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Xuanling Chen,1,&ast; Xuewei Qin,1,&ast; Yutong Zhuang,2 Zhengqian Li,3 Zhenhu Liang,4 Hua Zhang,5 Lan Yao,1 Xiaoli Li,6 Jianghong He,7 Xiangyang Guo3 1Department of Anesthesiology, Peking University International Hospital, Beijing, People’s Republic of China; 2Department of Neurosurgery, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Anesthesiology, Peking University Third Hospital, Beijing, People’s Republic of China; 4Institute of Electrical Engineering, Yanshan University, Qinhuangdao, People’s Republic of China; 5Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing, People’s Republic of China; 6The State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, People’s Republic of China; 7Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangyang Guo, Peking University, Third Hospital, 49 huayuan North Road, Haidian District, Beijing, 100191, People’s Republic of China, Email puthmzk@hsc.pku.edu.cn Jianghong He, Beijing Tiantan Hospital, 119 South Fourth Ring Road West, Fengtai District, Beijing, 100069, People’s Republic of China, Email hejianghong@sina.cnObjective: To observe whether maintaining the appropriate depth of anesthesia with Bispectral Index (BIS) can improve the prognosis of Spinal Cord stimulation (SCS) implantation in patients with chronic Disorders of consciousness (DoC).Methods: 103 patients with DoC undergoing SCS implantation were reviewed, and 83 patients with DoC were included according to the standard of inclusion and exclusion Criteria. Patients were divided into a BIS group (n =45) and a non-BIS group (n =38) according to whether BIS monitoring was used during the operation. The depth of anesthesia in the BIS group was maintained between 40– 60. The anesthesiologist adjusted the depth of anesthesia in the non-BIS group according to clinical experience. Relevant information such as disease course, cause, anesthesia time, and operation time were collected. Preoperative CRS-R(preoperative) score, postoperative CRS-R(24h), and postoperative CRS-R(3m) changes were collected.Results: The CRS-R(3m) score in the BIS group was higher than that in the non-BIS group (preoperative), and the difference was statistically significant (P < 0.05). In CRS-R (24h), the BIS group was higher than the non-BIS group, and the difference was statistically significant (X2=8.787, P =0.004). The improvement of consciousness was included in the multivariate Logistic regression analysis model, and it was found that the thalamus was an independent factor affecting the improvement of consciousness (P < 0.05). During follow-up, 1 patient in the BIS group had a decrease in consciousness from MCS− to VS/ UWS and 2 patients in the non-BIS group died during follow-up.Conclusion: Patients can be benefit in hearing in CRS-R (24h). We recommend the use of BIS to monitor the depth of anesthesia in patients with DoC to improve patient outcomes.Keywords: chronic disturbance of consciousness, vegetative state/unresponsive wakefulness syndrome, spinal cord stimulation, general anesthesia, bispectral index, improved coma recovery scale

Qianhan Lin,1 Jiajia Li,1 Zulimire Abudousalamu,1 Yating Sun,1 Mengyang Xue,1 Liangqing Yao,2 Mo Chen1 1Department of Gynecologic Oncology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Gynecologic Oncology, Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Liangqing Yao; Mo Chen, Email yaoliangqing@163.com; chenmo_nicy@163.comAbstract: Ovarian cancer (OC) is the most lethal reproductive system cancer and a leading cause of cancer-related death. The high mortality rate and poor prognosis of OC are primarily due to its tendency for extensive abdominal metastasis, late diagnosis in advanced stages, an immunosuppressive tumor microenvironment, significant adverse reactions to first-line chemotherapy, and the development of chemoresistance. Current adjuvant chemotherapies face challenges such as poor targeting, low efficacy, and significant side effects. Targeted drug delivery systems (TDDSs) are designed to deliver drugs precisely to the tumor site to enhance efficacy and minimize side effects. This review highlights recent advancements in the use of TDDSs for OC therapies, including drug conjugate delivery systems, nanoparticle drug delivery systems, and hydrogel drug delivery systems. The focus is on employing TDDS to conduct direct, effective, and safer interventions in OC through methods such as targeted tumor recognition and controlled drug release, either independently or in combination. This review also discusses the prospects and challenges for further development of TDDSs. Undoubtedly, the use of TDDSs shows promise in the battle against OCs.Keywords: targeted drug delivery, ovarian cancer, drug conjugates, nanoparticle, hydrogel

