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Yashi Ruan,1,* Lixia Guan,2,* Yuting Wang,2 Yifei Geng,2 Xiaoran Wang,2 Miao-Miao Niu,2 Li Yang,1 Cen Xu,1 Zhen Xu1 1Department of Urology, Reproductive Medicine and Oncology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, 225300, People’s Republic of China; 2Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Yang; Cen Xu, Department of Urology, Reproductive Medicine and Oncology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, 225300, People’s Republic of China, Email proyangli@163.com; cenxu263128@163.comPurpose: Dual inhibition of ataxia telangiectasia mutated (ATM) and histone deacetylase 2 (HDAC2) may be a potential strategy to improve antitumor efficacy in testicular cancer.Methods: A combined virtual screening protocol including pharmacophore modeling and molecular docking was used for screening potent dual-target ATM/HDAC2 inhibitors. In order to obtain the optimal lead compound, the dual ATM/HDAC2 inhibitory activity of the screened compounds was further evaluated using enzyme inhibition methods. The binding stability of the optimal compound to the dual targets was verified by molecular dynamics (MD) simulation. MTT assay and in vivo antitumor experiment were performed to validate antitumor efficacy of the optimal compound in testicular cancer.Results: Here, we successfully discovered six potent dual-target ATM/HDAC2 inhibitors (AMHs 1– 6), which exhibited good inhibitory activity against both ATM and HDAC2. Among them, AMH-4 showed strong inhibitory activity against both ATM (IC50 = 1.12 ± 0.03 nM) and HDAC2 (IC50 = 3.04 ± 0.08 nM). MD simulation indicated that AMH-4 binds to ATM and HDAC2 with satisfactory stability. Importantly, AMH-4 had significant antiproliferative activity on human testicular tumor cells, especially NTERA-2 cL.D1 cells, and no inhibitory effect on normal human testicular cells. In vivo experiments exhibited that AMH-4 was more effective than lartesertib and vorinostat in inhibiting the growth of NTERA-2 cL.D1 xenograft tumors with low toxicity.Conclusion: Overall, these results suggest that AMH-4 is an effective and low toxicity candidate for the treatment of testicular germ cell tumors.Keywords: ataxia telangiectasia mutated, histone deacetylase 2, dual-targeting inhibitors, testicular germ cell tumors, structure-based virtual screening

Zijun Liu,1,* Tianhao Bao,2 Zhilan Yang,2,* Ye Ruan,2 Changqing Gao,2 Jie Wu2 1The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Affiliated Mental Health Center of Kunming Medical University, Kunming, Yunnan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Wu, Affiliated Mental Health Center of Kunming Medical University, Kunming, Yunnan, 650224, People’s Republic of China, Email wujie@kmmu.edu.cn Tianhao Bao, Affiliated Mental Health Center of Kunming Medical University, Kunming, Yunnan, 650224, People’s Republic of China, Email Doctor@kmmu.edu.cnObjective: Based on Conservation of resources theory, process model of emotion regulation and attachment theory, the present study examined how psychological capital affects anxiety through the mediation of emotion regulation strategies and explored the moderating role of parent-child relationship.Methods: Using a longitudinal study method, 962 college students were surveyed twice at one-year intervals.Results: (1) College students’ emotion regulation strategies (including cognitive reappraisal and expressive suppression) partially mediated psychological capital and anxiety mood; (2) parent-child relationship moderated the pathways of psychological capital and expressive suppression on anxiety, respectively.Conclusion: College students with higher levels of parent-child relationship had stronger predictive effects of psychological capital and weaker predictive effects of expressive suppression on anxiety mood. The research findings clarify the combined effects of emotion regulation and parent-child relationships on anxiety among college students, providing valuable reference for the design and implementation of interventions to promote individual psychological well-being.Keywords: psychological capital, emotion regulation strategies, anxiety, parent-child relationship

Rongping Chen,1,* Jing Li,2,* Danqi Chen,3,* Weiheng Wen,1 Susu Zhang,1 Jitong Li,1 Yuting Ruan,1 Zhen Zhang,1 Jia Sun,1 Hong Chen1 1Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Endocrinology, HuaZhong University of Science and Technology Union ShenZhen Hospital, Guangdong, People’s Republic of China; 3Institute for Prevention and Control of Chronic Noncommunicable Diseases, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Chen; Jia Sun, Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China, Email chenhong123@smu.edu.cn; sunjia@smu.edu.cnObjective: Several oral antidiabetic regimens are available for treating type 2 diabetes mellitus (T2DM), dipeptidyl peptidase-4 inhibitors (DPP4i) being one of them. We conducted a network meta-analysis (NMA) comparing DPP4i plus metformin (Met) combination with other Met-based oral antidiabetic drug (OAD) combinations used in treating patients with T2DM.Methods: We searched PubMed and Embase from inception until 19th April, 2022 for phase II and phase III trials in patients with T2DM on Met-based traditional OADs. The primary outcome was assessed by change in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and 2-hour post-prandial blood glucose (2h-PPG). The secondary safety outcomes assessed were hypoglycemic events, serious adverse events (SAEs), cardiovascular (CV) events, and gastrointestinal (GI) events.Results: Sixty-two trials were included in the analysis. The combination of DPP4i + Met revealed a comparable mean reduction in HbA1c levels to the glinides (Gli) + Met combination (mean difference [MD]: − 0.03%, 95% CI: 0.69, − 0.65), although the difference was not statistically significant. The mean HbA1c reduction with DPP4i + Met was greater than with sulfonylureas (SU) + Met (MD: − 0.05, 95% CI: − 0.29, 0.39), thiazolidinedione (TZD) + Met (MD: − 0.69, 95% CI: − 1.39, − 0.02), and SU + TZD (MD: 0.21; 95% CI: − 1.30, 1.71), with no statistical significance. DPP4i + Met demonstrated a non-significant lower incidence of CV events in comparison to TZD + Met (RR: 1.01, 95% CI: 0.46, 2.45) and SU + Met (RR: 1.06, 95% CI: 0.61, 2.06).Conclusion: DPP4i in combination with Met was efficacious and had a well-tolerated safety profile compared with other traditional OADs. This combination can be considered as a suitable treatment option for patients with T2DM.Keywords: dipeptidyl peptidase-4 inhibitors, efficacy, safety, metformin, type 2 diabetes mellitus

