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JianJiang Pan,1,* XiXuan Cai,1,* JieRu Chen,1 MingYing Xu,1 JingYu Hu,1 YueChun Mao,1 Tao Chen,2 LuSha Li,1 MengQi Jin,1 LiYing Chen1 1Department of General Practice, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310020, People’s Republic of China; 2Department of General Practice, Jianqiao Community Health Service Center, Hangzhou, Zhejiang, 310021, People’s Republic of China*These authors contributed equally to this workCorrespondence: LiYing Chen, Department of General Practice, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Email 3197020@zju.edu.cnPurpose: Understanding the role of systemic inflammation in the development of Metabolic Syndrome (MetS) is crucial for identifying individuals at a higher risk of this cluster of conditions that increase the risk of heart disease, stroke, and diabetes.Patients and Methods: A retrospective cohort study was conducted with 4,312 participants who were free from MetS at the study’s onset and had high-sensitivity C-reactive protein (hsCRP) levels measured. Latent class trajectory modeling was utilized to identify distinct hsCRP trajectory patterns. Multivariable regression and proportional hazards analyses were employed to evaluate the predictive value of hsCRP trajectories for the development of MetS.Results: During the 1.63-year follow-up period, 1,308 participants developed metabolic syndrome (MetS). Individuals with high hsCRP levels exhibited a significantly increased risk of developing MetS compared to those with low hsCRP levels (HR = 1.062, 95% CI 1.103– 1.113). The hsCRP trajectory analysis identified three distinct groups: low-stable, increasing, and decreasing. The decreasing and increasing hsCRP trajectory groups demonstrated a 1.408-fold (95% CI 1.115– 1.779) and a 1.618-fold (95% CI 1.288– 2.033) increased risk of MetS, respectively.Conclusion: This study suggests that participants with higher baseline hsCRP levels and increasing hsCRP trajectories are associated with a progression toward MetS. Long-term hsCRP trajectories may serve as useful tools for identifying individuals at higher risk of MetS who could benefit from targeted preventive and therapeutic interventions.Keywords: high-sensitivity C-reactive protein, metabolic syndrome, trajectory analysis, retrospective cohort study, risk prediction

Yuping He,1,2,&ast; Minghao Xu,2,3,&ast; Chenhao Zhou,2,3 Qiongzhu Dong,2,4 Zhiqiu Hu,2,4,5 Ning Ren2– 4 1School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, People’s Republic of China; 2Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission, Shanghai, 201199, People’s Republic of China; 3Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, People’s Republic of China; 4Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, 201199, People’s Republic of China; 5Department of Hepatobiliary and Pancreatic Surgery, Minhang Hospital, Fudan University, Shanghai, 201199, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Ren, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, People’s Republic of China, Tel +86 21 64041990, Email ren.ning@zs-hospital.sh.cn Zhiqiu Hu, Department of Hepatobiliary and Pancreatic Surgery, Minhang Hospital, Fudan University, 170 Xinsong Road, Shanghai, 201199, People’s Republic of China, Tel +86 21 64923400, Email huzq@fudan.edu.cnPurpose: Cathepsin V (CTSV) is a cysteine protease peptidase, which is typically upregulated in cancer and is associated with various oncogenic processes, such as angiogenesis, proliferation, apoptosis, and invasion. The study explored the role of CTSV in hepatocellular carcinoma (HCC) and its potential as a potential biomarker.Patients and Methods: This study collected tumor and peritumoral archived specimens from 180 HCC patients who underwent surgical resection at Zhongshan Hospital, Fudan University (Shanghai, China) between 2009 and 2010. We extracted data from the TCGA and GEO databases and conducted differential expression analysis, univariate Cox regression, and Kaplan-Meier analysis. Ultimately, we determined that CTSV may emerge as a potential biomarker. Then, immunohistochemical staining for CTSV was performed on tumors and adjacent tissues of HCC patients, and a Cox proportional hazards model was constructed to evaluate the prognostic significance of CTSV expression levels. Applied functional enrichment analysis to reveal the underlying molecular mechanisms. Utilized ssGSEA enrichment analysis and TIMER2.0 algorithm to explore the correlation between CTSV expression and immune cells in HCC. In vitro and in vivo experiments were conducted using human liver cancer cell lines to further validate the clinical application value of CTSV.Results: In this study, we observed that CTSV expression was notably elevated in HCC (P < 0.001), and identified a significant association between elevated CTSV expression and reduced overall survival rates in patients. In vitro and in vivo experiments indicated that CTSV knockdown could significantly inhibit the proliferation, migration, and invasion of liver cancer cells, and it was found that the combination of CTSV knockdown with PD-1 inhibitors might enhance the therapeutic effect of PD-1 inhibitors in HCC.Conclusion: CTSV serves as a standalone negative prognostic indicator and possesses clinical significance in HCC.Keywords: Cathepsin V, HCC, biomarker, immune infiltrating cells, PD-1 inhibitor

Jiale Xu,&ast; Musen Xu,&ast; Xin Gao, Jiahang Liu, Jingchao Sun, Ruiqi Ling, Xuchen Zhao, Xifeng Fu, Shaojian Mo, Yanzhang Tian Department of Biliary and Pancreatic Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanzhang Tian, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, No. 99, Longcheng Street, Xiaodian District, Taiyuan, Shanxi Province, People’s Republic of China, Phone/Fax +86-13903512030, Email tyz2030@163.comObjective: To analyze the influence of diabetes mellitus on the clinical outcomes of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP).Methods: This retrospective study included patients diagnosed with MSAP and SAP at Shanxi Bethune Hospital from January 1, 2017, to December 31, 2021. Clinical data were collected, including patient demographics, 24-hour laboratory indicators, and inflammation indices. Propensity score matching (PSM) was used to compare outcomes before and after matching. Patients were randomized into training and validation sets (7:3) to develop and validate a clinical prediction model for infected pancreatic necrosis (IPN).Results: Among 421 patients, 79 had diabetes at admission. Before PSM, diabetic patients had higher incidences of peripancreatic fluid (71% vs 47%, p< 0.001) and IPN (48% vs 10%, p< 0.001), higher surgical intervention rates (24% vs 12%, p=0.008), and significant differences in abdominocentesis (22% vs 11%, p=0.014). After PSM, 174 patients were matched, and the diabetes group still showed higher incidences of peripancreatic fluid (69% vs 47%, p=0.008), IPN (48% vs 11%, p< 0.001), and surgical intervention rates (27% vs 13%, p=0.037). Diabetes, modified CT severity index (MCTSI), serum calcium, and HDL-c were identified as independent risk factors for IPN. The prediction model demonstrated good predictive value.Conclusion: In MSAP and SAP patients, diabetes mellitus can exert an influence on their clinical outcome and is an independent risk factor for IPN. The alignment diagram and web calculator constructed on the basis of diabetes mellitus, modified CT severity index (MCTSI), serum calcium and high-density lipoprotein cholesterol (HDL-c) have good predictive value and clinical guidance for the occurrence of IPN in MSAP and SAP.Keywords: acute pancreatitis, diabetes, propensity score matching, predictive model

Hua Liu,1,&ast; Wenxi Wu,1,&ast; Min Xu,2 Xiaoyang Ling,2 Wei Lu,2 Feng Cheng,1 Jian Wang2 1Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, People’s Republic of China; 2Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan, 215300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Cheng, Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, People’s Republic of China, Email chengf1215@163.com Jian Wang, Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan, 215300, People’s Republic of China, Email wj458381670@126.comBackground and Aim: Traumatic brain injury (TBI) is a severe public health problem in elderly patients, and frailty is associated with higher mortality rates in older patients. This study aims to assess the prognostic value of frailty in patients with TBI.Methods: Clinical data from 348 TBI patients treated at Affiliated Kunshan Hospital of Jiangsu University and Kunshan Hospital of Traditional Chinese Medicine between December 2018 and December 2020 were retrospectively collected. Univariate and multivariate logistic regression analyses were used to determine risk factors affecting in-hospital mortality, and receiver operating characteristic (ROC) curves were plotted to assess the discriminatory power of the frailty index. Frailty was assessed using the FRAIL scale, where FRAIL stands for Fatigue, Resistance, Ambulation, Illness, and Loss of weight, with each item scored as 0 or 1.Results: Using the FRIAL questionnaire, 122 patients had low frailty and 226 had high frailty. Multivariate logistic regression analysis showed that high frailty was a risk factor for in-hospital mortality in TBI patients (P< 0.001, OR=2.012 [1.788– 2.412]). The proportion of infections occurring in the two groups was statistically different (P=0.015), with severely infected TBI patients being more likely to develop complications. The ROC curve showed an area under the curve for the FRAIL score of 0.845 [0.752– 0.938].Conclusion: Frailty is an important risk factor for in-hospital mortality in elderly TBI patients, and more attention should be paid to patients with high levels of frailty. Clinicians should consider the degree of frailty when assessing TBI and making treatment decisions.Keywords: frailty, traumatic brain injury, in-hospital mortality, prognosis

Huifang Cai,1,&ast; Zongbi Wu,2,&ast; Jieling Xu,1 Taifen Wang,2 Yanfeng Li,3 Youli Jiang,3 Mingming Xu2 1Guangzhou University of Chinese Medicine Fourth Clinical Medical College, Shenzhen, People’s Republic of China; 2Nursing Department, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China; 3Department of Neurology, People’s Hospital of Longhua, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youli Jiang; Mingming Xu, Email h2362120381@163.com; szszyyhlb@163.comObjective: This study investigates the prevalence and determinants of social isolation in peritoneal dialysis (PD) patients, focusing on the influence of environmental systems and individual behaviors on their social well-being.Methods: We conducted a cross-sectional study from December 2023 to February 2024 at Shenzhen Traditional Chinese Medicine Hospital. A total of 259 PD patients were enrolled using a consecutive sampling method. Data were collected via validated tools including the Pittsburgh Sleep Quality Index (PSQI), Lubben Social Network Scale-6 (LSNS-6), Family APGAR Questionnaire, and Social Anxiety Subscale of Self-Consciousness Scale (SASS-CS). Statistical analyses utilized Spearman correlation and multiple linear regression to identify factors associated with social isolation.Results: The average score for social isolation was 11 (range 7– 15). Significant predictors of social isolation included education level, physical inactivity, and normal hemoglobin concentrations. Social isolation was negatively correlated with family functionality and positively correlated with social anxiety. Regression analysis confirmed education, family functionality, and social anxiety as significant independent predictors of social isolation.Conclusion: Social isolation is common among PD patients, driven by factors such as education level, physical inactivity, and unexpectedly, normal hemoglobin levels linked to greater family isolation. Targeted interventions like education, physical activity promotion, and innovative therapies such as animal-assisted activities and social gardening can help reduce isolation and improve patient well-being.Plain Language Summary: 1. Why is this study needed? Peritoneal dialysis is a common treatment for severe kidney disease. This study is crucial because it examines how being isolated affects patients undergoing this treatment, as social isolation can worsen their health outcomes. 2. What is the key problem/issue/question this manuscript addresses? The main issue addressed is understanding the factors that contribute to social isolation in peritoneal dialysis patients and how this isolation impacts their health and quality of life. 3. What is the main point of your study? The study explores how various factors such as education levels, physical activity, and family support influence social isolation among these patients. It also looks at the broader environmental and social settings that affect their interactions and mental health. 4. What are your main results and what do they mean? Our findings show that patients with higher education, better family support, and more physical activity are less socially isolated. Addressing these factors can greatly enhance the well-being and social interactions of peritoneal dialysis patients, suggesting the need for targeted support and community integration initiatives.Keywords: peritoneal dialysis, social isolation, social support systems, physical inactivity, educational disparities, mental health