Taiyu Song,&ast; Lulu Yao,&ast; Angang Zhu,&ast; Guangling Liu, Beibei Zhu, Qian Zhao, Yue Zhao, Jinya Wang Department of Pediatrics, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinya Wang, Email jinyawang@vip.163.comIntroduction: Asthma, a chronic respiratory disease closely associated with inflammation, presents ongoing treatment challenges. IALLIPF (le-Ala-Leu-Leu-Ile-Pro-Phe) is one of millet prolamins peptides (MPP) which shows anti-oxidant bioactivity by reducing the production of reactive oxygen species (ROS). Tryptophan (Trp, W) is an amino acid that has been demonstrated to possess anti-inflammatory effects. We introduce a novel cathepsin B-activatable bioactive peptides nanocarrier, PEG-IALLIPF-GFLG-W (MPP-Trp), designed for immunotherapy of asthma.Methods: MPP-Trp is synthesized, purified, and its characteristics are investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The yield of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) are examined to evaluate anti-inflammatory effects of IALLIPF, Trp and MPP-Trp. The immunomodulatory effects of IALLIPF, Trp and MPP-Trp on Th1/Th2 cell populations and cytokines are investigated by flow cytometry, qRT-PCR and ELISA assays. We explore the therapeutic effect of MPP-Trp in the mouse model of asthma by the analysis of lung histology and ELISA. It is necessary to study the biocompatibility of MPP-Trp by CCK8 assay and histopathologic analysis using hematoxylin and eosin (HE) staining.Results: In asthmatic peripheral blood mononuclear cells (PBMCs), IALLIPF, Trp and MPP-Trp are able to significantly alleviate inflammation by inhibiting the yield of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), especially MPP-Trp. MPP-Trp significantly upregulates Th1 cell levels while notably reducing Th2 cell levels. Furthermore, MPP-Trp effectively elevates the expression and production of interferon-gamma (IFN-γ), an essential cytokine from Th1 cells. Additionally, MPP-Trp markedly diminishes the mRNA expression and levels of key asthma pathogenesis cytokines, such as interleukin-4 (IL-4), interleukin-13 (IL-13), and interleukin-5 (IL-5), in asthma PBMCs. MPP-Trp ameliorates pulmonary pathological alterations and significantly inhibits OVA-induced inflammation in mice with asthma. It has little influence on the cell viability in Asthma-PBMCs treated with various concentrations or durations of MPP-Trp. No pathological changes, including in the heart, liver, spleen, lung, and kidney tissues, are observed in non-sensitized and non-challenged mice treated with MPP-Trp (20 mg/kg).Discussion: Our research demonstrates that MPP-Trp has immunomodulatory effects on Th1/Th2 cell populations, essential in managing asthma. It considerably alleviates OVA-induced asthma by shifting the immune response towards a Th1-dominant profile, thereby reducing Th2-driven inflammation. Therefore, this novel bioactive peptide nanocarrier, MPP-Trp, holds promise as a candidate for asthma immunotherapy.Keywords: asthma, cathepsin B, bioactive peptide nanocarrier, MPP-Trp, immunomodulatory

Juan Li,1,&ast; Ziqing Gao,1,&ast; Ning Li,1 Ling Yao,1 Chao Liu,1 Che Xu,1 Xiaohui Ren,1 Aiqin Wang,1 Siqi Gao,2 Miao Wang,2 Xiang Gao,2 Kun Li,3 Jianfeng Wang1 1Department of Ophthalmology, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233004, People’s Republic of China; 2School of Clinical Medicine, Bengbu Medical University, Bengbu, Anhui, 233004, People’s Republic of China; 3School of Life and Health Science, Anhui Science and Technology University, Fengyang, Anhui, 233100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kun Li; Jianfeng Wang, Email liangliang2419@126.com; wangjianfeng1969@163.comBackground: Drug therapy for eye diseases has been limited by multiple protective mechanisms of the eye, which can be improved using well-designed drug delivery systems. Mesoporous silica nanoparticles (MSNs) had been used in many studies as carriers of therapeutic agents for ocular diseases treatment. However, no studies have focused on ocular biosafety. Considering that MSNs containing tetrasulfur bonds have unique advantages and have drawn increasing attention in drug delivery systems, it is necessary to explore the ocular biosafety of tetrasulfur bonds before their widespread application as ophthalmic drug carriers.Methods: In this study, hollow mesoporous silica nanoparticles (HMSNs) with different tetrasulfur bond contents were prepared and characterized. The ocular biosafety of HMSN-E was evaluated in vitro on the three selected ocular cell lines, including corneal epithelial cells, lens epithelial cells and retinal endothelial cells (HREC), and in vivo by using topical eye drops and intravitreal injections.Results: In cellular experiments, HMSNs caused obvious S content-dependent cytotoxic effect. HMSNs with the highest tetrasulfur bond content (HMSN-E), showed the highest cytotoxicity among all the HMSNs, and HREC was the most vulnerable cell to HMSN-E. It was shown that HMSN-E could react with intracellular GSH to generate H2S and decrease intracellular GSH concentration. Treatment of HREC with HMSN-E increased intracellular ROS, decreased mitochondrial membrane potential, and induced cell cycle arrest at the G1/S checkpoint, finally caused apoptosis and necrosis of HREC. Topical eye drops of HMSN-E could cause corneal damage. The intravitreal injection of HMSN-E could induce inflammation in the vitreum and ganglion cell layers, resulting in vitreous opacities and retinal abnormalities.Conclusion: The incorporation of tetrasulfur bonds into HMSN can have toxic effects on ocular tissues. Therefore, when mesoporous silica nanocarriers are designed for ophthalmic pharmaceuticals, the ocular toxicity of the tetrasulfur bonds should be considered.Keywords: ophthalmic safety, hollow mesoporous silica nanoparticles, ophthalmic drug delivery, tetrasulfur bond

