– 11.5] hours vs.16.0 [95% CI:11.5– 22.5] hours; p< 0.001). The frequency (median; interquartile) of breakthrough pain (Btp) over 24 hours was significantly lower in the PCSA group (2.5;2.0– 3.5) than in the oxycontin group.(3.0; 2.5– 4.5) (p=0.04). The pain was evaluated by numeric rating scale (NRS) score at 12 hours after the start of titration. The pain score (median; interquartile) was significantly lower in the PCSA versus the oxycontin group (2.5;1.5– 3.0) vs 4.5;3.0– 6.0) (p=0.02). The equivalent dose of oral morphine (EDOM) for a successful titration was similar in both groups (p=0.29), but there was a significant improvement in quality of life (QoL) in both groups (p=0.03). No between-group difference in the incidence of opioid-related adverse effects was observed (p=0.32).Conclusion: Compared with oral oxycontin tablet, the use of PCSA with hydromorphone achieved a shorter titration duration for patients with cancer pain (p< 0.001), without significantly increasing adverse events (p=0.32).Keywords: cancer pain, opioid titration, oxycontin tablets, hydromorphone, patient-controlled subcutaneous analgesia

Yanxu Zhong,1,2 Huan Lu,3 Xiaodan Lu,4 Zhini He,4 Yuyan Jiang,1 Jie Chen,1 Tippawan Liabsuetrakul2 1Food Safety Monitoring and Evaluation Department, Guangxi Zhuang Autonomous Region Centre for Disease Control and Prevention, Nanning, Guangxi Region, 530000, People’s Republic of China; 2Department of Epidemiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand; 3Infectious Diseases Department, the Fourth People’s Hospital of Nanning, Nanning, Guangxi Region, 530000, People’s Republic of China; 4Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of ChinaCorrespondence: Tippawan Liabsuetrakul, Department of Epidemiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand, Tel +66 74 451165, Fax +66 74 281166, Email tippawan.l@psu.ac.thBackground: Cooking oil and dietary foods are easily contaminated by aflatoxins (AFs) in Guangxi, China where low birth weight and preterm birth were prevalent. However, there are no data on AF exposure in pregnant women or their impact on newborn birth outcomes. This study aims to measure the levels and correlations of AFs in cooking oil, estimated dietary intake (EDI) of AFs in dietary foods, and serum AFB1 albumin adducts (AFB1-alb) with newborn birthweight and gestational age at birth.Methods: A prospective study was conducted among 126 pregnant women in Guangxi, China. All recruited women were interviewed for demographic data and behavior and obstetric information and then followed up until giving birth. AF measurements were obtained from cooking oil, dietary foods, maternal serum, and cord blood and the correlations of AF levels with newborn birthweight and gestational age at birth were tested using correlation analysis.Results: The median EDI of AFs in cooking oil was 2.61 ng/kg.bw/day and in dietary foods 2.95 ng/kg.bw/day. High positive correlations among EDI of aflatoxin B1 (AFB1) from cooking oil and dietary foods were found (r > 0.7). Low positive correlations of AFB1-alb in maternal serum and cord blood and both EDI of AFB1 in both cooking oil and dietary foods were shown (r &ap;0.3). Significant correlations between AF levels in both cooking oil and dietary foods with birth weight were found, but very low negative correlations (r = - 0.244 ~ − 0.285). AFB1 levels in foods, maternal serum and cord blood levels were high in pregnant women with newborn low birth weight and preterm birth.Conclusion: The EDIs of AFB1 from both cooking oil and dietary foods were significantly correlated with AFB1-alb in maternal serum and cord blood. Negative correlations of AFs from cooking oils and foods with newborn birth weight should be paid more attention.Keywords: aflatoxins, EDI, birthweight, gestational age at birth, AFB1 albumin adducts

Yexiao Wang,1,&ast; Zibin He,2,&ast; Bingqin Luo,2 Hioteng Wong,1 Liangcai Wu,3 Hui Zhou1 1Department of Dermatology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 2MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Dermatology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangcai Wu; Hui Zhou, Tel +86 13380019222 ; +86 13660389658, Email wulc@mail.sysu.edu.cn; zhouhui5@mail.sysu.edu.cnBackground: Mesenchymal stem cell-derived exosomes (MSC-Exo) have therapeutic potential. However, the impact of MSC-Exo on the survival and melanogenesis of human primary melanocytes following H2O2-induced damage has not been clarified. We therefore investigated the effects of MSC-Exo on the H2O2-affected survival of human primary melanocytes and their proliferation, apoptosis, senescence, and melanogenesis in vitro.Methods: MSC-Exo were prepared from human MSCs by sequential centrifugations and characterized by Transmission Electron Microscopy, Western blot and Nanoparticle Tracking Analysis. Human primary melanocytes were isolated and treated with different concentrations of MSC-Exo, followed by exposing to H2O2. Furthermore, the impact of pretreatment with MSC-Exo on the proliferation, apoptosis, senescence and melanogenesis of melanocytes were tested by CCK-8, flow cytometry, Western blot, L-Dopa staining, tyrosinase activity and RT-qPCR.Results: Pretreatment with lower doses of MSC-Exo protected human primary melanocytes from the H2O2-triggered apoptosis, while pretreatment with higher doses of MSC-Exo enhanced the H2O2-induced melanocyte apoptosis. Compared with the untreated control, pretreatment with a lower dose (1 μg/mL) of MSC-Exo enhanced the proliferation of melanocytes, abrogated the H2O2-increased p53, p21, IL-1β, IL-6 and IL-8 expression and partially rescued the H2O2-decreased L-dopa staining reaction, tyrosinase activity, MITF and TRP1 expression in melanocytes.Conclusion: Our findings indicate that treatment with a low dose of MSC-Exo promotes the proliferation and melanogenesis of human primary melanocytes by ameliorating the H2O2-induced apoptosis and senescence of melanocytes. MSC-Exo may be a promising therapeutic strategy of vitiligo.Keywords: mesenchymal stem cell-derived exosomes, melanocytes, apoptosis, proliferation, senescence

Peng Lu,1,2,&ast; Tun Wang,1,2,&ast; Zicheng Wan,1,2 Mo Wang,1,2 Yang Zhou,1,2 Zhenyu He,1,2 Sheng Liao,1,2 Haiyang Liu,3 Chang Shu1,2,4 1Department of Vascular Surgery, the Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Institute of Vascular Diseases, Central South University, Changsha, People’s Republic of China; 3Department of Geriatrics, the Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 4Center of Vascular Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chang Shu, Department of Vascular Surgery, the Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China, Tel +86 136 0744 4222, Email Shuchang@csu.edu.cnPurpose: Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis, but the low maturation rate is concerning. Immune cells’ impact on AVF maturation lacks bioinformatics research. The study aims to investigate the potential predictive role of immune-related genes and immune cell infiltration characteristics in AVF maturation.Patients and Methods: We analyzed the high-throughput sequencing dataset to identify differentially expressed genes (DEGs). Then, we performed enrichment analyses (GO, KEGG, GSEA) on immune-related genes and pathways in mature AVF. We focused on differentially expressed immune-related genes (DEIRGs) and constructed a PPI network to identify hub genes. These hub genes were validated in other databases and experiments, including qPCR and immunohistochemistry (IHC). The immune cell infiltration characteristics in native veins, failed AVFs, and matured AVFs were analyzed by cibersortX. Partial experimental validation was conducted using clinical samples.Results: Our results showed that immune-related genes and signaling pathways are significantly enriched in mature AVF. We validated this in other databases and ultimately identified three hub genes (IL1B, IL6, CXCR4) in combination with experiments. Significant differences in immune cell infiltration characteristics were observed among native veins, failed AVFs, and matured AVFs. Immune cell infiltration analysis revealed that accumulation of CD4+ T cells, dendritic cells, mast cells and M2 macrophages contribute to AVF maturation. These immune-related genes and immune cells have the potential to serve as predictive factors for AVF maturation. We partially validated this experimentally.Conclusion: From a bioinformatics perspective, our results have identified, for the first time, a set of immune-related genes and immune cell infiltration features that can characterize the maturation of AVF and significantly impact AVF maturation. These features hold potential as predictive indicators for AVF maturation outcomes.Keywords: AVF maturation, bioinformatics, immune-related genes, inflammation

Xiangyu Zhang,1 Zelai He2 1Department of Pathology, Jining No.1 People’s Hospital, Jining, Shandong, 272000, People’s Republic of China; 2Department of Radiation Oncology, the First Affiliated Hospital of Bengbu Medical College & Tumor Hospital Affiliated to Bengbu Medical College, Bengbu, Anhui, 233004, People’s Republic of ChinaCorrespondence: Zelai He, Department of Radiation Oncology, The First Affiliated Hospital of Bengbu Medical College & Tumor Hospital Affiliated to Bengbu Medical College, Bengbu, 233004, People’s Republic of China, Email he.ze.lai@163.comAim: To produce pH-responsive bionic high photothermal conversion nanoparticles actively targeting tumors for sensitizing photothermal therapy (PTT).Materials and Methods: The bionic nanoparticles (ICG-PEI@HM NPs) were prepared by electrostatic adsorption of indocyanine green (ICG) coupled to polyethyleneimine (PEI) and modified with tumor cell membranes. In vitro and in vivo experiments were conducted to investigate the efficacy of ICG-PEI@HM-mediated PTT.Results: The intelligent responsiveness of ICG-PEI@HM to pH promoted the accumulation of ICG and enhanced the PTT performance of ICG-PEI@HM NPs. Compared with free ICG, NPs exhibited great photothermal stability, cellular uptake, and active tumor targeting for PTT.Conclusion: ICG-PEI@HM NPs can enhance the efficacy of PTT and can be used as a new strategy for the construction of photothermal agents.Keywords: photothermal therapy, pH-responsive, tumor membrane, active targeting, nanoparticle