Honglin Wang,1,2,&ast; Na Li,1,3,4,&ast; Ying Ye,5 Nan Zhao,6 Meizi Liu,1 Min Xu,3 Qiuhong Zhou3,4 1Xiangya School of Nursing, Central South University, Changsha, People’s Republic of China; 2School of Health and Nursing, Guangzhou Huali College, Jiangmen, People’s Republic of China; 3Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 4National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 5Department of Nursing, First People’s Hospital of Yunnan, Kunming, People’s Republic of China; 6School of Nursing, Zhengzhou Shuqing Medical College, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiuhong Zhou, Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, 410008, People’s Republic of China, Tel +8613786136512, Email 928555448@qq.comObjective: Timely screening and intervention can prevent the development of the diabetic foot. However, delayed visits to the clinic are common among diabetic foot patients. The study aimed to develop and validate a questionnaire to assess healthcare-seeking behavior among patients with diabetic high-risk foot.Methods: The questionnaire of healthcare-seeking intention for patients with diabetic high-risk foot was developed in two phases: (1) Developing the questionnaire: 1) questionnaire items were formulated after literature review, group discussion and semi-qualitative interview; 2) a two-round modified Delphi method was to examine the content validity and the degree of consistency in questionnaire items; 3) conducting pre-survey to revise the questionnaire items. (2) Assessing the internal reliability and construct validity.Results: The final questionnaire consisted of five main themes and 28 items with a five-point rating. Cronbach’s alpha coefficients for the five dimensions were respectively 0.937 (relevant knowledge of diabetic foot), 0.669 (attitudes toward seeking care), 0.896 (social support for seeking care), 0.621 (efficacy in coping with foot symptoms), 0.871 (intention to seek care). The Scale-level Content Validity Index of the five parts was 1.00, 0.80, 1.00, 1.00, and 1.00, respectively. The Kaiser-Meyer-Olkin values for each dimension was greater than 0.7, and the p-value for Bartlett’s test of sphericity was less than 0.05.Conclusion: This questionnaire showed good validity, internal consistency, and reliability. It provided a potentially useful instrument to evaluate healthcare-seeking intention among patients with diabetic high-risk foot.Keywords: healthcare-seeking intention, questionnaire development, high-risk foot, patients

Mingyu Xu, Chaoran Wu Department of Anesthesiology, Shenzhen People’s Hospital, Shenzhen, Guangdong, 518000, People’s Republic of ChinaCorrespondence: Chaoran Wu, Email chaoranwu@126.comAbstract: A patient who was 39 weeks pregnant was admitted to the hospital to be expecting labor and performed labor analgesia when the uterine orifice was opened to 2 cm. We successfully performed L2.3 epidural puncture in the lumbar space and equipped her with a self-controlled epidural analgesia infusion pump (100mL, 10mL 1% ropivacaine + 50ug sufentanil + 89mL normal saline) with a load of 8mL for continuous delivery. Continuous infusion of 8mL/h, patient controlled analgesia (PCA) 6 mL/ time at 15 minute intervals. The analgesic effect is good. In the following 40 minutes or so, due to fetal monitoring, fetal heart rate variation deceleration accompanied by late deceleration, the minimum was reduced to 85 times/min, and there was no improvement after treatment, and then the obstetrician prepared to perform an emergency cesarean section. The anesthesiologist evaluated the patient and then chose an epidural. The epidural dose was 3mL 1% lidocaine +0.5% rox mixture, and 7mL 1% lidocaine +0.5% rox mixture was administered 3 minutes later. During the administration, the patient complained of unbearable headache and rapid loss of consciousness. Immediate organization rescue, uterine dissection, pressure oxygen, preparation of tracheal intubation, cardiopulmonary resuscitation, cardiovascular active drugs, etc. After about 1 minute, the patient regained consciousness, responded smoothly, the vital signs were stable, the anesthesia plane T8 was measured. The patient’s surgery went smoothly, and there were no complications during postoperative follow-up. They were discharged 5 days later. Such cases are relatively rare, especially during cesarean section surgery has not been reported, so it is published for everyone’s reference.Keywords: labor analgesia, caesarean section, transient consciousness disorder

Rongrong Zhang,1,&ast; Wenjun Xu,1,&ast; Hongquan Wei,1,&ast; Boshi Li,1 Yaoxing Wang,1 Xueqing He,1 Jun Cao,1 Xinyu He,1 Mingxiang Xu,1,2 Wenjie Lu,1 Youzhi Xu1 1College of Basic Medicine, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2Center for Scientific Research, Anhui Medical University, Hefei, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youzhi Xu; Wenjie Lu, Email xuyouzhi@ahmu.edu.cn; wenjie63136@163.comPurpose: Currently, there is still no clear treatment for polycystic ovary syndrome (PCOS). YJKL has better therapeutic effects and lower toxic side effects for PCOS type infertility. This study aims to clarify the potential mechanism of YJKL Decoction in the treatment of PCOS based on network pharmacology and experiments verification.Patients and Methods: Network pharmacology and experimental validation approach were used to investigate the bioactive ingredients, critical targets and potential mechanisms of YJKL Decoction against PCOS. Firstly, we use network pharmacology methods to collect core targets, and then validate their effects on diseases through experiments.Results: Five core targets were screened, Threonine kinase 1 (AKT1), Cellular tumor antigen p53 (TP53), Tumor necrosis factor (TNF), Albumin (ALB) and Vascular endothelial growthfactor A (VEGFA). KEGG analysis showed that YJKL treatment for PCOS mainly include AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway and HIF-1 signaling pathway. The molecular docking results showed that compounds have higher affinity with targets. Finally, experimental results had shown that YJKL Decoction had an better therapeutic effects in the treatment of PCOS.Conclusion: Based on a systematic network pharmacology approach and experimental verification, our results comprehensively illustrated the active ingredients, potential targets, and molecular mechanism of YJKL for application to PCOS and helps to illustrate mechanism of action on a comprehensive level.Keywords: traditional Chinese Medicine, YJKL, polycystic ovary syndrome, PCOS, molecular docking, experimental validation

Xuefeng Hou,1– 4,&ast; Qi Chen,1,&ast; Ying Fang,5 Li Zhang,1 Shuoheng Huang,1 Minjie Xu,1 Yaning Ren,1 Zhansen Shi,1 Yan Wei,1 Lihua Li1– 4 1School of Pharmacy, Wannan Medical College, Wuhu, Anhui Province, People’s Republic of China; 2Anhui Provincial Engineering Laboratory for Screening and Re-Evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Wannan Medical College, Wuhu, Anhui Province, People’s Republic of China; 3Anhui Provincial Engineering Research Center for Polysaccharide Drugs, Wannan Medical College, Wuhu, Anhui Province, People’s Republic of China; 4Drug Research and Development Center, Wannan Medical College, Wuhu, Anhui Province, People’s Republic of China; 5School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Wei; Lihua Li, School of Pharmacy, Wannan Medical College, No. 22, West Wenchang Road, Wuhu, 241002, People’s Republic of China, Email yanwei@wnmc.edu.cn; llh05530226@126.comBackground: Breast cancer presents significant challenges due to the limited effectiveness of available treatments and the high likelihood of recurrence. iRGD possesses both RGD sequence and C-terminal sequence and has dual functions of targeting and membrane penetration. iRGD-modified nanocarriers can enhance drug targeting of tumor vascular endothelial cells and penetration of new microvessels, increasing drug concentration in tumor tissues.Methods: The amidation reaction was carried out between SiO2/AuNCs and iRGD/PTX, yielding a conjugated drug delivery system (SiO2/AuNCs-iRGD/PTX, SAIP@NPs). The assessment encompassed the characterization of the morphology, particle size distribution, physicochemical properties, in vitro release profile, cytotoxicity, and cellular uptake of SAIP@NPs. The tumor targeting and anti-tumor efficacy of SAIP@NPs were assessed using a small animal in vivo imaging system and a tumor-bearing nude mice model, respectively. The tumor targeting and anti-tumor efficacy of SAIP@NPs were assessed utilizing a small animal in vivo imaging system and an in situ nude mice breast cancer xenograft model, respectively.Results: The prepared SAIP@NPs exhibited decent stability and a certain slow-release effect in phosphate buffer (PBS, pH 7.4). In vitro studies had shown that, due to the dual functions of transmembrane and targeting of iRGD peptide, SAIP@NPs exhibited strong binding to integrin αvβ 3, which was highly expressed on the membrane of MDA-MB-231 cells, improving the uptake capacity of tumor cells, inhibiting the rapid growth of tumor cells, and promoting tumor cell apoptosis. The results of animal experiments further proved that SAIP@NPs had longer residence time in tumor sites, stronger anti-tumor effect, and no obvious toxicity to major organs of experimental animals.Conclusion: The engineered SAIP@NPs exhibited superior functionalities including efficient membrane permeability, precise tumor targeting, and imaging, thereby significantly augmenting the therapeutic efficacy against breast cancer with a favorable safety profile. Keywords: silicon dioxide nanoparticles, gold nanoclusters, iRGD penetrating peptide, integrin αvβ 3, tumor targeting, breast cancer

Hua Ji,1,&ast; YaTing Lu,1,&ast; Gui Liu,2 Xiaotong Zhao,1 Murong Xu,1 Mingwei Chen1 1Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, People’s Republic of China; 2Department of Endocrinology, The Second People’s Hospital of Lu’an City, Lu’an City, Anhui Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingwei Chen, Department of Endocrinology, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei City, Anhui Province, People’s Republic of China, Email chmw1@163.comObjective: To Study the Correlations of microRNA-155 (miR-155) and microRNA-146a (miR-146a) Expression in Peripheral Blood of Type 2 Diabetes Mellitus (T2DM) Patients with Diabetic Peripheral Neuropathy (DPN), and Explore the Clinical Value of miR-155 and miR-146a in the Diagnosis and Treatment Outcomes of DPN.Methods: The study included 51 T2DM patients without DPN (T2DM group), 49 T2DM patients with DPN (DPN group), and 50 normal controls (NC group). Quantitative real-time PCR was utilized to determine the expression levels of miR-155 and miR-146a. Clinical features and risk factors for DPN were assessed. Multivariate stepwise logistic regression analysis was conducted to confirm whether the expressions of miR-155 and miR-146a could independently predict the risk of DPN. ROC curve analysis evaluated their diagnostic value.Results: The T2DM group exhibited significantly lower expression levels of miR-155 and miR-146a compared to the NC group (P < 0.05). Moreover, the DPN group exhibited a significantly decreased expression level of miR-155 and miR-146a compared to the T2DM group (P < 0.01). Multivariate logistic regression analysis indicated that higher levels of miR-155 and miR-146a might serve as protective factors against DPN development. ROC curve analysis revealed that miR-155 (sensitivity 91.8%, specificity 37.3%, AUC 0.641,) and miR-146a (sensitivity 57.1%, specificity 84.3%, AUC 0.722) possess a strong ability to discriminate between T2DM and DPN. Their combined use further enhanced the diagnostic potential of DPN (sensitivity 83.7%, specificity 60.8%, AUC 0.775). A multi-index combination can improve DPN diagnostic efficiency.Conclusion: The decreased expression of miR-155 and miR-146a in the peripheral blood of T2DM patients is closely related to the occurrence of DPN, highlighting their potential as valuable biomarkers for diagnosing and prognosticating DPN.Keywords: miR-155, miR-146a, diabetic peripheral neuropathy, type 2 diabetes mellitus, biomarkers

Meilan Xu,1 Fuxiang Fang,2 Krishna Hamal,1 Shenhou Tang,3 Donghua Liu1 1Department of Dermatology and Venereology, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China; 2Department of Urology, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China; 3The First Affiliated Hospital of Guangxi University of Science and Technology, Liuzhou, 545001, People’s Republic of ChinaCorrespondence: Donghua Liu, Department of Dermatology and Venereology, the First Affiliated Hospital of Guangxi Medical University, No. 6, Shuang Yong Road, Nanning, Guangxi, People’s Republic of China, Email ldhgxmu@163.comAbstract: Genitourinary tuberculosis (GUTB), especially penile tuberculosis (PTB), is a disease often overlooked by urological specialists, especially in Europe, where the pathology is less frequent. In this report, we described a case of penile tuberculosis (PTB) characterized by ulcers on the penis. After the patient was administered three months of anti-tuberculosis treatment (isoniazid 0.3 g/qd, rifampicin 0.6 g/qw, and ethambutol 0.75 g/qd), the ulcer disappeared. The patient was followed up for seven months and showed no recurrence.Keywords: Mycobacterium tuberculosis, penile ulcers, dermatopathology, a case report