Qiong Wu,1,&ast; Shiying An,1,&ast; RueyJyh Lee,1 Dongwen Gao,2 Yinyifan Zhou,1 Longping Peng,1 Chunrui Hu,1 Lei Yao,3 Chang Zhou,4 Li Zhou,5 Junjie Gao,6 Min Cao,1 Meijiao Mao,1 Guanghao Li,1 Bing Deng,1 Yingjia Xu,4 Youhua Wang1 1Department of Cardiology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Ultrasound, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Cardiology, Shanghai Fifth People’s Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 5Department of Cardiology, Shanghai Jiading Nanxiang Hospital, Shanghai, People’s Republic of China; 6Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingjia Xu, Shanghai Fifth People’s Hospital, Fudan University, Minhang District, 128 Ruili Road, Shanghai, 200240, People’s Republic of China, Tel +862164308151, Email xuyingjia@5thhospital.com Youhua Wang, Department of cardiology, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Xunhui, 725 South Wan-Ping Road, Shanghai, 200032, People’s Republic of China, Tel +862164385700, Email doctorwyh@163.comBackground: Dilated cardiomyopathy (DCM) is a severe heterogeneous cardiomyopathy characterized by cardiac enlargement and declining heart function, often leading to refractory heart failure and life-threatening outcomes, particularly prevalent in China. The challenge lies in the scarcity of targeted therapies with substantial efficacy for DCM. Additionally, traditional anti-heart failure drugs are constrained due to hypotension propensity or limited symptom improvement. Kuoxin Formula (KXF), internally endorsed at Longhua Hospital, demonstrates clear biological evidence for enhancing cardiac function and myocardial remodeling. Previous clinical studies suggest its potential to enhance patients’ quality of life. This trial aims to further evaluate KXF’s safety and efficacy in managing DCM-related heart failure.Methods: This prospective, randomized, double-blind, placebo-controlled, multicenter trial aims to recruit 230 DCM patients from five centers. Participants will be randomly assigned to either KXF or placebo for 12 weeks, with careful monitoring of key indicators and adverse events. The primary outcome measures the proportion of patients with NT-proBNP reduction exceeding 30%. Secondary outcomes include New York Heart Association functional classification, Traditional Chinese Medicine syndrome scores, 6-minute walk test, Lee’s heart failure score, and Minnesota Heart Failure Quality of Life Scale score. Ventricular remodeling will be assessed using cardiac ultrasound and ELISA. Safety metrics and adverse events will be meticulously recorded.Discussion: This study will be the first multicentered research conducted in China that utilizes a randomized, double-blind, placebo-controlled design to investigate the use of TCM in the treatment of DCM. It seeks to develop new theoretical frameworks and provide solid clinical data to support the integration of TCM and modern medicine in treating heart failure in DCM patients.Trial Registration: China Clinical Trial Registry, ChiCTR2300068937. Registered on March 1, 2023. https://www.chictr.org.cn/bin/project/edit?pid=190926.Keywords: dilated cardiomyopathy, heart failure, Kuoxin Formula, traditional Chinese medicine, clinical trials

Jiewei Huang,1,2 Jiajing Zhuang,2,3 Huaxian Zheng,4 Ling Yao,5,6 Qingquan Chen,7,8 Jiaqi Wang,1,2 Chunmei Fan1 1The Clinical Laboratory Center of the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362018, People’s Republic of China; 2The Graduate School of Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China; 3Department of Ultrasound, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China; 4The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China; 5Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350000, People’s Republic of China; 6Department of Nephrology, Rheumatology and Immunology, Fujian Children’s Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350014, People’s Republic of China; 7The Sleep Disorder Medicine Center of the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362018, People’s Republic of China; 8The School of Public Health, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of ChinaCorrespondence: Chunmei Fan, The Clinical Laboratory Center of the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362018, People’s Republic of China, Tel +86 15906069575, Email fanchunmei9575@163.comObjective: Obstructive sleep apnea (OSA) is a common and potentially fatal sleep disorder. The purpose of this study was to construct an objective and easy-to-promote model based on common clinical biochemical indicators and demographic data for OSA screening.Methods: The study collected the clinical data of patients who were referred to the Sleep Medicine Center of the Second Affiliated Hospital of Fujian Medical University from December 1, 2020, to July 31, 2023, including data for demographics, polysomnography (PSG), and 30 biochemical indicators. Univariate and multivariate analyses were performed to compare the differences between groups, and the Boruta method was used to analyze the importance of the predictors. We selected and compared 10 predictors using 4 machine learning algorithms which were “Gaussian Naive Bayes (GNB)”, “Support Vector Machine (SVM)”, “K Neighbors Classifier (KNN)”, and “Logistic Regression (LR)”. Finally, the optimal algorithm was selected to construct the final prediction model.Results: Among all the predictors of OSA, body mass index (BMI) showed the best predictive efficacy with an area under the receiver operating characteristic curve (AUC) = 0.699; among the predictors of biochemical indicators, triglyceride-glucose (TyG) index represented the best predictive performance (AUC = 0.656). The LR algorithm outperformed the 4 established machine learning (ML) algorithms, with an AUC (F1 score) of 0.794 (0.841), 0.777 (0.827), and 0.732 (0.788) in the training, validation, and testing cohorts, respectively.Conclusion: We have constructed an efficient OSA screening tool. The introduction of biochemical indicators in ML-based prediction models can provide a reference for clinicians in determining whether patients with suspected OSA need PSG. Keywords: biochemical indicators, obstructive sleep apnea, machine learning, prediction model, triglyceride-glucose index