Song Wen,1,&ast; Yufeng Ruan,2,&ast; Zhongyu Shi,3 Shujie Dan,2 Ligang Zhou1– 4 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of General Practice, Huinan Health Service Center, Shanghai, People’s Republic of China; 3Department of International Medicine, Shanghai Pudong Hospital, Fudan University, Shanghai, People’s Republic of China; 4Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China, Tel +8613611927616, Email zhouligang1n1@163.comBackground: Despite the demonstrated benefits of insulin therapy, many general practitioners (GPs) are hesitant to administer it due to challenges such as a lack of knowledge, time constraints, and patient reluctance. The barriers that prevent a GP from initiating insulin therapy may vary in comparison to those encountered by a diabetic patient; this aspect of clinical research in the South Shanghai metropolitan area has received limited attention so far.Objective: This is a 6-months of interventional analytic cohort study. The prime aim is to investigate the barriers general practitioners (GPs) face when initiating insulin therapy for patients with type 2 diabetes (T2D).Materials and Methods: As part of a training program, all 189 registered GPs in Nanhui Health Service Center in Shanghai were given a structured online-multi-choice questionnaire before and after a six-month interval, during which the GPs received sessions of training on insulin therapy either on theoretic classes or clinical practices.Results: Before and after training, via the methods of multiple-response analyses, the results showed that social, GP’s, and patient barriers to initiating insulin therapy were comparable. However, through the crosstabs chi-square test, we found significant changes in the basal insulin initiation following the prescription of the senior endocrinologists, the titration of insulin, and the need for training (p< 0.05). The Spearman analyses discovered significant changes associated with the cause of initial insulin refusal and the factors influencing insulin administration. Finally, the binary logistic regression analysis revealed that distinct causes such as social factors, insurance, GP experience, insulin dosage calculation, follow-up, and patients’ feelings are related to insulin treatment application before and after training.Conclusion: According to this study, training increased general practitioners’ confidence in initiating insulin administration, especially basal insulin. General practitioners require additional education on insulin therapy, with a potential need for increased face-to-face training for insulin initiation.Keywords: diabetes mellitus, insulin initiation barrier, general practitioner, community

Yajuan Zheng,1,&ast; Peipei Yuan,1,2,&ast; Zhenkai Zhang,1 Yang Fu,1,2 Saifei Li,1 Yuan Ruan,1 Panying Li,1 Yi Chen,1 Weisheng Feng,1– 3 Xiaoke Zheng1– 3 1College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450008, People’s Republic of China; 2The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, 450046, People’s Republic of China; 3Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan province & Education Ministry of P. R. China, Zhengzhou, 450008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weisheng Feng; Xiaoke Zheng, Email fwsh@hactcm.edu.cn; zhengxk.2006@163.comPurpose: Fatty oil of Descurainia Sophia (OIL) has poor stability and low solubility, which limits its pharmacological effects. We hypothesized that fatty oil nanoparticles (OIL-NPs) could overcome this limitation. The protective effect of OIL-NPs against monocrotaline-induced lung injury in rats was studied.Methods: We prepared OIL-NPs by wrapping fatty oil with polylactic-polyglycolide nanoparticles (PLGA-NPs) and conducted in vivo and in vitro experiments to explore its anti-pulmonary hypertension (PH) effect. In vitro, we induced malignant proliferation of pulmonary artery smooth muscle cells (RPASMC) using anoxic chambers, and studied the effects of OIL-NPs on the malignant proliferation of RPASMC cells and phospholipase C (PLC)/inositol triphosphate receptor (IP3R)/Ca2+ signal pathways. In vivo, we used small animal echocardiography, flow cytometry, immunohistochemistry, western blotting (WB), polymerase chain reaction (PCR) and metabolomics to explore the effects of OIL-NPs on the heart and lung pathological damage and PLC/IP3R/Ca2+ signal pathway of pulmonary hypertension rats.Results: We prepared fatty into OIL-NPs. In vitro, OIL-NPs could improve the mitochondrial function and inhibit the malignant proliferation of RPASMC cells by inhibiting the PLC/IP3R/Ca2+signal pathway. In vivo, OIL-NPs could reduce the pulmonary artery pressure of rats and alleviate the pathological injury and inflammatory reaction of heart and lung by inhibiting the PLC/IP3R/Ca2+ signal pathway.Conclusion: OIL-NPs have anti-pulmonary hypertension effect, and the mechanism may be related to the inhibition of PLC/IP3R/Ca2+signal pathway. Keywords: pulmonary hypertension, PLC/IP3R/Ca2+, nanoparticles, RPASMC, fatty oil