Ying Lan,1 Die Hu,1 Shijing Huang,1 Qing Ma,1 Li Chen,2,3 Min Xu,1 Qin He1 1Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, 610031, People’s Republic of China; 2Department of Pharmacology, Faculty of Medicine, University of the Basque Country, UPV/EHU, Leioa, Spain; 3Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Ying Lan; Li Chen, Email lanying0212@126.com; chenl_hxey@scu.edu.cnPurpose: This study conducted a pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) database to compare the infection risk of inhaled or nasal Beclomethasone, Fluticasone, Budesonide, Ciclesonide, Mometasone, and Triamcinolone Acetonide.Methods: We used proportional imbalance analysis to evaluate the correlation between ICS /INCs and infection events. The data was extracted from the FAERS database from April 2015 to September 2023. Further analysis was conducted on the clinical characteristics, site of infection, and pathogenic bacteria of ICS and INCs infection adverse events (AEs). We used bubble charts to display their top 5 infection adverse events.Results: We analyzed 21,837 reports of infection AEs related to ICS and INCs, with an average age of 62.12 years. Among them, 61.14% of infection reports were related to females. One-third of infections reported to occur in the lower respiratory tract with Fluticasone, Budesonide, Ciclesonidec, and Mometasone; over 40% of infections reported by Triamcinolone Acetonide were eye infections; the rate of oral infections caused by Beclomethasone were 7.39%. The reported rates of fungal and viral infections caused by beclomethasone were 21.15% and 19.2%, respectively. The mycobacterial infections caused by Budesonide and Ciclesonidec account for 3.29% and 2.03%, respectively. Bubble plots showed that the ICS group had more fungal infections, oral infections, pneumonia, tracheitis, etc. The INCs group had more eye symptoms, rhinitis, sinusitis, nasopharyngitis, etc.Conclusion: Women who use ICS and INCs are more prone to infection events. Compared to Budesonide, Fluticasone seemed to have a higher risk of pneumonia and oral candidiasis. Mometasone might lead to more upper respiratory tract infections. The risk of oral infection was higher with Beclomethasone. Beclomethasone causes more fungal and viral infections, while Ciclesonide and Budesonide are more susceptible to mycobacterial infections.Keywords: data mining, FAERS, ICS, INCs, pharmacovigilance, infections

Ying Jiang,1,&ast; Chuankai Lin,1,&ast; Min Xu,2,&ast; Taiwen Zhu,1 Xuhong Li,1 Wei Wang1 1Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China; 2Medical and Nursing School, Wuhan Railway Vocational College of Technology, Wuhan, 430205, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wang, Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China, Tel +86 15071128246, Email wangwei1069@163.comIntroduction: Obstructive sleep apnea (OSA) is a respiratory disorder characterized by chronic intermittent hypoxia and fragmented sleep, leading to inflammatory response and oxidative stress. However, the differences in immune inflammatory response in OSA patients with different severity remain unclear.Purpose: This study aims to examine the differences in peripheral blood immune cells and their risk factors in OSA patients.Patients and Methods: A total of 277 snoring patients from the Sleep Respiratory Disorder Monitoring Center of Zhongnan Hospital of Wuhan University were recruited in this study. According to the diagnosis and severity criteria of OSA, the included patients were further divided into simple snoring, mild, moderate, and severe groups. Peripheral blood immune cell counts including white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, red blood cells, platelets, and polysomnography indicators were collected from the patients.Results: Compared with simple snoring patients, the OSA patients had increased circular monocyte and basophil count levels. In addition, correlation analysis results indicated that monocyte count was positively associated with chronic obstructive pulmonary disease (COPD), smoking, apnea-hypopnea index (AHI), the longest apnea duration, and Oxygen desaturation index (ODI), and negatively correlated with average SpO2 in snoring patients. Finally, multiple linear regression analysis revealed that AHI, COPD, smoking, and maximum heart rate were independent predictors of monocyte count.Conclusion: OSA patients had a significant increase in their peripheral blood monocyte count. AHI, COPD, smoking, and maximum heart rate were risk factors for increased peripheral blood monocyte count in OSA patients. These findings suggest that peripheral blood monocytes can be considered an inflammatory biomarker of OSA.Keywords: obstructive sleep apnea, peripheral blood cell count, monocytes, polysomnography, inflammatory biomarker

Mingyue Xu,&ast; Chunlin Zhang,&ast; Linlin Zhang, Hua Qu, Yuren Wang Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Second Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Qu; Yuren Wang, Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, the Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China, Tel +86 2368763255, Fax +86 2368755707, Email quhuahua120@163.com; 346577395@qq.comPurpose: To explore the expression of asprosin in subjects with pre-DKD and DKD and to analyze its relationship with kidney injury, inflammation, and glucose and lipid metabolism.Methods: Based on urine albumin:creatinine ratio (UACr), participants were divided into DM, pre-DKD, and DKD groups. Relevant human physiological and biochemical parameters were detected in the three groups.Results: We found relatively higher levels of asprosin in both pre-DKD and DKD groups than the DM group. Moreover, data from the Nephroseq database support increased gene expression of asprosin in kidney tissue from DKD patients. Further correlation analysis revealed that the plasma asprosin level was positively correlated with age, waist circumference, waist:hip ratio, systolic blood pressure, creatinine, UACr, triglycerides, HDL-c, fasting insulin, HOMA-IR, and the inflammatory marker G3P and negatively associated with eGFR. Multiple logistical regression analysis showed that asprosin concentration was significantly associated with pre-DKD and DKD after adjusting for sex, age, BMI, WHR, and HOMA-IR, while this correlation was lost after controlling for G3P.Conclusion: Plasma asprosin is associated with kidney injury in diabetic conditions, and this association might be connected through inflammatory response. Further studies are needed to assess the role and mechanism of asprosin in DKD.Keywords: asprosin, diabetes, diabetic kidney disease, kidney injury

Yongyi Xie,1,&ast; Nanhui Wu,1,&ast; Suwei Tang,1,&ast; Zhiyu Zhou,1 Jiashe Chen,1 Jie Li,1 Fei Wu,1 Mingyuan Xu,1 Xiaoxiang Xu,1 Yeqiang Liu,1 Xin Ma1,2 1Shanghai Skin Disease Hospital, Institute of Dermatology, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yeqiang Liu; Xin Ma, Shanghai Skin Disease Hospital, Institute of Dermatology, Baode Road 1278 Street, Shanghai, 200433, People’s Republic of China, Email 1500156@tongji.edu.cn; Nicole.ma@me.comAbstract: The endoplasmic reticulum (ER) is the main site of protein synthesis, transport, and modification. Its abnormal status has now emerged as an established cause of many pathological processes, such as tumors and autoimmune diseases. Recent studies also demonstrated that the defective functions of ER may lead to pigmentary diseases. Vitiligo is a depigmenting ailment skin disorder whose pathogenesis is now found to be associated with ER. However, the detailed mechanism is still unclear. In this review, we try to link the association between ER with its inter- and intra-organellar interactions in vitiligo pathogenesis and focus on the function, mechanism, and clinical potential of ER with vitiligo. Expand ER is found in melanocytes of vitiligo and ER stress (ERS) might be a bridge between oxidative stress and innate and adaptive immunity. Meanwhile, the tight association between ER and mitochondria or melanosomes in organelles levels, as well as genes and cytokines, is the new paradigm in the pathogenesis of vitiligo. This undoubtedly adds a new aspect to the understanding of vitiligo, facilitating the design of targeted therapies for vitiligo.Keywords: vitiligo, endoplasmic reticulum, organelles, cellular interactions, oxidative stress

Juanjuan Liu,1 Minqin Xu,1 Ling Zhou,1 Li Yang,1 Hong Li,2 Xue Li1 1Department of Obstetrics and Gynecology, Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Radiology, Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Xue Li, Department of Obstetrics and Gynecology, Second Affiliated Hospital of Soochow University, 1055 San Xiang Road, Suzhou, 215004, People’s Republic of China, Tel +8613584834618, Email zlanling@163.comObjective: To investigate the magnetic resonance imaging (MRI) features of women with prior second-trimester pregnancy loss, and to establish a nomogram prediction model for subsequent miscarriage.Methods: A retrospective cohort study of women with prior second-trimester pregnancy loss from January 2018 to December 2021 in Second Affiliated Hospital of Soochow University was performed. A total of 245 patients were included. Data from January 2018 to December 2019 were used to construct the model, and data from January 2020 to December 2021 were used to evaluate the model. Data on maternal demographic characteristics, MRI cervical measurements were extracted. The prediction model was constructed with independent variables determined by multivariate logistic regression analyses. Through receiver-operating characteristic (ROC) curve analysis, the predictive ability of the model for subsequent second trimester pregnancy loss in women was evaluated, and internal validation was performed through validation data.Results: Thin cervix was observed in 77 (31.42%) women with prior second-trimester pregnancy loss, the mean longitudinal diameter of cervical canal on MRI was 11.76± 2.75mm. The model reached a sensitivity of 80%, specificity of 75.90%, positive predictive value (PPV) of 55.80% and negative predictive value of 90.90%; ROC characteristics proved that the model was superior to any single parameter with an AUC of 0.826.Conclusion: Our observations showed that thin cervix and longitudinal diameter of cervical canal reliably predicted second trimester pregnancy loss. We developed and validated a nomogram model to predict the individual probability of second trimester pregnancy loss in the next pregnancy and hopefully improve the prediction and indication of interventions.Keywords: cervical insufficiency, MRI, nomogram, magnetic resonance imaging, CI

Chen Bai, Mingcan Xu, Yan Guo, Yanwu Jin, Xin Zhao Department of Anesthesiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, People’s Republic of ChinaCorrespondence: Yanwu Jin; Xin Zhao, Department of Anesthesiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, No. 247, Beiyuan Road, Jinan, Shandong, 250033, People’s Republic of China, Email jinyanwu_aa@163.com; lujnzx@sohu.comAbstract: Remimazolam is a novel ultrashort-acting benzodiazepine that allosterically modulates γ-aminobutyric acid type A (GABAA) receptors to exert sedative effects. Remimazolam has the properties of controllable sedation, rapid onset, and a short duration of action, along with minor depression of circulation and respiration. Remimazolam has been approved for clinical use since 2020 in Japan, and it has been applied for procedural sedation, general anesthesia induction and maintenance, and sedation in ICU patients, and has been proven to be safe and effective. Currently, no consensus has been reached on the clinical application of remimazolam in pediatric patients. This review introduces the clinical research progress and limitations of remimazolam in recent years, aiming to supply scientific guidance and a theoretical reference for the application of remimazolam in pediatric anaesthesia.Keywords: remimazolam, sedation, pediatric patient, clinical anesthesia

Xujie Zhang, Xinrui Huang, Feilin Ni, Xiaopei Mao, Danhua Yang, Min Xu Department of Nursing, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310003, People’s Republic of ChinaCorrespondence: Min Xu, Department of Nursing, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), No. 54, Youdian Road, Hangzhou, Zhejiang, 310003, People’s Republic of China, Email yudi1212@163.comObjective: We aimed to understand the commonly used acupoints and the acupoint combination rules in Guasha therapy for primary headaches using data mining technology, providing a reference for the clinical application of Guasha therapy for primary headaches.Methods: Literature related to Guasha therapy for primary headaches in PubMed, Web of Science, Chinese National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and Chinese Biomedical Literature Database were searched, up until May 12, 2023. A database of acupoints for Guasha therapy for primary headaches was established in Excel. The frequency of the acupoints used for Guasha in therapy of primary headaches were calculated by SPSS 25.0. The association rules between the acupoints were further described using SPSS Modeler 18.0.Results: A total of 67 papers were included, involving 51 acupoints for Guasha against primary headaches. The most commonly used acupoints were Fengchi, Baihui, Taiyang, Shuaigu, Tianzhu, and Hegu. The common acupoint combinations for Guasha therapy for primary headaches were Fengchi-Taiyang, Fengchi-Baihui, Fengchi-Taiyang-Baihui, Fengchi-Tianzhu-Baihui, and Fengchi-Shuaigu-Taiyang-Baihui.Conclusion: Data mining can effectively analyze the commonly used acupoints and the acupoint combination rules in Guasha therapy for primary headaches, providing a reliable basis for clinical acupoint selection.Keywords: primary headache, Guasha, data mining, acupoint selection rules, Chinese medicine nursing

Hong Yang,1 Maogang Chen,2 Ying Hu,1 Mengjiao Xu,1 Yiping Li,1 Lunhao Liu,1 Dan Yuan,1 Fengshun Yuan,1 Ling Li,1 Li Ye,1 Chang Zhou,1 Yan Zhang,1 Shu Liang,1 Ling Su1 1Department of AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention, Chengdu, People’s Republic of China; 2Department of Microbiology, Liangshan Yi Autonomous Prefecture Center for Disease Control and Prevention, Xichang, People’s Republic of ChinaCorrespondence: Shu Liang; Ling Su, Email liangshu523@163.com; sl7512@163.comBackground: Men who have sex with men (MSM) is one main type of high-risk activities facilitating HIV-1 transmission in Sichuan province. Previous works on HIV-1 incidence and prevalence among MSM only concentrated before 2018, the situation after that is unknown. In addition, the distribution of hot-spots related to current HIV-1 epidemic is also rarely known among MSM in Sichuan.Objective: To update trends of HIV-1 prevalence and incidence and to visualize hot-spots of ongoing transmission in Sichuan province during surveillance period among MSM between 2018 and 2022.Methods: Limiting Antigen Avidity assay was performed to detect recent infection within new HIV-1 diagnoses founded during surveillance period among MSM. The HIV-1 prevalence and incidence were calculated according to an extrapolation method proposed by publications and guidelines. Trend tests were performed using χ2 tests with linear-by-linear association. The spatial analysis was conducted with ArcGIS 10.7 to figure hot-spots of HIV-1 recent infections among MSM.Results: Between 2018 and 2022, 16,697 individuals participated in HIV-1 MSM sentinel surveillance program, of which 449 samples (98.25%) were tested with LAg-Avidity EIA, and 230 samples were classified as recent infection. Respectively, the overall prevalence and incidence were 2.74% and 3.69% (95% CI: 3.21, 4.16) and both had significant declining trends (p < 0.001). Luzhou city had a highest HIV-1 incidence (10.74%, 95% CI: 8.39, 13.10) over the study period and was recognized as a hot-spot for recent HIV-1 infection among MSM.Conclusion: During the surveillance period, both HIV-1 prevalence and incidence were declining. However, Luzhou city had an unusually high HIV-1 incidence and became an emerging hot-spot of recent HIV-1 infection among MSM. This finding suggested focused attention, cross-regional intervention strategies, and prevention programs are urgently required to curb the spread of ongoing transmission.Keywords: human immunodeficiency virus type 1, HIV-1 recent infection, incidence, hot-spots, men who have sex with men