Yan Feng,&ast; Jia-Feng Sun,&ast; Hai-Chao Wei,&ast; Ying Cao, Lei Yao, Bo-Xiang Du The Affiliated Hospital 2 of Nantong University, Nantong City, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo-Xiang Du; Lei Yao, Email boxiang_du@163.com; yaoleijiangsu1987@163.comPurpose: This study aims to investigate how the type of anesthesia used during major orthopedic surgery may impact adverse short-term postoperative outcomes depending on frailty.Methods: To conduct this investigation, we recruited individuals aged 65 years and older who underwent major orthopedic surgery between March 2022 and April 2023 at a single institution. We utilized the FRAIL scale to evaluate frailty. The primary focus was on occurrences of death or the inability to walk 60 days after the surgery. Secondary measures included death within 60 days; inability to walk without human assistance at 60 days; death or the inability to walk without human assistance at 30 days after surgery, the first time out of bed after surgery, postoperative blood transfusion, length of hospital stay, hospital costs, and the occurrence of surgical complications such as dislocation, periprosthetic fracture, infection, reoperation, wound complications/hematoma.Results: In a study of 387 old adult patients who had undergone major orthopedic surgery, 41.3% were found to be in a frail state. Among these patients, 262 had general anesthesia and 125 had neuraxial anesthesia. Multifactorial logistic regression analyses showed that anesthesia type was not linked to complications. Instead, frailty (OR 4.04, 95% CI 1.04 to 8.57, P< 0.001), age (OR 1.05, 95% CI 1.00– 1.10, P= 0.017), and aCCI scores, age-adjusted Charlson Comorbidity Index, (OR 1.36, 95% CI 1.12 to 1.66, P= 0.002) were identified as independent risk factors for death or new walking disorders in these patients 60 days after surgery. After adjusting for frailty, anesthesia methods was not associated with the development of death or new walking disorders in these patients (P > 0.05).Conclusion: In different frail populations, neuraxial anesthesia is likely to be comparable to general anesthesia in terms of the incidence of short-term postoperative adverse outcomes.Keywords: anesthesia, frailty, major orthopedic surgery, death, impaired walking ability

Tingting Zhang,1,&ast; Lan Yao,1,&ast; Tao Li,2 Haoxin Tian,3 Guirong Song4 1Nursing Department, the First Hospital Affiliated to Dalian Medical University, Dalian, People’s Republic of China; 2Department of Neurology, the First Hospital Affiliated to Dalian Medical University, Dalian, People’s Republic of China; 3The First Clinical College, Dalian Medical University, Dalian, People’s Republic of China; 4Department of Health Statistics, School of Public Health, Dalian Medical University, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guirong Song, Email songsara2016@dmu.edu.cnBackground: Promoting participation and autonomy (PA) in society has been highlighted as an ultimate goal of rehabilitation for people with chronic diseases by the World Health Organization, but few studies have focused on PA in people with Parkinson’s disease (PD). Therefore, this study aimed to determine the level of PA in PD patients and investigate the associated psychological and behavioural factors.Methods: PD patients were recruited from the Department of Neurology of the First Hospital Affiliated with Dalian Medical University using convenience sampling for this cross-sectional study. A questionnaire covering social-demographic and disease-related characteristics, Chinese version of Impact on Participation and Autonomy (IPA) Questionnaire, Connor-Davidson Resilience Scale (CD-RISC), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), Medical Coping Modes Questionnaire (MCMQ), Social Support Rating Scale (SSRS), Hoehn-Yahr Staging System and Unified Parkinson’s Disease Rating Scale (UPDRS) were used for investigation. A multivariate stepwise linear regression analysis was used to determine the factors that influence IPA.Results: A total of 326 PD patients responded to all the questionnaires. The patients had a mean IPA score of 46.6 (SD 21.79). Multiple linear regression analyses revealed that UPDRS II (β = 0.35, p < 0.001) had the strongest correlation with IPA, followed by tenacity, which was the second strongest factor (β = − 0.25, p < 0.001). Hoehn-Yahr stage (β = 0.19, p < 0.001) and availability of social support (β =− 0.12, p =0.001) were also strong factors.Conclusion: The average level of PA among PD patients was at the lower middle-level. Among PD patients, physical function, psychological resilience and social support were the strongest factors associated with PA. These findings provide valuable insights into PD patients’ PA and can help medical professionals identify the early risks of restricted PA among PD patients, implement interventions to promote PA and ultimately achieve rehabilitation.Keywords: participation and autonomy, psychological resilience, social support, Parkinson’s disease, medical coping modes

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

Jiakang Chen,1,&ast; Kasim Allel,2– 4,&ast; Chuyue Zhuo,1,&ast; Wenwei Luo,5 Nanhao He,1 Xu Yang,1 Yingyi Guo,1 Jiong Wang,1 Likang Yao,1 Jiahui Li,1 Yexin Lin,1 Ruiyang Tu,6 Laith Yakob,2,3 Chao Zhuo1 1State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Disease Control, Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK; 3Antimicrobial Resistance Centre, London School of Hygiene & Tropical Medicine, London, UK; 4Institute for Global Health, University College London, London, UK; 5Department of Clinical Laboratory, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 6Department of Science and Technology Studies, University College London, London, UK&ast;These authors contributed equally to this workCorrespondence: Chao Zhuo, State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, Guangdong, People’s Republic of China, Email chaosheep@gzhmu.edu.cnIntroduction: Although Extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) significantly contribute to bloodstream infections, their economic repercussions remain largely unquantified.Data Source and Methods: We performed a retrospective analysis of inpatients diagnosed with Escherichia coli or Klebsiella pneumoniae bacteremia in a tertiary hospital from January 2020 to December 2022 in Guangzhou, China. We employed the chi-square test to examine ESBL risk factors and utilized propensity score matching (PSM) to negate baseline confounding factors, assessing economic burden through disability-adjusted life years (DALYs), hospital costs and productivity losses. We employed mediation analysis to eliminate confounding factors and better identify ESBL sources of burden related.Results: We found 166 ESBL-EC/KP BSI patients (52.2% of the total examined 318 patients). Post-PSM analysis revealed that ESBL-producing EC/KP will reduce the effectiveness of empirical medication by 19.8%, extend the total length of hospitalization by an average of 3 days, and increase the patient’s financial burden by US&dollar;2047. No significant disparity was found in overall mortality and mean DALYs between the groups. Mediation analysis showed that the link between ESBL and hospital costs is predominantly, if not entirely, influenced by the appropriateness of empirical antibiotic treatment and length of hospital stay.Conclusion: Patients with BSI due to ESBL-producing ESBL-EK incur higher costs compared to those with non-ESBL-EK BSI. This cost disparity is rooted in varying rates of effective empirical antimicrobial therapy and differences in hospital stay durations. A nuanced approach, incorporating a thorough understanding of regional epidemiological trends and judicious antibiotic use, is crucial for mitigating the financial impact on patients.Keywords: Escherichia coli, Klebsiella pneumoniae, bacteremia, ESBL, risk factors, medical costs

