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Lijuan Fu,1,* Rui Zhou,2,* Wencai Jiang,1 Lan Lan,1 Xuemeng Chen,1 Yuansheng Cao,1 Leqiang Xia,1 Yukai Zhou,1 Jia Han,1 Dan Zhou,1 Xianjie Zhang1 1Department of Anesthesiology, Deyang People’s Hospital, Deyang City, Sichuan Province, People’s Republic of China; 2Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai City, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xianjie Zhang, Department of Anesthesiology, Deyang People’s Hospital, No. 173, Section 1 of North Taishan Road, Deyang City, Sichuan Province, 618000, People’s Republic of China, Tel +8613981088319, Email zhangxianjie791002@163.comBackground: While general anesthesia has been widely used in endovascular thrombectomy for acute ischemic stroke (AIS), the optimal anesthesia medication for hemodynamic management remains unclear.Purpose: To compare the effects of remimazolam and propofol on endovascular thrombectomy for AIS.Methods: This study is a single-center, double-blind and randomized controlled trial. Eligible patients will be randomly allocated into the remimazolam group and propofol group. Remimazolam and propofol will be administered to induce and maintain anesthesia respectively. The primary outcome is the incidence of intraoperative hypotension. The secondary outcomes include frequency of hypotension, the largest difference value of mean arterial pressure (MAP), dosage of vasopressors, extubation time, operation time, modified thrombolysis in cerebral infarction (mTICI) level, National Institutes of Health Stroke Scale (NIHSS) score and modified Rankin scale (mRS) score.Conclusion: This study evaluates the influences of remimazolam versus propofol on endovascular therapy for AIS patients. Results of this study are expected to provide more evidence of the choice of anesthetics in this kind of operation.Trial Registration: This study has been registered at the Chinese Clinical Trial Registry (ChiCTR2300076880).Keywords: remimazolam, acute ischemic stroke, endovascular thrombectomy, intraoperative hypotension, outcomes

Fulin Tao,1,* Lin Li,2,3,* Dawei Wang,1,2 Jinlei Dong,1 Dongsheng Zhou,1,2 Wenhao Song1,2,4 1Department of Orthopedic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 2Department of Orthopedic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 3Department of Orthopedic Surgery, Tengzhou Central People’s Hospital Affiliated to Jining Medical University, Tengzhou, Shandong, People’s Republic of China; 4Shandong Yuhuang Chemical Co., Ltd, Heze, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenhao Song, Department of Orthopedic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China, Email songwenhao0308@163.comIntroduction: This study aimed to compare the efficacy of three methods for isolated greater tuberosity fractures of the humerus.Methods: A retrospective review of patients with isolated humeral greater tuberosity fractures between January 2013 and June 2021 in our institution. We recorded data on patient demographics, injury characteristics, preoperative and postoperative imaging findings, length of incision, operative time, and intraoperative blood loss.Results: A total of 107 patients met the inclusion criteria and were divided into three groups. 50 patients in group A were administered a proximal humeral internal locking system (PHILOS) plate fixed using the deltopectoral approach, 26 patients in group B were administered a PHILOS plate fixed using the deltoid-splitting approach, and 31 patients in group C were administered a novel anatomical plate fixed using the deltoid-splitting approach. No significant differences were identified in sex, age, injury mechanism, type of fracture, dominant side limb, or shoulder anterior joint dislocation. However, the operative time, blood loss, and the length of incision was shorter than in Group C. Moreover, pain was evaluated on the third and fifth days after surgery; pain was lower in Group C, and pain at the last follow-up was not different between the groups. No significant differences were identified in the Constant score, DASH score, and ROM at the last follow-up. 2 patients were diagnosed with subacromial impingement, 1 in Group A one in Group B, and 1 patient in Group B experienced axillary nerve injury after surgery.Conclusion: The novel anatomical plate fixed using the deltoid-splitting approach can achieve good results in the treatment of isolated humeral greater tubercle fractures with less blood loss, shorter operative time, and shorter surgical incisions, and can relieve pain in the early postoperative period.Keywords: PHILOS plate, a novel anatomical plate, deltopectoral approach, deltoid-splitting approach, greater tuberosity fracture of humerus

Li Ye,1 Xiwei Sun,2 Yiping Li,1 Yali Zeng,1 Lacuo Zhuoma,1 Dinglun Zhou,2 Qinying He,3 Ju Wang,4 Wei Yang,1 Hang Yu,1 Yihui Yang,1 Shu Liang,1 Dan Yuan1 1Center for AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention, Chengdu, Sichuan, People’s Republic of China; 2West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Center for AIDS/STD Control and Prevention, Chengdu Center for Disease Control and Prevention, Chengdu, Sichuan, People’s Republic of China; 4Center for AIDS/STD Control and Prevention, Liangshan Center for Disease Control and Prevention, Xichang, Sichuan, People’s Republic of ChinaCorrespondence: Dan Yuan; Shu Liang, Email ydtv1130@163.com; liangshu523@163.comBackground: Sichuan Province was severely affected by the HIV, and there was a scarcity of data regarding the survival time and influencing factors for People Living with HIV/AIDS (PLWH) in Sichuan Province who have received Antiretroviral Therapy (ART). Therefore, it is necessary to conduct a survival analysis for PLWH receiving ART.Methods: A retrospective cohort study was conducted on PLWH who had received ART≥ 6 months in Sichuan Province from January 1, 2003, to December 31, 2022. The Kaplan-Meier method was used to calculate median survival time and plot survival curves, while a Cox proportional hazards regression model was applied to analyze factors affecting survival time. Bilateral tests were performed, with P≤ 0.05 considered statistically significant.Results: The cumulative survival rates at 1, 3, 5, and 10 years for the 223,386 subjects were 94.54%, 89.07%, 84.82%, and 76.44%, respectively. Multivariate analysis using the Cox regression model indicated lower mortality risks for females (HR=0.59, 95% CI: 0.54– 0.65), homosexual transmission (HR=0.43, 95% CI: 0.33– 0.55), and baseline BMI≥ 24 (HR=0.81, 95% CI: 0.72– 0.90). Higher mortality risks were associated with age≥ 50 years at diagnosis (HR=3.21, 95% CI: 2.94– 3.50), being unmarried or divorced (HR=1.23, 95% CI: 1.11– 1.37), living separately (HR=1.32, 95% CI: 1.22– 1.43), baseline BMI < 18.5 (HR=1.27, 95% CI: 1.13– 1.41), presence of single-drug resistance (HR=1.25, 95% CI: 1.15– 1.36), baseline WHO stage IV (HR=1.27, 95% CI: 1.09– 1.47), and a diagnosis-to-treatment interval > 12 months (HR=1.27, 95% CI: 1.15– 1.41). Compared to those with CD4(+) T cell count of 200– 350cells/μL, 350– 500cells/μL, and > 500cells/μL at baseline, individuals with < 200cells/μL had higher mortality risks (HR=0.73, 95% CI: 0.67– 0.79; HR=0.57, 95% CI: 0.51– 0.64; and HR=0.58, 95% CI: 0.51– 0.66, respectively).Conclusion: The survival rate for PLWH receiving ART in Sichuan Province was relatively high. Male gender, age over 50 at diagnosis, being unmarried, divorced, or living separately, presence of single-drug resistance, low baseline BMI, baseline CD4+ T cell < 200cells/μL, baseline WHO stage IV, and a diagnosis-to-treatment interval > 12 months were risk factors for the survival of PLWH.Keywords: PLWH, antiretroviral therapy, survival analysis

