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Juan Li,1,* Shu Wang,2,* Chaoping Ma,1,* Ning Ning,3,* Yingying Huang,1,4,* Min Jiao,1 Jiyuan Zhang,1 Wenwu Sun,3 Jiaoyan Li,3 Bing Zhao,3 Enqiang Mao,3 Zaiqian Che,3 Chengjin Gao1 1Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Intensive Care Medicine, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, 400016, People’s Republic of China; 3Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China; 4Dementia Research Center, Macquarie University, Sydney, Australia*These authors contributed equally to this workCorrespondence: Chengjin Gao, Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, People’s Republic of China, Email gaochengjin@xinhuamed.com.cn Zaiqian Che, Departments of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China, Email chezaiqian@163.comPurpose: New-onset atrial fibrillation (NOAF) and sepsis-induced coagulopathy (SIC) are severe complications in septic patients. However, the relationship between NOAF and SIC score has not been clearly defined. This study aims to investigate the association between SIC score and NOAF, as well as their effect on mortality in sepsis.Patients and Methods: This study was a two-center retrospective analysis. Medical data were collected from patients diagnosed with sepsis. The patients were divided into NOAF and non-NOAF groups, and the SIC score was calculated for each group. Univariable and multivariable logistic regression analyses were performed to explore the relationship between the SIC score and NOAF, as well as their effects on mortality. The Kaplan-Meier curve was used to assess the survival rate.Results: A total of 2,280 septic patients were included, with 132 (5.7%) suffering from NOAF. Multivariable logistic regression analyses indicated that age, gender, the Acute Physiology and Chronic Health Evaluation II score (APACHE II), heart rate, renal failure, stroke, chronic obstructive pulmonary disease (COPD), and the SIC score were independent risk factors for NOAF in sepsis. Moreover, NOAF was associated with an increased risk of in-hospital mortality, 28-day mortality, and 90-day mortality. These results were consistent across subgroup analyses.Conclusion: The SIC score was an independent risk factor for NOAF in septic patients, and NOAF was an independent risk factor for predicting mortality.Keywords: sepsis, sepsis-induced coagulopathy, new-onset atrial fibrillation, association, mortality

Kang He,1,* Jie Zang,2,* Tingting Ren,1,* Shaojie Feng,3 Mohan Liu,1 Xude Zhang,3 Wenchang Sun,2 Jinjin Chu,2 Donghua Xu,2 Fengxia Liu3 1Department of Clinical Medicine of Shandong Second Medical University, Weifang, People’s Republic of China; 2Central Laboratory, Weifang People’s Hospital, Shandong Second Medical University/Weifang People’s Hospital, Weifang, People’s Republic of China; 3Department of Allergy, Weifang People’s Hospital, Shandong Second Medical University, Weifang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Donghua Xu; Fengxia Liu, Email flower322@163.com; wf_lfx@163.comAbstract: Atopic dermatitis (AD) is a chronic and inflammatory skin disease with intense itchiness that is highly prevalent worldwide.The pathogenesis of AD is complex and closely related to genetic factors, immunopathogenic factors, environmental factors, and skin infections. Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells derived from the mesenchymal stroma. They have anti-inflammatory, anti-apoptotic, and regenerative properties. Numerous studies demonstrate that MSCs can play a therapeutic role in AD by regulating various immune cells, maintaining immune homeostasis, and promoting the repair of damaged tissues. The key mediators for their biological functions are extracellular vesicles (MSC-Evs) and soluble cytokines derived from MSCs. The safety and efficacy of MSCs have been demonstrated in clinical Phase I / IIa trials for AD. This paper provides a comprehensive review of the pathogenesis of AD and the currently published studies on the function of MSCs and MSC-Evs in AD, primarily including the pathogenesis and the immunomodulatory impacts of MSCs and MSC-Evs, along with advancements in clinical studies. It provides insights for comprehending AD pathogenesis and investigating treatments based on MSCs.Keywords: atopic dermatitis, mesenchymal stem cells, Th2-associated immunity, extracellular vesicle

Weitang Sun,1 Jingbin Zhong,1 Buyun Gao,2 Jieling Feng,1 Zijie Ye,1 Yueling Lin,3 Kelan Zhang,3 Wenqi Su,3 Shibo Zhu,1 Yinghua Li,4 Wei Jia1 1Department of Pediatric Urology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2School of Pharmacy, Fudan University, Shanghai, People’s Republic of China; 3Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Center Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Wei Jia, Email jiawei198044@hotmail.comPurpose: Hydroxyapatite-based nanoparticles have found diverse applications in drug delivery, gene carriers, diagnostics, bioimaging and tissue engineering, owing to their ability to easily enter the bloodstream and target specific sites. However, there is limited understanding of the potential adverse effects and molecular mechanisms of these nanoparticles with varying geometries upon their entry into the bloodstream. Here, we used two commercially available hydroxyapatite nanoparticles (HANPs) with different geometries (less than 100 nm in size each) to investigate this issue.Methods: First, the particle size, Zeta potential, and surface morphology of nano-hydroxyapatite were characterized. Subsequently, the effects of 2~2000 μM nano-hydroxyapatite on the proliferation, migration, cell cycle distribution, and apoptosis levels of umbilical vein endothelial cells were evaluated. Additionally, the impact of nanoparticles of various shapes on the differential expression of genes was investigated using transcriptome sequencing. Additionally, we investigated the in vivo biocompatibility of HANPs through gavage administration of nanohydroxyapatite in mice.Results: Our results demonstrate that while rod-shaped HANPs promote proliferation in Human Umbilical Vein Endothelial Cell (HUVEC) monolayers at 200 μM, sphere-shaped HANPs exhibit significant toxicity to these monolayers at the same concentration, inducing apoptosis/necrosis and S-phase cell cycle arrest through inflammation. Additionally, sphere-shaped HANPs enhance SULT1A3 levels relative to rod-shaped HANPs, facilitating chemical carcinogenesis-DNA adduct signaling pathways in HUVEC monolayers. In vivo experiments have shown that while HANPs can influence the number of blood cells and comprehensive metabolic indicators in blood, they do not exhibit significant toxicity.Conclusion: In conclusion, this study has demonstrated that the geometry and surface area of HANPs significantly affect VEC survival status and proliferation. These findings hold significant implications for the optimization of biomaterials in cell engineering applications.Keywords: hydroxyapatite nanoparticle, circulatory system, biocompatibility, survival, proliferation

Wei Sun,1,* Yun Liu,2,* Li Wang3 1Department of Oncology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 2Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 3Department of Oncology, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Wang, Department of Oncology, Beijing Luhe Hospital, Capital Medical University, No. 82, Xinhua South Road, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel +86 18010279916, Email lhyywl@163.comObjective: This study aimed to investigate the feasibility of the efficacy and safety of TACE combined with Lenvatinib and PD-1 blockade in HCC with portal vein tumor thrombus (PVTT).Methods: Patients with HCC and PVTT who underwent TACE combined with Lenvatinib and PD-1 blockade as first-line therapy in clinical practice were retrospectively included. All subjects were followed-up regularly to obtain prognostic outcomes. The safety profile observed during the combination therapy was collected and documented. The Log rank test was used for exploratory analysis of prognosis and baseline characteristics and Cox regression analysis was used for multivariate analysis.Results: A total of 67 HCC patients with PVTT who received TACE combined with Lenvatinib and PD-1 blockade were included in this study. The best therapeutic response during treatment suggested that 4 patients achieved complete response, 30 patients showed partial response, 25 patients were stable disease, 5 patients had disease progression and 3 patients were not available. Objective response rate of this regimen was 50.7% [95% confidence interval (CI): 38.2– 63.2%] and disease control rate was 88.1% (95% CI: 77.8– 94.7%). The median progression-free survival of 67 HCC patients with PVTT who received TACE combined with Lenvatinib and PD-1 blockades was 9.3 months (95% CI: 5.85– 12.75), and the median overall survival was 24.4 months (95% CI: 19.11– 29.69). The safety profile highlighted that 65 patients experienced adverse reactions regardless of grade during treatment (97.0%), among whom 34 patients were deemed as grade ≥ 3 adverse reactions (50.7%). The most common adverse reactions were hypertension, fatigue, abnormal liver function, nausea, vomiting, and diarrhea. Overall adverse reactions were acceptable and controllable.Conclusion: TACE combined with Lenvatinib and PD-1 blockades as first-line therapy for HCC with PVTT demonstrated potential feasibility and encouraging clinical outcomes, providing long-term survival benefits for HCC patients. This conclusion should be confirmed in prospective large-scale clinical trials.Keywords: hepatocellular carcinoma, portal vein tumor thrombus, TACE, Lenvatinib, PD-1 blockades, efficacy, safety

Zengyan Lu, Yangjin Li, Zhihao Yan, Qingsong Sang, Wenqiang Sun College of Educational Science, Anhui Normal University, Wuhu, People’s Republic of ChinaCorrespondence: Wenqiang Sun; Qingsong Sang, College of Educational Science, Anhui Normal University, Wuhu, Anhui, 241000, People’s Republic of China, Email sunwq2007@163.com; s7210qs1@ahnu.edu.cnBackground: College students’ insomnia symptoms is a topic of growing interest and studies have begun to explore the factors that influence college students’ insomnia symptoms. This study investigated the relationship between perceived stress and college students’ insomnia symptoms, as well as the chain mediating roles of fear of missing out and mobile phone dependence, and the moderating roles of environmental sensitivity.Methods: In this study, 748 college students (M = 20.59, SD = 2.65) as a sample for cross-sectional study. The Perceived Stress Questionnaire, Brief Fear of Missing Out Scale, Self-Rating Questionnaire for Adolescent Problematic Mobile Phone Use, Athens Insomnia Scale and Highly Sensitive Child Scale were used.Results: (1) Perceived stress significantly positively predicts the insomnia symptoms of college students; (2) Fear of missing out and mobile phone dependence play a chain mediating role between perceived stress and the insomnia symptoms of college students; (3) environmental sensitivity moderated the pathways of mobile phone dependence on insomnia symptoms.Conclusion: We revealed the underlying mechanisms between perceived stress and insomnia symptoms. The findings highlight the importance of interventions for fear of missing out and mobile phone dependence, as well as the role of environmental sensitivity in influencing insomnia symptoms.Keywords: perceived stress, fear of missing out, mobile phone dependence, environmental sensitivity, insomnia symptoms, college students

Min Sun,1 Guanchi Yan,2 Siming Sun,3 Xiaonan Li,1 Wei Sun,4 Yuehui Wang1 1Department of Geriatrics, The First Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 3Department of Clinical Research, The First Hospital of Jilin University, Changchun, People’s Republic of China; 4Education Department, The First Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yuehui Wang, Department of Geriatrics, The First Hospital of Jilin University, No. 1 Xinmin Street, Chaoyang District, Changchun, Jilin, 130061, People’s Republic of China, Tel +86-13614303457, Email yuehuiwang300@jlu.edu.cn Wei Sun, Education Department, The First Hospital of Jilin University, No. 1 Xinmin Street, Chaoyang District, Changchun, Jilin, 130061, People’s Republic of China, Tel +86-16604302962, Email 18504381676@163.comBackground: Serum trace elements and oxidative stress factors are related to diabetic microvascular complications. The study was to investigate the complex relationship between trace elements, oxidative stress factors, and the severity of microvascular complications of diabetes in older adults.Methods: The present study included patients with or without type 2 diabetes, and blood glucose, blood lipids, trace elements (iron, magnesium, zinc), oxidative stress factors (malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC)) were evaluated. Risk factors for the severity of diabetic microvascular complications in older adults with diabetes were also estimated.Results: There were statistically significant differences in fasting blood glucose (FBG), triglycerides (TG), low density lipoprotein (LDL), glycated hemoglobin (HbAlc), MDA, NO, SOD, T-AOC, magnesium, and zinc between the two groups (P< 0.05). Iron (rZinc = 0.147, rSOD = 0.180, rT-AOC = 0.193, P < 0.05) was positively correlated with zinc, SOD and T-AOC. Iron was negatively correlated with MDA (rMDA = − 0.146, P < 0.05). Magnesium was positively correlated with SOD (rMagnesium = 0.147, P < 0.05). Zinc (rSOD = 0.616, rT-AOC = 0.575, P < 0.01) was positively correlated with SOD and T-AOC. Zinc (rMDA =− 0.636, rNO=− 0.616, P< 0.01) was positively correlated with MDA and negatively correlated with NO. The course of disease (18.653, [5.726; 60.764], P < 0.01), FBG (1.265, [1.059; 1.511], P < 0.05), HbAlc (1.545, [1.431; 1.680], P < 0.01), MDA (2.989, [1.900; 4.702], P < 0.01) were risk factor for the severity of diabetic microvascular complications. Zinc (0.680, [0.503; 0.919], P < 0.05) and SOD (0.820, [0.698; 0.964], P < 0.05) were protective factors for the severity of diabetic microvascular complications.Conclusion: Serum trace elements are related to oxidative stress levels in older adults with type 2 diabetes. The more stable trace element in older adults with diabetes, the lower the oxidative stress and the fewer microvascular complications of diabetes.Keywords: type 2 diabetes mellitus, older adults, trace elements, diabetic microvascular complications, oxidative stress