Fang Cao,1,2 Fuyuan Hong,1 Yiping Ruan,1 Miao Lin1 1Department of Nephrology, Provincial Clinical College, Fujian Medical University, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China; 2Department of Nursing, Provincial Clinical College, Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian, 350001, People’s Republic of ChinaCorrespondence: Fang Cao; Miao Lin, Department of Nephrology, Provincial Clinical College, Fujian Medical University, Fujian Provincial Hospital, 134 East Street, Fuzhou, 350001, People’s Republic of China, Tel +86-591-87557768, Email 422512642@qq.com; 10151246@qq.comObjective: This study was conducted to understand the influencing factors for home peritoneal dialysis patients choosing APD and to provide a scientific basis for improving the completion rate of APD treatment and the follow-up of peritoneal dialysis patients.Methods: The study was a cross-sectional questionnaire-based study. A total of 588 patients on peritoneal dialysis were randomly selected from 6 regions in Fujian Province in southern China using a stratified cluster sampling method.Results: The mean age of the patients were 56.5 ± 14.73 years. In the univariate analysis, knowledge, user experience and family support were the factors that affected patients’ choice of APD (all P < 0.05) and were positively correlated with the treatment utilization rate. In the multivariate analysis, 3 factors (treatment with APD, knowledge of APD, and family support) remained significantly associated not choosing APD. The selection rate for APD was 2.594 times higher among patients who had received APD than among patients who had never received APD. The selection rate for patients with “a lot of knowledge” about APD was 10.75 times that of patients with “no knowledge”.Conclusion: Patients’ knowledge of APD, experience in application and family support were the main factors affecting the choice of APD as a treatment mode (P < 0.05) and were positively correlated with the treatment utilization rate. Further studies are needed to improve the APD treatment completion rates by modulation the above-mentioned factors.Relevance to Clinical Practice: This study provides scientific evidence for improving APD treatment completion rates and improving patient quality of life.Keywords: peritoneal dialysis, APD, dialysis mode, influencing factors, follow up, end-stage kidney disease

Yanfeng Zhang,1 Yujia Luo,1 Yachao Ruan,2 Xiang Qian,3 Zhiying Feng1 1Department of Pain Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China; 3Stanford University School of Medicine Pain Management Center, Redwood City, CA, 94063, USACorrespondence: Zhiying Feng, Email fzy1972@zju.edu.cnIntroduction: Early diagnosis of SAPHO syndrome is easily confused with other common spine-related diseases and infections. There is currently no consensus regarding the diagnosis of SAPHO syndrome, and specific treatments are empirical because of its rarity.Case Presentation: A 62-year-old woman was referred to our department with complaints of low back and lower extremity pain for 2 years, 1.5 years after lumbar spine surgery, and recurrent low back pain for 1 year. Laboratory test results revealed elevated hs-CRP levels and erythrocyte sedimentation rate. Combined with her surgical history and lumbar CT results, adjacent segment degeneration (ASD) was first considered. NSAIDs, analgesics, and supplemental therapies were also administered. However, the patient’s symptoms were not significantly relieved. During re-examination, hyperkeratosis with active pustulosis was observed on the patient’s palms. Osteitis of the left sacroiliac joint was revealed on imaging. Skeletal ECT revealed a typical “horn sign”. The patient was diagnosed with SAPHO syndrome. Based on the original treatment, sulfasalazine enteric-coated tablets, adalimumab (a biological agent of TNF-α), pregabalin, and tramadol sustained-release tablets were administered. The patient reported that her pain was significantly relieved. He was discharged from the hospital and received adalimumab treatment (40 mg once per fortnight in the first 6 months and 40 mg once per month after month 6) in the outpatient clinic. The hyperkeratosis with active pustulosis on both palms fully recovered after 12 months of treatment. The patient was followed up 6 months after full recovery, and no recurrence was found in the symptoms of low back and lower extremity pain and palmar hyperkeratosis with active pustulosis.Conclusion: SAPHO syndrome should be suspected in patients present with osteoarticular and/or dermatological manifestations. Biological agents can be used to treat patients with refractory SAPHO syndrome.Keywords: SAPHO syndrome, low back pain, osteitis, pustulosis, adalimumab