Boyong Qiu,1,2,&ast; Siyu Qiao,2,&ast; Xiujuan Shi,2 Lin Shen,2 Bing Deng,2 Zilin Ma,2 Duan Zhou,2 Yihong Wei2 1Heart Center/National Regional (Traditional Chinese Medicine) Cardiovascular Diagnosis and Treatment Center, The First Affiliated Hospital of Henan University of CM, Zhengzhou, Henan, People’s Republic of China; 2Cardiovascular Department, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yihong Wei; Duan Zhou, Email weiyihong2022@shutcm.edu.cn; zhouduan@126.comBackground: In China, Shen’ge formula (SGF), a Traditional Chinese Medicine blend crafted from ginseng and gecko, holds a revered place in the treatment of cardiovascular diseases. However, despite its prevalent use, the precise cardioprotective mechanisms of SGF remain largely uncharted. This study aims to fill this gap by delving deeper into SGF’s therapeutic potential and underlying action mechanism, thus giving its traditional use a solid scientific grounding.Methods: In this study, rats were subjected to abdominal aortic constriction (AAC) to generate pressure overload. Following AAC, we administered SGF and bisoprolol intragastrically at specified doses for two distinct durations: 8 and 24 weeks. The cardiac function post-treatment was thoroughly analyzed using echocardiography and histological examinations, offering insights into SGF’s influence on vital cardiovascular metrics, and signaling pathways central to cardiac health.Results: SGF exhibited promising results, significantly enhanced cardiac functions over both 8 and 24-week periods, evidenced by improved ejection fraction and fractional shortening while moderating left ventricular parameters. Noteworthy was SGF’s role in the significant mitigation of myocardial hypertrophy and in fostering the expression of vital proteins essential for heart health by the 24-week mark. This intervention markedly altered the dynamics of the Akt/HIF-1α/p53 pathway, inhibiting detrimental processes while promoting protective mechanisms.Conclusion: Our research casts SGF in a promising light as a cardioprotective agent in heart failure conditions induced by pressure overload in rats. Central to this protective shield is the modulation of the Akt/HIF-1α/p53 pathway, pointing to a therapeutic trajectory that leverages HIF-1α promotion and p53 nuclear transport inhibition. Keywords: Shen’ge formula, heart failure, hypertrophy, apoptosis, angiogenesis

Rui Zhou,1,2,&ast; Lijuan Fu,2,&ast; Shu Liu,2,&ast; Sanjie Gao,2 Zhifu Zhao,2 Wencai Jiang,2 Li Liu,2 Weiqiao Ren,2 Dongmei Xiang,2 Xing You,2 Chunyong Tang,2 Yukai Zhou,2 Yanqing Song,2 Juan Xie,2 Li Xie,2 Ru Yu,2 Xianjie Zhang,2 Dan Zhou,2 Jia Han,2 Leqiang Xia,2 Lize Xiong1 1Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Clinical Research Center for Anesthesiology and Perioperative Medicine, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 2Department of Anesthesiology, Deyang People’s Hospital, Deyang, 618000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leqiang Xia, Department of Anesthesiology, Deyang People’s Hospital, No. 173, Section 1, North Taishan Road, Deyang, Sichuan, 618000, People’s Republic of China, Tel +8613547098458, Email xialq123184@163.com Lize Xiong, Shanghai Fourth People’s Hospital, No. 1279, Sanmen Road, Shanghai, 200434, People’s Republic of China, Tel +86-21-55603002, Fax +86-21-56660851, Email mzkxlz@126.com; lizexiong@tongji.edu.cnPurpose: To compare the influences of propofol, ciprofol and remimazolam on dreaming during painless gastrointestinal endoscopy.Methods: This study was a single-center, prospective, parallel-design, double-blind, randomized clinical trial. Between May 2023 and October 2023, patients undergoing elective painless gastrointestinal endoscopy were recruited and randomly allocated into one of the three groups. Demographic data, intraoperative information, incidence of dreaming, insufficient anesthesia and intraoperative awareness, type of dream, patient satisfaction score, adverse events, and improvement of sleep quality were collected.Results: The difference in incidence of dreaming among the three groups was not significant (33.33% vs 48.33% vs 41.67%, p=0.061). The number of patients with intraoperative hypotension in the propofol group was larger than that of the remimazolam group (32 vs 12, p=0.001). However, the cases of intraoperative hypotension between propofol group and ciprofol group or ciprofol group and remimazolam group were comparable (32 vs 22, p=0.122; 22 vs 12, p=0.064). The percentage of insufficient anesthesia between propofol group and remimazolam group was significant (13.33% vs 1.67%, p=0.001), while no statistical difference was detected between propofol group and remimazolam group or ciprofol group and remimazolam group (13.33% vs 5.00%, p=0.025; 5.00% vs 1.67%, p=0.150). The ability of propofol to improve sleep quality at 1st post-examination day was significantly better than that of remimazolam (86.21% vs 72.88%, p=0.015), while it was not significant between propofol group and ciprofol group or ciprofol group and remimazolam group (86.21% vs 80.36%, p=0.236; 72.88% vs. 72.88%, p=0.181). Incidence of intraoperative awareness, intraoperative hypoxia, type of dream, satisfaction score, adverse events during recovery, and sleep improvement on the 7th post-examination day was not significant among the groups.Conclusion: Anesthesia with propofol, ciprofol and remimazolam, respectively, for gastrointestinal endoscopy did not induce statistical difference in the incidence of dreaming, despite that all of them are more likely to induce pleasant dreams.Keywords: propofol, ciprofol, remimazolam, endoscopic sedation, dreaming

Jiaqi He,1,&ast; Xiuhui Lu,2,&ast; Chenchen Yuan,1 Yali Zheng,2 Fangzhou Chen,2 Jing Luo,2 Kejiao Ma,2 Fan Yang,2 Peng Wang,2 Dongsheng Zhou,2 Li Wang,1 Zhe Yin2 1Department of Clinical Laboratory, The First Affiliated Hospital of Henan University, Kaifeng, 475000, People’s Republic of China; 2State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Wang, Department of Clinical Laboratory, The First Affiliated Hospital of Henan University, Kaifeng, 475000, People’s Republic of China, Email wangli851217@163.com Zhe Yin, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China, Email jerry9yin@163.comPurpose: Pseudomonas aeruginosa is a common causative bacteria in nosocomial infections. This study aims to describe the structure and evolutionary characteristics of mobile genetic elements (MGEs) carrying antibiotic resistance genes (ARGs) from P. aeruginosa and to conduct bioinformatics and comparative genomic analysis to provide a deeper understanding of the genetic characteristics and diversity of MGEs in P. aeruginosa.Methods: Fifteen clinical isolates of P. aeruginosa from China were collected and sequenced in this study, and 15 novel MGEs were identified. Together with four MGEs from GenBank, a total of 19 MGEs were used to perform detailed modular structure dissection and sequence comparison. Then, the biological experiments were carried out to verify the biological characteristics of these isolates and MEGs.Results: The novel MGEs identified in this study displayed diversification in modular structures, which showed complex mosaic natures. The seven types of 19 MGEs included in this study were divided into three groups: i) novel MGEs (firstly identified in this study): four IncpSE5381-aadB plasmids and three Tn 7495-related integrative and mobilizable elements (IMEs); ii) newly defined MGEs (firstly designated in this study, but with previously determined sequences): four Tn 7665-related IMEs; iii) novel transposons with reference prototypes identified in this study: two Tn 6417-related integrative and conjugative elements (ICEs), two IS-based transposition units, two Tn 501-related unit transposons, two Tn 1403-related unit transposons. At least 36 ARGs involved in resistance to 11 different classes of antimicrobials and heavy metals were identified. Additionally, three novel blaOXA variants were identified. Antimicrobial susceptibility testing showed that these variants were resistant to some β-lactamase antibiotics and blaOXA-1204 was additionally resistant to cephalosporins.Conclusion: The continuous evolution of ARG-carrying MGEs during transmission, leading to the emergence of novel MGEs or ARGs, which facilitates the spread of antibiotic resistance in P. aeruginosa and enhances the diversity of transmission modes of bacterial resistance.Keywords: Pseudomonas aeruginosa, genome sequencing, mobile genetic elements, antimicrobial resistance, OXA

