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Baoyu Chen,1,* Qi Wang,1,* Chaobo Bai,1 Jing Chen,1 Danhua Zhao,1 Yuan Li,1 Junyi Chen,1 Xintong Guo,1 Jinjin Wang,1 Hongguang Chen,1 Xiaoxing Lai,2 Qiaoqin Wan,3 Zhiwen Wang,3 Nan Hu,4 Bing-Wei Zhang,4 Xuqiao Chen,5 Tao Ma,6 Junliang Yuan1 1Department of Neurology, Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University, Beijing, 100191, People’s Republic of China; 2Department of Health Care, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 3School of Nursing, Peking University, Beijing, 100191, People’s Republic of China; 4Department of Neurology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, People’s Republic of China; 5Department of Neurosciences, University of California San Diego, La Jolla, CA, 92093, USA; 6Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA*These authors contributed equally to this workCorrespondence: Junliang Yuan, Department of Neurology, Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), No. 51 hua Yuan Bei Road, Haidian District, Beijing, 100191, People’s Republic of China, Email junliangyuan@bjmu.edu.cnBackground: Behavioral and psychological symptoms of dementia (BPSD), as neuropsychiatric manifestations within dementia, constitute core features of dementia. However, there remains a gap in understanding the recognition of BPSD in China. Our current study was to explore the clinical awareness and treatment approaches for BPSD in China, focusing especially on the perspectives of neurologists and psychiatrists.Methods: A multicenter national survey was designed and a semi-structured questionnaire was distributed to healthcare professionals including doctors and nurses across all provinces of China. The questionnaire incorporated either closed (yes/no) and multiple-choice questions. The questions centered on the following areas: the perceived global frequency and relevance of BPSD; the assessment tools employed for evaluating BPSD; pharmacological approaches for addressing psychosis, apathy, agitation, aggression, depression, anxiety, sleep, and nutrition disorders; drug-related side effects; non-pharmacological treatment strategies. The anonymity of questionnaire responses was maintained to encourage participants to candidly express their viewpoints.Results: The majorities of respondents recognized the importance of BPSD. There were apparent differences in the perception of BPSD between neurologists and psychiatrists, encompassing variances in symptoms recognition, diagnostic approaches, and treatment strategies. A notable high percentage of neurology (27.8%) and psychiatry staff (23.6%) would not choose non-pharmacological interventions. Meanwhile, antipsychotics was overused in China. For aggression and agitation, more than half of neurologist and psychiatrist preferred antipsychotics. For psychosis, more than 80% of doctors chose antipsychotics. Nearly one-third of the medical staff expressed a preference for traditional Chinese medicine including ginkgo biloba extract.Conclusion: In summary, this study in China has shed light on the features related to perception, recognition, management, treatment options, and observed side effects associated with BPSD. Our findings have the potential to significantly enhance the understanding of BPSD characteristics among medical practitioners and offering valuable insights into improved management and treatment strategies of neuropsychic symptoms of dementia in China.Keywords: dementia, BPSD (behavioral and psychological symptoms of dementia), BPSD management, psychosis

Yi Yu,1 Ricong Xu,1 Zhijian Li,2,3 Qijun Wan1 1Department of Nephrology, The First Affiliated Hospital of Shenzhen University, The Second People’s Hospital of Shenzhen, Shenzhen, 518039, People’s Republic of China; 2Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China; 3NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, 510080, People’s Republic of ChinaCorrespondence: Qijun Wan, Department of Nephrology, The First Affiliated Hospital of Shenzhen University, The Second People’s Hospital of Shenzhen, Shenzhen, 518039, People’s Republic of China, Email yiyuan2224@sina.comAbstract: Primary membranous nephropathy (PMN) is one of the prevalent pathological types of adult primary nephrotic syndrome. Pathogenic autoantibodies targeting podocyte antigens such as phospholipase A2 receptor (PLA2R) lead to the disease. Patients frequently experience notable adverse effects when treated with conventional immunosuppressive therapies. Rituximab (RTX), a mouse/human monoclonal antibody, selectively depletes B cells and leads to a decrease in the antibody levels in the circulation, which helps to alleviate membranous nephropathy. Various RTX dosage regimens have been applied globally in the PMN treatment with satisfactory effects. Nevertheless, the optimal dosage of RTX has yet to be determined. This article reviews the application of different doses of RTX in the management of PMN so far.Keywords: membranous nephropathy, nephrotic syndrome, rituximab, dosage

