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Mingyue Shang,* Zhehong Li,* Guangzhong Xu, Dongbo Lian, Zhaohui Liao, Dezhong Wang, Buhe Amin, Zheng Wang, Weijian Chen, Dexiao Du, Nengwei Zhang, Liang Wang Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038, People’s Republic of China*These authors contributed equally to this workCorrespondence: Nengwei Zhang; Liang Wang, Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, No. 10, Tieyi Road, Yangfangdian, Haidian District, Beijing, 100038, People’s Republic of China, Tel +8613801068802 ; +8619800320171, Email zhangnw@ccmu.edu.cn; 1911110644@pku.edu.cnPurpose: Gastroesophageal reflux disease (GERD) is a common complication after laparoscopic sleeve gastrectomy (LSG); This study aimed to construct a model that can predict the incidence of GERD after LSG by exploring the correlation between the results of high-resolution esophageal manometry (HREM) and the incidence of GERD after LSG.Patients and Methods: We collected the clinical data of patients who had undergone HREM before bariatric surgery from September 2013 to September 2019 at the bariatric center of our hospital. The Gerd-Q scores during the postoperative follow-up were collected to determine the incidence of GERD. A logistic regression analysis was performed to explore the correlation of the HREM results and general clinical data with the incidence of GERD after LSG.Results: The percentage of synchronous contractions, lower esophageal sphincter (LES) resting pressure, and history of smoking were correlated with the development of GERD after LSG, with the history of smoking and percentage of synchronous contractions as risk factors and LES resting pressure as a protective factor. The training set showed an area under the ROC curve (AUC) of the nomogram model of 0.847. The validation set showed an AUC of 0.761. The decision and clinical impact curves showed a high clinical value for the prediction model.Conclusion: The HREM results correlated with the development of GERD after LSG, with the percentage of synchronous contractions and LES resting pressure showing predictive value. Combined with the history of smoking, the predictive model showed a high confidence and clinical value.Keywords: gastroesophageal reflux disease, laparoscopic sleeve gastrectomy, high-resolution esophageal manometry, complications

Shanshan Ai,1,&ast; Yue Wang,2 Pengli Niu,2 Wenjun Xiao,2 Guojun Xu,2 Chang Zhu3,&ast; 1Department of Nursing, Linping District Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Nursing, The First Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Department of Expanded Program on Immunisation, Linping District Centre for Disease Control and Prevention, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guojun Xu, Department of Nursing, The First Affiliated Hospital of Dalian Medical University, No. 222, Zhongshan Road, Xigang District, Dalian, Liaoning, 116011, People’s Republic of China, Email xgj1973@163.comPurpose: This study aimed to investigate the correlation between preoperative pain catastrophizing and social support, and acute post-surgical pain in patients who underwent knee arthroplasty. The study also aimed to determine whether social support moderates the role of pain catastrophizing psychologically in acute post-surgical pain after knee arthroplasty.Patients and Methods: This study recruited participants to survey a tertiary hospital in Dalian, China, between November 2022 and October 2023. Participants completed pain catastrophizing scales and social support reevaluated scales one day (T1) before they were confirmed to undergo knee arthroplasty, and finished the Numeric Rating Scale at 24h (T2), 48h (T3), and 72h (T4) postoperatively. Pearson correlation analyses were used to explore the relationship between social support, pain catastrophizing, and acute post-surgical pain, hierarchical regression analysis was used to test the moderating role of social support between pain catastrophizing and acute post-surgical pain.Results: This study recruited 178 knee arthroplasty patients. The results of the t-test or one-way ANOVA indicated that there were statistically significant differences in gender, age, education, occupation, disease duration, whether the knee replacement was performed for the first time, preoperative pain scores, and operation time in patients with knee arthroplasty (P < 0.05). The correlation analysis of social support, pain catastrophization, and acute post-surgical pain in knee arthroplasty patients showed that social support was negatively correlated with acute post-surgical pain (r=− 0.584, P< 0.01), and pain catastrophizing was positively correlated with postoperative acute pain (r=0.601, P< 0.01); The hierarchical regression analysis revealed that social support had a significant moderating effect on the relationship between pain catastrophizing and acute post-surgical pain (ΔR2=0.606, P< 0.05).Conclusion: The acute post-surgical pain of knee arthroplasty patients was affected by gender, age, education, occupation, disease duration, whether the knee arthroplasty was performed for the first time, preoperative pain scores, and operation time. Acute Post-surgical pain in patients with knee arthroplasty was affected by social support and pain catastrophizing, and social support had a moderating effect on the relationship between pain catastrophizing and acute post-surgical pain.Keywords: knee arthroplasty, pain, pain catastrophizing, social support

Ganzhe Xu,1 Guoyu Dai,2 Zhongli Huang,3 Qiunong Guan,2 Caigan Du,2 Xiaoming Xu4 1Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Department of Biomedical Engineering, Guoke Ningbo Life Science and Health Industry Research Institute, Ningbo, Zhejiang, People’s Republic of China; 3Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Urology, Ningbo No. 2 Hospital, Ningbo, Zhejiang, People’s Republic of ChinaCorrespondence: Caigan Du, Department of Biomedical Engineering, Guoke Ningbo Life Science and Health Industry Research Institute, Ningbo, Zhejiang, People’s Republic of China, Email ducaigan@ucas.ac.cn Xiaoming Xu, Department of Urology, Ningbo No. 2 hospital, Ningbo, Zhejiang, People’s Republic of China, Email xiaomingxu6@sohu.comAbstract: Benign prostatic hyperplasia (BPH) mainly causes lower urinary tract symptoms in ageing men, but its exact etiology and pathogenesis have not been established. The objective of this review was to design an update on the advances of human BPH research. We undertook a literature search for identifying studies of the roles of sex hormones (androgens and estrogens) in the onset and development of human BPH using the Pubmed database. In literature, many studies have indicated that ageing and obesity are the factors for preceding the onset of BPH. No evidence for the role of testosterone (T) or dihydrotestosterone (DHT) is found in BPH initiation. Since BPH exclusively occurs in the transitional zone (TZ) surrounding the urethra, it is postulated that years of exposure to uncharacterized urinary toxins could disrupt the homeostasis of the stroma and/or epithelium of this prostatic zone that are typically occurring in ageing men. After cellular damage and subsequent inflammation generated, the intraprostatic DHT produced mainly from T by 5α-reductase promotes BPH development. Further, estrogens could take part in the nodular proliferation of stromal cells in some BPH patients. The confounding of BPH may attenuate the development of prostate tumor in the TZ. In conclusion, evidence in literature suggests that androgens are not etiological factors for BPH, and intraprostatic DHT along with chronic inflammation are mainly responsible for nodular proliferation of stromal and/or epithelial cells in prostatic TZ. The urinary factors for the etiology of BPH and BPH as a prediction of PCa progression still need further investigation.Keywords: benign prostatic hyperplasia, tissue homeostasis, etiology, nodular proliferation, stroma, epithelium, androgens, steroid sex hormones

Mingyue Shang,&ast; Zhehong Li,&ast; Dexiao Du,&ast; Guangzhong Xu, Dongbo Lian, Zhaohui Liao, Dezhong Wang, Buhe Amin, Zheng Wang, Weijian Chen, Nengwei Zhang, Liang Wang Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nengwei Zhang; Liang Wang, Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, No. 10, Tieyi Road, Yangfangdian, Haidian District, Beijing, 100038, People’s Republic of China, Tel +8613801068802 ; +8619800320171, Email zhangnw@ccmu.edu.cn; 1911110644@pku.edu.cnPurpose: Obesity and related complications are managed by One Anastomosis Gastric Bypass (OAGB) and Single Anastomosis Duodeno-Jejunal Bypass with Sleeve Gastrectomy (SADJB-SG), both of which are adapted from traditional gastric bypass procedures. However, there are no current comparative studies on the safety and efficacy of these two surgical procedures.Patients and Methods: Preoperative baseline data of patients who had undergone OAGB and SADJB-SG surgeries from June 2019 to June 2021 were retrospectively analyzed at our bariatric facility. Postoperative data, including weight changes, improvement in type 2 diabetes (T2DM), and complication rates were collected over 2 years. This was followed by a comprehensive evaluation of the safety and efficacy of the two surgical procedures.Results: A total of 63 patients completed the follow-up in this study. At the 24-month follow-up, excess weight loss percentage (EWL%) for the OAGB and SADJB-SG was 73.970± 5.005 and 75.652± 7.953, respectively (P-value = 0.310); total weight loss percentage (TWL%) was 24.006± 8.231 and 23.171± 6.600, respectively (P-value = 0.665). The diabetes remission rates for the two groups were 71.429% and 69.048%, respectively (P-value = 0.846). The cost for OAGB was 55088.208± 1508.220 yuan, which was significantly lower than the 57538.195± 1374.994 yuan for SADJB-SG (P-value< 0.001).Conclusion: The two surgical procedures are reliable in terms of safety and efficacy, and each has distinct advantages. While OAGB has reduced operational expenses, SADJB-SG offers a broader range of applicability.Keywords: one anastomosis gastric bypass, single anastomosis duodeno-jejunal bypass with sleeve gastrectomy, safety, efficacy

Yueqin Wang,&ast; Gufeng Xu,&ast; Chenqi Yan, Fang Wang, Min Yang, Yue Wang Department of Ambulatory Surgery, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Wang, Women’s Hospital, Zhejiang University School of Medicine, Xueshi Road, Hangzhou, 310000, Zhejiang, People’s Republic of China, Tel +86 87061501, Email Misswangyue@zju.edu.cnBackground: This study investigates the differences in the cost, time, pre-operative education and patient satisfaction levels of patients requiring a second hysteroscopic surgery using a full-service model of remote preoperative assessment, surgical appointments, and preoperative education.Methods: Forty-one patients who were proficient in the use of telemedicine platforms, planned to undergo a second hysteroscopic surgery, and selected either telemedicine (N=21) or face-to-face (N=20) models for their preoperative assessments, surgical appointments, and preoperative education were included. The data were analyzed using the Mann–Whitney U-test and Fisher’s exact test.Results: No significant demographic differences were observed between patients who used telemedicine and those who did not. The telemedicine group demonstrated significantly lower median travel time (40 min vs 205 min, P < 0.01), time spent in hospital (60 min vs 155 min, P < 0.01), meal time (0 min vs 60 min, P < 0.01), and total time spent (108 min vs 415 min, P < 0.01). Similarly, the telemedicine group had significantly lower median travel expenses (40 yuan vs 300 yuan, P < 0.01) and meal expenses (0 yuan vs 135 yuan, P < 0.01), and overall, total expenses (255 yuan vs 837 yuan, P < 0.01). 95.2% of the telemedicine group completely understood the preoperative education, compared to 100% who completely understood in the face-to-face group (P = 1.00). All patients in the telemedicine group were very satisfied compared to 80% in the face-to-face group (P = 1.00).Conclusion: Telemedicine may be a feasible and advantageous method for preoperative assessment, surgical appointments, and preoperative education in gynecological day surgery. The application of telemedicine has demonstrated notable time and cost efficiency with high patient satisfaction levels. Future research should explore the full potential of telemedicine in this setting and for other surgical procedures.Keywords: telemedicine, gynecological day surgery, patient satisfaction, cost and time efficiency

Guoqiang Xu,1,2,&ast; Xiaona Song,2,&ast; Xiaotang Wang,1,2,&ast; Rui Xue,1,2 Xiaoru Yan,1,2 Litao Qin,1,2 Xiaoqi Chang,1,2 Jiping Gao,1 Zhaoyang Chen,1 Guohua Song1 1Laboratory Animal Center Shanxi Key Laboratory of Experimental Animal Science and Human Disease Animal Model, Shanxi Medical University, Taiyuan, People’s Republic of China; 2School of Basic Medical Science, Shanxi Medical University, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guohua Song, Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Human Disease Animal Model, Shanxi Medical University, Road Xinjian 56, Taiyuan, 030001, People’s Republic of China, Tel +86-351-4135919, Email ykdsgh@sxmu.edu.cnPurpose: Oral squamous cell carcinoma is the most common type of malignant tumor in the head and neck region. Despite advancements, metastasis and recurrence rates remain high, and patient survival has not significantly improved. Although miRNA therapies are promising for cancer gene therapy, their applications in treating oral cancer are limited. Targeted medication delivery systems based on nanotechnology offer an efficient way to enhance oral cancer treatment efficacy.Methods: We synthesized nanosilver (AgNPs) and loaded them with the tumor suppressor miR-181a-5p. In vitro experiments were conducted to investigate the inhibitory effects of AgNPs and their composites on the malignant behavior of oral cancer cell lines. The xenograft experiment was utilized to examine their effects on tumorigenesis and the potential molecular mechanisms involved.Results: The nanosilver exhibited a spherical morphology with a size distribution ranging from 50 to 100 nm. They exhibited a distinct absorption peak at 330 nm and could be excited to emit green fluorescence. The biocompatible AgNPs effectively shielded miRNA from degradation by RNase and serum. The nanocomposites significantly inhibited the proliferation, invasion, migration, and colony formation of oral cancer cell lines. Notably, treatment with the nanocomposites resulted in substantial tumor growth suppression in the xenograft model. Mechanistically, these composites directly targeted BCL2 and exerted their antitumor effects by suppressing the β-catenin signaling pathway and other downstream genes without inducing acute toxicity.Conclusion: Collectively, the findings demonstrate that the miR-181a-5p/AgNPs combination significantly impedes the growth and progression of oral cancer both in vitro and in vivo, highlighting a pivotal role for the β-catenin signaling pathway. This multifaceted approach holds promise as a prospective therapeutic strategy for oral cancer management in the future. Keywords: silver nanoparticles, nanocomposite, combination therapy, β-catenin signaling pathway