Wenjie Sun,1,&ast; Yeshan Li,2,&ast; Shuxin Tan1 1Graduate School, Wannan Medical College, Wuhu, Anhui, People’s Republic of China; 2Respiratory Department, The Second People’s Hospital of Wuhu City, Wuhu, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yeshan Li, Respiratory Department, The Second People’s Hospital of Wuhu City, Wuhu, Anhui, 241000, People’s Republic of China, Tel +8618055317993, Email liyeshan9177@163.comPurpose: Patients with chronic obstructive pulmonary disease (COPD) often face unknown risks during acute exacerbation of the disease (AECOPD), which could potentially result in mortality. This study aimed to develop and validate a nomogram model for predicting the risk of in-hospital mortality in AECOPD patients.Patients and Methods: Clinical data of patients hospitalized at The Second People’s Hospital of Wuhu City for AECOPD between January 2013 and December 2022 were retrospectively collected. Variables underwent selection through LASSO regression and multivariable logistic regression to develop a nomogram model. The model’s predictive performance was assessed using the concordance index, calibration curve, and decision curve analysis (DCA), with internal validation conducted using the bootstrap method.Results: A total of 1224 patients were included in this study, with 98 (8%) deaths occurring during hospitalization. LASSO regression identified 11 variables, used to construct model A. Further multivariable logistic regression was conducted to select variables with P < 0.05 to establish model B. model B was selected as the final model based on discrimination, calibration, and clinical utility, encompassing variables including acute respiratory failure, lung cancer, heart rate, hemoglobin, absolute neutrophil count, serum albumin, blood urea nitrogen, and serum chloride. The nomogram model achieved a concordance index of 0.858. Internal validation of the model was conducted using the bootstrap method with 500 repetitions, resulting in a concordance index of 0.851 (95% CI: 0.805, 0.893). The calibration curve demonstrated a good fit, with a Hosmer-Lemeshow goodness-of-fit test P-value of 0.520. Moreover, DCA findings suggested patient benefit within a threshold probability range of 0.02 to 0.73, with a maximum net benefit of 0.07.Conclusion: The model constructed in this study has good predictive performance, which helps clinical doctors identify patients at high risk of death early.Keywords: acute exacerbation of chronic obstructive pulmonary disease, prediction model, nomogram

Qian Li,1,2 Caifeng Luo,1 Jianqin Ye,3 Zekun Bian,1 Weiyi Sun,1 Man Zhou,4 Mingzhu Rong4 1School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 2Department of Neurosurgery, Xiangcheng People’s Hospital, Suzhou, Jiangsu, People’s Republic of China; 3Department of Nursing, Xiangcheng People’s Hospital, Suzhou, Jiangsu, People’s Republic of China; 4Department of Neurology, Suzhou Municipal Hospital, Suzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Caifeng Luo, School of Medicine, Jiangsu University, No. 301 Xuefu Road, Jingkou District, Zhenjiang, 212013, People’s Republic of China, Email lcf0105@163.comPurpose: Stroke is a major disease endangering the health of Chinese people, and patients need to rely on the care of family members, which brings heavy caregiving burdens and pressures to caregivers and families, thus disrupting the stable family structure. In view of this, this study was to analyse the current status of family resilience among caregivers of stroke patients in Chinese nuclear families, and to explore the correlation and mechanism of action among perceived stress, illness uncertainty and family resilience.Patients and Methods: This study used a cross-sectional research design. A total of 350 carers of stroke patients in nuclear families from four tertiary hospitals in Suzhou City, Jiangsu Province, China were selected by convenience sampling method and assessed by using demographic questionnaires, the Chinese Perceived Stress Scale (CPSS), the Parental Perceptions of Uncertainty Scale-Family (PPUS-FM), and a short Chinese version of the Family Resilience Assessment Scale (FRAS-C). Based on the above data, structural equation model was used to test the mediating role of perceived stress between illness uncertainty and family resilience.Results: Family resilience among caregivers of stroke patients in nuclear families was at the medium lower level, illness uncertainty was at the medium level, and perceived stress was at the relatively high level. Illness uncertainty was positively correlated with perceived stress (P< 0.01) and negatively correlated with family resilience (P< 0.01). Illness uncertainty directly predicted family resilience (β = − 0.516, p < 0.05). And the pathway between illness uncertainty and family resilience was partially mediated by perceived stress (Effect= − 0.091, 95% CI [− 0.141, − 0.055]).Conclusion: Healthcare professionals should pay adequate attention to the level of illness uncertainty and perceived stress among carers of stroke patients, with the need to take measures to reduce carers’ illness uncertainty and perceived stress in order to improve family resilience.Keywords: nuclear family, stroke, caregivers, perceived stress, illness uncertainty, family resilience

Wenshe Sun,1– 3,&ast; Shaowei Xie,4,&ast; Shi Feng Liu,1,&ast; Xiaokun Hu,1 Dongming Xing1,2 1The Affiliated Hospital of Qingdao University, Qingdao, 266071, People’s Republic of China; 2Qingdao Cancer Institute, Qingdao University, Qingdao, 266071, People’s Republic of China; 3Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China; 4Department of Ultrasound, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaokun Hu; Dongming Xing, The Affiliated Hospital of Qingdao University, Qingdao, 266071, People’s Republic of China, Email huxiaokun770@163.com; xdm_tsinghua@163.comAbstract: Typical physiological characteristics of tumors, such as weak acidity, low oxygen content, and upregulation of certain enzymes in the tumor microenvironment (TME), provide survival advantages when exposed to targeted attacks by drugs and responsive nanomedicines. Consequently, cancer treatment has significantly progressed in recent years. However, the evolution and adaptation of tumor characteristics still pose many challenges for current treatment methods. Therefore, efficient and precise cancer treatments require an understanding of the heterogeneity degree of various factors in cancer cells during tumor evolution to exploit the typical TME characteristics and manage the mutation process. The highly heterogeneous tumor and infiltrating stromal cells, immune cells, and extracellular components collectively form a unique TME, which plays a crucial role in tumor malignancy, including proliferation, invasion, metastasis, and immune escape. Therefore, the development of new treatment methods that can adapt to the evolutionary characteristics of tumors has become an intense focus in current cancer treatment research. This paper explores the latest understanding of cancer evolution, focusing on how tumors use new antigens to shape their “new faces”; how immune system cells, such as cytotoxic T cells, regulatory T cells, macrophages, and natural killer cells, help tumors become “invisible”, that is, immune escape; whether the diverse cancer-associated fibroblasts provide support and coordination for tumors; and whether it is possible to attack tumors in reverse. This paper discusses the limitations of targeted therapy driven by tumor evolution factors and explores future strategies and the potential of intelligent nanomedicines, including the systematic coordination of tumor evolution factors and adaptive methods, to meet this therapeutic challenge.Keywords: smart nanomedicine, tumor evolution, immune cells, fibroblasts

Wenyan Sun,1,&ast; Xuetong Zhao,2– 4,&ast; Nicola Dalbeth,5,&ast; Robert Terkeltaub,6 Lingling Cui,1 Zhen Liu,1 Lin Han,1 Can Wang,1 Hui Zhang,1,7 Yiming Bao,2– 4 Changgui Li,1,7 Jie Lu1,7 1Shandong Provincial Key Laboratory of Metabolic Diseases, Shandong Provincial Clinical Research Center for Immune Diseases, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2National Genomics Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, 100101, People’s Republic of China; 3CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Science and China National Center for Bioinformation, Beijing, People’s Republic of China; 4University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China; 5Department of Medicine, University of Auckland, Auckland, New Zealand; 6VA San Diego VA Healthcare Center, University of California San Diego, San Diego, CA, USA; 7Institute of Metabolic Diseases, Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Lu, Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, Shandong Provincial Clinical Research Center for Immune Diseases, the Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China, Email 13127006046@163.com Changgui Li, Shandong Provincial Key Laboratory of Metabolic Diseases, Shandong Provincial Clinical Research Center for Immune Diseases, the Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China, Email changguili@vip.163.comObjective: This study aimed to understand predictors of inadequate response (IR) to low-dose febuxostat treatment based on clinical variables.Methods: We pooled data from 340 patients of an observational cohort and two clinical trials who received febuxostat 20 mg/day for at least 3 months. IR was defined as failure to reach the target serum urate level (sUA< 6 mg/dL) at any time point during 3 months treatment. The potential predictors associated with short- or mid-term febuxostat IR after pooling the three cohorts were explored using mixed-effect logistic analysis. Machine learning models were performed to evaluate the predictors for IR using the pooled data as the discovery set and validated in an external test set.Results: Of the 340 patients, 68.9% and 51.8% were non-responders to low-dose febuxostat during short- and mid-term follow-up, respectively. Serum urate and triglyceride (TG) levels were significantly associated with febuxostat IR, but were also selected as significant features by LASSO analysis combined with age, BMI, and C-reactive protein (CRP). These five features in combination, using the best-performing stochastic gradient descent classifier, achieved an area under the receiver operating characteristic curve of 0.873 (95% CI [0.763, 0.942]) and 0.706 (95% CI [0.636, 0.727]) in the internal and external test sets, respectively, to predict febuxostat IR.Conclusion: Response to low-dose febuxostat is associated with early sUA improvement in individual patients, as well as patient age, BMI, and levels of TG and CRP.Keywords: gout, febuxostat, urate-lowering therapy, machine learning model

Zixia Wu,1,&ast; Weibo Xia,1,&ast; Liling Ou,1 Ling Zheng,1 Bingying Hou,1 Tonghe Pan,2 Wenjie Sun,1 Leo H Koole,1 Yongqing Shao,2 Lei Qi1 1National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, the People’s Republic of China; 2Ningbo Eye Hospital, Affiliated to Wenzhou Medical University, Ningbo, Zhejiang, 310000, the People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongqing Shao, Ningbo Eye Hospital, Affiliated to Wenzhou Medical University, Ningbo, Zhejiang, 310000, the People’s Republic of China, Tel +86-574 87862193, Email sunniesyq@163.com Lei Qi, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, the People’s Republic of China, 325027, Tel +86-577-88067973, Email imdoll@163.comPurpose: Patients afflicted with dry eye disease (DED) experience significant discomfort. The underlying cause of DED is the excessive accumulation of ROS on the ocular surface. Here, we investigated the nitrogen doped-graphene quantum dots (NGQDs), known for their ROS-scavenging capabilities, as a treatment for DED.Methods: NGQDs were prepared by using citric acid and urea as precursors through hydrothermal method. The antioxidant abilities of NGQDs were evaluated through: scavenging the ROS both extracellular and intracellular, regulating the nuclear factor-erythroid 2-related factor (Nrf2) antioxidant pathway of human corneal epithelial cells (HCECs) and their transcription of inflammation related genes. Furthermore, NGQDs were modified by Arg-Gly-Asp-Ser (RGDS) peptides to obtain RGDS@NGQDs. In vivo, both the NGQDs and RGDS@NGQDs were suspended in 0.1% Pluronic F127 (w/v) and delivered as eye drops in the scopolamine hydrobromide-induced DED mouse model. Preclinical efficacy was compared to the healthy and DPBS treated DED mice.Results: These NGQDs demonstrated pronounced antioxidant properties, efficiently neutralizing free radicals and activating the intracellular Nrf2 pathway. In vitro studies revealed that treatment of H2O2-exposed HCECs with NGQDs induced a preservation in cell viability. Additionally, there was a reduction in the transcription of inflammation-associated genes. To prolong the corneal residence time of NGQDs, they were further modified with RGDS peptides and suspended in 0.1% Pluronic F127 (w/v) to create RGDS@NGQDs F127 eye drops. RGDS@NGQDs exhibited superior intracellular antioxidant activity even at low concentrations (10 μg/mL). Subsequent in vivo studies revealed that RGDS@NGQDs F127 eye drops notably mitigated the symptoms of DED mouse model, primarily by reducing ocular ROS levels.Conclusion: Our findings underscore the enhanced antioxidant benefits achieved by modifying GQDs through nitrogen doping and RGDS peptide tethering. Importantly, in a mouse model, our novel eye drops formulation effectively ameliorated DED symptoms, thereby representing a novel therapeutic pathway for DED management.Keywords: dry eye disease, antioxidant, nitrogen doped graphene quantum dots, Nrf2 antioxidant pathway