Xinzuo Qin,1,* Xu Guo,2,* Yijiang Liu,1,3,* Zijian Wang,1 Xinyu Wang,1 Qi Wan,4 Mingjie Gao,5 Juexian Song1 1Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing, People’s Republic of China; 3School of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 4No. 904 Hospital of Joint Logistics Unit, Jiangsu, Wuxi, People’s Republic of China; 5Department of Ultrasonography, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingjie Gao; Juexian Song, Email mingjie.gao@xwh.ccmu.edu.cn; songjuexian@vip.163.comPurpose: Asymptomatic cerebral carotid artery stenosis (ACCAS) benefits from secondary prevention via statins and antiplatelets; nonetheless, the impact of medication alone is often limited. Evidence has suggested enhanced therapeutic outcomes when Chinese patent medicine—specifically, compound dilong capsules (CDC)—is integrated with conventional secondary prevention measures.Patients and Methods: We retrospectively analyzed 319 ACCAS patients from January 2018 to December 2022 at Xuanwu Hospital, Capital Medical University. Depending on the clinical outcomes—improvement or stabilization versus progression—patients were classified into effective or ineffective treatment groups. Patient medical records and questionnaire responses were the primary data sources. The study accounted for demographic variables, clinical history, and medication details, with the primary focus on CDC use and its duration. Treatment outcomes were gauged alongside Transcranial color-coded sonography and Carotid Doppler ultrasonography findings. We employed both univariate and multivariate statistical methods to assess the data.Results: CDC administration (aOR=2.51, 95% CI 1.39– 4.54, P=0.002) and extended usage beyond six months (aOR=3.54, 95% CI 1.71– 7.32, P=0.001) demonstrate a statistically significant correlation with treatment efficacy. Gender (aOR=2.54, 95% CI 1.30– 5.00, P=0.007), hypertension management (aOR=0.56, 95% CI 0.33– 0.95, P=0.031), and antiplatelet therapy with aspirin (aOR=9.53, 95% CI 1.15– 78.89, P=0.037) or clopidogrel (aOR=9.97, 95% CI 1.10– 90.12, P=0.041) also influenced the therapeutic outcome significantly.Conclusion: Incorporating CDC as part of a secondary prevention strategy for over six months can beneficially modulate and limit the progression of vascular stenosis in ACCAS. These findings underscore the value of combining traditional Chinese medicine with modern pharmacological interventions in ACCAS management.Keywords: asymptomatic cerebral carotid artery stenosis, case-control study, secondary prevention, compound dilong capsules

Ying Miao,1– 6 Yu Wang,7 Yi Wang,8 Pijun Yan,1– 6 Zhuang Chen,9 Qin Wan1– 6 1Department of Endocrinology and Metabolism, Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Southwest Medical University, Luzhou, People’s Republic of China; 3Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, People’s Republic of China; 4Sichuan Clinical Research Center for Diabetes and Metabolism, Luzhou, People’s Republic of China; 5Sichuan Clinical Research Center for Nephropathy, Luzhou, People’s Republic of China; 6Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China; 7Department of Cardiology, Luzhou People’s Hospital, Luzhou, People’s Republic of China; 8Department of Pharmacy, Luzhou People’s Hospital, Luzhou, People’s Republic of China; 9Experimental Medicine Center, the Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Qin Wan, Email wanqin3@126.comBackground: Lower extremity peripheral artery disease (LEAD) is a significant chronic complication of type 2 diabetes mellitus (T2DM) that significantly contributes to disability and mortality. The subtle presentation of LEAD symptoms often leads to underrecognition and misdiagnosis. Therefore, identifying simple and effective evaluation indicators is essential for the early detection and management of LEAD. Insulin resistance is closely associated with diabetes and its complications. However, the specific relationship between insulin resistance—measured by the triglyceride-glucose (TyG) index—and obesity indicators in relation to LEAD remains unclear.Objective: This study aims to investigate the association between the TyG index and its combination with obesity indicators in participants with T2DM and LEAD.Methods: We performed a univariate analysis on 3176 T2DM patients to identify risk factors for LEAD. Patients were then divided into quartiles based on the TyG index combined with various obesity indicators. The chi-square test was used to compare the prevalence of LEAD across these groups. Logistic regression analysis was conducted to examine the association between the TyG index, in combination with different obesity indicators, and the occurrence of LEAD. Finally, we assessed the predictive ability of the TyG index combined with obesity indicators for LEAD by comparing the area under the ROC curve (AUC).Results: The study included 3176 T2DM patients (1691 males and 1485 females) with a mean age of 56.16± 10.60 years. Among them, 106 individuals had LEAD. The prevalence of LEAD varied significantly across quartiles of the TyG index, TyG-WC, and TyG-WHR (Q4 > Q3 > Q2 > Q1; P < 0.05). Multiple logistic regression analysis showed that the TyG index, TyG-WC, and TyG-WHR were positively associated with the risk of LEAD in T2DM patients. ROC curve analysis identified the best cutoff values for predicting LEAD: 9.8059 for the TyG index (sensitivity: 49.1%, specificity: 67.9%, AUC: 0.583), 808.8397 for TyG-WC (sensitivity: 70.8%, specificity: 47.8%, AUC: 0.603), and 8.8543 for TyG-WHR (sensitivity: 75.5%, specificity: 44.6%, AUC: 0.607).Conclusion: In T2DM patients, the TyG index, TyG-WHR, and TyG-WC are positively associated with the occurrence of LEAD. TyG-WHR and TyG-WC exhibit a stronger correlation with LEAD compared to the TyG index alone, indicating their superior diagnostic value.Keywords: type 2 diabetes mellitus, lower extremity peripheral artery disease, TyG-WC, TyG-WHR, insulin resistance