Chunhong Li,1,&ast; Zhen Wang,1,&ast; Yifeng Zhang,1 Yuqing Zhu,1 Maochang Xu,1 Hui Lei,1 Dan Zhang1,2 1Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Green Pharmaceutical Technology Key Laboratory of Luzhou, School of Pharmacy, Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Lei; Dan Zhang, Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, 1-1 Xianglin Road, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 17360593759 ; +86 18982700067, Email huilei@swmu.edu.cn; zhangdan@swmu.edu.cnPurpose: Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. However, the effect of current treatment strategies by inducing tumor cell apoptosis alone is not satisfactory. The growth, metastasis and treatment sensitivity of tumors can be strongly influenced by cancer-associated fibroblasts (CAFs) in the microenvironment. Effective cancer therapies may need to target not only the tumor cells directly but also the CAFs that protect them.Methods: Celastrol and small-sized micelles containing betulinic acid were co-encapsulated into liposomes using the thin-film hydration method (CL@BM). Folic acid was further introduced to modify liposomes as the targeting moiety (F/CL@BM). We established a novel NIH3T3+4T1 co-culture model to mimic the tumor microenvironment and assessed the nanocarrier’s inhibitory effects on CAFs-induced drug resistance and migration in the co-culture model. The in vivo biological distribution, fluorescence imaging, biological safety evaluation, and combined therapeutic effect evaluation of the nanocarrier were carried out based on a triple-negative breast cancer model.Results: In the present study, a novel multifunctional nano-formulation was designed by combining the advantages of sequential release, co-loading of tretinoin and betulinic acid, and folic acid-mediated active targeting. As expected, the nano-formulation exhibited enhanced cytotoxicity in different cellular models and effectively increased drug accumulation at the tumor site by disrupting the cellular barrier composed of CAFs by tretinoin. Notably, the co-loaded nano-formulations proved to be more potent in inhibiting tumor growth in mice and also showed better anti-metastatic effects in lung metastasis models compared to the formulations with either drug alone. This novel drug delivery system has the potential to be used to develop more effective cancer therapies.Conclusion: Targeting CAFs with celastrol sensitizes tumor cells to chemotherapy, increasing the efficacy of betulinic acid. The combination of drugs targeting tumor cells and CAFs may lead to more effective therapies against various cancers.Keywords: liposomes, targeted delivery, triple-negative breast cancer, anti-tumor, combination therapy, sequential drug delivery

Xin Gao,1 Jiale Xu,2 Musen Xu,2 Pengzhe Han,2 Jingchao Sun,2 Ruifeng Liang,1 Shaojian Mo,2,&ast; Yanzhang Tian2,&ast; 1School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Biliary and Pancreatic Surgery, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Shanxi Bethune Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaojian Mo; Yanzhang Tian, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China, Tel +8619834514208 ; +8613903512030, Email 1009184648@qq.com; tyz2030@163.comPurpose: Acute pancreatitis is a common gastrointestinal emergency. Approximately 20% of patients with acute pancreatitis develop organ failure, which is significantly associated with adverse outcomes. This study aimed to establish an early prediction model for persistent organ failure in acute pancreatitis patients using 24-hour admission indicators.Patients and Methods: Clinical data and 24-h laboratory indicators of patients diagnosed with acute pancreatitis from January 1, 2017 to January 1, 2022 in Shanxi Bethune Hospital were collected. Patients from 2017 to 2021 were used as the training cohort to establish the prediction model, and patients from 2021 to 2022 were used as the validation cohort. Univariate logistic regression and LASSO regression were used to establish prediction models. The performance of the model was evaluated using area under the curve (AUC), calibration curves, and decision curve analysis (DCA), and subsequently validated in the validation group.Results: A total of 1166 patients with acute pancreatitis were included, a total of 145 patients suffered from persistent organ failure from 2017 to 2021. Data were initially selected for 100 variables, and after inclusion and exclusion, 46 variables were used for further analysis. Two prediction models were established and nomogram was drawn respectively. After comparison, the prediction values of the two models were similar (The univariate model AUC was 0.867, 95% CI (0.834– 0.9). The LASSO model AUC was 0.864, 95% CI (0.828– 0.895)), and the model established by LASSO regression was more parsimonious. A web calculator was developed using the model established by LASSO.Conclusion: Predictive model including 6 risk indicators can be used to predict the risk of persistent organ failure in patients with acute pancreatitis.Keywords: prediction model, LASSO regression, acute pancreatitis, nomogram, organ failure

Minghao Li,1,2,&ast; Hua Liu,1,3,&ast; Mingyang Xu,1,3 Baiyang Yu,3,4 Minwang Guo,1,3 Xiaorong Wang,1,3 Guomei Shi,1,3 Rujuan Zhou1,3 1Stroke Center, Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of China; 2Department of Vascular Surgery, Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of China; 3Department of Neurology, Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of China; 4Department of Neurology, Taixing Clinical College of Bengbu Medical College, Bengbu, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guomei Shi; Rujuan Zhou, Stroke Center, Taixing People’s Hospital, No. 1 Changzheng Road, Taixing, Jiangsu Province, 225400, People’s Republic of China, Tel +86-15240200702 ; +86-13951158499, Email 15240200702@yzu.edu.cn; zhourujuan123@163.comBackground: The correlation between glial fibrillary acidic protein (GFAP) and symptomatic intracranial hemorrhage (sICH) in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT) treatment remains uncertain. We aimed to assess the association between levels of GFAP in the bloodstream and the occurrence of sICH.Methods: Between June 2019 and May 2023, 142 consecutive AIS patients undergoing EVT at Stroke Center and 35 controls from the Physical Examination Center were retrospectively included. The levels of GFAP in the bloodstream were quantified using enzyme-linked immunosorbent assay prior to endovascular treatment (T1) and 24 h after the procedure (T2). The identification of sICH was based on the Heidelberg Bleeding Classification.Results: Serum GFAP levels at T1 in AIS patients were significantly higher than those in the controls (0.249 [0.150– 0.576] versus 0.065 [0.041– 0.110] ng/mL, p = 0.001), and there was a notably elevation in GFAP levels at T2 compared to T1 (3.813 [1.474, 5.876] versus 0.249 [0.150– 0.576] ng/mL, p = 0.001). Of the 142 AIS patients, 18 (14.5%) had sICH after EVT. Serum GFAP levels at T2 showed significant associations with sICH in both the unadjusted model (OR 1.513, 95% CI 1.269– 1.805, p = 0.001) and multivariable adjusted model (OR 1.518, 95% CI 1.153– 2.000, p = 0.003). Furthermore, the addition of GFAP at T2 to conventional model resulted in a significant enhancement of risk reclassification for sICH (integrated discrimination improvement [IDI] 0.183, 95% CI 0.070– 0.295, p = 0.001).Conclusion: Serum GFAP levels were notably increased in AIS patients 24 h after EVT. Elevated GFAP levels were correlated to an elevated risk of sICH. GFAP could potentially serve as a dependable indicator for sICH in AIS individuals who treated with EVT.Keywords: glial fibrillary acidic protein, stroke, symptomatic intracranial hemorrhage, indicator, endovascular thrombectomy

Dapeng Hu,1,2 Junwen Huang,1 Wenqu Zhao,1 Maosheng Xu,1 Yanyan Ma,1 Zhaoqian Gong,1 Qian Zhang,1 Haijin Zhao1 1Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, NanFang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Department of Emergency Medicine, Dalian Municipal Friendship Hospital, Dalian, Liaoning, 116001, People’s Republic of ChinaCorrespondence: Haijin Zhao, Chronic Airway Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China, Tel/Fax +86-2062787112, Email zhjin@smu.edu.cnPurpose: Identifying prognosis for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is challenging. Eosinophils and platelet are involved in the development of COPD, which may predict adverse events. The objective of this study was to determine the effect of the eosinophil to platelet ratio (EPR) in predicting adverse events in patients with AECOPD who visited the emergency department.Patients and Methods: The records of patients with AECOPD treated at Dalian Municipal Friendship Hospital from January 2018 to December 2020 were retrospectively reviewed. The relationship between the clinical characteristics and EPR, as cut-off value of 0.755, was evaluated.Results: A total of 508 patients with an AECOPD (316 male, 192 female) were included. An optimal AUC cutoff of 0.755 for the EPR segregated the patients into 2 groups with significantly different mortality (25.3% vs 5.5%, P < 0.001). The same mortality risk with lower EPR was observed among the patients with emergency room attendance (35.6% vs 11.1%, P < 0.001). A model including EPR < 0.755, exacerbation history, PaO2 < 60mmHg, PaCO2 > 50 mm Hg, hypoalbuminemia and age ≥ 80 was developed to predict death risk and showed good performance.Conclusion: During severe COPD exacerbation, an EPR < 0.755 preceding therapy can predict worse outcomes in patients with an AECOPD.Keywords: eosinophil, COPD, eosinophil to platelet ratio, emergency department

Xueyu Li,1,&ast; Kaushik Chattopadhyay,2,&ast; Xiaoting Chen,3 Jialin Li,1 Miao Xu,1 Xueqin Chen,4 Li Li1 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Ningbo University, Ningbo, People’s Republic of China; 2Lifespan and Population Health, School of Medicine, University of Nottingham, Nottingham, UK; 3School of Medicine, Ningbo University, Ningbo, People’s Republic of China; 4Department of Traditional Chinese Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Li, Email lilyningbo@163.comAim: The study aimed to investigate the association between physical activity and arterial stiffness in patients with type 2 diabetes mellitus (T2DM) in Ningbo, China.Methods: A cross-sectional study was conducted using the Metabolic Management Center (MMC) dataset of The First Affiliated Hospital of Ningbo University from 1st March 2018 to 28th February 2023. 4444 adults with T2DM were included in the study. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ)-Short and was categorized into high, moderate, and low. Arterial stiffness was defined as brachial-ankle pulse wave velocity (baPWV) ≥ 1800cm/s or common carotid artery intima-media thickness (CCA IMT) ≥ 1mm. Multiple logistic regression analyses were performed to identify the association between physical activity and arterial stiffness.Results: 6.5%, 47.0%, and 46.5% of patients with T2DM had high, moderate, and low physical activity, respectively. 18.8% and 17.5% of patients had arterial stiffness based on baPWV and CCA IMT, respectively. The odds of arterial stiffness (based on baPWV) were lower in patients having moderate to high physical activity (OR 0.82, 95% CI 0.68 to 0.98 and OR 0.58, 95% CI 0.39 to 0.87, respectively). The odds of arterial stiffness (based on CCA IMT) were found to be lower in patients having high physical activity (OR 0.49, 95% CI 0.33 to 0.74).Conclusion: Higher physical activity was found to be associated with lower arterial stiffness in patients with T2DM in Ningbo, China. This was a cross-sectional study, and there is a need to conduct longitudinal studies on this topic.Keywords: type 2 diabetes mellitus, physical activity, arterial stiffness, China