Zhe Zhao,1,&ast; Yinghui Gao,2,&ast; Junling Lin,3,&ast; Ruyi Xu,4 Zijun He,5 Libo Zhao,1 Fengfeng Fang,5 Weimeng Cai,6 Kaibin Chen,7 Li Fan,1 Lin Liu6 1Cardiology Department of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2PKU-Upenn Sleep Center, Peking University International Hospital, Beijing, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, People’s Republic of China; 4Sixth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 5Medical College, Yan’an University, Yan’an, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China; 7Sleep Center, The Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Fan, Cardiology Department of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, People’s Republic of China, Tel +86 13301100573, Email fl6698@163.com Lin Liu, Department of Respiratory and Critical Care Medicine of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, People’s Republic of China, Tel +86 13263189578, Email liulin715@qq.comIntroduction: Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease (CVD). Depression is a crucial factor among the various factors that are associated with OSA and CVD.Purpose: This study was conducted with an aim to assess the prognostic significance of depression on the MACE in older patients with OSA.Patients and Methods: 1106 older patients with OSA, without myocardial infarction (MI), history of hospitalization for unstable angina, or heart failure at baseline were enrolled and followed up prospectively. Incidence rates were expressed as cumulative incidence. Cox proportional hazards analysis was used to estimate the risk of all events. The primary outcomes were major adverse cardiovascular events (MACE). Each patient underwent polysomnography (PSG) and GDS-12 scale assessment. Those with an apnea-hypopnea index (AHI) greater than 5 were diagnosed with OSA, while those with a scale score greater than 3 were diagnosed with depression.Results: Among the 1106 older patients with OSA, depression was found in 133(12.0%) patients, 96(8.7%) patients experienced MACE during the follow-up. Depression was associated with a higher cumulative incidence of MACE in older patients with OSA. Multivariate analysis revealed that depression independently increased the risk of MACE (adjusted hazard ratio [aHR] = 2.29; 95% confidence interval [CI]: 1.34– 3.90; P = 0.002). Subgroup analyses showed that male patients (aHR = 2.96; 95% CI: 1.52– 5.77; P = 0.001), overweight-obese individuals (aHR = 2.98; 95% CI: 1.49– 6.00; P = 0.002), and those with moderate-severe OSA (aHR = 2.82; 95% CI: 1.55– 5.14; P = 0.001) and concurrent depression were at a higher risk for MACE.Conclusion: Depression is common in older patients with OSA in the absence of MI, hospitalization for unstable angina, or heart failure, and confers an independent, increased risk of MACE.Keywords: obstructive sleep apnea, OSA, depression, major adverse cardiovascular events, MACE, older adults

Arbuscular mycorrhizal fungi (AMF) play an important role on litter decomposition, which is increasing suffering the negative impact of acid deposition. In this study, we investigated the AMF effects on litter decomposition via suppressing AMF and simulating acid deposition in a subtropical Cinnamomum camphora forest. The results showed that acid deposition and AMF suppression decelerated C. camphora leaf litter decomposition, especially at late decomposition stage; soil water content was the main factor restricting early-stage decomposition. The inhibiting effect of acid deposition was enhanced with acid intensity increase and AMF suppression aggravated the negative effect of acid stress on decomposition. Nitrogen-cycling enzymatic activity was significantly higher in later than in early decomposition stage, and acid deposition and AMF suppression significantly decreased microbial activity. Despite the seasonal effect was overwhelming, we still detected the effects of acid deposition and AMF suppression on litter nutrient release. Without or under low acid deposition, AMF suppression significantly increased organic matter and decreased alkali-hydrolyzable nitrogen content of detritusphere soil. Acid deposition significantly reduced soil organic matter content, while high acid deposition intensity increased alkali-hydrolyzable nitrogen content after 2- and 12-month decomposition, and decreased it at other months. Both acid deposition and AMF suppression decreased available phosphorus content, but did not affect phosphatase activity. AMF effects on invertase and nitrogen-release enzyme activities, and alkali-hydrolyzable nitrogen and available phosphorus contents of detritusphere soil were highly sensitive to acid deposition. Our results revealed that AMF effects on microbial activity and nutrient release during litter decomposition are sensitive to acid deposition.

Zemin He,1 Hong Li,1 Boxiong Cao,1 Ziliang Zan,1 Hao Feng,1 Qiang Wei,1 Keting Liu2 1Department of Thoracic Surgery, The First People’s Hospital of Shuangliu District (West China Airport Hospital of Sichuan University), Chendu, Sichuan Province, People’s Republic of China; 2Department of Neurology, Chengdu Seventh People’s Hospital, Chendu, Sichuan Province, People’s Republic of ChinaCorrespondence: Qiang Wei, Department of Thoracic Surgery, The First People’s Hospital of Shuangliu District (West China Airport Hospital of Sichuan University), 120 Chengbei Upper Street, Dongsheng Town, Shuangliu District, Chendu, Sichuan Province, People’s Republic of China, Tel +86 13778533702, Email 993092572@qq.comPurpose: To explore the predictive value of skeletal muscle function measurement combined with stair climbing test for postoperative cardiopulmonary complications in patients with chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC).Patients and Methods: A prospective study was conducted from June 2022 to July 2023 at West China Hospital of Sichuan University, including 335 COPD patients with lung cancer who underwent surgery. The patients were divided into two groups based on the occurrence of postoperative cardiopulmonary complications: the complication group and the non-complication group. The demographic data, including gender, age, smoking history, quadriceps strength, body mass index (BMI), respiratory muscle strength, 6-minute walk test (6MWD), stair climbing test, and preoperative pulmonary function tests, were compared between the two groups. Logistic regression analysis was performed to evaluate the predictive power of each parameter for postoperative cardiopulmonary complications.Results: Among the enrolled patients, 103 (30.7%) developed postoperative cardiopulmonary complications. Significant differences were observed between the two groups in terms of quadriceps strength, respiratory muscle strength, 6MWD, smoking history, stair climbing test, DLCO%, FEV1%, heart rate, oxygen saturation, surgical duration, surgical approach, resection range, and blood loss (P< 0.05). Logistic regression analysis revealed that respiratory muscle strength, quadriceps strength, stair climbing test, FEV1%, DLCO%, ΔHR, ΔSPO2, surgical approach were identified as risk factors for postoperative cardiopulmonary complications in patients with COPD and lung cancer.Conclusion: Skeletal muscle function measurement, stair climbing test, FEV1, surgical approach, and DLCO% can serve as assessment tools for surgical risk in patients with COPD and lung cancer. They can predict the occurrence of postoperative cardiopulmonary complications to a certain extent, providing valuable predictive value for these complications in patients with COPD and NSCLC.Keywords: respiratory muscle function, Cardiopulmonary complications, lung cancer surgery, Climbing test

Dong Zhang,1,2 Siwei Duan,3 Zhangyou He,4 Zeming Zhu,3 Zhiping Li,3 Qincheng Yi,4 Tiantian Cai,1,2 Juanjuan Li,1,2 Nan Chen,1,2 Shaoju Guo1,2 1Gastrointestinal Ward, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 2Gastrointestinal Ward, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen, People’s Republic of China; 3Institute of Gastroenterology, Science and Technology Innovation Center of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4Institute of Gastroenterology, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of ChinaCorrespondence: Shaoju Guo, Gastrointestinal Ward, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China, Tel +86-0755-82571384, Email gsj1080@163.comPurpose: This study was conducted to explore the mechanism of Sijunzi Decoction (SJZ) in the treatment of ulcerative colitis (UC).Methods: The study aimed to investigate the active components and targets of SJZ in the treatment of UC by screening databases such as TCMSP, GeneCards, OMIM, Distinct, TTD, and Drugbank. An online Venn tool, Cytoscape 3.7.2, and Autodock Tools were used to analyze the components and targets. The study also used a mouse model of UC to further investigate the effects of SJZ. HE staining, immunofluorescence, ELISA, qPCR, and Western blot were used to detect various indices.Results: Eighty-three active components and 112 action targets were identified from SJZ, including 67 targets for treating UC-related NETs. The five core targets identified were AKT1, JUN, IL1B, PTGS2, and TNF, and molecular docking studies indicated that the five targets were well-docked with ginsenoside Rh2, isoflavones, and formononetin. Animal experiments demonstrated that SJZ could alleviate various parameters such as weight, colon length, spleen index, disease activity index, and intestinal pathology of the UC mice. Immunofluorescence and Western blot showed that SJZ could reduce the expression of IL1B and TNF in intestinal neutrophils while increasing the expression of Occludin. Cellular immunofluorescence suggests that SJZ can reduce the expression of TNF and IL1B in NETs. The qPCR results also suggested that SJZ could inhibit TNF signal. Furthermore, ELISA results suggested that SJZ could inhibit the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) while promoting the expression of anti-inflammatory cytokines (IL-10, IL-37, TGF-β).Conclusion: SJZ treats UC by reducing the content of intestinal NETs, with primary targets on the NETs being IL1B and TNFand suppress TNF signal. The practical components of SJZ may be ginsenoside Rh2, isoflavones, and formononetin.Graphical Abstract: Keywords: ulcerative colitis, Sijunzi decoction, network pharmacology, IL1B, TNF

Zisu Wang,1 Kai Li,1 Shuangshuang Guo,2 Xili Wen,1 Ziyi He,1 Yujun Cai1 1School of Physical Education, Shanghai University of Sport, Shanghai, People’s Republic of China; 2Physical education Group, High school Attached to Shanghai Normal University Minhang Campus, Shanghai, People’s Republic of ChinaCorrespondence: Yujun Cai, School of Physical Education, Shanghai University of Sport, Shanghai, People’s Republic of China, Email caiyujun@sus.edu.cnPurpose: The purpose of this study was to examine the relationships between academic engagement and moderate-to-vigorous physical activity (MVPA), muscle-strengthening exercise (MSE) and sedentary behavior (SB) among adolescents, so as to provide evidence from the perspective of exercising for students to learn efficiently, teachers to improve classroom teaching, and schools to improve educational quality.Methods: A questionnaire survey was conducted in 12 junior high schools in Shanghai, China, which were selected by a multi-stage stratified cluster sampling method. Then, with the valid data of 2078 students collected from the survey. A data analysis was performed using SPSS Statistics 26.0. Multiple linear regression models were adopted to analyze the factors affecting adolescent academic engagement and to determine whether MVPA, MSE, and SB play roles in it.Results: (1) The differences in academic engagement depended on the exercise adherence to the recommended amount of MVPA, MSE, and screen-based SB. (2) In terms of the three independent variables of total time, MSE (β = 0.206) and MVPA (β = 0.175) showed a significant positive correlation with academic engagement, while SB (β = − 0.155) was negatively correlated with academic engagement. (3) From the linear regression model of eight combination groups divided by the exercise adherence to the recommended amount of MVPA, MSE and SB, the group that met none of the recommendations (β = − 0.235) showed a significant negative effect on academic engagement, while the groups that met any two or all three of the recommendations demonstrated strong positive correlations with academic engagement (P < 0.001).Conclusion: Increasing adolescents’ muscle-strengthening exercise and moderate-to-vigorous physical activity and reducing sedentary behavior can effectively promote academic engagement. Therefore, adolescents are suggested to reach the recommended amounts of physical activity, muscle-strengthening exercise, and sedentary behavior so as to improve academic engagement more effectively.Keywords: moderate-to-vigorous physical activity, muscle-strengthening exercise, academic engagement, sedentary behaviors