Gang Xu,1,2,&ast; Tao Pan,2,&ast; Si Li,2,3,&ast; Jing Guo,2 Ya Zhang,2 Qi Xu,2 Renwei Chen,4 Yanlin Ma,2 Yongsheng Li2,3 1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China, Harbin, 150081, People’s Republic of China; 2Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Reproductive Medical Center, National Center for International Research, The First Affiliated Hospital of Hainan Medical University, College of Biomedical Information and Engineering, Hainan Medical University, Haikou, Hainan, 571199, People’s Republic of China; 3School of Interdisciplinary Medicine and Engineering, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 4Hainan Women and Children’s Medical Center, Hainan Medical University, Haikou, Hainan, 571199, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongsheng Li; Yanlin Ma, Email liyongsheng@ems.hrbmu.edu.cn; mayanlinma@hotmail.comBackground: The heterogeneity and dynamic changes of endometrial cells have a significant impact on health as they determine the normal function of the endometrium during the menstrual cycle. Dysfunction of the endometrium can lead to the occurrence of various gynecological diseases. Therefore, deconvolution of immune microenvironment that drives transcriptional programs throughout the menstrual cycle is key to understand regulatory biology of endometrium.Methods: Herein, we comprehensively analyzed single-cell transcriptome of 59,397 cells across ten human endometrium samples and revealed the dynamic cellular heterogeneity throughout the menstrual cycle.Results: We identified two perivascular cell subtypes, four epithelial subtypes and four fibroblast cell types in endometrium. Moreover, we inferred the cell type-specific transcription factor (TF) activities and linked critical TFs to transcriptional output of diverse immune cell types, highlighting the importance of transcriptional regulation in endometrium. Dynamic interactions between various types of cells in endometrium contribute to a range of biological pathways regulating differentiation of secretory. Integration of the molecular biomarkers identified in endometrium and bulk transcriptome of 535 endometrial cancers (EC), we revealed five RNA-based molecular subtypes of EC with highly intratumoral heterogeneity and different clinical manifestations. Mechanism analysis uncovered clinically relevant pathways for pathogenesis of EC.Conclusion: In summary, our results revealed the dynamic immune microenvironment of endometrium and provided novel insights into future development of RNA-based treatments for endometriosis and endometrial carcinoma.Keywords: single-cell sequencing, cell–cell interaction, biological pathways, molecular subtypes, RNA biomarkers

Zheng Wang,1,&ast; Guangzhong Xu,1,&ast; Guanyang Chen,2,3,&ast; Buhe Amin,1 Liang Wang,1 Zhehong Li,1 Jing Wang,1 Weijian Chen,1 Chengyuan Yu,3 Chenxu Tian,1 Qiqige Wuyun,1 Qing Sang,3 Mingyue Shang,1 Dongbo Lian,1 Nengwei Zhang1 1Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, People’s Republic of China; 2Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 3Surgery Centre of Diabetes Mellitus, Peking University Ninth School of Clinical Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongbo Lian; Nengwei Zhang, Shijitan Hospital, Tieyi Road, Haidian District, Beijing, People’s Republic of China, Tel +8613681299755 ; +8613801068802, Email lian.dongbo@126.com; zhangnw1@sohu.comBackground: Some research have indicated that Bariatric and metabolic surgery (BMS) can reduce the risk of cardiovascular disease (CVD) among individuals with obesity. However, there are few reports available that focuses on assessing effect of BMS on the risk of CVD in Chinese population using multiple models.Objective: This research aims to assess the function of BMS on the risk of CVD in Chinese patients with obesity using multiple CVD risk models.Methods: We performed a retrospective analysis of the basic data and glycolipid metabolism data preoperatively and postoperatively from patients with obesity at our hospital. Subgroup analysis was carried out according to different surgical procedures. Then, the function of BMS on the risk of CVD in the Chinese population was assessed using four models, including: China-PAR risk model, Framingham risk score (FRS), World Health Organization (WHO) risk model, and Globorisk model.Results: We enrolled 64 patients, 24 (37.5%) of whom underwent laparoscopic sleeve gastrectomy (LSG) while 40 (62.5%) underwent Roux-en-Y gastric bypass (RYGB). The 10-year CVD risk for patients calculated using the China-PAR risk model decreased from 6.3% preoperatively to 2.0% at 1 year postoperatively and was statistically significantly different. Similarly, the 10-year CVD risk of patients calculated using the FRS, WHO, Global risk model decreased significantly at 1 year postoperatively compared to preoperatively. When the FRS risk model was used to calculate the patients’ 30-year postoperative CVD risk, there was a significant decrease at 1 year after surgery compared to the preoperative period. When employing various models to evaluate the 10-year CVD risk for LSG and RYGB, no statistically significant difference was found in the 1-year postoperative RRR between the procedures.Conclusion: The CVD risk after BMS was significantly reduced compared to preoperatively. In terms of improving cardiovascular risk, SG and RYGB appear to be equally effective.Keywords: obesity, metabolic surgery, T2DM, CVD risk model

Yamei Bai,&ast; Yuqing Chen,&ast; Meng Tian, Jiaojiao Gao, Yulei Song, Xueqing Zhang, Haiyan Yin, Guihua Xu School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guihua Xu, School of Nursing, Nanjing University of Chinese Medicine, No. 138, Xianlin Avenue, Qixia District, Nanjing, Jiangsu Province, 210023, People’s Republic of China, Tel +86-153-6513-2927, Email 7115@njucm.edu.cnPurpose: Social isolation and depression have an impact on cognitive frailty. However, the underlying mechanisms between these variables have not been well defined. This study aims to investigate the mediating role of depressive symptoms in the association between social isolation and cognitive frailty among older adults in China.Methods: From Mar 2023 to Aug 2023, a cross-sectional study was conducted with 496 community-dwelling older adults aged ≥ 60 years in Nanjing, Jiangsu Province, China. Demographic information was collected using the General Information Questionnaire. The Lubben Social Network Scale-6 (LSNS-6), Geriatric Depression Scale 15-item (GDS-15), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating (CDR), and FRAIL scale were used for the questionnaire survey. Multiple linear regression and binary logistic regression were utilized to explore the associations among social isolation, depressive symptoms, and cognitive frailty, and Bootstrap analysis was used to explore the mediating role of depressive symptoms in social isolation and cognitive frailty.Results: Linear regression results revealed that social isolation was positively associated with depressive symptoms (β = 0.873, p < 0.001). Logistic regression analysis showed that social isolation (OR = 1.769, 95% CI = 1.018~3.075) and depressive symptoms (OR = 1.227, 95% CI = 1.108~1.357) were significantly associated with cognitive frailty. Mediation analysis demonstrated that depressive symptoms significantly mediated the relationship between social isolation and cognitive frailty, with an indirect effect of 0.027 (95% CI = 0.003~0.051), and the mediating effect accounted for 23.6% of the total effect.Conclusion: Social isolation is associated with cognitive frailty in community-dwelling older adults, and depressive symptoms partially mediate the effect between social isolation and cognitive frailty. Active promotion of social integration among older individuals is recommended to enhance their mental health, reduce the incidence of cognitive frailty, and foster active aging.Keywords: cognitive frailty, social isolation, depressive symptoms, older adults

Summary: Pregnancy is a risk factor for increased severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory infections, but the mechanisms underlying this risk are poorly understood. To gain insight into the role of pregnancy in modulating immune responses at baseline and upon SARS-CoV-2 infection, we collected peripheral blood mononuclear cells and plasma from 226 women, including 152 pregnant individuals and 74 non-pregnant women. We find that SARS-CoV-2 infection is associated with altered T cell responses in pregnant women, including a clonal expansion of CD4-expressing CD8+ T cells, diminished interferon responses, and profound suppression of monocyte function. We also identify shifts in cytokine and chemokine levels in the sera of pregnant individuals, including a robust increase of interleukin-27, known to drive T cell exhaustion. Our findings reveal nuanced pregnancy-associated immune responses, which may contribute to the increased susceptibility of pregnant individuals to viral respiratory infection.

Yanling Li,&ast; Li Ji,&ast; Tian Liu, Guang Xu, Kaihe Wang, Leixin Mu, Yuying Guo, Qun Ma School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qun Ma, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email maqun99@126.comBackground: Qiguiyin decoction (QGYD) is a traditional Chinese medicine (TCM) and its combined application with levofloxacin (LVFX) has been confirmed effective in the clinical treatment of multidrug-resistant Pseudomonas aeruginosa (MDR PA) infection. This study investigated the therapeutic effect and possible mechanism of QGYD in sensitizing LVFX against MDR PA infection.Materials and Methods: Pulmonary infections were induced in rats by MDR PA. The changes in pharmacokinetics-pharmacodynamics (PK-PD) parameters of LVFX after combined with QGYD were investigated in MDR PA-induced rats. Subsequently, the correlation between PK and PD was analyzed and PK-PD models were established to elucidate the relationship between QGYD-induced alterations in LVFX metabolism and its sensitization to LVFX. Antibody chip technology was used to detect the levels of inflammatory factors, suggesting the relationship between the beneficial effect of immune regulation and the sensitization of QGYD.Results: QGYD significantly enhanced the therapeutic efficacy of LVFX against MDR PA infection. The combination of QGYD changed the PK parameters of LVFX such as Tmax, t1/2, MRT, Vd/F, CL/F and PD parameters such as MIC, AUC0-24h/MIC. Predicted results from PK-PD models demonstrated that the antibacterial effect of LVFX was significantly enhanced with the combination of QGYD, consistent with experimental findings. Antibody chip results revealed that the combination of QGYD made IL-1 β, IL-6, TNF- α, IL-10, and MCP-1 levels more akin to those of the blank group.Conclusion: These findings indicated that QGYD could change the PK-PD behaviors of LVFX and help the body restore immune balance faster. This implied that a potential drug interaction might occur between QGYD and LVFX, leading to improved clinical efficacy when combined.Keywords: multidrug-resistant Pseudomonas aeruginosa infection, combination therapy, PK/PD model, Qiguiyin decoction, levofloxacin

Runqian Huang,1,&ast; Chunling Zheng,1,2,&ast; Guixiao Xu,1 Xuanwei Chen,1 Jingxian Shen,1 Siyue Mao1 1Department of Radiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingxian Shen; Siyue Mao, Department of Radiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, 651 Dongfeng Road East, Guangzhou, 510060, People’s Republic of China, Tel/Fax +86-20-87343217, Email shenjx@sysucc.org.cn; maosiy@sysucc.org.cnObjective: To identify imaging features that help distinguish between HCCs and non-HCC malignancies assigned to LI-RADS M (LR-M) and evaluate the diagnostic performance of a LI-RADS with targetoid criteria using thin-rim arterial phase hyperenhancement (APHE).Materials and Methods: This retrospective study included 381 patients (387 observations) at high-risk for HCC who underwent enhanced-MRI before surgery. Three radiologists reviewed images for LI-RADS categorization of hepatic observations. Univariate and multivariate analysis was conducted to determine reliable features to differentiate between HCC and non-HCC malignancies among the LR-M lesions. The thin-rim (< 30%) APHE was defined based on the thickest thickness of rim APHE compared with the tumor radius, and a modified LI-RADS emphasizing thin-rim APHE as a specific feature of LR-M was established. We compared the diagnostic performance of modified LR-M and LI-RADS 5 (LR-5) with the conventional one.Results: Thin-rim APHE and targetoid diffusion-weighted imaging (DWI) were found as independent predictive factors of non-HCC malignancies, while enhancing capsule, thick-rim APHE and peripheral washout were noted as independent variables significantly associated with HCC of LR-M (P< 0.05). The noticeable diagnostic performance of thin-rim APHE in distinguishing non-HCC malignancies from HCCs using the ROC curve. Emphasizing thin-rim APHE on targetoid features, the modified LR-M revealed significantly superior specificity and accuracy (89.4% vs 81.1%, P=0.004; and 87.9% vs 82.2%, P=0.027, respectively) while maintaining high sensitivity (82.2% vs 86.0%; P=0.529) compared with the LR-M. Meanwhile, the modified LR-5 achieved greater sensitivity and accuracy (88.6% vs 79.7%, P=0.004; and 85.8% vs 80.1%, P=0.036, respectively) for diagnosing HCC, without compromising specificity (78.3% vs.81.1%; P=0.608) compared with the LR-5.Conclusion: Thin-rim APHE may be the specific imaging feature for differentiating non-HCC malignancies from HCCs within LR-M. The modified targetoid criteria emphasizing thin-rim APHE can improve the diagnostic performance of LI-RADS for hepatic malignancies.Keywords: hepatic tumors, malignant, targetoid feature, Rim APHE, liver imaging reporting and data system