Meng Xu,1,&ast; Ke Che,1,&ast; Cong Wang,2,&ast; Ya-Ru Chen,1 Meng-Yuan Chen,1 Guang-Lei Zhang,1 Hao Yu,3 Hao-Nan Xu,1 Ya-Bao Li,1 Ping Sheng,1 Hao Chen1 1College of Life and Health Sciences, Anhui Science and Technology University, Fengyang, 233100, People’s Republic of China; 2School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, 210094, People’s Republic of China; 3Bozhou University, Bozhou, 236800, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Chen; Ping Sheng, Email chenhao@ahstu.edu.cn; astu100@126.comIntroduction: Cholestasis is a common liver disorder that currently has limited treatment options. Gardenia Iridoid Glucosides (GIG) have been found to possess various physiological activities, such as cholagogic, hypoglycemic, antibacterial, and anti-inflammatory effects. The objective of this study was to investigate the effects of GIG on bile acid enterohepatic circulation and explore the underlying mechanism in cholestatic rats.Methods: In order to identify key pathways associated with cholestasis, we conducted Gene Ontology (GO) Enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. In vivo experiments were then performed on alpha-naphthylisothiocyanate (ANIT)-treated rats to assess the impact of GIG. We measured bile flow and various biomarkers including total bilirubin (TB), total bile acids (TBA), total cholesterol (TC), malondialdehyde (MDA), glutamic-pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), and total superoxide dismutase (T-SOD) in the serum. We also examined the expression levels of bile salt export pump (BSEP), ATP-binding cassette subfamily B member 4 (ABCB4), far-nesoid X receptor (FXR), small heterodimer partner (SHP), cholesterol 7α-hydroxylase (CYP7A1), and sodium taurocholate cotransporting polypeptide (NTCP) in liver tissue. In vitro experiments were conducted on primary hepatocytes to further investigate the mechanism of action of GIG on the expression of SHP, CYP7A1, NTCP, and FXR.Results: Our in vivo experiments demonstrated that GIG significantly increased bile flow and reduced the levels of TB, TBA, TC, MDA, GPT, and GOT, while increasing T-SOD levels in ANIT-treated rats. Addi-tionally, GIG ameliorated liver tissue damage induced by ANIT, upregulated the expression of BSEP and ABCB4, and modulated the protein expression of FXR, SHP, CYP7A1, and NTCP in model rats. In vitro experiments further revealed that GIG inhibited the expression of SHP, CYP7A1, and NTCP by suppressing the expression of FXR.Conclusion: This study provides new insights into the therapeutic potential of GIG for the treatment of cholestasis. GIG demonstrated beneficial effects on bile acid enterohepatic circulation and liver biomarkers in cholestatic rats. The modulation of FXR and its downstream targets may contribute to the mechanism of action of GIG. These findings highlight the potential of GIG as a therapeutic intervention for cholangitis.Keywords: Gardenia Iridoid Glucosides, FXR, SHP, cholestasis

Minglu Xu,1,2,&ast; Lingli Fang,1,2,&ast; Qin Xue,1,2 Xuyang Zhang,1,2 Yao He1,3 1Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Oral Disease and Biomedical Sciences, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yao He, Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, 426 North of Songshi Avenue, Chongqing, 401147, People’s Republic of China, Email yaohe@hospital.cqmu.edu.cnObjective: Oxidative stress is involved in the mechanisms associated with temporomandibular joint (TMJ) diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial oxidative stress marker, but the specific mechanisms of its regulation in the early stages of mandibular condylar cartilage (MCC) degeneration remain unclear. This study aimed to explore the regulatory role of Nrf2 and its related oxidative stress signaling pathway in the early stage of MCC degeneration.Materials and Methods: Overloading force-induced MCC degeneration was performed in wild-type and Nrf2 knockout mice, as well as in mice after treatment with the Nrf2 activator cardamonin. Changes in MCC degeneration and the expression of oxidative stress markers in the corresponding situations were observed.Results: Nrf2 and NADPH oxidase 2 (NOX2) expression were elevated during early MCC degeneration induced by an overloading force. MCC degeneration was aggravated when Nrf2 was knocked out, accompanied by increased NOX2 and superoxide dismutase 2 (SOD2) expression. The MCC degeneration process was alleviated after cardamonin treatment, with activation of the Nrf2 pathway and decreased NOX2 and SOD2 expression.Conclusion: Early MCC degeneration is accompanied by mild oxidative stress progression. Activated Nrf2 and related pathways could alleviate the degeneration of MCC.Keywords: NF-E2-related factor 2, oxidative stress, temporomandibular joint, cartilage, mechanical force

Maimaiti Nuliqiman, Mingyu Xu, Yiming Sun, Jing Cao, Pengjie Chen, Qi Gao, Peifang Xu, Juan Ye Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Peifang Xu; Juan Ye, Tel +86-571-8778-3897, Fax +86-571-8706-8001, Email xpf1900@zju.edu.cn; yejuan@zju.edu.cnAbstract: Artificial Intelligence (AI) has found rapidly growing applications in ophthalmology, achieving robust recognition and classification in most kind of ocular diseases. Ophthalmic surgery is one of the most delicate microsurgery, requiring high fineness and stability of surgeons. The massive demand of the AI assist ophthalmic surgery will constitute an important factor in boosting accelerate precision medicine. In clinical practice, it is instrumental to update and review the considerable evidence of the current AI technologies utilized in the investigation of ophthalmic surgery involved in both the progression and innovation of precision medicine. Bibliographic databases including PubMed and Google Scholar were searched using keywords such as “ophthalmic surgery”, “surgical selection”, “candidate screening”, and “robot-assisted surgery” to find articles about AI technology published from 2018 to 2023. In addition to the Editorials and letters to the editor, all types of approaches are considered. In this paper, we will provide an up-to-date review of artificial intelligence in eye surgery, with a specific focus on its application to candidate screening, surgery selection, postoperative prediction, and real-time intraoperative guidance.Keywords: ophthalmic surgery, AI, machine learning, surgery selection, candidate screening, robot-assisted surgery

Cong Zhou,1 Hui Zhang,1 Maosuo Xu,1 Yajuan Liu,1 Baoyu Yuan,2 Yong Lin,1 Fang Shen1 1Department of Clinical Laboratory, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Clinical Laboratory, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaCorrespondence: Fang Shen; Yong Lin, Department of Clinical Laboratory, Shanghai Fifth People’s Hospital, Fudan University, No. 128, Ruili Road, Minhang District, Shanghai, 200240, People’s Republic of China, Tel +86 18021073261 ; +86 18718168695, Email shenfang5th@aliyun.com; linyong7007@163.comBackground: Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) has recently aroused an extremely severe health challenge and public concern. However, the underlying mechanisms of fitness costs that accompany antibiotic resistance acquisition remain largely unexplored. Here, we report a hv-CRKP-associated fatal infection and reveal a reduction in virulence due to the acquisition of aminoglycoside resistance.Methods: The bacterial identification, antimicrobial susceptibility, hypermucoviscosity, virulence factors, MLST and serotypes were profiled.The clonal homology and plasmid acquisition among hv-CRKP strains were detected by XbaI and S1-PFGE. The virulence potential of the strains was evaluated using Galleria mellonella larvae infection model, serum resistance assay, capsular polysaccharide quantification, and biofilm formation assay. Genomic variations were identified using whole-genome sequencing (WGS).Results: Four K. pneumoniae carbapenemase (KPC)-producing CRKP strains were consecutively isolated from an 86-year-old patient with severe pneumonia. Whole-genome sequencing (WGS) showed that all four hv-CRKP strains belonged to the ST11-KL64 clone. PFGE analysis revealed that the four ST11-KL64 hv-CRKP strains could be grouped into the same PFGE type. Under the pressure of antibiotics, the antimicrobial resistance of the strains increased and the virulence potential decreased. Further sequencing, using the Nanopore platform, was performed on three representative isolates (WYKP586, WYKP589, and WYKP594). Genomic analysis showed that the plasmids of these three strains underwent a large number of breaks and recombination events under antibiotic pressure. We found that as aminoglycoside resistance emerged via acquisition of the rmtB gene, the hypermucoviscosity and virulence of the strains decreased because of internal mutations in the rmpA and rmpA2 genes.Conclusion: This study shows that ST11-KL64 hv-CRKP can further evolve to acquire aminoglycoside resistance accompanied by decreased virulence to adapt to antibiotic pressure in the host.Keywords: hypervirulent carbapenem-resistant Klebsiella pneumoniae, within-host evolution, plasmids, whole-genome sequencing

Wenyan Zhu,1 Tiange Xie,2 Mengru Xu,1 Ruxuan Chen,1 Ting Zhang1 1Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of General Practice, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Ting Zhang; Ruxuan Chen, Email tintin-03@163.com; nandao2006@126.comBackground: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still rampant around the world. Immunocompromised patients are prone to have long-term infection with coronavirus disease 2019 (COVID-19). However, it is difficult to decide on an appropriate treatment for persistent SARS-CoV-2 infection.Case Presentation: We present a case of prolonged SARS-CoV-2 infection in a patient who had undergone B-cell depletion therapy. Chest computed tomography (CT) revealed notable migratory pulmonary infiltrates, and bronchoalveolar lavage fluid was positive for SARS-CoV-2 (day-120). The patient responded well to the combination treatment of antiviral medication, convalescent plasma, and corticosteroid.Conclusion: When chest CT shows migratory pulmonary infiltrates in patients with recent COVID-19, it is necessary to be alert to the possibility of persistent SARS-CoV-2 infection, especially in B-cell-depleted immunocompromised patients. Once the diagnosis is confirmed, repeated antiviral therapy and intravenous convalescent plasma should be considered.Keywords: SARS-CoV-2, migratory pulmonary infiltrates, B-cell depletion, antiviral therapy, convalescent plasma

Mengzhen Xu,1 Jin Liu,1 Hui Zhang,2 Ruiting Li,3 Junni Wei1 1School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Pain Management, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Pain Management, Taiyuan Central Hospital, Taiyuan, People’s Republic of ChinaCorrespondence: Hui Zhang, Department of Pain Management, First Hospital of Shanxi Medical University, Taiyuan, 030000, People’s Republic of China, Tel +86 351 13934043126, Fax + 0351-4639114, Email hzhang1974@163.comPurpose: To investigate the clinical outcome of trigeminal ganglion electrical stimulation for the treatment of trigeminal postherpetic neuralgia (TPHN).Patients and Methods: A retrospective analysis of clinical data was performed on six patients who suffered from severe postherpetic neuralgia involving the trigeminal nerve maxillary and mandibular branch. They were admitted under the Pain Management Department of the First Hospital of Shanxi Medical University from July 2022 to February 2023 and underwent trigeminal ganglion electrical stimulation therapy. Visual analogue scale (VAS) scores, pregabalin dosage, pittsburgh sleep quality index (PSQI), self-rating anxiety scale (SAS), and self-rating depression scale (SDS) were recorded before treatment, as well as after treatment at 1, 4, 8, 12, and 24-week. Adverse reactions related to the treatment were also documented.Results: After trigeminal ganglion electrical stimulation therapy, the VAS scores, PSQI scores, anxiety scores, depression scores, and pregabalin dosage of six patients showed significant reductions at 1, 4, 8, 12, and 24 weeks. (P < 0.05). No serious adverse reactions occurred in any of the patients.Conclusion: Trigeminal ganglion electrical stimulation effectively relieved postherpetic neuralgia in the distribution areas of the trigeminal nerve 2 and 3 branches, reduced the dosage of analgesics, improved the quality of sleep, and alleviated anxiety and depression symptoms in patients. Our data suggested that It was a safe and effective clinical.Keywords: trigeminal postherpetic neuralgia, trigeminal ganglion stimulation, therapy, efficacy

Jiong Zhou,&ast; Yang Yang,&ast; Mengjun Xu, Zhongfa Lyu, Xianjie Wu Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xianjie Wu, Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, People’s Republic of China, Email wuxianjie@zju.edu.cnObjective: To evaluate and explore the efficacy, safety, and pharmacoeconomics of three common strategies for pediatric alopecia areata.Methods: Chinese pediatric alopecia areata patients meeting the criteria were included and divided into three groups based on the received treatments. The efficacy, adverse events and pharmacoeconomics of these treatments were retrospectively analyzed.Results: Twenty-four pediatric AA patients were recruited in this study. 100% (12/12) of patients from the traditional group achieved SALT100. In the tofacitinib group, 40.0% (2/5) of patients achieved SALT50. 20.0% (1/5) of patients achieved SALT75 and 40.0% (2/5) of patients achieved SALT100. In the MN group, 42.86% (3/7) of patients were non-responders. 14.28 (1/7) of patients achieved SALT75 and 42.86% (3/7) of patients achieved SALT100. The adverse effects (AEs) were mild in all three groups, and none of the patients discontinued the treatments due to the AEs. Comparing the other two groups, the MN treatment would be more time-intensive and more expensive.Conclusion: For newly diagnosed or naive pediatric patients, the traditional treatment was the first-line approach. For long-duration, severe and refractory patients, tofacitinib and microneedling can be alternative options.Keywords: pediatric, alopecia areata, tofacitinib, microneedling, efficacy