Fang Cao, Fuyuan Hong, Yiping Ruan, Miao Lin Department of Nephrology, Provincial Clinical College, Fujian Medical University, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of ChinaCorrespondence: Fang Cao; Miao Lin, Department of Nephrology, Provincial clinical college, Fujian Medical University, Fujian Provincial Hospital, 134 East Street, Fuzhou, People’s Republic of China, 350001, Tel/Fax +86-591-87557768, Email 422512642@qq.com; 10151246@qq.comObjective: Patient empowerment can be achieved through the PBL model. The purpose of the present study was to evaluate the effectiveness and feasibility of patient empowerment through the PBL model in health continuing education of peritoneal dialysis (PD) patients.Methods: From March 2017 to April 2017, a total of 94 participants were randomly assigned to the PBL group and the traditional group, with 47 patients in each group. Patients of the PBL group were divided into 5 study groups; and six PBL health education activities were held. The basic knowledge, self-management behavior, quality of life, anxiety, and depression were assessed among the traditional group and the PBL group. The average follow-up duration was 10.6± 1.5 months.Results: Compared with patients in the traditional group, patients in the PBL group had higher scores of basic knowledges for PD (84.33± 3.55 vs 91.19± 3.07; P< 0.001), higher scores of self-management (61.19± 3.71 vs 71.47± 2.89; P< 0.001), better scores of quality of life (85.99± 14.33 vs 102.64± 9.43; P < 0.001), and better scores of satisfaction (90.78± 1.32 vs 98.21± 1.25; P < 0.001). Furthermore, the scores of anxieties (52.39± 4.55 vs 46.46± 4.63; P < 0.001) and the scores of depressions were lower (49.95± 6.76 vs 45.80± 8.77; P =0.01) in patients who participated in the PBL mode of education than in the traditional educational group.Conclusion: The empowerment model of PBL health education can effectively improve the knowledge, skills and quality of life of PD patients.Relevance to Clinical Practice: The findings identified in this study will help to improve the quality of nursing care and health education for PD patients.Patient or Public Contribution: The study design involved patients on PD training. The knowledge and skills of PD and quality of life will improve after they participate the PBL health education activities.Keywords: patient empowerment, PBL, peritoneal dialysis, patient education, quality of life, chronic kidney disease

Yang Fu,1,2 Peipei Yuan,1,2 Yajuan Zheng,1 Yaxin Wei,1 Liyuan Gao,1 Yuan Ruan,1 Yi Chen,1 Panying Li,1 Weisheng Feng,1,2 Xiaoke Zheng1,2 1Department of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, People’s Republic of China; 2The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, 450046, People’s Republic of ChinaCorrespondence: Xiaoke Zheng; Weisheng Feng, Department of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, People’s Republic of China, Email zhengxk.2006@163.com; fwsh@hactcm.edu.cnPurpose: Pseudoephedrine (PSE) has rapid absorption and metabolism, which limits its pharmacologic actions. We postulated that pseudoephedrine nanoparticles (PSE-NPs) with high bioavailability could overcome this limitation. The defensive function of PSE-NPs nanoparticles against adriamycin-induced reproductive toxicity in mice was studied.Methods: We encapsulated PSE in polylactide-polyglycolide nanoparticles (PLGA-NPs) and verified their protective activity against testicular injury in vivo and in vitro.Results: We report a promising delivery system that loads PSE into PLGA-NPs and finally assembles it into a nanocomposite particle. In vitro, PSE-NPs reduced the adriamycin-induced apoptosis of GC-1 cells significantly, improved mitochondrial energy metabolism and promoted expression of the proteins related to the gonadotropin-releasing hormone (GnRh) receptor signaling pathway. In vivo, evaluation of sperm indices and histology showed that adriamycin could induce testicular toxicity. PSE-NPs significantly increased the sperm motility of mice, reduced the percent apoptosis and oxidative stress of testes, increased serum levels of GnRh, activated the GnRhR signaling pathway in testes and promoted expression of meiosis-related factors.Conclusion: In view of their safety and efficiency, these PSE-NPs have potential applications in alleviating adriamycin-induced reproductive toxicity.Graphical Abstract: Keywords: pseudoephedrine nanoparticles, adriamycin, reproductive toxicity, GnRhR signaling pathway, sperm meiosis

Hai-Yun Zhang,1– 3 Qiu-Meng Xie,1– 3 Cui-Cui Zhao,1– 3 Jia-Feng Sha,1– 3 Ya Ruan,1– 3 Hui-Mei Wu1– 3 1Anhui Geriatric Institute, Department of Geriatric Respiratory and Critical Care, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Key Laboratory of Geriatric Molecular Medicine of Anhui Province, Hefei, Anhui, People’s Republic of China; 3Key Laboratory of Respiratory Disease Research and Medical Transformation of Anhui Province, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Hui-Mei WuAnhui Geriatric Institute, Department of Geriatric Respiratory and Critical Care, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaTel +86 551 65120742Email wuhm@ahmu.edu.cnPurpose: CpG-ODN has been found to attenuate allergic airway inflammation in our previous study. Here, we aimed to further investigate whether CpG-ODN exerts such effect via regulating endoplasmic reticulum (ER) stress and revealed the underlying mechanism.Methods: Five-week-old C57BL/6 mice were randomly grouped and treated with or without CpG-ODN or/and SP600125. Meantime, RAW264.7 cells were used to investigate the effect of CpG-ODN on OVA-induced ER stress in vitro. The cellularity of bronchoalveolar lavage fluid (BALF) was classified and counted after Wright–Giemsa staining. HE and PAS staining methods were applied to analyze airway inflammation. The protein levels of IL-4, IL-5, IL-13, p-JNK, JNK, CHOP, XBP1, ATF6α and GRP78 in lung tissues were detected by Western blotting. Correspondingly, the ER stress markers were detected by Western blotting and immunofluorescence in RAW264.7 cells.Results: In OVA-induced allergic airway inflammation, CpG-ODN significantly suppressed inflammatory cells infiltration, goblet cell hyperplasia and the protein expression of Th2 cytokines. Moreover, OVA exposure strongly increased the activation of ER stress with higher protein expressions of CHOP, XBP1, ATF6α and GRP78. However, these OVA-induced increase of ER stress markers were markedly suppressed by CpG-ODN treatment. In addition, exposure to OVA significantly increased the phosphorylation of JNK, which was significantly reduced by CpG-ODN treatment. Remarkably, single treatment of SP600125, an antagonist of JNK, functioned similarly as CpG-ODN in mitigating allergic airway inflammation and suppressing OVA-induced activation of ER stress; however, no significant synergistic effect was evidenced by combined treatment of SP600125 and CpG-ODN. Furthermore, in OVA-stimulated RAW264.7 cells, we also found that OVA stimulation increased the expressions of ER stress markers, and CpG-ODN significantly reduced their expression levels via suppressing the phosphorylation of JNK.Conclusion: These results indicated that CpG-ODN mitigates allergic airway inflammation via suppressing the activation of JNK-medicated ER stress.Keywords: asthma, CpG-ODN, SP600125, endoplasmic reticulum homeostasis