Haohua Yuan,1 Huan Gui,1 Shuanghui Chen,1 Lan Zhu,1 Chenglv Wang,1 Qianyu Jing,2 Hang Lv,1 Quan Wan,2 Shuyi Wang,1 Shengwen Zhou,1 Xiaodong Ren,1 Yingjie Nie,1,3 Linzhao Li1 1Medical College, Guizhou University, Guizhou Province, 550025, People’s Republic of China; 2School of Preclinical Medicine of Zunyi Medical University, Zunyi, Guizhou Province, 563000, People’s Republic of China; 3NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, 550002, People’s Republic of ChinaCorrespondence: Yingjie Nie; Linzhao Li, Medical College of Guizhou University, Guiyang, Guizhou Province, 550025, People’s Republic of China, Tel +86-085188274013; +86-085188274016, Email nienyj@hotmail.com; lzli@gzu.edu.cnPurpose: This study aimed to develop a novel and feasible modification strategy to improve the solubility and antitumor activity of resiquimod (R848) by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-β-CD).Methods: R848-loaded PLGA nanoparticles modified with 2-HP-β-CD (CD@R848@NPs) were synthesized using an enhanced emulsification solvent-evaporation technique. The nanoparticles were then characterized in vitro by several methods, such as scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, particle size analysis, and zeta potential analysis. Then, the nanoparticles were loaded with IR-780 dye and imaged using an in vivo imaging device to evaluate their biodistribution. Additionally, the antitumor efficacy and underlying mechanism of CD@R848@NPs in combination with an anti-TNFR2 antibody were investigated using an MC-38 colon adenocarcinoma model in vivo.Results: The average size of the CD@R848@NPs was 376 ± 30 nm, and the surface charge was 21 ± 1 mV. Through this design, the targeting ability of 2-HP-β-CD can be leveraged and R848 is delivered to tumor-supporting M2-like macrophages in an efficient and specific manner. Moreover, we used an anti-TNFR2 antibody to reduce the proportion of Tregs. Compared with plain PLGA nanoparticles or R848, CD@R848@NPs increased penetration in tumor tissues, dramatically reprogrammed M1-like macrophages, removed tumors and prolonged patient survival.Conclusion: The new nanocapsule system is a promising strategy for targeting tumor, reprogramming tumor -associated macrophages, and enhancement immunotherapy.Keywords: R848, 2-HP-β-CD, anti-TNFR2, TIME, immunotherapy

Xinting Wang,1,&ast; Jiahui Yang,1,&ast; Cheng Lu,2 Yinqin Hu,1 Zhaohui Xu,1 Qiqi Wan,1 Meng Zhang,1 Tianyun Shi,1 Zhirui Liu,1 Yongming Liu1 1Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, People’s Republic of China; 2Department of Cardiology, Seventh People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongming Liu, Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No. 185, Pu’an Road, Huangpu District, Shanghai, 200021, People’s Republic of China, Email liuyongming@foxmail.comPurpose: This study aimed to elucidate the protective mechanism of Traditional Chinese Medicine (TCM) Qifu Yixin formula (QFYXF) to improve heart failure (HF) by promoting β-arrestin2 (β-arr2)-mediated SERCA2a SUMOylation.Materials and Methods: The transverse aortic constriction (TAC)-induced HF mice were treated with QFYXF or carvedilol for 8 weeks. β-arr2-KO mice and their littermate wild-type (WT) mice were used as controls. Neonatal rat cardiomyocytes (NRCMs) were used in vitro. Cardiac function was evaluated by echocardiography and serum NT-proBNP. Myocardial hypertrophy and myocardial fibrosis were assessed by histological staining. β-arr2, SERCA2a, SUMO1, PLB and p-PLB expressions were detected by Western blotting, immunofluorescence and immunohistochemistry. SERCA2a SUMOylation was detected by Co-IP. The molecular docking method was used to predict the binding ability of the main active components of QFYXF to β-arr2, SERCA2a, and SUMO1, and the binding degree of SERCA2a to SUMO1 protein.Results: The HF model was constructed 8 weeks after TAC. QFYXF ameliorated cardiac function, inhibiting myocardial hypertrophy and fibrosis. QFYXF promoted SERCA2a expression and SERCA2a SUMOylation. Further investigation showed that QFYXF promoted β-arr2 expression, whereas Barbadin (β-arr2 inhibitor) or β-arr2-KO reduced SERCA2a SUMOylation and attenuated the protective effect of QFYXF improved HF. Molecular docking showed that the main active components of QFYXF had good binding activities with β-arr2, SERCA2a, and SUMO1, and SERCA2a had a high binding degree with SUMO1 protein.Conclusion: QFYXF improves HF by promoting β-arr2 mediated SERCA2a SUMOylation and increasing SERCA2a expression.Keywords: heart failure, Qifu Yixin Formula, β-arrestin2, SERCA2a, SUMOylation