Xingrui Li,1,&ast; Yue Wang,1,&ast; Denghao Huang,1 Zhonghao Jiang,1 Zhiyu He,1 Maoxuan Luo,2 Jie Lei,1,2 Yao Xiao1– 3 1Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, the Affiliated Stomatological Hospital of Southwest Medical University, Institute of Stomatology, Southwest Medical University, Luzhou, People’s Republic of China; 2Department of Orthodontics, the Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Chengbei Outpatient, the Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yao Xiao; Jie Lei, Email orthoxiaoyao@outlook.com; 1067233579@qq.comAbstract: The critical challenges in repairing oral soft and hard tissue defects are infection control and the recovery of functions. Compared to conventional tissue regeneration methods, nano-bioactive materials have become the optimal materials with excellent physicochemical properties and biocompatibility. Dental-derived mesenchymal stem cells (DMSCs) are a particular type of mesenchymal stromal cells (MSCs) with great potential in tissue regeneration and differentiation. This paper presents a review of the application of various nano-bioactive materials for the induction of differentiation of DMSCs in oral and maxillofacial restorations in recent years, outlining the characteristics of DMSCs, detailing the biological regulatory effects of various nano-materials on stem cells and summarizing the material-induced differentiation of DMSCs into multiple types of tissue-induced regeneration strategies. Nanomaterials are different and complementary to each other. These studies are helpful for the development of new nanoscientific research technology and the clinical transformation of tissue reconstruction technology and provide a theoretical basis for the application of nanomaterial-modified dental implants. We extensively searched for papers related to tissue engineering bioactive constructs based on MSCs and nanomaterials in the databases of PubMed, Medline, and Google Scholar, using keywords such as “mesenchymal stem cells”, “nanotechnology”, “biomaterials”, “dentistry” and “tissue regeneration”. From 2013 to 2023, we selected approximately 150 articles that align with our philosophy.Keywords: nano-material, stem cell, tissue reconstruction, cell differentiation

Zhaoyan Wang,1,&ast; Leping Zhang,1,2,&ast; Yinxiang Yang,1 Qian Wang,1 Suqing Qu,1 Xiaohua Wang,1 Zhixu He,2,3 Zuo Luan1 1Laboratory of Pediatrics, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, People’s Republic of China; 2Guizhou Medical University, Guiyang, 550004, People’s Republic of China; 3Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, 563100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zuo Luan; Zhixu He, Email guizuo8493@163.com; runxu636596@163.comBackground: Cerebral white matter injury (WMI) is the most common brain injury in preterm infants, leading to motor and developmental deficits often accompanied by cognitive impairment. However, there is no effective treatment. One promising approach for treating preterm WMI is cell replacement therapy, in which lost cells can be replaced by exogenous oligodendrocyte progenitor cells (OPCs).Methods: This study developed a method to differentiate human neural stem cells (hNSCs) into human OPCs (hOPCs). The preterm WMI animal model was established in rats on postnatal day 3, and OLIG2+/NG2+/PDGFRα+/O4+ hOPCs were enriched and transplanted into the corpus callosum on postnatal day 10. Then, histological analysis and electron microscopy were used to detect lesion structure; behavioral assays were performed to detect cognitive function.Results: Transplanted hOPCs survived and migrated throughout the major white matter tracts. Morphological differentiation of transplanted hOPCs was observed. Histological analysis revealed structural repair of lesioned areas. Re-myelination of the axons in the corpus callosum was confirmed by electron microscopy. The Morris water maze test revealed cognitive function recovery.Conclusion: Our study showed that exogenous hOPCs could differentiate into CC1+ OLS in the brain of WMI rats, improving their cognitive functions.Keywords: preterm infant, cerebral white matter injury, oligodendrocyte progenitor cells, cell replacement therapy, rat model

Zhiqiang He,1 Huan Yang,1 Yufan Gu,1 Yuhan Xie,1 Jianan Wu,1 Chen Wu,1 Jiawei Song,1 Maofang Zhao,2,3 Da Zong,1 Wenlong Du,1 Jiaju Qiao,1 Yipeng Pang,1– 3 Yi Liu1– 3 1Department of Biophysics, School of Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 2School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 3Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of ChinaCorrespondence: Yi Liu; Yipeng Pang, Department of Biophysics, School of Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China, Tel/Fax +86-0516-83262084, Email cbpeliuyinew@163.com; pangyipeng.xzmu@foxmail.comPurpose: Herein, an emerging drug delivery system was constructed based on zeolite imidazole backbone (ZIF-8) to improve antibacterial defects of nanosilver (AgNPs), such as easily precipitated and highly cytotoxic.Methods: The homogeneous dispersion of AgNPs on ZIF-8 was confirmed by UV-Vis spectroscopy, FTIR spectroscopy, particle size analysis, zeta potential analysis, and SEM. The appropriate AgNPs loading ratio on ZIF-8 was screened through the cell and antibacterial experiments based on biosafety and antibacterial performance. The optimal environment for AgNPs@ZIF-8 to exert antibacterial performance was probed in the context of bacterial communities under different acid-base conditions. The potential mechanism of AgNPs@ZIF-8 to inhibit the common clinical strains was investigated by observing the biofilm metabolic activity and the level of reactive oxygen species (ROS) in bacteria.Results: The successful piggybacking of AgNPs by ZIF-8 was confirmed using UV-Vis spectroscopy, FTIR spectroscopy, particle size analysis, zeta potential analysis, and SEM characterization methods. Based on the bacterial growth curve (0– 24 hours), the antibacterial ability of AgNPs@ZIF-8 was found to be superior to AgNPs. When the mass ratio of ZIF-8 and AgNPs was 1:0.25, the selection of AgNPs@ZIF-8 was based on its superior antimicrobial efficacy and enhanced biocompatibility. Notably, under weakly acidic bacterial microenvironments (pH=6.4), AgNPs@ZIF-8 demonstrated a more satisfactory antibacterial effect. In addition, experiments on biofilms showed that concentrations of AgNPs@ZIF-8 exceeding 1×MIC resulted in more than 50% biofilm removal. The nanomedicine was found to increase ROS levels upon detecting the ROS concentration in bacteria.Conclusion: Novel nanocomposites consisting of low cytotoxicity drug carrier ZIF-8 loaded with AgNPs exhibited enhanced antimicrobial effects compared to AgNPs alone. The pH-responsive nano drug delivery system, AgNPs@ZIF-8, exhibited superior antimicrobial activity in a mildly acidic environment. Moreover, AgNPs@ZIF-8 effectively eradicated pathogenic bacterial biofilms and elevated the intracellular level of ROS.Graphical Abstract: Keywords: MOF, ZIF-8, AgNPs, nanocomplex, ROS, pathogenic biofilm

Siyao Wu,1,&ast; Ting Guo,2,&ast; Hui Zhang,1 Zhiyi He,1 Jianquan Zhang,3 Wen Zeng1 1Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 2Department of Dermatology and Venereology, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China; 3Department of Respiratory and Critical Medicine, the Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, 518000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Zeng, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Tel +86 18589883694, Email zengwen@stu.gxmu.edu.cnAbstract: Adult-onset acquired immunodeficiency caused by anti-IFN-γ autoantibodies is associated with severe opportunistic infection. Due to lack of specific symptoms and different manifestations, this form of infection can be easily misdiagnosed or overlooked. Herein, we present a case of Nocardia farcinica and Talaromyces marneffei co-infection in a patient with anti-IFN-γ autoantibodies (AIGAs). The patient, a 54-year-old man, presented with a 1-month history of fever, coughing and expectoration, dizziness, headache and gait imbalance. Laboratory workup revealed increased inflammatory markers, negative anti-HIV antibody and a high positive titer of AIGAs. Chest computed tomography (CT) showed multiple patches of high-density shadows in both lungs, and brain enhanced magnetic resonance imaging (MRI) showed an irregular lesion. The patient underwent a craniotomy for resection of the lesion. Pulmonary T. marneffei infection was diagnosed through sputum and bronchoalveolar lavage fluid culture, and brain nocardiosis was confirmed via purulent fluid culture of brain tissue. With regular antibiotic therapy, his symptoms improved and there was no recurrence during 18-month follow-up. This may be the first detailed case report detailing infection with these two distinct pathogens in disparate anatomical locations.Keywords: nocardia, Talaromyces marneffei, adult-onset acquired immunodeficiency, anti-IFN-γ autoantibodies, brain abscess

Zhenwu You,&ast; Meng Wang,&ast; Zhiwu He&ast; School of Journalism and Information Communication, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiwu He, School of Journalism and Information Communication, Huazhong University of Science and Technology, 1037 Luoyu Road, Hongshan District, Wuhan, Hubei Province, 430000, People’s Republic of China, Email hezhiwu2001@sina.comBackground: During the ongoing COVID-19 pandemic, the resident’s WeChat group has created a new material foundation for dialogue to occur and become a powerful platform for resident communication. This study explores the mechanism behind and the effects of residents’ WeChat group use on residents’ community trust, community attachment, and pro-community behavior.Methods: An online survey questionnaire was used for data collection. The authors collected data from 500 commercial housing community residents in Wuhan, China, and analyzed the data using SPSS 26.0 and Mplus 8.3 software.Results: This study’s findings uncover that (1) residents’ usage of WeChat groups has a statistically significant and positive impact on their community trust, community attachment, and pro-community behavior; (2) community trust and community attachment both play a mediating role in the mechanism behind residents’ usage of WeChat groups in improving pro-community behavior; and (3) the transmission and united effects between community trust and community attachment form a distal mediating role.Conclusion: The model systematically and comprehensively reveals the internal mechanism behind residents’ adoption of pro-community behavior. Community managers can actively participate in the resident’s WeChat group to ensure the dissemination of positive information in the community; enhance residents’ awareness of risk, community trust, and belonging; and cultivate community resilience. At the same time, community managers should also fully recognize the important transformative roles that community trust and community belonging play between the use of WeChat groups by residents and the formation of pro-community behavior. Community managers should actively establish a warm and trusting community culture, strive to create a community atmosphere with a sense of belonging, make residents develop emotional attachment to the community, and then form behavior that is beneficial to the community, greatly enhancing the resilience and self-management of the community in disaster situations.Keywords: COVID-19, residents’ WeChat group use, pro-community behavior, community attachment, community trust