Fei Shu,&ast; Hong Chen,&ast; Zhihao Zhang, Zhiyue Dun, Weijin Lv, Wangxinyue Sun, Mei Liu Department of Prosthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei Liu, Department of Prosthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, People’s Republic of China, Tel +86-25-69593081, Fax +86-25-69593186, Email liumei2017@njmu.edu.cnIntroduction: Poor interfacial bonding between the fibers and resin matrix in fiber-reinforced composites (FRCs) is a significant drawback of the composites. To enhance the mechanical properties of FRC, fibers were modified by depositing SiO2 nanofilms via the atomic layer deposition (ALD) technique. This study aims to evaluate the effect of ALD treatment of the fibers on the mechanical properties of the FRCs.Methods: The quartz fibers were modified by depositing different cycles (50, 100, 200, and 400) of SiO2 nanofilms via the ALD technique and FRCs were proposed from the modified fibers. The morphologies, surface characterizations of nanofilms, mechanical properties, and cytocompatibility of FRCs were systematically investigated. Moreover, the shear bond strength (SBS) of FRCs to human enamel was also evaluated.Results: The SEM and SE results showed that the ALD-deposited SiO2 nanofilms have good conformality and homogeneity. According to the results of FTIR and TGA, SiO2 nanofilms and quartz fiber surfaces had good chemical combinations. Three-point bending tests with FRCs showed that the deposited SiO2 nanofilms effectively improved FRCs’ strength and Group D underwent 100 deposition cycles and had the highest flexural strength before and after aging. Furthermore, the strength of the FRCs demonstrated a crescendo-decrescendo tendency with SiO2 nanofilm thickness increasing. The SBS results also showed that Group D had outstanding performance. Moreover, the results of cytotoxicity experiments such as cck8, LDH and Elisa, etc., showed that the FRCs have good cytocompatibility.Conclusion: Changing the number of ALD reaction cycles affects the mechanical properties of FRCs, which may be related to the stress relaxation and fracture between SiO2 nanofilm layers and the built-up internal stresses in the nanofilms. Eventually, the SiO2 nanofilms could enhance the FRCs’ mechanical properties and performance to enamel by improving the interfacial bonding strength, and have good cytocompatibility. Keywords: atomic layer deposition, SiO2 nanofilms, surface modification, interfacial bonding

Xiangli Qing,1,2 Lin Wang,1 Shuangshuang Fang,1 Yanran Ban,1,3 Zhuotai Zhong,1 Weiqi Sun,1 Chenhui Zhang,4 Tao Zhang,1 Yang Yang,1 Wei Wei1 1Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China; 3Graduate School of Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Department of General Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of ChinaCorrespondence: Wei Wei, Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China, Email weiwei3816@mail.cintcm.ac.cnBackground: An unmet medical need for the treatment of inflammatory bowel disease (IBD) exists. A part of antidiabetic drugs had potential effects on IBD in various observational research.Objective: To investigate the potential of antidiabetic drugs on IBD.Methods: We undertook a summary-data-based Mendelian randomization (SMR) using the expression quantitative trait loci (eQTL) expressed in the blood or colon and a two sample Mendelian randomization (TSMR) utilizing single nucleotide polymorphism (SNP) of antidiabetic drug target genes mediated by blood glucose traits. Participants encompassed patients with IBD (25,042 cases/34,915 controls), UC (12,366 cases/33,609 controls), and CD (12,194 cases/28,072 controls). Data on eQTL in the blood or the colon were from the eQTLGen consortium (31,684 individuals) or GTEx Consortium V8, respectively. SMR was performed by SMR software (20,220,322); the primary method for TSMR was inverse-variance weighted (IVW) or Wald ratio through R studio (2023.06.0+421). Sensitivity analyses were carried out.Results: A 1-SD upper expression of the KCNJ11 gene (target gene of sulfonylureas) in the blood reduced the risk of CD (OR per 1-SD = 0.728, 95% CI = 0.586– 0.903, P = 0.004) according to the result of SMR. ABCC8 (target gene of sulfonylureas) expressed in the colon did not affect CD, UC, or IBD. T2D-mediated KCNJ11 has a protective effect on CD (OR = 0.475, 95% CI = 0.297– 0.761, P = 0.002). Gene predicted no relationship between T2D and CD.Conclusion: Sulfonylureas (SUs) may have side effects on CD. This work provides some suggestions for the selection of antidiabetic drugs in patients with CD.Keywords: antidiabetic drugs, inflammatory bowel disease, Mendelian randomization

Lingbo Bi,&ast; Chaofan Wang,&ast; Yimei Du,&ast; Changpei Lu, Min Zhao, Yunbu Ding, Weiling Sun, Weixin Fan Department of Dermatology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weixin Fan; Weiling Sun, Department of Dermatology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, 210029, People’s Republic of China, Tel +86-13327805737 ; +86-13813955963, Email swl0560@sina.com; hairmanfwx@163.comPurpose: To investigate whether increased levels of lipids-related metabolites (LRMs) result in androgenic alopecia (AGA).Patients and Methods: A two-sample Mendelian randomization (MR) study was designed, and single nucleotide polymorphisms (SNPs) respectively related to nine LRMs were selected from the genome-wide association study (GWAS) dataset. An MR analysis was performed to assess the causal association between LRMs and AGA.Results: Through the fixed-effect inverse variance weighting (IVW) method, MR analysis indicated that Apolipoprotein B (ApoB), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) had a causal relationship with AGA. No obvious heterogeneity or pleiotropy was observed.Conclusion: The risk of AGA increases significantly when the serum levels of ApoB, LDL, and VLDL increase. This causal relationship is solid and free of interference from confounding factors.Keywords: androgenic alopecia, apolipoprotein B, VLDL, LDL

Yanbei Duo,1 Shuoning Song,1 Xiaolin Qiao,2 Yuemei Zhang,3 Jiyu Xu,4 Jing Zhang,5 Zhenyao Peng,6 Yan Chen,2 Xiaorui Nie,2 Qiujin Sun,7 Xianchun Yang,7 Ailing Wang,8 Wei Sun,4 Yong Fu,1 Yingyue Dong,1 Zechun Lu,8 Tao Yuan,1,&ast; Weigang Zhao1,&ast; 1Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Obstetrics, Beijing Chaoyang District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 3Department of Obstetrics, Haidian District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 4Core Facility of Instrument, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Laboratory, Haidian District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 6Department of Dean’s Office, Haidian District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 7Department of Clinical Laboratory, Beijing Chaoyang District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 8National Center for Women and Children’s Health, China CDC, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Yuan; Weigang Zhao, Email t75y@sina.com; xiehezhaoweigang@163.comObjective: Gestational diabetes mellitus (GDM) is a condition of glucose intolerance, which may be accompanied with inflammation. The levels of hematological parameters during pregnancy can reflect inflammatory conditions in pregnant women. This study aims to describe the dynamic change of blood cell parameters from the first trimester (6– 12 weeks of gestation) to the second trimester (24– 28 weeks of gestation) and to investigate the associations of these biomarkers with the risk of GDM.Methods: This study was a prospective double-center study conducted in Beijing, China (clinical trial number: NCT03246295). Hematological parameters were tested four times during the follow-up. Logistic regression analysis and Receiver Operating Characteristic (ROC) curve analysis were used to explore the association and predictive ability of hematological parameters for GDM.Results: There were 258 of 1027 pregnant women in our study developed GDM. Among the 1027 pregnant women, white blood cells (WBC) gradually increased, and red blood cells (RBC), hemoglobin (HGB), and platelet (PLT) tended to decrease from the first trimester to second trimester. After adjusting for confounding factors, higher levels of RBC, HGB, and PLT in both early and middle pregnancy were positively associated with GDM risk, whereas the level of WBC was associated with GDM risk only in early pregnancy. WBC, RBC, HGB, and PLT in early and middle pregnancy were all correlated with fasting insulin (FINS) in early pregnancy.Conclusion: Higher levels of hematological parameters in early and middle pregnancy were associated with glucose metabolism in early pregnancy and the subsequent risk of GDM.Keywords: hematological parameters, gestational diabetes mellitus, inflammation, insulin resistance, prospective study

A novel tungsten carbide (WC)-reinforced nickel (Ni)-based laser cladding layer was prepared through an in-situ synthesis process. The influence of different concentrations of CeO2/Y2O3 on the microstructure, wear, and corrosion resistance of the in-situ synthesized WC-reinforced Ni-based cladding layer was analyzed. The results revealed that the coatings doped with rare-earth oxides exhibited good micro-hardness (660 HV0.2) and wear resistance when the rare-earth oxide content reached 0.75% CeO2 and 1.50% Y2O3. Additionally, the minimum corrosion rates of the coating were measured at 0.002770 mm/a and 0.0022548 mm/a at 1.5% CeO2 and 1.5 Y2O3 doping, with noble Ecorr values ranging from -0.12549 V to -0.49924 V and lower Icorr values ranging from 2.3550×10-7 A·cm2 to 1.9170×10-7 A·cm2. Furthermore, the wear resistance of the cladding layer was significantly higher than that of the substrate. Both the cladding layer and the substrate exhibited a mixed-wear mode, and they exhibit adhesive wear in wet friction environments.

Yi Yao,1,&ast; Juan Li,2,&ast; Wenwu Sun,1,&ast; Chaoping Ma,2,&ast; Ning Ning,1 Jiaoyan Li,1 Tongtian Ni,1 Menglu Gui,1 Ying Chen,1 Bing Zhao,1 Jiyuan Zhang,2 Jiyue Zhu,3 Chengjin Gao,2 Huiqiu Sheng,1 Enqiang Mao1 1Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China; 2Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 3Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiqiu Sheng, Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China, Tel +86-15801971839, Email shenghq803@163.com Chengjin Gao, Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China, Tel +86-18221088783, Email gaochengjin@xinhuamed.com.cnPurpose: Both nonthyroidal illness syndrome (NTIS) and disseminated intravascular coagulation (DIC) are commonly occurred in sepsis. The objective of this study is to evaluate the association between NTIS and DIC, as well as their impacts on the mortality in adults with sepsis.Patients and methods: A total of 1219 septic patients in two Chinese academic centers from October 2012 and October 2022 were enrolled in analysis. We conduct logistic regression models to analyze the independent risk factors for DIC. Modified Poisson regression models are used to estimate the relative risk (RR) of NTIS on the 28 days mortality in septic patients with DIC. Correlation analysis between thyroid function parameters and coagulation parameters is performed with Pearson coefficient be reported.Results: DIC is diagnosed on 388 (31.8%) of all the 1219 enrolled septic patients within 72 hours after admission. In multivariate logistic regression models, NTIS (OR 3.19; CI 2.31– 4.46; p< 0.001) is a statistically significant independent risk factor for DIC after adjustment for potential confounders. Twenty-eight days mortality is significantly higher in DIC patients complicated with NTIS compared with the other DIC patients (23.2% vs 14.0%, p=0.024). This result is also robust in different modified Poisson regression models (Model 1: RR 1.46; CI 1.25– 1.70; p< 0.001; Model 2: RR 1.35; CI 1.14– 1.60; p< 0.001; Model 3: RR 1.18; CI 1.02– 1.37; p=0.026). Correlation analysis reveals that the thyroid function parameters of FT3, FT4 and TSH only have weak correlations with coagulation parameters of platelet count, fibrinogen, FDP, D-dimers, PT, APTT and INR in sepsis.Conclusion: NTIS is an independent risk factor for DIC in adults with sepsis. DIC patients complicated with NTIS have significantly higher severity and higher rate of mortality.Keywords: sepsis, low T3 syndrome, nonthyroidal illness syndrome, thyroid function, disseminated intravascular coagulation

Changyu Yao,&ast; Jian Kong,&ast; Fei Xu, Shaohong Wang, Shilun Wu, Wenbing Sun, Jun Gao Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenbing Sun; Jun Gao, Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Capital Medical University, No. 5 Jingyuan Road, Shijingshan District, Beijing, 100043, People’s Republic of China, Tel +86-010-51718382, Fax +86-010-51718372, Email sunwenbing@bjcyh.com; gaojun8430@163.comPurpose: Systemic inflammatory response syndrome (SIRS) is a common complication of radiofrequency ablation (RFA) for hepatic hemangiomas. RFA can cause hemolytic reactions during hepatic hemangioma ablation. However, the mechanisms underlying RFA-induced SIRS remain unclear.Methods: We established an orthotopic liver hemangioma model and performed radiofrequency ablation. The levels of interleukin (IL)-1β and IL-18 and the production of ROS were measured. The wet-to-dry lung ratio, inflammation score, and in vivo endothelial cell permeability were examined. GSDMD−/− mice were used to investigate the effect of heme-inducing SIRS. RNA sequencing (RNA-seq) was performed to identify the main pathways underlying heme-induced SIRS. Western blotting and immunoprecipitation were used to determine the changes and interactions of associated proteins.Results: The levels of heme, IL-1β, and IL-18 were significantly increased after RFA. The wet-to-dry lung ratio increased in hepatic hemangiomas after RFA, indicating that SIRS occurred. Heme induced increased levels of IL-1β and IL-18, cell death, wet-to-dry lung radio, and inflammation score in vitro and in vivo, indicating that heme induced SIRS and pyroptosis. Furthermore, GSDMD participates in heme-induced SIRS in mice, and GSDMD deletion in mice reverses the effect of heme. Heme regulates NLRP3 activation through the NOX4/ROS/TXNIP-TRX pathway, and an N-acetyl-L-cysteine (NAC) or NOX4 inhibitor (GLX351322) reverses heme-induced SIRS.Conclusion: Our findings suggest that heme induces endothelial cell pyroptosis and SIRS in mice and decreasing heme levels and ROS scavengers may prevent SIRS in hepatic hemangioma after RFA. Keywords: hemangioma, radiofrequency ablation, systemic inflammatory response syndrome, pyroptosis, endothelial cells