Pijun Yan,1– 5 Jia Li,1– 5 Yi Zhang,1– 5 Xiaofang Dan,1– 5 Xian Wu,1– 5 Xing Zhang,1– 5 Yuxia Yang,1– 5 Xiping Chen,6 Shengxi Li,6 Pan Chen,1– 5 Qin Wan,1– 5 Yong Xu1– 5 1Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, People’s Republic of China; 3Sichuan Clinical Research Center for Diabetes and Metabolism, Luzhou, People’s Republic of China; 4Sichuan Clinical Research Center for Nephropathy, Luzhou, People’s Republic of China; 5Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China; 6Clinical medical College, Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Pijun Yan, Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Tel/Fax +86-830-3165361, Email peter2007110361@126.comObjective: Very few and conflicting data are available regarding the correlation between circulating carbohydrate antigen 19-9 (CA19-9) levels and diabetic kidney disease (DKD) and its components including albuminuria and a low estimated glomerular filtration rate (eGFR). This study aimed to examine the association of circulating CA19-9 and DKD in Chinese patients with type 2 diabetes mellitus (T2DM).Methods: A total of 402 hospitalized T2DM patients between September 2017 and December 2021 were included in this cross-sectional study. There were 224 and 178 subjects in non-DKD and DKD groups, respectively. Serum CA19-9 was measured by chemiluminescence method, and its potential relationship with DKD was evaluated by multivariate logistic regression and correlation analyses, and receiver operating characteristic (ROC) curve analysis.Results: T2DM patients with DKD had significantly higher serum CA19-9 levels than those without, and serum CA19-9 levels were positively related to urinary albumin-to-creatinine ratio and negatively to eGFR (P< 0.01). Multivariate regression analysis revealed that serum CA 19-9 was an independent factor of DKD [odds ratio (OR), 1.018; 95% confidence interval (CI), 1.002– 1.035; P< 0.05]. Moreover, an increased progressively risk of DKD with an increase in serum CA19-9 quartiles was observed (P for trend < 0.001), and T2DM patients in the highest serum CA19-9 quartile were associated with an increased likelihood of DKD when compared to those in the lowest quartile (OR: 2.936, 95% CI 1.129– 7.633, P< 0.05). Last, the analysis of ROC curves suggested that serum CA 19-9 at a cut of 25.09 U/mL resulted in the highest Youden index with sensitivity 43.8% and 75.4% specificity to predict the presence of DKD.Conclusion: These results showed that high circulating CA19-9 was related to DKD and may serve as a useful biomarker of DKD in hospitalized Chinese T2DM patients.Keywords: carbohydrate antigen 19-9, urinary albumin-to-creatinine ratio, diabetic kidney disease, estimated glomerular filtration rate, Chinese population

Jia Li,1– 5,&ast; Xing Zhang,1– 5,&ast; Yi Zhang,1– 5,&ast; Xiaofang Dan,1– 5 Xian Wu,1– 5 Yuxia Yang,1– 5 Xiping Chen,6 Shengxi Li,7 Yong Xu,1– 5 Qin Wan,1– 5 Pijun Yan1– 5 1Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, People’s Republic of China; 3Sichuan Clinical Research Center for Nephropathy, Luzhou, People’s Republic of China; 4Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China; 5Sichuan Clinical Research Center for Diabetes and Metabolism, Luzhou, China, Luzhou, People’s Republic of China; 6Clinical medical college, Southwest Medical University, Luzhou, People’s Republic of China; 7Basic Medical College, Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pijun Yan, Department of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Tel/Fax +86-830-3165361, Email peter2007110361@126.comBackground: Systemic immune-inflammation index (SII), a novel inflammatory marker, has been demonstrated to be associated with type 2 diabetes mellitus (T2DM) and its vascular complications, however, the relation between SII and diabetic peripheral neuropathy (DPN) has been never reported. We aimed to explore whether SII is associated with DPN in Chinese population.Methods: A cross-sectional study was conducted among 1460 hospitalized patients with T2DM. SII was calculated as the platelet count × neutrophil count/lymphocyte count, and its possible association with DPN was investigated by correlation and multivariate logistic regression analysis, and subgroup analyses.Results: Patients with higher SII quartiles had higher vibration perception threshold and prevalence of DPN (all P< 0.01), and SII was independently positively associated with the prevalence of DPN (P< 0.01). Multivariate logistic regression analysis showed that the risk of prevalence of DPN increased progressively across SII quartiles (P for trend < 0.01), and participants in the highest quartile of SII was at a significantly increased risk of prevalent DPN compared to those in the lowest quartile after adjustment for potential confounding factors (odds rate: 1.211, 95% confidence intervals 1.045– 1.404, P< 0.05). Stratified analysis revealed positive associations of SII quartiles with risk of prevalent DPN only in men, people less than 65 years old, with body mass index < 24 kg/m2, duration of diabetes > 5 years, hypertension, dyslipidaemia, poor glycaemic control, and estimated glomerular filtration rate < 90 mL/min/1.73 m2 (P for trend < 0.01 or P for trend < 0.05). The receiver operating characteristic curve analysis revealed that the optimal cut-off point of SII for predicting DPN was 617.67 in patients with T2DM, with a sensitivity of 45.3% and a specificity of 73%.Conclusion: The present study showed that higher SII is independently associated with increased risk of DPN, and SII might serve as a new risk biomarker for DPN in Chinese population.Keywords: systemic immune-inflammation index, diabetic peripheral neuropathy, vibration perception threshold, type 2 diabetes mellitus, Chinese population

