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Xiao Wang,1,* Ying Cao,2,* Jing Hu,3 Lian-Cheng Jia,4 Bo Li,3 Baoli Liu,5 Wei-Hai Yao,2 Xiao-Lu Pei,6 Wei Peng,2 Shuang Wang,2 Cun-Zhi Liu,1,7 Jian-Feng Tu,1,7 Zhi-Cheng Qu2 1School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Emergency Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 3Evidence Based Medicine Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 4Urinary Surgery, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 5Nephrology Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 6Nursing Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 7International Acupuncture and Moxibustion Innovation Institute, Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhi-Cheng Qu, Emergency Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Meishuguanhou Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Email qzhch0824@163.com Jian-Feng Tu, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, People’s Republic of China, Email tujianfeng1@126.comIntroduction: Analgesia is often delayed for suspected acute renal colic due to urinary calculi (ARCUC) even in emergency department. Acupuncture has a rapid onset and is effective for analgesia, however, evidence about early-acupuncture for suspected ARCUC is limited. This trial aims to evaluate the efficacy of early-intervention acupuncture compared with sham acupuncture on pain relief among emergency department suspected ARCUC patients.Methods and Analysis: A total of 84 eligible patients who are suspected diagnosed with ARCUC will be randomly allocated to the acupuncture group or the sham acupuncture group. Each patient will receive 1 session of acupuncture or sham acupuncture before diagnostic imaging. The primary outcome will be the response rate at 10 min after needle manipulation, defined as the proportion of patients whose Numeric Rating Scale (NRS) score decrease by at least 50% from baseline. Secondary outcomes will include pain intensity assessed by NRS, further analgesia requirement, revisit rate, surgical intervention rate, satisfaction evaluation, and adverse events. The final diagnosis rate determined by radiography will be recorded and reported. All patients who receive randomization will be included in the intention-to-treat analysis.Conclusion: This study’s findings are anticipated to evaluate the analgesic effect of early-intervention acupuncture for acute renal colic in emergency department, which could be useful for moving the timing of analgesia forward and aligning pain management for acute renal colic more with the guidelines.Trial Registration Number: ChiCTR2100049069 (https://www.chictr.org.cn/showproj.html?proj=125338).Keywords: acupuncture, complementary medicine, pain management, emergency medicine, renal colic

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

Jing Hu, Yang Song, Yuxing Zhang, Peng Yang, Siyu Chen, Zhaoyan Wu, Jun Zhang Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Jun Zhang, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, People’s Republic of China, Tel +86 13953109816, Fax +86 53188382923, Email zhangj@sdu.edu.cnPurpose: This study examines the effects and mechanisms of catalpol (CAT) on the proliferation and osteogenic differentiation of cultured human periodontal ligament stem cells (hPDLSCs) in vitro and assesses the impact of CAT on periodontal remodeling in vivo using an orthodontic tooth movement (OTM) model in rats.Methods: hPDLSCs were cultured in a laboratory setting, and their proliferation and osteogenic differentiation were assessed using the Cell-counting Kit-8 (CCK-8), Alizarin Red Staining (ARS), quantitative calcium assay, alkaline phosphatase (ALP) staining and activity assay, and immunofluorescence assay. Additionally, the expression of collagen type 1 (COL-1), ALP, and runt-related transcription factor-2 (RUNX-2) was evaluated through qRT-PCR and Western blot analysis. To verify the function of the estrogen receptor-α (ER-α)-mediated phosphatidylinositol-3-kinase-protein kinase B (PI3K/AKT) pathway in this mechanism, LY294002 (a PI3K signaling pathway inhibitor) and the ER-α specific inhibitor methyl-piperidine-pyrazole (MPP) were used. The osteogenic markers ER-α, AKT, and p-AKT (phosphoprotein kinase B) were identified through Western blot analysis. Eighteen male Sprague-Dawley rats were assigned to two groups randomly: a CAT group receiving CAT and a control group receiving an equivalent volume of saline. Micro-computed tomography (micro-CT) analysis was employed to evaluate tooth movement and changes in alveolar bone structure. Morphological changes in the periodontal tissues between the roots were investigated using hematoxylin and eosin (HE) staining and tartaric-resistant acid phosphatase (TRAP) staining. The expression of COL-1, RUNX-2, and nuclear factor-κB (NF-κB) ligand (RANKL) was assessed through immunohistochemical staining (IHC) to evaluate periodontal tissue remodeling. Tests were analyzed using GraphPad Prism 8 software. Differences among more than two groups were analyzed by one-way or two-way analysis of variance (ANOVA) followed by the Tukey’s test. Values of p

Xiaoqin Ji,1,* Xuebing Shi,2,* Jun Hu,3 Wanrong Jiang,3 Bin Zhou,3 Houlong Zhou,3 Xi Yuan,3 Yikun Li,3 Hua Huang,3 Jiasheng Wang,3 Wei Ding,3 Yong Wang,4 Xiangdong Sun3 1Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Radiation Oncology, Nanjing Jiangbei Hospital, Nanjing, People’s Republic of China; 3Department of Radiation Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 4Department of Outpatient Clinic, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Wang; Xiangdong Sun, Email 292917354@qq.com; sunxd_81@126.comPurpose: The objective of this study was to compare the clinical outcomes of stereotactic body radiation therapy (SBRT) in elderly patients aged 65 or older with clinical stage I–II non-small-cell lung cancer (NSCLC), specifically examining the differences between centrally located lung tumors and peripherally located lung tumors.Methods: From April 2009 to January 2020, a total of 136 patients with 136 tumors (65 central, 71 peripheral; NSCLC) at an early stage (T1-3N0M0) were treated with SBRT at a single institution. Central/peripheral location was assessed retrospectively on planning CT scans. A propensity score matching analysis was utilized to compare the two groups. In addition, the prognosis and related toxicity were compared between the two study arms.Results: A total of 33 central tumors and 33 peripheral tumors were matched and analyzed. The results showed no significant differences in overall survival (OS) and progression-free survival (PFS) between the two groups. The 2-year OS was 71.88% (95% CI, 57.87%-89.27%) in the central lung cancer group, while it was 93.94% (95% CI, 86.14%-100.00%) in the peripheral lung cancer group (P=0.462). The 2-year PFS was 43.75% in the central lung cancer group, while it was 78.79% in the peripheral lung cancer group (P=0.279). Further subgroup analysis indicated that the location of peripheral tumor have a positive impact on OS in patients with adenocarcinoma. The occurrence of local failure, regional failure, or distant failure was comparable between central and peripheral tumors. There was no statistically significant difference in toxicity between the central and the peripheral tumor groups.Conclusion: The outcomes of SBRT for central tumors versus peripheral lung tumors in elderly patients with early-stage NSCLC were similar. SBRT demonstrated a similar level of safety in terms of toxicity for both central and peripheral lung tumors.Keywords: Non-small cell lung cancer, stereotactic body radiation therapy, central lung cancer, elderly patients, propensity score matching

Liangliang Zhang, Bo Zhang, Wenzhang Yuan, Jiefeng Hu, Junying Yuan, Xuejie Wang Department of Rehabilitation, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Junying Yuan; Xuejie Wang, Department of Rehabilitation, The Third Affiliated Hospital of Zhengzhou University, No. 7 Rehabilitation Front Street, Erqi District, Zhengzhou, 450052, People’s Republic of China, Tel +86 15890092671, Email junyingzzu@outlook.com; xuejieot@163.comPurpose: Different types of activities have independent and additive benefits for adult health. This study intended to assess the association between aerobic activity and muscle-strengthening activities and health-related quality of life (HRQoL) and physical and mental health in patients with neck pain.Methods: This cross-sectional study included data on patients with neck pain from the National Health and Nutrition Examination Survey (NHANES) dataset between 2001 and 2004. Weighted logistic regression analyses were applied to estimate the odds ratio (OR) and 95% confidence interval (CI) for the associations between aerobic activity, muscle-strengthening activities, and their combination, and HRQoL, physically unhealthy days (≥ 14 days/month), and mentally unhealthy days (≥ 14 days/month). Subgroup analyses were performed according to age, gender, and screen time.Results: A total of 794 patients with neck pain were included, of whom 504 had good HRQoL and 290 had poor HRQoL. Aerobic activity (OR=0.35, 95% CI: 0.21– 0.57) and muscle-strengthening activities (OR=0.50, 95% CI: 0.26– 0.98) were associated with good HRQoL in patients with neck pain, but only aerobic activity (OR=0.42, 95% CI: 0.28– 0.63) was linked to shorter physical unhealthy days. No associations were found between aerobic activity, muscle-strengthening activities, and mentally unhealthy days (P> 0.05). The trends for the combined result of aerobic activity and muscle-strengthening activities on HRQoL, physically unhealthy days, and mentally unhealthy days were significant (Ptrend< 0.001). Subgroup analyses found that the combined result of aerobic and muscle-strengthening activities was only more significant on HRQoL in patients aged < 60 years or ≥ 60 years, males or females, and patients with screen time < 3 hours or ≥ 3 hours (Ptrend< 0.05).Conclusion: Aerobic and muscle-strengthening activities were associated with good prognosis in patients with neck pain, but the effect of aerobic activity may be more pronounced.Keywords: neck pain, health-related quality of life, aerobic activity, muscle-strengthening activities, combined result

Jie Xu,1,2 Liujun Tao,1 Liangyan Jiang,1 Jie Lai,1 Juntao Hu,1 Zhanhong Tang1 1Department of Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Critical Care Medicine, Suining Central Hospital, Suining, Sichuan, 629000, People’s Republic of ChinaCorrespondence: Zhanhong Tang; Juntao Hu, Department of Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, Tel +86 13978816316 ; +86 18978866565, People’s Republic of China, Email tangzhanhong139@sina.com; hujuntao80@126.comPurpose: Sepsis-associated acute lung injury (SA-ALI) is a common complication in patients with sepsis, contributing to high morbidity and mortality. Excessive inflammation and oxidative stress are crucial contributors to lung injury in sepsis. This study aims to examine the protective effects of moderate hypothermia on SA-ALI and explore the underlying mechanisms.Methods: Sepsis was induced in rats through cecal ligation and puncture followed by intervention with moderate hypothermia (32– 33.9°C). Blood, bronchoalveolar lavage fluid, and lung tissues were collected 12 hours post-surgery. Inflammatory responses, oxidative injury, SA-ALI-related pathophysiological processes, and Keap1/GSK3β/Nrf2/GPX4 signaling in septic rats were observed by ELISA, lung W/D ratio, immunohistochemistry, immunofluorescence, histological staining, Western blotting, RT-qPCR, and TEM assays.Results: Moderate hypothermia treatment alleviated lung injury in septic rats, reflected in amelioration of pathological changes in lung structure and improved pulmonary function. Further, moderate hypothermia reduced arterial blood lactate production and suppressed the expression of inflammatory factors IL-1β, IL-6, and TNF-α; downregulated ROS, MDA, and redox-active iron levels; and restored GSH and SOD content. TEM results demonstrated that moderate hypothermia could mitigate ferroptosis in PMVECs within lung tissue. The underlying mechanism may involve regulation of the Keap1/Nrf2/SLC7A11/GPX4 signaling pathway, with the insulin pathway PI3K/Akt/GSK3β also playing a partial role.Conclusion: Collectively, we illustrated a novel potential therapeutic mechanism in which moderate hypothermia could alleviate ferroptosis induced by excessive inflammation and oxidative stress via the regulation of Keap1/GSK3β/Nrf2/GPX4 expression, hence ameliorating acute lung injury in sepsis.Keywords: moderate hypothermia, sepsis, acute lung injury, ferroptosis, Nrf2, inflammation

Wentao Wu,1,&ast; Fei Wen,1,&ast; Jiaxin Hu,1 Leijun Li2 1Department of Psychiatry, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou City, Guangdong Province, People’s Republic of China; 2Department of Psychiatry, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou City, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leijun Li, Email lljzssyxl@163.comBackground: Anxiety disorders seriously impair patients’ mental health and quality of life, with limited effectiveness of current treatments. Dysregulation of activating transcription factor 4 (ATF4) is involved in various mental diseases, but the research on its potential roles in alleviating anxiety disorders remains limited.Methods: ATF4 was screened out by bioinformatic analysis and its expression was verified in vivo. Mice were treated with 21 d of chronic restraint stress to establish the anxiety mice model. The anxiolytic effect of ATF4 was assessed by a battery of behavior tests and evaluation of hippocampal tissue damage after overexpressing ATF4. Ferroptosis-related indicators were detected by enzyme-linked immunosorbent assay and Western blotting. Then the transforming growth factor beta (TGF-β) signaling pathway was predicted as the downstream regulatory pathway of ATF4 by bioinformatic methods. Western blotting was conducted to detect the protein expression level of TGF-β 1, small mothers against decapentaplegic 3 (Smad3), and phospho-Smad3 (p-Smad3).Results: ATF4 was screened out as a ferroptosis-related anxiolytic gene after bioinformatics analysis and was down-regulated in the anxiety mice model. Mice with ATF4 overexpression spent more time in the open arms in the elevated plus-maze test, appeared more frequently in the central area in the open-field test, and decreased the immobility time in the forced swimming and tail suspension tests. Hippocampal tissue damage was alleviated, ferroptosis was suppressed, and the levels of TGF-β 1 and p-Smad3/Smad3 were increased by AFT4 overexpression.Conclusion: ATF4 overexpression can repress ferroptosis to improve anxiety disorders by activating the TGF-β signaling pathway.Keywords: anxiety disorders, ATF4, ferroptosis, hippocampus, TGF-β signaling pathway