Yong Li,1,2,&ast; Senbo Zhu,2,&ast; Junchao Luo,2 Yu Tong,2 Yixuan Zheng,1 Lichen Ji,2 Zeju He,2 Qiangan Jing,1 Jiaqing Huang,2 Yinjun Zhang,1 Qing Bi2 1College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, People’s Republic of China; 2Laboratory Medicine Center, Department of Laboratory Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yinjun Zhang, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86-13735494556, Email zhangyj@zjut.edu.cn Qing Bi, Laboratory Medicine Center, Department of Laboratory Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86-13588302991, Email bqzjsrmyy@163.comIntroduction: Osteoarthritis (OA) is a common chronic joint disease characterized by articular cartilage degeneration. OA usually manifests as joint pain, limited mobility, and joint effusion. Currently, the primary OA treatment is non-steroidal anti-inflammatory drugs (NSAIDs). Although they can alleviate the disease’s clinical symptoms and signs, the drugs have some side effects. Selenium nanoparticles (SeNPs) may be an alternative to relieve OA symptoms.Materials and Results: We confirmed the anti-inflammatory effect of selenium nanoparticles (SeNPs) in vitro and in vivo experiments for OA disease in this study. In vitro experiments, we found that SeNPs could significantly reduce the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the major inflammatory factors, and had significant anti-inflammatory and anti-arthritic effects. SeNPs can inhibit reactive oxygen species (ROS) production and increased glutathione peroxidase (GPx) activity in interleukin-1beta (IL-1β)-stimulated cells. Additionally, SeNPs down-regulated matrix metalloproteinase-13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) expressions, while up-regulated type II collagen (COL-2) and aggrecan (ACAN) expressions stimulated by IL-1β. The findings also indicated that SeNPs may exert their effects through suppressing the NF-κB p65 and p38/MAPK pathways. In vivo experiments, the prevention of OA development brought on by SeNPs was demonstrated using a DMM model.Discussion: Our results suggest that SeNPs may be a potential anti-inflammatory agent for treating OA.Keywords: osteoarthritis, NF-κB p65 signaling pathway, p38/MAPK signaling pathway, selenium nanoparticles

Jian Lin,1,&ast; Tianpeng Shi,2,&ast; Yi Wang,1 Zhiqi He,1 Zhixiang Mu,1 Xiaojun Cai,1 Hui Deng,1 Jianliang Shen,3– 5 Fen Liu6 1School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Stomatology, PLA Strategic Support Force Medical Center, Beijing, People’s Republic of China; 3State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology & Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, People’s Republic of China; 5Department of Regenerative Medicine, Vision, and Brain Health, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), Wenzhou, People’s Republic of China; 6Department of Histology and Embryology, Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Deng; Fen Liu, Email dh0726@gmail.com; liufen6459@163.comBackground: Much attention has been paid to sustained drug release and anti-infection in wound management. Hydrogels, which are biocompatible materials, are promising tools for controlled drug release and infective protection during wound healing. However, hydrogels also demonstrate limitations in the highly efficient treatment of wounds because of the diffusion rate. In this work, we explored pH-sensitive hydrogels that enable ultra-long-acting drug release and sustained antibacterial properties.Methods: We constructed a hybrid gelatin methacrylate (GelMA) system with sustainable antibacterial properties combining hyaluronic acid (HA)-coated mesoporous silica nanoparticles (MSN), which loaded host-guest complexes of chlorhexidine (CHX) with β-cyclodextrins (β-CD) (CHX⊂CD-MSN@HA@GelMA). The release mechanism of CHX was explored using UV-vis spectra after intermittent diffusion of CHX. The hybrid hydrogels were characterized, and the drug content in terms of the release profile, bacterial inhibition, and in vivo experiments were investigated.Results: Except for dual protection from both hydrogels, MSN in the HA improved the drug loading efficiency to promote the local drug concentration. It showed that complicated CHX-loaded MSN releases CHX more gradually and over a longer duration than CHX-loaded MSNs. This demonstrated a 12-day CHX release time and antibacterial activity, primarily attributable to the capacity of β-CD to form an inclusion complex with CHX. Meanwhile, in vivo experiments revealed that the hydrogels safely promote skin wound healing and enhance therapeutic efficacy.Conclusion: We constructed pH-sensitive CHX⊂CD-MSN@HA@GelMA hydrogels that enable ultra-long-acting drug release and sustained antibacterial properties. The combination of β-CD and MSN would be better suited to release a reduced rate of active molecules over time (slow delivery), making them great candidates for wound dressing anti-infection materials.Keywords: mesoporous silica, cyclodextrin, pH-responsive, antibacterial property, wound healing

Jiaxin Cao,1,2 Huimin Zhang,1,2 Zhien He,2 Zhongwan Piao,1 Xianchun Zong,1 Baolin Sun1,2 1College of Life Science and Technology, Mudanjiang Normal University, Mudanjiang, People’s Republic of China; 2School of Life Science and Medicine, University of Science and Technology of China, Hefei, People’s Republic of ChinaCorrespondence: Baolin Sun; Zhongwan Piao, Email sunb@ustc.edu.cn; jwcpzw@126.comBackground: Staphylococcus aureus is a highly successful pathogen that can cause various infectious diseases, from relatively mild skin infections to life-threatening severe systemic diseases. The widespread pathogenicity of S. aureus is mainly due to its ability to produce many virulence factors that help destroy various host cells, causing disease. Our primary goal in this study was to explore the genes of highly virulent strains, to identify genes closely associated with high virulence, and to provide ideas for the treatment of infection by highly virulent clinical strains.Results: This study collected 221 clinical strains from The First Affiliated Hospital Of The University of Science and Technology of China (USTC); their hemolytic abilities were tested. Eight isolates were selected based on their highly hemolytic ability and tested their hemolytic activity again; their phenotypes and gene sequences were also explored. Whole-genome sequencing (WGS) showed six plasmids (pN315, pNE131, pSJH901, pSJH101, SAP106B, and MSSA476), eight antibiotic resistance genes [blaR1, blaI, blaZ, mecA, erm(C), erm(T), tet(38), and fosB-Saur] and seventy-two virulence related genes. Three highly virulent strains, namely X21111206, 21092239, and 21112607, were found according the Galleria mellonella infection model. Therefore, we selected 10 representative virulence genes for qRT-PCR: psmα, psmβ, hlgA, hlgB, hlgC, hla, clfA, clfB, spa, and sak. Among them, the expression levels of psmα and psmβ, the three isolates, were significantly higher than the positive control NCTC8325.Conclusion: Significant differences appear in the expression of virulence genes in the highly virulent strains, particularly the psmα and psmβ, It may be that the high expression of psm gene is the cause of the high virulence of Staphylococcus aureus. We can reduce the pathogenicity of Staphylococcus aureus by inhibiting the expression of psm gene, which may provide a strong basis for psm as a new target for clinical treatment of S. aureus infection.Keywords: Staphylococcus aureus, virulence factors, qRT-PCR, next-generation sequencing, psm

Huimin Zhang,1 Jiaxin Cao,1 Zhien He,2,3 Xianchun Zong,1 Baolin Sun2,3 1College of Life Science and Technology, Mudanjiang Normal University, Mudanjiang, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital, University of Science and Technology of China, Hefei, People’s Republic of China; 3School of Life Science and Medicine, University of Science and Technology of China, Hefei, People’s Republic of ChinaCorrespondence: Baolin Sun, Email sunb@ustc.edu.cnPurpose: This study aimed to investigate the molecular characteristics, antimicrobial resistance and hemolytic phenotype of Staphylococcus aureus isolated from Anhui, China.Results: From August 2021 to January 2022, 214 S. aureus isolates were collected from the Anhui Provincial Hospital. This study identified 117 methicillin-resistant S. aureus and 97 methicillin-sensitive S. aureus isolates, and the detection rate of methicillin-resistant isolates was 1.8-fold higher than the average isolates reported in China (53.9% vs 30.5%). S. aureus isolates share identity at five or more of the seven MLST-based housekeeping loci, referred to as the clonal complex (CC). Forty ST types were found in 214 clinical S. aureus isolates, with the most extensive distribution of ST59 and ST6697 typing numbers and higher CC5 detection rates than any other clonal group. (The ST typing is the result of the MLST typing website query.) To detect the virulence of ST types of S. aureus, hemolysis experiments were performed on 214 clinical isolates, and it was concluded that ST59 had a relatively robust hemolytic capacity.Conclusion: Anhui S. aureus isolates have unique molecular and antibiotic resistance profiles. The antibiotic resistance profile may be related to the random use of antibiotics.Keywords: Staphylococcus aureus, epidemiological analysis, multilocus sequence typing, phenotype, hemolytic

Poyu Chen1– 3&ast;, Chuangwei Zhang1– 3&ast;, Ping He,4 Shengyuan Pan,1– 3 Wenjie Zhong,1– 3 Yue Wang,1– 3 Qingyue Xiao,1– 3 Xinyan Wang,1– 3 Wenliang Yu,1– 3 Zhangmin He,1– 3 Xiang Gao,1– 3 Jinlin Song1– 3 1College of Stomatology, Chongqing Medical University, Chongqing, 401147, People’s Republic of China; 2Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 401147, People’s Republic of China; 3Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, People’s Republic of China; 4Department of Stomatology, Dazhou Central Hospital, Dazhou, SiChuan, 635000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Gao; Jinlin Song, Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing, 401147, People’s Republic of China, Tel/Fax +86 23 88860105 ; Tel/Fax +86 23 88860026, Email xiangg@hospital.cqmu.edu.cn; songjinlin@hospital.cqmu.edu.cnIntroduction: The functional reconstruction of periodontal tissue defects remains a clinical challenge due to excessive and prolonged host response to various endogenous and exogenous pro-inflammatory stimuli. Thus, a biomimetic nanoplatform with the capability of modulating inflammatory response in a microenvironment-responsive manner is attractive for regenerative therapy of periodontal tissue.Methods: Herein, a facile and green design of engineered bone graft materials was developed by integrating a biomimetic apatite nanocomposite with a smart-release coating, which could realize inflammatory modulation by “on-demand” delivery of the anti-inflammatory agent through a pH-sensing mechanism.Results: In vitro and in vivo experiments demonstrated that this biocompatible nanoplatform could facilitate the clearance of reactive oxygen species in human periodontal ligament stem cells under inflammatory conditions via inhibiting the production of endogenous proinflammatory mediators, in turn contributing to the enhanced healing efficacy of periodontal tissue. Moreover, this system exhibited effective antimicrobial activity against common pathogenic bacteria in the oral cavity, which is beneficial for the elimination of exogenous pro-inflammatory factors from bacterial infection during healing of periodontal tissue.Conclusion: The proposed strategy provides a versatile apatite nanocomposite as a promising “inflammation scavenger” and propels the development of intelligent bone graft materials for periodontal and orthopedic applications.Graphical Abstract: Keywords: periodontal bone regeneration, pH-responsive, inflammatory modulation, antibacterial activity, biomimetic nanoplatform