Yuhui Ruan,1 Weisin Chen,2 Chenyang Zhuang,2 Hong Lin2,3 1School of International and Public Affairs, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Institute of Medical Science Popularization, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Hong LinDepartment of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of ChinaTel +86 13636526656Email lin.hong1@zs-hospital.sh.cnPurpose: This study aimed to elucidate the quality of life of older adults/patients with degenerative lumbar diseases (ODLs) and analyse its association with some of their health-related perceptions.Materials and Methods: This mixed-methods study consisted of a questionnaire survey and an in-depth interview, which was designed within this study. ODLs were recruited from January 12, 2017 to June 27, 2018. The independent sample t-test and grounded theory coding method were employed for data analysis.Results: Of the 125 participants who returned valid questionnaires, 18 were included in the in-depth interviews. ODLs’ quality of life was associated with the following health-related perceptions: “life barriers”, “subjective health status”, and “treatment outcomes” across the domains of physiology, psychology, social relations, and environment.Conclusion: Our findings indicate that ODLs’ quality of life is associated with their health-related perceptions. Thus, to improve older adults’ quality of life, more attention should be paid to enhancing non-medical factors such as their health-related perceptions.Keywords: life barriers, subjective health status, treatment outcomes

Dixing Liu, Jiana Zhong, Weiheng Wen, Yuting Ruan, Zhen Zhang, Jia Sun, Hong Chen Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Hong Chen; Jia SunDepartment of Endocrinology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, Guangdong, 510282, People’s Republic of ChinaTel +86 13602759769; +86 13751822925Email chenhong123@smu.edu.cn; sunjia@smu.edu.cnPurpose: Either visceral fat or muscle mass is identified to be correlated with cardiometabolic diseases, especially in type 2 diabetes (T2DM). But, the synergistical effect of visceral fat along with skeletal muscle on the risk of cardiovascular diseases (CVD) in T2DM still remains controversial. Thus, we investigated the relationship between skeletal muscle mass to visceral fat area ratio (SVR) and 10-yr CVD risk scores.Patients and Methods: A total of 291 T2DM patients aged 40– 80 years were enrolled in the current study. SVR was evaluated based on bioelectrical impedance measurements. Both Framingham risk score system and China-PAR risk model were applied to estimate future 10-yr CVD risk in T2DM population.Results: The 10-yr CVD risk scores increased with the decreased SVR tertiles in T2DM (All P< 0.001). SVR value was obviously lower in the high-risk group than that of low- or moderate-risk group (All P< 0.05). However, no significant differences were observed in BMI among different CVD risk groups. Besides, SVR was correlated with Framingham risk score (r=− 0.408; P< 0.001) and China-PAR risk score (r=− 0.336; P< 0.001). HOMA-IR, triglycerides and blood pressure were also inversely related to SVR (All P< 0.05). Furthermore, SVR value was independently correlated with both Framingham 10-yr CVD risk score (β=− 0.074, P=0.047) and China-PAR risk score (β=− 0.100, P=0.004) after adjustment for confounding factors, including age, gender, BMI, FPG, HbA1c, diabetes duration, albumin, creatinine, uric acid, smoking, blood pressure and blood lipid. The linear regression analysis was also conducted for men and women, respectively, indicating that the negative relationship between SVR and 10-yr CVD risk was observed in men but not in women.Conclusion: T2DM populations who have lower SVR value are more likely to increase CVD risk. SVR levels show marked and inverse correlation with estimated 10-yr CVD risk in T2DM, indicating that SVR could be a valuable parameter to assess the risk of CVD events in clinical practice, especially in men.Keywords: type 2 diabetes mellitus, cardiovascular diseases, skeletal muscle mass to visceral fat area ratio, risk assessment