Guocan Yu,1 Yanqin Shen,2 Liwei Yao,2 Xudong Xu1 1Zhejiang Tuberculosis Diagnosis and Treatment Center, Hangzhou Red Cross Hospital, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Nursing, Hangzhou Red Cross Hospital, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Liwei Yao; Xudong Xu, Email ylwmed@163.com; xuxudong234@163.comPurpose: This study aimed to evaluate the efficacy of nanopore sequencing for diagnosing pulmonary tuberculosis (PTB) using smear-negative clinical specimens.Methods: We conducted a retrospective study based on a review of patient medical records to assess the accuracy of nanopore sequencing as a diagnostic tool for smear-negative PTB. Compared with clinical diagnosis, we determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of nanopore sequencing.Results: A total of 647 patients were evaluated. Nanopore sequencing demonstrated an overall sensitivity of 91.7%, specificity of 85.3%, PPV of 95.1%, NPV of 76.4%, and AUC of 0.88. Notably, the overall diagnostic accuracy of nanopore sequencing was significantly higher than that of Mycobacterium tuberculosis (MTB) culture technique.Conclusion: Nanopore sequencing exhibited satisfactory overall diagnostic accuracy for smear-negative PTB, regardless of MTB culture status. Therefore, if conditions permit, nanopore sequencing is recommended as a diagnostic method for smear-negative PTB.Keywords: nanopore sequencing, smear-negative specimens, pulmonary tuberculosis, diagnostic accuracy

Rong Wang,1 Li Yao2 1School of Nursing, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 2Department of Cardiovascular Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of ChinaCorrespondence: Li Yao, Department of Cardiovascular Medicine,General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China, Email 13995088029@163.com

Rong Wang,1 Li Yao2 1School of Nursing, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 2Department of Cardiovascular Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of ChinaCorrespondence: Li Yao, Department of Cardiovascular Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China, Email 13995088029@163.com

Qin Hu,1,2 Haoran Liu,1,2 Ruiyu Wang,3 Li Yao,3 Shikun Chen,4 Yang Wang,3 Chuanzhu Lv2,3,5 1Emergency and Trauma College, Hainan Medical University, Haikou, People’s Republic of China; 2Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Medical University, Haikou, People’s Republic of China; 3Emergency Medicine Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 4Department of Anesthesiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 5Research Unit of Island Emergency Medicine, Chinese Academy of Medical Sciences (No. 2019RU013), Hainan Medical University, Haikou, People’s Republic of ChinaCorrespondence: Yang Wang, Emergency Medicine Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China, Tel +86-15086867864, Email young0416@163.com Chuanzhu Lv, Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Medical University, Research Unit of Island Emergency Medicine, Chinese Academy of Medical Sciences (No. 2019RU013), Hainan Medical University, Haikou, People’s Republic of China, Tel +86- 19113953671, Email lvchuanzhu677@126.comPurpose: Acute lung injury (ALI) is a severe pulmonary disease characterized by damage to the alveoli and pulmonary blood vessels, leading to severe impairment of lung function. Studies on the effect of capsaicin (8-methyl-N-geranyl-6-nonamide, CAP) on lipopolysaccharide (LPS)-induced ALI in bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B) are still limited. This study aimed to investigate the effect and specific mechanism by which CAP improves LPS-induced ALI.Methods: The present study investigated the effect of CAP and the potential underlying mechanisms in LPS-induced ALI in vitro and vivo via RNA sequencing, Western blotting (WB), quantitative real-time reverse transcription PCR (qRT‒PCR), enzyme-linked immunosorbent assay (ELISA), and transmission electron microscopy (TEM). The TRPV1 inhibitor AMG9810 and the AKT agonist SC79 were used to confirm the protective effect of the TRPV1/AKT axis against ALI. The autophagy agonist rapamycin (Rapa) and the autophagy inhibitors 3-methyladenine (3-MA) and bafilomycin A1 (Baf-A1) were used to clarify the characteristics of LPS-induced autophagy.Results: Our findings demonstrated that CAP effectively suppressed inflammation and autophagy in LPS-induced ALI, both in vivo and in vitro. This mechanism involves regulation by the TRPV1/AKT signaling pathway. By activating TRPV1, CAP reduces the expression of P-AKT, thereby exerting its anti-inflammatory and inhibitory effects on pro-death autophagy. Furthermore, prior administration of CAP provided substantial protection to mice against ALI induced by LPS, reduced the lung wet/dry ratio, decreased proinflammatory cytokine expression, and downregulated LC3 expression.Conclusion: Taken together, our results indicate that CAP protects against LPS-induced ALI by inhibiting inflammatory responses and autophagic death through the TRPV1/AKT signaling pathway, presenting a novel strategy for ALI therapy.Keywords: capsaicin, acute lung injury, Inflammation, autophagy, TRPV1, AKT