Zhenshuo He,1,&ast; Haizhi Wang,2,&ast; Shan Wang,3,&ast; Lu Li4 1Department of Laboratory Medicine, The Sixth People’s Hospital of Hengshui City, Hengshui, 053099, People’s Republic of China; 2Department of Laboratory Medicine, The People’s Hospital of Hengshui City, Hengshui, 053099, People’s Republic of China; 3Department of Laboratory Medicine, The People’s Hospital of Huangmei, Huanggang, 435599, People’s Republic of China; 4Department of Nephrology, The First People’s Hospital of Jiangxia District, Wuhan, 430299, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Li, Department of Nephrology, The first People’s hospital of jiangxia district, No. 1 of Cultural Avenue, Wuhan, 430299, People’s Republic of China, Tel +86027-87958740, Email 307034153@qq.comBackground: We wanted to demonstrate whether the initial platelet-to-albumin ratio (PAR) had predictive value for cardiac surgery-associated acute kidney injury (CSA-AKI) and prognosis of critical care patients.Methods: This is an observational and multi-center study from the MIMIC-IV database, the eICU-CRD database as well as CS patients at our institution. Logistic regression and Cox regression analyses were applied to determine the predictive value for CSA-AKI and in-hospital mortality. LASSO and SVM-RFE models were then employed to discover the coincident variables connected with CSA-AKI. The main objective of this research was the incidence of CSA-AKI, whereas the secondary endpoint was in-hospital death.Results: The higher PAR value (≥ 4.67) had a higher risk of CSA-AKI (adjusted OR = 4.02, 95% CI 3.41– 4.75, P < 0.001) and in-hospital mortality (HR = 2.41 95% CI 1.44– 4.03, P = 0.001) after adjusted for other confounding factors including patients with or without chronic kidney disease. The proposed nomogram based on PAR and others clinical factors selected by LASSO and SVM-RFE models for CSA-AKI had the C-index 0.821 (95% CI 0.807– 0.834), 0.808 (95% CI 0.787– 0.829), 0.745 (95% CI 0.728– 0.762), and 0.826 (95% CI 0.753– 0.899) in these cohorts, respectively. The nomogram exhibited both remarkable calibration capacity and therapeutic helpfulness in all groups.Conclusion: PAR is a relative excellent measure for the event AKI and prognosis of ICU patients who undergone CS. The suggested nomogram based on PAR resulted in an accurate prediction for the detection of critical care patients with CSA-AKI.Keywords: platelet to albumin ratio, cardiac surgery, acute kidney injury, nomograms, prognosis

Xinmei Yang,1– 3 Xijun Wu,4 Xiaosen Wu,5 Lei Huang,1,2 Jingrui Song,1,2 Chunmao Yuan,1,2 Zhixu He,3,6 Yanmei Li1,2 1State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, People’s Republic of China; 2The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guizhou Medical University, Guiyang, 550014, People’s Republic of China; 3Stem Cell and Tissue Engineering Research Center, Guizhou Medical University, Guiyang, 550004, People’s Republic of China; 4Department of Laboratory, The Affiliated Jinyang Hospital of Guizhou Medical University, Guiyang, 550023, People’s Republic of China; 5FuRong Tobacco Research Station, Xiangxi Autonomous Prefecture Tobacco Company Yongshun Branch, Yongshun, 416700, People’s Republic of China; 6Department of Pediatrics, Affiliated Hospital of Guizhou Medical University, Guiyang, 550001, People’s Republic of ChinaCorrespondence: Yanmei Li, State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, People’s Republic of China, Tel/Fax +86 85183805081, Email liyanmei518@hotmail.com Zhixu He, Stem Cell and Tissue Engineering Research Center, Guizhou Medical University, Guiyang, 550004, People’s Republic of China, Tel/Fax +86 13595019670, Email hzx@gmc.edu.cnPurpose: Chronic myelogenous leukemia (CML) is a hematological malignancy with increased proliferation of cells of the myeloid series. This can disrupt normal hematopoiesis. The 1-(2-(dimethylamino)acetyl)-rocaglaol (MQ-16) is a new synthetic flavagline compound that showed promising activity in chronic myeloid leukemia K562 cells. This study aims to analyze the underlying mechanisms of MQ-16 against CML.Methods: Growth, cell cycle progression, and apoptosis were assessed in K562 cells following MQ-16 exposure by MTT assay and flow cytometry. The effect of MQ-16 on DNA strands between nucleosomes was examined by 1% agarose gel electrophoresis. PI3K/Akt/mTOR, JAK2/STAT3, and mitogen-activated protein kinase (MAPK) pathway-related proteins were detected in MQ-16–treated K562 cells by Western blot.Results: MQ-16 significantly inhibited the proliferation of K562 cells and arrested the cell cycle at the G2/M phase in a time- and concentration-dependent manner. MQ-16 induced mitochondria-dependent apoptosis by downregulating the anti-apoptotic proteins Bcl-2 and Bcl-xL and induced time- and concentration-dependent DNA fragmentation. In addition, MQ-16 affected the expression of PI3K/Akt/mTOR, JAK2/STAT3, and MAPK pathway-related proteins.Conclusion: In summary, MQ-16 appears to be a promising chemotherapeutic drug for treating CML.Keywords: CML, flavagline, cycle arrest, apoptosis, PI3K/Akt/mTOR, JAK2/STAT3, MAPK

Pengfei Huan,1,2 Li Wang,1,2 Zhuqing He,1,2 Jiancheng He1,2 1School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Shanghai Key Laboratory of Health Identification and Assessment, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Jiancheng He, Email hejc8163@163.comAbstract: Parkinson’s disease (PD) is a common degenerative disease of the nervous system that seriously affects the quality of life of the patients. The pathogenesis of PD is not yet fully clear. Previous studies have confirmed that patients with PD exhibit obvious gut microbiota imbalance, while intervention of PD by regulating the gut microbiota has become an important approach to the prevention and treatment of this disease. Traditional Chinese medicine (TCM) has been shown to be safe and effective in treating PD. It has the advantages of affecting multiple targets. Studies have shown TCM can regulate gut microbiota. However, the specific mechanism of action is still unclear. Therefore, this article will mainly discuss the association of the alteration of the gut microbiota and the incidence of PD, the advantages of TCM in treating PD, and the mechanism of regulating gut microbiota by TCM to treat PD. It will clarify the target and mechanism of TCM treating PD by acting gut microbiota and provided a novel methodology for the prevention and treatment of PD.Keywords: Parkinson’s disease, gut microbiota, traditional Chinese medicine, pathogenesis

Huabin Wang,1,2,&ast; Junbin Huang,1,2,&ast; Wenfang Yi,1,2,&ast; Jiahong Li,3 Nannan He,4 Liangliang Kang,4 Zhijie He,5 Chun Chen1,2 1Division of Hematology/Oncology, Department of Pediatrics, the Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518107, People’s Republic of China; 2Department of Pediatric Intensive Care Unit, the Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518107, People’s Republic of China; 3Department of Neonatal Intensive Care Unit, the Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518107, People’s Republic of China; 4Department of Pediatric Intensive Care Unit, Shenzhen Children’s Hospital, Shenzhen, 518000, People’s Republic of China; 5Department of Intensive Care Unit, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijie He; Chun Chen, Email hezhijie@mail.sysu.edu.cn; chenchun69@126.comObjective: The pathogenesis of sepsis is still unclear due to its complexity, especially in children. This study aimed to analyse the immune microenvironment and regulatory networks related to sepsis in children at the molecular level and to identify key immune-related genes to provide a new basis for the early diagnosis of sepsis.Methods: The GSE145227 and GSE26440 datasets were downloaded from the Gene Expression Omnibus. The analyses included differentially expressed genes (DEGs), functional enrichment, immune cell infiltration, the competing endogenous RNA (ceRNA) interaction network, weighted gene coexpression network analysis (WGCNA), protein–protein interaction (PPI) network, key gene screening, correlation of sepsis molecular subtypes/immune infiltration with key gene expression, the diagnostic capabilities of key genes, and networks describing the interaction of key genes with transcription factors and small-molecule compounds. Finally, real-time quantitative PCR (RT–qPCR) was performed to verify the expression of key genes.Results: A total of 236 immune-related DEGs, most of which were enriched in immune-related biological functions, were found. Further analysis of immune cell infiltration showed that M0 macrophages and neutrophils infiltrated more in the sepsis group, while fewer activated memory CD4+ T cells, resting memory CD4+ T cells, and CD8+ T cells did. The interaction network of ceRNA was successfully constructed. Six key genes (FYN, FBL, ATM, WDR75, FOXO1 and ITK) were identified by WGCNA and PPI analysis. We found strong associations between key genes and constructed septic molecular subtypes or immune cell infiltration. Receiver operating characteristic analysis showed that the area under the curve values of the key genes for diagnosis were all greater than 0.84. Subsequently, we successfully constructed an interaction network of key genes and transcription factors/small-molecule compounds. Finally, the key genes in the samples were verified by RT–qPCR.Conclusion: Our results offer new insights into the pathogenesis of sepsis in children and provide new potential diagnostic biomarkers for the disease.Keywords: sepsis in children, key immune-related genes, transcriptomic analysis, Gene Expression Omnibus, diagnostic biomarkers