Zongfeng Zhao,1,&ast; Jie Cheng,2,&ast; Wanqun Sun,1 Jian Zhu,3 Sheng Lu,3 Yanyan Feng,4 Zhendong Song,5 Yali Yang,6 Xiujuan Wu3 1Department of Scientific Research, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Urology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Dermatology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, People’s Republic of China; 4Chengdu Second People’s Hospital, Chengdu, Sichuan Province, People’s Republic of China; 5WLSA Shanghai Academy, Shanghai, People’s Republic of China; 6Department of Dermatology, Shanghai Ninth Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yali Yang, Department of Dermatology, Shanghai Ninth Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, No. 639, Manufacturing Bureau Road, Huangpu District, Shanghai, 200011, People’s Republic of China, Email ky7812@126.com Xiujuan Wu, Department of Dermatology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, No. 966, Huaihai Middle Road, Xuhui District, Shanghai, 200031, People’s Republic of China, Email xjwuxj@sina.comPurpose: Psoriasis is an incurable chronic inflammatory skin disease. The exact function and regulatory mechanism of non-coding RNA upregulation in psoriasis remains to be elucidated. The aim of this study was to analyse the role of the lncRNA-miRNA-mRNA network of psoriasis and LINC01176 in the pathogenesis of psoriasis.Patients and Methods: We performed miRNA, lncRNA, and mRNA sequencing analysis in pretreatment and treatment psoriatic tissues and normal tissues, constructed an lncRNA-miRNA-mRNA coexpression network and screened mRNA-associated pathways using bioinformatics analysis. We further validated the regulatory role of LINC01176-miR-218-5p on the proliferation and inflammation of the psoriatic model by dual-luciferase reporter assay, cell transfection, CCK-8 method, TUNEL staining and animal model construction method. An lncRNA-miRNA-mRNA coexpression network was successfully constructed by RNA-seq data analysis.Results: We obtained the relationship between LINC01176, miR-218-5p and IL36-G. Analysis of the apoptotic and proliferative capacity of the transfected cells showed that miR-218-5p up-regulation significantly inhibited cell proliferation and promoted apoptosis. A mouse model of psoriasis was successfully established. Phenotypic observations revealed that keratin-forming cells in mice coated with LINC01176-shRNA emulsifier were significantly lower than those in the model group and close to those in the normal group. HE and immunohistochemical experiments were performed, and the results showed the role and mechanism of action of LINC01176-shRNA. Suppression of LINC01176 significantly inhibited the expression of IL-36G in psoriatic tissues. LINC01176 showed a targeting and positive correlation with IL36-G expression.Conclusion: Our study shows that LINC01176 promotes the proliferation and invasion of keratinocytes and inhibits apoptosis by targeting miR-218-5p, which acts as a repressor of the psoriasis-associated IL-36G. The shRNA-LINC01176 emulsion showed potential treatment capability in alleviating symptoms of psoriasis.Keywords: psoriasis, LINC01176, IL-36G, inflammation

Xian Sun,1 Xi Zhou,1 Weiming He,2 Wei Sun,2 Zheng Xu1 1School of Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 2Department of Nephrology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of ChinaCorrespondence: Zheng Xu, School of Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Tel +86-15951978958, Email xuzheng@njucm.edu.cn Wei Sun, Department of Nephrology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China, Tel +86-13505199810, Email yfy0074@njucm.edu.cnAbstract: Dysregulation of the gut microbial ecosystem (GME) (eg, alterations in the gut microbiota, gut-derived metabolites, and gut barrier) may contribute to the onset and progression of extra-intestinal diseases. Previous studies have found that Traditional Chinese Medicine herbs (TCMs) play an important role in manipulating the GME, but a prominent obstacle in current TCM research is the causal relationship between GME and disease amelioration. Encouragingly, co-housing and fecal microbiota transplantation (FMT) provide evidence-based support for TCMs to treat extra-intestinal diseases by targeting GME. In this review, we documented the principles, operational procedures, applications and limitations of the key technologies (ie, co-housing and FMT); furthermore, we provided evidence that TCM works through the GME, especially the gut microbiota (eg, SCFA- and BSH-producing bacteria), the gut-derived metabolites (eg, IS, pCS, and SCFAs), and intestinal barrier to alleviate extra-intestinal diseases. This will be beneficial in constructing microecological pathways for TCM treatment of extra-intestinal diseases in the future.Keywords: gut microbial ecosystem, TCM herb, extra-intestinal disease, co-housing, fecal microbiota transplantation

Yuqi Li,1,2,&ast; Changjin Ji,1,2,&ast; Weiao Sun,1,2 Huahui Xiong,1,2 Zheng Li,3 Xiaoqing Huang,1,2 Tingting Fan,1,2 Junfang Xian,3 Yaqi Huang1,2 1School of Biomedical Engineering, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Fundamental Research on Biomechanics in Clinical Application, Capital Medical University, Beijing, People’s Republic of China; 3Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaqi Huang, School of Biomedical Engineering, Capital Medical University, Beijing, People’s Republic of China, Tel +86-10-83911809, Email yqhuang@ccmu.edu.cn Junfang Xian, Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China, Email cjr.xianjunfan@vip.163.comPurpose: Upper airway collapse during sleep in patients with obstructive sleep apnea (OSA) is a complex and dynamic phenomenon. By observing and analyzing the dynamic changes in the upper airway and its surrounding tissues during airway obstruction, we aim to reveal dynamic characteristics in different obstruction patterns, and the relationship between anatomical features during normal breathing and dynamic characteristics of airway obstruction.Patients and Methods: Dynamic MRI was performed in 23 male patients (age range 26– 63) with severe OSA diagnosed by overnight polysomnography, and obstruction events were identified from their images. Dynamic changes in parameters of the upper airway and surrounding tissues were measured to assess the key characteristics in different obstruction patterns.Results: We categorized airway obstruction into four types based on the obstruction location and motion characteristics of tissues during collapse, and detailed the alterations in the airway and surrounding tissues under each obstruction pattern. In all 112 obstruction events extracted from the dynamic images of 23 patients, type A (retropalatal obstruction caused by the soft palate separated from the tongue), BI, BII (both retropalatal obstructions caused by the soft palate attached to the tongue, and C (retropalatal and retroglossal obstruction caused by the soft palate and the tongue), accounted for 28.6%, 44.6%, 12.5%, and 14.3% respectively. In severe OSA patients with tongue and palatal obstruction related to type B or C, the more posterior hyoid position, shorter distance between tongue and uvula, and wider retropalatal space, the larger the tongue displacement and deformation during collapse, and the greater the reduction in airway space.Conclusion: There are multiple airway obstruction patterns, each with its own anatomical characteristics and behaviors during collapse. Hyoid position, tongue and uvula distance, and retropalatal space play an important role in airway collapse and should be paid more attention in the treatment of OSA.Keywords: airway obstruction patterns, obstruction location, tissue motion characteristics, hyoid position, retropalatal space

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

Wenwen Sun,1,&ast; Jun Shen,1,&ast; Ru Sun,1 Dan Zhou,1 Haihong Li2 1Department of Breast Surgery, the First People’s Hospital of Lianyungang, the Affiliated Hospital of XuZhou Medical University, LianYunGang, Jiangsu, 222002, People’s Republic of China; 2Department of Nursing, the First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, LianYunGang, Jiangsu, 222002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haihong Li, Department of Nursing, the First People’s Hospital of Lianyungang, the affiliated hospital of XuZhou medical university, No. 6 Zhenhua East Road, High-Tech Square, LianYunGang, Jiangsu Province, 222002, People’s Republic of China, Tel +86 18961322059, Email haihonglired@126.comObjective: In this study, we aim to establish and evaluate a predictive model for post-treatment anxiety state based on basic patient attributes and pre-treatment SAS scores, with the expectation that this model will guide clinical precision intervention.Methods: Data were collected from 606 patients with breast cancer who underwent surgery at our hospital between January 1, 2015 and December 30, 2018 and 144 newly diagnosed patients with breast cancer who were admitted between June 1, 2019 and December 30, 2019, for a total of 750 patients with breast cancer. The relationship between SAS_A scores and prognosis was verified by analyzing patient baseline characteristics, follow-up data, pre-treatment self-rating anxiety scale (SAS) scores, and SAS_A scores in follow-up period after the end of treatment. A risk prediction model was developed in view of the SAS_A scores, which was then screened, validated, and simplified by scoring, with a nomogram plotted.Results: The SAS_A score can be utilized to differentiate prognosis. In K-M analysis, the high SAS_A score group had a significantly poorer progression-free survival rate than the low score group, p-value < 0.0001. Through model feature selection and clinical analysis, all variables were finally incorporated to establish a predictive model with a ROC AUC of 0.721 (0.637– 0.805) for the validation set and external data, and an AUC of 0.810 (0.719– 0.902) for external data, demonstrating good predictive performance. Calibration curves and probability distribution maps were constructed. DCA and CIC analyses demonstrated that model intervention could boost clinical benefits more effectively than intervention for all patients.Conclusion: Using a predictive model to guide clinical management for anxiety in breast cancer patients is feasible, but additional research is required.Keywords: breast cancer, negative emotions, nomogram, predictive model

Tong Mo,1,&ast; Wenxian Huang,2,&ast; Weisheng Sun,1 Yan Hu,3 Leroy Mcdonald,4 Zhanqi Hu,3 Li Chen,3 Jianxiang Liao,3 Bruce Hermann,5 Vivek Prabhakaran,4– 6 Hongwu Zeng1,6 1Department of Radiology, Shenzhen Children’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Department of Pediatrics, Shenzhen Children’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 3Department of Neurology, Shenzhen Children’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 4Neurosciences Training Program, University of Wisconsin, Madison, WI, USA; 5Department of Neurology, University of Wisconsin, Madison, WI, USA; 6Department of Radiology, University of Wisconsin, Madison, WI, USA&ast;These authors contributed equally to this workCorrespondence: Hongwu Zeng, Shenzhen, Guangdong, People’s Republic of China, Tel +86 18938691099, Email homerzeng@126.com Vivek Prabhakaran, Department of Radiology, University of Wisconsin, Madison, WI, USA, Tel +1 608 265 5269, Email VPrabhakaran@uwhealth.orgObjective: Neuropsychological evidence revealed language impairment in children with benign epilepsy with centrotemporal spikes (BECTS). This study investigates language function using task-activated fMRI.Methods: We conducted a language task fMRI study on three groups on a 3.0T MRI scanner, including a new onset drug naïve group (NODN-BECTS, n=11, age=9.6± 1.6), an established epilepsy with medication-treated group (Med-BECTS, n=17, age=10.7± 2.2) and a healthy control group (HC, n=18, age=10.8± 1.7). We use MATLAB14 and SPM12 to pre-process and analyze the data. A one-sample t-test was used to identify task-related brain activation changes in each group, based on the general linear model (GLM). And, then two sample t-test was performed to compare different activated regions between groups. In addition, scores on the most recent Mandarin school exams were acquired to examine and contrast extra-scanner language performance.Results: Statistical results show that some language-related brain regions (such as the left superior frontal gyrus and cerebellar vermis) were additionally activated in the NODN-BECTS group compared with the HC group. Compared with NODN-BECTS and HC groups, decreased activations were found in language-related regions in the Med-BECTS group, including the left insula, superior and middle frontal gyri, and bilateral middle occipital gyri. On the Mandarin school exams, the average score for HC was 87.3± 8.2, NODN was 84.8± 7.8, and Med was 78.2± 13.2. There was a trend toward statistical significance between the Med and the HC (p = 0.074) as well as NODN (p = 0.092) groups. No statistically significant differences were found between the HC and the NODN-BECTS groups.Significance: Language task fMRI reveals additional areas of activation in new onset BECTS compared to healthy controls which may be compensatory in nature. Antiseizure medications (ASMs) and/or longer duration of BECTS additionally appears to affect language-related regions and reduce their functional ability.Keywords: benign epilepsy with centrotemporal spikes, cognition, language impairment, functional magnetic resonance imaging

Xi Wang,1,&ast; Jiyu Xu,2,&ast; Guodong Feng,1 Zhiqiang Gao,1 Wei Sun2 1Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Institute of Basic Medical Sciences, School of Basic Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiqiang Gao; Wei Sun, Email gzqent@163.com; sunwei@ibms.pumc.edu.cnBackground: Proteins found in middle ear effusion play crucial roles in the physiological and pathological processes of otitis media with effusion (OME), influencing the etiology and clinical characteristics of this disease. The qualitative and quantitative composition of these proteins depending on the underlying pathogenesis of middle ear effusion. Understanding their physiological and pathological functions is of great importance.Methods: We collected samples from 19 volunteers diagnosed with OME. After offline separation using high-pH reversed-phase liquid chromatography (RPLC), the pooled sample was subjected to LC-MS/MS analysis to obtain a comprehensive profile of the OME proteome. Functional analysis was performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Ingenuity Pathway Analysis (IPA) annotations. Data-independent acquisition (DIA) technology was utilized to analyze samples and fix whether the OME proteome could replicate the pathophysiological features associated with this disease. We conducted a differential proteomic analysis between patients with simple OME and patients who had received radiotherapy. The radiotherapy-reduced group was further divided into two subgroups: nasopharyngeal carcinoma (NPC) and other types of carcinoma. Parallel reaction monitoring (PRM) technology was used for validation of 36 differentially expressed proteins (DEPs).Results: A number of 732 proteins were identified in the OME proteome database. Among them, 527 proteins were quantified using peak intensity-based semi-quantification (iBAQ), covering a wide dynamic range of approximately 8 orders of magnitude. Based on the functional analysis, we proposed a hypothetical mechanism of OME.Conclusion: This study managed to put up an inclusive analysis of the OME proteome, establishing the first human OME proteome database. We focused on differential proteomic analysis among different groups to gain a more comprehensive concept of the OME proteome and search for meaningful biomarkers.Keywords: otitis media with effusion, proteome, function annotation, radiotherapy-reduced OME, nasopharyngeal carcinoma