Ran Zheng, Yang Ruan, Yiqun Yan, Zhihao Lin, Naijia Xue, Yaping Yan, Jun Tian, Xinzhen Yin, Jiali Pu, Baorong Zhang Department of Neurology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, 310009, People’s Republic of ChinaCorrespondence: Baorong Zhang; Jiali PuDepartment of Neurology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, People’s Republic of ChinaFax +86-571-87784752Email brzhang@zju.edu.cn; jialipu@zju.edu.cnBackground: Inflammasome-induced neuroinflammation is a key contributor to the pathology of Parkinson’s disease (PD). NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation has been implicated in PD in postmortem human PD brains, indicating it as a potential target for PD treatment. Melatonin, a multitasking molecule, has been found to have anti-inflammatory activities, mediated by silence information regulator 1 (SIRT1). However, whether and how melatonin is involved in inflammasome-induced neuroinflammation in PD pathogenesis remains unclear.Methods: We investigated the potential anti-inflammatory effects of melatonin in vitro and in vivo, using 1-methyl-4-phenylpyridinium (MPP+)-simulated BV2 and primary microglia cell models, and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced murine PD model, with or without melatonin treatment. Rotarod, grip strength, and open-field tests were performed to measure the effects of melatonin on MPTP-induced motor disorders. Degeneration of dopaminergic neurons was evaluated by immunofluorescence. Changes in microglia were examined by immunofluorescence and Western blotting, and the expression levels of the involved signaling molecules were assessed by Western blotting and enzyme-linked immunosorbent assay (ELISA). Intracellular reactive oxygen species (ROS) was detected using fluorescent probes via flow cytometry.Results: We found that melatonin significantly alleviated motor dysfunction and prevented MPTP-induced neurotoxicity in dopaminergic neurons. Additionally, melatonin reduced MPTP-induced microglial activation and suppressed NLRP3 inflammasome activity, and also inhibited IL-1β secretion. Moreover, in MPP+-primed BV2 cells, melatonin markedly restored the downregulation of SIRT1 and attenuated the activation of the NLRP3 inflammasome. This was reversed by SIRT1 inhibitor treatment.Conclusion: In conclusion, our data demonstrated that melatonin attenuates neuroinflammation by negatively regulating NLRP3 inflammasome activation via a SIRT1-dependent pathway in MPTP-induced PD models. These findings provide novel insights into the mechanism underlying the anti-inflammatory effects of melatonin in PD.Keywords: inflammasomes, melatonin, NLRP3, Parkinson disease, sirtuin 1

Jingjie Hu,&ast; Liuyuan Wang,&ast; Kaili Fan, Wenwei Ren, Qiongzhang Wang, Yiting Ruan, Chengxiang Yuan, Guiqian Huang, Jincai He Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jincai He; Guiqian HuangDepartment of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, People’s Republic of ChinaTel +86 577-555780166; +86 577-555781380Fax +86 577-55578033; +86 577-55578999Email hjc@wmu.edu.cn; huangguiqian123@126.comObjective: Inflammation plays an important role in stroke. Many inflammatory markers in peripheral blood are proved to be associated with stroke severity or prognosis. But few comprehensive models or scales to evaluate the post-stroke depression (PSD) have been reported. In this study, we aimed to compare the level of systemic inflammation markers between PSD and non-PSD patients and explore the association of these inflammatory markers with PSD.Methods: Totally, 432 ischemic stroke patients were consecutively enrolled in the study and received 1 month follow-up. We used the 17-Hamilton Rating Scale to measure depressive symptoms at 1 month after stroke. With the Hamilton Depression Scale score of > 7, patients were diagnosed with PSD. Systemic immune-inflammation index (SII), neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and derived neutrophil-to-lymphocyte ratio (dNLR) were calculated from the admission blood work.Results: Finally, 129 patients (30.5%) were diagnosed with PSD at 1 month. PSD patients showed significantly higher levels of SII (501.27 (345.43– 782.58) vs 429.60 (315.64– 570.98), P=0.001), NLR (2.36 (1.77– 3.82) vs 2.17 (1.56– 2.80), P=0.010), dNLR (1.67 (1.30– 2.51) vs 1.54 (1.16– 1.99), P=0.009), PLR (124.65 (95.25– 155.15) vs 109.22 (92.38– 142.03), P=0.015), especially SII at admission as compared to non-PSD patients. In the logistic analysis, SII value (> 547.30) was independently associated with the occurrence of PSD (OR=2.181, 95% CI=1.274– 3.732, p =0.004), better than dNLR (OR=1.833, 95% CI=1.071– 3.137, p =0.027), PLR (OR= 1.822, 95% CI=1.063– 3.122, p =0.029) and NLR (OR =1.728, 95% CI=1.009– 2.958, p =0.046).Conclusion: Increased SII, PLR, dNLR, NLR, particularly SII at admission, are significantly correlated with PSD and may add some prognostic clues to find early discovery of PSD.Keywords: inflammatory markers, post-stroke depression, systemic immune-inflammation index, neutrophil-to-lymphocyte, platelet-to-lymphocyte, derived neutrophil-to-lymphocyte ratio