Huidan Zhang,1– 3,&ast; Jing Xu,1,2,4,&ast; Qingrui Wu,3,&ast; Heng Fang,1,2,4 Xin Shao,1,2 Xin Ouyang,1 Zhimei He,2 Yiyu Deng,2– 4 Chunbo Chen1,3,4 1Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 2Department of Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 3School of Medicine, South China University of Technology, Guangzhou, 510006, People’s Republic of China; 4The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiyu Deng; Chunbo Chen, Tel +86-20-83827812 ext. 61526, Fax +86-20-83827712, Email yiyudeng666@163.com; gghccm@163.comPurpose: Neuroinflammation plays an important part in the pathophysiology of sepsis-associated encephalopathy (SAE). Gut microbiota and gut brain axis are considered as important mediators in the development of neurological diseases. The aim of this study was to investigate the role of intestinal microbiota in sepsis-related brain injury and to explore the underlying mechanisms.Methods: Mouse model of SAE was established using cecal ligation and puncture (CLP). Based on the mouse mortality and the associated time of death, light SAE (LSAE) and severe SAE (SSAE) were classified. Fecal microbiota transplantation (FMT) was performed to verify the role of intestinal microbiota. Feces of mice in the two groups which collected before operation were sequenced for 16S and targeted short chain fatty acids.Results: Intestinal microbiota from SSAE and LSAE mice displayed diverse functions. Interestingly, LSAE mice produced more butyric acid compared with SSAE mice. In the in vivo experiments, sodium butyrate (NaB) reduced the high oxidative stress levels in mice hippocampus and conferred a marked survival superiority to sepsis mice. In addition, NaB prevented the increase in intracellular reactive oxygen species (ROS) generation and inducible nitric-oxide synthase expression in LPS-stimulated primary microglia. The GPR109A/Nrf2/HO-1 signaling pathway was found to be involved in the activation of antioxidant response of primary microglia induced by sodium butyrate.Conclusion: Our findings indicate a crucial role of gut microbiota in the susceptibility to SAE. Butyrate, a metabolite of intestinal microbiota, may have a neuroprotective effect in the process of sepsis by GPR109A/Nrf2/HO-1 pathway.Keywords: gut microbiome, butyrate, sepsis-related brain injury, primary microglia, oxidative stress

Ruijie Dang,1,&ast; Meiling Jin,2,&ast; Jingzhu Nan,3 Xuege Jiang,4 Zheng He,5 Fang Su,6 Diangeng Li7 1Department of Oncology, The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Nephrology, Beijing-Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 3Department of Clinical Laboratory, the First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 4Respiratory Diseases Department, Second Medical Center of PLA General Hospital, Beijing, 100853, People’s Republic of China; 5Department of Clinical Laboratory, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 6Aeronautical Physiological Identification Training Laboratory, Air Force Medical Center, PLA, Beijing, 100142, People’s Republic of China; 7Department of Scientific Research, Beijing-Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Diangeng LiDepartment of Scientific Research, Beijing-Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of ChinaTel/Fax +86-10-85231049Email lidiangeng@126.comPurpose: Papillary renal cell carcinoma (PRCC) is a common renal cell carcinoma. Recent studies have reported that ferroptosis is involved in the occurrence and development of tumors. Long non-coding RNAs can be used as independent biomarkers for the diagnosis and prognosis of a variety of tumors.Methods: Gene expression profile and clinical information of patients with PRCC were obtained from The Cancer Genome Atlas (TCGA) database. Lasso penalized Cox regression and univariate Cox regression analysis were utilized for model construction. The Kaplan–Meier (K-M) and receiver operating characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signature. Immune cell infiltration and immune function were compared between the high-risk and low-risk groups. Chemotherapy sensitivity analysis was also performed.Results: We constructed a prognostic signature consisting of 15 ferroptosis-related lncRNAs. The K-M curves validated the fine predictive accuracy of the prognostic signature (p

Lan Tang,1 Wenhui Jiang,1 Lan Wu,1 Xiaolan Yu,1 Zheng He,1 Weiguang Shan,1 Lulu Fu,1 Zhenhai Zhang,2 Yunchun Zhao3 1College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, People’s Republic of China; 2Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, People’s Republic of China; 3Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaCorrespondence: Zhenhai ZhangHospital of Integrated Traditional Chinese and Western Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210018, People’s Republic of ChinaTel +86 13758190403Email david23932@163.comYunchun ZhaoWomen’s Hospital, School of Medicine, Zhejiang University, 1, Xueshi Road, Hangzhou, 310016, People’s Republic of ChinaTel +86 15858178673Email 5515059@zju.edu.cnBackground: Doxorubicin (DOX) is an anthracycline antibiotic that inhibits the growth of several solid and hematologic malignant tumors. Increasing the targeting ability of DOX and reducing the multi-drug resistance (MDR) of tumor cells to DOX are major aims for researchers.Purpose: In this study, to increase therapeutic efficiency, reduce the side effects and the MDR of tumor cells to DOX, D-alpha-tocopheryl polyethylene glycol 2000 succinate monoester (TPGS2000)-DOX prodrug micelles were developed by grafting DOX to TPGS2000 via an amide bond that release DOX in the slightly acidic conditions in tumor tissue.Materials and Methods: The TPGS2000-DOX micelles were constructed using polyethylene glycol 12-hydroxy stearate (Solutol HS15) as the carrier. The in vitro drug release profile and dilution stability of the nanomicelles were determined. The in vitro cytotoxicity and distribution of the nanomicelles in the tumor cells were also investigated. Moreover, we explored the therapeutic outcomes using the MCF-7/ADR tumor-bearing murine model.Results: The average particle size was approximately 30 nm with a narrow distribution, which was conducive for solid tumor accumulation. The results of in vivo imaging and in vitro cellular uptake assays demonstrated that the TPGS2000-DOX micelles increased the tumor-targeting ability and cellular uptake of DOX. The anticancer potential of TPGS2000-DOX micelles was higher than that of DOX, as revealed by in vitro cytotoxic assays with MCF-7/ADR cells and in vivo antitumor assays with MCF-7 tumor-bearing nude mice.Conclusion: TPGS2000-DOX prodrug micelles reverse the MDR of tumor cells, achieve passive targeting by forming nanomicelles, and subsequently enhance the efficacy and reduce the toxicity of DOX.Keywords: doxorubicin, D-alpha-tocopheryl polyethylene glycol 2000 succinate monoester, breast cancer, multi-drug resistance, polymer prodrug nanomedicine

Lu Yang,1 Zhen’an He,2 Xuan Gu,3 Hao Cheng,4 Lin Li5 1Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital City, Hangzhou, Zhejiang Province, People’s Republic of China; 2Shaanxi Institute of Medical Device Quality Supervision and Inspection, Xi’an City, Shaanxi Province, People’s Republic of China; 3Xi’an Hospital of Civil Aviation, Xi’an City, Shaanxi Province, People’s Republic of China; 4Department of Ultrasonography, Shaanxi Cancer Hospital Affiliated to Xi’an Jiaotong University, Xi’an City, Shaanxi Province, People’s Republic of China; 5Shaanxi Cancer Hospital Affiliated to Xi’an Jiaotong University, Xi’an City, Shaanxi Province, People’s Republic of ChinaCorrespondence: Hao Cheng; Lin Li Email uschenghao@163.com; lloyd_115599@sina.comObjective: The purpose of the current study is to explore the demographic characteristics of hyperuricemia in China.Study Design: The cross-sectional study was conducted, and the CHARLS dataset in 2011 was used.Methods: Logistic regression model was used to assess the association between BMI and hyperuricemia. We also used restricted cubic spline with three knots to assess the dose–response relationship. To investigate the differences in dose–response relationships in various groups, stratification analysis was conducted.Results: Of the 9408 middle and older participants, those who were overweight or obese had higher risk for hyperuricemia (OR=1.26, 95% CI=1.01– 1.57; OR=1.90, 95% CI=1.46– 2.47). In the subgroup, the effect of obesity on hyperuricemia was robust in varying gender and age. However, among overweight group, those with being male and aged over 60 years had higher risk for hyperuricemia (male: OR=1.42, 95% CI=1.07– 1.90; over 60 years: OR=1.28, 95% CI=1.03– 1.60). A dose-response relationship was examined between BMI and the risk of hyperuricemia. The result showed that the odds ratio of hyperuricemia and BMI displayed U-shaped nonlinear relationship (Ptrend< 0.001, non-linear P< 0.001).Conclusion: The association between BMI and hyperuricemia showed positive relationship. Specifically, the group with male and age over 60 years had higher risk of hyperuricemia along with increased weight.Keywords: body mass index, hyperuricemia, CHARLS, middle and older people

Hua Cao,1 Chungang Xiao,1 Zhangxiu He,2 Hong Huang,3,4 Huifang Tang1,4 1The First Affiliated Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 2The First Affiliated Hospital, Department of Nephrology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 3The First Affiliated Hospital, Institute of Clinical Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 4The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of ChinaCorrespondence: Hong Huang; Huifang TangThe First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of ChinaEmail trave1@126.com; tanghuifang999@163.comAbstract: Cardiac remodeling is accompanied by cardiac hypertrophy, fibrosis, and dysfunction, eventually leading to heart failure (HF). However, the molecular mechanisms involved in cardiac remodeling are complicated, especially the association with immune. Immunoglobulin E (IgE) is a class of immunoglobulins involved in immune response to specific allergens. Recently, Zhao et al characterized a novel specific role of IgE and its high affinity receptor (Fc&epsiv;R1) in directly promoting pathological myocardial remodeling and cardiac dysfunction. Additionally, upon blocking IgE-Fc&epsiv;R1 signaling using Fc&epsiv;R1 genetic depletion or by administrating the anti-IgE monoclonal antibody omalizumab (Oma) in mice, they observed that cardiac hypertrophy and cardiac interstitial fibrosis induced by angiotensin II (Ang II) or transverse aortic constriction (TAC) were significantly suppressed. In contrast, IgE administration alone can aggravate pathological cardiac remodeling and dysfunction. RNA-seq and downstream analysis indicated that TGF-β was the common pathway and the most pivotal mediator in IgE-Fc&epsiv;R1-induced cardiac remodeling and dysfunction. Furthermore, the administration of a TGF-β inhibitor could ameliorate cardiac remodeling and improve cardiac function. Therefore, these findings suggest that IgE-Fc&epsiv;R1 maybe promising therapeutic targets for cardiac remodeling and provide an experimental basis for the use of omalizumab for HF patients combined with high serum IgE levels or allergic diseases.Keywords: cardiac remodeling, IgE- Fc&epsiv;R1, immunoglobulins, TGF-&#x03B2