Dongfang Huang,1– 3 Jianhuai Zhang,3 Jianbo Xu,3 Qiang Niu,2 Dinghua Zhou2 1Department of Hepatobiliary Surgery, Medical College of Soochow University, Suzhou, People’s Republic of China; 2Department of Hepatobiliary Surgery, PLA Rocket Force Characteristic Medical Center, Beijing, People’s Republic of China; 3Department of Hepatobiliary Surgery, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, People’s Republic of ChinaCorrespondence: Dinghua Zhou, Department of Hepatobiliary Surgery, PLA Rocket Force Characteristic Medical Center, No. 16 Xinjiekou Outer Street, Xicheng District, Beijing, 100088, People’s Republic of China, Tel +86 010-66343003, Fax +86 010-66343055, Email zhoudinghua3528@126.comObjective: To investigate the utility of alpha-fetoprotein (AFP) and ultrasound in the diagnosis and prognosis of patients with hepatocellular liver cancer (HCC).Methods: Using retrospective convenience sampling, 401 patients with HCC who underwent transarterial chemoembolisation at the Department of Oncology of The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University between June 2015 and January 2020 were recruited and assigned to the case group. Simultaneously, patients matched to the case group in terms of gender and age but excluded for HCC were enrolled at a 1:1 ratio and classified as the control group. Relevant parameters were collected from both groups for comparison.Results: Both AFP levels and ultrasound results demonstrated diagnostic value for patients with HCC (P < 0.05). Their combined use exhibited the highest diagnostic accuracy for the cancer, with an area under the curve of 0.896 (95% confidence interval [CI]: 0.876, 0.923), a sensitivity of 67.65% and a specificity of 91.22%. In terms of overall survival (OS), statistically significant differences in the OS rates were observed between the low-AFP (L-AFP) group and high-AFP (H-AFP) group as well as between the low-tumour-diameter (LTD) group and high-tumour-diameter (HTD) group (81.31% vs 52.22% and 85.11% vs 63.41%, respectively; P < 0.05). Regarding the progression-free survival (PFS), significant differences in the PFS rates were also noted between the L-AFP and H-AFP groups and between the LTD and HTD groups (81.31% vs 52.22% and 85.11% vs 63.41%, respectively; P < 0.05).Conclusion: Ultrasound and AFP display notable distinctions when used in the diagnosis of HCC. The sensitivity of ultrasound as a standalone diagnostic tool surpasses that of AFP alone. However, their combined use results in much higher specificity than the use of either test individually. In addition, both techniques hold predictive value for patients’ OS and PFS, enabling timely prognostic assessment.Keywords: alpha-fetoprotein, hepatocellular liver cancer, ultrasound, survival analysis, prognosis

Ruichen Fang,1,2 Yihong Cheng,1,2 Fan Li,3 Yan Xu,1,2 Yuanhui Li,4 Xiang Liu,4 Simin Guo,4 Yuling Wang,1,2 Jinnong Jiang,1,2 Dan Zhou,1,2 Bin Zhang1,2 1Department of Psychiatry, Sleep Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Key Laboratory of Mental Health of the Ministry of Education, Guangzhou, People’s Republic of China; 3School of Biomedical Engineering, Faculty of Medicine, Dalian University of Technology, Dalian, 116024, People’s Republic of China; 4Adai Technology (Beijing) Co., Ltd, Beijing, People’s Republic of ChinaCorrespondence: Bin Zhang, Department of Psychiatry, Sleep Medicine Center, Nanfang Hospital, No. 1838 North, Guangzhou Avenue, Guangzhou, 510515, People’s Republic of China, Email zhang73bin@hotmail.comPurpose: In this study, we established the Chinese Clinical Sleep Database (CCSD), aiming to provide a safe, scalable, and user-friendly database that includes high-quality clinical data from Chinese population to facilitate sleep research.Material and Methods: We collect individual’s demographic data, scales, anthropometric measurements, clinical diagnosis, and polysomnography (PSG) recordings from the routine medical process of sleep medicine centers using standardized procedures. The distributed cluster storage technology are utilized to store these data. The structured data are stored in a high-performance MySQL database, while the unstructured data are stored in an object storage service. And we have developed an online data platform to share and manage our data.Results: The data collection has been conducted in three hospitals. In the preliminary stage of data collection (from October 18, 2022 to September 4, 2023), our database included a total of 1183 patients. Among them, 56.8% were male and their ages ranged from 3 to 88 years. These patients were diagnosed with various types of sleep disorders.Conclusion: Since the CCSD’s inception, it has demonstrated good stability, security, and scalability. As an public database, the CCSD also exhibits user-friendliness. The CCSD contains comprehensive clinical data, which can contribute to the advancement of the diagnosis and treatment strategies for sleep disorders, ultimately promoting sleep health.Keywords: sleep medicine, methodology, database, data collection, collaboration tool

Nan Liu, Jinlei Dong, Lianxin Li, Dongsheng Zhou, Fanxiao Liu Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of ChinaCorrespondence: Fanxiao Liu, Department of Orthopedics, Shandong Provincial Hospital affiliated to Shandong First Medical University, No. 324, Road Jing Wu Wei Qi, Jinan, Shandong, 250021, People’s Republic of China, Tel +86-15069058755, Email woshi631@126.comAbstract: Metrnl, recently identified as an adipokine, is a secreted protein notably expressed in white adipose tissue, barrier tissues, and activated macrophages. This adipokine plays a pivotal role in counteracting obesity-induced insulin resistance. It enhances adipose tissue functionality by promoting adipocyte differentiation, activating metabolic pathways, and exerting anti-inflammatory effects. Extensive research has identified Metrnl as a key player in modulating inflammatory responses and as an integral regulator of muscle regeneration. These findings position Metrnl as a promising biomarker and potential therapeutic target in treating inflammation-associated pathologies. Despite this, the specific anti-inflammatory mechanisms of Metrnl in immune-mediated osteolysis and arthritis remain elusive, warranting further investigation. In this review, we will briefly elaborate on the role of Metrnl in anti-inflammation function in inflammation-related osteolysis, arthritis, and pathological bone resorption, which could facilitate Metrnl’s clinical application as a novel therapeutic strategy to prevent bone loss. While the pathogenesis of elbow stiffness remains elusive, current literature suggests that Metrnl likely exerts a pivotal role in its development.Keywords: osteolysis, bone resorption, bone loss, Metrnl, arthritis, stiff elbow