Lei Zhu,1,&ast; Ryan Au,2,&ast; Luming Dai,3,&ast; Yanan Li,2 Feng Xu,2 Yuan Cui,2 Jingyi Hu,1 Hong Shen1 1Digestive Disease Research Institute, Affiliated Hospital of Nanjing University of Chinese Medicine, City Nanjing, People’s Republic of China; 2First Clinical Medical College, Nanjing University of Chinese Medicine, City Nanjing, People’s Republic of China; 3Digestive Department, Affiliated Hospital of Nanjing University of Chinese Medicine, City Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Shen; Jingyi Hu, Digestive Disease Research Institute, Affiliated Hospital of Nanjing University of Chinese Medicine, City Nanjing, People’s Republic of China, Email Shenhong999@njucm.edu.cn; hjytcm@163.comBackground: Electroacupuncture (EA) exerts beneficial effects on ulcerative colitis. However, its underlying mechanisms remain elusive. In this study, we investigated the impact of high and low-frequency EA at Zusanli (ST36) on the gut microbiota and metabolite profile in the dextran sulfate sodium (DSS)-induced colitis mouse model.Methods: Colitis was established using DSS, and daily electroacupuncture at ST36 with varying frequencies was administered. Changes in body weight and fecal characteristics were monitored. Pro-inflammatory cytokines were detected, and the core molecule of intestinal barrier function were analyzed. The composition of intestinal flora was analyzed using 16S sRNA sequencing, while the changes of metabolites in colon tissue were detected by Ultra-performance liquid chromatography–tandem mass spectrometry (UPLC/MS/MS).Results: Treatment with both high and low frequencies of EA at ST36 significantly ameliorated the symptoms of colitis, while also exerting systemic and local anti-inflammatory effect by downregulating the proinflammatory cytokines, iNOS and MPO. EA at ST36 enhanced the intestinal barrier by upregulating the expression of MUC2 and ZO-1. Furthermore, high-frequency EA at ST36 remarkably restored the gut microbial composition and diversity, as well as modulated the gut microbial metabolism of phenylalanine.Conclusion: Our results suggest that EA treatment may alleviate colitis by reducing colon damage through gut microbiota-phenylalanine metabolism, which provides insight into EA’s underlying mechanisms in the treatment of colitis.Keywords: ulcerative colitis, electroacupuncture, gut microbiota, phenylalanine metabolism

Qinliang Zheng,1– 3,&ast; Meng Chen,4,&ast; Jennifer Hu,5 Ting Zhou,5 Peipei Wang6 1Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China; 2Shandong Provincial Key Medical and Health Discipline of Pediatric Internal Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China; 3Jining Key Laboratory for Prevention and Treatment of Severe Infection in Children, Affiliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China; 4Department of Cardiology, Affiliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China; 5Department of Medical Psychology, School of Health Humanities, Peking University, Beijing, People’s Republic of China; 6Sleep and Psychosomatic Medicine Center, Sanya Central Hospital/The Third People’s Hospital of Hainan Province, Sanya, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ting Zhou, Department of Medical Psychology, School of Health Humanities, Peking University, N0.38 Xueyuan Road, Haidian District, Beijing, 100191, People’s Republic of China, Email zhouting.92@bjmu.edu.cn Peipei Wang, Sleep and Psychosomatic Medicine Center, Sanya Central Hospital/The Third People’s Hospital of Hainan Province, No. 1154 Jiefangsi Road, Sanya, Hainan, 572000, People’s Republic of China, Email peipeiwang@pku.edu.cnObjective: This study aimed to examine the association between appearance comparison and adolescent depressive symptoms, the mediating role of body appreciation, and the moderating roles of gender and body-mass index (BMI) among adolescents in different age groups.Methods: A cross-sectional sample of 2645 Chinese students aged 12– 16 years (44.7% girls) participated. The measurements included depressive symptoms, appearance comparison, body appreciation, weight, and height. Multigroup path analysis was used to examine the moderated mediation model.Results: Compared with boys, adolescent girls presented greater levels of appearance, which increased with age. Body appreciation mediated the association between appearance comparison and depressive symptoms in girls, whereas appearance comparison directly correlated with depressive symptoms in boys. Body appreciation decreased with increasing BMI in boys but remained relatively stable in girls. Similar patterns were observed among junior and senior high school students.Conclusion: This study underscores the significant relationship between appearance comparison and adolescent depressive symptoms, suggesting varied mechanisms based on gender and BMI levels.Keywords: appearance comparison, body appreciation, adolescent depressive symptoms, gender difference, age group difference, body-mass index

Fengfeng Guo,1,&ast; Yuxi Xia,2,&ast; Qingqian Wei,1 Jun Zhuang,1 Jinge Li,2 Jintian Hu1 1Department of Cosmetic Injection Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, People’s Republic of China; 2School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jintian Hu, Department of Cosmetic Injection Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China, Tel +86-10-53968253, Email hujintian@vip.163.comAbstract: The increasing use of hyaluronic acid (HA) implants has made adverse effects more apparent. Here, we present a rare case of massive allergic dermatitis due to HA injections. We performed dermoscopy and color ultrasound, which clarified that this was an allergic dermatitis caused by fillers, and analyzed the possible causes of the allergy. Common treatments were compared, and the advantages of 5-FU-based treatment regimens and their associated mechanisms were noted. A low dose of 5-fluorouracil and triamcinolone acetonide was administered to the patient’s entire face and neck, and significant efficacy was achieved. We aimed to gather evidence on extensive dermatitis caused by HA injection, provide new perspectives and solutions for subsequent HA injections, and promote further research on the potential mechanisms of extensive skin inflammation and allergies caused by local HA injections.Keywords: hyaluronic acid, massive allergic dermatitis, 5-fluorouracil

Yuqing Li,1,&ast; Jiachen Zhang,2,&ast; Yingjuan Gu,1 Ling Wang,1 Jing Hu1 1Department of Nosocomial Infection Administration, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Clinical Research Center, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Hu, Department of Nosocomial Infection Administration, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, People’s Republic of China, Tel +8620-61643605 ; +8615622316318, Email hjalzh@smu.edu.cnBackground: Acinetobacter baumannii (A. baumannii) is an widespread pathogen and carbapenem-resistant strains are great threat to hospitalized patients. This study is aimed to investigate the clinical characteristics, antimicrobial resistance patterns, and risk factors associated with carbapenem resistance in nosocomial, healthcare-associated (HCA), and community-acquired (CA) A. baumannii infections.Methods: This study retrospectively reviewed cases in a tertiary hospital in southern China between January 1, 2019, and December 31, 2021. Univariate and multivariate logistic regression analyses were performed to identified the risk factors of carbapenem resistance in nosocomial, HCA and CA A. baumannii infections.Results: A total of 391 patients with A. baumannii infection were included. Of these patients, 96 (24.6%) had nosocomial infections, 215 (55.0%) had HCA infections, and 80 (20.5%) had CA infections. The overall 30-day mortality rates of nosocomial and HCA infection patients was significantly higher than that of CA infection (P< 0.05). The incidence of antimicrobial resistance was also higher in nosocomial and HCA bacteremia than that in CA bacteremia (P< 0.05). Logistic regression analysis identified age ≥ 60 years, urethral catheterization, and exposure to two or more antibiotics as the independent risk factors for carbapenem-resistant A. baumannii (CRAB) infection in the nosocomial infection group and exposure to two or more antibiotics and endotracheal intubation in the HCA infection group. However, malignant tumors and hematological diseases were identified as protective factors against CRAB infection in the HCA group.Conclusion: These data suggest that HCA A. baumannii infection is quite different from CA infection, with antimicrobial resistance and 30-day mortality rates similar to those of nosocomial infections. Additionally, the risk factors for CRAB development in the CA, HCA, and nosocomial groups were not the same, which may provides the help for controlling practices and instruction empirical clinical medication.Keywords: Acinetobacter baumannii, community-acquired, healthcare-associated, nosocomial, antimicrobial resistance, risk factor

Huanhuan Wang,1,&ast; Dan Xiao,2,&ast; Hua Zhou,3,&ast; Shu Chen,4 Guangjun Xiao,4 Juan Hu,4 Hui Quan,2 Miao Luo,5 Shaocheng Zhang2,6 1School of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 2Department of Laboratory Medicine, the Second Affiliated Hospital of Chengdu Medical College (Nuclear Industry 416 Hospital), Chengdu, Sichuan, People’s Republic of China; 3Department of Laboratory Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Laboratory Medicine, Suining Central Hospital, Suining, Sichuan, People’s Republic of China; 5Department of Laboratory Medicine, the People’s Hospital of Yubei District of Chongqing, Chongqing, People’s Republic of China; 6School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaocheng Zhang; Miao Luo, Email 102024001@cmc.edu.cn; 536513878@qq.comPurpose: Visceral adiposity is a significant risk factor for severe COVID-19. However, the impact of the Chinese visceral adiposity index (CVAI) on the efficacy of SARS-CoV-2 vaccines remains poorly understood. This study aims to explore the impact of CVAI on the production of neutralizing antibodies (NAb) in inactivated SARS-CoV-2 vaccines and the potential mechanism, thereby optimizing vaccination guidance.Methods: In this cross-sectional study, 206 health workers (completed two SARS-CoV-2 vaccination on February 8th and March 10th, 2021, respectively) were recruited. All baseline anthropometric parameters of the participants were collected, and venous blood samples were obtained 6 weeks later to measure peripheral innate immune cells, inflammatory cytokines, and NAb titers against SARS-CoV-2. CVAI were calculated according to the formula and divided participants into two groups depending on CVAI median.Results: The median NAb titer among healthcare workers was 12.94 AU/mL, with an efficacy of 87.86% for the SARS-CoV-2 vaccine. NAb titers were lower in the CVAI dysfunction group than in the CVAI reference group (median: 11.40 AU/mL vs 15.57 AU/mL), the hsCRP levels (median: 0.50 mg/L vs 0.30 mg/L) and peripheral monocyte count (mean: 0.47 × 109/L vs 0.42 × 109/L) in the CVAI dysfunction group were higher than in the CVAI reference group. Additionally, CVAI showed positive correlations with hsCRP, monocytes, lymphocytes, and B-lymphocytes, and a negative correlation with NAb titers.Conclusion: CVAI may inhibit SARS-CoV-2 neutralizing antibody expression through inducing immune dysfunction and chronic inflammation. Thus, more attention should be paid to the vaccination for high CVAI population to improve the effectiveness of vaccination, which could provide more robust support for COVID-19 epidemic prevention and control.Keywords: Chinese visceral adiposity index, immune function, chronic inflammation, SARS-CoV-2 vaccine, neutralizing antibody

Yishan Duan,1,&ast; Jing Ren,2,&ast; Jing Wang,3,&ast; Suyan Wang,4 Rui Zhang,1 Huohuo Zhang,1 Jinrui Hu,1 Wen Deng,1 Weimin Li,1,3,4 Bojiang Chen1,3 1Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 2The Integrated Care Management Center, West China Hospital of Sichuan University, Chengdu, Chengdu, Sichuan Province, 610041, People’s Republic of China; 3Precision Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 4Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bojiang Chen; Weimin Li, Email cjhcbj@outlook.com; weimin003@163.comPurpose: Early empiric antibiotics were prescribed to numerous patients during the Coronavirus disease 2019 (COVID-19) pandemic. However, the potential impact of empiric antibiotic therapy on the clinical outcomes of patients hospitalized with COVID-19 is yet unknown.Methods: In this retrospective cohort study, early antibiotics use cohort was defined as control group, which was compared with no antibiotic use and delayed antibiotic use cohorts for all-cause mortality during hospitalization. The 1:2 propensity score matched patient populations were further developed to adjust confounding factors. Survival curves were compared between different cohorts using a Log rank test to assess the early antibiotic effectiveness.Results: We included a total of 1472 COVID-19 hospitalized patients, of whom 87.4% (1287 patients) received early antibiotic prescriptions. In propensity-score-matched datasets, our analysis comprised 139 patients with non-antibiotic use (with 278 matched controls) and 27 patients with deferred-antibiotic use (with 54 matched controls). Patients with older ages, multiple comorbidities, severe and critical COVID-19 subtypes, higher serum infection indicators, and inflammatory indicators at admission were more likely to receive early antibiotic prescriptions. After adjusting confounding factors likely to influence the prognosis, there is no significant difference in all-cause mortality (HR=1.000(0.246– 4.060), p = 1.000) and ICU admission (HR=0.436(0.093– 2.04), p = 0.293), need for mechanical ventilation (HR=0.723(0.296– 1.763), p = 0.476) and tracheal intubation (HR=1.338(0.221– 8.103), p = 0.751) were observed between early antibiotics use cohort and non-antibiotic use cohort.Conclusion: Early antibiotics were frequently prescribed to patients in more severe disease condition at admission. However, early antibiotic treatment failed to demonstrate better clinical outcomes in hospitalized patients with COVID-19 in the propensity-score-matched cohorts.Keywords: Coronavirus disease 2019, COVID-19, early antibiotics use, bacterial co-infections, clinical outcomes

Nan Tang,1 Mengyue Pei,2 Huihui Liu,3 Jingru Chen,1 Youting Wang,1 Lei Xie,4 Junping Hu,3,5 Jing Wang,6 Yuan Gao1 1Department of Nursing, 1st Medical Centre of PLA General Hospital, Beijing, People’s Republic of China; 2School of Medicine, Henan Kaifeng College of Science Technology and Communication, Kaifei, Henan Province, People’s Republic of China; 3School of Nursing, Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China; 4Renji Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 5Department of Reproductive Medicine, The First Hospital of Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China; 6Department of Gynecology, 1th Medical Centre of PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jing Wang; Yuan Gao, Email wangjing353535@163.com; gaoyuanzd@163.comBackground: The purpose of this study was to explore the relationship between infertility-related stress and dyadic coping with quality of life (QoL) in couples with infertility issues, and verify gender differences and dyadic interactions in the associations between them.Methods: This cross-sectional study included 340 couples who were recruited from the First Affiliated Hospital of Lanzhou University between March 2022 and November 2022. The Fertility Problem Inventory, Dyadic Coping Inventory and FertiQoL were used to measure infertility-related stress, dyadic coping and QoL. The Actor-Partner Interdependence Model was used to analyze the effects of infertility-related stress and dyadic coping on the couple’s own QoL (actor effect) as well as on their partner’s QoL (partner effect).Results: Female patients perceived significantly lower levels of QoL and dyadic coping than those of husbands. There was no statistically significant difference in the infertility-related stress between wives and husbands. Husbands’ infertility-related stress had actor and partner effects on their own and their wives’ QoL, while wives’ infertility-related stress only had an actor effect on their own QoL. Husbands’ dyadic coping had both actor effect and partner effects on their own and their wives’ QoL, meanwhile wives’ dyadic coping had both actor effect and partner effects on their own and their husbands’ QoL.Conclusion: Husbands’ QoL was impacted by their own infertility-related stress, dyadic coping and their wives’ dyadic coping. Whereas wives’ QoL was influenced by infertility-related stress and dyadic coping from both their own and their spouses. Therefore, elevating the level of dyadic coping may contribute to improving QoL for both husbands and wives. Moreover, enhancing the ability to cope with infertility-related stress might be useful for husbands and indirectly contribute to wives’ QoL.Keywords: infertility, couple, infertility-related stress, dyadic coping, QoL