Chunyan Yang,&ast; Hao Tian,&ast; Guixing Xu, Qin Luo, Mingsheng Sun, Fanrong Liang Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fanrong Liang, Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, No. 37 Shi’er Qiao Road, Chengdu, Sichuan, 610075, People’s Republic of China, Email acuresearch@126.comPurpose: The effect of acupuncture as adjunctive therapy for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) was controversial. Thus, we aimed to evaluate the effects of acupuncture for treating AECOPD.Methods: Eight databases were searched from database inception to July 30, 2023. All RCTs compared acupuncture plus conventional western medicine with conventional western medicine alone were included. Outcomes were quality of life, lung function, blood oxygen condition, exercise capacity, daily symptoms, duration of hospitalization, and adverse events. The statistical analyses were conducted using Stata 17.0, and methodological quality was measured by the Cochrane bias risk assessment tool. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence.Results: Twelve studies including 915 patients were included. Compared with conventional western medicine alone, acupuncture combined with conventional western therapy significantly improved quality of life (CAT: MD: − 3.25; 95% CI: − 3.73 to − 2.78, P< 0.001) and arterial blood gas (PaCO2: MD: − 1.85; 95% CI: − 2.74 to − 0.95, P< 0.001; PaO2: MD: 5.15; 95% CI: 1.22 to 9.07, P = 0.01). And for lung function, statistical benefits were found in FEV1/FVC (MD: 4.66; 95% CI: 2.21 to 7.12, P< 0.001), but no difference was seen for FEV1% (MD: 1.83; 95% CI: − 0.17 to 3.83, P = 0.073). There was no significant improvement in exercise capacity (6MWD: MD: 96.69; 95% CI: − 0.60 to 193.98, P = 0.051), hospitalization duration (MD: − 5.70; 95% CI: − 11.97 to 0.58, P = 0.075), and dyspnea (mMRC: MD: − 0.19; 95% CI: − 0.61 to 0.63, P = 0.376) between two groups. Overall bias for CAT and mMRC was in “high” risk, FEV1%, FEV1/FVC, PaCO2, and PaO2 was in “some concern” and 1 RCT assessing hospitalization duration was in “low” risk. And the overall assessments were either moderate, low or very low certainty. Seven trials performed safety assessment of acupuncture, and no serious adverse events were reported.Conclusion: Acupuncture might have auxiliary effects on AECOPD. However, the quality of the evidence is limited, and more high-quality RCTs are needed to be performed in the future.Keywords: acute exacerbation of chronic obstructive pulmonary disease, acupuncture, systematic review, meta-analysis

Liwei Deng,1,2 Yanyuan Sun,2 Haiqing Wang,3 Changli Liao,2 Deshan Li,2 Guohui Xu,2,&ast; Xuegang Yang2,&ast; 1School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Interventional Therapy, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Chengdu, People’s Republic of China; 3Department of Hepato-Biliary-Pancreatic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guohui Xu; Xuegang Yang, Department of Interventional Therapy, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, 55 Renmin South Road 4th Section, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-13708010123, Fax +86-02885420195, Email xgh0913@hotmail.com; yanggangxue@163.comPurpose: To compare the efficacy and safety of transarterial chemoembolization (TACE) plus donafenib with immune checkpoint inhibitors (ICIs) (T+D+I) versus TACE plus donafenib (T+D) as the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC).Methods: This retrospective study included patients with unresectable HCC who received T+D+I or T+D between June 2021 and February 2023. The tumor response was analyzed according to the modified Response Evaluation Criteria in Solid Tumors. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) in the two groups were compared before and after propensity score matching (PSM). Cox’s proportional-hazards regression model was used to analyze factors affecting PFS and OS.Results: This study included 69 patients: 41 patients in the T+D group and 28 patients in the T+D+I group. After PSM, 26 patients in each group were analyzed. Patients in the T+D+I group had a higher DCR (96.2% vs 73.1%, P = 0.021), longer median PFS (13.1 vs 7.2 months, P = 0.017), and longer median OS (23.1 vs 14.7 months, P = 0.021) than those in the T+D group. The ORR in the two groups was similar (53.8% vs 50.0%, P = 0.781). Multivariate analyses revealed that T+D+I treatment and total bilirubin levels of < 20 μmol/L were independent prognostic factors for long PFS. T+D+I treatment, Child–Pugh class A, and single-lobe tumor distribution were independent prognostic factors for long OS. The incidence of TRAEs in the two groups was similar (P > 0.05).Conclusion: In comparison with TACE plus donafenib, TACE plus donafenib with ICIs could significantly improve DCR, PFS, and OS as a potential first-line treatment for unresectable HCC with an acceptable safety profile.Keywords: unresectable hepatocellular carcinoma, transarterial chemoembolization, donafenib, immune checkpoint inhibitor, combined therapy

Guangyi Xu,1 Ting Liu,1 Yunxia Jiang,1 Yanhong Xu,2 Taohua Zheng,2 Xiaona Li3 1Author affiliations School of Nursing, Qingdao University, Shandong, People’s Republic of China; 2Author affiliations Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Shandong, People’s Republic of China; 3Author Affiliations Endoscopic Diagnosis and Treatment Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Qingdao, People’s Republic of ChinaCorrespondence: Ting Liu, School of Nursing, Qingdao University, 1 Ningde Road, Qingdao, Shandong, 266073, People’s Republic of China, Tel +86 15066237573, Email liuting201516@163.comPurpose: To identify the distinct profiles of psychosocial adaptation of Chinese inflammatory bowel disease (IBD) patients and the predictive factors.Patients and Methods: A cross-sectional survey method was used to recruit 263 IBD patients who were treated in a tertiary hospital in Shandong Province from July 2022 to April 2023. The general information questionnaire, Inflammatory Bowel Disease Psychosocial Adaptation Questionnaire, Resilience Scale for Inflammatory Bowel Disease, Chinese Benefit Finding Scale, and Stigma Scale for Chronic Illnesses, Medical Coping Modes Questionnaire and Inflammatory Bowel Disease-Disk were used as the instruments for investigation. Latent profile analysis was conducted with the six dimensions of the IBD Psychosocial Adaptation Questionnaire as the explicit indicators. The predictors of profile membership were analyzed by multinomial logistic regressions.Results: Four profiles of psychosocial adaptation in IBD patients were identified: Low level psychosocial adaptation (14.1%), Medium level psychosocial adaptation – High body image distress (25.5%), Medium level psychosocial adaptation – Low body image distress (30.0%) and High level psychosocial adaptation (30.4%). Compared with Low level psychosocial adaptation group, High level psychosocial adaptation group had a higher level of positive cognition (OR=2.930, 95%IC 0.017– 0.305, p< 0.001) and overall psychological resilience (OR=1.832, 95%IC 0.000– 0.016, p < 0.001), more health behaviors (OR= 2.520, 95%IC 0.191– 1.358, p=0.001), a lower level of internal stigma (OR=0.135, 95%IC 0.043– 0.420, p < 0.001) and overall stigma (OR=0.010, 95%IC 0.003– 0.118, p=0.001), less acceptance-resignation coping style (OR=0.055, 95%IC 0.209– 3.200, p < 0.001) and lower disease burden (OR=0.407, 95%IC 0.298– 0.698, p=0.006).Conclusion: About a half of IBD patients had a medium level of psychosocial adaptation. Psychological resilience, benefit finding, stigma, medical coping styles and disease burden predicted psychosocial adaptation profiles. Healthcare providers need to focus on the heterogeneity of psychosocial adaptation of IBD patients and formulate personalized intervention programs for patients with different profiles to improve their psychosocial adaptation.Keywords: inflammatory bowel disease, latent profile analysis, psychosocial adaptation, benefit finding, resilience, coping, stigma

Qinglin Ye,1,&ast; Guiling Xu,1,&ast; Hao Yuan,2,3 Junhao Mi,2,3 Yuli Xie,2,3 Haoyu Li,1 Zhejun Li,1 Guanwen Huang,1 Xuesong Chen,1 Wei Li,1 Rirong Yang2,3 1Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530005, People’s Republic of China; 2Centre for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, 530021, People’s Republic of China; 3Department of Immunology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rirong Yang, Centre for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Department of Immunology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Fax +86 0771 5317061, Email yangrirong@sr.gxmu.edu.cn; 520yrr@163.com Wei Li, Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530005, People’s Republic of China, Email liwei030514@126.comBackground: Diabetic kidney disease (DKD) is a chronic renal disease which could eventually develop into renal failure. Though albuminuria and estimated glomerular filtration rate (eGFR) are helpful for the diagnosis of DKD, the lack of specific biomarkers reduces the efficiency of therapeutic interventions.Methods: Based on bulk-seq of 56 urine samples collected at different time points (including 11 acquired from DKD patients and 11 from healthy controls), in corporation of scRNA-seq data of urine samples and snRNA-seq data of renal punctures from DKD patients (retrieved from NCBI GEO Omnibus), urine-kidney specific genes were identified by Multiple Biological Information methods.Results: Forty urine-kidney specific genes/differentially expressed genes (DEGs) were identified to be highly related to kidney injury and proteinuria for the DKD patients. Most of these genes participate in regulating glucagon and apoptosis, among which, urinary PART1 (mainly derived from distal tubular cells) and PLA2R1 (podocyte cell surface marker) could be used together for the early diagnosis of DKD. Moreover, urinary PART1 was significantly associated with multiple clinical indicators, and remained stable over time in urine.Conclusion: Urinary PART1 and PLA2R1 could be shed lights on the discovery and development of non-invasive diagnostic method for DKD, especially in early stages. Keywords: diabetic kidney disease, urine, non-invasive, diagnosis, biomarker

Lei Meng,1,&ast; Jun Cao,1,2,&ast; Li Kang,3,&ast; Gang Xu,1 Da-Wei Yuan,1 Kang Li,1 Kun Zhu1 1Department of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 2The Third Affiliated Hospital of Xi’an Medical University, Xi’an, 710068, People’s Republic of China; 3Department of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kang Li; Kun Zhu, Department of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China, Tel +86 13087566643, Email healthlee@xjtu.edu.cn; dr.zhkun@mail.xjtu.edu.cnObjective: Regimens of S-1-based adjuvant chemotherapy are of great significance in attenuating recurrence risk in postoperative patients with gastric cancer (GC). Kinase insert-domain receptor (KDR) gene plays an essential role in tumor growth and metastasis. This study aimed to investigate the implication of KDR genotyping on the therapeutic outcomes of patients with gastric cancer (GC) who received S-1-based adjuvant chemotherapy.Methods: A total of 169 postoperative GC with pathological staging of II and III and no metastasis who received S-1-based adjuvant chemotherapy were included retrospectively. Peripheral blood specimens were collected and prepared for KDR genotyping and KDR mRNA expression. Correlation between KDR genotype status and prognosis was performed using Kaplan–Meier survival analysis, and multivariate analysis was ultimately adopted using Cox regression analysis.Results: Median disease-free survival (DFS) of the 169 patients with GC was 5.1 years [95% confidence interval (CI): 4.25– 5.95] and median overall survival (OS) was 6.7 years (95% CI: 5.44– 7.96). Rs2071559 was located at the upstream region, and the prevalence among 169 patients with GC was as follows: AA genotype in 104 cases (61.5%), AG genotype in 57 cases (33.7%), and GG genotype in 8 cases (4.7%), yielding a minor allele frequency of 0.22, which was consistent with Hardy-Weinberg equilibrium (P=0.958). Median DFS of patients with AA and AG/GG genotypes was 6.0 years and 4.0 years, respectively (P=0.002). Additionally, patients with the AA genotype had longer OS than those with the AG/GG genotype [median OS: not reached (NR) vs 5.5 years, P=0.011]. Additionally, KDR mRNA expression was significantly higher in patients with the AG/GG genotype than that in those with the AA genotype (P< 0.001).Conclusion: Rs2071559 in KDR gene might be a promising biomarker for evaluating the recurrence risk and OS of patients with GC who received S-1-based adjuvant chemotherapy. This conclusion should be confirmed in randomized clinical trials.Keywords: gastric cancer, S-1, KDR, polymorphism, prognosis, biomarker