Hong Yang, Yiping Li, Mengjiao Xu, Ying Hu, Fengshun Yuan, Lunhao Liu, Ling Li, Dan Yuan, Li Ye, Chang Zhou, Yan Zhang, Ling Su, Shu Liang Center for AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention, Chengdu, People’s Republic of ChinaCorrespondence: Shu Liang; Ling Su, Email liangshu523@163.com; sl7512@163.comBackground: Sichuan Province has gradually become a hot-spot for HIV/AIDS. Little is known about the HIV-1 incidence and prevalence among four sub-groups since 2015. Meanwhile, the distributions of hot-spot areas related to recent infection cases that indicate current transmission among the four subgroups are also rare.Objective: The main purpose of this study was to assess the HIV-1 prevalence and incidence and to visualize the distributions of hot-spot areas of current transmission among four subgroups (people who inject drugs, male STD clinic attendees, female sex workers and men who had sex with men) during the surveillance period in Sichuan province between 2016 and 2022.Results: Of the 267,617 individuals, 2158 HIV-positive samples were tested with Lag-Avidity EIA, among which 493 samples were identified as recent infections. Among people who inject drugs (PWID), both HIV-1 prevalence (from 1.41% to 0.34%) and incidence (from 0.03% to 0.140%) showed a significant decreasing trend. Among men who had sex with men (MSM), female sex workers (FSWs), and male STD clinic attendees, HIV-1 prevalence indicated significant decreasing trends, whereas HIV-1 incidence showed no significant changes. Spatial analysis demonstrated the formation of hot-spots and clusters of current transmissions sharing regional differences, mainly concentrated in the southeast, and most of these were consecutive hot-spots.Conclusion: The prevention and control were efficacious and persistent. However, among the other three subgroups, there is a need for a regional cooperative in prevention and control approaches and collaborative research in many aspects.Keywords: human immunodeficiency virus, recent infection, hot spots, people who inject drugs, PWID, male STD clinic attendees, mSTD, female sex workers, FSWs

Ying Lan,1 Nan Yang,2 Yirong Wang,1 Yan Yang,1 Min Xu,1 Qin He1 1Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, the Third People’s Hospital of Chengdu, Chengdu, Sichuan, 610031, People’s Republic of China; 2West China School of Pharmacy, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Ying Lan, Email lanying0212@126.comPurpose: Tiotropium/olodaterol (TIO/OLO) fixed-dose combination (FDC) can improve lung function and quality of life for patients with chronic obstructive pulmonary disease (COPD), and is not inferior to other LAMA/LABAs. The aim of this study was to assess the cost-effectiveness of TIO/OLO FDC in patients with moderate to very severe COPD in China.Methods: A Markov model was developed to estimate the cost-effectiveness of TIO/OLO FDC versus TIO in the treatment of COPD from Chinese health system perspective. Four health states were based on 2021 Global Initiative for Chronic Obstructive Lung Disease (GOLD 2021), which included moderate (GOLD II, 50% ≤ FEV1 ≤ 80% of predicted), severe (GOLD III, 30% ≤ FEV1 ≤ 50% of predicted) and very severe (GOLD IV, FEV1 > 30% of predicted) COPD and death. The model simulated in cycles yearly. The indicators of total costs, number of COPD exacerbations, life years (LYs) and quality-adjusted life-years (QALYs) were used as the model output. Costs and outcomes were discounted at a 5% annual rate. A cost-effectiveness analysis was conducted over a 10-year time horizon. The threshold of incremental total cost per unit effectiveness gained (ICER) was 1.5 times of GDP per capita. Uncertainty was assessed by one-way and probabilistic sensitivity analysis.Results: TIO/OLO was 0.007 QALYs more than TIO but 0.012 LYs lower, which increased the total cost by &dollar;2268.17 per patient, but the total exacerbations number was less. Incremental cost effectiveness analysis had shown that the ICER exceeded the willingness to pay threshold. Results were robust under most parameter variation, except the parameters of total drug cost of TIO/OLO FDC in univariate sensitivity analyses.Conclusion: Although TIO/OLO FDC could reduce the exacerbation risk, it was not cost-effective, and needed to be repriced.Keywords: tiotropium, olodaterol, cost-effectiveness, chronic obstructive pulmonary disease, COPD, Markov

Xinlin Li,1,2,&ast; Baojuan Yang,3,4,&ast; Mengfei Xu,1,2 Fangyi Li,3,4 Zhaoli Geng,1,2 Weiqiang Cui,3,4 Xingfu Sun,3,4 Yanle Li,3,4 Yi Liu1,2 1Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Shandong Key Laboratory of Oral Tissue Regeneration, Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, 250012, People’s Republic of China; 3Key Laboratory of High Efficiency and Clean Mechanical Manufacture, Ministry of Education, School of Mechanical Engineering, Shandong University, Jinan, 250061, People’s Republic of China; 4National Demonstration Center for Experimental Mechanical Engineering Education, Shandong University, Jinan, 250061, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Liu, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, People’s Republic of China, Tel +86-531-88381630, Email yiliu@sdu.edu.cn Yanle Li, Key Laboratory of High Efficiency and Clean Mechanical Manufacture, Ministry of Education, Shandong University School of Mechanical Engineering, No. 17923, Jingshi Road, Jinan, 250061, People’s Republic of China, Tel +86-531-88392208, Email yanle.li@sdu.edu.cnIntroduction: The lack of osteoinductive, angiogenic and antimicrobial properties of hydroxyapatite coatings (HA) on titanium surfaces severely limits their use in orthopedic and dental implants. Therefore, we doped SiO2, Gd2O3 and CeO2 nanoparticles into HA to fabricate a HASiGdCe coating with a combination of decent antibacterial, angiogenic and osteogenic properties by the plasma spraying technique.Methods: The HASiGdCe coating was analyzed by SEM (EDS), surface roughness tests, contact angle tests, XRD, FTIR spectroscopy, tensile tests and electrochemical dynamic polarization tests. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAO-1) were used as representative bacteria to verify the antibacterial properties of the HASiGdCe coating. We evaluated the cytocompatibility and in vitro osteoinductivity of the HASiGdCe coating by investigating its effect on the cell viability and osteogenic differentiation of MC3T3-E1 cells. We assessed the in vitro angiogenic activity of the HASiGdCe coating by migration assay, tube formation assay, and RT‒PCR analysis of angiogenic genes in HUVECs. Finally, we used infected animal femur models to investigate the biosafety, antimicrobial and osteointegration properties of the HASiGdCe coating in vivo.Results: Through various characterization experiments, we demonstrated that the HASiGdCe coating has suitable microscopic morphology, physical phase characteristics, bonding strength and bioactivity to meet the coating criteria for orthopedic implants. The HASiGdCe coating can release Gd3+ and Ce4+, showing strong antibacterial properties against MRSA and PAO-1. The HASiGdCe coating has been shown to have superior osteogenic and angiogenic properties compared to the HA coating in in vitro cellular experiments. Animal implantation experiments have shown that the HASiGdCe coating also has excellent biosafety, antimicrobial and osteogenic properties in vivo.Conclusion: The HASiGdCe coating confers excellent antibacterial, angiogenic and osteogenic properties on titanium implants, which can effectively enhance implant osseointegration and prevent bacterial infections, and it accordingly has promising applications in the treatment of bone defects related to orthopedic and dental sciences.Graphical Abstract: Keywords: hydroxyapatite coatings, SiO2, Gd2O3, CeO2, osseointegration, antibacterial

Xu M, Fu Y, Fang Y, et al. Infect Drug Resist. 2019;12:641–653. Page 647, Molecular characteristics of the K. pneumoniae isolates, first paragraph, right column, second sentence from the bottom, the text “The PFGE results showed that the homology of 44 isolates was diverse (Figure 3)” should read “The PFGE results showed that the homology of 44 isolates was diverse (Figure 4)”. Page 648, left column, last sentence, the text “In general, ST11 KPC-2-producing hvKP strains harbored more antibioticresistant genes and less virulence factors when compared with the non-ST11 KPC-2-producing hvKP (Figure 5)” should read “In general, ST11 KPC-2-producing hvKP strains harbored more antibioticresistant genes and less virulence factors when compared with the non-ST11 KPC-2-producing hvKP (Figure 6)”. Page 648, right column, first sentence, the text “Among the 15 KPC-2-producing hvKP strains, 4 strains (KP35, KP37, KP43, and KP44) shared >75% similarity and classified into one cluster (Figure 3), while the remaining 11 strains exhibited distinct genetic relationship” should read “Among the 15 KPC-2-producing hvKP strains, 4 strains (KP35, KP37, KP43, and KP44) shared >75% similarity and classified into one cluster (Figure 4), while the remaining 11 strains exhibited distinct genetic relationship”. Page 649, left column, second paragraph, first sentence, the text “Consistent with the epidemiology trend of K. pneumoniae meningitis in some Asian countries especially in Taiwan,3,4” should read “Consistent with the epidemiology trend of K. pneumoniae meningitis in Taiwan,3,4”. The authors apologize for these errors.

Ruyan Jie,&ast; Jing Qian,&ast; Ying Tang,&ast; Yutong Li, Murong Xu, Xiaotong Zhao, Mingwei Chen Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaotong Zhao; Mingwei Chen, Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, 230032, People’s Republic of China, Tel +86-551-2923631, Fax +86-551-2922160, Email zxt522154846@163.com; chmw1@163.comPurpose: To study the correlations of miR-222-3p expression in the peripheral blood and wound marginal tissues of type 2 diabetes mellitus (T2DM) patients with the onset of diabetic foot ulcer (DFU), as well as explore the clinical value possessed by miR-222-3p in the diagnosis and treatment outcomes of DFU.Methods: The study included 70 T2DM patients who did not suffer foot ulcers (T2DM group), 146 T2DM patients who suffered foot ulcers (DFU group), as well as 70 normal controls (NC group). Quantitative real-time PCR determined the MiR-222-3p relative expression. Clinical features and risk factors regarding DFU were assessed. Multiple stepwise logistic regression analysis assisted in confirming whether miR-222-3p expression could serve for independently predicting the risk factors for DFU. ROC curve analysis evaluated the diagnostic value exhibited by miR-222-3p level against DFU.Results: T2DM group exhibited an obviously higher MiR-222-3p expression relative to NC group [1.98 (0.98, 3.62) vs 0.92 (0.61, 1.87)] (P < 0.01), but DFU group exhibited an obviously higher miR-222-3p expression relative to T2DM group [5.61 (1.98, 10.24) vs 1.98 (0.98, 3.62)] (P < 0.01). Besides, miR-222-3p expression presented a negative correlation with DFU healing rate (P < 0.05). According to Kaplan–Meier survival curve analysis, the group with high miR-222-3p expression showed higher unhealed DFU cumulative rate relative to the group with low expression (log-rank, P = 0.011, 0.001, respectively). Multivariate logistic regression analysis confirmed that high miR-222-3p expressions could independently predict DFU risk (OR=3.85, 95% CI 1.18~12.37, P = 0.008). According to the ROC curve analysis, the AUC of miR-222-3p specific to DFU diagnosis reached 0.803, with the best sensitivity of 95.93% and best specificity of 96.27%.Conclusion: The increased expression of miR-222-3p in the peripheral blood of T2DM patients is closely related to the occurrence of DFU. MiR-222-3p is a biomarker with potential clinical value in diagnosing and evaluating the prognosis of DFU.Keywords: miR-222-3p, diabetic foot ulcer, type 2 diabetes mellitus, microRNA, biomarker

Yuxin Tan,1 Xiuyun Lin,1,2 Hui Chen,1 Min Xu,1 Yingying Tang,1 Pengfei Gao,1 Wei Ren,1 Di Zhang1 1Faculty of Psychology, Beijing Normal University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Applied Experimental Psychology, Faculty of Psychology, Beijing Normal University, Beijing, People’s Republic of ChinaCorrespondence: Xiuyun Lin, Faculty of Psychology, Beijing Normal University, Beijing, 100875, People’s Republic of China, Email linxy@bnu.edu.cnIntroduction: During emergencies, individuals and communities often react in a variety of ways, including panic response. However, the study of panic response is limited due to narrow assessment tools that measure only one or two dimensions of human response (eg, physiology, cognition, emotion, and behavior). To address this limitation and to explore the risk and protective factors of panic response during the global spread of the Coronavirus Disease 2019 (COVID-19), the current study developed and evaluated the Panic Response Scale (PRS).Methods: Four samples were recruited for the following purposes: interview analysis (n = 26); item analysis and exploratory factor analysis (n = 604); confirmatory factor analysis and reliability analysis (n = 603); and retest reliability, validity analysis, and regression analysis (n = 349).Results: The PRS consists of 21 items with four subscales: Physical Discomfort, Anxious Fluster, Sensitive Depression, and Excessive Prevention. Each of these subscales demonstrated good internal consistency (rs > 0.73), test-retest reliability (rs > 0.77), criterion validity (r = 0.69, p < 0.01), and convergent validity (rs = 0.31– 0.65, p < 0.01). Regression analysis revealed significant predicting effects of COVID-19 knowledge and neuroticism on panic response. Additionally, cognitive reappraisal moderated the association between neuroticism and panic response.Discussion: Following a traumatic event, the PRS offers a potential tool for identifying individuals in need of mental health services. Moreover, during the COVID-19 pandemic, knowledge and neuroticism served as risk factors for heightened panic response, while cognitive reappraisal served as a protective factor for coping with panic response.Keywords: COVID-19, panic response, knowledge, neuroticism, cognitive reappraisal