Yanan Li,1,2,&ast; Jingyi Hu,1,2,&ast; Ryan Au,1– 3 Cheng Cheng,1,2 Feng Xu,1,2 Weiyang Li,1,2 Yuguang Wu,1,2 Yuan Cui,1,2 Lei Zhu,1,2 Hong Shen1,2 1Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 2Jiangsu Provincial Hospital of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 3Academy of Chinese Culture and Health Sciences, Oakland, CA, 94612, USA&ast;These authors contributed equally to this workCorrespondence: Hong Shen; Lei Zhu, Jiangsu Provincial Hospital of Chinese Medicine (Affiliated Hospital of Nanjing University of Chinese Medicine), 155 Hanzhong Road, Qinhuai District, Nanjing, Jiangsu Province, People’s Republic of China, Tel\Fax +86-025- 86617141, Email shenhong999@njucm.edu.cn; zhulei5100@njucm.edu.cnBackground: Qingchang Tongluo Decoction (QTF) is clinically used for the treatment of intestinal fibrosis in Crohn’s Disease (CD). However, the role of QTF in CD-associated fibrosis and its potential pharmacological mechanism remains unclear.Purpose: The objective of this study was to elucidate the potential mechanism of QTF in treating CD-associated fibrosis, employing a combination of bioinformatics approaches — encompassing network pharmacology and molecular docking — complemented by experimental validation.Methods: To investigate the material basis and potential protective mechanism of QTF, a network pharmacology analysis was conducted. The core components and targets of QTF underwent molecular docking analysis to corroborate the findings obtained from network pharmacology. In vitro, a colon fibrotic model was established by stimulating IEC-6 cells with 10 ng/mL of transforming growth factor(TGF-β 1). In vivo, an intestinal fibrosis model was induced in BALB/c mice by TNBS. The role of QTF in inhibiting the TGF-β 1/Smad signaling pathway was investigated through RT-qPCR, Western blotting, immunohistochemistry staining, and immunofluorescence staining.Results: Network pharmacology analysis revealed that QTF could exert its protective effect. Bioinformatics analysis suggested that Flavone and Isoflavone might be the key components of the study. Additionally, AKT1, IL-6, TNF, and VEGFA were identified as potential therapeutic targets. Furthermore, experimental validation and molecular docking were employed to corroborate the results obtained from network pharmacology. RT-qPCR, Immunofluorescence, and Western blotting results demonstrated that QTF significantly improved colon function and inhibited pathological intestinal fibrosis in vivo and in vitro.Conclusion: Through the application of network pharmacology, molecular docking, and experimental validation, QTF could be confirmed to inhibit the proliferation of intestinal fibroblasts associated with CD and reduce the expression of Collagen I and VEGFA. This effect is achieved through the attenuation of ECM accumulation, primarily via the inhibition of the TGF-β 1/Smad signaling pathway. Keywords: Qingchang Tongluo Decoction, Crohn’s Disease, intestinal fibrosis, network pharmacology, Pharmacology

Yadong Sun,1 Yanjie Shan,1 Jiaqiong Xie,1 Ke Chen,1 Jia Hu2 1Faculty of Social Sciences, Chongqing University, Chongqing, People’s Republic of China; 2Institute for Advanced Studies in Humanities and Social Science, Chongqing University, Chongqing, People’s Republic of ChinaCorrespondence: Ke Chen; Jia Hu, Chongqing University, Shapingba, Chongqing, People’s Republic of China, 400044, Tel +86-13628362626, Email chenke197729@163.com; hujia827@cqu.edu.cnPurpose: With the development of information technology and various social media, recommendation algorithms have increasingly more influence on users’ social media usage. To date, there has been limited research focused on analyzing the impact of recommendation algorithms on social media use and their corresponding role in the development of problematic behaviors. The present study analyzes the impact of recommendation algorithms on college students’ information sharing and internalizing, externalizing problem behaviors to address the aforementioned shortcomings.Methods: An online questionnaire survey was conducted among 34,752 college students in China. A latent profile analysis was conducted to explore the various behavioral patterns of Chinese college students’ information sharing across the three social media platforms identified for this study. The Bolck–Croon–Hagenaars (BCH) method Regression Mixture Modeling was then used to analyze the differences in internalizing and externalizing problem behaviors among the different subgroups of Chinese college students.Results: The level of information sharing by college students across different social media platforms could be divided into “WeChat Moments low-frequency information sharing”, “middle-frequency comprehensive information sharing”, “TikTok high-frequency information sharing”, and “Sina Weibo high-frequency information sharing”. Significant differences were observed regarding internalizing and externalizing problem behaviors among college students in different information-sharing subgroups.Conclusion: This study identified four subgroups with different information-sharing characteristics using latent profile analysis. Among them, college students who are in subgroup of social media information sharing influenced by recommendation algorithms exhibit higher frequency of information sharing and higher level of internalizing and externalizing problematic behaviors. These results expand our understanding of college students’ social media usage and problem behaviors from a technological perspective. In future, the negative impacts of recommendation algorithms on college students can be reduced by improving their awareness of these algorithms and optimizing the algorithms themselves.Keywords: user-generated content, recommendation algorithms, latent profile analysis, internalizing problem behaviors, externalizing problem behaviors

Haishui Sun,1,&ast; Xiao Wang,2,3,&ast; Zhaoyang Guo,4,&ast; Zhenrong Hu,5 Yuanchen Yin,4 Shuhan Duan,6 Wenwen Jia,2 Wei Lu,2,3 Jingzhou Hu1,7 1Department of Oral and Maxillofacial - Head and Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, People’s Republic of China; 2Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of D&A for Metal Functional Materials, School of Materials Science and Engineering, Tongji University, Shanghai, People’s Republic of China; 4School of Stomatology, Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 5Department of Stomatology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 6Shanghai Key Laboratory of Stomatology, Department of Oral Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 7Department of Oral and Maxillofacial Surgery, Zhang Zhiyuan Academician Workstation, Hainan Western Central Hospital, Shanghai Ninth People’s Hospital, Danzhou, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingzhou Hu; Wei Lu, Email huyayi@shsmu.edu.cn; weilu@tongji.edu.cnIntroduction: Traditional surgical resection, radiotherapy, and chemotherapy have been the treatment options for patients with head and neck squamous cell carcinoma (HNSCC) over the past few decades. Nevertheless, the five-year survival rate for patients has remained essentially unchanged, and research into treatments has been relatively stagnant. The combined application of photothermal therapy (PTT) and immunotherapy for treating HNSCC has considerable potential.Methods: Live-dead cell staining and CCK-8 assays proved that Fe3O4 nanoparticles are biocompatible in vitro. In vitro, cellular experiments utilized flow cytometry and immunofluorescence staining to verify the effect of Fe3O4 nanoparticles on the polarisation of tumor-associated macrophages. In vivo, animal experiments were conducted to assess the inhibitory effect of Fe3O4 nanoparticles on tumor proliferation under the photothermal effect in conjunction with BMS-1. Tumour tissue sections were stained to observe the effects of apoptosis and the inhibition of tumor cell proliferation. The histological damage to animal organs was analyzed by hematoxylin and eosin (H&E) staining.Results: The stable photothermal properties of Fe3O4 nanoparticles were validated by in vitro cellular and in vivo animal experiments. Fe3O4 photothermal action not only directly triggered immunogenic cell death (ICD) and enhanced the immunogenicity of the tumor microenvironment but also regulated the expression of tumor-associated macrophages (TAMs), up-regulating CD86 and down-regulating CD206 to inhibit tumor growth. The PD-1/PD-L1 inhibitor promoted tumor suppression, and reduced tumor recurrence and metastasis. In vivo studies demonstrated that the photothermal action exhibited a synergistic effect when combined with immunotherapy, resulting in significant suppression of primary tumors and an extension of survival.Conclusion: In this study, we applied Fe3O4 photothermolysis in a biomedical context, combining photothermolysis with immunotherapy, exploring a novel pathway for treating HNSCC and providing a new strategy for effectively treating HNSCC.Keywords: photothermal therapy, immunotherapy, tumor-associated macrophages, head and neck squamous cell carcinoma

Jiahao Hu, Neha Kulkarni, Peter Maliha, George Grossberg Department of Psychiatry and Behavioral Neuroscience, Saint Louis University School of Medicine, St Louis, MO, USACorrespondence: Jiahao Hu, Monteleone Hall, 1438 South Grand Blvd, St Louis, MO, 63104, USA, Tel +1 314-617-2777, Fax +1 314-977-4876, Email Jiahao.hu@slucare.ssmhealth.comAbstract: Substance misuse, traditionally seen as a problem of early to mid-adulthood, is becoming increasingly prevalent among the older adult population (ages ≥ 65). Diagnosing and treating substance misuse in this vulnerable population is challenging because of multiple pre-existing medical comorbidities as well as polypharmacy. As such, it remains underdiagnosed and underrepresented in the literature. This review provides an overview of the three most commonly misused substances in older adults: alcohol, cannabis, and prescription drugs. It examines epidemiology, societal trends, and treatment options, highlighting the need for targeted research to address the unique challenges faced by older adults. This review also briefly comments on the prevalence and treatment of other illicit drugs in this population.Keywords: older adult, elderly, alcohol use, cannabis use, prescription drug misuse, prevalence

Fan Zhao,1,2 Jitong Wang,1,2 Yu Zhang,1,2 Jinru Hu,1,2 Chenyang Li,3 Shuainan Liu,4,5 Ruixiang Li,2 Ruofei Du1,2 1Engineering Research Center of Modern Preparation Technology of TCM, Ministry of Education, Shanghai, 201203, People’s Republic of China; 2Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518055, People’s Republic of China; 4State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, People’s Republic of China; 5Diabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Ruixiang Li, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China, Email ruixiangli@shutcm.edu.cn Ruofei Du, Engineering Research Center of Modern Preparation Technology of TCM, Ministry of Education, Shanghai, 201203, People’s Republic of China, Email drf790101@shutcm.edu.cnAbstract: This review aimed to systematically investigate the intracellular and subcellular fate of various types of targeting carriers. Upon entering the body via intravenous injection or other routes, a targeting carrier that can deliver therapeutic agents initiates their journey. If administered intravenously, the carrier initially faces challenges presented by the blood circulation before reaching specific tissues and interacting with cells within the tissue. At the subcellular level, the car2rier undergoes processes, such as drug release, degradation, and metabolism, through specific pathways. While studies on the fate of 13 types of carriers have been relatively conclusive, these studies are incomplete and lack a comprehensive analysis. Furthermore, there are still carriers whose fate remains unclear, underscoring the need for continuous research. This study highlights the importance of comprehending the in vivo and intracellular fate of targeting carriers and provides valuable insights into the operational mechanisms of different carriers within the body. By doing so, researchers can effectively select appropriate carriers and enhance the successful clinical translation of new formulations.Plain language summary: Nowadays, scientists are actively researching nanocarrier drugs. After administration via injection or other methods, these drugs experience in the body and reach the target treatment site to relieve or cure symptoms. As research progresses, scientists are gaining more insights into the behavior of nanocarrier drugs in the body, which is useful in developing safer and more effective drugs. Historically, research has focused primarily on the drug itself. However, it is important to understand that the carrier that delivers and protects the drug (often described as the drug sitting in a “car” or under an “umbrella”) plays an essential role in the drug’s therapeutic effect. This paper aims to highlight the importance of the carrier’s role, which is vital for developing new drugs and advancing basic research. Keywords: drug carriers, targeted delivery, in vivo fate, subcellular fate

Xian Du,1,&ast; Jun Hu,1,&ast; Jianhua Xue,1 Yuan Zhuang,2 Xuefeng Tang,1 Zhiyue Xu1 1Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), Wuxi, People’s Republic of China; 2The Affiliated Hospital of Nantong University, Nantong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiyue Xu; Xuefeng Tang, Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), 67 Dajishan, Wuxi, 214065, People’s Republic of China, Email hepenxiaozi@163.com; 978665164@qq.comPurpose: Fatigue was a common symptom of non-alcoholic fatty liver disease (NAFLD), which seriously affected patients’ quality of life. The aim of this study was to detect fatigue rate and to evaluate factors associated with fatigue in NAFLD patients.Patients and Methods: A cross-sectional study was carried out from the Huadong Sanatorium between April 2022 and May 2023, and 133 NAFLD patients were included in this study. They completed Fatigue Severity Scale to assess fatigue, the Hospital Anxiety and Depression Scale to estimate psychological status, and the Pittsburgh Sleep Quality Index for sleep quality. Data were analyzed by independent samples t-tests, χ 2 tests and logistic regression models.Results: We found that 51.1% of NAFLD patients had fatigue. Exercise, anxiety, depression, subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disorders, daytime dysfunction and overall sleep quality were related to fatigue among NAFLD patients. Moreover, logistic regression models indicated anxiety, habitual sleep efficiency and sleep disorders as important predictors of fatigue.Conclusion: This was the first time to explore demographic, clinical, psychological and sleeping correlated factors for fatigue in Chinese NAFLD patients. Our study showed that more than half of NAFLD patients had fatigue, and anxiety, habitual sleep efficiency and sleep disorders were significantly associated with fatigue in NAFLD. The findings indicated that it was very necessary to pay more attention to fatigue of NAFLD patients, especially those with negative emotions and poor sleep quality by favorable intervention to relieve fatigue symptoms, so as to improve quality of life.Keywords: non-alcoholic fatty liver disease, fatigue, exercise, anxiety, sleep