Longhao Hu,1,&ast; Xi Yang,2,3,&ast; Jing Yin,1 Xuan Rong,1 Xinlei Huang,1 Peiquan Yu,3 Zhiqiang He,1 Yi Liu1– 3 1Department of Biophysics, School of Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 2School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 3Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi LiuDepartment of Biophysics, School of Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of ChinaTel/Fax +86-516-83262084Email cbpeliuyinew@163.comPurpose: The aim was to evaluate the antimicrobial potential of AgNPs synthesized with Artemisia argyi leaf extract and investigate the antimicrobial synergistic effects of AgNPs combined with domiphen and provide an efficient and broad-spectrum combination drug strategy.Methods: AgNPs synthesized with Artemisia argyi leaf extract were studied using UV–vis spectroscopy, FTIR spectroscopy and particle size analysis. Then, Artemisia argyi leaf extract-synthesized AgNPs and domiphen were tested against Acinetobacter baumannii (ATCC 19606), Staphylococcus aureus (ATCC 6538), Escherichia coli (8099) and Candida albicans (ATCC 10231), respectively. Then, we explore synergistic antimicrobial effect and synergistic anti-biofilm effect through combined drug susceptibility test and combined drug minimum biofilm eradication concentration (MBEC50) test.Results: Characteristic absorption bands of AgNPs were found near 430 nm in the UV–vis spectrum. Particle size analysis results revealed that the average particle size of Artemisia argyi leaf extract-synthesized AgNPs was 77.6 nm. Artemisia argyi leaf extract-synthesized AgNPs showed high antimicrobial activity against the above four strains. Minimum inhibitory concentration (MIC) of Artemisia argyi leaf extract-synthesized AgNPs against strains was 1 μg/mL for Acinetobacter baumannii, 2 μg/mL for Staphylococcus aureus, Escherichia coli and Candida albicans. MBEC50 of Artemisia argyi leaf extract-synthesized AgNPs against strains was 2 μg/mL for Acinetobacter baumannii, 4 μg/mL for Staphylococcus aureus, 1/2 μg/mL for Escherichia coli and 2 μg/mL for Candida albicans. The combination of Artemisia argyi leaf extract-synthesized AgNPs and domiphen has synergistic antimicrobial effect and synergistic anti-biofilm effect. Fractional inhibitory concentration (FIC) was ≤ 0.5.Conclusion: Artemisia argyi leaf extract-synthesized AgNPs had antimicrobial activity against the above four strains. The combination of Artemisia argyi leaf extract-synthesized AgNPs and domiphen has synergistic antimicrobial effects to reduce the dosage of each antimicrobial drugs. Artemisia argyi leaf extract-synthesized AgNPs and domiphen have synergistic anti-biofilm effects.Keywords: AgNPs, domiphen, synergy, pathogenic biofilm, combination medication

Ruohao Wu,1,2,&ast; Wenting Tang,3,4,&ast; Kunyin Qiu,1,2 Pinggan Li,1,2 Yu Li,1,2 Dongfang Li,1,2 Zhanwen He1,2 1Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong High Education Institutes, Sun Yat-sen Memorial Hospital, Guangzhou, People’s Republic of China; 2Department of Pediatrics, Sun Yat-sen Memorial Hospital, Guangzhou, People’s Republic of China; 3State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen Cancer Center, Guangzhou, People’s Republic of China; 4Department of Molecular Diagnostics, Sun Yat-sen Cancer Center, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhanwen He; Dongfang LiKey Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong High Education Institutes, Sun Yat-sen Memorial Hospital, Guangzhou, People’s Republic of ChinaEmail hezhanw@mail.sysu.edu.cn; lidf@mail.sysu.edu.cnBackground: Although emerging animal- or cell-based evidence supports the relationship between casein kinase 2 alpha protein 1 (CSNK2A1) and cancers, no pan-cancer analysis is available. Thus, this report aimed to display the prognostic landscape of CSNK2A1 in pan-cancer and investigate the relationship between CSNK2A1 and tumor immunity.Methods: In the current study, we investigated the expression pattern, genetic alterations and survival analysis of CSNK2A1 in pan-cancer across multiple datasets and online platforms. The correlations between CSNK2A1 expression and tumor immunity were explored and visualized via Rlanguage software. Following this, immunohistochemical (IHC) staining and Kaplan–Meier survival analysis were conducted in clinical patients for proving the bioinformatic findings. Analysis of protein–protein interaction and gene functional enrichment was conducted using GeneMANIA platform and gene set enrichment analysis (GSEA), respectively.Results: In TCGA, tumor tissue had ahigher expression level of CSNK2A1 compared with that in corresponding normal tissue. An increased expression level of CSNK2A1 was related to poor clinical prognosis in most types of cancer such as LIHC. The following expression and survival analysis in clinical liver hepatocellular carcinoma (LIHC) patients confirmed these TCGA findings. CSNK2A1 expression had significant positive correlations with pro-tumor-infiltrating immune cells (TIICs) like M1-macrophages and fibroblasts, and significant negative correlations with anti-tumor-TIICs like activated CD8+ Tcells and NK cells, suggesting specific interactions between CSNK2A1 and certain TIICs subtypes. Furthermore, CSNK2A1 expression had the most significant positive correlations with common markers of immune checkpoint including programmed death ligand-1 (PDL1) in LIHC. These findings were validated by an IHC analysis. GSEA analysis demonstrated that high expression of CSNK2A1 was related to cell signaling pathways and immunity-related activities.Conclusion: These findings suggested that CSNK2A1 was not only related to poor clinical prognosis in cancer like LIHC but also anovel immunotherapy-related biomarker in cancers, especially in LIHC, shedding new light on anti-tumor strategy.Keywords: casein kinase 2 alpha protein 1, pan-cancer, dataset, survival analysis, tumor immunity, tumor microenvironment

Zelai He,1,&ast; Jia Liu,1,&ast; Yuwei Ma,1,&ast; Hao Jiang,1 Zhen Cui,1 Guowen Wang,1 Yufeng Wu,2 Jiuzhou Liu,3 Xixi Cai,4 Jing Qian,1 Jingwen Huang,1 Huijun Zhang,5 Hongwei Li1 1The First Affiliated Hospital of Bengbu Medical College & Tumor Hospital Affiliated to Bengbu Medical College, Bengbu, 233004, People’s Republic of China; 2Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, 450008, People’s Republic of China; 3The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, People’s Republic of China; 4Department of Radiation Oncology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, People’s Republic of China; 5Department of Cardiothoracic Surgery, Huashan Hospital of Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huijun Zhang; Hongwei Li Email zhanghuijunhp@163.com; 1249223318@qq.comIntroduction: Cranial radiotherapy (CRT) is the main treatment for non-small cell lung cancer (NSCLC) with brain metastasis (BM) and non-EGFR/ALK/ROS1-TKIs indication, and anlotinib can improve overall prognosis. However, the clinical effects of CRT combined with anlotinib for the treatment of NSCLC with BM remain unclear.Methods: We retrospectively analyzed the clinical effects of anlotinib + CRT versus CRT alone in NSCLC patients with BM and non-EGFR/ALK/ROS1-TKIs indication from September 2016 to June 2020. The progression-free survival (PFS) and overall survival (OS) of anlotinib + CRT versus CRT alone were analyzed. After evaluation of the clinical characteristics to generate a baseline, the independent prognostic factors for intracranial PFS (iPFS) and OS were subjected to univariate and multivariate analysis. Finally, subgroup analysis for iPFS and OS was performed to assess treatment effects using randomized stratification factors and stratified Cox proportional hazards models.Results: This study included data for 73 patients with BM at baseline. Of the 73 patients, 45 patients received CRT alone, and 28 patients received CRT + anlotinib. There was no significant difference in clinical features between the two groups (P > 0.05). Compared with the CRT group, the combined group had longer iPFS (median iPFS [miPFS]: 3.0 months vs 11.0 months, P = 0.048). However, there were no significant differences in OS, extracranial PFS, and systemic PFS. For clinical features, univariate and multivariate analysis showed that the plus anlotinib treatment was an independent advantage predictor of iPFS (hazard ratio [HR] 0.51; 95% confidence interval [CI] 0.27– 0.95; P = 0.04), and age ≥ 57 years (HR 1.04, 95% CI 1.01– 1.08, P = 0.014) and KPS score ≤ 80 (HR 1.04, 95% CI 1.01– 1.08, P = 0.014) were independent disadvantage predictors of OS (P < 0.05). In addition, although this difference was not statistically significant (p > 0.05), the patients with the anlotinib + local CRT (LCRT) treatment had the longest iPFS (miPFS: 27.0 months) and OS (median OS [mOS]: 36 months). The miPFS and mOS values for the LCRT group were 11 months and 18 months, respectively, with shorter values for whole-brain RT (WBRT) + anlotinib group, WBRT + LCRT + anlotinib group, WBRT, and WBRT + LCRT.Conclusion: Anlotinib can improve the intracranial lesion control and survival prognosis of NSCLC patients with CRT.Keywords: radiotherapy, lung cancer, brain metastases, progression-free survival, overall survival

Xiao-Ling Zou,1,&ast; Jin-Jie Wu,2,&ast; Hui-Xia Ye,3,&ast; Ding-Yun Feng,1,&ast; Ping Meng,1 Hai-Ling Yang,1 Wen-Bin Wu,1 Hong-Tao Li,1 Zhen He,2 Tian-Tuo Zhang1 1Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Gynecology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tian-Tuo ZhangDepartment of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, People’s Republic of ChinaEmail zhtituli@163.comZhen HeDepartment of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, Guangdong, People’s Republic of ChinaEmail hezh5@mail.sysu.edu.cnObjective: This study aimed to investigate the gut microbiome profile in different inflammatory phenotypes of treatment-naive newly diagnosed asthmatic adults, to gain insight on the associations between intestinal microbiota and phenotypic features that characterize asthma heterogeneity to develop new treatments for asthma.Methods: Fresh stool samples were obtained from 20 healthy subjects and 47 newly diagnosed asthmatic patients prior to any interventions. The asthmatics were divided into allergic and non-allergic cohorts. Intestinal microbiota was analyzed by 16S rRNA next-generation sequencing. Demographic and clinical parameters were collected. Alpha and beta diversity analysis were calculated to detect differences within sample phylotype richness and evenness between controls and asthmatic patients. Statistically significant differences between samples were analyzed for all used metrics, and features of gut bacterial community structure were evaluated in relation to extensive clinical characteristics of asthmatic patients.Results: Gut microbial compositions were significantly different between asthmatic and healthy groups. Alpha-diversity of the gut microbiome was significantly lower in asthmatics than in controls. The microbiome between allergic and non-allergic asthmatic patients were also different, and 28 differential species were identified. PPAR signaling pathway, carotenoid biosynthesis, and flavonoid biosynthesis were significantly positively correlated with allergy-associated clinical index, including FENO value, blood eosinophil counts, and serum IgE and IL-4 levels. A combination of Ruminococcus bromii, Brevundimonas vesicularis, and Clostridium disporicum showed an AUC of 0.743 in the specific allergic/non-allergic cohort. When integrating C. disporicum, flavone, flavonol biosynthesis, and serum IL-4 values, the AUC achieved 0.929 to classify asthmatics. At the same time, C. colinum and its associated functional pathway exhibited an AUC of 0.78 to distinguish allergic asthmatics from those without allergies.Conclusion: We demonstrated a distinct taxonomic composition of gut microbiota in different asthmatic phenotypes, highlighting their significant relationships. Our study may support considerations of intestinal microbial signatures in delineating asthma phenotypes.Keywords: asthma, phenotypes, gut microbiota, 16S rRNA next-generation sequencing, functional pathway