Liqing Yao,1,2 Kaixin Liang,3,4 Qiu Zhang,5 Xinli Chi3,4 1School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2Faculty of Medicine, Medical Sciences Division, Macau University of Science and Technology, Macau, People’s Republic of China; 3School of Psychology, Shenzhen University, Shenzhen, People’s Republic of China; 4The Shenzhen Humanities & Social Sciences Key Research Bases of the Center for Mental Health, Shenzhen University, Shenzhen, People’s Republic of China; 5The Center for Health Economics and Health Promotion Research, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaCorrespondence: Qiu Zhang, The Center for Health Economics and Health Promotion Research, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China, Email zhangqiu@gdpu.edu.cn Xinli Chi, School of Psychology, Shenzhen University, Shenzhen, 518060, People’s Republic of China, Email xinlichi@szu.edu.cnPurpose: This study aimed to evaluate the associations between unhealthy eating habits and insomnia symptoms with Internet addiction (IA) among Chinese left-behind children (LBC) based on potential gender difference.Methods: This cross-sectional study was conducted in junior high schools from an economically disadvantaged area of China in May 2020. Participants were asked to complete the information and scales of socio-demographic characteristics, eating habits (the frequency of eating carbohydrates, fruits, vegetables, protein, and breakfast), insomnia severity and IA. A total of 3156 LBCs (43.9% males and 56.1% females, aged 14.2 years in average) were used for final analyses. Associations between eating habits and insomnia symptoms with IA were analyzed by generalized linear model with binary logistic regression.Results: The study found that left-behind children (LBCs) had unhealthy eating habits, particularly among females. Females reported more insomnia symptoms than males. The prevalence of IA was similar across genders. Consuming fewer fruits and vegetables and skipping breakfast were linked to increased IA risk, especially in females. Insomnia was significantly associated with higher IA risk in both genders.Conclusion: In LBCs, unhealthy eating and sleep were notably linked to IA, especially in females. Addressing these factors might reduce the prevalence of IA among LBCs.Keywords: eating habits, insomnia, Internet addiction, left-behind children, gender difference

Yifan Yang,1,&ast; Huayu Yang,1,&ast; Zongli Diao,2 Xu Liu,2 Lan Yao,1 Liyan Wang,2 Xiaotian Shi,1 Xu Li,1 Qing Ma1 1Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Nephrology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Ma, Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, 95, Yong-an Road, Xicheng District, Beijing, 100050, People’s Republic of China, Tel +86 10 63137641, Fax +86 10 63138730, Email maqing3@163.comPurpose: Frailty is an important geriatric syndrome associated with aging and adverse events, especially in patients with severe infection. To help guide prognosis for elderly patients undergoing maintenance hemodialysis (MHD) who experience acute infection, this study investigated whether baseline (pre-infection) frailty may be associated with adverse outcomes in elderly patients undergoing MHD who suffer SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection.Patients and Methods: Patients (aged ≥ 60 y) receiving MHD had been assessed for overall frailty and the 5 frailty components based on the Fried Frailty Phenotype scale within 3 months prior to SARS-CoV-2 infection.Results: There were 59 and 98 patients in the frail and non-frail groups, respectively. Three months after SARS-CoV-2 infection, 21 (13.4%) and 45 (28.7%) patients had died or were in hospital. The multivariate COX proportional risk model suggested that the all-cause mortality rate in patients judged overall frail or with low activity was significantly higher compared with that of the non-frail (P = 0.049; 0.003). The multivariate logistic regression analysis showed that hospitalization 3 months after SARS-CoV-2 infection was associated with both overall frailty and low activity (OR 2.276, 95% CI: 1.034– 5.010, P = 0.041; OR 2.809, 95% CI: 1.311– 6.020, P = 0.008, respectively).Conclusion: Overall frailty and specifically low activity were significantly associated with all-cause mortality and hospitalization in this elderly MHD population after SARS-CoV-2 infection. Early assessment of frailty and effective interventions are recommended to improve the prognosis of patients receiving MHD who are at higher risk of acute infection.Keywords: SARS-CoV-2, COVID-19, hemodialysis, frailty, elderly, prognosis

Linxi Zeng,1 Sen Feng,1 Lulu Yao,1 Jiaqing Zhao,1 Guoqiang Zhang1,2 1Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, People’s Republic of China; 2Candidate Branch of National Clinical Research Center for Skin Diseases, Shijiazhuang, People’s Republic of ChinaCorrespondence: Guoqiang Zhang, The First Hospital of Hebei Medical University, 89 Donggang Road, Yuhua District, Shijiazhuang City, Hebei Province, People’s Republic of China, Email zlx090702@163.comAbstract: Herpes zoster is typically a blister rash involving a single skin group, caused by the reactivation of primary varicella zoster virus infection. Disseminated herpes zoster refers to the presence of more than 20 small blisters outside the primary or adjacent skin, which is rare and usually occurs in individuals with weakened immune function. This case described a patient diagnosed with disseminated herpes zoster, with a decrease in CD4 count (379 cells/mm3) and certain skin lesions. He was subsequently screened positive for HIV. Also, we summarized other studies on the CD4 value of HIV patients with herpes zoster. Overall, for herpes zoster patients with decreased CD4 levels and certain skin manifestations, such as diffuse, ulcerative, or pustular lesions, clinicians should be aware of HIV infection.Keywords: disseminated herpes zoster, CD4, HIV infection

Li Yao,1 Song Wang2 1Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 2West China School of Nursing/West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Song Wang, West China School of Nursing/West China Hospital, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Email wangzhikang2018@126.com

Li Yao,1 Song Wang2 1Department of Cardiovascular Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 2West China School of Nursing/West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Song Wang, West China School of Nursing/West China Hospital, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Email wangzhikang2018@126.com