Jianwen Zhao,1– 5,&ast; Xintian Cai,1– 5,&ast; Junli Hu,1– 5 Shuaiwei Song,1– 5 Qing Zhu,1– 5 Di Shen,1– 5 Wenbo Yang,1– 5 Qin Luo,1– 5 Xiaoguang Yao,1– 5 Delian Zhang,1– 5 Jing Hong,1– 5 Nanfang Li1– 5 1Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830001, People’s Republic of China; 2Xinjiang Hypertension Institute, Urumqi, Xinjiang, 830001, People’s Republic of China; 3NHC Key Laboratory of Hypertension Clinical Research, Urumqi, Xinjiang 830001 People’s Republic of China; 4Key Laboratory of Xinjiang Uygur Autonomous Region ”Hypertension Research Laboratory”, Urumqi, Xinjiang, 830001, People’s Republic of China; 5Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, Urumqi, Xinjiang, 830001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumuqi, Xinjiang, 830001, People’s Republic of China, Tel +86 8564818, Email lnanfang2016@sina.comBackground: A newly introduced obesity-related index, the weight-adjusted-waist index (WWI), emerges as a promising predictor of cardiovascular disease (CVD). Given the known synergistic effects of hypertension and obstructive sleep apnea (OSA) on cardiovascular risk, we aimed to explore the relationship between the WWI and CVD risk specifically within this high-risk cohort.Methods: A total of 2265 participants with hypertension and OSA were included in the study. Multivariate Cox regression analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD events. The restricted cubic spline (RCS) was used to further evaluate the nonlinear dose-response relationship.Results: During a median follow-up period of 6.8 years, 324 participants experienced a CVD event. Multivariate Cox regression analysis revealed that compared to the reference group, the HRs for the second, third, and fourth groups were 1.12 (95% CI, 0.79– 1.59), 1.35 (95% CI, 0.96– 1.89), and 1.58 (95% CI, 1.13– 2.22), respectively. Moreover, RCS analysis illustrated a clear J-shaped relationship between the WWI and CVD risk, particularly notable when WWI exceeded 11.5 cm/, signifying a significant increase in CVD risk.Conclusion: There was a J-shaped relationship between WWI and CVD in hypertensive patients with OSA, especially when the WWI was greater than 11.5 cm/, the risk of CVD was significantly increased.Keywords: hypertensive, obstructive sleep apnea, weight-adjusted-waist index, cardiovascular disease, visceral obesity

Shuaiwei Song,1– 5,&ast; Xintian Cai,1– 5,&ast; Junli Hu,1– 5 Qing Zhu,1– 5 Di Shen,1– 5 Huimin Ma,1– 5 Yingying Zhang,1– 5 Rui Ma,1– 5 Wenbo Yang,1– 5 Jing Hong,1– 5 Delian Zhang,1– 5 Nanfang Li1– 5 1Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830001, People’s Republic of China; 2Xinjiang Hypertension Institute, Urumqi, Xinjiang, 830001, People’s Republic of China; 3NHC Key Laboratory of Hypertension Clinical Research, Urumqi, Xinjiang, 830001, People’s Republic of China; 4Key Laboratory of Xinjiang Uygur Autonomous Region ”Hypertension Research Laboratory”, Urumqi, Xinjiang, 830001, People’s Republic of China; 5Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, Urumqi, Xinjiang, 830001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumqi, Xinjiang, 830001, People’s Republic of China, Tel +86 8,564,818, Email lnanfang2016@sina.comObjective: While the role of aldosterone in bone metabolism is well established, the specific effects of the widely used aldosterone antagonist, spironolactone, on bone health are not fully understood. This study aimed to investigate the effects of spironolactone on osteoporosis and future fracture risk in middle-aged and elderly hypertensive patients, revealing its potential benefits for bone health.Methods: Propensity score matching was employed in this study to create matched groups of spironolactone users and non-users at a 1:4 ratio. We investigated the association between spironolactone use and the risk of osteoporosis using multivariate logistic regression analysis. Furthermore, we conducted multivariate linear regression analysis to explore the relationship between cumulative dosage and the FRAX score. Subgroup analysis was also performed to assess the effects under different stratification conditions.Results: In both pre-match and post-match analyses, multivariable logistic regression revealed a significant reduction in the risk of osteoporosis in the spironolactone usage group (pre-match: odds ratios [OR] 0.406, 95% confidence interval [CI], 0.280– 0.588; post-match: OR 0.385, 95% CI, 0.259– 0.571). Furthermore, post-match multivariable linear regression demonstrated a clear negative correlation between cumulative spironolactone dosage and the FRAX score. Subgroup analyses consistently supported these findings.Conclusion: This study offers evidence supporting the significant positive impact of the antihypertensive drug spironolactone on bone health, resulting in a substantial reduction in the risk of osteoporosis and future fractures in hypertensive patients. Future research should consider conducting large-scale, multicenter, randomized controlled trials to further investigate the long-term effects of spironolactone on bone health in hypertensive patients.Keywords: hypertensive, spironolactone, aldosterone, osteoporosis, FRAX score

Jifeng Li,1 Dongxiao Zhang,1 Jing Hu,1 Jianchun Cui,2 Khattak Mazher Mansoor2 1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Liaoning Provincial People’s Hospital (Department of Thyroid and Breast Surgery, People’s Hospital of China Medical University), Shenyang, People’s Republic of ChinaCorrespondence: Dongxiao Zhang, Department of Galactophore, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23, Art Museum Back Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Tel +8617864190977, Email morningdong@163.comObjective: This study aims to systematically evaluate the effectiveness and safety of acupuncture in treating mammary hyperplasia.Methods: A comprehensive search was conducted in various databases, including PubMed, Web of Science, Cochrane Library, Embase, SinoMed, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP Database, from their inception until July 2023. Only randomized controlled trials (RCTs) researching the use of acupuncture for mammary hyperplasia were included. Quality assessment and data analysis were performed using RevMan 5.3 software.Results: Eight RCTs, comprising 573 patients, were included in this analysis. The meta-analysis revealed that in the acupuncture group, the experimental group was better than the control group in improving breast pain, breast lump extent, and the texture of breast lump (P=0.0007, I2=61%; P=0.02, I2=0%; P=0.0002, I2=0%). We found that both could be improved, but after statistical analysis, there was no significant advantage in the acupuncture group compared with the patent Chinese medicine group (p> 0.05).Conclusion: Acupuncture appears to be an effective and safe treatment for mammary hyperplasia, providing pain relief and reducing mass volume, texture, and extent. However, the insufficient quality of the available evidence indicates the need for further methodologically rigorous and convincingly designed studies to determine the efficacy and safety of acupuncture in the treatment of breast hyperplasia.Keywords: acupuncture, mammary hyperplasia, efficacy, meta-analysis, review, safety

Jiawen Hu,1,2 Yiwen Wang,1 Xiaojian Ji,1 Yinan Zhang,1 Kunpeng Li,1 Feng Huang1 1Department of Rheumatology and Immunology, First Medical Center of Chinese PLA General Hospital, Beijing, China; 2Medical School of Chinese PLA, Beijing, ChinaCorrespondence: Feng Huang, Department of Rheumatology and Immunology, First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China, Email frankfhuang@126.comAbstract: This article focuses on a range of non-pharmacological strategies for managing sarcopenia in chronic diseases, including exercise, dietary supplements, traditional Chinese exercise, intestinal microecology, and rehabilitation therapies for individuals with limited limb movement. By analyzing multiple studies, the article aims to summarize the available evidence to manage sarcopenia in individuals with chronic diseases. The results strongly emphasize the role of resistance training in addressing chronic diseases and secondary sarcopenia. Maintaining the appropriate frequency and intensity of resistance training can help prevent muscle atrophy and effectively reduce inflammation. Although aerobic exercise has limited ability to improve skeletal muscle mass, it does have some positive effects on physical function. Building upon this, the article explores the potential benefits of combined training approaches, highlighting their helpfulness for overall quality of life. Additionally, the article also highlights the importance of dietary supplements in combating muscle atrophy in chronic diseases. It focuses on the importance of protein intake, supplements rich in essential amino acids and omega-3, as well as sufficient vitamin D to prevent muscle atrophy. Combining exercise with dietary supplements appears to be an effective strategy for preventing sarcopenia, although the optimal dosage and type of supplement remain unclear. Furthermore, the article explores the potential benefits of intestinal microecology in sarcopenia. Probiotics, prebiotics, and bacterial products are suggested as new treatment options for sarcopenia. Additionally, emerging therapies such as whole body vibration training, blood flow restriction, and electrical stimulation show promise in treating sarcopenia with limited limb movement. Overall, this article provides valuable insights into non-pharmacological strategies for managing sarcopenia in individuals with chronic diseases. It emphasizes the importance of a holistic and integrated approach that incorporates exercise, nutrition, and multidisciplinary interventions, which have the potential to promote health in the elderly population. Future research should prioritize high-quality randomized controlled trials and utilize wearable devices, smartphone applications, and other advanced surveillance methods to investigate the most effective intervention strategies for sarcopenia associated with different chronic diseases.Keywords: sarcopenia, resistance training, nutrition, chronic disease, inflammation

Jie Hu,1,2,&ast; Lin Ouyang,3,&ast; Jinxiu Li,1 Xia Li,2 Yanjun Zhong,1 Can Hou2 1Critical Care Medicine Center, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, Key Laboratory Diseases Immunology, Ministry of Education, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Critical Care Medicine Center, Guilin Hospital of the Second Xiangya Hospital, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Can Hou, National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, Key Laboratory Diseases Immunology, Ministry of Education, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China, Email houcan84@csu.edu.cn Yanjun Zhong, Critical Care Medicine Center, The Second Xiangya Hospital, Center South University, Changsha, People’s Republic of China, Email zhongyanjun@csu.edu.cnObjective: To investigate the potential prognostic value of mean blood glucose (MBG) in hospital for prognosis of COVID-19 adult patients in the intensive unit care unit (ICU).Methods: A single-site and retrospective study enrolled 107 patients diagnosed as COVID-19 from department of critical care medicine in the Second Xiangya Hospital between October 2022 and June 2023. Demographic information including glucose during ICU hospitalization, comorbidity, clinical data, types of medications and treatment, and clinical outcome were collected. The multivariate logistic and cox regression was used to explore the relationship between blood glucose changes and clinical outcomes of COVID-19 during ICU stay.Results: In total, 107 adult patients confirmed with COVID-19 were included. Multivariate logistic regression results showed an increase in MBG was associated with ICU mortality rate. Compared with normal glucose group (MBG 7.8mmol/L).Conclusion: MBG level during ICU hospitalization was strongly correlated to all-cause mortality and co-infection in COVID-19 patients. These findings further emphasize the importance of overall glucose management in severe cases of COVID-19.Keywords: mean blood glucose, intensive care medicine, ICU mortality, COVID-19

Zeyu Xie, Jia Hu, Mengting Li, Xiao Hu, Jisheng Chen Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaCorrespondence: Jisheng Chen, Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, People’s Republic of China, Tel +86 20-87622305, Fax +86 20-61321967, Email cjslym@163.comPurpose: This study provides a reference for healthcare organizations in the selection and rational use of glucagon-like peptide-1 receptor agonists (GLP-1RAs), based on the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition).Methods: According to the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition) released in 2023, relevant databases such as PubMed, Cochrane, and Embase, drug labels, and clinical guidelines were searched for drug information. We systematically evaluated 7 GLP-1RAs marketed in China for safety, efficacy, economy, pharmacological properties, and other attributes using a percentage scoring method.Results: The final assessment result scores from highest to lowest were semaglutide (71.5 points), dulaglutide (68.9 points), liraglutide (68.7 points), exenatide (62.5 points), lixisenatide (59.9 points), polyethylene glycol loxenatide (55.9 points), and benaglutide (45.1 points).Conclusion: When a healthcare organization introduces GLP-1RAs to their hospital, they can refer to the assessment results and use the top three recommended medications: semaglutide, dulaglutide, and liraglutide.Keywords: glucagon-like peptide-1 receptor agonist, health technology assessment, type 2 diabetes mellitus, drug evaluation

Jianzhong Hu,1 Martin Chandler,1 Christopher Matthew Manuel,1 Jorge Caicedo,2 Michael Denne,2 Bruce Ewenstein,2 Ali G Mokdad,2 Shan Xing,3 Michael Recht1,4,5 1American Thrombosis and Hemostasis Network, Rochester, NY, USA; 2Rare Diseases and Hematology, Takeda Pharmaceuticals, U.S.A., Inc, Lexington, MA, USA; 3US Value and Evidence Generation, Takeda Pharmaceuticals, U.S.A., Inc, Lexington, MA, USA; 4Yale Center for Bleeding and Clotting Disorders, Yale University School of Medicine, New Haven, CT, USA; 5National Bleeding Disorders Foundation, New York, NY, USACorrespondence: Michael Recht, National Bleeding Disorders Foundation, 7 Penn Plaza, New York, NY, 10001, USA, Tel +1 800-360-2846, Email mrecht@hemophilia.orgIntroduction: Intracranial hemorrhage (ICH), a serious complication in persons with hemophilia A (PWHA), causes high rates of mortality and morbidity. Identified ICH risk factors from patient data spanning 1998– 2008 require reassessment in light of changes in the current treatment landscape.Aim and methods: PWHA identified in the ATHNdataset were evaluated retrospectively to assess incidence of ICH and determine the association between ICH risk and key characteristics using time-to-event analyses (Cox proportional-hazards models, survival curves, and sensitivity analyses).Results: Over a median follow-up time of 10.7 patient-years, 135 of 7837 PWHA over 2 years of age in the ATHNdataset (1.7%) experienced an ICH. Stratification by prophylaxis status and inhibitor status resulted in an incidence rate (IR) ratio (IRR) (IR+/IR−) of 0.63 (95% confidence interval [CI], 0.43– 0.94; P=0.020) and 1.76 (95% CI, 0.97– 3.20; P=0.059), respectively. Characteristics associated with greater risk of developing ICH include being aged 2– 12 years; being covered by Medicaid; having had HIV, hepatitis C, or hypertension; and never having received factor VIII or prophylactic treatment. In multivariable analysis with interaction, the estimated hazard ratio for PWHA never receiving prophylaxis was 7.67 (95% CI, 2.24– 26.30), which shrunk to 2.03 (95% CI, 1.30– 9.12) in bootstrapping analysis and 3.09 in the highest-penalty ridge-regression analysis but was still significant. Inhibitor status was found not to be statistically associated with ICH in all analyses.Conclusion: These results align with previous studies demonstrating that prophylaxis confers a protective effect against ICH. Previously, inhibitor positivity had been shown to increase risk for ICH; however, this study did not corroborate those findings.Keywords: bleeding, factor VIII, health insurance, hematologic disease, prophylaxis, risk factors