Min Xu,1,&ast; Ting Liu,2,&ast; Menghua Ye,1 Xiaoxue Tan,1 Qiuhua Sun2 1The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2The School of Nursing, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiuhua Sun, Zhejiang Chinese Medical University, The School of Nursing, 548 Binwen Road, Binjiang District, Hangzhou City, Zhejiang Province, People’s Republic of China, Email sunqiuhua@zcmu.edu.cnBackground: Aplastic anemia is characterized by anemia, hemorrhage and infection, and is accompanied by a variety of complications and psychological burden. Therefore, the quality of life of AA patients is not optimistic. Our team is committed to developing an assessment tool for the quality of life of AA patients, and adopting an iterative strategy of cognitive interview and expert consultation to solve the challenges encountered in item revision.Purpose: We aim to use the strategy of cognitive interview and expert consultation to inform revision of the QLS-AA into a user-friendly tool with unambiguous items and improve the content validity of the scale.Methods: We used an iterative strategy of cognitive interview and expert consultation. Two rounds of cognitive interview were conducted to identify problems with item comprehension, recall and other cognitive processes. As well as, a multi-disciplinary group of expert consultation was consulted to review the rationality of item revisions.Results: In the first round of cognitive interview, 16 participants responded to 107 items. Among them, the most common problems were “clarification” and “item duplication”. Based on the results of the first round of interview, an expert consultation was organized. A total of 16 amendments were put forward by the expert and 14 were adopted. In the second round of cognitive interviews, A total of 5 participants were included and 64 items were evaluated. Two items were suggested to be revised, and the remaining items were accurately understood and recognized by all participants.Couclusion: This study highlights the key issues to consider when incorporating patient perspectives into quality measurement. The revision of QLS-AA through the strategy of cognitive interview and expert consultation may provide valuable insights into the measurement of quality of life in aplastic patients.Trial Registration Number: ChiCTR2100047575.Keywords: cognitive interview, expert consultation, aplastic anemia, quality of life

Mengjun Xu, Jiong Zhou, Jianliang Yan, Jianyou Wang Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Jianyou Wang, Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, People’s Republic of China, Email 2101087@zju.edu.cnAbstract: Lipoid proteinosis (LP) is a rare autosomal recessive disorder caused by mutations in extracellular matrix protein 1 (ECM1), a glycoprotein expressed in skin. Whole-exome sequencing (WES) was used to investigate two Chinese siblings with suggestive clinical features of LP. They shared one known (c.960G>A) and one novel (c.1081G>T) pathogenic variant in ECM1 gene, inherited from their unaffected parents. The novel mutation (c.1081G>T) led to a termination codon at position 361 and caused nonsense-mediated mRNA decay and lost the function. Our finding expands the genetic etiology spectrum of LP.Keywords: lipoid proteinosis, mutation, extracellular matrix protein 1, ECM1

Dong Xi,1 Mengying Xu,1 Meiwen Han,1 Qianting Guan,1 Qinghao Guo,1 Fangfei Yan,1 Junxia Yao,2 Qin Ning1 1Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of ChinaCorrespondence: Junxia Yao, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Tel +86-18502711578, Email yaojunxia@163.com Qin Ning, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Tel/Fax +86-27-83665959, Email qning@vip.sina.comPurpose: A retrospective analysis of hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE) to identify risk factors was conducted, and a novel predictive nomogram model was constructed.Patients and Methods: A total of 346 HCC patients who underwent TACE as initial treatment were retrospectively included, of which 208 were randomly allocated to the derivation cohort and 138 were allocated to the validation cohort. Progression-free survival (PFS) was used as the follow-up endpoint according to mRECIST. Kaplan‒Meier analysis and the Cox regression model screened out some indicators associated with short-term prognosis, and R language was further used to construct a nomogram model. The nomogram was compared with the classical BCLC staging system.Results: The independent predictors affecting PFS in HCC patients undergoing TACE included the following: 1. Baseline indicators: age (P=0.013), albumin-bilirubin (ALBI) grade (grade 2 vs grade 1, P=0.029; grade 3 vs grade 1, P< 0.001), and portal vein tumour thrombus (PVTT, P< 0.001); 2. Indicators at the 1-month follow-up: Neutrophil To Lymphocyte Ratio (NLR, P=0.032) and changes in alpha-fetoprotein (AFP, P< 0.05) and des-γ-carboxy prothrombin (DCP, P< 0.001); and 3. Cumulative treatment numbers of TACE in 6 months (P=0.007). In the derivation cohort, the calibration curve of the nomogram showed a high consistency between the predicted and actual PFS probability, and the nomogram outperformed the BCLC staging system (P=0.004). This result was also confirmed in the validation cohort (P=0.012).Conclusion: The constructed nomogram was suggested to have good predictive efficacy and could be used as a complementary assessment to predict the survival and prognosis of HCC patients treated with TACE.Keywords: primary liver cancer, transarterial chemoembolization, progression-free survival, modified response evaluation criteria in solid tumours, prognosis, nomogram

Yiting Zhang, Meiqi Gan, Yuqin He, Tingting Liu, Mei Xu The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing Municipality Division, National Clinical Research Center for Ocular Diseases, Chongqing, People’s Republic of ChinaCorrespondence: Mei Xu, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing, 400016, People’s Republic of China, Email meixu1666@163.comPurpose: Primary Sjögren’s syndrome (pSS), a disease that is associated with a high prevalence of psychological disorders, has become increasingly important. Interactions between the gut microbiota and ocular conditions have been identified in pSS. As mental intervention is frequently needed, this study aims to investigate the relationship between anxiety disorders and the gut microbiome in patients with pSS-mediated dry eye.Methods: Demographics and self-administered questionnaires were obtained. Faecal samples were evaluated using 16S ribosomal RNA gene sequencing.Results: The Hospital Anxiety and Depression Scale (HADS-A) cut-off point of ≥ 8 points showed a sensitivity and specificity of 76.5% and 80.0%, respectively. In all participants, we found that the prevalence of anxiety disorder was 30.4%. Dry eye discomfort could promote an anxious state, and conversely, anxiety could threaten tear film and increase the risk of pSS activity. There was a certain correlation between anxiety disorder and gut dysbiosis. Prevotella was associated with dry eye severity (p < 0.001). Bacteroidetes (p =0.046) and Odoribacter (p =0.001) were correlated with pSS activity.Conclusion: There is a bidirectional relationship between anxiety disorder and the gut microbiota in pSS-mediated dry eye. Alterations in certain classes of gut microbiota are associated with pSS activity and dry eye severity. Main gut microbiota alterations that have a facilitating impact on anxiety are emerging in pSS-mediated dry eye. Future studies are needed to explore specific therapeutic targets for improving mental health in pSS-mediated dry eye by microbiota intervention.Keywords: primary Sjögren’s syndrome, dry eye, anxiety, gut microbiota

Jinjie Yu,1,2,* Mengwen Liu,3,* Xiaokaiti Mijiti,4,* Haican Liu,2,* Quan Wang,4 Chunjie Yin,3 Aiketaguli Anwaierjiang,5 Miao Xu,4 Machao Li,2 Lele Deng,2,6 Hui Xiao,3 Xiuqin Zhao,2 Kanglin Wan,2 Guilian Li,2 Xiuqin Yuan1 1School of Public Health, University of South China, Hengyang, 421001, People’s Republic of China; 2State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China; 3School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 4The Eighth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830049, People’s Republic of China; 5College of Xinjiang Uyghur Medicine, Hetian, 848000, People’s Republic of China; 6National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guilian Li, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China, Email liguilian@icdc.cn Xiuqin Yuan, School of Public Health, University of South China, Hengyang, 421001, People’s Republic of China, Email wtjysh@126.comBackground: The aim of the present study was to investigate the association between vitamin D receptor (VDR) gene polymorphism and tuberculosis susceptibility, as well as the potential interaction of host genetic factors with the heterogeneity of Mycobacterium tuberculosis in the population from Xinjiang, China.Methods: From January 2019 to January 2020, we enrolled 221 tuberculosis patients as the case group and 363 staff with no clinical symptoms as the control group from four designated tuberculosis hospitals in southern Xinjiang, China. The polymorphisms of Fok I, Taq I, Apa I, Bsm I, rs3847987 and rs739837 in the VDR were detected by sequencing. M. tuberculosis isolates were collected from the case group and identified as Beijing or non-Beijing lineage by multiplex PCR. Propensity score (PS), univariate analysis and multivariable logistic regression models were used to perform the analysis.Results: Our results showed that the allele and genotype frequencies of Fok I, Taq I, Apa I, Bsm I, rs3847987 and rs739837 in VDR were not correlated with tuberculosis susceptibility or lineages of M. tuberculosis. Two out of six loci of the VDR gene formed one haplotype block, and none of the haplotypes was found to correlate with tuberculosis susceptibility or lineages of M. tuberculosis infected.Conclusion: Polymorphisms in the VDR gene may not indicate susceptibility to tuberculosis. There was also no evidence on the interaction between the VDR gene of host and the lineages of M. tuberculosis in the population from Xinjiang, China. Further studies are nonetheless required to prove our conclusions.Keywords: vitamin D receptor, VDR, polymorphism, tuberculosis, Mycobacterium tuberculosis, Beijing lineage

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

Pei Guo,1,&ast; Mingmin Xu,2,&ast; Jiongwei Pan,2 Jiayi Lin,2 Tiannuo Hu,2 Yulong Wei,3 Yue Chen,3 Yu Guo2,4 1School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu City, People’s Republic of China; 2School of Traditional Chinese Medicine, Jinan University, Guangzhou City, People’s Republic of China; 3School of Acupuncture–Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing City, People’s Republic of China; 4Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University, Guangzhou City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Guo, School of Traditional Chinese Medicine, Jinan University, No. 601 Huangpu Road West, Tianhe District, Guangzhou City, People’s Republic of China, Email guoy046@jnu.edu.cnBackground: Many studies have now investigated the effects of common clinical acupoint stimulation-related therapies (ASRTs) following the meridian theory of traditional Chinese medicine for the management of insomnia. However, ASRT choice is currently based on personal clinical experience or patient preference. This study will review the common ASRTs reported in clinical trials and analyze their efficacy and safety for managing insomnia with or without co-morbidities.Methods: English and Chinese databases will be thoroughly searched, and other potentially eligible trials will be obtained by reviewing reference lists of identified studies and previous reviews. Only randomized controlled trials (RCTs) of common clinical ASRTs to manage insomnia published in peer-reviewed journals will be considered. Sleep quality questionnaires or indices will be considered as the main outcome, while the secondary outcomes will include sleep parameters, daytime dysfunction, quality of life, and adverse effects. Two reviewers will independently investigate eligible RCTs, extract information, analyze their methodological quality, and employ Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria to evaluate the strength of the evidence. The treatment impact of various ASRTs will be calculated using meta-analysis techniques, and the degree of study heterogeneity will be assessed using Cochrane’s Q and I-squared statistics. Subgroup and sensitivity analyses will be used to evaluate the reliability of the results.Results: Our systematic review and meta-analysis will present up-to-date evidence on: 1) which common clinical ASRTs are beneficial for the management of insomnia; and 2) whether the effects of common clinical ASRTs on insomnia vary depending on clinical, participant, and treatment characteristics.Conclusion: The results of our review should help decision-makers make educated choices regarding evidence-based non-pharmacological management options for insomnia.Study Registration: The International Platform of Registered Systematic Review and Meta-analysis (INPLASY), record INPLASY2021120137.Keywords: acupoint stimulation-related therapies, insomnia, systematic review and meta-analysis, randomized controlled trial, protocol