Qiuyu Pan,1,2 Cheng Zhang,3 Lansicheng Yao,4 Chenyao Mai,1 Jinpeng Zhang,5 Zhitong Zhang,6 Jun Hu7 1Medical College, Tibet University, Lhasa, Tibet, 850000, People’s Republic of China; 2School of Public Health, North Sichuan Medical College, Nanchong, Sichuan, 637100, People’s Republic of China; 3Policy Research Room 2, Sichuan Health Development Research Center, Chengdu, Sichuan, 610042, People’s Republic of China; 4Foreign Affairs Office, North Sichuan Medical College, Nanchong, Sichuan, 637100, People’s Republic of China; 5School of Public Health, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 6Dalla Lana School of Public Health, University of Toronto, Toronto, ON, M5T 3M7, Canada; 7School of Management, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, People’s Republic of ChinaCorrespondence: Jun Hu, School of Management, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, People’s Republic of China, Email sunnyhj@163.comPurpose: To develop and empirically test a conceptual model that explains the factors influencing antihypertensive medication adherence behavior in elderly patients in a city in western China.Patients and Methods: The conceptual model was based on the Theory of Planned Behavior and the Health Belief Model and was empirically tested using cross-sectional survey data from Nanchong City, a city in western China, collected between October and December 2020. Data were analyzed using structural equation modeling.Results: Behavioral intentions were the main predictor of medication adherence behavior (path coefficient of 0.353). Perceived benefits and perceived barriers directly (path coefficient = 0.201 and − 0.150, respectively), and indirectly (path coefficient = 0.118 and − 0.060) through behavioral intentions, influenced medication adherence behavior. Perceived susceptibility (path coefficient = 0.390) and perceived severity (path coefficient = 0.408) influenced behavioral attitudes, which influenced behavioral intentions (path coefficient = 0.298).Conclusion: The conceptual model demonstrates a robust ability to predict and explain medication adherence behavior among elderly patients with hypertension, facilitating the adoption and maintenance of changes in adherence behavior and the potential for preventing disease progression and improving quality of life.Keywords: compliance, theory of planned behavior, health belief model, elderly patients, China

Mengyang Zhao,1 Liu Yao,2 Rao Ma,3 Muhammad Sarmad,4 Orangzab,5 Arslan Ayub,6 Zhou Jun7 1School of Economics and Management, Harbin Engineering University, Harbin, Heilongjing, 150001, People’s Republic of China; 2Faculty of Management Engineering, Huaiyin Institute of Technology, Huai’an, Jiangsu, People’s Republic of China; 3Business School, University of International Business and Economics, Beijing, 100029, People’s Republic of China; 4Riphah School of Leadership, Riphah International University, Islamabad, Pakistan; 5Department of Management Sciences, COMSATS University Islamabad, Vehari, Pakistan; 6Department of Management Studies, the University of Faisalabad, Faisalabad, Pakistan; 7Faculty of Transportation Engineering, Huaiyin Institute of Technology, Huai’an, 223003, People’s Republic of ChinaCorrespondence: Mengyang Zhao, Email zhaomy_92@163.comAim: The study is based on the self-determination theory and aims to investigate the mediating role of green intrinsic motivation and the moderating role of green shared vision in the association between frontline managers’ green mindfulness and green creative behavior to leverage their capacity to think creatively and act sustainably.Methods: The study employs a time-lagged, multi-source research methodology to collect data from frontline managers of service businesses in the tourism and hospitality industry. Data are analyzed using SmartPLS Structural Equation Model to evaluate the structural and measurement models. The authors evaluated the measurement model by employing the criteria of internal consistency: reliability and Cronbach’s alpha, validity: convergent and discriminant validity; and the structural model using the path coefficient, coefficient of determination, predictive relevance, and goodness-of-fit metrics.Results: Our findings indicate that green mindfulness significantly improves frontline managers’ green creative behavior. Additionally, green intrinsic motivation mediates the connection between green mindfulness and green creative behavior. In addition, the direct effect of green mindfulness on green intrinsic motivation as well as the indirect effect of green mindfulness on green creative behavior through green intrinsic motivation, are both significantly moderated by green shared vision.Discussion: To the best of the authors’ knowledge, this is one of the few efforts that outstretch the boundary conditions of green mindfulness and green creative behavior through the mediating role of green intrinsic motivation and the moderating role of green shared vision.Keywords: green mindfulness, green creative behavior, green intrinsic motivation, green shared vision, self-determination theory

Yijia He,1 Sen Feng,1 Lulu Yao,1 Guoqiang Zhang1,2 1Department of Dermatology, the First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Candidate Branch of National Clinical Research Center for Skin Diseases, Shijiazhuang, People’s Republic of ChinaCorrespondence: Guoqiang Zhang, Department of Dermatology, the First Hospital of Hebei Medical University, No. 89, Donggang Road, Shijiazhuang, Hebei Province, People’s Republic of China, Email zlx090702@163.comAbstract: We report the case of a patient with Lymphocytic thrombophilic arteritis (LTA) with a history of 67 years. This is a relatively rare disease with no recognised guidelines for diagnosis and treatment. The long medical history from birth of this patient and the lack of positive progression may provide some new ideas for the treatment of this disease.Keywords: lymphocytic thrombophilic arteritis, macular lymphocytic arteritis, vasculitis, treatment, case report