Zhiqiang Fan,1 Yang He,1 Wei Sun,2 Zuojun Li,2 Min Zhu,3 Chunjiang Wang2 1Department of Pharmacy, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China; 2Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 3Department of Ophthalmology, Central South University, Changsha, Hunan, 410013, People’s Republic of ChinaCorrespondence: Chunjiang Wang, Department of Pharmacy, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, YueLu District, Changsha, Hunan, 410013, People’s Republic of China, Email wongcj@csu.edu.cnObjective: Trimethoprim sulfamethoxazole (TMP-SMX) is related to aseptic meningitis. However, a detailed description of its phenotype is lacking, which easily leads to misdiagnosis. The purpose of this article is to explore the clinical characteristics of TMP-SMX-induced aseptic meningitis (TSIAM).Methods: We collected literature related to TSIAM published before July 31, 2023, by searching Chinese and English databases. Data were extracted and analyzed descriptively.Results: The 55 patients were mostly female (60.0%), with a median age of 43 years (range: 2.5– 90 years). The first onset time was from a few minutes to 3 months after administration, and the time of reonset was within 12 hours. Fever (98.2%), headache (78.2%), altered mental status (42.3%), nausea and vomiting (41.8%), and neck pain (34.5%) were the most common symptoms. In severe cases, patients presented with low blood pressure, seizures, unconsciousness, or coma. Typical cerebrospinal fluid analysis showed elevated white blood cell counts, with polymorphonuclear leukocytes predominating, elevated protein levels, and normal glucose levels. Brain imaging usually showed no abnormalities. Symptoms resolved rapidly after the discontinuation of TMP-SMX, within a median time of 2 days (range: 1, 60). Readministration of TMP-SMX led to another relapse of aseptic meningitis. Aseptic meningitis usually culminated in a full recovery, although one patient experienced permanent paraplegia.Conclusion: Clinicians should be aware that aseptic meningitis is a rare adverse effect of TMP-SMX. TMP-SMX should be discontinued in patients with TSIAM to reduce unnecessary testing and treatment, and readministration of TMP-SMX should be avoided.Keywords: aseptic meningitis, trimethoprim-sulfamethoxazole, drug-induced aseptic meningitis, headache, trimethoprim

Fei Song,1,2,&ast; Yan Wang,1,&ast; Xiao-ge Wei,1,2 Nan Yang,1 Wenjing Sun,1 Kaiying Li,1 Huisheng Ma,1,2 Jing Mu1 1College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 2Key Laboratory of Modernization of Minority Medicine, Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Mu; Huisheng Ma, Email mujing930@163.com; madoctor@163.comObjective: In this study, we analyzed the differential expression and key signaling pathways of proteins in the skin of guinea pigs with melanin deposition caused by two different modeling methods by utilizing proteomics techniques.Methods: Guinea pig skin melanin deposition models were: (1) induced by ultraviolet (UV) irradiation alone (U group), (2) induced by UV combined with progesterone injection (P group), and guinea pigs treated without any treatment were used as blank group (B group). H&E staining and Masson staining were used to observe the extent of skin damage and melanin deposition in guinea pigs. The differentially expressed proteins (DEPs) in the skin tissues of melanin-deposited guinea pigs were screened by proteomic techniques, the functions of DEPs were analyzed, and a protein-protein interaction network (PPI) was constructed.Results: There was a significant difference in grayscale between the U and P groups of guinea pig skin before and after modeling (P < 0.01). H&E and Masson staining showed that the U and P groups both exhibited incomplete keratinization of the stratum corneum, increased proliferation of epidermal cells with large nuclei and disordered arrangement, neovascularization of the dermis, and increased the number of melanin particles in the epidermis of the U and P groups of guinea pigs compared with the B group. Proteomics analysis showed that there were 171 DEPs between the U and P groups. These DEPs focused on biological processes such as fibrillar collagen trimer, extracellular matrix containing collagen proteins, metalloproteinase activity, and peroxidase activity.Conclusion: The melanin pigmentation model induced solely by UV radiation negatively regulates biological processes such as extracellular matrix and collagen synthesis, while inducing significant skin photoaging. The combination of progesterone injections and UV radiation-induced melanin pigmentation model can cause abnormal protein expression in fatty acid and phospholipid metabolism, possibly being closer to the environment of melasma formation.Keywords: melasma, skin melanin, melanin deposition, ultraviolet, progesterone

Pengxin Ge,1,&ast; Huijie Duan,2,&ast; Chunrong Tao,3,&ast; Sensen Niu,4 Yiran Hu,5 Rui Duan,6 Aizong Shen,7 Yancai Sun,1 Wen Sun3 1Department of Pharmacy, Anhui Provincial Cancer Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230031, People’s Republic of China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China; 3Stroke Center and Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, People’s Republic of China; 4Digestive System Department, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of China; 5Department of Scientific Research, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, People’s Republic of China; 6Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People’s Republic of China; 7Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Sun; Aizong Shen, Email sunwen_medneuro@163.com; 1649441800@qq.comObjective: Stroke is a kind of cerebrovascular disease with high mortality. TMAO has been shown to aggravate stroke outcomes, but its mechanism remains unclear.Materials and Methods: Mice were fed with 0.12% TMAO for 16 weeks. Then, mice were made into MCAO/R models. Neurological score, infarct volume, neuronal damage and markers associated with inflammation were assessed. Since microglia played a crucial role in ischemic stroke, microglia of MCAO/R mice were isolated for high-throughput sequencing to identify the most differentially expressed gene following TMAO treatment. Afterward, the downstream pathways of TMAO were investigated using primary microglia.Results: TMAO promoted the release of inflammatory cytokines in the brain of MCAO/R mice and promoted the activation of OGD/R microglial inflammasome, thereby exacerbating ischemic stroke outcomes. FTO/IGF2BP2 inhibited NLRP3 inflammasome activation in OGD/R microglia by downregulating the m6A level of NLRP3. TMAO can inhibit the expression of FTO and IGF2BP2, thus promoting the activation of NLRP3 inflammasome in OGD/R microglia. In conclusion, these results demonstrated that TMAO promotes NLRP3 inflammasome activation of microglia aggravating neurological injury in ischemic stroke through FTO/IGF2BP2.Conclusion: Our results demonstrated that TMAO promotes NLRP3 inflammasome activation of microglia aggravating neurological injury in ischemic stroke through FTO/IGF2BP2. These findings explained the molecular mechanism of TMAO aggravating ischemic stroke in detail and provided molecular mechanism for clinical treatment.Keywords: stroke, TMAO, NLRP3 inflammasome, OGD/R, microglia, FTO, IGF2BP2

Wei Sun,1 Qiao Wu,1 Li Gao,2 Zhong Zheng,3 Hu Xiang,1 Kun Yang,1 Bo Yu,1 Jing Yao1 1Department of Psychiatry, the Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang City, Sichuan Province, People’s Republic of China; 2Department of Neurology, The Third People’s Hospital of Chengdu, Chengdu Institute of Neurological Diseases, Chengdu City, Sichuan Province, People’s Republic of China; 3Neurobiological Detection Center, West China Hospital Affiliated to Sichuan University, Chengdu City, Sichuan Province, People’s Republic of ChinaCorrespondence: Qiao Wu, Department of Psychiatry, the Third People’s Hospital of Mianyang, Sichuan Mental Health Center, Mianyang City, Sichuan Province, People’s Republic of China, Email bridgeqiao@foxmail.comAbstract: Transcranial magnetic stimulation (TMS) has become increasingly popular in clinical practice in recent years, and there have been significant advances in the principles and stimulation modes of TMS. With the development of multi-mode and precise stimulation technology, it is crucial to have a comprehensive understanding of TMS. The neuroregulatory effects of TMS can vary depending on the specific mode of stimulation, highlighting the importance of exploring these effects through multimodal application. Additionally, the use of precise TMS therapy can help enhance our understanding of the neural mechanisms underlying these effects, providing us with a more comprehensive perspective. This article aims to review the mechanism of action, stimulation mode, multimodal application, and precision of TMS.Keywords: transcranial magnetic stimulation, mechanism, stimulation mode, multimodal application, precision

Hui Ke,&ast; Xuwei Gui,&ast; Wenwen Sun, Shaojun Zhang, Yan Yang, Zhemin Zhang, Lin Fan Department of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Fan; Zhemin Zhang, Email fanlinsj@163.com; zhemindoc@163.comObjective: To evaluate the safety, tolerability, and efficacy of prolonged bedaquiline (Bdq) treatment in patients with multi-drug/rifampin-resistant tuberculosis (MDR/RR-TB).Methods: This prospective cohort study was performed from August 2018 to August 2021. Patients diagnosed with MDR/RR-TB who met the inclusion criteria were prospectively included. Patients were treated with individual regimens of 18– 20 months containing Bdq for six months or a prolonged course of nine or 12 months according to treatment demands, and the efficacy and safety with a different course of Bdq-containing regimens were compared and evaluated.Results: A total of 159 MDR/RR-TB patients were included in the study, including 96 cases with six months of Bdq, 50 cases with nine months of Bdq, and 13 patients with 12 months of Bdq. The treatment success rates were 89.6%, 90%, and 84.6% in Bdq at six months, nine months, and 12 months, respectively, which were not statistically different (P = 0.85). The main adverse events (AEs) were anemia, thrombocytopenia, and liver dysfunction in all patients, with no significant difference among the three groups. Patients who had fewer drugs chosen, disseminated lesions or lesions that were slowly absorbed, and severe cavities were the common reasons for prolonged use of Bdq.Conclusion: Prolonged course use of Bdq from six months to 12 months clinically proved to be safe and efficient, and patients with severe or disseminated lesions had the chance to prolong the use of Bdq for more than six months to achieve optimal treatment outcomes.Keywords: bedaquiline, prolonged course, MDR-TB, RR-TB, safety

Menglu Gui,1,&ast; Jun Huang,2,&ast; Huiqiu Sheng,1,&ast; Ying Chen,1 Zhitao Yang,1 Li Ma,1 Daosheng Wang,3 Lili Xu,1 Wenwu Sun,1 Junling Liu,4 Yanyan Xu,4 Erzhen Chen,1 Bing Zhao,1 Enqiang Mao1 1Department of Emergency in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 3Department of Laboratory Medicine in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 4Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Enqiang Mao; Bing Zhao, Department of Emergency in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China, Tel +8613501747906 ; +8618017117871, Email maoeq@yeah.net; zhaobing124@163.comBackground: Platelet activation in the early stage of pancreatitis is the key step developing into pancreatic necrosis. Studies suggested that vitamin C (Vit C) can inhibit platelet activity by targeting CXCL12/CXCR4 pathway. High-dose Vit C were showed to reduce pancreatic necrosis in severe acute pancreatitis (SAP) but the mechanism remains unclear. Here we speculate high-dose Vit C reduce pancreatic necrosis by inhibiting platelet activation through downregulating CXCL12/CXCR4 pathway.Methods: The pancreatic microcirculation of rats was observed by intravital microscopy. The platelet activity of SAP rats treated with or without high-dose Vit C was analyzed by platelet function test. Besides, the activity of platelets preincubated with high-dose Vit C or vehicle from SAP patients was also evaluated. Then, the TFA (CXCR4 agonist) and rCXCL12 were used to neutralize the effect of high-dose Vit C in SAP rats treated with high-dose Vit C. Meanwhile, the levels of enzymes and inflammatory cytokines in rat plasma, and rats’ pancreatic histopathology and mortality were assessed.Results: Platelets from animals and patients with SAP are more sensitive to agonists and are more easily activated. Administration of high-dose Vit C significantly ameliorated excessive activation of platelets in SAP rats, ultimately increasing the microvessel density and inducing microthrombus and blood stasis; these results were consistent with clinical sample analysis. Moreover, high-dose Vit C significantly inhibited the release of amylase, lipase, TNF-α, and IL-6 in SAP rat plasma, reducing pancreatic damage and the mortality of SAP rats. However, using TFA and rCXCL12 significantly reversed the effect of high-dose Vit C on excessive activation of platelets, aggravating microcirculation impairment and pancreatic damage.Conclusion: The present study suggests that high-dose Vit C can ameliorate pancreatic necrosis by improving microcirculation disorders of SAP. For the first time, the underlying mechanism is related with inhibiting platelet activation through the CXCL12/CXCR4 pathway.Keywords: severe acute pancreatitis, microcirculation impairment, platelets activity, vitamin C, CXCL12/CXCR4 pathway