Xuqing Zhou,1,2,&ast; Xu Wang,1,2,&ast; Jiaqi Li,3,&ast; Mengxue Zhang,4 Yi Yang,1 Shihui Lei,1 Ying He,3 Hua Yang,3 Desheng Zhou,4 Chun Guo1,2 1Experiment Center of Medical Innovation, the First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China; 2The First Clinical College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China; 3College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan, 410128, People’s Republic of China; 4Department of Neurology, the First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun Guo, Email chunguosm@163.comBackground: Annao Pingchong decoction (ANPCD) is a traditional Chinese decoction which has definite effects on treating intracerebral hemorrhage (ICH) validated through clinical and experimental studies. However, the impact of ANPCD on oxidative stress (OS) after ICH remains unclear and is worth further investigating.Aim: To investigate whether the therapeutic effects of ANPCD on ICH are related to alleviating OS damage and seek potential targets for its antioxidant effects.Materials and Methods: The therapeutic candidate genes of ANPCD on ICH were identified through a comparison of the target genes of ANPCD, target genes of ICH and differentially expressed genes (DEGs). Protein–protein interaction (PPI) network analysis and functional enrichment analysis were combined with targets-related literature to select suitable antioxidant targets. The affinity between ANPCD and the selected target was verified using macromolecular docking. Subsequently, the effects of ANPCD on OS and the selected target were further investigated through in vivo experiments.Results: Forty-eight candidate genes were screened, in which silent information regulator sirtuin 1 (SIRT1) is one of the core genes that has antioxidant effects and ICH significantly affected its expression. The good affinity between 6 compounds of ANPCD and SIRT1 was also demonstrated by macromolecular docking. The results of in vivo experiments demonstrated that ANPCD significantly decreased modified neurological severity scoring (mNSS) scores and serum MDA and 8-OHdG content in ICH rats, while significantly increasing serum SOD and CAT activity, complicated with the up-regulation of ANPCD on SIRT1, FOXO1, PGC-1α and Nrf2. Furthermore, ANPCD significantly decreased the apoptosis rate and the expression of apoptosis-related proteins (P53, cytochrome c and caspase-3).Conclusion: ANPCD alleviates OS damage and apoptosis after ICH in rats. As a potential therapeutic target, SIRT1 can be effectively regulated by ANPCD, as are its downstream proteins. Keywords: intracerebral hemorrhage, Annao Pingchong decoction, oxidative stress, network pharmacology, vivo experiments, SIRT1

Antao Lin,&ast; Yan Wang,&ast; Hao Zhang, Kai Zhu, Dan Zhou, Jianwei Guo, Wenhao Zhao, Chuanli Zhou, Xuexiao Ma Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuexiao Ma; Chuanli Zhou, Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, Shandong, 266000, People’s Republic of China, Tel +8618661807895 ; +8618661809796, Email maxuexiaospinal@163.com; justin_5257@hotmail.comObjective: We explore the endoscopic revision and surgical techniques for L4/5 recurrent disc herniation (rLDH) after percutaneous endoscopic transforaminal discectomy (PETD).Methods: A retrospective study was conducted. From January 2016 to September 2022, 96 patients who underwent percutaneous endoscopic lumbar discectomy for L4/5 rLDH after PETD were enrolled in the study. Based on the revision approach, the patients were divided into PETD group (57 cases) and percutaneous endoscopic interlaminar discectomy (PEID) group (39 cases). Visual Analogue Scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), and modified MacNab standard were recorded to evaluate the clinical outcomes.Results: No significant differences were found in the demographic data and intraoperative blood loss between the two groups (P> 0.05), but the time of operation and intraoperative X-ray fluoroscopy exposures in the PEID group were significantly less than that in the PETD group (P< 0.05). The patients’ postoperative clinical indexes gradually improved, and the VAS score, ODI index, and JOA score of the patients in both groups showed significant improvement compared with the preoperative period at the 1-week, 1-month, and 6-month postoperative follow-ups (P < 0.05). There was no serious complication observed during the follow-up.Conclusion: For recurrent LDH after PETD of L4/5 segments, percutaneous endoscopic revision can achieve satisfactory results. Among them, PEID has a shorter operative and fluoroscopy time and allows avoidance of the scar that forms after the initial surgery, so it can be considered preferred when both procedures can remove the disk well. However, for some specific types of herniation, a detailed surgical strategy is required.Keywords: endoscopic revision, recurrent lumbar disc herniation, percutaneous endoscopic lumbar discectomy

Wenwei Feng,&ast; Jiancong Zhou,&ast; Zhubin Lun, Dianhua Zhou, Peiwen Li, Jianfeng Ye Department of Cardiology, Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianfeng Ye, Department of Cardiology, Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan, Guangdong, People’s Republic of China, Email yipjf@hotmail.comBackground: Contrast-associated acute kidney injury (CA-AKI) is a prevalent complication following coronary angiography (CAG). However, there is ongoing controversy surrounding its precise definition. Although previous studies have demonstrated the successful application of appropriate definitions in managing high-risk CA-AKI patients, there remains limited research on the association between different definitions and prognosis specifically in patients with chronic kidney disease (CKD).Methods: A total of 4197 CKD patients undergoing coronary angiography (CAG) were included in this study. Two definitions of contrast-associated acute kidney injury (CA-AKI) were used: CA-AKIA, which was defined as an increase of ≥ 0.5 mg/dL or > 25% in serum creatinine (SCr) from baseline within 72 hours after CAG, and CA-AKIB, which was defined as an increase of ≥ 0.3 mg/dL or > 50% in SCr from baseline within 48 hours after CAG. Cox regression analysis was employed to assess the association between these two definitions and long-term mortality. Additionally, population attributable risks (PARs) were calculated to evaluate the impact of CA-AKI definitions on long-term prognosis.Results: During the median follow-up period of 4.70 (2.50– 7.78) years, the overall long-term mortality was 23.6%, and the long-term mortality in patients with CA-AKI according to both CA-AKIA and CA-AKIB criteria were 33.5% and 33.8%, respectively. We found that CA-AKIA (HR: 1.45, 95% CI: 1.23– 1.70, p< 0.001) and CA-AKIB (HR: 1.44, 95% CI: 1.23– 1.69, p< 0.001) were associated with long-term mortality. The PARs were the highest for CA-AKIA (5.87%), followed by CA-AKIB (5.70%).Conclusion: Contrast-associated acute kidney injury (CA-AKI) is a frequently observed complication in CKD patients undergoing coronary angiography (CAG), and both definitions of CA-AKI are significantly correlated with a poor long-term prognosis. Consequently, in the clinical management of CKD patients, it is crucial to prioritize CA-AKI, irrespective of the specific CA-AKI definition used.Keywords: contrast-associated acute kidney injury, chronic kidney disease, definitions, long-term mortality, population attributable risks

Liu M, Luo G, Wang Y, et al. Int J Nanomedicine. 2017;12:6827-6840. The authors have advised due to an error that occurred inadvertently at the time of figure assembly, Figure 7B on page 6834 is incorrect. The authors have also advised the magnification in the note section is incorrect. The correct Figure 7 and caption are as follows. Figure 7 Fluorescence microscopy photographes of GFP transgenic fibroblasts on the (A) PCL/DA, (B) PCL/NS0.5, (C) PCL/NS1.0 and (D) PCL/NS2.0 films. (E) The cell viability measured using CCK8 assay at day 1, 3 and 5 post-seeding.Abbreviations: CCK8, Cell Counting Kit-8; DA, dopamine; GFP, green fluorescent protein; NS, nanosilver; PCL, polycaprolactone.Notes: Magnification ×100. *p

Cheng Qin, Zhiping Qi, Su Pan, Peng Xia, Weijian Kong, Bin Sun, Haorui Du, Renfeng Zhang, Longchuan Zhu, Dinghai Zhou, Xiaoyu Yang Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, 130041, People’s Republic of ChinaCorrespondence: Xiaoyu Yang, Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, TX, 130041, People’s Republic of China, Email yangxiaoy@jlu.edu.cnAbstract: Spinal cord injury (SCI) treatment represents a major challenge in clinical practice. In recent years, the rapid development of neural tissue engineering technology has provided a new therapeutic approach for spinal cord injury repair. Implanting functionalized electroconductive hydrogels (ECH) in the injury area has been shown to promote axonal regeneration and facilitate the generation of neuronal circuits by reshaping the microenvironment of SCI. ECH not only facilitate intercellular electrical signaling but, when combined with electrical stimulation, enable the transmission of electrical signals to electroactive tissue and activate bioelectric signaling pathways, thereby promoting neural tissue repair. Therefore, the implantation of ECH into damaged tissues can effectively restore physiological functions related to electrical conduction. This article focuses on the dynamic pathophysiological changes in the SCI microenvironment and discusses the mechanisms of electrical stimulation/signal in the process of SCI repair. By examining electrical activity during nerve repair, we provide insights into the mechanisms behind electrical stimulation and signaling during SCI repair. We classify conductive biomaterials, and offer an overview of the current applications and research progress of conductive hydrogels in spinal cord repair and regeneration, aiming to provide a reference for future explorations and developments in spinal cord regeneration strategies. Keywords: neural tissue engineering, electrical stimulation, electrical signal, conductive biomaterials, spinal cord injury microenvironment