Hanxin Zhao, Yu Ruan Department of Endocrinology and Metabolism, Zhejiang University Affiliated Sir Run Run Shaw Hospital, School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Yu RuanDepartment of Endocrinology and Metabolism, Zhejiang University Affiliated Sir Run Run Shaw Hospital, School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, People’s Republic of ChinaTel +86 571 86006171Email ruanyu2019@zju.edu.cnIntroduction: In recent years, radioactive iodine (RAI) therapy has become a main choice for Graves’ disease. The rapid release of thyroid hormones following RAI may on occasion trigger severe events, such as thyroid storm or heart block. This study presents two cases of possible acute adrenocortical insufficiency precipitated by radioiodine therapy.Case Presentation: Two females aged 65 and 19 years with long-standing Graves’ disease underwent radioiodine treatment at our clinical center. Both patients suffered nausea, fatigue, aggravated palpitation, and relative hypotension thereafter. Laboratory data showed severe thyrotoxicosis with free thyroxine higher than three times the upper limit, while basal serum cortisol (8 AM) was below the lower limit (5.08 μg/dL and 2.08 μg/dL respectively) under stress, indicating a potential relative adrenocortical insufficiency. There was then full recovery after adequate hydrocortisone therapy. As thyrotoxicosis resolved, the levels of basal cortisol were subsequently raised to normal.Conclusion: Post-RAI adrenocortical insufficiency might occur in patients with severe Graves’ disease. Basal serum cortisol might be a cost-effective parameter for the identification of potential patients.Keywords: Graves’ disease, hyperthyroidism, adrenal insufficiency, radioiodine therapy

Chengxiang Yuan,1,* Siyan Chen,1,* Yiting Ruan,1 Yuntao Liu,1 Haoran Cheng,1 Yaying Zeng,1 Yunbin Chen,1 Qianqian Cheng,2 Guiqian Huang,1 Weilei He,1 Jincai He1 1Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of China; 2School of Mental Health, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jincai HeDepartment of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, People’s Republic of ChinaTel/Fax +86 0577 55579363Email hjc@wmu.edu.cnBackground: Hemorrhagic transformation (HT) is a severe complication occurring in acute ischemic stroke (AIS) patients. Stress hyperglycemia is frequent in patients with acute illness such as stroke. We aimed to explore the association between stress hyperglycemia and HT in AIS patients.Methods: A total of 287 consecutive participants with HT and 285 age- and sex-matched stroke patients without HT were enrolled in this study. Baseline glucose and glycated hemoglobin (HbA1c) levels were collected to measure stress hyperglycemia. The stress hyperglycemia ratio (SHR) was calculated by dividing the fasting plasma glucose at admission with HbA1c. HT was diagnosed by follow-up imaging assessment, and was radiologically classified as hemorrhagic infarction type (HI) 1 or 2 or parenchymal hematoma type (PH) 1 or 2.Results: Univariate analysis showed that SHR is significantly higher among patients with HT than those without HT. Compared to the patients in the lower three quartiles of SHR, the incidence of HT was significantly higher among patients with the highest quartile of SHR in total population, diabetic and non-diabetic population. We also observed that patients with the highest SHR quartile were associated with an increased risk of hemorrhagic transformation after adjusted for potential covariates (68.4% versus 39.1%; adjusted odds ratio, 2.320; 95% confidence interval, 1.207– 4.459; P=0.012).Conclusion: The stress hyperglycemia ratio, representing the state of stress hyperglycemia, was significantly associated with an increased risk of hemorrhagic transformation in patients with acute ischemic stroke.Keywords: hyperglycemia, hemorrhagic transformation, acute ischemic stroke, stress hyperglycemia

Pengyu Zhang,1,* Jun Xiao,2,* Yingxin Ruan,3,* Zhenzhen Zhang,1 Xuejun Zhang2 1Department of Blood Transfusion, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin 300060, People’s Republic of China; 2Department of Immunology, Key Laboratory of Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, People’s Republic of China; 3Department of Nephrology, General Hospital of Tianjin Medical University, Tianjin 300052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xuejun ZhangDepartment of Immunology, Key Laboratory of Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, People’s Republic of ChinaTel +86 151 2280 0672Email xjzhimmunology@163.comPurpose: The aim of this study was to investigate the monitoring value of serum HER2 in patients with metastatic breast cancer.Patients and Methods: We firstly evaluated the association of serum HER2 levels with tissue HER2 expression and imaging results in 420 breast cancer patients admitted into Tianjin Medical University Cancer Institute and Hospital between April 2016 and December 2018. Secondly, we analyzed serum HER2 levels in breast cancer patients with different metastatic degrees.Results: There is a higher correlation between serum HER2 and tissue HER2 in breast cancer patients with stage III (κ=0.670, p< 0.001) and stage IV (κ=0.464, p< 0.001). Serum HER2 levels were significantly associated with imaging results (κ=0.478, p< 0.001). The ROC curve analysis showed that serum HER2 was superior to other serum markers for predicting metastatic breast cancer. Multinomial logistic regression revealed that the patients with higher serum HER2 levels would be more likely to have breast cancer metastasis.Conclusion: Serum HER2 levels in breast cancer patients can partly reflect tissue HER2 expression and tumor imaging changes, and serum HER2 may be used as a biomarker for evaluating metastatic status in patients with breast cancer.Keywords: serum HER2, breast cancer, tumor metastasis, biomarker