Shen Ma,1,&ast; Ran Hao,2,&ast; Yi-Wei Lu,1 Hui-Po Wang,1 Jie Hu,2,3 Yi-Xin Qi1 1Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050035, People’s Republic of China; 2Institutes of Health Research, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of China; 3Department of Science and Technology, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi-Xin Qi; Jie Hu, Tel +86-13932153600 ; +86-311-86266321, Email qiyixin@hebmu.edu.cn; Hujie@hebmu.edu.cnBackground: Distant metastasis remains the leading cause of death among patients with breast cancer (BRCA). The process of cancer metastasis involves multiple mechanisms, including compromised immune system. However, not all genes involved in immune function have been comprehensively identified.Methods: Firstly 1623 BRCA samples, including transcriptome sequencing and clinical information, were acquired from Gene Expression Omnibus (GSE102818, GSE45255, GSE86166) and The Cancer Genome Atlas-BRCA (TCGA-BRCA) dataset. Subsequently, weighted gene co-expression network analysis (WGCNA) was performed using the GSE102818 dataset to identify the most relevant module to the metastasis of BRCA. Besides, ConsensusClusterPlus was applied to divide TCGA-BRCA patients into two subgroups (G1 and G2). In the meantime, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a metastasis-related immune genes (MRIGs)_score to predict the metastasis and progression of cancer. Importantly, the expression of vital genes was validated through reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC).Results: The expression pattern of 76 MRIGs screened by WGCNA divided TCGA-BRCA patients into two subgroups (G1 and G2), and the prognosis of G1 group was worse. Also, G1 exhibited a higher mRNA expression level based on stemness index score and Tumor Immune Dysfunction and Exclusion score. In addition, higher MRIGs_score represented the higher probability of progression in BRCA patients. It was worth mentioning that the patients in the G1 group had a high MRIGs_score than those in the G2 group. Importantly, the results of RT-qPCR and IHC demonstrated that fasciculation and elongation protein zeta 1 (FEZ1) and insulin-like growth factor 2 receptor (IGF2R) were risk factors, while interleukin (IL)-1 receptor antagonist (IL1RN) was a protective factor.Conclusion: Our study revealed a prognostic model composed of eight immune related genes that could predict the metastasis and progression of BRCA. Higher score represented higher metastasis probability. Besides, the consistency of key genes in BRCA tissue and bioinformatics analysis results from mRNA and protein levels was verified.Keywords: breast cancer, metastasis, immune genes, weighted gene co-expression network analysis, prognostic mode

Wen Wen,1,&ast; Ping Lei,1,&ast; Wantai Dang,2 Liwen Ma,1 Jing Hu,1 Jian Liu1 1Department of Ultrasound, First Affiliated Hospital, Clinical Medical College of Chengdu Medical College, Chengdu, People’s Republic of China; 2Department of Rheumatology, First Affiliated Hospital, Clinical Medical College of Chengdu Medical College, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Liu, Department of Ultrasound, First Affiliated Hospital of Chengdu Medical College, 278 Baoguang Avenue, Xindu District, Chengdu, Si Chuan, 610500, People’s Republic of China, Email liujiansh@126.comObjective: This study aimed to employ echocardiography for measuring the markers of left ventricular (LV) diastolic function to investigate the effects of family history of gout on the LV diastolic function in patients with primary gout.Methods: Two hundred and eighty-four patients with primary gout who visited the Department of Rheumatology and Immunology of the First Affiliated Hospital of Chengdu Medical College from September 2020 to July 2022 were selected and their family history of gout, general information, and laboratory markers were recorded. Parameters of LV diastolic function were measured via echocardiography. The correlation between family history and LV diastolic function markers was analyzed using univariate and multivariate regression and the receiver operating characteristic (ROC) curve analyses.Results: LV diastolic function parameters, peak early mitral diastolic velocity (E)/peak late mitral diastolic velocity (A), and early septal mitral annulus diastolic motion velocity (Sepe’), early lateral mitral annulus diastolic motion velocity (Late’) and their mean (e’), were significantly lower in patients with familial primary gout, while left atrial volume index (LAVI) and E/e’ were markedly elevated in patients with sporadic primary gout. In patients with family history, the proportion of grade ≥ 2 LV diastolic insufficiency was distinctly higher than that in patients without family history (41.6% vs 12.3%). Even after adjusting for confounding variables, LAVI, E/A, Sepe’, Late’, e’, E/e’ were obviously associated with family history of gout. The area under ROC of family history combined with SUA level for identifying grade ≥ 2 LV diastolic insufficiency in patients with primary gout was 0.872 (P< 0.05).Conclusion: Family history of gout was closely related to echocardiographic LV diastolic function parameters in patients with gout, what is more, family history of gout combined with SUA level was found to be a valuable indicator for discriminating grade ≥ 2 LV diastolic insufficiency in patients with primary gout.Keywords: primary gout, family history, echocardiography, left ventricular diastolic function

Xiaoli Zhu,1 Yijun Chen,1 Mingan Zhu,2 Jinxi Hu3 1Department of Laboratory Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China; 2Department of Medical Laboratory, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 3Department of Oncological Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of ChinaCorrespondence: Mingan Zhu, Department of Medical Laboratory, Renmin Hospital, Hubei University of Medicine, No. 39 Chaoyang Middle Road, Shiyan, Hubei Province, 442000, People’s Republic of China, Tel +86 13872767288, Email 839239972@qq.com Jinxi Hu, Department of Oncological Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No. 150 Ximen Road of Linhai, Taizhou, Zhejiang Province, 317000, People’s Republic of China, Tel +86 18257689350, Email hujinxi6886@163.comBackground: Prior research has established an association between small dense low-density lipoprotein cholesterol (sdLDL-C) and dyslipidemia, serving as a significant marker for predicting cardiovascular diseases. Nevertheless, the connection between sdLDL-C and metabolic syndrome (MetS) remains unclear.Methods: This study retrospectively analyzed 23,187 individuals who underwent health checkups at Taizhou Hospital’s health management center. Here, we investigated the relationship between sdLDL-C and MetS, along with its components, utilizing Spearman correlation analysis, receiver operating characteristic (ROC) curve analysis, logistic regression, and mediation analysis.Results: The MetS group exhibited significantly higher level of sdLDL-C compared to the non-MetS group (P< 0.001). We observed a strong correlation between sdLDL-C and several key factors: TG (r = 0.711), TC (r = 0.672), LDL-C (r = 0.781), GGT (r = 0.420), and HDL-C (r = − 0.417). After adjusting for age and gender, the odds ratio (OR) (95% confidence interval [CI]) for MetS incidence in the second, third, and fourth quartiles versus the first quartile of sdLDL-C concentration were 2.264 (95% CI: 1.851, 2.770), 4.053 (95% CI: 3.350, 4.903), and 9.034 (95% CI: 7.531, 10.837). The optimal cut-off value for diagnosing MetS using sdLDL-C was determined to be 0.98 mmol/L, with an area under the ROC curve (AUC) of 0.716 (95% CI: 0.705, 0.726). Additionally, mediation analysis revealed that sdLDL-C mediated a 12.8% correlation between GGT and TG concentration.Conclusion: The sdLDL-C is correlated with MetS and it can successfully mediate the relationship between GGT and TG. Our data suggests that sdLDL-c and GGT are suitable parameters for preventing and monitoring MetS.Keywords: metabolic syndrome, small dense low-density lipoprotein cholesterol, mediation analysis, GGT

Yudong Miao,1 Ruizhe Ren,1 Zhanlei Shen,1 Yi Li,1 Wanliang Zhang,1 Junwen Bai,1 Dongfang Zhu,1 Jingbao Zhang,1 Dan Guo,1,2 Clifford Silver Tarimo,3 Rongmei Liu,4 Qiuping Zhao,4 Jianping Hu,5 Xue Zhou,6 Wenyong Dong7 1College of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Neurology, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 3Department of Science and Laboratory Technology, Dar es Salaam Institute of Technology, Dar es Salaam, Tanzania; 4Henan Key Laboratory for Health Management of Chronic Diseases, Central China Fuwai Hospital, Zhengzhou, People’s Republic of China; 5Henan Medical Communication and Project Forward Center, Zhengzhou, People’s Republic of China; 6College of Health Management, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 7Department of Hypertension, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of ChinaCorrespondence: Rongmei Liu, Assistant research fellow. Fuwai Central China Cardiovascular Hospital, Zhengzhou University Affiliated Central China Fuwai Hospital, &num;1, Fuwai Avenue, Zhengdong New District, Zhengzhou, 450014, People’s Republic of China, Tel +8615038204525, Email liuyongmei0203@163.comObjective: To evaluate the prevalence and influencing factors of long COVID, and measure the difference in health status between long COVID and non-long COVID cases.Methods: A cross-sectional survey was conducted from February 1 to 8, 2023, using a stratified random sampling method in four regions (eastern [Changzhou], central [Zhengzhou], western [Xining] and northeastern [Mudanjiang]) of China. The survey collected COVID-19 patients’ socio-demographic characteristics and lifestyles information. The scores of lifestyles and health status range from 5 to 21 and 0 to 100 points, respectively. The criteria of “persistent health problems after 4 weeks of COVID-19 infection” issued by the US Centers for Disease Control and Prevention was used to assess long COVID. Multiple linear regression was used to analyze the influencing factors of the health. The bootstrap method was used to analyze the lifestyles’ mediating effect. Propensity score matching (PSM) was used to evaluate the net difference in health scores between long COVID and non-long COVID cases.Results: The study included 3165 COVID-19 patients, with 308 (9.73%) long COVID cases. The health score of the long COVID cases (74.79) was lower than that of the non-long COVID cases (81.06). After adjusting for potential confounding variables, we found that never focused on mental decompression was a common risk factor for the health of both groups. Lifestyles was the mediating factor on individuals’ health. After PSM, the non-long COVID cases’ health scores remained higher than that of long COVID cases.Conclusion: The proportion of long COVID cases was low, but they were worse off in health. Given the positive moderating effect of healthy lifestyles on improving the health of long COVID cases, healthy lifestyles including mental decompression should be considered as the core strategy of primary prevention when the epidemic of COVID-19 is still at a low level.Keywords: long COVID, lifestyles, self-reported health status, propensity score matching, effect of mediation

Jiying Liu,1– 3 Guangyao Fang,2,4 Cong Lan,2 Chenming Qiu,5 Li Yao,2 Qian Zhang,2 Jingtang Hu,2 Yaolei Zhang,6 Yongjian Yang,1,2 Yan Zhang1,2 1Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Department of Cardiology, General Hospital of Western Theater Command, Chengdu, Sichuan, 610083, People’s Republic of China; 3Department of Cardiology, The Third People’s Hospital of Yibin, Yibin, Sichuan, 644000, People’s Republic of China; 4College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, 610083, People’s Republic of China; 5Department of Burn and Plastic Surgery, General Hospital of Western Theater Command, Chengdu, Sichuan, 610083, People’s Republic of China; 6Basic Medical Laboratory, General Hospital of Western Theater Command, Chengdu, Sichuan, 610083, People’s Republic of ChinaCorrespondence: Yongjian Yang, Department of Cardiology, General Hospital of Western Theater Command, Chengdu, Sichuan, 610083, People’s Republic of China, Tel +86-13880827421, Email yangyongjian38@sina.com Yan Zhang, Department of Cardiology, General Hospital of Western Theater Command, Chengdu, Sichuan, 610083, People’s Republic of China, Tel +86-18980530960, Email zhangyan610083@126.comPurpose: Pulmonary arterial hypertension (PAH) is a devastating disease with little effective treatment. The proliferation of pulmonary artery smooth muscle cells (PASMCs) induced by the nuclear factor-κB (NF-κB) signaling activation plays a pivotal role in the pathogenesis of PAH. Forsythoside B (FTS•B) possesses inhibitory effect on NF-κB signaling pathway. The present study aims to explore the effects and mechanisms of FTS•B in PAH.Methods: Sprague–Dawley rats received monocrotaline (MCT) intraperitoneal injection to establish PAH model, and FTS•B was co-treated after MCT injection. Right ventricular hypertrophy and pulmonary artery pressure were measured by echocardiography and right heart catheterization, respectively. Histological alterations were detected by H&E staining and immunohistochemistry. FTS•B’s role in PASMC proliferation and migration were evaluated by CCK-8 and wound healing assay. To investigate the underlying mechanisms, Western blotting, immunofluorescence staining and ELISA were conducted. The NF-κB activator PMA was used to investigate the role of NF-κB in FTS•B’s protective effects against PAH.Results: FTS•B markedly alleviated MCT-induced vascular remodeling and pulmonary artery pressure, and improved right ventricular hypertrophy and survival. FTS•B also reversed PDGF-BB-induced PASMC proliferation and migration, decreased PCNA and CyclinD1 expression in vitro. The elevated levels of IL-1β and IL-6 caused by MCT were decreased by FTS•B. Mechanistically, MCT-triggered phosphorylation of p65, IκBα, IKKα and IKKβ was blunted by FTS•B. FTS•B also reversed MCT-induced nuclear translocation of p65. However, all these protective effects were blocked by PMA-mediated NF-κB activation.Conclusion: FTS•B effectively attenuates PAH by suppressing the NF-κB signaling pathway to attenuate vascular remodeling. FTS•B might be a promising drug candidate with clinical translational potential for the treatment of PAH.Keywords: Forsythoside B, pulmonary arterial hypertension, NF-κB signaling pathway, pulmonary vascular remodeling, pulmonary artery smooth muscle cell