Jicheng Jia,1,2 Yongchao Ma,3 Shengnan Xu,1 Jiaqi Zheng,2 Xinli Ma,2 Yuzhen Zhang,2 Weijuan Sun,2 Lizhi Liu2 1Department of Education, The National University of Malaysia, Kuala Lumpur, Malaysia; 2Department of Talent Development and Continuing Education, Shandong Shengli Vocational College, Dongying, Shandong, People’s Republic of China; 3Computer Science, North Dakota State University, Fargo, ND, USACorrespondence: Jicheng Jia, Tel +86 15689138097, Email wabajjc@163.comObjective: This study aimed to investigate the impact of academic self-efficacy on test anxiety among higher vocational students, as well as the role of sense of life meaning, fear of failure, and gender difference in mediating this relationship.Methods: A total of 2231 higher vocational students from Shandong Province were surveyed by means of Academic Self-efficacy Questionnaire, Meaning in Life Questionnaire, and Test Anxiety Scale.Results: There were significant negative correlations among academic self-efficacy, sense of life meaning, and test anxiety. Fear of failure was positively correlated with test anxiety. Sense of life meaning and fear of failure played a mediating role in the relationship between academic self-efficacy and test anxiety. The chain mediating effect was significant only in the female group, not in the male group. In contrast, academic self-efficacy indirectly predicted test anxiety by the independent mediating effect of sense of life meaning or fear of failure in the male group.Conclusion: Academic self-efficacy may influence test anxiety through the independent mediating effect of sense of life meaning, fear of failure, and the chain mediating effect, and there is a gender difference in these effects.Keywords: higher vocational students, academic self-efficacy, sense of life meaning, fear of failure, test anxiety

Yichun Zhang, Jun Peng, Wenjun Sun, Haipeng Zhang, Guang Yang Department of Pharmacy, Hebei Yanda Hospital, Langfang City, Hebei Province, People’s Republic of ChinaCorrespondence: Yichun Zhang, Department of Pharmacy, Hebei Yanda Hospital, Yanjiao Simhuilan West Road, Sanhe City, Langfang City, Hebei Province, 065200, People’s Republic of China, Tel +86-316-3306055, Email yi2022chun@163.comObjective: Home pharmaceutical care delivers individualised, whole-process and continuous pharmaceutical services and health education. This study aims to explore the feasibility of home pharmaceutical services as a combination of medical and nursing care.Methods: Patient information was collected from 1 October 2020 to 30 September 2021 and was analysed and evaluated. We then developed a family medication plan and investigated its effectiveness and any issues encountered during the implementation process.Results: A total of 102 patients received services, and 100% of the patients were satisfied with these. Moreover, using home pharmaceutical care saved approximately USD1,359.64 (RMB9,360.45) in outpatient costs and USD41,077.76 (RMB282,700) in inpatient costs, and the number of hospitalisations was reduced by 16%.Conclusion: It is beneficial to make home pharmaceutical services available as a combination of medical and nursing care. Pharmacists can help patients solve medication-related problems and reduce the number of hospitalisations and medical costs through standardised service models while ensuring safe, effective, economical and rational drug use for patients.Keywords: medical care, nursing, home care, home pharmacist, standard services

Wenwen Sun,1,2 Yuling Xing,2 Fei Zhou,2,3 Yingao Ma,2,3 Xiaozheng Wan,2,4 Huijuan Ma3,5 1Graduate School of North China University of Science and Technology, Tangshan, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Graduate School of Hebei North University, Zhangjiakou, People’s Republic of China; 5Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Huijuan Ma, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China, Tel +86 18032838686, Email huijuanma76@163.comObjective: In view of the high prevalence of osteoporosis in diabetic patients, this study aimed to investigate the correlation between TyG-BMI, which represents insulin resistance, and bone loss markers, which represent bone metabolism, in an attempt to provide new ideas for the early prevention and diagnosis of osteoporosis in patients with T2DM.Patients and Methods: A total of 1148 T2DM were enrolled. The clinical data and laboratory indicators of the patients were collected. TyG-BMI was calculated based on fasting blood glucose (FBG), triglycerides (TG), and body mass index (BMI) levels. Patients were divided into Q1-Q4 groups according to TyG-BMI quartiles. According to gender, two groups were divided into men and postmenopausal women. Subgroup analysis was performed according to age, course of disease, BMI, TG level and 25(OH)D3 level. The correlation between TyG-BMI and BTMs was investigated by correlation analysis and multiple linear regression analysis using SPSS25.0 statistical software.Results: 1. Compared with Q1 group, the proportion of OC, PINP and β-CTX in Q2, Q3 and Q4 groups decreased significantly. 2. Correlation analysis and multiple linear regression analysis showed that TYG-BMI was negatively correlated with OC, PINP and β-CTX in all patients and male patients. In postmenopausal women, TyG-BMI was negatively correlated with OC and β-CTX, but not with PINP. 3. Subgroup analysis of male patients and postmenopausal female patients according to age, course of disease, BMI, TG and 25(OH)D3 showed that TyG-BMI had a stronger negative correlation with BTMs in male patients with age < 65, disease duration < 10, BMI≥ 24, TG < 1.7, and 25(OH)D3≥ 20.Conclusion: This study was the first to show an inverse association between TyG-BMI and BTMs in T2DM patients, suggesting that high TyG-BMI may be associated with impaired bone turnover.Keywords: type 2 diabetes mellitus, triglyceride glucose-body mass index, bone turnover markers, inflammation

Wei Sun,1,2,&ast; Songyi Xu,3,&ast; Tianlun Shen,1,3,&ast; Guangyao Li,1 Jingfeng Zhang,2 Chunshu Pan,1,2 Wei Lu,1,2 Xiangrui Liu,1 Jianjun Zheng,2 Jun Ling,1,3 Jihong Sun1 1Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Radiology, Ningbo No. 2 Hospital, Ningbo, People’s Republic of China; 3MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jihong Sun, Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Tel +86 13857176538, Email sunjihong@zju.edu.cn Jianjun Zheng, President of Ningbo No. 2 Hospital, Ningbo, People’s Republic of China, Tel +86 574 83870280, Email zhjjnb2@163.comPurpose: Chemotherapy treatments for cancer are always accompanied by a low concentration of drug delivered in the tumor area and severe side effects including systemic toxicity. Improving the concentration, biocompatibility, and biodegradability of regional chemotherapy drugs is a pressing challenge in the field of materials.Methods: N-Phenyloxycarbonyl-amino acids (NPCs) which exhibit significant tolerance to nucleophiles, such as water and hydroxyl-containing compounds, are promising monomers for the synthesis of polypeptides and polypeptoids. Cell line and mouse models were used to comprehensively explore how to enhance the tumor MRI signal and evaluate the therapeutic effect of Fe@POS-DOX nanoparticles.Results: In this study, poly(3,4-dihydroxy-L-phenylalanine)-b-polysarcosine (PDOPA-b-PSar, simplified as POS) was synthesized by the block copolymerization of DOPA-NPC with Sar-NPC. Fe@POS-DOX nanoparticles were prepared in order to utilize the strong chelation of catechol ligands to iron (III) cations and the hydrophobic interaction between DOX and DOPA block to deliver chemotherapeutics to tumor tissue. The Fe@POS-DOX nanoparticles exhibit high longitudinal relaxivity (r1 = 7.06 mM− 1·s− 1) and act as T1-weighted magnetic resonance (MR) imaging contrast agents. Further, the main focus was improving tumor site-specific bioavailability and achieving therapeutic effects through the biocompatibility and biodegradability of Fe@POS-DOX NPs. The Fe@POS-DOX treatment exhibited excellent antitumor effects.Conclusion: Upon intravenous injection, Fe@POS-DOX delivers DOX specifically to the tumor tissues, as revealed by MR, and leads to the inhibition of tumor growth without overt toxicity to normal tissues, thus displaying considerable potential for use in clinical applications.Graphical Abstract: Keywords: poly (α-amino acid)s, polypeptides, polypeptoids, MRI, chemotherapy, nanoparticles

Yin-Gen Luo, Xiao-Wu Zhang, Jiay-Wei Tsauo, Ying Li, Jin-Gui Li, Qing Peng, Ya-Wei Li, Wei Sun, He Zhao, Xiao Li Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Xiao Li; He Zhao, Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Tel/Fax +86 010 8778 8502, Email simonlixiao@gmail.com; hezhaoo@gmail.comObjective: This study aimed to investigate the shortest compression time to achieve hemostasis and the optimal hemostasis strategy in patients treated with transradial access chemoembolization (TRA-TACE).Methods: From October 2019 to October 2021, 119 consecutive patients with hepatocellular carcinoma (HCC) who underwent 134 sessions of TRA-TACE were included in this prospective single-center study. The compression time was measured by decompressing the device for 30 min, and thereafter, every 10 min after the procedure until complete hemostasis was achieved.Results: Technical success was achieved for all TRA procedures. None of the patients experienced major TRA-related adverse events. Minor adverse events occurred in 7.5% of the patients. The mean compression time was 31.8 ± 5.0 min. Factors that may impact hemostasis were analyzed by univariate and multivariate analyses, and a platelet count < 100× 109 /L (p = 0.016, odds ratio = 3.942) was found to be an independent factor that could predict the failure to achieve hemostasis within 30 min. For patients with a platelet count < 100× 109 /L, the compression time required to achieve hemostasis was 60 min. For patients with a platelet count ≥ 100× 109 /L, the compression time required to achieve hemostasis was 40 min.Conclusion: To achieve hemostasis in patients with HCC treated with TRA-TACE, compression for 60 min is sufficient for those with a platelet count < 100× 109 /L, and compression for 40 min is sufficient for those with a platelet count ≥ 100× 109 /L.Keywords: hepatocellular carcinoma, transarterial chemoembolization, transradial access, hemostasis

Tongsong Zhang,1,&ast; Fangfang Shang,2,&ast; Yanhui Ma,3 Yanxia Xu,1 Weihong Sun,4 Haiping Song1 1Department of Oncology, Affiliated Qingdao Central Hospital of Qingdao University, Qingdao Cancer Hospital, Qingdao, Shandong, 266042, People’s Republic of China; 2Department of Pathology, No. 971 Hospital of People’s Liberation Army Navy, Qingdao, 266071, People’s Republic of China; 3Department of Clinical Laboratory, Biotherapy Center, Affiliated Qingdao Central Hospital, Qingdao University, Qingdao, 266042, People’s Republic of China; 4Affiliated Qingdao Central Hospital of Qingdao University, Qingdao Cancer Hospital, Qingdao, Shandong, 266042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiping Song; Yanxia Xu, Department of Oncology, Affiliated Qingdao Central Hospital of Qingdao University, Qingdao Cancer Hospital, 127 Siliu South Road, Qingdao, 266042, People’s Republic of China, Tel +86 532 8496 2202 ; +86 532 84962203, Fax +86 532-84963506, Email yanguangcanlanning@163.com; xyx1021@126.comObjective: To investigate whether the expression of Hsp70 is associated with Cav-1 in promoting the imbalance of Th17/Treg cells in COPD.Methods: The plasma Cav-1, Hsp70 expression were quantified by enzyme-linked immunosorbent assay (ELISA). The frequencies of circulating Th17, Treg cells and Th17/Treg ratio were determined by flow cytometry. Peripheral blood mononuclear cells (PBMCs) from subjects were transfected with Cav-1 or control plasmids and Hsp70 plasmid.Results: We found that Cav-1 expression was lower but the levels of Hsp70 and Th17 cells were higher in COPD than in healthy control (HC). Hsp70 expressions were positively correlated with Cav-1 levels, Th17 cells, and Th17/Treg ratio in COPD but not in HC. Cav-1 over-expression resulted in an increase in Hsp70 and Th17 levels. Suppressing Hsp70 expressing by small interfering RNA (siRNA), the decline of Th17 frequency was observed in Cav-1-overexpressed PBMCs.Conclusion: Collectively, our results illuminate that Cav-1 contributes to the imbalance of Th17/Treg through potentially regulating Hsp70 expression.Keywords: caveolin-1, COPD, Hsp70, IL-17+ Th17 cells, Foxp3+ Treg cells

Ting Duan,1,2,&ast; Xin Yang,3,&ast; Jingyu Kuang,4 Wenjie Sun,3 Jin Li,3 Juan Ge,3 Mohan Zhang,3 Xiaobo Cai,3 Peilin Yu,3 Jun Yang,5 Xinqiang Zhu6 1School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, People’s Republic of China; 2Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, People’s Republic of China; 3Department of Toxicology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, People’s Republic of China; 4Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, 410073, People’s Republic of China; 5Department of Nutrition and Toxicology, Hangzhou Normal University School of Public Health, Hangzhou, Zhejiang, 311121, People’s Republic of China; 6Medical Research Center, The Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, 322000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinqiang Zhu; Jun Yang, Email zhuxq@zju.edu.cn; gastate@zju.edu.cnPurpose: The uncoordinated-51 like kinase 1 (ULK1) is an important serine/threonine protein kinase involved in autophagy, especially for the initiation stage. Previous studies have shown that ULK1 could be used as a prognostic marker in predicting poor progression-free survival and a therapeutic target for hepatocellular carcinoma (HCC) when treated with sorafenib; however, its role during hepatocarcinogenesis remains to be elucidated.Methods: CCK8 and colony formation assay were used to detect cell growth ability. Western blotting was performed to determine expression level of protein. Data from public database were downloaded to analyze expression of ULK1 at mRNA level and predict survival time. RNA-seq was conducted to reveal disturbed gene profile orchestrated by ULK1 depletion. A diethylnitrosamine (DEN)-induced HCC mice model was used to uncover the role of ULK1 in hepatocarcinogenesis.Results: ULK1 was up-regulated in liver cancer tissues and cell lines, and knockdown of ULK1 promoted apoptosis and suppressed proliferation of liver cancer cells. In in vivo experiments, Ulk1 depletion attenuated starvation-induced autophagy in mice liver, reduced diethylnitrosamine (DEN)-induced hepatic tumor number and size, and prevented tumor progression. Further, RNA-seq analysis revealed a close relationship between Ulk1 and immunity with significant changes in gene sets enriched in the interleukin and interferon pathways.Conclusion: ULK1 deficiency prevented hepatocarcinogenesis and inhibited hepatic tumor growth, and might be a molecular target for the prevention and treatment of HCC.Keywords: hepatocellular carcinoma, ULK1, RNA-sequencing, apoptosis, autophagy