Shasha Lin, 1,* Xiaoqian Luan, 1,* Weilei He, 1,* Yiting Ruan, 1 Chengxiang Yuan, 1 Aiyue Fan, 1 Xiachan Chen, 2 Jincai He 1 1Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, People’s Republic of China; 2Department of Neurology, Wenzhou 325000, Zhejiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jincai HeDepartment of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, People’s Republic of ChinaTel/Fax +86 577 5557 9363Email hjc@wmu.edu.cnPurpose: Post-stroke depression (PSD) is a frequent comorbidity in patients presenting with acute ischemic stroke. Impaired kidney function has been associated with depression in non-stroke subjects. We would like to evaluate whether the estimated glomerular filtration rate (eGFR) on admission is associated with the development of PSD.Patients and methods: Total of 268 patients with acute ischemic stroke were recruited and completed 1-month follow-up visit. eGFR was calculated from the serum creatinine value, race, age, and sex by using the chronic kidney disease epidemiology collaboration equation (CKD-EPI creatinine equation). The 17-item Hamilton Depression Scale was used to evaluate depression symptoms. Patients with a depression score of ≥ 7 were evaluated using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition, for diagnosing post-stroke depression at 1 month. Meanwhile, 114 normal control subjects were also recruited.Results: Ninety-three (34.7%) patients were diagnosed as having PSD at 1 month. There was a significant intergroup difference in eGFR levels within 24 hrs after admission (F=13.608, p< 0.001). The levels of eGFR within 24 hrs after admission were significantly lower in both non-PSD patients and PSD patients than in normal controls. In logistic regression, the level of eGFR (< 82mL/min/1.73m 2) was independently associated with increased risk of PSD even after adjusting for confounders (OR=2.328, 95% CI:1.092– 4.965, p=0.029).Conclusion: Reduced eGFR was found to be correlated with the development of PSD and it suggests the need for greater attentions and potential interventions for depression in patients with stroke and with reduced eGFR.Keywords: estimated glomerular filtration rate, eGFR, post-stroke depression, stroke, Depression

Ligen Du,1–3 Enping Chen,2 Ting Wu,4 Yunjun Ruan,1 Saizhu Wu1 1Department of Geriatrics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; 2Department of Cardiology, The Second People’s Hospital of Longgang District, Shenzhen, Guangdong, China; 3Department of Cardiology, Longgang District People’s Hospital of Shenzhen, Guangdong, China; 4Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, China Purpose: Resveratrol (RESV; trans-3,5,4'-trihydroxystilbene) has emerged as a potential new therapeutic for age-related atherosclerotic diseases. However, the effect of RESV on cellular aging and its underlying mechanisms remain unknown. Therefore, the aim of this study was to examine whether RESV can delay cellular aging through upregulation of autophagy. Materials and methods: Human umbilical endothelial vein cells (HUVECs) were divided into four groups: the control group, and the hydrogen peroxide (H2O2) alone, H2O2 + RESV pretreatment, and H2O2 + 3-methyladenine (3-MA) + RESV pretreatment intervention groups. The cell viability was evaluated by a cell counting kit-8 assay. Superoxide dismutase (SOD) activity and intracellular reactive oxygen species (ROS) levels were tested using commercial kits. Senescence-related β-galactosidase activities were detected by immunohistochemical staining. The expression levels of aging-related and autophagy-related markers, including phosphorylated Rb (p-Rb), LC3, and p62, with or without RESV were measured by Western blotting. Results: Pretreatment with 10 µM RESV increased the cell viability and SOD levels. The remarkably higher positive rate of senescence-associated β-galactosidase and increased intracellular ROS levels in the H2O2 treatment group were reversed by treatment with 10 µM RESV. As compared to the H2O2 treatment group, 10 µM RESV could upregulate autophagy through the regulation of p-Rb, LC3, and p62 levels. The anti-aging effect of RESV via an autophagy regulation mechanism was further confirmed by the suppression of these effects with 3-MA treatment. Conclusion: RESV may reverse and delay the aging process of HUVECs via upregulation of autophagy and could be a candidate therapeutic for age-related atherosclerotic diseases. Keywords: oxidative stress, senescence, LC3, p62, p-Rb

Disrupted-in-Schizophrenia-1 (DISC1) is a genetic susceptibility locus for major mental illness, including schizophrenia and depression. The Disc1 protein was recently shown to interact with the Wnt signaling protein, DIX domain containing 1 (Dixdc1). Both proteins participate in neural progenitor proliferation dependent on Wnt signaling, and in neural migration independently of Wnt signaling. Interestingly, their effect on neural progenitor proliferation is additive. By analogy to Disc1, mutations in Dixdc1 may lead to abnormal behavior in mice, and to schizophrenia or depression in humans. To explore this hypothesis further, we generated mice mutant at the Dixdc1 locus and analyzed their behavior. Dixdc1(-/-) mice had normal prepulse inhibition, but displayed decreased spontaneous locomotor activity, abnormal behavior in the elevated plus maze and deficits in startle reactivity. Our results suggest that Dixdc1(-/-) mice will be a useful tool to elucidate molecular pathophysiology involving Disc1 in major mental illnesses.

Ye Ruan,1 Xueling Xiao,2 Jia Chen,2 Xianhong Li,2 Ann Bartley Williams,3 Honghong Wang2 1Nursing Department, Second Xiangya Hospital, 2Xiangya School of Nursing, Central South University, Changsha, Hunan, People’s Republic of China; 3School of Nursing, Yale University, West Haven, CT, USA Aim: The aim of this study was to examine the acceptability and efficacy of interactive short message service (SMS) in improving medication adherence in antiretroviral treatment (ART)-naïve individuals living with HIV/AIDS in Hengyang, Hunan, China.Background: SMS via mobile phone has emerged as a potential tool for improving ART adherence. However, most studies used SMS only as a medication reminder, with few studies exploring the effect of comprehensive, interactive SMS.Patients and methods: In a randomized controlled trial, 100 HIV-positive patients on ART for