Shu-xian Xu,1,&ast; Xin-hui Xie,1,&ast; Lihua Yao,1 Li-chang Chen,2 Qirong Wan,1 Zhen-hua Chen,1 Zhongchun Liu1,3 1Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 3Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongchun Liu, Department of Psychiatry, Renmin Hospital of Wuhan University, No. 238, Jiefang Road, Wuhan, Hubei, ZIP 430060, People’s Republic of China, Tel +86-8804191181399, Email zcliu6@whu.edu.cnObjective: Little is known about the effectiveness and cognitive side-effects of electroconvulsive therapy (ECT) in young adults with treatment-resistant depression (TRD). The primary aim of this prospective longitudinal observational trial was to examine the clinical features and cognitive outcomes of young adults with TRD undergoing ECT.Methods: Changes in depressive symptoms and objective and subjective cognitive function were assessed using repeated evaluation at baseline, after each ECT session, and at one-month follow-up using the Montgomery-Äsberg Depression Rating Scale (MADRS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Forward Digital Span Test (FDST), and part of the Columbia Subjective Side Effects Schedule.Results: Of 41 inpatients, 35 (85.4%) and 12 (29.3%) met the criteria for response and remission after ECT, respectively. The greatest clinical improvements occurred during the first 3– 4 ECT sessions. While 34 patients reported subjective cognitive impairment increased with ECT, immediate and delayed memory (RBANS) significantly increased after ECT, consistent with FDST results. Objective cognition significantly improved during follow-up, but subjective cognition remained impaired.Conclusion: ECT is effective in young adults with TRD. Although subjective cognitive impairment increased during treatment, objective cognitive impairments were not observed.Keywords: electroconvulsive therapy, young adults, cognitive function, treatment-resistant depression

Yuru Wu,1– 4 Qin Wan,1– 4 Yong Xu,1– 4 Jia Li,1– 4 Ke Li,1– 4 Zhihong Zhang,5 Qian Tang,1– 4 Ying Miao,1– 4 Pijun Yan1– 4 1Department of Endocrinology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, Sichuan, People’s Republic of China; 3Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, People’s Republic of China; 4Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China; 5Department of General Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaCorrespondence: Pijun Yan, Department of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Tel/Fax +86-830-3165361, Email peter2007110361@126.comObjective: There is preliminary evidence that visceral fat area (VFA) was associated with the presence of type 2 diabetic peripheral neuropathy (DPN) in the Korean population; however, no studies have reported the association in Chinese population. The purpose of this study was to explore the possible correlation of VFA with DPN in such a population.Methods: A total of 2498 hospitalized patients with type 2 diabetes mellitus (T2DM) undergone VFA measurement, and were divided into DPN group (n=900) and non-DPN group (n=1594). The association of VFA with the presence of DPN was evaluated by correlation and multiple logistic regression analyses, generalized additive model with a smooth curve fitting, and receiver operating characteristic (ROC) curve analysis.Results: The VFA was significantly lower in the DPN group than in the non-DPN group (P < 0.001). VFA was significantly and positively associated with sural nerve conduction velocity (SNCV) and amplitude potential (SNAP) and negatively associated with the presence of DPN (all P< 0.001); there was no significant difference in the curve fitting (P = 0.344). Multivariate logistic regression analysis showed that the risk of presence of DPN decreased progressively across the VFA quartiles (P for trend < 0.001) and was significantly lower in patients in the highest VFA quartile than in those in the lowest quartile (OR: 0.382, 95% CI 0.151– 0.968, P< 0.001) after multivariate adjustment. The ROC analysis revealed that the best cut-off value of VFA for predicting the presence of DPN was 50.5cm2 (sensitivity 84.40%; specificity 34.00%).Conclusion: These results suggest that lower VFA level may be associated with increased risk of the presence of DPN in T2DM patients.Keywords: visceral fat area, diabetic peripheral neuropathy, sural nerve conduction velocity, sural nerve amplitude potential, Chinese population