Shina Qiao, Xiaoming Zhang, Weilan Xiang, Linyan Yao, Xuemei Xian Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Shina Qiao, Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Tel +86 13575764508, Email qiaoshina08@zju.edu.cnBackground: Compared to Western countries, palliative and hospice care services are used less often in Asian countries. While both types have been implemented in mainland China in recent years, their utilization rates have not increased satisfactorily. Moreover, few hospitals in mainland China implement hospice care using the hospice shared care model.Objective: This study investigated a case in which the hospice shared care model was implemented for one patient with advanced colon cancer who had received treatment at a general tertiary hospital in mainland China.Methods: Critical points of care included pain symptom management, nutritional support, application of the SHARE model for disease notification, family meetings to assist medical decision-making, relaxation therapy to relieve depressive symptoms, provisions to address end-of-life wishes, and support for primary caregivers.Results: The patient’s basic pain was controlled (Numeric Rating Scale, NRS2-3), and the score of the Depression Screening Scale (PHQ-9) decreased from 15 to 10 after intervention during hospitalization. In the end, the patient died comfortably and peacefully at home.Conclusion: The hospice shared care team helped the patient with her physical and psychological pain, met her end-of-life wishes, and provided support for the families.Keywords: advanced colon cancer, palliative care, symptom management, hospice share care, case report

Jinjuan Zhang,1 Caifang Bu,1 Liwei Yao,1,&ast; Kan Xu2,&ast; 1Department of Nursing, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liwei Yao, Department of Nursing, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, No. 208 East Huancheng Road, Hangzhou, Zhejiang, People’s Republic of China, Email ylwmed@163.com Kan Xu, Zhejiang Tuberculosis Diagnosis and Treatment Center, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, No. 208 East Huancheng Road, Hangzhou, Zhejiang, People’s Republic of China, Email xukanmed@163.comPurpose: To assess the accuracy of the Mycobacterium tuberculosis (MTB)-RNA assay using pericardial tissue specimens for tuberculous pericarditis (TBP) diagnosis.Methods: MTB culture and MTB-RNA assay were performed for patients with suspected TBP. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of these two assays were analyzed.Results: This study included 79 patients. The sensitivity, specificity, PPV, NPV, and AUC were 28.1% (18/64), 100.0% (15/15), 100.0% (18/18), 24.6% (15/61), and 0.64 for the MTB culture and 37.5% (24/64), 100.0% (15/15), 100.0% (24/24), 27.3% (15/55), and 0.69 for the MTB-RNA assay, respectively. Patients with positive pericardial tissue culture were defined as having definite TBP; in other words, culture was the gold standard for this group of patients and had a sensitivity, specificity, PPV, and NPV of 100% and an AUC of 1.00. However, these values were found to be 72.2% (13/18), 100.0% (15/15), 100.0% (13/13), 75.0% (15/20), and 0.86 for the MTB-RNA assay, respectively. Among patients with probable TBP (culture-negative patients), the sensitivity, specificity, NPV, and AUC of MTB culture were 0.0% (0/46), 100.0% (15/15), 24.6% (15/61), and 0.50, respectively, but the PPV could not be determined. These values were found to be 23.9% (11/46), 100.0% (15/15), 100.0% (11/11), 30.0% (15/50), and 0.62 for the MTB-RNA assay, respectively.Conclusion: MTB-RNA assay using pericardial tissues had limited diagnostic efficacy for TBP. In culture-positive TBP, the diagnostic accuracy of MTB-RNA was good. In contrast, in culture-negative TBP, its diagnostic accuracy was unsatisfactory.Keywords: tuberculous pericarditis, RNA, culture, polymerase chain reaction, accuracy

Wenbo Yang,1,&ast; Xintian Cai,1,2,&ast; Junli Hu,1 Wen Wen,1 Heizhati Mulalibieke,1 Xiaoguang Yao,1 Ling Yao,1 Qing Zhu,1 Jing Hong,1 Qin Luo,1 Shasha Liu,1 Nanfang Li1 1Hypertension Center, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China; 2Graduate School, Xinjiang Medical University, Urumqi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, NO. 91 TianChi Road, Urumqi, 830001, People’s Republic of China, Tel +86 8564818, Email lnanfang2016@sina.comObjective: We aimed to evaluate the METS-IR (metabolic score for insulin resistance) index for the prediction of incident cardiovascular disease (CVD) and its subtypes (coronary artery disease and stroke) in patients with hypertension and obstructive sleep apnea (OSA).Methods: A retrospective cohort study was conducted with 2031 adults with hypertension and OSA, participants from the Urumqi Research on Sleep Apnea and Hypertension study (UROSAH). The hazard ratios and 95% CIs (credibility interval) for CVD and its subtypes were estimated using multivariate Cox proportional hazards regression models.Results: After a median follow-up of 6.80 years (interquartile range: 5.90– 8.00 years), a total of 317 (15.61%) participants developed new-onset CVD, including 198 (9.75%) incident coronary heart disease (CHD) and 119 (5.86%) incident stroke. After adjusting for as many relevant confounding factors as possible, each SD increase in METS-IR was associated with a 30% increased risk of new onset overall CVD events, a 32% increased risk of new onset CHD, and a 27% increased risk of new onset stroke. When METS-IR was assessed as tertiles, after adjustment for fully confounding factors, the highest tertiles versus the lowest tertiles were associated with a greater hazard of CVD (HR 2.05; 95% CI 1.52,-2.77), CHD (HR 1.96; 95% CI 1.35– 2.84), and stroke (HR 2.24; 95% CI 1.35– 3.72). The results of various subgroups and sensitivity analyses were similar. When METS-IR was added, CVD predictions were reclassified and identified more accurately than baseline models for the C-index, continuous net reclassification improvement, and integrated discrimination index. CHD and stroke showed similar results.Conclusion: METS-IR is a powerful predictor of CVD and its subtypes in patients with hypertension and OSA, which can facilitate the identification of high-risk individuals and provide individualized CVD prevention.Keywords: cohort study, METS-IR, cardiovascular disease, hypertension, obstructive sleep apnoea