Chunjie Yin,1,&ast; Xiaokaiti Mijiti,2,&ast; Haican Liu,3,&ast; Quan Wang,2 Bin Cao,3,4 Aiketaguli Anwaierjiang,5 Machao Li,3 Mengwen Liu,1 Yi Jiang,3 Miao Xu,2 Kanglin Wan,3 Xiuqin Zhao,3 Guilian Li,3 Hui Xiao1 1School of Public Health, Xinjiang Medical University, Urumqi, People’s Republic of China; 2The Eighth Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 3State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 4School of Public Health, University of South China, Hengyang, People’s Republic of China; 5College of Xinjiang Uyghur Medicine, Hetian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guilian Li; Hui Xiao, Email liguilian@icdc.cn; xh20108262@sina.comBackground: In the last decades, the molecular epidemiological investigation of Mycobacterium tuberculosis has significantly increased our understanding of tuberculosis epidemiology. However, few such studies have been done in southern Xinjiang, China. We aimed to clarify the molecular epidemic characteristics and their association with drug resistance in the M. tuberculosis isolates circulating in this area.Methods: A total of 347 isolates obtained from southern Xinjiang, China between Sep, 2017 and Sep, 2019 were included to characterize using a 15-locus MIRU-VNTR (VNTR-15China) typing and spoligotyping, and test for drug susceptibility profiles. Then the lineages and clustering of the isolates were analyzed, as well as their association with drug resistance.Results: Spoligotyping results showed that 60 spoligotype international types (SITs) containing 35 predefined SITs and 25 Orphan or New patterns, and 12 definite genotypes were found, and the top three prevalent genotypes were Beijing genotype (207, 59.7%), followed by CAS1-Delhi (46, 13.6%), and Ural-2 (30, 8.6%). The prevalence of Beijing genotype infection in the younger age group (≤ 30) was more frequent than the two older groups (30~59 and ≥ 60 years old, both P values < 0.05). The Beijing genotype showed significantly higher prevalence of resistance to isoniazid, rifampicin, ethambutol, multi-drug or at least one drug than the non-Beijing genotype (All P values ≤ 0.05). The estimated proportion of tuberculosis cases due to transmission was 18.4% according to the cluster rate acquired by VNTR-15China typing, and the Beijing genotype was the risk factor for the clustering (OR 9.15, 95% CI: 4.18– 20.05).Conclusion: Our data demonstrated that the Beijing genotype is the dominant lineage, associated with drug resistance, and was more likely to infect young people and contributed to tuberculosis transmission in southern Xinjiang, China. These findings will contribute to a better understanding of tuberculosis epidemiology in this area.Keywords: MIRU-VNTR, spoligotyping, Beijing genotype, drug resistance, genetic diversity, Mycobacterium tuberculosis

Sirou Han,1,2 Min Xu,1 Jiahui Lao,3 Zhanming Liang4 1Hospital Administration Department, The Second Affiliated Hospital of Shandong First Medical University, Taian, People’s Republic of China; 2School of Public Health, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, People’s Republic of China; 3Center for Big Data Research in Health and Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, People’s Republic of China; 4College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD, AustraliaCorrespondence: Min Xu, Hospital Administration Department, The Second Affiliated Hospital of Shandong First Medical University, No. 366 Taishan Street, Taian, Shandong Province, 271000, People’s Republic of China, Tel +86-137-9112-0603, Email 13791120603@139.com Zhanming Liang, College of Public Health, Medical and Veterinary Sciences, James Cook University, JCU Townsville Campus, Douglas, Building 41, Room 217, Townsville, QLD, 4870, Australia, Tel +61-7-4781-5040, Email zhanming.liang@jcu.edu.auPurpose: Patient feedback plays a significant role in hospital service improvement. However, how to encourage patient feedback that can guide hospital service improvement is still being explored. By examining patient feedback data related to a tertiary hospital in China that was collected from the “ 12345” Government Service Convenience Hotline (GSCH), the paper discusses the learnings from GSCH in encouraging patient feedback and how quality improvement initiatives have effected the number and types of complaints made by patients and their families via GSCH.Methods: The study retrospectively collected and analyzed complaints on a Tertiary General University-affiliated hospital made via GSCH between 2016 and 2020. Patient care process-related complaints were coded using the health care complaint analysis tool (HCAT) and other complaint data were categorized based on the nature of the complaints. The autoregressive integrated moving average (ARIMA) models and mosaic plots were used to observe complaints trends and different complaint variables, respectively. The relationship between various quality improvement initiatives introduced since 2018 and patient complaints was also tested.Results: Close to 67% (n=2688) of calls made to the GSCH hotlines about the hospital were classified as a complaint including 60.6% vs 39.4% related to patient care process and nonpatient care process, respectively. For patient care process-related complaints, specifically against departments and personnel, 57.72% (n=961) were on clinical departments and 55.87% (n=471) were on doctors. Comparing the proportion of the complaint data in different categories in the two-year period of 2017– 2018 and 2019– 2020, an increase in management problems (47.73% vs 58.50%, P< 0.001) and decrease in relationship problems (33.65% vs 25.69%, P=0.002) were recorded.Conclusion: A unified, transparent, and impartial GSCH platform greatly encourages feedback from patients and families. Feedbacks provide evidence to guide health care organizations in improving the overall experience of patients and the quality of services that they provide.Keywords: patient feedback, medical service, hospital management, hotline, quality improvement, hospital services

Guomei Shi,1,2,&ast; Dongdong Ke,2,3,&ast; Pengyu Gong,4,5 Peng Yu,2,6 Junshan Zhou,5 Meng Wang,5 Xiaohao Zhang,5 Xiaorong Wang,1,2 Minwang Guo,1,2 Mingyang Xu,1,2 Rujuan Zhou1,2 1Department of Neurology, the Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of China; 2Stroke Center, the Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of China; 3Department of Rehabilitation, the Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of China; 4Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 5Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 6Department of Radiology, the Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rujuan Zhou, Tel +86-13951158499, Email zhourujuan123@163.comBackground: White matter hyperintensity (WMH) is associated with risk of acute ischemic stroke (AIS) and poor outcomes after AIS. The purpose of this prospective study was to evaluate the association between serum YKL-40 levels and WMH burden in patients with AIS.Methods: From February 2020 to March 2021, a total of 672 consecutive AIS patients with magnetic resonance imaging data were prospectively recruited form two centers. Serum YKL-40 levels were quantified using enzyme-linked immunosorbent assay. The burden of WMH was semiquantitatively measured by the Fazekas visual grading scale. According to severity of overall WMH, patients were dichotomized into none–mild WMH group (Fazekas score 0– 2) or moderate–severe WMH group (Fazekas score 3– 6). Besides, based on severity of periventricular WMH (PV-WMH) and deep WMH (D-WMH), patients were categorized as none–mild (Fazekas score 0– 1) or moderate–severe (Fazekas score 2– 3).Results: Among the 672 patients, 335 (49.9%) participants were identified with moderate–severe overall WMH, 326 (48.5%) with moderate–severe PV-WMH and 262 (39.0%) with moderate–severe D-WMH. Compared with the first quartile of serum YKL-40, the adjusted odds ratio (OR) of the fourth quartile for moderate–severe PV-WMH was 2.473 (95% confidence interval [CI] 1.316– 4.646; P=0.005). No significant association was observed between YKL-40 and overall WMH (OR 0.762; 95% CI 0.434– 1.336; P=0.343) or D-WMH (OR 0.695; 95% CI 0.413– 1.171; P=0.172).Conclusion: Our results suggested that higher YKL-40 levels appeared to be associated with PV-WMH, but not with overall WMH or D-WMH in patients with AIS.Keywords: acute ischemic stroke, YKL-40, white matter hyperintensities, biomarkers

Mengxin Xu,1 Changrui Qian,2 Huaiyu Jia,1 Luozhu Feng,3 Shiyi Shi,1 Ying Zhang,3 Lingbo Wang,1 Jianming Cao,3 Tieli Zhou,1 Cui Zhou1 1Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, People’s Republic of China; 2School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Medical Laboratory Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Tieli Zhou; Cui Zhou, Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University; Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, 325035, People’s Republic of China, Tel +86 0577 8668 9885, Email wyztli@163.com; ZHOUCUI0826@163.comIntroduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a serious threat to human public health. Ceftazidime–avibactam (CZA) is currently one of the few effective antibiotics for carbapenem-resistant Enterobacteriaceae (CRE).Methods and Results: Here, we analyzed two longitudinal Klebsiella pneumoniae clinical isolates (FK8578, FK8695) that were isolated from an ICU patient during antimicrobial treatment. Broth microdilution method, whole-genome sequencing (WGS) and comparative genomic analysis were used to elucidate the dynamics and mechanisms of antibiotic resistance. String test, quantification of capsule, biofilm inhibition test and Galleria mellonella (G. mellonella) infection model were used to explore the changes in virulence of the two clinical isolates. During antibiotic treatment, CRKP FK8578 underwent a series of drug resistance and virulence changes, including CZA resistance, carbapenem susceptibility and virulence attenuation. The results of WGS showed that mutation of blaKPC-2 to blaKPC-33 was responsible for the change of drug resistance phenotype between FK8578 and FK8695. pLVPK-like virulence plasmid without siderophore synthesis operon was identified in the two strains. On the other hand, the loss of hypermucoviscosity phenotype in the FK8695 strain may be related to a single nucleotide deletion of the rmpA gene, which would further lead to a decrease in virulence. Virulence results showed that compared with FK8578, FK8695 was negative in the string test, with decreased capsular production, smaller amounts of biofilm formation and higher survival rate of G. mellonella.Conclusion: This is the first report of CZA resistance and decreased virulence in ST11 CRKP strains during antimicrobial treatment. It is urgent to monitor CZA resistance and timely adjust anti-infective treatment strategies.Keywords: ceftazidime–avibactam, carbapenem-resistantKlebsiella pneumoniae, whole-genome sequencing, hypermucoviscosity, pLVPK-like plasmid, virulence attenuation

Hui Tang,1 Junxue Lyu,1 Meiyan Xu2 1School of Education, Zhaoqing University, Zhaoqqing, People’s Republic of China; 2Division of Biology, Dawang High School, Zhaoqqing, People’s Republic of ChinaCorrespondence: Hui Tang, Zhaoqing University, Zhaoqing Ave, Duanzhou District, Zhaoqing, Guangdong, 526061, People’s Republic of China, Email tanghui@zqu.edu.cnPurpose: A growing amount of research has been dedicated to the protective role of strength-based parenting in psychological distress. Strength-based parenting is a style of parenting in which parents are conscious of their children’s strengths, and encourage them to develop and make use of those strengths. However, the mechanisms linking strength-based parenting to depression are not well known. Drawing on the social–emotional learning model, this study examined the association between strength-based parenting and depression and the indirect role of emotion regulation (ie, cognitive reappraisal and expression suppression).Materials and Methods: A total of 750 Chinese middle school students from two middle schools completed questionnaires comprising the Strength-based Parenting Scale, the Emotion Regulation Scale, the Center for Epidemiologic Studies Depressive Scale, and sociodemographic characteristics. A total of 695 students provided accurate responses to the two validity check questions, and were thus retained in the final study sample. Of the final sample, 348 (50.1%) were girls, and the respondents overall had an average age of 16.22 years. The direct and indirect paths from strength-based parenting to depression were analyzed using structural equation modeling.Results: The results showed that strength-based parenting negatively predicted depression and cognitive reappraisal, while strength-based parenting positively predicted depression. Strength-based parenting indirectly predicted depression through cognitive reappraisal and expression suppression.Conclusion: These findings suggest an underlying process by which high strength-based parenting resists depression by increasing cognitive reappraisal and decreasing expression suppression. It is necessary to implement a comprehensive intervention strategy that focuses on strength-based parenting and emotion regulation (eg, cognitive reappraisal).Keywords: strength-based parenting, depressive, cognitive reappraisal, expression suppression, Chinese

Meifang Yang,1,2,&ast; Min Xu,3,&ast; Xuan Zhang,1,2 Hong Zhao,1,2 Jianhua Hu,1,2 Jie Wang1,2 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 2Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang Province, People’s Republic of China; 3Nursing Department, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Wang, Email 1195040@zju.edu.cnAbstract: Healthcare workers (HCWs) are highly at risk for tuberculosis (TB) exposure, particularly those in high TB burden countries. Inoculation TB secondary to needlestick injury is uncommon but can occur in HCWs. Herein, we report an unusual case of primary multidrug‐resistant tuberculosis (MDR-TB) in a surgeon secondary to a needlestick injury while performing thoracentesis on a TB patient, and the surgeon recovered and returned to work after 22 months of anti-TB treatment. We searched the PubMed database and identified 19 cases of inoculation TB secondary to sharp injury in HCWs including the present case. Those cases highlight that primary inoculation of TB even MDR-TB infection should not be neglected in patients suffered needlestick injury when the sharp instrument suspected or confirmed contaminated with TB. In this situation, if the HCWs need for additional protection or prophylactic anti-TB is worthy of further study.Keywords: cutaneous tuberculosis, tubercular tenosynovitis, inoculation tuberculosis, occupational exposure