Qingyu Zhang,1 Wei Sun,2,3 Tengqi Li,4,5 Fanxiao Liu1 1Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 2Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 3Centre for Osteonecrosis and Joint-Preserving & Reconstruction, Orthopaedic Department, China Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 4Department of Orthopedics, Peking University Shougang Hospital, Beijing, People’s Republic of China; 5Department of Orthopedics, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of ChinaCorrespondence: Fanxiao Liu, Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China, Tel/Fax +86-531-68773195, Email woshi631@126.comAbstract: Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a disabling disease with high mortality in China but the detailed molecular and cellular mechanisms remain to be investigated. Macrophages are considered the key cells in osteoimmunology, and the cross-talk between bone macrophages and other cells in the microenvironment is involved in maintaining bone homeostasis. M1 polarized macrophages launch a chronic inflammatory response and secrete a broad spectrum of cytokines (eg, TNF-α, IL-6 and IL-1β) and chemokines to initiate a chronic inflammatory state in GIONFH. M2 macrophage is the alternatively activated anti-inflammatory type distributed mainly in the perivascular area of the necrotic femoral head. In the development of GIONFH, injured bone vascular endothelial cells and necrotic bone activate the TLR4/NF-κB signal pathway, promote dimerization of PKM2 and subsequently enhance the production of HIF-1, inducing metabolic transformation of macrophage to the M1 phenotype. Considering these findings, putative interventions by local chemokine regulation to correct the imbalance between M1/M2 polarized macrophages by switching macrophages to an M2 phenotype, or inhibiting the adoption of an M1 phenotype appear to be plausible regimens for preventing or intervening GIONFH in the early stage. However, these results were mainly obtained by in vitro tissue or experimental animal model. Further studies to completely elucidate the alterations of the M1/M2 macrophage polarization and functions of macrophages in glucocorticoid-induced osteonecrosis of the femoral head are imperative.Keywords: osteonecrosis, macrophage polarization, osteoimmunity, osteoclast differentiation, osteogenesis, glucocorticoid

Abstract Genomic studies are uncovering extensive cryptic diversity within reef‐building corals, suggesting that evolutionarily and ecologically relevant diversity is highly underestimated in the very organisms that structure coral reefs. Furthermore, endosymbiotic algae within coral host species can confer adaptive responses to environmental stress and may represent additional axes of coral genetic variation that are not constrained by taxonomic divergence of the cnidarian host. Here, we examine genetic variation in a common and widespread, reef‐building coral, Acropora tenuis, and its associated endosymbiotic algae along the entire expanse of the Great Barrier Reef (GBR). We use SNPs derived from genome‐wide sequencing to characterize the cnidarian coral host and organelles from zooxanthellate endosymbionts (genus Cladocopium). We discover three distinct and sympatric genetic clusters of coral hosts, whose distributions appear associated with latitude and inshore–offshore reef position. Demographic modelling suggests that the divergence history of the three distinct host taxa ranges from 0.5 to 1.5 million years ago, preceding the GBR's formation, and has been characterized by low‐to‐moderate ongoing inter‐taxon gene flow, consistent with occasional hybridization and introgression typifying coral evolution. Despite this differentiation in the cnidarian host, A. tenuis taxa share a common symbiont pool, dominated by the genus Cladocopium (Clade C). Cladocopium plastid diversity is not strongly associated with host identity but varies with reef location relative to shore: inshore colonies contain lower symbiont diversity on average but have greater differences between colonies as compared with symbiont communities from offshore colonies. Spatial genetic patterns of symbiont communities could reflect local selective pressures maintaining coral holobiont differentiation across an inshore–offshore environmental gradient. The strong influence of environment (but not host identity) on symbiont community composition supports the notion that symbiont community composition responds to habitat and may assist in the adaptation of corals to future environmental change.

Sun W, Luo Z, Jin J, Cao Z, Ma Y. Int J Chron Obstruct Pulmon Dis. 2021;16:2267–2277. The authors have advised the author list on page 2267 is incorrect. The text “Yingmin Ma2” should read “Yingmin Ma1,2”. The authors apologize for this error.

Wenju Sun,1,&ast; Yuqing Cui,1,&ast; Xiaojuan Zhang,1,&ast; Yuze Wang,1 Zihao Zhang,2 Xianfei Ding,1 Huoyan Liang,1 Dong Wang,1 Yali Sun,1 Shaohua Liu,1 Xiaoguang Duan,1 Yibin Lu,3 Tongwen Sun1 1General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, Zhengzhou, 450052, People’s Republic of China; 2Department of Clinical Medicine, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China; 3Department of Critical Care Medicine, Xinyang Hospital Affiliated to Zhengzhou University, Xinyang, 464000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tongwen Sun, General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, Zhengzhou, Henan Province, 450052, People’s Republic of China, Email suntongwen@163.comBackground: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. However, there is still no single drug that could reduce septic mortality. Previous studies have reported gabexate mesylate (GM) significantly reduced serum inflammatory factors, alleviated sepsis-induced lung injury and improved clinical outcomes. This study aimed to combine with microbiome sequencing and metabolomics analysis to explore the effects of GM administration in septic rats.Methods: Sixty SD rats were randomly divided into the sham control (SC), cecal ligation and puncture (CLP), and GM injection (GM) groups. The mortality was measured and colonic feces were collected to examine the gut microbiota and metabolism 24 h after the procedure. The lung tissues were collected for hematoxylin-eosin staining.Results: We observed the relative abundance of Pygmaiobacter, which contributed to short-chain fatty acids (SCFAs) promotion, Lactobacillus and Erysipelotrichaceae UCG-003 increased in the GM-treated rats, while Escherichia–Shigella and Akkermansia decreased compared to the sepsis-induced lung injury group. Furthermore, these 3 metabolites including Palmitoylethanolamide, Deoxycholic acid and Chenodeoxycholic acid correlated significantly to CLP- and GM-rich genus (P < 0.05). Besides, the lung tissues of CLP group showed more severe inflammatory infiltration and edema, and the mortality rate in the CLP group (10/20) was significantly higher than in the SC group (0/20) (P < 0.001) and GM group (4/20) (P < 0.05).Conclusion: Our findings showed that GM attenuated sepsis-induced lung injury rats and regulated metabolites related to gut microbiota, which may provide an effective treatment for sepsis patients.Keywords: sepsis, gabexate mesylate, gut microbiota, metabolomics, rats

Yanan Feng,1,&ast; Wenxiu Sun,2,&ast; Fengcui Sun,1 Guoliang Yin,1 Pengpeng Liang,1 Suwen Chen,1 Xiangyi Liu,1 Tongfei Jiang,3 Fengxia Zhang4 1Shandong University of Traditional Chinese Medicine, Jinan, 250000, People’s Republic of China; 2Department of Nursing, Taishan Vocational College of Nursing, Taian, People’s Republic of China; 3Capital Medical University, Beijing, 100069, People’s Republic of China; 4Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengxia Zhang, Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China, Tel +86-131-5317-5246, Email fxzhang0987@163.comAbstract: Non-alcoholic fatty liver disease (NAFLD), a spectrum of liver disorders from non-alcoholic fatty liver (NAFL) to the more severe non-alcoholic steatohepatitis (NASH), is the leading etiology of chronic liver disease and its global prevalence is increasing. Hepatic steatosis, a condition marked by an abnormal buildup of triglycerides in the liver, is the precursor to NAFLD. Differentiated cluster 36 (CD36), a scavenger receptor class B protein, is a membrane receptor that recognizes multiple lipid and non-lipid ligands. It is generally agreed that CD36 contributes significantly to hepatic steatosis by taking part in fatty acid uptake as well as triglyceride storage and secretion. While there has not been any conclusive research on how CD36 inhibitors prevent NAFLD from progressing and no clinically approved CD36 inhibitors are currently available for use in NAFLD, CD36 remains a target worthy of further investigation in NAFLD. In recent years, the potential role of natural products acting through CD36 in treating non-alcoholic fatty liver disease has attracted much attention. This paper offers an overview of the pathogenesis of CD36 in NAFLD and summarizes some of the natural compounds or extracts that are currently being investigated for modulating NAFLD via CD36 or the CD36 pathway, providing an alternative approach to the development of CD36-related drugs in NAFLD.Keywords: NAFLD, CD36, natural inhibitors, FFA, TG

Zixing Bai1 &ast;, Xuhan Cao1 &ast;, Yanjun Yang,1 Xudong Sun,1 Yongli Dong,2 Jianmin Wen,1 Weidong Sun1 1Second Department of Orthopedics, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Scientific Research Department, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weidong Sun, Wangjing Hospital of China Academy of Chinese Medical Sciences, No. 6 Central South Road, Wangjing, Chaoyang District, Beijing, 100102, People’s Republic of China, Tel +86-84739140, Email sunweidong8239@aliyun.comObjective: To investigate the risk factors for hallux valgus complicated with pain under the second metatarsal and construct an effective model and method for predicting hallux valgus complicated with pain under the second metatarsal based on risk factors.Methods: A total of 545 patients with hallux valgus who were admitted to our hospital were divided randomly into a training set and a validation set. The demographic characteristics, imaging indices and gait test indices of the patients were collected. The risk factors were identified by univariate and multivariate logistic regression analyses. A risk prediction model for hallux valgus with pain under the second metatarsal was established, and the area under the curve (AUC) of the receiver operating characteristic and a decision curve analysis were used for verification and identification. The value of the model was tested in the verification group.Results: Second metatarsal length, second metatarsal peak pressure, hallux valgus angle (HVA), intermetatarsal angle 1– 2 (IMA1– 2) and weight were the risk factors for hallux valgus complicated with pain under the second metatarsal. Based on the weighting of these seven risk factors, a prediction model was established. The AUC of the prediction model was 0.84 (95% confidence interval [CI]: 0.802~0.898, P < 0.05), and the results of a Hosmer–Lemeshow test showed a good degree of calibration (χ2 = 10.62, P > 0.05). The internal validation of the AUC was 0.83 (95% CI: 0.737– 0.885, P < 0.05). The model had obvious net benefits when the threshold probability was 10%– 70%.Conclusion: Second metatarsal length, second metatarsal peak pressure, HVA, IMA1– 2 and weight were the risk factors for hallux valgus combined with second metatarsal pain. The risk prediction model for hallux valgus complicated with pain under the second metatarsal based on these seven variables was proven effective.Level of Evidence: Level III, retrospective comparative study.Keywords: hallux valgus, metatarsalgia, nomogram, predictive model, risk factors

Changshui Wang,1,&ast; Shuzhen Zhao,2,&ast; Yuan Xu,3 Wenxue Sun,4 Yuanyuan Feng,2 Deshuai Liang,5 Yun Guan3 1Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 272000, People’s Republic of China; 2Children’s Rehabilitation Center, Jining Maternal and Child Health Family Planning Service Center, Jining, 272000, People’s Republic of China; 3Department of Hematology, Jining NO. 1 People’s Hospital, Jining, 272000, People’s Republic of China; 4Institute of Clinical Pharmacy and Pharmacology, Jining NO. 1 People’s Hospital, Jining Medical University, Jining, 272000, People’s Republic of China; 5Department of pharmacy, Jining NO. 1 People’s Hospital, Jining, 272000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Guan; Deshuai Liang, Jining NO. 1 People’s Hospital, 6 Jiankang Road, Jining, Shandong, 272000, People’s Republic of China, Tel/Fax +86-0537 2087092, Email gyuanun1989@163.com; 13468322037@163.comPurpose: We designed this study to investigate the potential correlations between gut microbiota compositions and hepatic metabolomic disorders in mice with methotrexate (MTX)-induced hepatoxicity.Methods: We used MTX to induce hepatoxicity in healthy Kunming mice, and we determined plasma ALT and AST levels and assessed the liver tissue histopathology. We applied an integrated gas chromatography-mass spectrometry (GC-MS) and 16S ribosomal RNA (rRNA) gene sequencing approach to evaluate the effects of MTX on the gut microbiota and hepatic metabolic profiles of mice. We uncovered correlations between the gut microbiota and hepatic metabolomic profiles by calculating the Spearman correlation coefficient.Results: MTX caused ALT and AST level elevations and hepatoxicity in our mouse model. MTX disrupted amino acid metabolic pathways (including biosyntheses of valine, leucine, and isoleucine; and arginine; and, metabolism of alanine, aspartate, and glutamate; histidine; beta-alanine; and glycine, serine, and threonine); biosyntheses of aminoacyl-tRNA; and pantothenate, and CoA; and, metabolic pathways of energy, glutathione, and porphyrin; and chlorophyll. In addition, MTX increased the abundances of Staphylococcus, Enterococcus, Collinsella, Streptococcus, and Aerococcus, but decreased the amounts of Lactobacillus, Ruminococcus, norank_f_Muribaculaceae, unclassified_f_Lachnospiraceae, norank_f_Lachnospiraceae, A2, Eubacterium_xylanophilum_group, Phascolarctobacterium, Bifidobacterium, and Faecalibaculum. Our correlation analyses showed that different flora abundance changes including those of Phascolarctobacterium, Faecalibaculum, norank_f_Muribaculaceae, Streptococcus, Enterococcus, Staphylococcus, and Collinsella were associated with liver injury.Conclusion: We present evidence supporting the notion that MTX causes hepatoxicity by altering the gut microbiota and hepatic metabolite profiles, our findings provide new venues for the management of MTX-induced hepatoxicity.Keywords: gas chromatography-mass spectrometry, 16S ribosomal RNA, methotrexate, hepatoxicity