Qi Wang,1,2,&ast; Min Wen,2,3,&ast; Shaohang Fan,2,4 Jinning Liu,2 Xiaowen Wang,5 Wentao Guo,2 Jinyun Hu,6 Jialan Zhang,2 Bing Li,2,7 Lili Zhang,2,7 Yunshu Zhang,1,2,7 Keqing Li2,7 1Clinical Medicine College, Hebei University, Hebei, People’s Republic of China; 2Hebei Provincial Mental Health Center, Hebei, People’s Republic of China; 3Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 4School of Psychology and Mental Health, North China University of Science and Technology, Tangshan, People’s Republic of China; 5Psychosomatic Medicine Department, Jiangxi Provincial People’s Hospital, Nanchang, People’s Republic of China; 6Psychiatric Department, The Second People’s Hospital of Yuxi, Yunnan, People’s Republic of China; 7Hebei Provincial Key Laboratory of Major Mental and Behavioral Disorders, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Keqing Li, Hebei Provincial Mental Health Center, Hebei, People’s Republic of China, Email like2125@sina.com Yunshu Zhang, Hebei Provincial Mental Health Center, Hebei, People’s Republic of China, Email yunshucoffee@sina.comObjective: Suicidal behavior is strongly correlated with depressive symptoms and the degree of suicidal ideation. Cognitive impairment may have varying degrees of influence on suicidal ideation (SI) and suicidal attempts (SA). The aim of this study was to identify the cognitive biomarkers that distinguish suicidal ideation from suicidal attempts in adolescents.Methods: The cross-sectional sample comprised 54 adolescents with major depressive disorder (MDD) and 32 healthy controls (HC). The THINC-it was utilized to assess cognitive function of all the samples. Suicidal ideation was examined by the Positive and Negative Suicide Ideation Scale (PANSI). Based on the type of data, one-way ANOVA or Kruskal–Wallis was performed to investigate group differences. Bonferroni post-hoc analysis was employed for regulating type I error for pairwise comparisons. Network analysis was used to compare the networks associated with suicidal ideation, depression symptoms, and cognitive function between SA and SI.Results: The depression symptoms (HAMD-17) (F=72.515, P< 0.001) and suicidal ideation (PANSI) (F=267.952, P< 0.001) in the SA were higher than those in the SI. Analysis of between-group differences showed SA performed worse in THINC-it, especially in “Spotter (SP)” (P=0.033), “Objective cognition score (OS)” (P=0.027) and “Composite score (CS)” (P=0.017). Compared with SI, network analysis revealed that SA had a unique network of cognitive function, depressive symptoms, and suicidal ideation. Nevertheless, both networks exhibit comparable performance concerning the node strength of cognitive function. Within their separate networks, the aspects of CS, OS, and SP have emerged as the three most crucial elements.Conclusion: Adolescents with SI or SA exhibit a broad spectrum of cognitive impairments. Attention impairment can be beneficial in discerning between SI and SA. Future interventions for adolescent suicide can center on attention and the comprehensive cognitive ability that it represents.Keywords: attention impairment, suicide ideation, suicide attempts, adolescent, THINC-it tool, network analysis

Jiaji Hu,1,2,&ast; Binbin Xu,3,&ast; Nian Yao,1,2 Sha Peng,1,2 Ran Xu,1,2 Guiyuan Ma,1,2 Jinghui Zhang1,2,4 1Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, 410008, People’s Republic of China; 2Xiangya School of Nursing, Central South University, Changsha, Hunan Province, 410000, People’s Republic of China; 3School of Nursing, Hunan University of Chinese Medicine, Changsha, Hunan Province, 410000, People’s Republic of China; 4National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, 410008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinghui Zhang, Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, 410008, People’s Republic of China, Tel +86 158 7403 2339, Email 401212@csu.edu.cnBackground: Medical personnel contact with the patient closely, and their knowledge of vascular catheter-associated infections (VCAIs) is closely related to the prevention of VCAIs. Researchers mainly pay attention to the VCAIs knowledge of doctors and nurses but rarely pay attention to the nursing students in the hospital internship stage.Purpose: To investigate the current situation of knowledge of intern-nursing students in VCAIs, and analyze its influencing factors.Patients and Methods: 843 intern-nursing students were selected from 10 hospitals in five regions of eastern, western, southern, northern, and central China from June 26 to July 31, 2023, using a two-stage random sampling method. A self-designed questionnaire with good reliability and validity was used to investigate their knowledge of VCAIs, and t-test, multiple linear regression analysis, and Welch t-test were used to analyze the collected data by using SPSS Statistics 26.0 (IBM Corp., Armonk, NY).Results: Intern nursing students’ mean score of VCAIs knowledge was 48.66 (SD=15.77), with a score below 60 (unqualified) accounting for 75.4%, a score of 60– 79 (qualified) accounting for 19.7%, a score of 80– 89 (good) accounting for 3.6%, and a score of above 90 accounting for 1.3%. Students who attended VCAIs training three or more times had higher scores than those who did not attend training (B: 4.706, p=0.001), knowledge scores of students with a bachelor’s degree or above were higher than those with junior college degree or below (B: 8.479, p< 0.001), students who interned in tertiary hospitals had higher scores than those practicing in secondary hospitals (B:12.381, p< 0.001) and scores of students in hospital training were significantly higher than study independently (B:4.116, p=0.007).Conclusion: Intern-nursing students have a relatively low level of knowledge about VCAIs. It is recommended to strengthen clinical systematic and standardized training, improve the knowledge mastery level of intern-nursing students, and enhance their ability to handle VCAIs.Keywords: catheter-related bloodstream infections, intern-nursing students, knowledge, vascular catheter-associated infections

Yanjuan Song,1 Jing Hu,2 Chunlian Ma,3– 5 Hua Liu,3– 5 Zhanghua Li,6 Yi Yang3– 5 1Graduate School, Wuhan Sports University, Wuhan, Hubei Province, People’s Republic of China; 2Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei Province, People’s Republic of China; 3Fitness Monitoring and Chronic Disease Intervention Research Center, Wuhan Sports University, Wuhan, Hubei Province, People’s Republic of China; 4College of Sports Medicine, Wuhan Sports University, Wuhan, Hubei Province, People’s Republic of China; 5Hubei Key Laboratory of Exercise Training and Monitoring, Wuhan Sports University, Wuhan, Hubei Province, People’s Republic of China; 6Department of Orthopedics, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of ChinaCorrespondence: Yi Yang, Fitness Monitoring and Chronic Disease Intervention research center, Wuhan Sports University, Wuhan, Hubei Province, 430079, People’s Republic of China, Tel +86 139 7129 3990, Email yangyi999999@foxmail.com Zhanghua Li, Department of Orthopedics, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei Province, 430074, People’s Republic of China, Tel +86 189 7161 0121, Email lizhanghua_123@163.comAbstract: The development of numerous diseases is significantly influenced by inflammation. Macrophage-derived exosomes (M-Exos) play a role in controlling inflammatory reactions in various conditions, including chronic inflammatory pain, hypertension, and diabetes. However, the specific targets and roles of M-Exos in regulating inflammation in diseases remain largely unknown. This review summarizes current knowledge on M-Exos biogenesis and provides updated information on M-Exos’ biological function in inflammation modulation. Furthermore, this review highlights the functionalization and engineering strategies of M-Exos, while providing an overview of cutting-edge approaches to engineering M-Exos and advancements in their application as therapeutics for inflammation modulation. Finally, multiple engineering strategies and mechanisms are presented in this review along with their perspectives and challenges, and the potential contribution that M-Exos may have in diseases through the modulation of inflammation is discussed.Keywords: inflammation, macrophage-derived exosomes, biological functions, inflammation modulation, engineering strategies

Xuefang Wu,1,2 Shuang Li,2 Yingchun Yang,2 Jianjun Hu,2 Tongyin Yang2 1Department of Pathology, The Affiliated People’s Hospital of Ningbo University, Ningbo, 315100, People’s Republic of China; 2Department of Pathology, Guizhou Provincial People’s Hospital, Guiyang, 550002, People’s Republic of ChinaCorrespondence: Tongyin Yang; Shuang Li, Department of Pathology, Guizhou Provincial People’s Hospital, Guiyang, 550002, People’s Republic of China, Email 36486565@qq.com; 52kukiss@163.comAim: To investigate the correlation between doublecortin and CaM kinase-like-1 (DCAMKL-1) protein expression, K-ras gene mutation, and their impact on patient prognosis in colorectal cancer (CRC).Methods: Immunohistochemistry was used to detect the expression of DCAMKL-1 protein in 60 cases of colorectal adenoma, 82 cases of CRC (including 65 cases of lymph node metastasis) and paraffin-embedded paracancerous intestinal mucosal tissue. K-ras gene mutations in primary CRC lesions were detected using an amplification-refractory mutation system and fluorescent polymerase chain reaction. The relationship between DCAMKL-1 protein expression and K-ras gene mutations with the clinicopathological characteristics of patients with CRC was analyzed. Univariate Kaplan‒Meier survival analysis and multivariate Cox regression analysis were performed using follow-up data.Results: The mutation rate of the K-ras gene in 82 cases of CRC was 48.8% (40/82). The positivity rate for the presence of DCAMKL-1 protein in CRC was 70.7% (58/82), significantly higher than that for colorectal adenomas (53.3%; 32/60) and paracancerous intestinal mucosa (0%; 0/82) (P< 0.05). The positive expression rate for the presence of DCAMKL-1 protein in 65 patients with lymph node metastasis was higher in the primary lesions (69.2%; 45/65) than in the lymph node metastases (52.3%; 34/65) (χ2=12.087, P=0.001). The K-ras gene mutation status was positively correlated with DCAMKL-1 protein expression (r=0.252, P=0.022).Conclusion: In this study, a potential positive correlation between K-ras gene mutation and DCAMKL-1 protein expression was identified in CRC tissues. The assessment of K-ras gene mutation status and DCAMKL-1 protein expression holds promise for augmenting early diagnosis and prognosis evaluation in CRC. This approach may improve the overall prognosis and survival outcomes for CRC patients.Keywords: colorectal cancer, DCAMKL-1 protein, K-ras gene, mutation

Ying Liu, Jinsheng Hu Department of Psychology, Liaoning Normal University, Dalian, People’s Republic of ChinaCorrespondence: Jinsheng Hu, Department of Psychology, Liaoning Normal University, No. 850 Huanghe Road Shahekou District, Dalian, Liaoning Province, People’s Republic of China, Email hujspsy@126.comIntroduction: Social disturbance is a significant autism spectrum disorder (ASD) symptom. Action representation, which is a fundamental component of social interaction, can be investigated through kinesthetic motor imagery (KMI). KMI has been commonly studied with the well-developed laterality judgment paradigm, wherein participants are required to discriminate the laterality of a hand rotated by different angles along one or more axes. Here, we investigated the KMI processing in individuals with ASD by hand laterality judgment paradigm with eye-tracking methodology.Methods: The current study included 22 participants with ASD and 22 typical developing (TD) peers matched for age, gender, and intelligence. Participants were asked to judge the laterality of hand-with-tooth brush images.Results: Compared to the TD controls, individuals with ASD performed KMI with lower accuracy and longer response time in both correct and incorrect action conditions. The incorrect action representation had greater effect on KMI for individuals with ASD. Differences in eye-movement patterns were also observed, characterized by individuals with ASD were more focused on the object area while TD peers were more focused on the hand area.Conclusion: Results suggest that while altered KMI performance was observed, the incorrect action representation elicited more engagement of KMI in both groups. The object-centered eye-movement pattern may contribute to the refine of motor simulation intervention for individuals with ASD.Keywords: autism spectrum disorder, kinesthetic motor imagery, action representation, eye-tracking

Qiuyu Pan,1,2,&ast; Jun Hu,1,3,&ast; Yangzong,1 Xiuling Zhang,4 Zhaxidawa1 1Medical College of Tibet University, Lhasa, Tibet, 850000, People’s Republic of China; 2School of Public Health, North Sichuan Medical College, Nanchong, Sichuan, 610037, People’s Republic of China; 3School of Management, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, People’s Republic of China; 4The Hospital of Shandong Normal University, Jinan, Shandong, 250014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaxidawa, Medical College of Tibet University, Lhasa, Tibet, 850000, People’s Republic of China, Email zhaxi0891@qq.comBackground: Aging and its consequences are receiving considerable global attention in developed and developing countries. The health-related quality of life (HRQoL) of elderly individuals is crucial for public health and social welfare. Despite advances in understanding the health status of the elderly population in Tibet, a region located on China’s southwest border, a significant research gap remains regarding their HRQoL.Methods: We conducted a cross-sectional study in Tibet, China, in 2018, which thoroughly examined HRQoL and its determinants in individuals aged 60 and above. The EQ-5D-VAS instrument, consisting of two standardized scales (EQ-5D-3L and EQ-VAS), was utilized to measure HRQoL. We based the selection of potential determinants on a novel health ecological model encompassing various environmental and personal factors. We employed the Least Absolute Shrinkage and Selection Operator regression to systematically pinpoint key predictive factors for dimensionality reduction. The Tobit regression analysis further elucidated the relationship between these factors and the EQ-VAS and EQ-5D-index scores.Results: Our study encompassed 1604 elderly participants. They presented varying severity levels across all five dimensions of the EQ-5D-3L. The most commonly observed issue was pain/discomfort, with a prevalence of 40.27%. The average EQ-VAS score was 56.15 (SD=21.15), and the mean EQ-5D-index score was 0.78 (SD=0.25). Our multivariate analysis revealed that determinants such as age, sex, number of chronic illnesses, vision problems, hearing problems, physical activity, employment status, social participation, place of residence, and insurance type were significantly associated with HRQoL.Conclusion: The HRQoL of Tibet’s elderly population presents significant concerns, especially given the region’s challenging natural conditions. This underscores the urgent need for focused policy interventions at the socio-economic strata to extend vital support and aid.Keywords: HRQoL, the elderly, ecological model, Tibet, high altitude