Guihua Xu, Juanjuan Wang, Yiting Zhang, Zilin Chen, Ruidong Deng Eye Department, Huizhou Municipal Central Hospital, Huizhou, Guangdong, People’s Republic of ChinaCorrespondence: Ruidong Deng; Zilin Chen, Email 359849662@qq.com; boydongdong1@126.comBackground: Glaucoma is a neurodegenerative disorder characterized with optic nerve injury and the loss of retinal ganglion cells (RGCs). Ferroptosis has been proved to be associated with the degradation of RGCs. The aim of this study is to elucidate the relationship between ferroptosis and glaucoma pathogenesis, and unveil the underlying mechanism.Methods: Methyl thiazolyl tetrazolium (MTT) assay was used to evaluate the proliferation of RGCs. The accumulation of cellular iron was measured by Iron assay kit, and the level of reactive oxygen species (ROS) was detected by fluorescence probe. The mitochondrial morphology and autophagosomes were analysed by using transmission electron microscopy (TEM). The contents of glutathione (GSH) and malondialdehyde (MDA) were tested by a GSH assay kit and an MDA detection kit, respectively. The expression of autophagy-related proteins was detected by Western blotting.Results: A serious cell damage, aberrant iron homeostasis, and oxidative stress was shown in RGC-5 after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment and gamma-Glutamyl transpeptidase 1 (GGT1) knockdown, but these effects were significantly alleviated by overexpression of GGT1 or ferroptosis inhibitors. The TEM and immunofluorescent results indicated that mitochondria impairment and autophagosome accumulation in OGD/R-treated cells was improved after GGT1 overexpression, while the phenomenon in GGT1-silenced cells was aggravated. Furthermore, we found that GGT1 can interact with glutamate cysteine ligase catalytic subunit (GCLC) to inhibit autophagy and ferroptosis in RGC-5 cells.Conclusion: GGT1 represses autophagy in RGC-5 cells by targeting GCLC, which further restrains the development of ferroptosis in cells.Keywords: glaucoma, gamma-glutamyl transpeptidase 1, ferroptosis, autophagy, glutamate cysteine ligase catalytic subunit

Zhiyu Li,1 Zhongying Cao,1 Nanxi Li,2 Luying Wang,2 Cong Fu,2 Ran Huo,1,2 Guangqi Xu,2 Chonglin Tian,2,&ast; Jianhai Bi1– 3,&ast; 1Department of Plastic and Aesthetic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Plastic and Aesthetic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 3Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianhai Bi, Department of Plastic and Aesthetic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, No. 324, Jingwu Road, Huaiyin District, Jinan, Shandong Province, 250021, People’s Republic of China, Tel +86-15110080702, Email bijianhai@126.com Chonglin Tian, Department of Plastic and Aesthetic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Road, Huaiyin District, Jinan, Shandong Province, 250021, People’s Republic of China, Tel +86-15666966900, Email chonglin2014@126.comPurpose: Infantile hemangiomas (IHs) are commonly observed benign tumors that can cause serious complications. M2-polarized macrophages in IHs promote disease progression. In this study, we investigated the role of M2 macrophage-derived exosomal lncRNA MIR4435-2HG in IHs.Patients and Methods: Exosomes derived from M2 polarized macrophages were extracted. Next, using cell co-culture or transfection, we investigated whether M2 polarized macrophage-derived exosomes (M2-exos) can transport MIR4435-2HG to regulate the proliferation, migration, invasion, and angiogenesis of hemangioma-derived endothelial cells (HemECs). RNA-seq and RNA pull-down assays were performed to identify targets and regulatory pathways of MIR4435-2HG. We explored the possible mechanisms through which MIR4435-2HG regulates the biological function of HemECs.Results: M2-exos significantly enhanced the proliferation, migration, invasion, and angiogenesis of HemECs. Thus, HemECs uptake M2-exos and promote biological functions through the inclusion of MIR4435-2HG. RNA-seq and RNA pull-down experiments confirmed that MIR4435-2HG regulates of HNRNPA1 expression and directly binds to HNRNPA1, consequently affecting the NF-κB signal pathway.Conclusion: MIR4435-2HG of M2-exos promotes the progression of IHs and enhances the proliferation, migration, invasion, and angiogenesis of HemECs by directly binding to HNRNPA1. This study not only reveals the mechanism of interaction between M2 macrophages and HemECs, but also provides a promising therapeutic target for IHs.Graphical Abstract: Keywords: hemangioma-derived endothelial cell, infantile hemangioma, M2-polarized macrophage, MIR4435-2HG, HNRNPA1

Wanying Shan,1,&ast; Jie Zhao,2,&ast; Chunfang Qiu,1 Guoli Xu,1 Jie Feng1 1Department of Neurology, Suzhou Ninth People’s Hospital, Soochow University, Suzhou, Jiangsu, 215200, People’s Republic of China; 2Department of Gerontology, Suzhou Ninth People’s Hospital, Soochow University, Suzhou, Jiangsu, 215200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Feng, Department of Neurology, Suzhou Ninth People’s Hospital, Soochow University, No. 2666 Ludang Road, Suzhou, Jiangsu, 215200, People’s Republic of China, Tel/Fax +86 051282881332, Email fengjie6769@163.comBackground and Purpose: Increased glial fibrillary acidic protein (GFAP) levels were found in cerebrovascular disease patients. The pathogenesis of depression after ischemic stroke remains largely unknown. Here, we aim to determine whether GFAP concentrations were associated with post-stroke depression (PSD) at 3 months.Methods: From March 2022 to September 2022, patients with first-ever ischemic stroke were prospectively recruited. GFAP concentrations were detected within 24 h using an enzyme-linked immunosorbent assay. The PSD was defined as a Hamilton Depression Rating Scale 24-Item score ≥ 8.Results: A total of 206 subjects with ischemic stroke (mean age: 63.6 years; 49.0% female) were enrolled. During the 90-day follow-up, 57 participants (27.7%) were observed in PSD. The median serum GFAP concentrations were 0.67 ng/mL. After adjustment for the covariates, higher increased GFAP levels were associated with increased risk of PSD (odds ratio [OR], 7.12; 95% confidence interval [CI], 3.29– 15.44; P < 0.001). Also, the multivariate-adjusted OR of PSD associated with the fourth quartile of GFAP was 10.89 (95% CI, 3.53– 33.60; P < 0.001) compared with the first quartile. Furthermore, the restricted cubic spline confirmed a linear association between GFAP and the risk of PSD (P for linearity < 0.001).Conclusion: Our results indicated that increased circulating GFAP concentrations were significantly correlated with the risk of PSD at 3 months. Measuring the GFAP levels after ischemic stroke may add some values for the risk stratifying of PSD.Keywords: post-stroke depression, ischemic stroke, prognosis, glial fibrillary acidic protein, prospective study

Gang Xu,1,2 Weiwei Gong,2,3 Shihong Dong,2 Guojiong Hu,2,4 Weizhen Tang,1 Hecheng Yu1 1Department of Rehabilitation Medicine, Affiliated Tenth People’s Hospital of Tongji University, Shanghai Tenth People’s Hospital, Shanghai, 200072, People’s Republic of China; 2Department of Rehabilitation Medicine, Tongji University School of Medicine, Shanghai, 200092, People’s Republic of China; 3Department of Rehabilitation Medicine, Shanghai First Rehabilitation Hospital, Shanghai, 200090, People’s Republic of China; 4Department of Rehabilitation Medicine, Affiliated Yangzhi Rehabilitation Hospital of Tongji University, Shanghai, 201619, People’s Republic of ChinaCorrespondence: Gang Xu, Department of Rehabilitation Medicine, Affiliated Tenth People’s Hospital of Tongji University, Shanghai Tenth People’s Hospital, Shanghai, 200072, People’s Republic of China, Tel +86 21-66306496, Fax +86 21-66301051, Email sykfsci@126.comPurpose: Mechanical allodynia is reportedly common during herpetic neuralgia. The purpose of this study was to establish a risk prediction model to predict the individual risk of allodynia in herpetic neuralgia.Methods: Three hundred and eighty-six patients with trunk herpetic neuralgia were divided into two regions, T2-5 and T6-11. The causality between allodynia and other factors was analyzed by a binary logistic regression model.Results: 42.2% of subjects had allodynia, 137 suffered from dynamic allodynia, and 110 with dynamic allodynia experienced local sweating. The following 5 items as predictors determined this model: local sweating (Odd Ratio = 27.57, P< 0.001), lesion location (Odd Ratio=2.46, P =0.017), pain intensity (Odd Ratio=1.38, P =0.020), pain duration (Odd Ratio=0.94, P =0.006), and local scars (Odd Ratio=0.07, P< 0.001). The presence and development of allodynia are associated with local sweating. The positive proportion of the Iodine-starch test between the T2-5 (50.0%) with the T6-11 (23.7%) had a statistically significant difference (χ2=5.36, P=0.021). 29.5% of patients at the T2-6 had obvious sweating, which was different from only sticky feelings at the T6-11 (70.5%, χ2=10.88, P=0.001). 19.2% of patients with residual scars and allodynia was significantly lower than 48.5% of patients without allodynia (χ2=15.28, P< 0.001).Conclusion: This analysis suggests that local sweating is a concomitant symptom in dynamic allodynia, which imply the sympathetic nerves innervating the sweat glands of the skin were also involved during herpetic neuralgia. This may assist in the evaluation of dynamic allodynia and prove the role of sympathetic nerve intervention for herpetic neuralgia.Keywords: herpetic neuralgia, mechanical dynamic allodynia, sweating, sympathetic nerves, peripheral sensitization

Qiang Guo,1,2,&ast; Xiao-Li Liu,3,&ast; Kui Zhai,4,&ast; Cheng Chen,1 Xi-Xian Ke,1 Jun Zhang,2 Gang Xu1 1Department of Thoracic Surgery, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China; 2Department of Cardiothoracic Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 3Department of Ultrasound, The People’s Hospital of Jianyang City, Jianyang, Sichuan, People’s Republic of China; 4Department of Thoracic Surgery, Xingyi People’s Hospital, Xinyi, Guizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gang Xu; Jun Zhang, Email xglhl333@163.com; 13508684276@139.comAbstract: Cancer was one of the common causes of death in the world, and it was increasing year by year. At present, Progestin and AdipoQ receptor family member 3 (PAQR3) was widely studied in cancer. It has been found that PAQR3 was down regulated in various cancers, such as the gastric cancer, osteosarcoma, glioma, hepatocellular carcinoma, acute lymphoblastic leukemia, laryngeal squamous cell carcinoma, esophageal cancer, breast cancer, non-small cell lung cancer, and colorectal cancer. The decreased expression of PAQR3 was associated with short overall survival and disease-free survival in patients with gastric cancer, hepatocellular carcinoma, laryngeal squamous cell carcinoma, esophageal cancer, breast cancer, and non-small cell lung cancer. PAQR3 could inhibit cancer progression by using the Ras/Raf/MEK/ERK, PI3/AKT, EMT and other mechanisms, and was negatively regulated by the miR-543, miR-15b-5p and miR-15b. The roles and signaling mechanisms of PAQR3, and the relationship between the expression of PAQR3 and prognosis in cancer progression are reviewed in this article, and provides new tumor marker and idea to guide cancer treatment.Keywords: PAQR3, overall survival, disease-free survival, tumor suppressor

Zaijun Zou,1,2 Han Li,1,2 Gang Xu,1,3 Yunxiang Hu,2 Weiguo Zhang,1,3 Kang Tian1,3 1Department of Sports Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 2School of Graduates, Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China; 3Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopaedic Disease, Dalian, Liaoning Province, 116011, People’s Republic of ChinaCorrespondence: Kang Tian; Weiguo Zhang, Tel +86-18098871513 ; +86-18041191111, Email dmu-tiankang@outlook.com; dlmedu126@126.comAbstract: Exosomes, as natural nanocarriers, characterized with low immunogenicity, non-cytotoxicity and targeted delivery capability, which have advantages over synthetic nanocarriers. Recently, exosomes have shown great potential as diagnostic markers for diseases and are also considered as a promising cell-free therapy. Engineered exosomes have significantly enhanced the efficacy and precision of delivering therapeutic agents, and are currently being extensively employed in targeted therapeutic investigations for various ailments, including oncology, inflammatory disorders, and degenerative conditions. Particularly, engineered exosomes enable therapeutic agent loading, targeted modification, evasion of MPS phagocytosis, intelligent control, and bioimaging, and have been developed as multifunctional nano-delivery platforms in recent years. The utilization of bioactive scaffolds that are loaded with exosome delivery has been shown to substantially augment retention, extend exosome release, and enhance efficacy. This approach has advanced from conventional hydrogels to nanocomposite hydrogels, nanofiber hydrogels, and 3D printing, resulting in superior physical and biological properties that effectively address the limitations of natural scaffolds. Additionally, plant-derived exosomes, which can participate in gut flora remodeling via oral administration, are considered as an ideal delivery platform for the treatment of intestinal diseases. Consequently, there is great interest in exosomes and exosomes as nanocarriers for therapeutic and diagnostic applications. This comprehensive review provides an overview of the biogenesis, composition, and isolation methods of exosomes. Additionally, it examines the pathological and diagnostic mechanisms of exosomes in various diseases, including tumors, degenerative disorders, and inflammatory conditions. Furthermore, this review highlights the significance of gut microbial-derived exosomes. Strategies and specific applications of engineered exosomes and bioactive scaffold-loaded exosome delivery are further summarized, especially some new techniques such as large-scale loading technique, macromolecular loading technique, development of multifunctional nano-delivery platforms and nano-scaffold-loaded exosome delivery. The potential benefits of using plant-derived exosomes for the treatment of gut-related diseases are also discussed. Additionally, the challenges, opportunities, and prospects of exosome-based nanocarriers for disease diagnosis and treatment are summarized from both preclinical and clinical viewpoints.Keywords: exosomes, nanocarriers, diseases, diagnosis, treatment