Dongchu Zhou,1 Xinrui Dong,1 Zhen Zhou,2 Qiao Liu1 1Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, AustraliaCorrespondence: Qiao Liu, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410000, People’s Republic of China, Email liuqiao6767@csu.edu.cnPurpose: The market price of adebrelimab, the first Chinese-developed anti-PD-L1 antibody used as a first-line treatment for extensive stage-small-cell lung cancer (ES-SCLC), has garnered significant public attention. This study sought to investigate the affordable price of adebrelimab for Chinese patients with untreated ES-SCLC through a cost-effectiveness analysis.Patients and Methods: We conducted a cost-effectiveness analysis using a Markov model, incorporating a what-if scenario of adding adebrelimab to first-line etoposide/platinum (EP) chemotherapy is cost-effective for ES-SCLC patients from the perspective of the Chinese healthcare system. The model included three mutually exclusive health states, with transition probabilities derived from the CAPSTONE-1 trial. Health state utilities and costs were acquired from a myriad of authoritative sources. We compared the incremental cost-effectiveness ratios (ICERs) for adebrelimab plus EP chemotherapy (AEP) versus EP with a willingness-to-pay threshold of &dollar;37,654 per quality-adjusted life-years (QALYs) to estimate the affordable price ceiling of the upcoming adebrelimab.Results: For the entire ES-SCLC population, the estimated price ceiling of adebrelimab/mg was &dollar;0.542 (95% CI, &dollar;0.542-&dollar;0.552). Subgroup analyses found that the highest price ceiling of adebrelimab/mg was observed in ES-SCLC patients with lactate dehydrogenase concentration ≤ upper normal limit [&dollar;0.824 (95% CI, &dollar;0.815-&dollar;0.830)]; and the lowest was found in ES-SCLC patients with liver metastasis [&dollar;0.252 (95% CI, &dollar;0.250- &dollar;0.256)]. Sensitivity analysis revealed a heightened probability of cost-effectiveness for the first-line AEP as the price of adebrelimab decreased, encompassing both the entire ES-SCLC population and its subgroups.Conclusion: The affordable price range for adebrelimab/mg Chinese patients with untreated ES-SCLC was estimated to be between &dollar;0.252 and &dollar;0.824, with variations observed across different subgroups. In the context of universal healthcare coverage, our study provides valuable evidence to inform the implementation of a value-based pricing strategy for cancer treatment.Keywords: cost-effectiveness, extensive stage-small-cell lung cancer (ES-SCLC), adebrelimab, drug pricing, China

Zhiyuan Chen,1,&ast; Xiaohuan Li,2,&ast; Yu Zhang,2 Yiming Yang,1 Yan Zhang,3 Dongjing Zhou,1 Yu Yang,4 Shuping Zhang,1 Yupin Liu1 1Department of Radiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 2The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 3Integrated Department, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 4Department of Pathology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yupin Liu, Department of Radiology, the Second Affiliated Hospital University of Guangzhou Traditional Chinese Medicine, No. 111 Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, People’s Republic of China, Tel +8613688878398, Fax +862034728881, Email mdliuyupin@163.comPurpose: To identify MRI features of hepatocellular carcinoma (HCC) that predict microvascular invasion (MVI) and postoperative intrahepatic recurrence in patients without peritumoral hepatobiliary phase (HBP) hypointensity.Patients and Methods: One hundred and thirty patients with HCC who underwent preoperative gadoxetate-enhanced MRI and curative hepatic resection were retrospectively reviewed. Two radiologists reviewed all preoperative MR images and assessed the radiological features of HCCs. The ability of peritumoral HBP hypointensity to identify MVI and intrahepatic recurrence was analyzed. We then assessed the MRI features of HCC that predicted the MVI and intrahepatic recurrence-free survival (RFS) in the subgroup without peritumoral HBP hypointensity. Finally, a two-step flowchart was constructed to assist in clinical decision-making.Results: Peritumoral HBP hypointensity (odds ratio, 3.019; 95% confidence interval: 1.071– 8.512; P=0.037) was an independent predictor of MVI. The sensitivity, specificity, positive predictive value, negative predictive value, and AUROC of peritumoral HBP hypointensity in predicting MVI were 23.80%, 91.04%, 71.23%, 55.96%, and 0.574, respectively. Intrahepatic RFS was significantly shorter in patients with peritumoral HBP hypointensity (P< 0.001). In patients without peritumoral HBP hypointensity, the only significant difference between MVI-positive and MVI-negative HCCs was the presence of a radiological capsule (P=0.038). Satellite nodule was an independent risk factor for intrahepatic RFS (hazard ratio,3.324; 95% CI: 1.733– 6.378; P< 0.001). The high-risk HCC detection rate was significantly higher when using the two-step flowchart that incorporated peritumoral HBP hypointensity and satellite nodule than when using peritumoral HBP hypointensity alone (P< 0.001).Conclusion: In patients without peritumoral HBP hypointensity, a radiological capsule is useful for identifying MVI and satellite nodule is an independent risk factor for intrahepatic RFS.Keywords: hepatocellular carcinoma, microvascular invasion, postoperative recurrence, peritumoral hypointensity, magnetic resonance imaging

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

Donghai Zhou,1,&ast; Xue Yu,2,&ast; Kai Yu,3 Yating Ren,2 Kepeng Yang,1 Xinchang Wang,1 Qiao Wang4 1Department of Rheumatology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310005, People’s Republic of China; 2The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310005, People’s Republic of China; 3Department of Hepatology 1, Xixi Hospital of Hangzhou, Hangzhou, Zhejiang Province, 310023, People’s Republic of China; 4College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiao Wang; Xinchang Wang, Email wangqiao0309@163.com; ossani@126.comBackground: Primary Sjögren’s syndrome (pSS) is an autoimmune disease with lymphocytic infiltration of the salivary and lachrymal glands, whose present disease-specific objective indicators are few and have shortcomings that should be addressed. An integrated analysis of sequencing data from different cohorts has the potential to unveil novel biomarkers in pSS.Methods: We identified 3 GEO datasets, including gene expression data from minor salivary gland (MSG) biopsy samples of 49 patients with pSS and 31 non-pSS and whole blood cells of 30 pSS patients and 30 healthy controls (HCs). Differentially expressed genes (DEGs) involved in pSS were identified from these datasets. Function Enrichment Analyses of common upregulated DEGs and PPI (protein-protein interaction) networks were performed. Furthermore, we have carried out further analysis of these DEGs to explore their potential clinical significance and diagnostic efficacy as a biomarker for pSS. Sterile Alpha Motif Domain Containing 9 Like (SAMD9L), one of the DEGs, has been identified as a promising candidate biomarker that correlates with the severity of pSS. This has been validated by analyzing local clinical samples from 30 pSS and non-pSS patients’ MSG biopsies, as well as serum samples of 18 pSS and HC individuals. Finally, we performed correlation analysis to understand the relationship between SAMD9L and infiltrated immune cells.Results: We identified 10 common highly expressed DEGs in pSS of different tissues. These genes were mainly involved in virus infection-related pathways and inferno-related pathways. GEO data and our clinical data showed that SAMD9L increases with disease severity. Public and local cohorts showed that SAMD9L has high diagnostic performance (AUC=0.845– 0.867) as a biomarker, and its AUC was comparable to the Focus score when combined with RF or SSA.Conclusion: Up-regulated SAMD9L may serve as a promising novel pSS diagnostic biomarker and have potential value for evaluating the severity of pSS.Keywords: Sjögren’s syndrome, SAMD9L, biomarker, integrated analysis