Yuanbo Wu,1,* Jiandong Zhang,2,* Jiangwei Ni,2 Zhihao Yang,2 Kun Chen,2 Liangcheng Zheng,2 Zhifeng He2 1Department of Cardiothoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liangcheng Zheng; Zhifeng He Email dr.zlc@163.com zhif_he@126.comBackground: This study aimed to evaluate the properties and functions of polysaccharide-based porous microsphere (PPM) for drug delivery, as well as its inhibitory effect on malignant tumors.Materials and Methods: PPM was prepared using the inverse emulsion polymerization method. FT-IR measurements were conducted to measure the wavenumber of PPM. Particle size distribution was tested with a particle analyzer, and surface morphologies of PPM were observed using a scanning electron microscope (SEM). Dialysis method, Cell Counting Kit-8 (CCK-8), and cell apoptosis analysis were adopted to evaluate the drug release, cytotoxicity and biocompatibility of mitomycin-C (MMC), respectively. Finally, an in vivo study was performed in C57BL/6 mice to confirm the function of MMC-loaded PPM on tumor growth.Results: FT-IR spectra proved the successful preparation of MMC-loaded PPM. PPM had an average size of 25.90 ± 0.34 μm and then increased to 30.10 ± 0.20 μm after drug loading. Under SEM, the surface morphology was lotus seedpod surface-like, with macropits on the surface and micropores in macropits. Compared with the free MMC group, MMC-loaded PPM exhibited a delayed drug release rate in a pH-dependent manner and higher cell viability. Flow cytometry results showed that the cell apoptosis in the PPM/MMC group was lower than that in the free MMC group. In vivo experiment revealed the inhibitory efficacy of MMC-loaded PPM on malignant tumors.Conclusion: In summary, MMC-loaded PPM exhibited favorable surface morphology, sustained drug release ability, nontoxicity and excellent biocompatibility, suggesting that PPM might be a potential drug carrier for tumor treatment.Keywords: polysaccharide-based porous microsphere, tumor treatment, mitomycin-C, drug release, inverse emulsion polymerization

Zhang LF, Zhou ZW, Wang ZH, et al. Drug Des Devel Ther. 2014;9:241–272. The Editor and Publisher of Drug Design, Development and Therapy wish to retract the published article. Concerns were raised regarding the alleged duplication of bands in the western blot images from Figures 12, 15 and 16. Specifically, Western blot bands for Figure 12D, Coff+Mel, β-actin appear to have been duplicated with the same bands from Figure 15A, Coff+Mel, β-actin, and Figure 15A, Caff+Mel, β-actin. Western blot bands for Figure 14A, Coff+Mel, β-actin appear to have been duplicated with the same bands for Figure 14A, Caff+Mel, β-actin. Western blot bands for Figure 14A, Coff+Mel, β-actin, and Caff+Mel, β-actin appear to have been duplicated with the same bands for Figure 16A, Coff+Mel, β-actin, and Figure 16A, Caff+Mel, β-actin. Western blot bands for Figure 15A, Coff+Mel, β-actin appear to have been duplicated with the same bands for Figure 15A, Caff+Mel, β-actin. The western blot band for Figure 16A, Coff+Mel, p-Akt, Lane C, appears to have been duplicated with the same band for Figure 16A, Caff+Mel, p-Akt, Lane C. The authors responded to our queries but were unable to provide a satisfactory explanation for the alleged duplication, nor were they able to provide original data that could adequately verify the findings. The Editor requested to retract the article and the authors were notified of this. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Dan Tang,1,2,* Haihai Luo,1,* An Xie,3 Zhichun He,1 Bin Zou,4 Fei Xu,1 Wei Zhang,1 Xinping Xu1 1Jiangxi Institute of Respiratory Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of General Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Jiangxi Institute of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 4Department of Thoracic Surgery, Jiangxi Cancer Hospital, Nanchang, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinping Xu; Wei ZhangJiangxi Institute of Respiratory Disease, The First Affiliated Hospital of Nanchang University, No. 17 Yongwai St, Nanchang, Jiangxi, 330006, People’s Republic of ChinaEmail xinpingxu@ncu.edu.cn; zhangweiliuxin@163.comPurpose: Lung cancer has been recognized as the most fatal malignant tumor with the highest morbidity and mortality in recent years.Materials and Methods: In this study, we found that LMNB1, which is an important component protein of the nuclear skeleton, was significantly upregulated in lung adenocarcinoma (LUAD) and correlated with the pathological stage as well as lymphatic metastasis.Results: In vitro loss-of-function study utilizing LMNB1 knockdown LUAD cell lines demonstrated that depletion of LMNB1 inhibited development of LUAD through regulating cell proliferation, cell apoptosis, cell cycle and cell motility. Decreased tumorigenesis of LMNB1 knockdown LUAD cells was proved in mice xenograft models. Moreover, the mechanism by which LMNB1 promotes LUAD was explored through the expression evaluation of apoptosis-related proteins and cancer-related signaling pathways.Conclusion: In conclusion, our study identified LMNB1 as a tumor promotor and a potential therapeutic target in LUAD.Keywords: lung cancer, lung adenocarcinoma, LMNB1, cell proliferation, cell apoptosis

Ding Ye,1 Bin Liu,1 Zhixing He,2 Lin Huang,2 Yu Qian,1 Keding Shao,2 Chengping Wen,2 Yingying Mao1 1Department of Epidemiology and Biostatistics, Zhejiang Chinese Medical University School of Public Health, Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Institute of Basic Research in Clinical Medicine, Zhejiang Chinese Medical University School of Basic Medical Sciences, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaCorrespondence: Yingying MaoDepartment of Epidemiology and Biostatistics, Zhejiang Chinese Medical University School of Public Health, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaTel +86-571-8661-3536Email myy@zcmu.edu.cnChengping WenInstitute of Basic Research in Clinical Medicine, Zhejiang Chinese Medical University School of Basic Medical Sciences, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaTel +86-571-8663-3377Email wengcp@163.comObjective: To investigate the potential causal associations of circulating levels of growth differentiation factor 15 (GDF-15) with the risk of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) using a Mendelian randomization (MR) design.Methods: A genome-wide association study (GWAS) of GDF-15 among 5,440 individuals of European ancestry was used to identify genetic instruments. Summary statistics of SLE, RA and IBD were obtained from publicly available GWASs. We conducted an MR study using the inverse-variance weighted (IVW) method, supplemented with simple-median and weighted-median methods. Cochran Q test and MR-Egger regression were used to detect potential heterogeneity and directional pleiotropy. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.Results: We found that genetically predicted high circulating GDF-15 levels were associated with a decreased risk of SLE (OR 0.80, 95% CI 0.68– 0.92 by IVW), with similar results in sensitivity analyses. In replication analysis using summary data from another SLE GWAS, the results were consistent (OR 0.82, 95% CI 0.71– 0.93 by IVW). Moreover, no evidence of heterogeneity or pleiotropy was detected. However, genetically determined circulating levels of GDF-15 were not associated with risk of RA or IBD in the primary analysis and subsequent sensitivity analyses.Conclusions: Our study suggested an inverse association between circulating GDF-15 levels and risk of SLE, and further studies are warranted to elucidate the underlying biological mechanisms. There was limited evidence supporting a causal association of circulating GDF-15 levels with risk of RA and IBD.Keywords: growth differentiation factor 15, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Mendelian randomization, single nucleotide polymorphism

Yanjun Mi,1,* Yongwen Li,2,* Zhuo He,3,* Donghan Chen,2 Qingqi Hong,2 Jun You2 1Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, Fujian Province, 361003, People’s Republic of China; 2Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, Fujian Province, 361003, People’s Republic of China; 3Department of Gastropancreatoduodenal Surgery, Hunan Cancer Hospital, Changsha, Hunan Province, 410013, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun YouDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, No. 55 Zhenhai Road, Si Ming District, Xiamen, Fujian Province, 361003, People’s Republic of ChinaTel +86 13906051681Email youjun1681@163.comBackground: Linc-ROR is a long non-coding RNA, that is found aberrantly expressed in various human cancers. We aim here to unveil the role of Linc-ROR in gastric cancer (GC) progression.Methods: qPCR was used to determine gene expression. Cell viability was measured by CCK-8 assay. Transwell assays were performed to evaluate the GC cells’ migratory and invasive abilities. Xenograft mouse model was conducted to measure tumor growth.Results: We found that Linc-ROR were overexpressed in GC tissues compared to the adjacent tissues. High Linc-ROR predicts poor prognosis of GC patients. The prediction of bioinformatics online revealed that Linc-ROR could bind to miR-212-3p. Further, dual-luciferase reporter assay confirmed a direct interaction between Linc-ROR and miR-212-3p. Overexpression of miR-212-3p facilitated GC cells’ migration and invasion, while the silencing of miR-212-3p attenuated GC cell migratory and invasive abilities. Moreover, Linc-ROR knockdown significantly suppressed the proliferation, migration, and invasion of GC cells, whereas miR-212-3p antagomir partially reversed Linc-ROR knockdown-induced phenotypes. Fibroblast growth factor 7 (FGF7), a downstream molecule of miR-212-3p, was overexpressed in GC cells. The recovery of FGF7 expression partially reversed the phenotypes caused by Linc-ROR silencing. Mechanistically, silencing of Linc-ROR contributed to the downregulation of CDK4, CDK6, Cyclin D1, N-Cadherin, Vimentin, MMP-9, MMP-2, but caused the upregulation of P21, P27, E-Cadherin, CK-19 in MGC-803 cells; however, FGF7 treatment could reverse the results induced by Linc-ROR silencing. Results in vivo further suggested that Linc-ROR knockdown repressed GC tumor growth, where the expression of miR-212-3p was up-regulated and FGF7 expression was downregulated in tumor tissues of mice.Conclusion: These findings indicated that Linc-ROR/miR-212-3p/FGF7 axis played an important role in gastric cancer progression. Linc-ROR expression level was associated with the prognosis of GC patients.Keywords: Linc-ROR, miR-212-3p, FGF7, gastric cancer