Jie Lin,1– 4 Hang Li,1– 4 Qin Wan1– 4 1Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, People’s Republic of China; 3Sichuan Clinical Research Center for Nephropathy, Luzhou, People’s Republic of China; 4Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of ChinaCorrespondence: Qin Wan, Tel +86 138 8274 6971, Email wanqin360@swmu.edu.cnAbstract: Purpose: The main objective of this study was to examine the possible association between the atherogenic index of plasma (AIP) and the prevalence of nonalcoholic fatty liver disease (NAFLD) in Chinese individuals with type 2 diabetes mellitus (T2DM).Patients and methods: In this survey, data from 1074 patients with T2DM were retrospectively extracted. The correlations between each variable and NAFLD were determined by univariate analysis, and then, the statistically significant variables were evaluated for their association with AIP and NAFLD by multivariate regression analysis.Results: AIP levels were significantly higher in all males and females with NAFLD than those without NAFLD (p< 0.001). The prevalence of NAFLD increased progressively throughout the AIP quartiles (trend P < 0.001) and accounted for possible variables in Model 3 of the multivariate logistic regression analysis (OR: 2244.984). In terms of sensitivity and specificity, the AIP index was found to be 65.0% and 90.1% accurate, respectively, with a 95% CI of 0.804– 0.893. According to a stratified analysis, females, patients over the age of 56 and current nonsmokers were found to have a higher chance of developing NAFLD.Conclusion: T2DM individuals with NAFLD were found to have a higher AIP index than those without NAFLD. The prevalence and progression of NAFLD in T2DM patients may be influenced by the AIP index.Keywords: type 2 diabetes mellitus, nonalcoholic fatty liver disease, atherogenic index of plasma, diagnostic ability, cross-sectional study

Cheng Chen,1,2,&ast; Xin Dong,1,&ast; Ping Gu,1 Keyan Chen,1 Qi Wan,1 Haiyue Xie,3 Zhaochun Shi,1 Teng Wang1 1Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241000, People’s Republic of China; 3The First Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Teng Wang; Zhaochun ShiDepartment of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of ChinaTel +86 256 830 6050; +86 256 830 3613Fax +86 258 371 8836Email tengwnjmu@163.com; 290694748@qq.comBackground and Purpose: Migraine suffering is more than the onset of head pain. The broad non-painful clinical symptoms associated with migraine are not well recognized. Recent researches support that migraineurs suffer attention deficits, but these findings are not conclusive. The purpose of our study was to assess whether patients with migraine without aura (MwoA) during the interictal period have attention impairment and to identify the migraine characteristics related to attention deficits.Methods: We enrolled subjects with MwoA during the interictal period and healthy controls matched for age, gender, and education level in this cross-sectional study. The attention network test (ANT) and a battery of neuropsychological tests, including the trail-making test (TMT), the digit span test (DST), and the Stroop test, were administered to the participants during the headache-free period.Results: Forty-four subjects with MwoA (4 males, 40 females) and 20 controls matched for age, gender, and literacy education were included. Patients in MwoA were more anxious (P = 0.007) and depressed (P = 0.001) than healthy subjects. Significant differences between the two groups were detected in the executive network (P = 0.006) but not in the alerting and orienting networks of ANT. Mean reaction time of ANT in the MwoA group was significantly longer than that in the control group (P = 0.028). Patients showed worse performance on DST-forward (P < 0.001), DST-backward (P < 0.001), DS Total (P < 0.001), TMT-A (P < 0.001), TMT-B (P < 0.001) and TMT-d (P = 0.002). Differences found in executive functions between the two groups were unrelated to gender, age, literacy, anxiety, and depression. Multiple regression analysis revealed no relation between clinical characteristics of headache and scores on the executive function with MwoA.Conclusion: Our study suggested that patients in MwoA present worse performances on the executive control of attention networks during the headache-free period, which appear not be associated with measures of migraine severity. Although more studies are needed in this area, our results could be useful to find specific neuropsychological biomarker for migraine pathophysiology.Keywords: migraine without aura, attention, attention network test, executive function, reaction time