Kaixuan Zhao,1,&ast; Siqi Pu,2,&ast; Liyun Sun,1 Dongmei Zhou1 1Dermatology Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 10010, People’s Republic of China; 2School of Clinical Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liyun Sun, Dermatology Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Art Musuem Back Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Email doctorsunny@sina.cn Dongmei Zhou, Dermatology Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Art musuem Back Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Email 52176857@163.comPurpose: In this study, we aimed to report the biological characteristics of the first successful synthesis of gentiopicroside-loaded chitosan nanoparticles and to evaluate the therapeutic effects and preliminary mechanisms of gentiopicrin-loaded chitosan on psoriasis-like cell and mouse models.Methods: Gentiopicroside-loaded chitosan nanoparticles (CHI-GEN) were prepared, and their biological characteristics were evaluated. HaCaT keratinocytes were stimulated with TNF-α to establish a psoriatic keratinocyte model. MTT assay and flow cytometry were used to measure cell viability and apoptosis, respectively. mRNA levels of K17, VEGF A, and IL-6 and IL-23A were detected using qRT-PCR. These tests were used to preliminarily assess the effects of CHI-GEN on keratinocyte proliferation and inflammation. Imiquimod was used to construct a psoriasis-like mice model. The severity of psoriasis was scored based on the psoriasis area severity index (PASI), H&E staining was used to observe the histological changes and the level of inflammation and cell proliferation of skin lesions was evaluated by measuring the mRNA levels of K17, IL-23A, and IL-17A using qRT-PCR.Results: The average particle size of CHI-GEN nanoparticles was approximately 100 nm, and the zeta potential was 2.69 ± 0.87 mV. The cumulative release was 67.2% in solutions of pH 5.5 at 24 h. GEN reduced TNF-α-induced excessive proliferation of HaCaT keratinocytes and downregulated mRNA levels of K17, VEGF A, and inflammatory cytokines IL-6 and IL-23A, which was more obvious in the CHI-GEN treatment group. Additionally, CHI-GEN significantly improved the severity of skin lesions in psoriasis-like mice and downregulated the mRNA expressions of IL-6, IL-23A, and IL-17A in mice skin lesions.Conclusion: In conclusion, we successfully prepared gentiopicrin-chitosan nanoparticles. Our results show that these nanoparticles have anti-psoriasis activity, inhibits keratinocyte proliferation and improves symptoms in psoriasis model mice and can be used to develop an effective strategy for the treatment of psoriasis.Keywords: chitosan, nanoparticles, gentiopicroside, chitosan-loaded nano cream for external use, psoriasis, proliferation and inflammation

Meili Cai,1,&ast; Yuqin Zhang,1,&ast; Jingyang Gao,1,&ast; Diliqingna Dilimulati,1 Le Bu,1,2 Xiaoyun Cheng,1,2 Lei Du,2,3 Donglei Zhou,2,3 Jiangfang Zhu,2,3 Shen Qu,1,2 Manna Zhang1,2 1Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 2National Metabolic Management Center, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 3Department of Gastrointestinal Surgery, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shen Qu; Manna Zhang, Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, 301 Middle Yanchang Road, Shanghai, 200072, People’s Republic of China, Tel +86-021-66301004, Email qushencn@hotmail.com; mannazhang@126.comObjective: To explore the predictors of menstrual recovery in polycystic ovary syndrome (PCOS) women with obesity following laparoscopic sleeve gastrectomy (LSG).Methods: A total of 88 PCOS patients with obesity and 76 control patients with obesity aged 18– 45 years were enrolled between May 2013 and December 2020. PCOS was diagnosed using the Rotterdam diagnostic criteria (2003). Anthropometric measurements, biochemical parameters, sex hormones, and circulating fibrinogen-like protein 1 (FGL-1) levels were collected before and six-month after LSG. The data on postoperative menstrual status, body weight, and fertility were obtained through telephone follow-ups for all individuals with PCOS.Results: Patients with PCOS were followed up for at least six months after surgery, and the mean follow-up time was 3.23 years. At 6 months after LSG, circulating total testosterone (TT), calculated free testosterone (cFT), and FGL-1 levels declined significantly. The mean percent excess weight loss (%EWL) and percent total weight loss (%TWL) in PCOS patients at the final follow-up was 97.52% ± 33.90% and 31.65% ± 10.31%, respectively. The proportion of regular menstruation in PCOS patients significantly increased within six months (75.86% vs 0.03% at baseline). In the logistic regression analysis, time from PCOS diagnosis (P=0.007), body mass index (BMI) (P=0.007), TT (P=0.038) at baseline were demonstrated to be independent predictive factors for the regular menstruation in women with PCOS and obesity within 6 months after LSG.Conclusion: In PCOS patients with obesity, time from PCOS diagnosis, BMI, and TT levels at baseline were independently and negatively associated with menstrual recovery within 6 months after LSG, which could be applied in preoperative evaluation.Keywords: polycystic ovary syndrome, obesity, laparoscopic sleeve gastrectomy, menstruation, fibrinogen-like protein 1

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

Binzhi Dan,&ast; Heping Dai,&ast; Dangui Zhou, Hongfang Tong, Mei Zhu Department of Clinical Laboratory, the Affiliated Chaohu Hospital of Anhui Medical University, Chaohu, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei Zhu, Tel +86 551 8232 4254, Email meizhu532@sina.comObjective: To conduct epidemiological analysis of Klebsiella pneumoniae (K. pneumoniae) with hypervirulence, and to investigate its drug resistance phenotype, Extended-spectrum β-lactamase (ESBLs) gene, virulence factor, capsular serotype and biofilm formation, so as to provide theoretical basis for further understanding of the drug resistance mechanism of K. pneumoniae with hypervirulence.Methods: K. Pneumoniae were isolated from clinical samples collected from inpatients. All strains were identified by VITEK2 Compact using fully automatic microbial analyzer, the minimal inhibitory concentration (MIC) of antibiotics was determined by microbroth dilution test. The double disk diffusion method was used to detect the production of ESBLs, modified carbapenem inactivation method (mCIM) was used to detect the production of carbapenemase, and hypermucoviscosity phenotype was detected by wire drawing test. PCR was used to detect ESBLs gene, virulence factor and capsular serotype. Crystal violet staining was used to detect the ability of biofilm formation.Results: The ESBLs genes detected in this study included strains blaTEM 35 (36.5%), blaSHV 51 (53.1%), and blaCTX-M 49 (51.0%). Most strains carried multiple ESBLs genes, but not all of them produce ESBLs. K1 and K2 accounted for 14.6% and 11.5% respectively. Most (91.7%) strains carried the fimH gene, and the other virulence genes were ybtS (53.1%), entB (46.9%), rmpA (41.7%), aerobactin (32.3%), allS (15.6%), kfu (15.6%). Of all the Klebsiella pneumoniae strains, 33 (34.4%) exhibited ESBLs phenotype, 16 (16.7%) were carbapenemase-producing, and 20 (20.8%) with ESBLs phenotype tested were resistant to all four drugs. The correlation between ESBLs-producing strains and biofilm formation was significantly increased compared to strains without ESBLs phenotype (P=0.035).Conclusion: Compared to hypervirulent Klebsiella pneumoniae (hvKP), classical Klebsiella pneumoniae (cKP) has a tendency to acquire antibiotic resistance. Our study showed that genes encoding rmpA, K1 or K2, and kfu were highly associated with hvKP.Keywords: Klebsiella pneumoniae, antimicrobial resistance, hypermucoviscosity, virulence factors, epidemiology