Qinglin Ye,&ast; Guiling Xu,&ast; Haizhen Huang,&ast; Shuting Pang, Boji Xie, Bingmei Feng, Peng Liang, Yijie Qin, Siji Li, Yin Luo, Chao Xue, Wei Li Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li; Chao Xue, Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email liwei030514@126.com; xccqh@126.comPurpose: Chronic kidney disease (CKD) progression is complex. There are not standardized methods for predicting the prognosis of CKD. Nicotinamide N-methyltransferase (NNMT) has been shown to be associated with renal fibrosis. This study aimed to validate NNMT as a prognostic biomarker of progressive CKD.Patients and Methods: We explored the relationship between NNMT expression and CKD-related outcome variables using the NephroseqV5 and GEO databases. Additionally, a validation set of 37 CKD patients was enrolled to measure the correlation between NNMT expression levels and CKD outcomes. Furthermore, single-cell RNA sequencing data and the Human Protein Atlas were reanalyzed to investigate the expression specificity of NNMT in the kidney. Finally, to detect the status of NNMT expression with tubular fibrosis in vivo, we constructed a unilateral ureteral obstruction (UUO) mouse treated with an NNMT inhibitor.Results: Analyzing the datasets showed that NNMT was expressed mainly in proximal tubule compartments. And patients with high NNMT expression levels had a significantly lower overall survival rate compared to those with low NNMT expression levels (P = 0.013). NNMT was independent of prognosis factors in the multivariate Cox regression model, and the AUCs for CKD progression at 1, 3, and 5 years were 0.849, 0.775, and 0.877, respectively. Pathway enrichment analysis indicated that NNMT regulates the biological processes of tubulointerstitial fibrosis (TIF). In the validation group, NNMT levels were significantly higher in the CKD group combined with interstitial fibrosis. In vivo, NNMT was a high expression in the UUO group, peaking at postoperative day 21. Treatment with an NNMT inhibitor improved renal tubular interstitial fibrosis, and expression levels of FN, α-SMA, VIM, and TGF-β 1 were decreased compared with UUO (P < 0.05).Conclusion: NNMT was expressed mainly in tubular renal compartments, and associated with CKD prognosis. It holds potential as a diagnostic biomarker for tubular fibrosis in CKD.Graphical Abstract: Keywords: nicotinamide N-methyl transferase, tubular fibrosis, chronic kidney disease, biomarker diagnosis

Jianmin Li,1,2,&ast; Wenyi Zhang,1,2,&ast; Shuang Liu,1,2,&ast; Fan Yang,2 Yupeng Zhou,2 Lin Cao,1,2 Yiming Li,1,2 Yunfei Guo,1,2 Xiang Qi,1,2 Guoping Xu,1 Jing Peng,1 Yang Zhao1,2 1Department of Radiology, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 2Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Zhao; Jing Peng, Department of Radiology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China, Email yang.zhao@tmu.edu.cn; jing.peng@tmu.edu.cnPurpose: BSA-biomineralized Gd nanoparticles (Gd@BSA NPs) have been recognized as promising nanoscale MR contrast agents. The aim of this study was to carry out a preclinical evaluation of these NPs in a middle-sized animal model (rabbits).Methods: New Zealand white rabbits were treated intravenously with Gd@BSA NPs (0.02 mmol Gd/kg) via a clinically-used high-pressure injector, with commercial Gd-diethylene triamine pentaacetate (Gd-DTPA)-injected group as control. Then MR angiography was performed according to the standard clinical protocol with a 3.0-T MR scanner. The SNR and CNR of the main arteries and branches were monitored. Pharmacokinetics and bioclearance were continuously evaluated in blood, urine, and feces. Gd deposition in vital organs was measured by ICP‒MS. Weight monitoring, HE staining, and blood biochemical analysis were also performed to comprehensively estimate systemic toxicity.Results: The ultrasmall Gd@BSA NPs (< 6 nm) exhibited high stability and T1 relaxivity. Compared to Gd-DTPA, Gd@BSA NPs demonstrated superior vascular system imaging performance at ultralow doses, especially of the cardiac artery and other main branches, and exhibited a significantly higher SNR and CNR. Notably, the Gd@BSA NPs showed a shorter half-life in blood, less retention in organs, and improved biocompatibility.Conclusion: The preclinical evaluations here demonstrated that Gd@BSA NPs are promising and advantageous MR CA candidates that can be used at a low dose with excellent MR imaging performance, thus suggesting its further clinical trials and applications.Keywords: preclinical evaluation, ultralow dose, high-pressure injector, MR angiography

Meng Zhang,1,2,&ast; Juan Zhang,1,2,&ast; Gezhi Xu,1,2 Lu Ruan,1,2 Xin Huang1,2 1Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China; 2Institute of Eye Research, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Huang, Department of Ophthalmology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Tel +86-021-64377134, Fax +86-021-64377151, Email fd2017huangxin@163.comPurpose: Proliferative diabetic retinopathy (PDR) is a leading cause of poor vision in young adults. This study sought to evaluate the clinical characteristics and outcomes of primary vitrectomy for PDR in young adults.Patients and Methods: Medical data were retrospectively collected at a large ophthalmology hospital in China. We analyzed data for 99 patients (140 eyes) aged < 45 years with T1D or T2D who underwent primary vitrectomy for PDR-related complications.Results: There were 18 patients with T1D and 81 patients with T2D. The proportion of males was significantly greater than that of females in both groups. The T1D group had a longer duration of diabetes (P = 0.008), younger age at primary vitrectomy (P = 0.049), and lower body mass index (P < 0.001) than the T2D group. The proportion of eyes with rhegmatogenous retinal detachment (RRD) was greater but the proportion of eyes with traction retinal detachment (TRD) was lower in the T1D group than in the T2D group. The final best-corrected visual acuity (BCVA) improved or remained stable in 100% and 85.3% of eyes and decreased in 0% and 14.7% of eyes in the T1D and T2D groups, respectively. After surgery, the incidence of postoperative complications was significant greater in the T2D group than in the T1D group (P = 0.045). Factors influencing the final visual acuity included preoperative BCVA in both groups, the duration of diabetes (P = 0.031) and preoperative FVP (P = 0.004) in the T1D group, and preoperative RRD (P < 0.001) and postoperative NVG (P < 0.001) in the T2D group.Conclusion: In this retrospective study, young adults with T2D who underwent vitrectomy had worse final visual acuity and more complications than young adults with T1D.Keywords: diabetic retinopathy, vitrectomy, type 1 diabetes, type 2 diabetes

Summary: As the principal effector cell population of the innate immune system, natural killer (NK) cells may make critical contributions to natural, immune-mediated control of HIV-1 replication. Using genome-wide assessments of activating and inhibitory chromatin features, we demonstrate here that cytotoxic NK (cNK) cells from elite controllers (ECs) display elevated activating histone modifications at the interleukin 2 (IL-2)/IL-15 receptor β chain and the BCL2 gene loci. These histone changes translate into increased responsiveness of cNK cells to paracrine IL-15 secretion, which coincides with higher levels of IL-15 transcription by myeloid dendritic cells in ECs. The distinct immune crosstalk between these innate immune cell populations results in improved IL-15-dependent cNK cell survival and cytotoxicity, paired with a metabolic profile biased toward IL-15-mediated glycolytic activities. Together, these results suggest that cNK cells from ECs display a programmed IL-15 response signature and support the emerging role of innate immune pathways in natural, drug-free control of HIV-1.

Gang Xu,1,2 Site Xu,3 Weiwei Gong,2,4 Shihong Dong,2 Hecheng Yu1 1Department of Rehabilitation Medicine, Affiliated Tenth People’s Hospital of Tongji University, Shanghai Tenth People’s Hospital, Shanghai, 20072, People’s Republic of China; 2Department of Rehabilitation Medicine, Tongji University School of Medicine, Shanghai, 200092, People’s Republic of China; 3Division of Information and Statistics, Affiliated Ruijin Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Rehabilitation Medicine, Shanghai First Rehabilitation Hospital, Shanghai, 200090, People’s Republic of ChinaCorrespondence: Gang Xu, Department of Rehabilitation Medicine, Affiliated Tenth People’s Hospital of Tongji University, Shanghai Tenth People’s Hospital, Shanghai, 20072, People’s Republic of China, Tel +8621-66306496, Fax +8621-66301051, Email sykfsci@126.comBackground: Herpes zoster (HZ) is a skin disease that can also cause virus-infectious peripheral neuropathies. Despite this, there is limited information on patient preferences for seeking medical attention for HZ and zoster-associated pain (ZAP). Our study aimed to evaluate how frequently patients with ZAP choose to visit neurologists for their symptoms.Methods: This study conducted a retrospective review of electronic health records in three general hospitals from January 2017 to June 2022. Using association rule mining, the study analyzed referral behaviors.Results: We identified 33,633 patients with 111,488 outpatient visits over 5.5 years. The study found that the majority of patients (74.77– 91.22%) visited dermatologists during their first outpatient visit, while only a small percentage (0.86– 1.47%) preferred to consult a neurologist. The proportion of patients referred to a specialist during their medical visit varied significantly between different specialties within the same hospital (p < 0.05) and even within the same specialty (p< 0.05). There was a weak association (Lift:1.00– 1.17) of referral behaviors between dermatology and neurology. Across the three hospitals, the average number of visits to a neurologist for ZAP was 1.42– 2.49, with an average electronic health record duration of 11– 15 days per patient. After consulting with a neurologist, some patients were referred to other specialists.Conclusion: It was observed that patients with HZ and ZAP tended to visit a variety of specialists, with only a small number seeking the assistance of neurologists. However, from the perspective of neuroprotection, it is the duty of neurologists to provide more means.Keywords: herpes zoster, zoster-associated pain, neuropathy, electronic health records, visit preferences

Gang Xu,1 Weizhen Tang,1 Chaosheng Zhou,1 Jie Xu,1 Chao Cheng,1 Weiwei Gong,2,3 Shihong Dong,2 Yu Zhang1 1Department of Rehabilitation Medicine, Affiliated Tenth People’s Hospital of Tongji University, Shanghai Tenth People’s Hospital, Shanghai, 200072, People’s Republic of China; 2Department of Rehabilitation Medicine, Tongji University School of Medicine, Shanghai, 200092, People’s Republic of China; 3Department of Rehabilitation Medicine, Shanghai First Rehabilitation Hospital, Shanghai, 200090, People’s Republic of ChinaCorrespondence: Gang Xu, Department of Rehabilitation Medicine, Affiliated Tenth People’s Hospital of Tongji University, Shanghai Tenth People’s Hospital, 301 Middle Yanchang Road, Shanghai, 200072, People’s Republic of China, Tel +8621-66306496, Fax +8621-66301051, Email sykfsci@126.comPurpose: To evaluate the efficacy and pain fluctuations of methylcobalamin in combination with lidocaine local injection treatment for subacute herpetic neuralgia (SHN).Methods: Seventy-nine women (60.4 ± 2.7 years) with thoracic SHN were enrolled and randomized to receive a combination of methylcobalamin and lidocaine local injection (MI, N=40), or a combination of lidocaine patch 5% and oral methylcobalamin (PO, N=39) for four weeks. Repeated-measures analyses of variance were used to evaluate the effect on pain levels. Generalized estimation equations were used to analyze the cause-effect relationship between pain fluctuations and influencing factors.Results: At the treatment endpoint, the group, treatment time, and group interacted with treatment time effects of the pain scores and area were statistically significant (P< 0.001), The pain scores were 2.9 ± 0.9 (MI) and 4.3 ± 1.5 (PO). 80.00% (MI) or 28.21% (PO) of patients had pain scores ≤ 3, the odds ratio was 2.84 (95% CI: 1.68 to 4.79). The incidence of postherpetic neuralgia was 5.0% (2/40) at 3 months. Pain fluctuated repeatedly during treatment. The pain fluctuation increased from 8.75 log folds in the afternoon, to 79.85 log folds at night. With the ADLs level increasing from 1 to 3, the pain fluctuated from 4.28 to 17.70 log folds. Allodynia, itching, sleep quality, and ADLs were the significant influencing factors (P< 0.05).Conclusion: This study validated the efficacy of methylcobalamin combined with lidocaine for SHN, and confirmed that pain levels in patients with SHN had an obvious circadian rhythm. ADLs were an important cause of pain fluctuations.Keywords: subacute herpetic neuralgia, methylcobalamin, lidocaine, pain fluctuation, activities of daily living