Tongming Zhu,1,&ast; Junyan Fu,2,&ast; Di Zang,1,3,&ast; Zhe Wang,1,4,&ast; Xiangru Ye,1 Xuehai Wu,1 Jin Hu1 1Department of Neurosurgery, Fudan University Huashan Hospital, National Center for Neurological Disorders, National Key Laboratory for Medical Neurobiology, Shanghai Key Laboratory of Brain Function and Regeneration, Institutes of Brain Science, MOE Frontiers Center for Brain Science, Shanghai Medical College-Fudan University, Shanghai, People’s Republic of China; 2Department of Radiology, Fudan University Huashan Hospital, Shanghai, People’s Republic of China; 3Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 4Department of Medical Imaging Technology, SJTU-Ruijin-UIH Institute for Medical Imaging Technology, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuehai Wu; Jin Hu, Department of Neurosurgery, Fudan University Huashan Hospital, No. 12, Middle Wulumuqi Road, Shanghai, People’s Republic of China, Email wuxuehai2013@163.com; hujin@fudan.edu.cnBackground: The effect of Ommaya reservoirs on the clinical outcomes of patients with intraventricular hemorrhage (IVH) remains unclear.Objective: We aimed to determine the effect of combining the Ommaya reservoir and external ventricular drainage (EVD) therapy on IVH and explore better clinical indicators for Ommaya implantation.Methods: A retrospective analysis was conducted on patients diagnosed with IVH who received EVD-Ommaya drainage between January 2013 and March 2021. The patient population was divided into two groups: the Ommaya-used group, comprising patients in whom the Ommaya drainage system was activated post-surgery, and the Ommaya-unused group, comprising patients in whom the system was not activated. The study analyzed clinical, imaging, and outcome data of the patient population.Results: A total of 123 patients with IVH were included: 75 patients in the Ommaya-used group and 48 patients in the Ommaya-unused group. The patients in the Ommaya-used group showed a lower 3-month GOS than those in the Ommaya-unused group (p< 0.0001). The modified Graeb scale (mGS) in the Ommaya-unused group was significantly lower than that in the Ommaya-used group before the operation (p< 0.01) but not after surgery (p> 0.05). The GCS in the Ommaya-unused group was significantly lower than that in the other group, and there was a close correlation between the GCS and 3-month GOS (p< 0.0001). The GCS score showed significance in predicting the use of Ommaya (p< 0.001).Conclusion: The study demonstrated that combining EVD and Ommaya drainage was a safe and feasible treatment for IVH. Additionally, preoperative GCS was found to predict the use of Ommaya drainage in subsequent treatment, providing valuable information for pre-surgery decision-making.Keywords: intraventricular hemorrhage, Ommaya, external ventricular drainage

Nan Tang,1,2,&ast; Mengyue Pei,2,3,&ast; Lei Xie,2,4 Xueping Liang,2 Junping Hu,2,5 Yuan Gao1 1Department of Nursing, 1th Medical Centre of PLA General Hospital, Beijing, People’s Republic of China; 2School of Nursing, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 3Henan Kaifeng College of Science Technology and Communication, Kaifei, Henan, People’s Republic of China; 4Renji Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 5The First hospital of Lanzhou University, Lanzhou, Gansu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junping Hu; Yuan Gao, Email hjplandashengzhi@126.com; gaoyuanzd@163.comBackground: This study aims to examine the relationship between anxiety and depression and dyadic coping in infertile couples, exploring gender differences and dyadic interactions in these associations.Methods: A cross-sectional study was conducted involving 288 couples recruited from the First Affiliated Hospital of Lanzhou University between November 2021 and November 2022. The Dyadic Coping Scale, Anxiety Scale, and Depression Scale were utilized to measure dyadic coping, anxiety, and depression, respectively. The Actor-Partner Interdependence Model was used to analyze the actor effect and partner effect.Results: Wives exhibited significantly higher anxiety and depression scores compared to husbands (p< 0.001). No statistically significant difference was found in dyadic coping between wives and husbands. Positive dyadic coping in infertile couples had significant actor effects on anxiety and depression (p< 0.05) and partner effects (p< 0.05). Positive dyadic coping negatively predicted anxiety and depression of oneself and one’s partner. Negative dyadic coping in infertile couples also had significant actor effects on anxiety and depression (p< 0.05) and partner effects (p< 0.05). Negative dyadic coping positively predicted anxiety and depression of oneself and one’s partner.Conclusion: The dyadic coping style of infertile couples has both actor and partner effects on their own and their partner’s anxiety and depression. Anxiety and depression in infertile couples are influenced by their own and their partner’s dyadic coping style, respectively. Therefore, dyadic coping serves as an important indicator for predicting psychological outcomes in these couples.Keywords: infertility couple, dyadic coping, anxiety, depression

Xing Zhang,1,&ast; Yuanyuan Song,1,&ast; Hongyang Gong,1,&ast; Chunyan Wu,1 Binquan Wang,1 Wenxuan Chen,2 Jiawei Hu,2 Hanhui Xiang,2 Ke Zhang,1 Mingkuan Sun1 1Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2The Second Clinical Medical School, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingkuan Sun, Department of Toxicology, School of Public Health, Nanjing Medical University, No. 101 Longmian Avenue, Jiangning District, Nanjing, 211166, People’s Republic of China, Email sunmk@njmu.edu.cnAbstract: The increasing use of titanium dioxide nanoparticles (TiO2 NPs) across various fields has led to a growing concern regarding their environmental contamination and inevitable human exposure. Consequently, significant research efforts have been directed toward understanding the effects of TiO2 NPs on both humans and the environment. Notably, TiO2 NPs exposure has been associated with multiple impairments of the nervous system. This review aims to provide an overview of the documented neurotoxic effects of TiO2 NPs in different species and in vitro models. Following exposure, TiO2 NPs can reach the brain, although the specific mechanism and quantity of particles that cross the blood-brain barrier (BBB) remain unclear. Exposure to TiO2 NPs has been shown to induce oxidative stress, promote neuroinflammation, disrupt brain biochemistry, and ultimately impair neuronal function and structure. Subsequent neuronal damage may contribute to various behavioral disorders and play a significant role in the onset and progression of neurodevelopmental or neurodegenerative diseases. Moreover, the neurotoxic potential of TiO2 NPs can be influenced by various factors, including exposure characteristics and the physicochemical properties of the TiO2 NPs. However, a systematic comparison of the neurotoxic effects of TiO2 NPs with different characteristics under various exposure conditions is still lacking. Additionally, our understanding of the underlying neurotoxic mechanisms exerted by TiO2 NPs remains incomplete and fragmented. Given these knowledge gaps, it is imperative to further investigate the neurotoxic hazards and risks associated with exposure to TiO2 NPs. Keywords: TiO2 NPs, neurotoxic effects, oxidative stress, neuronal damage, neurotoxic mechanisms

Yuan Cui,1,2 Jingyi Hu,2 Yanan Li,1,2 Ryan Au,1,2 Yulai Fang,2 Cheng Cheng,1 Feng Xu,1,2 Weiyang Li,1,2 Yuguang Wu,1,2 Lei Zhu,2 Hong Shen2 1Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of ChinaCorrespondence: Lei Zhu; Hong Shen, Tel/Fax +86-25- 86617141, Email shenhong999@njucm.edu.cn; zhulei5100@njucm.edu.cnBackground: Baiyu Decoction (BYD), a clinical prescription of traditional Chinese medicine, has been proven to be valuable for treating ulcerative colitis (UC) by enema. However, the mechanism of BYD against UC remains unclear.Purpose: A combination of bioinformatics methods including network pharmacology and molecular docking and animal experiments were utilized to investigate the potential mechanism of BYD in the treatment of UC.Materials and Methods: Firstly, the representative compounds of each herb in BYD were detected by liquid chromatography-mass spectrometry. Subsequently, we predicted the core targets and potential pathways of BYD for treating UC through network pharmacology. And rat colitis model was established with dextran sodium sulfate. UC rats were subjected to BYD enema administration, during which we recorded body weight changes, disease activity index, and colon length to assess the effectiveness of BYD. Besides, quantitative real-time PCR, western blotting, ELISA and immunofluorescence were used to detect intestinal inflammatory factors, intestinal barrier biomarkers and TOLL-like receptor pathway in rats. Finally, the core components and targets of BYD were subjected to molecular docking so as to further validate the results of network pharmacology.Results: A total of 41 active compositions and 203 targets related to BYD-UC were subjected to screening. The results of bioinformatics analysis showed that quercetin and kaempferol may be the main compounds. Additionally, AKT1, IL-6, TP53, TNF and IL-1β were regarded as potential therapeutic targets. KEGG results explained that TOLL-like receptor pathway might play a pivotal role in BYD protecting against UC. In addition, animal experiments and molecular docking validated the network pharmacology results. BYD enema treatment can reduce body weight loss, lower disease activity index score, reverse colon shortening, relieve intestinal inflammation, protect intestinal barrier, and inhibit TOLL-like receptor pathway in UC rats. Besides, molecular docking suggested that quercetin and kaempferol docked well with TLR4, AKT1, IL-6, TP53.Conclusion: Utilizing network pharmacology, animal studies, and molecular docking, enema therapy with BYD was confirmed to have anti-UC efficacy by alleviating intestinal inflammation, protecting the intestinal barrier, and inhibiting the TOLL-like receptor pathway. Researchers should focus not only on oral medications but also on the rectal administration of medications in furtherance of the cure of ulcerative colitis. Keywords: network pharmacology, ulcerative colitis, enema therapy, TLR4/MyD88/NF-κB pathway

Jinyu Hu,1,&ast; Yuanyi Xiao,1,&ast; Guilin Jiang,2 Xiaorong Hu2 1School of Graduate and Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang City, People’s Republic of China; 2Department of Clinical Medicine, The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaorong Hu; Guilin Jiang, The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang City, Jiangxi Province, People’s Republic of China, Email 414496410@qq.com; j1333070957788@163.comBackground: Acupuncture is considered an important means of analgesic, which has been widely used in chronic pelvic pain syndrome (CPPS) management and treatment in recent years, published a large number of related documents. However, the relevant literature in this field has not been summarized and quantitatively analyzed. Therefore, this study aims to analyze the hotspots and predicting future research trends of acupuncture on pelvic pain syndrome.Methods: Search for the relevant publications of the web of science database from 2000 to 2022 about the treatment of acupuncture on chronic pelvic pain syndrome. The Citespace software and VosViewer software are used to analyze the visualization of the countries, institutions, authors, keywords and references and references in the literature.Results: A total of 173 publications were included. The annual number of essays gradually showed an overall growth trend over time. Medicine magazine is the most published journal in this field. J UROLOGY and Acupunct Med are the most cited journals and the most influential magazines; The most active and influential country is China, and the most produced institutions are Beijing University of Chinese Medicine; The most produced authors are Liu Zhishun. The most cited and most influential authors are Nickel JC and Armour M; keywords and cited reference analysis show that the quality of life, mechanism research, alternative medicine and electro-acupuncture will be the scientific hotspot of acupuncture treatment for chronic pelvic pain syndrome.Conclusion: This study shows that acupuncture on CPPS is increasingly valued and recognized. The future research hotspots will focus on the effects and mechanisms. In the future, more high-quality animal basic research will be required to explore the exact mechanism of acupuncture on CPPS. In addition, different parameters of acupuncture such as electric-acupuncture, stimulating frequency, duration and strength are also the focus of future research. More clinical trials are required to verify its safety and effectiveness.Keywords: acupuncture, chronic pelvic pain syndrome, bibliometrics, CiteSpace

Heng Wang,1,&ast; Tingting Gao,1,&ast; Ruijing Zhang,2,&ast; Jie Hu,1 Siqi Gao,1 Yuwen Wang,1 Xiaotong Qi,1 Yun Zhou,3 Guoping Zheng,1,4 Honglin Dong1 1Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Shanxi Provincial Integrated TCM and WM Hospital, Taiyuan, People’s Republic of China; 4Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia&ast;These authors contributed equally to this workCorrespondence: Honglin Dong, Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Xinghualing District, Taiyuan City, Shanxi Province, 030001, People’s Republic of China, Email honglindong@sxmu.edu.cn Guoping Zheng, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia, Email guoping.zheng@sydney.edu.auBackground: Contrast-induced acute kidney injury (CI-AKI) is considered to be the third leading cause of hospital-acquired kidney injury. Current studies mostly suggest that contrast agents mainly harm renal tubular epithelial cells, but we hypothesized that the development of CI-AKI should be the result of the interaction of renal vascular and tubular injury.Methods: First we constructed a CI-AKI mouse model and verified the success of the model by pathological injury and serum creatinine level. Immunohistochemistry, protein quantification and qRT-PCR were used to detect the location and level of expression of neutrophil extracellular traps (NETs) in the kidney. Then, we blocked the in vivo accumulation of NETs using GSK484 and DNase I and detected the expression of NETs and the damage of glomerular and peritubular capillaries.Results: We first identified the presence of NETs in CI-AKI mice, and NETs were mainly accumulated in glomeruli and peritubular capillaries. The expression of NETs was positively correlated with the severity of CI-AKI kidney. After inhibition of NETs release or promotion of NETs degradation by drugs, renal vascular endothelial cell injury was reduced and renal pathological changes and creatinine levels were reversed in CI-AKI mice. In addition, inhibition of NETs reduced apoptosis and pyroptosis of renal cells and attenuated inflammation in vivo.Conclusion: These findings suggest that NETs are involved in the development of CI-AKI by damaging glomerular and peritubular capillary endothelial cells. This study will provide a new strategy for clinical prevention and treatment of CI-AKI.Keywords: contrast-induced acute kidney injury, neutrophils, neutrophil extracellular traps, glomeruli, peritubular capillaries