Yang Liu,1,2,* Yun Wang,1,2,* Jie Wang,2 Kang Chen,2 Lingzi Jin,3 Weiqing Wang,4 Zhengnan Gao,5 Xulei Tang,6 Li Yan,7 Qin Wan,8 Zuojie Luo,9 Guijun Qin,10 Lulu Chen,11 Yiming Mu2 1Graduate School, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Endocrinology, The First Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of International Medical Services, Peking Union Medical College Hospital (Xidan Campus), Beijing, People’s Republic of China; 4Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 5Department of Endocrinology, Dalian Central Hospital, Dalian, Liaoning, People’s Republic of China; 6Department of Endocrinology, First Hospital of Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 7Department of Endocrinology, Zhongshan University Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, People’s Republic of China; 8Department of Endocrinology, Southwest Medical University Affiliated Hospital, Luzhou, Sichuan, People’s Republic of China; 9Department of Endocrinology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 10Department of Endocrinology, First Affiliated Hospital of Zhengzhou University, Zhenzhou, Henan, People’s Republic of China; 11Department of Endocrinology, Wuhan Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiming MuDepartment of Endocrinology, The First Medical Center of Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, People’s Republic of ChinaTel +86-10-5549 9001Email muyiming@301hospital.com.cnBackground: Lipid accumulation product (LAP) as a powerful marker of visceral obesity is an independent risk factor of chronic kidney disease. The present study attempted to explore the association between LAP and albuminuria in prediabetic individuals.Methods: We conducted a cross-sectional study and enrolled 26,529 participants with prediabetes over 40 years old with prediabetes from seven provinces in China. LAP was calculated from waist circumference and fasting triglycerides. Elevated albuminuria was defined by urinary albumin-creatinine ratio (uACR) ≥ 30 mg/g. Propensity score matching was applied to reduce bias, comparison between LAP and other traditional visceral obesity indices was performed and multiple logistic regression models were conducted to assess the association between LAP and albuminuria in the prediabetic population.Results: Individuals with uACR ≥ 30 mg/g were older and had higher BP, BMI, WC, TG, fasting insulin, glycohemoglobin and LAP, as well as lower eGFR and HDL level. Multiple logistic regression analysis showed elevated LAP was associated with increased odds of albuminuria (OR [95%CI]Q2 vs Q1 1.09 [0.94, 1.27], OR [95%CI]Q3 vs Q1 1.13 [0.97, 1.31], OR [95%CI]Q4 vs Q1 1.42 [1.21, 1.67], P for trend=0.018), and superior over waist-to-hip ratio or waist-to-height ratio. Stratification indicated that the prediabetic population with higher LAP level and characterized by female gender, middle age, being overweight, and rise in blood pressure were more likely to have increased uACR.Conclusion: Elevated level of LAP was associated with increased albuminuria in the prediabetic population in China.Keywords: albuminuria, lipid accumulation product, prediabetes, visceral obesity

Xiaofen Hu,1,2,* Ruijie Li,1,2,* Ming Sun,1,2 Ying Kong,1,2 Haifeng Zhu,1,2 Fujiang Wang,1 Quanqing Wan1,2 1The Third Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, 310005, People’s Republic of China; 2Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Quanqing WanThe Third Affiliated Hospital of Zhejiang Chinese Medicine University, 219 Moganshan Road, Hangzhou, 310005, Zhejiang, People’s Republic of ChinaEmail 13003678819@163.comPurpose: Osteoarthritis (OA) is a multifactorial joint disease and inflammatory processes contribute to joint destruction. Isovitexin (IVX) is a flavone component found in passion flower, Cannabis and, and the palm that is known for its anti-inflammatory properties.Materials and Methods: This study investigated in vitro the role and underlying mechanism used by IVX in its regulation of OA development. Effects of IVX on the viability of chondrocytes were measured by CCK-8 assays. The phenotypes of extracellular matrix (ECM) degeneration and inflammation were measured by qPCR, Western blot, and ELISA; and NF-κB pathway was detected by immunofluorescence and Western blot. Molecular docking was applied to predict the interacting protein of IVX, while Nrf2 was knocked down by siRNAs to confirm its role.Results: We demonstrated that IVX suppressed ECM degeneration and suppressed pro-inflammatory factors in IL-1β-treated chondrocytes. Additionally, IVX impact on NF-κB signaling in IL-1β-exposed chondrocytic cells; Mechanistically, it was also demonstrated in molecular docking and knock down studies that IVX might bind to Nrf2 to suppress NF-κB pathway.Conclusion: Our data suggest that IVX halts OA disease advancement through the Nrf2/NF-κB axis, suggesting a possibility of IVX as a target for OA therapy.Keywords: osteoarthritis, isovitexin, extracellular matrix, NF-κB, Nrf2

Yun Deng,1 Quan Wan,2 Wangxiang Yan1 1Department of Stomatology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, Sun Yat-Sen Memorial Hospital, Guangzhou, People’s Republic of ChinaCorrespondence: Wangxiang YanDepartment of Stomatology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510000, People’s Republic of ChinaEmail ywx_sysu@163.comBackground: Integrin signalling is involved in cell migration, invasion, proliferation and motility. Integrin α5/ITGA5 is a subunit of Integrin and contributes to the activation of Integrin signalling. The potential role of Integrin α5/ITGA5 in oral squamous cancer remains unknown. The aim of this study was to uncover the effect and mechanism of Integrin α5/ITGA5 in the progression of oral squamous carcinoma.Method: TCGA database scanning, qRT-PCR, immunohistochemistry and Western blotting assays were used to detect the expression of Integrin α5/ITGA5 in tissues and cell lines. We established stable Integrin α5/ITGA5 overexpressing and Integrin α5/ITGA5 knockdown cell lines. We investigated the biological function and the underlying mechanism of Integrin α5/ITGA5 through a series of experiments.Results: Integrin α5/ITGA5 was upregulated in cancer tissue, and its levels negatively correlated with the overall survival (OS) of patients. Integrin α5/ITGA5 promoted proliferation, migration and invasion in an oral squamous carcinoma cell line by EMT (epithelial–mesenchymal transition).Conclusion: Integrin α5/ITGA5 promotes the proliferation, migration and invasion of oral squamous carcinoma.Keywords: oral squamous carcinoma, Integrin α5/ITGA5, EMT