Guangzhong Xu,1,&ast; Zheng Wang,1,&ast; Chengyuan Yu,1,&ast; Buhe Amin,1 Dexiao Du,1 Tianxiong Li,1 Guanyang Chen,2 Liang Wang,2 Zhehong Li,1 Weijian Chen,1 Chenxu Tian,1 Qiqige Wuyun,1 Qing Sang,2 Mingyue Shang,1 Dongbo Lian,1 Nengwei Zhang1 1Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, People’s Republic of China; 2Surgery Centre of Diabetes Mellitus, Peking University Ninth School of Clinical Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nengwei Zhang; Dongbo Lian, Tel +8613801068802 ; +8613681299755, Email zhangnw1@sohu.com; lian.dongbo@126.comBackground: Many studies have reported that bariatric surgery may reduce postoperative cardiovascular risk in patient with obesity, but few have addressed this risk in the Chinese population.Objective: To assess the impact of bariatric surgery on cardiovascular disease (CVD) risk in the Chinese population using the World Health Organization (WHO) risk model, the Global risk model, and the Framingham Risk Score.Methods: We retrospectively analyzed data collected on patient with obesity who underwent bariatric surgery at our institution between March 2009 and January 2021. Their demographic characteristics, anthropometric variables, and glucolipid metabolic parameters were assessed preoperatively and at their 1-year postoperative follow-up. Subgroup analysis compared body mass index (BMI) < 35 kg/m2 and BMI ≥ 35 kg/m2, as well as gender. We used the 3 models to calculate their CVD risk.Results: We evaluated 61 patients, of whom 26 (42.62%) had undergone sleeve gastrectomy (SG) surgery and 35 (57.38%) Roux-en-Y gastric bypass (RYGB) surgery. Of the patients with BMI ≥ 35 kg/m2, 66.67% underwent SG, while 72.97% with BMI < 35 kg/m2 underwent RYGB. HDL levels were significantly higher at 12 months postoperatively relative to baseline. When the models were applied to calculate CVD risk in Chinese patients with obesity, the 1-year CVD risk after surgery were reduced lot compared with the preoperative period.Conclusion: Patient with obesity had significantly lower CVD risks after bariatric surgery. This study also demonstrates that the models are reliable clinical tools for assessing the impact of bariatric surgery on CVD risk in the Chinese population.Keywords: obesity, bariatric surgery, CVD, World Health Organization risk model, global risk model, Framingham Risk Score

Min Li,1 Hongzhen Xie,2 Qing Luo,3 Guangbin Huang,1 Guoxian Xu,1 Ye Cheng,1 Jun Li4 1Department of Traumatology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, People’s Republic of China; 2Department of Health Medicine, General Hospital of Southern Theatre Command, Guangzhou, People’s Republic of China; 3Department of Neurosurgery, General Hospital of Southern Theatre Command, Guangzhou, People’s Republic of China; 4Chongqing Metropolitan College of Science and Technology, Chongqing, People’s Republic of ChinaCorrespondence: Jun Li, Chongqing Metropolitan College of Science and Technology, No. 368, Guangcai Avenue, Yongchuan District, Chongqing, 402160, People’s Republic of China, Tel +86 18084067947, Email lijun20228@163.comBackground: International stroke care guidelines recommend the routine assessment and management of psychological and emotional problems in patients and their families after a stroke. This study aimed to explore the humanistic nursing needs of patients with stroke and their families and provide a basis for the construction of humanistic nursing practice guidelines for advanced stroke.Methods: From September to October 2019, using the descriptive phenomenological research method, a semi-structured interview outline was formed based on a literature review and subject group discussions. A targeted sampling method was used to investigate 21 patients with stroke and 21 family members, respectively, and their care needs were investigated in depth. Colaizzi’s thematic cluster analysis was used to analyse the data, and a total of 6 themes and 14 sub-themes were summarised.Results: The 6 themes and 14 sub-themes were as follows: ① psychological care, ② security concerns (professional personal integrity, timely response), ③ emotional care (service consciousness, positive incentives, empathy, effective communication, provision of a communication platform, personalised care), ④ respect for rights, ⑤ rehabilitation care (rehabilitation programme, professional guidance, rehabilitation configuration, continuation of services) and ⑥ family care (physical and psychological support, care guidance).Conclusion: Among the humanistic care needs of patients with stroke and their families, the most basic physiological care accounts for the largest proportion of emotional and rehabilitation care, followed by safety care, respect for rights and family care. Based on the actual humanistic care needs of patients with stroke and their families, the practical effect of humanistic care in stroke wards can be improved. This study provides a reference for the construction of humanistic nursing practice guidelines for late stroke.Keywords: stroke, humanistic care, qualitative research

Jiyong Yang,1 Tao Jiang,2 Guangming Xu,3 Wengang Liu2 1The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Orthopedics, Guangdong Second Traditional Chinese Medicine Hospital, Guangzhou, People’s Republic of China; 3Department of Orthopedics, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, People’s Republic of ChinaCorrespondence: Wengang Liu, Department of Orthopedics, Guangdong Second Traditional Chinese Medicine Hospital, Guangzhou, 510095, People’s Republic of China, Email liuwengang2022@gmail.comPurpose: Recent years have seen an increased awareness of sarcopenia in the cross field of osteoporosis and sarcopenia. The goal of this study was to evaluate current bibliometric characteristics and the status of cross-sectional studies between osteoporosis and sarcopenia.Methods: Publications related to osteoporosis and sarcopenia published between January 2000 and November 2022 were extracted from the Web of Science Core Collection; bibliometric and visualization were performed by Microsoft Office Excel, VOSviewer, Citespace, and R.Results: A total of 1128 documents written by 5791 authors from 1758 organizations in 62 countries and published in 405 journals were identified. USA was the leading country with the highest publication and total citation. University of Melbourne contributed the most publications, while Tufts University had the largest citations. Osteoporosis International was the most influential journals in this field with the highest publications, citations and H index. Cooper C was the most influential author, who published the 20 studies, had the highest local citations and the highest H index. The keywords were classified into 6 clusters: Cluster 1 (aging), Cluster 2 (frailty) and Cluster 3 (osteosarcopenia).Conclusion: Our bibliometric results revealed that the global osteoporosis and sarcopenia-related research increased rapidly from 2000 to 2022, suggesting it was a promising area of research for the future. The future trends in the cross field of sarcopenia and osteoporosis would be the molecular mechanisms of crosstalk between muscles and bones, safety and efficacy interventions with a dual effect on muscle and bone and osteosarcopenia.Keywords: osteoporosis, sarcopenia, bibliometric analysis, CiteSpace, VOSviewer

Zhou D, Huang G, Xu G, et al. Infect Drug Resist. 2022;15:7577–7599. The authors have advised that the funding statement on page 7596 is incorrect. The text “(Grant No. 8196080379 and 8217081828, respectively)” should read “(Grant No. 81960353 and 82172238, respectively)”. The authors apologize for this error.

Guoling Xu, Yuechou Nong Department of Endocrinology and Metabolism, The Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Yuechou Nong, Email yuechou_gx@163.com

HIV-1 reservoir cells that circulate in peripheral blood during suppressive antiretroviral therapy (ART) have been well characterized, but little is known about the dissemination of HIV-1-infected cells across multiple anatomical tissues, especially the CNS. Here, we performed single-genome, near full-length HIV-1 next-generation sequencing to evaluate the proviral landscape in distinct anatomical compartments, including multiple CNS tissues, from 3 ART-treated participants at autopsy. While lymph nodes and, to a lesser extent, gastrointestinal and genitourinary tissues represented tissue hotspots for the persistence of intact proviruses, we also observed intact proviruses in CNS tissue sections, particularly in the basal ganglia. Multi-compartment dissemination of clonal intact and defective proviral sequences occurred across multiple anatomical tissues, including the CNS, and evidence for the clonal proliferation of HIV-1-infected cells was found in the basal ganglia, in the frontal lobe, in the thalamus and in periventricular white matter. Deep analysis of HIV-1 reservoirs in distinct tissues will be informative for advancing HIV-1 cure strategies.

Xuegang Yang,1,2 Heping Deng,3 Yanyuan Sun,1 Yi Zhang,3 Yujie Lu,3 Guohui Xu,1,&ast; Xiaoqi Huang2,&ast; 1Department of Interventional Therapy, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Chengdu, People’s Republic of China; 2Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, Department of Radiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of Radiology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guohui Xu, Department of Interventional Therapy, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, 55 Renmin South Road 4th Section, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-13708010123, Fax +86-02885420195, Email xgh0913@hotmail.com Xiaoqi Huang, Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, Department of Radiology, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, People’s Republic of China, Tel +86-18980605806, Fax +86-02885420195, Email julianahuang@163.comPurpose: We compare the efficacy and safety of regorafenib plus immune checkpoint inhibitors (ICIs) with transarterial chemoembolization (R+ICIs+TACE) versus regorafenib plus ICIs (R+ICIs) as the second-line treatment for patients with advanced hepatocellular carcinoma (HCC).Methods: This retrospective study included patients with advanced HCC who received R+ICIs+TACE or R+ICIs as the second-line treatment from January 2019 to April 2022. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between the two groups. The propensity score matching (PSM) was used to reduce the influence of confounding factors on the outcomes. Factors affecting PFS and OS were analyzed using a Cox proportional-hazards regression model.Results: In total, 52 patients were included in this study, of whom 28 patients received R+ICIs+TACE and 24 patients received R+ICIs. After PSM (n=23 in each group), patients who received R+ICIs+TACE had a higher ORR (34.8% vs 4.3%, P=0.009), a longer PFS (5.8 vs 2.6 months, P< 0.0001), and a longer OS (15.0 vs 7.5 months, P=0.014) than those who received R+ICIs. Age ≤ 50 years old, Child-Pugh class A6 and B7, and R+ICIs were found as independent prognostic factors for poor PFS. R+ICIs, α-fetoprotein > 400 ng/mL, and platelet-to-lymphocyte ratio > 133 were noted as independent prognostic factors for poor OS. The difference in the incidence of TRAEs between the two groups was not statistically significant (P> 0.05).Conclusion: Compared to regorafenib plus ICIs, regorafenib plus ICIs with TACE was tolerated and improved survival as the second-line treatment for patients with advanced HCC.Keywords: advanced hepatocellular carcinoma, regorafenib, immune checkpoint inhibitors, transarterial chemoembolization, second-line treatment

Jing Li,1,&ast; Yuzhen Mo,2,&ast; Qingqing Wei,1 Jian Chen,3 Guozeng Xu1 1Department of Oncology, Liuzhou People’s Hospital of Guangxi Medical University, Liuzhou, Guangxi, People’s Republic of China; 2Department of Radiation Oncology, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Medical Oncology, Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guozeng Xu; Jian Chen, Email lzry19831002@yeah.net; chenjianyt@163.comBackground: Activated mast cells (AMCs) have been fully researched in inflammation and allergic reactions. However, the protumoral role of AMCs and their biomarker CD203c has not yet been investigated in colorectal cancer (CRC).Methods: We retrospectively collected 449 postoperative patients with stage II–III CRC at two different hospitals as the training (n=310) and validation (n=139) cohorts. These findings were further validated in the independent cohort (Integration of GSE39582 and GSE17536, n=489). The AMC density was assessed using CD203c staining or the CIBERSORT method. The main analysis was recurrence-free survival (RFS) and overall survival (OS).Results: As an independent factor, high AMC infiltration was associated with worse RFS/OS in the training (hazard ratio [HR]=3.437/3.014, all p< 0.001) and validation (HR=3.537/2.382, all p< 0.001) cohorts. We developed and validated an AMC-based nomogram for better stratification for postoperative recurrence in these two cohorts. The role of AMC density was further validated in the independent cohort. High AMC infiltration was associated with decreased RFS/OS after adjuvant chemotherapy (all p< 0.05). Approximately 74.2% of intramural CD203c+ AMCs expressed a high level of PD-L1. Multiple immunosuppressive pathways were enriched in high AMC infiltration tumors, including upregulation of the TNF-α/NF-κB and angiogenesis pathways and downregulation of the IFN-γ and IFN-α responses. AMC infiltration was reversely associated with CD8+ T-cell infiltration (all p< 0.05).Conclusion: High AMC infiltration is associated with worse survival outcomes in stages II–III CRC. AMC density may serve as a potential biomarker for survival benefit in patients receiving adjuvant chemotherapy. This AMC-based nomogram could provide better recurrence stratification. Immunosuppression in tumors with high AMC infiltration might contribute to promoting tumor progression.Keywords: CD203c, colorectal cancer, activated mast cell, immunosuppression, prognostic benefit