Han Zhao,1 Dexin Zhou,2 Cong Liu,1 Le Zhang1 1Department of Endocrinology, Shengjing Hospital, China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of Endocrinology, Dalian Third People´s Hospital, Dalian, Liaoning, People’s Republic of ChinaCorrespondence: Cong Liu; Le Zhang, Department of Endocrinology, Shengjing Hospital, China Medical University, Shenyang, Liaoning, People’s Republic of China, Email liucongjp@163.com; zhangle198626@163.comBackground: Anti-Mullerian hormone (AMH) is vital in the pathophysiological process of polycystic ovary syndrome (PCOS). The exact relationship between obesity and insulin resistance (IR) with AMH levels remains unclear.Methods: A retrospective, single-center cohort study of 220 women with PCOS who underwent physical, endocrine, and metabolic assessments were performed. Patients were grouped by age, body mass indices (BMI), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and different phenotypes. Pearson correlation analysis assessed the correlation between AMH and HOMA-IR, BMI, and other PCOS indicators, and multiple linear regression analysis was performed to determine factors influencing AMH.Results: In 220 patients with PCOS, serum AMH levels decreased with age and were significantly higher in the IR group than in the non-IR group (P < 0.01). AMH increased significantly in anovulatory patients with hyperandrogenemia and/or polycystic ovary, with no significant difference between obese and non-obese individuals. AMH levels correlated positively with luteinizing hormone (LH), LH/follicular stimulating hormone (FSH), testosterone, fasting insulin (FINS), and HOMA-IR levels; negatively with age and BMI levels (P < 0.05) and weakly with fasting plasma glucose in the classical PCOS phenotype (r=0.148, P < 0.05). Regression analysis showed that age, testosterone, FINS, LH, LH/FSH, and BMI influenced AMH levels (P < 0.05).Conclusion: Chinese women with PCOS-IR showed associations with greater AMH levels. AMH levels correlated positively with HOMA-IR levels and negatively with BMI. AMH combined with BMI and HOMA-IR levels may help determine PCOS severity.Keywords: polycystic ovary syndrome, anti-Mullerian hormone, insulin resistance, obesity, metabolic abnormality

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

Zhe Liu,1– 3,&ast; Dong Zhou,4,&ast; Xuan Yan,1 Lan Xiao,5,6 Pei Wang,1– 3 Junchao Wei,1– 4 Lan Liao1– 3 1The Affiliated Stomatological Hospital of Nanchang University, Nanchang, People’s Republic of China; 2The Key Laboratory of Oral Biomedicine, Nanchang, People’s Republic of China; 3Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang, People’s Republic of China; 4School of Chemistry and Chemical Engineering, Nanchang University, Nanchang, People’s Republic of China; 5School of Mechanical, Medical & Process Engineering, Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, Australia; 6Australia China Centre for Tissue Engineering and Regenerative Medicine, Kelvin Grove, Brisbane, Australia&ast;These authors contributed equally to this workCorrespondence: Junchao Wei; Lan Liao, Email weijunchao@ncu.edu.cn; Liaolan5106@ncu.edu.cnPurpose: The translation of nanocarrier-based theranostics into cancer treatment is limited by their poor cellular uptake, low drug-loading capacity, uncontrolled drug release, and insufficient imaging ability.Methods: In this study, novel hybrid nanogels were fabricated as theranostic nanocarriers by modifying chitosan (CTS)/tripolyphosphate (TPP) nanoparticles (NPs) with polyacrylic acid (PAA) and further conjugating cysteine-functionalized gold nanoparticles (AuNPs).Results: The resultant nanogels, referred to as CTS/TPP/PAA@AuNPs (CTPA), exhibited excellent colloidal stability and a high encapsulation rate of 87% for the cationic drug doxorubicin (DOX). In the tumour microenvironment, the acidic pH and overexpression of lysozyme triggered CTPA@DOX to degrade and emit smaller nanoblocks (30– 40 nm), which sequentially released the drug in a tumour-responsive manner. Cellular uptake experiments demonstrated that CTPA facilitates the entry of DOX into the cytoplasm. Furthermore, as visualised through AuNP-mediated computed tomography (CT) imaging, CTPA@DOX enabled favourable accumulation in the tumour. Our in vitro and in vivo data demonstrated that CTPA enabled advanced tumour cell-targeting delivery of DOX, which showed greater anti-tumour activity and biosafety than free DOX.Conclusion: The natural polymer CTS was developed for degradable nanogels, which can precisely track drugs with high antitumour activity. Additionally, the surface adjustment strategy can be assembled to achieve cationic drug loading and high drug-loading capacity, controlled drug release, and sufficient imaging ability. Therefore, multifunctional CTPA enables efficient drug delivery and CT imaging, which is expected to provide a valuable strategy for designing advanced theranostic systems.Keywords: theranostic nanomaterial, degradability, computed tomography imaging, hybrid nanogel

Zhigang Liu,1,2,&ast; Baisheng Fu,2,&ast; Weicheng Xu,2 Fanxiao Liu,2 Jinlei Dong,2 Lianxin Li,2 Dongsheng Zhou,2 Zhenhai Hao,2 Shun Lu2 1Department of Orthopaedics Surgery, Haining People’s Hospital, Jiaxing, People’s Republic of China; 2Department of Orthopaedics Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shun Lu, Department of Orthopaedics Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Tel +8618653189700, Email sdqdpdlushun@163.comPurpose: Traumatic sciatic nerve injury is one of the most serious consequences of acetabular fracture. However, reports on this type of injury are rare. In this study, we investigated the demographics of acetabular fracture with traumatic sciatic nerve injury, the clinical characteristics of patients with these injuries, and potential risk factors.Patients and Methods: We retrospectively reviewed patients diagnosed to have acetabular fracture at our trauma center between January 2014 and June 2021. Data on patient demographics, characteristics of the acetabular fracture, whether or not sciatic nerve injury occurred, types of sciatic nerve injury, and risk factors were analyzed.Results: A total of 195 patients met the diagnostic criteria for acetabular fractures. The average Injury Severity Score was 25.9 and the average Abbreviated Injury Scale score was 12.4. Road traffic accidents and falls from height were the main causes. Chest injuries and lower extremity fractures were the most common associated injuries. Posterior wall fractures were the most common fracture type. After exclusion of spinal cord and iatrogenic sciatic nerve injuries, 18 patients with acetabular fractures had traumatic sciatic nerve injury. Four of the 19 sides with traumatic sciatic nerve injury involved the common peroneal nerve division and 15 involved both the common peroneal and tibial nerve divisions. Logistic regression analysis identified a higher AIS score, posterior column fracture, and posterior hip dislocation to be predictors of traumatic sciatic nerve injury.Conclusion: Acetabular fractures were mostly high-energy injuries. Posterior wall fractures were the most common acetabular fracture types. Most patients sustained injury to the sciatic nerve as well as injury to the common peroneal and tibial nerve divisions. A higher AIS score, posterior column fracture, and posterior hip dislocation were predictors of acetabular fracture combined with traumatic sciatic nerve injury.Keywords: acetabular fractures, traumatic sciatic nerve injury, posterior hip dislocation