Tingting Xu,1,&ast; Wei Sun,2,&ast; Hongqing Zhao,3,&ast; Xinmin Wang,4 Qi Yuan,1 Xijie Zhang,1 Shan Mao,5 Xiuwei Zhang,6 Mingming Zhao,7 Zebo Sheng,8 Mingshun Zhang,9 Mao Huang,1 Ningfei Ji1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Xishan People’s Hospital of Wuxi City, Wuxi, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Wuxi Second People’s Hospital, Wuxi, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Shuyang Hospital of Traditional Chinese Medicine, Suqian, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Nanjing First Hospital, Nanjing, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Nanjing Jiangning Hospital, Nanjing, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Nanjing Gaochun People’s Hospital, Nanjing, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Changshu First People’s Hospital, Suzhou, People’s Republic of China; 9Department of Immunology, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mao Huang; Ningfei Ji, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel/Fax +86-13813886116 ; +86-18951080699, Email hm6114@163.com; jiningfei@163.comPurpose: Hospitalization for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is considered as severe exacerbations. Readmission for severe exacerbations is a crucial event for COPD patients. However, factors associated with readmission for severe exacerbations are incomplete. The study aimed to investigate different characteristics between the severe and non-severe exacerbation groups.Patients and Methods: Patients hospitalized for severe AECOPD were included in multi-centers, and their exacerbations in next 12 months after discharge were recorded. According to exacerbations, patients were separated into the severe-exacerbation group and the non-severe exacerbation group. Propensity-score matching (PSM) and multivariable analyses were performed to compare the baseline characteristics of two groups. The Hosmer-Lemeshow test and receiver operating characteristic curve were applied to evaluate how well the model could identify clusters.Results: The cohort included 550 patients with severe AECOPD across 27 study centers in China, and 465 patients were finally analyzed. A total of 41.5% of patients underwent readmission for AECOPD within 1 year. There were no significant differences in baseline characteristics between groups after PSM. Severe exacerbations in the 12 months were related to some factors, eg, the duration of COPD (13 vs 8 years, P< 0.001), the COPD Assessment Test (CAT) score (20 vs 17, P< 0.001), the blood eosinophil percentage (1.5 vs 2.0, P< 0.05), and their inhaler therapies. Patients readmitted with AECOPD had a longer time of diagnosis (≥ 9 years), more symptoms (CAT ≥ 10), and lower blood eosinophils (Eos < 2%). A clinical model was derived to help identify patients at risk of readmission with severe exacerbations.Conclusion: These analyses confirmed the relevance of COPD at admission with future severe exacerbations. A lower blood eosinophils percentage appears to be related to readmission when combined with clinical history. Further studies are needed to evaluate whether this study can predict the risk of exacerbations.Keywords: chronic obstructive pulmonary disease, acute exacerbation, eosinophils, prognosis

Song Hu,1– 3,&ast; Mingxia Wang,2,3,&ast; Siyu Li,2,&ast; Wenyu Zhou,3 Yi Zhang,2 Haobing Shi,2 Pengcheng Ye,2 Jixiong Sun,2 Feng Liu,2 Wei Zhang,2 Li Zheng,3 Qianhao Hou,2 Yue Wang,2 Weixin Sun,2 Yuanli Chen,2 Zhenzhen Lu,4 Zhonghua Ji,2 Lijun Liao,2 Xin Lv,3 Yinglin Wang,2 Xiangrui Wang,2 Hao Yang2,3 1Graduate School, Wannan Medical College, Wuhu, 241002, People’s Republic of China; 2Department of Anesthesiology and Pain Management, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People’s Republic of China; 3Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People’s Republic of China; 4Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Yang; Xiangrui Wang, Department of Anesthesiology and Pain Management, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, People’s Republic of China, Email yanghaozunyi@sina.com; wangxiangruirjyy@sina.comObjective: Propofol-based sedation has been widely used for gastroscopy, but the risk of respiratory suppression in elderly patients should not be overlooked. Intravenous (IV) lidocaine during surgery can reduce the demand for propofol and the incidence of cardiopulmonary complications. We examined whether IV lidocaine reduces the dose of propofol and the occurrence of adverse events during gastroscopy in elderly patients.Methods: We conducted a prospective, single-center, double-blind randomized controlled trial in elderly patients aged ≥ 65 years with ASA I-II. Subjects were randomly assigned to the lidocaine group (Group L, n=70), who received IV 1.5 mg kg− 1 lidocaine followed by a continuous infusion of 4 mg kg− 1 h− 1 lidocaine, or the normal saline group (Group N, n=70), who received an equal volume of saline in the same way.Results: IV lidocaine reduced the total and maintenance propofol dose in Group L (p< 0.001), with no significant effect on the induction dose. The incidence of intraoperative hypoxia (p=0.035), emergency airway management events (p=0.005), duration of gastroscopy (p< 0.05), consciousness recovery time (p< 0.001), and postoperative pain (p=0.009) were all reduced in Group L. Patient (p=0.025) and gastroscopist (p=0.031) satisfaction was higher in Group L. Intraoperative hemodynamic parameters, the respiratory rate, the incidence of sedation-related events and anesthesiologist satisfaction were similar between the two groups.Conclusion: IV lidocaine can significantly reduce the amount of propofol, the incidence of hypoxia and postoperative pain during gastroscopy in elderly patients, with a higher patient and gastroscopist satisfaction.Keywords: lidocaine, propofol, gastroscopy, elderly patient, sedation

Wei Sun,&ast; Liyan Ma,&ast; Yana Li, Ying Xu, Jingjuan Wei, Lei Sa, Xinxin Chen, Jianrong Su Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianrong Su, Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, No. 95, Yong’an Road, Xicheng District, Beijing, 100050, People’s Republic of China, Email youyilab@163.comObjective: This study aimed to investigate the antimicrobial susceptibilities, drug resistance mechanisms, and biofilm formation capacities of non-diphtheriae Corynebacterium strains isolated from sterile midstream urine of hospitalized patients with clinical urinary tract infections (UTIs).Methods: A total of 45 non-diphtheriae Corynebacterium isolates were recovered from sterile midstream urine. The available data of 45 patients were collected. Minimum inhibitory concentrations (MICs) of 10 commonly used antibiotics were determined. Meanwhile, the molecular resistance mechanisms of each agent were performed through PCR with specific primers. Moreover, the biofilm formation capability of each isolate on abiotic surfaces was detected with the MTT method.Results: In this study, the most prevalent three species were C. striatum (15/45, 33.3%), C. glucuronolyticum (9/45, 20.0%) and C. urealyticum (8/45, 17.8%). These three species also accounted for most renal and ureteral calculi cases. Male patients older than 50 years, especially those with underlying diseases, were more susceptible to non-diphtheriae Corynebacterium infection. All the 45 isolates were 100% susceptible to vancomycin and linezolid, but highly resistant to macrolide–lincosamide–streptogramin B (MLSB), fluoroquinolones, tetracyclines and β-lactams with corresponding mechanisms. The detection rate of multidrug–resistant (MDR) non-diphtheriae Corynebacterium is 91.1%. All isolates are able to form biofilm on abiotic surfaces, except those of C. urealyticum, C. tuberculostearicum and C. jeikeium. Isolates of C. glucuronolyticum and C. Striatum possessed the strongest biofilm formation capacity. C. amycolatum could form biofilm, but varied greatly among different isolates.Conclusion: C. striatum, C. glucuronolyticum and C. urealyticum were the most prevalent species relevant to UTIs. The high occurrence of MDR isolates and high diversities in resistance profiles, and the distinctive abilities of biofilm formation highlighted the urgency for identification to species level. We should pay more attention to the drug resistance profiles of non-diphtheriae Corynebacterium, which would help improve empirical antibiotic therapy and reduce drug resistance transmission.Keywords: non-diphtheriae Corynebacterium, antimicrobial susceptibility, resistance, mechanism, biofilm

Meng-meng Zheng,&ast; Li-min Shang,&ast; Chun-kai Du,&ast; Lei Zhang, Wen Sun, Zhi-peng Wang, Yi-chen Zhu, Ye Tian Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi-chen Zhu; Ye Tian, Department of Urology, Capital Medical University, Beijing Friendship Hospital, No. 95 Yong’an Road, Xicheng District, Beijing, 100050, People’s Republic of China, Email zhuyc82@sina.com; tianye166@126.comBackground: Potent immune-suppressive therapy has been demonstrated to increase the risk of infective endocarditis (IE) in renal recipients. Reports of Corynebacterium striatum (C. striatum) endocarditis in renal recipients are scarce, thus limiting understanding of the disease.Case Presentation: We describe a case of native valve endocarditis caused by C. striatum in a 35-year-old male patient. The young man with end-stage renal failure underwent kidney transplantation because of autosomal dominant polycystic kidney disease. Ceftazidime was administered after the surgery according to routine procedures, and the patient was discharged on the 14th day after the surgery without any evidence of infection. The patient experienced fever on the 56th day, and Corynebacterium was cultured from the patient’s blood, in agreement with the results of testing of the donor kidney preservation solution. On the 64th day, multiple thromboses were found in the right external iliac artery, particularly around the anastomotic orifice of the transplanted renal artery. Vegetation was found in the posterior mitral valve tip on the 65th day. The patient had symptoms of persistent angina pectoris and chest tightness and underwent mitral valve replacement and vegetative resection. The patient eventually died. C. striatum was detected in the mitral valve and vegetation tissue with metagenomic next-generation sequencing.Conclusion: C. striatum may cause endocarditis and endanger patients’ lives and thus warrants greater attention. Genotypic assays such as metagenomic next-generation sequencing are demonstrated to be effective in confirming species identity. Adequate anti-infection therapy and early surgery are required after IE is discovered.Keywords: kidney transplantation, infection, endocarditis, Corynebacterium striatum, case report

Wei Sun,1 Zhixin Cao,1 Yingmin Ma,2 Jing Wang,1 Liming Zhang,1 Zujin Luo1 1Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Zujin Luo, Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China, Email xmjg2002@163.comBackground: Fibrinogen is increasingly being studied as an inflammatory biomarker in chronic obstructive pulmonary disease (COPD), but there are limited data on the role of fibrinogen in assessing the severity of acute exacerbation of COPD (AECOPD). This study aimed to explore whether circulating fibrinogen could be used as a surrogate to measure the severity and predict the prognosis of AECOPD.Methods: A total of 535 AECOPD patients diagnosed at our center from January 2016 to June 2021 were retrospectively enrolled in this study. The electronic medical record of each patient was retrieved to collect data on baseline characteristics and laboratory parameters, as well as the use of noninvasive positive-pressure ventilation (NPPV) and prognosis. Multiple linear regression analysis was used to identify independent factors associated with circulating fibrinogen values. Receiver-operating characteristic curve and multivariate logistic regression analysis were applied to further verify the use of fibrinogen to predict NPPV failure.Results: Compared to patients with fibrinogen < 4 g/L, patients with increased fibrinogen levels (> 4 g/L) tended to have elevated inflammatory response and higher incidence of DVT/PTE, emphysema, pneumonia, and atherosclerosis. In addition, fibrinogen levels in NPPV-failure patients were significantly higher than non-NPPV patients and NPPV-success ones. The presence of emphysema, pneumonia, and history of long-term oxygen therapy and higher CRP levels and leukocyte counts were independent risk factors associated with increased fibrinogen levels in AECOPD. Furthermore, our data indicated that fibrinogen could be considered as a reliable biomarker to predict NPPV failure (AUC, 0.899, 95% CI 0.846– 0.952), with an OR of 7.702 (95% CI 2.984– 19.875; P< 0.001).Conclusion: The level of circulating fibrinogen can be used to measure severity of AECOPD, and among AECOPD patients managed with NPPV, fibrinogen > 3.55 g/L can independently predict NPPV failure.Keywords: COPD, noninvasive positive-pressure ventilation, acute exacerbation, fibrinogen, predictor