Yanxiong Huang,1 Zhilong Zhang,2 Shihao Lin,3 Haobin Zhou,4 Guiyun Xu5 1Department of Clinical Psychology, Affiliated Longhua People’s Hospital, Southern Medical University (Longhua People’s Hospital), Shenzhen, Guangdong, People’s Republic of China; 2The First People’s Hospital of Huizhou City, Huizhou, Guangdong, People’s Republic of China; 3The Second Clinical College, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 4The First Clinical College, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 5The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Guiyun Xu, Department of Affective Disorder, the Affiliated Brain Hospital of Guangzhou Medical University, 36 Mingxin Road, Guangzhou, Guangdong Province, 510370, People’s Republic of China, Tel +86-81268189, Email 13650774898@163.comAbstract: Bipolar disorder (BD) is a common chronic mental disorder usually characterized by manic, hypomanic and depressive episodes. Patients diagnosed with BD have cognitive impairments in both the mood attack and remission stages, that is impairment of attention, memory and executive function. Up till the present moment, the causative mechanisms of cognitive impairment in BD patients remain poorly understood. Several studies have demonstrated that cognitive impairment in patients with bipolar disorder is not associated with a single factor, but with gene polymorphism, brain structural and functional variables, inflammatory and metabolic factors. Herein, we reviewed and summarized the recent reports on cognitive impairment mechanisms in patients with BD. To prevent or alleviate cognitive damage at an early stage, we propose that future research should focus on investigating the pathological mechanism of specific cognitive dimension damage as well as the pathological mechanism network between the damage of each dimension. It is crucial to recognize mechanisms of cognitive impairment for improving the symptoms and prognosis of BD patients, restoring their social function and integration.Keywords: bipolar disorder, cognitive impairment, mechanism, attention impairment, memory impairment, impairment of executive function

Background: The persistence of HIV-1-infected cells during antiretroviral therapy is well documented but may be modulated by early initiation of antiretroviral therapy in infants. Methods: Here, we longitudinally analyzed the proviral landscape in nine infants with vertical HIV-1 infection from Mozambique over a median period of 24 months, using single-genome, near full-length, next-generation proviral sequencing. Results: We observed a rapid decline in the frequency of intact proviruses, leading to a disproportional under-representation of intact HIV-1 sequences within the total number of HIV-1 DNA sequences after 12-24 months of therapy. In addition, proviral integration site profiling in one infant demonstrated clonal expansion of infected cells harboring intact proviruses and indicated that viral rebound was associated with an integration site profile dominated by intact proviruses integrated into genic and accessible chromatin locations. Conclusion: Together, these results permit rare insight into the evolution of the HIV-1 reservoir in infants infected with HIV-1 and suggest that the rapid decline of intact proviruses, relative to defective proviruses, may be attributed to a higher vulnerability of genome-intact proviruses to antiviral immunity. Technologies to analyze combinations of intact proviral sequences and corresponding integration sites permit a high-resolution analysis of HIV-1 reservoir cells after early antiretroviral treatment initiation in infants.

Weitong Li,1,&ast; Haiyan Yin,1,&ast; Yulei Song,1 Wenjing Tu,1 Lulu Wang,1 Yongqi Liang,1 Yamei Bai,1,&ast; Guihua Xu2,&ast; 1School of Nursing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guihua Xu, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China, Email 7115@njucm.edu.cnBackground: Social isolation is a serious and pervasive health issue among older people, and it is difficult to identify and assess effectively. Based on a thorough and scientific evaluation index system, AHP-Fuzzy comprehensive evaluation could be a valuable technique.Objective: It is crucial to establish interventions that focus on risk factors for the prevention of social isolation in order to give a strong scientific foundation for enhancing older people’s health habits. This can be achieved by using a fuzzy comprehensive evaluation method to assess the risk of social isolation in older people.Methods: A hundred community members over 60 from Nanjing were selected as the evaluation subjects in China. After the element layer was split into three categories of “social risk, economic risk, and cultural risk” using the analytic hierarchy process approach, a total of 22 assessment indicators were picked to develop a risk evaluation index system.Results: The risk level of social isolation belonging to the “low risk, relatively low risk, medium risk, relatively high risk, high risk” of membership degree are respectively “ 0.3392, 0.2632, 0.2257, 0.1069, 0.0650”. Fuzzy comprehensive evaluation analysis showed that social relations (0.4934), monthly income (0.4654), health status (0.5960) were significant factors of social isolation risk in older people. The results showed that factors related to social risk had the most significant impact on social isolation.Conclusion: It is scientific and feasible to construct the risk evaluation index model of social isolation risk for the elderly by using AHP-Fuzzy comprehensive evaluation method. In preventing social isolation of older people in the future, we should pay attention to the impact of social and cultural factors on them, and provide practical intervention programs and references from the government, community, family.Keywords: AHP, fuzzy comprehensive evaluation method, social isolation, older people

Meng Zhang,1,2 Gezhi Xu,1,2 Lu Ruan,1,2 Xin Huang,1,2,* Ting Zhang1,2,* 1Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China; 2Institute of Eye Research, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Huang; Ting Zhang, Department of Ophthalmology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Tel +86-21-64377134, Fax +86-21-64377151, Email fd2017huangxin@163.com; tina-chang07@163.comPurpose: Proliferative diabetic retinopathy (PDR) is a leading vision-threatening disease. In this study, we investigated the clinical features of PDR and the surgical outcomes of its complications in patients with type 2 diabetes (T2D).Patients and Methods: We retrospectively reviewed the medical data of patients with T2D who underwent vitrectomy for PDR between January 2016 and June 2021. The patients were divided into two groups by age (young patients, < 45 years; older patients, ≥ 45 years).Results: There were 149 eyes (100 patients) in the young patient group and 315 eyes (256 patients) in the older patient group. The proportion of males and the proportion of patients requiring binocular surgery were much higher in the young patient group than in the older patient group (P = 0.005 and P < 0.001, respectively). In the young patient group, 26.2% of eyes had active fibrovascular proliferation compared with only 11.4% in the older patient group (P < 0.001). The final best-corrected visual acuity (BCVA) was significantly improved relative to the preoperative BCVA in both groups (P < 0.001). After surgery, there were no significant differences in the incidence of postoperative neovascular glaucoma (NVG) or recurrent vitreous hemorrhage (VH) between the two groups. The incidence of postoperative recurrent retinal detachment was higher in the young patient group (P = 0.033). The risk factors associated with the visual outcomes in the young patient group included preoperative BCVA (P < 0.001), renal diseases (P = 0.001), postoperative NVG (P < 0.001), and recurrent VH (P = 0.028).Conclusion: In this retrospective study, young patients who underwent vitrectomy for PDR had more severe clinical characteristics before vitrectomy. However, vitrectomy (combined with cataract surgery when necessary) achieved better final visual outcomes in young patients than in older patients with T2D.Keywords: proliferative diabetic retinopathy, vitrectomy, fibrovascular proliferation, risk factors

Dapeng Zhou,1,2,&ast; Guangtao Huang,1– 4,&ast; Guangchao Xu,1,2 Lijuan Xiang,5 Siyi Huang,1,2 Xinchong Chen,1,2 Yixin Zhang,4 Dali Wang1,2 1Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China; 2The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, People’s Republic of China; 3Department of Burn and Plastic Surgery, Department of Wound Repair, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, People’s Republic of China; 4Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Department of Clinical Laboratory, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yixin Zhang, Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, People’s Republic of China, Tel +86-21-23271699, Email zhsh06089@163.com Dali Wang, Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, People’s Republic of China, Tel +86-851-28645801, Email daliwangzy@sina.comPurpose: Pseudomonas aeruginosa is a common pathogen of infection in burn and trauma patients, and multi-drug resistant P. aeruginosa has become an increasingly important pathogen. Essential genes are key to the development of novel antibiotics. The PA0715 gene is a novel unidentified essential gene that has attracted our interest as a potential antibiotic target. Our study aims to determine the exact role of PA0715 in cell physiology and bacterial pathogenicity, providing important clues for antibiotic development.Patients and Methods: The shuttle vector pHERD20T containing an arabinose inducible promoter was used to construct the CRISPRi system. Alterations in cellular physiology and bacterial pathogenicity of P. aeruginosa PAO1 after PA0715 inhibition were characterized. High-throughput RNA-seq was performed to gain more insight into the mechanisms by which PA0715 regulates the vital activity of P. aeruginosa.Results: We found that down-regulation of PA0715 significantly reduced PAO1 growth rate, motility and chemotaxis, antibiotic resistance, pyocyanin and biofilm production. In addition, PA0715 inhibition reduced the pathogenicity of PAO1 to the greater galleria mellonella larvae. Transcriptional profiling identified 1757 genes including those related to amino acid, carbohydrate, ketone body and organic salt metabolism, whose expression was directly or indirectly controlled by PA0715. Unexpectedly, genes involved in oxidative phosphorylation also varied with PA0715 levels, and these findings support a hitherto unrecognized critical role for PA0715 in oxidative respiration in P. aeruginosa.Conclusion: We identified PA0715 as a global regulator of the metabolic network that is indispensable for the survival and reproduction of P. aeruginosa. Our results provide a basis for future studies of potential antibiotic targets for P. aeruginosa and offer new ideas for P. aeruginosa infection control.Keywords: P. aeruginosa, reverse transcriptase, prokaryotes, antibiosis, CRISPRi, bioinformatics

Zhuo Zhou,1 Guixing Xu,1 Liuyang Huang,1 Yunjie Shu,1 Hao Tian,1 Fengyuan Huang,1 Yilin Liu,1 Fanrong Liang,2 Mingsheng Sun1 1Acupuncture and Tuina School/The 3rd Teaching Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Acupuncture and Tuina School/The 3rd Teaching Hospital, Chengdu University of Traditional Chinese Medicine/Clinical Research Center for Acupuncture and Moxibustion in Sichuan Province, Chengdu, People’s Republic of ChinaCorrespondence: Fanrong Liang, Acupuncture and Tuina School/The 3rd Teaching Hospital, Chengdu University of Traditional Chinese Medicine/Clinical Research Center for Acupuncture and Moxibustion in Sichuan Province, Chengdu, People’s Republic of China, Tel +86 136 0805 8216, Fax +86-28-87683962, Email acuresearch@126.comIntroduction: Chronic pain is one of the major health problems worldwide in recent years, and acupuncture-related therapies have been reported to have definite analgesic effects. However, it is still unclear which treatment is the most effective. Our systematic review and network meta-analysis protocol aims to summarize the evidence and determine the most effective method to treat the chronic musculoskeletal pain.Methods and Analysis: Our literature search will be performed in five electronic databases—the Cochrane Library, EMBASE, and PubMed, AMED, CINAHL, until May 20, 2022. All randomized controlled trials of acupuncture-related therapies for chronic musculoskeletal pain will be included. The primary outcomes will be common pain-related scales, and the secondary outcomes will include quality of life and incidence of adverse events. Excel 2019 will be used for data extraction, RoB2 will be used for bias risk assessment. R 3.6.2 and WinBUGS V.1.4.3 software will be used for network data synthesis and to produce related plots. During the study, literature selection, data extraction, quality assessment and bias risk assessment will be independently completed by two reviewers, and differences will be judged by the third reviewer. Finally, the risk of bias and sources of heterogeneity in the study will be analyzed and explained in order to obtain reliable results.Results: Our study will evaluate the effectiveness and safety of acupuncture-related therapies for the treatment of chronic musculoskeletal pain, and we will rank all methods to recommend the best appropriate treatment option.Conclusion: This study will provide a good foundation for complementary and alternative medicine to treat chronic musculoskeletal pain. It will be also helpful to promote the clinical practice by providing evidence-based medical evidence.Keywords: systematic review, network meta-analysis, acupuncture-related therapies, chronic musculoskeletal pain