Xin-Yu Liao,1,* Yang Lei,2,* Song-Feng Chen,2 Jing Cheng,3 Dan Zhao,4 Zhi-Feng Zhang,2 Xin Han,5 Ya Zhang,2 Hua-Bao Liao,2 Yang Zhuang,2 Juan Chen,6 Hai-Bing Zhou,5 Qi Wan,7 Ying-Ying Zou,11Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming 650500, People’s Republic of China; 2Department of Physiology, School of Basic Medical Sciences, Wuhan University School of Medicine, Wuhan 430071, People’s Republic of China; 3Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, People’s Republic of China; 4Department of Physiology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, People’s Republic of China; 5School of Pharmacy, Wuhan University, Wuhan 430071, People’s Republic of China; 6Department of Neurology, The Central Hospital of Wuhan, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430013, People’s Republic of China; 7Institute of Neuroregeneration & Neurorehabilitation, Collaborative Innovation Center for Brain Science, Department of Neurosurgery of the Affiliated Hospital, Qingdao University, Qingdao 266071, People’s Republic of China*These authors contributed equally to this work Background: The authors have recently designed a new compound bisperoxovandium (pyridin-2-squaramide) [bpV(pis)] and verified that bpV(pis) confers neuroprotection through suppressing PTEN and activating ERK1/2, respectively. Intracerebral hemorrhage (ICH) is the second most common cause of stroke and has severe clinical outcome. In this study, we investigate the effect of bpV(pis) in ICH model both in vivo and in vitro.Materials and methods: The novel drug bpV(pis) was synthesized in the Faculty of Pharmacy, Wuhan University School of Medicine. An ICH model was generated on both SD rats and cells. bpV(pis) was injected into intracerebroventricular or culture media. Western blotting was applied to test the signal pathway. To determine the effect of bpV(pis) on PTEN inhibition and ERK1/2 activation, we measured the phosphorylation level of AKT (a direct downstream target of PTEN that negatively regulates AKT) and ERK1/2. FJC, MTT, and LDH were applied to measure the cell viability. Neurobehavioral tests were performed to measure the effect of bpV(pis).Results: The in vivo results showed that intracerebroventricular administration of bpV(pis) significantly alleviates hematoma, the damage of brain–blood barrier and brain edema. The in vitro results demonstrated that bpV(pis) treatment reduces ICH-induced neuronal injury. Western blotting results identified that bpV(pis) exerts a neuroprotective effect by significantly increasing the phosphorylation level of AKT and ERK1/2 after experimental ICH. Neurobehavioral tests indicate that bpV(pis) promotes functional recovery in ICH animals.Conclusion: This study provides first and direct evidence for a potential role of bpV(pis) in ICH therapy.Keywords: bpV(pis), intracerebral hemorrhage, PTEN, AKT, ERK1/2, neuroprotection

Feifei Shen,1,* Xin Dong,1,* Xin Zhou,2 Lanyun Yan,1 Qi Wan11Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Department of Ophthalmology, The Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, People’s Republic of China *These authors contributed equally to this workBackground and purpose: It has been generally thought that activation and sensitization of the trigeminovascular system may contribute to the pathogenesis of migraine. Nevertheless, there is little evidence on abnormalities in peripheral trigeminal afferent nerves from humans in vivo. Alterations of corneal nerves from the ophthalmic branch of the trigeminal nerve may support the notion that trigeminal afferent nerves are involved in migraine pathophysiology. The aim of the present study was to investigate the structural changes in corneal subbasal nerve plexus in patients with episodic migraine (EM) with in vivo confocal microscope (IVCM).Methods: In this cross-sectional observational study, 10 EM patients and 10 age- and sex-matched healthy controls were included. Analysis of IVCM images with Image J software was performed to quantify the changes in the corneal subbasal nerve plexus.Results: EM patients showed an increase in nerve fiber length (25.0±2.65 vs 22.3±2.41 mm/mm,2 p=0.047) and nerve fiber density (36.3±7.29 vs 30.5±6.19 fibers/mm,2 p=0.104) as compared with normal controls, but this difference was not statistically significant. Nerve branching and tortuosity were significantly increased in the EM subjects compared to the normal subjects (91.3±13.8 vs 75.0±14.2 branches/mm,2 p=0.030 and 2.30±0.46 versus 1.63±0.52, p=0.011, respectively). In addition, nerve sprouts and increased number of Langerhans cells were observed in the EM patients.Conclusion: The morphologic changes of corneal subbasal nerve plexus and Langerhans cell aggregation suggest the presence of nerve regeneration and inflammation in EM. Furthermore, the alterations of corneal nerves from the ophthalmic branch of the trigeminal nerve offer support for the hypothesis that the peripheral trigeminal system may be involved in the pathogenesis of migraine.Keywords: migraine, corneal nerves, subbasal nerve plexus, in vivo confocal microscopy