Ling Zhou,1,&ast; Yu Gan,1,&ast; Yanjun Wu,1 Dongdong Xue,1 Jianhong Hu,1 Yilan Zhang,2 Yang Liu,3 Siyuan Ma,1 Junyi Zhou,1 Gaoxing Luo,1 Daizhi Peng,1 Wei Qian1 1Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China; 2Department of Oral and Maxillofacial Head and Neck Surgery, Army Medical Center of PLA/Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, People’s Republic of China; 3Department of Urology, Urology Institute of PLA, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daizhi Peng; Wei Qian, Email dzpengpub@126.com; weiqian87@126.comIntroduction: Indocyanine green (ICG) fluorescence imaging has been used in the resection surgery and sentinel lymph node biopsy of many tumors. The aim of the present study is to verify the feasibility and effectiveness of ICG fluorescence imaging used for guiding the biopsy and resection of skin squamous cell carcinoma (SSCC).Methods: Sixty patients were enrolled, including 18 patients of suspected SSCC and 42 patients of diagnosed SSCC on admission. The ICG fluorescence imaging-guided skin biopsy was performed preoperatively in the 18 cases of suspected SSCC. Fifty-three patients underwent ICG fluorescence imaging-guided radical excision.Results: The results showed that 138 skin tissue samples in 60 patients with preoperative or intraoperative ICG fluorescence imaging-guide biopsy were collected. For a total number of 138 biopsies, 122 specimens were squamous cell carcinoma, and the accuracy rate was 88.4%, which was significantly higher than that of the group without preoperative ICG fluorescence imaging (41/62, 66.1%, P < 0.05). Fifty-three patients underwent surgery guided with ICG fluorescence imaging. Residual fluorescent signals in 24 patients were intraoperatively found and the excision was then expanded until the signals disappeared. Follow-up to November 2022, 12 patients died, of which 5 cases died from the tumor recurrence, and the others died due to advanced ages or other reasons. The recurrence rate was 9.4%, which was not significantly different from that of the group received routine radical resection (4/35, 11.4%, P > 0.05). Moreover, sentinel lymph nodes were successfully detected under ICG fluorescence imaging in the 4 patients with suspected lymph node metastases, and the location of lymph nodes can be precisely identified.Conclusion: ICG fluorescence imaging technique can guide the pathology biopsy to improve the accuracy of pathological examination, and help to identify the boundaries of tumor tissues and sentinel lymph nodes to resect tumor radically during operation.Keywords: indocyanine green, ICG, near-infrared fluorescence imaging, skin squamous cell carcinoma, biopsy, radical resection

Xintian Cai,1,&ast; Shuaiwei Song,1,&ast; Junli Hu,2 Lei Wang,2 Di Shen,1 Qing Zhu,2 Wenbo Yang,2 Qin Luo,2 Jing Hong,2 Nanfang Li2 1Graduate School, Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Hypertension Research Laboratory, Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Hypertension Research Laboratory, Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, No. 91 Tianchi Road, Urumqi, Xinjiang, 830001, People’s Republic of China, Tel +86 8564818, Email lnanfang2016@sina.comObjective: This study aimed to evaluate the relationship between the systemic inflammation response index (SIRI) and the risk of stroke and its subtypes in elderly patients with hypertension and to explore its predictive accuracy and any potential effect modifiers.Methods: The study included 4749 participants with no history of stroke at baseline. Cox regression was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CIs). Interaction tests and subgroup analyses were conducted. The predictive performance of various inflammatory indicators for stroke was compared using the area under the curve (AUC), continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI).Results: During a median follow-up period of 3.2 years, 640 strokes were recorded, of which 526 were ischemic and the remainder hemorrhagic. After adjustment for confounders, compared to the reference group, the HRs (95% CI) of stroke were 1.28 (95% CI, 1.01– 1.64) and 1.46 (95% CI, 1.14– 1.88) for participants in the second and third tertiles, respectively. We observed interactions between SIRI and homocysteine levels (< 15 vs. ≥ 15 μmol/L) (p for interaction = 0.014) on ischemic stroke risk. Furthermore, the AUC, NRI, and IDI analyses demonstrated that SIRI exhibited better predictive value for stroke risk when compared to other indicators. Similar results were observed for both ischemic and hemorrhagic strokes.Conclusion: Elevated SIRI levels were significantly associated with the risk of stroke and its subtypes in elderly patients with hypertension, suggesting its potential as a promising indicator for stroke risk in this population. However, larger prospective studies are needed to confirm these findings.Keywords: systemic inflammation response index, stroke, elderly, hypertension, inflammation, cohort study

Dandan Wu,1,&ast; Junxiao Cong,1,&ast; Jiali Wei,1 Jing Hu,1 Wenhao Sun,1 Wei Ran,2 Chenghui Liao,1 Housheng Zheng,1 Liang Ye1 1Department of Immunology, International Cancer Center, Shenzhen University Health Science Center, Shenzhen, People’s Republic of China; 2State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Ye, Department of Immunology, International Cancer Center, Shenzhen University Health Science Center, Shenzhen, 518055, People’s Republic of China, Tel +86-0755-26631420, Fax +86-0755-86671943, Email liangyeszu@163.comBackground: The emergence of the coronavirus disease 2019 (COVID-19) pandemic and the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VOCs) requires the continuous development of safe, effective, and affordable prevention and therapeutics. Nanobodies have demonstrated antiviral activity against a variety of viruses, providing a new candidate for the prevention and treatment of SARS-CoV-2 and its variants.Methods: SARS-CoV-2 glycoprotein spike 1 subunit (S1) was selected as the target antigen for nanobody screening of a naïve phage display library. We obtained a nanobody, named Nb-H6, and then determined its affinity, inhibition, and stability by ELISA, Competitive ELISA, and Biolayer Interferometry (BLI). Infection assays of authentic and pseudotyped SARS-CoV-2 were performed to evaluate the neutralization of Nb-H6. The structure and mechanism of action were investigated by AlphaFold, docking, and residue mutation assays.Results: We isolated and characterized a nanobody, Nb-H6, which exhibits a broad affinity for S1 and the receptor binding domain (RBD) of SARS-CoV-2, or Alpha (B.1.1.7), Delta (B.1.617.2), Lambda (C.37), and Omicron (BA.2 and BA.5), and blocks receptor angiotensin-converting enzyme 2 (ACE2) binding. Moreover, Nb-H6 can retain its binding capability after pH or thermal treatment and effectively neutralize both pseudotyped and authentic SARS-CoV-2, as well as VOC Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (BA.2 and BA.5) pseudoviruses. We also confirmed that Nb-H6 binds two distinct amino acid residues of the RBD, preventing SARS-CoV-2 from interacting with the host receptor.Conclusion: Our study highlights a novel nanobody, Nb-H6, that may be useful therapeutically in SARS-CoV-2 and VOC outbreaks and pandemics. These findings also provide a molecular foundation for further studies into how nanobodies neutralize SARS-CoV-2 and variants and imply potential therapeutic targets for the treatment of COVID-19.Keywords: COVID-19, antiviral medication, single-domain antibody, neutralizing antibody, bio-screening

Lumin Liu,1,&ast; Junwei Hu,1,&ast; Junjie Lu,2 Jiaxin Yang3 1Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Social and Behavioral Sciences, Harvard University T.H. Chan School of Public Health, Boston, MA, USA; 3Yueyang 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: Jiaxin Yang, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437, People’s Republic of China, Email love_yangjiaxin@163.comPurpose: The objective of this study is to evaluate the immediate and time-dependent effects of AA in treating PD and assess its safety.Methods/Design: This study is a randomized, single-blinded, controlled trial that will enroll 92 patients in a 1:1 allocation ratio. Patients will be assigned to either the treatment group (n=46) or the control group (n=46). During the first menstrual period, the treatment group will receive AA treatment, while the control group will receive sham AA treatment for 7 days. The second menstrual period will serve as the follow-up period. The primary outcome measure is the Visual Analog Scale (VAS) score 30 min after the first treatment. Secondary outcome measures include the VAS score immediately after the first treatment, onset time of analgesic effect, duration of pain, extra dosing rate of ibuprofen, and change of the Menstrual Distress Questionnaire (MDQ) score. The outcomes will be assessed at baseline, during the intervention period, and during the follow-up period.Conclusion: The study results will provide evidence on the efficacy and safety of AA in managing PD by analyzing its immediate effect, time-effect relationship, and reduction of painkiller use.Trial Registration: Chinese Clinical Trial Registry (ChiCTR2300069741).Keywords: acupressure, dysmenorrhea, menstrual pain, ear

Xuan Zhang,1 Yaqing Lin,2 Huixin Chen,1 Jianhua Hu,1 Hong Zhao,1 Meifang Yang,1 Dongsheng Han3– 5 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, People’s Republic of China; 2Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 4Key Laboratory of Clinical in vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 5Institute of Laboratory Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Dongsheng Han, Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Tel +86-571-87236394, Fax +86-571-87236394, Email hands@zju.edu.cnPurpose: Metagenomic next-generation sequencing (mNGS) has been widely used to diagnose infectious diseases. However, there are few studies on its diagnostic performance in the central nervous system (CNS) cryptococcosis. This study examined the diagnostic efficacy of mNGS in identifying Cryptococcus spp. in cerebrospinal fluid (CSF) samples.Patients and Methods: From March 2021 to March 2023, 290 patients with suspected CNS infection were recruited from the First Affiliated Hospital, School of Medicine, Zhejiang University, and 74 patients were ultimately included in the study. Lastly, 22 patients with CNS cryptococcosis were included. Of these patients, 25 CSF samples were enrolled. The diagnostic performance of conventional assays [including India ink, cryptococcal antigen (CrAg) testing, and culture] and mNGS was evaluated for CNS cryptococcosis.Results: In the 25 samples collected, the coincidence rates of mNGS with India ink, CrAg, and culture were 64.0% (16/25), 80.0% (20/25), and 80.0% (20/25), respectively. Without antifungal drug exposure, the coincidence rates were increased to 66.7% (10/15), 100.0% (15/15), and 93.3% (14/15), respectively. The coincidence rates after antifungal therapy were all decreased to 60.0% (6/10), 50.0% (5/10), and 60.0% (6/10), respectively. Moreover, in the 25 samples, the sensitivity of mNGS reached 80.0%, and of India ink, CrAg testing, and culture were 68.0, 100.0, and 60.0%, respectively. The mNGS showed an excellent positive rate (100.0%) in the 15 samples collected without antifungal drug exposure, which was significantly higher than the antifungal drug-exposed group (n = 10) (50.0%) (P = 0.005). The reads of Cryptococcus spp. before antifungal therapy were significantly higher than after it (median, 25,915 vs 2, P = 0.008).Conclusion: mNGS is an effective tool for diagnosing CNS cryptococcosis using CSF; however, its sensitivity decreases considerably in patients who have been effectively treated with antifungal drugs.Keywords: metagenomic next-generation sequencing, central nervous system cryptococcosis, cerebrospinal fluid, invasive fungal infection

Zhen Li,1,&ast; Bin Zhu,2,&ast; Weiqin Chen,1 Jun Hu,1 Yingjun Xue,1 Hongmei Yin,1 Xiaobo Hu,3 Weiwei Liu1 1Department of Laboratory Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 2Department of Rehabilitation, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People’s Republic of China; 3General Office, Centre for Clinical Laboratory, Shanghai, 200126, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiwei Liu, Department of Laboratory Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China, Email huashanvivian@126.com Xiaobo Hu, General Office, Centre for Clinical Laboratory, Shanghai, 200126, People’s Republic of China, Email huxiaobo@vip.sina.comPurpose: The non-albicans Candida (NAC) species have recently gained great importance worldwide due to the increasing proportion in candida causing bloodstream infections. This investigation aimed to explore the efficacy of Pseudolaric acid A (PAA, a diterpenoid derived from Pseudolarix kaempferi) and its synergistic effect with fluconazole (FLC) against NAC species, including C. tropicalis, C. parapsilosis complex, and C. glabrata.Methods: The microdilution checkerboard assay and time-killing curves were performed to detect the antifungal efficiency. To examine the integrity of cell walls and membranes, calcofluor white stain and propidium iodide stain were used. The changes of intracellular ultrastructure in Candida cells after treatment were observed using transmission electron microscopy. Changes in cell viability with the autophagy inhibitor 3-MA were assessed by the XTT method.Results: It was revealed that PAA alone is effective on C. tropicalis, C. parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis (MIC 8– 128 μg/mL). Strong synergism against FLC-resistant C. tropicalis was observed (FICI 0.07– 0.281), when PAA and FLC were combined. PAA had dose-dependently detrimental effects on C. tropicalis cell membranes. Moreover, increased vacuoles and autophagosome formation were found in C. tropicalis exposed to PAA. And the inhibitory effect of PAA against C. tropicalis can be relieved by autophagy inhibitor 3-MA in a certain concentration range. Ultrastructural alterations of C. tropicalis were more pronounced under the combination of PAA and FLC, including separation of the cell membrane from the cell wall, increased number of vacuoles, and degradation of organelles.Conclusion: These observations indicated that PAA and its combination with FLC could be a promising therapeutic candidate for treating infections caused by NAC species.Keywords: pseudolaric acid A, fluconazole, antifungal, combination, non-albicans Candida, synergy, autophagy