Ruihuan Du,1 Gang Xu,1,2 Xujue Bai,1 Zhonghai Li1,2 1Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, People’s Republic of ChinaCorrespondence: Zhonghai Li, The Third Department of the First Affiliated Hospital of Dalian Medical University, No. 5 Longbin Road, Development Zone, Dalian, 116011, People’s Republic of China, Tel +86-18098876419, Fax +86-411-83635963, Email lizhonghaispine@126.comAbstract: Facet joint osteoarthritis (OA) is the most frequent form of facet joint syndrome. Medical history, referred pain patterns, physical examination, and diagnostic imaging studies (standard radiographs, magnetic resonance imaging, computed tomography and single-photon emission computed tomography) may suggest but not confirm lumbar facet joint (LFJ) syndrome as a source of low back pain (LBP). However, the diagnosis and treatment of facet joint syndrome is still controversial and needs further study. It is widely acknowledged that block with local anesthetic is perhaps the most effective method to establish a diagnosis of pain from LFJ. Particularly, there are different rates of success among different populations selected for diagnostic block with various positive criteria. Currently, in addition to conservative treatments for pain such as painkillers, functional exercises, and massage, there are many other methods, including block, denervation of the nerves that innervate the joints by radiofrequency, freezing or endoscopy, and injections. Due to the limited duration of pain relief from neurolysis of medial branch, many scholars have recently turned their targets to dorsal roots and LFJ capsules. Therefore, we reviewed the latest research progress of facet joint syndrome from diagnosis to treatment.Keywords: low back pain, medial branch, block, radiofrequency, neurolysis

Min Yang,1,&ast; Gufeng Xu,1,&ast; Zhi Ruan,2 Yue Wang1 1Department of Ambulatory Surgery, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Wang, Women’s hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou, Zhejiang, 310000, People’s Republic of China, Email misswangyue@zju.edu.cn Zhi Ruan, Sir Run Run Shaw hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, Zhejiang, 310016, People’s Republic of China, Email r_z@zju.edu.cnBackground: Public health is seriously threatened by the rise of carbapenem-resistant Enterobacterales (CRE). However, the genomic characteristics of CRE detected in pediatric patients are largely unknown. Here, we reported the genomic characteristics of a multidrug-resistant Escherichia coli strain containing the plasmid-borne blaNDM-5 and blaCTX-M-14 genes recovered from a Chinese pediatric patient.Methods: The genome sequence of E. coli strain B379 was determined using Illumina NovaSeq 6000 and Oxford Nanopore MinION. Multiple bioinformatics tools were used to annotate the genome sequence, identify antimicrobial resistance genes and plasmid replicons and perform the in silico multilocus sequence typing (MLST) analysis. Using BacWGSTdb 2.0 server, a core genome MLST (cgMLST) comparison was made between E. coli B379 and all ST746 E. coli strains downloaded from the public database.Results: The E. coli B379 genome sequence is comprised of six contigs totaling 5,152,502 bp, including one chromosome and five plasmids. Nineteen antimicrobial resistance genes were predicted. The blaNDM-5, which is located on a 46,161 bp IncX3 plasmid and the blaCTX-M-14 gene which is located on a 147,204 bp IncFII/IncFIA/IncFIB plasmid are two examples of these 19 genes. E. coli B379 was resistant to ampicillin, ampicillin/sulbactam, ceftriaxone, ceftazidime, imipenem, cefepime, ciprofloxacin, ertapenem, trimethoprim-sulfamethoxazole. This isolate belonged to ST746 and the closest relative was another one originating from a human material specimen in Denmark, which differed by 273 cgMLST alleles.Conclusion: Our study reports the emergence of a multidrug-resistant E. coli strain co-carrying blaNDM-5 and blaCTX-M-14 recovered from a pediatric patient in China. These data would help us better understand the prevalence, genetic characteristics, and mechanisms of antimicrobial resistance of this recently identified multidrug-resistant bacteria in children.Keywords: whole-genome sequencing, Escherichia coli, multidrug-resistant, blaNDM-5, blaCTX-M-14, pediatrics

Yuan Ge1 &ast;, Gufeng Xu1 &ast;, Zhi Ruan,2 Yue Wang1 1Department of Ambulatory Surgery, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Wang, Women’s hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou, Zhejiang, 310000, People’s Republic of China, Email misswangyue@zju.edu.cn Zhi Ruan, Sir Run Run Shaw hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, Zhejiang, 310016, People’s Republic of China, Email r_z@zju.edu.cnBackground: Listeria monocytogenes is a foodborne gram-positive bacterium which causes adverse pregnancy outcomes. Here, the genomic and phylogenetic characteristics of a L. monocytogenes isolate obtained from blood sample of a third trimester pregnant woman with stillbirth are investigated.Methods: Whole genome DNA of L. monocytogenes ST1 was sequenced with HiSeq X Ten platform. The NCBI Prokaryotic Genome Annotation Pipeline was used to annotate the genome sequence. The sequence type (ST) and antimicrobial resistance genes were then identified. The core genome multilocus sequence typing (cgMLST) analysis with other closely related L. monocytogenes stored in the NCBI GenBank database was performed using BacWGSTdb 2.0.Results: The complete genome sequence of L. monocytogenes ST1 is made up of 20 contigs totaling 2,914,725 bp, with 2886 protein-coding sequences and a GC content of 37.9%. Fosfomycin [fosX], Lincosamide antibiotic [lin] and peptide antibiotic [mprF] were discovered as antimicrobial resistance genes. In silico serogroup typing prediction revealed that L. monocytogenes ST1 belonged to serotype IVb. The closest relative of L. monocytogenes ST1, obtained from Poland in 2015, differs by only 15 cgMLST alleles.Conclusion: We identified a L. monocytogenes ST1 strain from blood sample of a woman with third trimester stillbirth in China. These discoveries would aid in our understanding of the genomic characteristics, mechanisms of antimicrobial resistance, and epidemiological features of this pathogen.Keywords: whole genome sequencing, Listeria monocytogenes, stillbirth

Summary: Although therapeutic B cell depletion dramatically resolves inflammation in many diseases in which antibodies appear not to play a central role, distinct extrafollicular pathogenic B cell subsets that accumulate in disease lesions have hitherto not been identified. The circulating immunoglobulin D (IgD)−CD27−CXCR5−CD11c+ DN2 B cell subset has been previously studied in some autoimmune diseases. A distinct IgD−CD27−CXCR5−CD11c− DN3 B cell subset accumulates in the blood both in IgG4-related disease, an autoimmune disease in which inflammation and fibrosis can be reversed by B cell depletion, and in severe COVID-19. These DN3 B cells prominently accumulate in the end organs of IgG4-related disease and in lung lesions in COVID-19, and double-negative B cells prominently cluster with CD4+ T cells in these lesions. Extrafollicular DN3 B cells may participate in tissue inflammation and fibrosis in autoimmune fibrotic diseases, as well as in COVID-19.

Zijia Liu,1 Guangyan Xu,1 Yuelun Zhang,2 Hanyu Duan,3 Yuanyuan Zhu,4 Li Xu1 1Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Anesthesiology, Tibet Autonomous Region People’s Hospital, Lhasa, People’s Republic of China; 4Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Li Xu, Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, People’s Republic of China, Tel +86 10 6915 2020, Fax +86 10 6915 5580, Email pumchxuli@163.comPurpose: Guidelines have not recommended routine transthoracic echocardiography (TTE) for elderly patients prior to noncardiac surgery. We aimed to evaluate the significance of preoperative TTE to predict perioperative cardiac complications (PCCs) for elderly patients with coronary artery disease (CAD) undergoing noncardiac surgery.Patients and methods: We retrospectively reviewed 2204 patients over 65 years of age with CAD who underwent TTE before intermediate- or high-risk noncardiac surgery in a teaching hospital in China between September 2013 and August 2019. The revised cardiac risk index (RCRI) was assessed. PCCs comprised acute coronary syndrome, heart failure, new-onset severe arrhythmia, nonfatal cardiac arrest, and cardiac death. Logistic regression was used to build the prediction model for PCCs. Discrimination was evaluated using receiver operating characteristic curves, and a nomogram of the predictive model was constructed.Results: PCCs occurred in 189 (8.6%) patients. Multivariable analysis showed that eight clinical risk factors (age, history of myocardial infarction, insulin therapy for diabetes, New York Heart Association classification, preoperative serum creatinine, preoperative electrocardiogram ST-T abnormality and pathological Q wave, and American Society of Anesthesiologists classification) and five TTE parameters (left atrial anteroposterior dimension, left ventricular ejection fraction, left ventricular diastolic dysfunction, pulmonary hypertension, and regional ventricular wall motion abnormality) were associated with PCCs. The receiver operating characteristic curve for the clinical plus TTE model provided better discrimination for PCCs compared with the RCRI model (area under the curve: 0.731 vs 0.564; P < 0.001) and the clinical model (area under the curve: 0.731 vs 0.697, P = 0.001), respectively. The clinical plus TTE model was presented as a prognostic nomogram.Conclusion: Preoperative TTE may help predict PCCs in elderly patients with CAD undergoing noncardiac surgery, and the prognostic nomogram from this study appeared to be useful for the assessment of perioperative cardiac risk.Keywords: transthoracic echocardiography, elderly, coronary artery disease, noncardiac surgery, perioperative cardiac complication

Yanhong Xu,1 Ting Liu,1 Yunxia Jiang,1 Xianzhi Zhao,2 Fei Meng,1 Guangyi Xu,1 Mengjiao Zhao1 1School of Nursing, Qingdao University, Qingdao, People’s Republic of China; 2Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Ting Liu, School of Nursing, Qingdao University, 1 Ningde Road, Qingdao, Shandong, 266073, People’s Republic of China, Tel +86 15066237573, Email liuting201516@163.comPurpose: Patients with inflammatory bowel disease (IBD) suffer from physical symptoms and psychosocial issues. This generates risks of psychosocial maladjustment that is closely linked with self-care ability and health-related quality of life. The study aimed to explore psychosocial adaptation of IBD patients in China and the influencing factors from individual and family levels.Patients and Methods: Using a cross-sectional design, 191 Chinese patients with IBD were recruited from October 2020 to September 2021. General information questionnaire, general family functioning scale, resilience scale for IBD, and psychosocial adaptation questionnaire for IBD were used for investigation. Multivariate linear regression was used to identify predictive factors of psychosocial adaptation.Results: IBD patients reported a moderate level of psychosocial adaptation. Regression analysis showed that personal resilience especially the three dimensions (i.e., positive illness perception, disease management, and support from fellow IBD patients), general family functioning, and disease conditions (i.e., extra-intestinal manifestations and current disease status) were the main contributing factors of psychosocial adaptation, explaining 49.3% of the total variance.Conclusion: The findings suggest that healthcare providers could focus on improving patients’ illness perception about IBD and strengthening their disease management abilities, together with optimizing patients’ family functioning to enhance their psychosocial adaptation level.Keywords: inflammatory bowel disease, psychosocial adaptation, family functioning, resilience

Liang Wang,1 Chenxu Tian,2 Guangzhong Xu,2 Qing Sang,1 Guanyang Chen,2 Chengyuan Yu,1 Qiqige Wuyun,2 Zheng Wang,2 Weijian Chen,2 Buhe Amin,2 Dezhong Wang,3 Dongbo Lian,2 Nengwei Zhang2 1Surgery Centre of Diabetes Mellitus, Peking University Ninth School of Clinical Medicine, Beijing, People’s Republic of China; 2Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, People’s Republic of China; 3General Surgery, Aerospace Center Hospital, Beijing, People’s Republic of ChinaCorrespondence: Dongbo Lian; Nengwei Zhang, Email lian.dongbo@126.com; zhangnw1@sohu.comPurpose: To evaluate the predictive effect of the initial weight loss on the long-term weight loss in Chinese patients with a body mass index (BMI) ≥ 32.5 kg/m2 who underwent LSG.Patients and Methods: The follow-up was completed via phone or WeChat for outpatients and at the hospital for inpatients. We evaluated the BMI, percentage of excess weight loss (%EWL), and type 2 diabetes mellitus, hypertension, and hyperlipidemia statuses. Linear and logistic regression analyses were performed on the relationship between the initial and long-term weight loss. The optimal cut-off value was determined by receiver operating characteristic (ROC) curve analysis.Results: We enrolled 307 patients, with a median preoperative BMI of 39.68 (35.68, 45.47) kg/m2. %EWL ≥ 50% was regarded as successful weight loss, and 76.55% of the patients lost their weight successfully. (Reviewer #1, comment #4) %EWL at 6 months and 5 years were positively correlated (P < 0.001). Further, the following linear equation could express the relationship: (%EWL5 years = 29.193 + 0.526 × %EWL6 months). %EWL ≥ 58.57% at 6 months was the best predictor of successful weight loss at 5 years after LSG (Reviewer #1, comment #5) (sensitivity, 73.62%; specificity, 73.61%; AUC value, 0.780). Internal verification of the prediction model revealed satisfactory results in terms of discrimination and calibration.Conclusion: In Chinese patients with BMI ≥ 32.5 kg/m2 who underwent LSG, %EWL at 6 months and 5 years were correlated. %EWL ≥ 58.57% at 6 months was a predictor of successful long-term weight loss.Keywords: laparoscopic sleeve gastrectomy, obesity, weight loss, prognosis