Qiang Zhang,1 Dong Zhou,2 Yu Liang1 1Department of Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Orthopaedic, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of ChinaCorrespondence: Dong Zhou, Department of Orthopaedic, The Affiliated Hospital of Nanjing Medical University, Changzhou No. 2 People’s Hospital, Xinglong Road 29&num;, Changzhou, Jiangsu, 213003, People’s Republic of China, Email dongzhou_no2@163.com Yu Liang, Department of Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, People’s Republic of China, Email hugoliang@126.comIntroduction: Injury-related cellular senescence may be involved in heterotopic ossification, and no research has been performed about this before.Methods and Results: The study utilized integrated single-cell RNA-sequencing (scRNA-seq) data from heterotopic ossification samples. The number of senescent cells increased from day 3 and reached the highest level at day 21. However, the expression level of Cyclin Dependent Kinase Inhibitor 2A (Cdkn2a) has no such tendency as the change of cell amount, indicating that the expression level of Cdkn2a may be different in different types of senescent cells or the same time of senescent cell at different time points. The expression level of SASPs (senescence associated secret phenotypes) was also different in different types of senescent cells or at different time points. The GO (gene ontology) analysis revealed that the senescent cells were significantly correlated with the ossification processes, like ECM organization, cell adhesion, ossification, cartilage development, etc. Trajectory analysis showed that injury-related senescent fibroblasts (day 7 and 21) and age-related senescent fibroblasts (day 0 and 42) were in different branches. GO analysis demonstrated that injury-related senescent fibroblasts were mainly related to ossification and ECM remodeling. The KEGG (Kyoto Encyclopedia of Genes and Genomes) results revealed that the ossification was significantly corrected with protein processing in PI3K-Akt signaling, MAPK signaling, focal adhesion, etc.Conclusion: Consequently, we demonstrated that, unlike age-related senescence, the injury-related senescence demonstrated significantly different SASP phenotypes. The injury-related senescence of fibroblasts is associated with heterotopic ossification formation and may act through PI3K/Akt-induced SASPs.Keywords: senescence, fibroblasts, heterotopic ossification, single-cell RNA-sequencing, scRNA, senescence associated secret phenotypes, SASPs

Shun Lu,1 Fanxiao Liu,1 Weicheng Xu,1 Xiaofeng Zhou,2 Lianxin Li,1 Dongsheng Zhou,1 Qinghu Li,1 Jinlei Dong1 1Department of Orthopaedics Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan City, Shandong Providence, People’s Republic of China; 2Department of Orthopaedics Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan City, Shandong Providence, People’s Republic of ChinaCorrespondence: Qinghu Li; Jinlei Dong, Department of Orthopaedics, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan City, Shandong Providence, People’s Republic of China, Tel +8613402214695 ; +861509874540, Email sdliqinghu@163.com; dongjinlei@163.comBackground: Open Tile C pelvic fractures are particularly severe. However, reports on their management and outcomes are relatively rare. This study analyzed the demographic and clinical characteristics of patients with open Tile C pelvic fractures and describes our management and outcomes of these injuries.Methods: This retrospective review included all patients with open Tile C pelvic fractures treated in our department between January 2014 and June 2021. Data on patient demographics, characteristics of the injuries, surgical management, and outcomes were analyzed.Results: Thirty patients with a mean age of 34.0 years met the diagnostic criteria. The average Injury Severity Score was 40.3. According to the Tile fracture classification, 6 patients sustained type C1.1, 12 sustained type C1.2, 3 sustained type C1.3, 5 sustained C2 and 4 sustained type C3. Most patients had soft tissue injuries in multiple zones. All patients sustained associated injuries. Management consisted of bed rest in 8 cases, external fixation as the final strategy in 14, conversion from external fixation to internal fixation in 3, open reduction with internal fixation in 5, and amputation in 6. The average amount of packed red blood cells transfused was 33.3 units, the average intensive care unit stay was 11.3 days, the mean number of operations required was 6.2, and the mean length of hospital stay was 81.8 days. The main complications were early soft tissue infections and venous thrombosis. One patient died of sepsis and multi-organ failure. Soft tissue injuries in multiple zones increased utilization of hospital resources whereas anorectal injuries did not. Vascular damage accompanying truck crush injuries had a high amputation rate.Conclusion: Open Tile C pelvic fractures require multidisciplinary diagnosis and management and consume considerable hospital resources. More emphasis needs to be placed on this complex injury.Keywords: open tile C fractures, management, outcomes

Jun Liu,1,2,&ast; Siyu Wu,1,2,&ast; Jiayi Ma,1,2 Chun Liu,1 Ting Dai,1 Xiaoyu Wu,1 Hongbin Zhao,1 Dong Zhou1 1Medical Research Centre, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, 213164, People’s Republic of China; 2Dalian Medical University, Dalian, 116044, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongbin Zhao; Dong Zhou, Medical Research Centre, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, 213164, People’s Republic of China, Tel/Fax +86 13919761032 ; Tel/Fax +86 13861298585, Email zhao761032@163.com; zhoudong1012@163.comPurpose: To enhance the osteoinductive effect of Hydroxyapatite (HA) in bone tissue engineering, this study manufactured polycaprolactone (PCL)/gelatin (GEL)/HA nanofibrous scaffolds incorporated with different ratios of attapulgite (ATP): HA (0:3, 0:0, 1:1, 2:1 and 3:0) by high-voltage electrospinning. The synergistic effect exerted by ATP and HA on bone formation was explored both in vivo and in vitro.Methods and Results: First, we determined the group composition and crystal structure of the nanosheets by Fourier transform infrared (FTIR) and X-ray diffraction (XRD) analyses. Then, the physical properties of the scaffolds, including the modulus of elasticity, porosity and water absorption were evaluated. Moreover, the surface microstructure of the nanofibrous scaffolds was captured by Scanning electron microscopy (SEM) and Transmission Electron Microscope (TEM). The biocompatibility of the fabricated scaffolds represented by cell counting kit 8 (CCK-8) and phalloidin staining was also assessed. Next, in vitro osteogenesis was evaluated. Real-time PCR, alkaline phosphatase (ALP) staining and Alizarin red S (ARS) staining results showed that the materials incorporated with HA and ATP at a ratio of 2:1 synergistically promoted more osteoblastic differentiation and extracellular mineralization than scaffolds doped with HA and ATP alone. Last, in vivo, Hematoxylin-Eosin staining (HE staining) and Masson staining showed that groups treated with HA and ATP acquired optimal patterns of bone regeneration.Conclusion: This study clarified for the first time that the combination of HA and ATP orchestrated biomaterial-induced osseointegration, and the synergistic effect was more significant when the ratio of ATP/HA was 2:1. This conclusion also provides new ideas and a scientific basis for the development of functionalized nanomaterials in bone tissue engineering.Keywords: attapulgite, hydroxyapatite, bone regeneration, electrospinning technology

Hongying Yang, Dahui Zhou School of Business and Tourism Management, Yunnan University, Kunming, People’s Republic of ChinaCorrespondence: Dahui Zhou, School of Business and Tourism Management, Yunnan University, Kunming, People’s Republic of China, Tel +86 183 1378 3472, Email dahuizhou@mail.ynu.edu.cnBackground: The impact of perceived organizational support on the creativity of science-technology talents in the digital era is an important domain for fostering innovation power and the long-term competitive advantage of enterprises. The main purpose of this study is to reveal the “black box” mechanism of perceived organizational support on the creativity of science-technology talents in the digital environment, guide enterprises to attach importance to perceived organizational support and enhance the creativity of science-technology talents.Methods: Based on resource conservation theory and social exchange theory, this study took the science-technology talents of Chinese high-tech enterprises as the research object, combined 380 matching data of science-technology talents and supervisors, and used AMOS, MPLUS, and SPSS software to test all hypotheses.Results: Perceived organizational support has a significant positive impact on the creativity of science-technology talents, affective commitment and innovative self-efficacy. Affective commitment and innovative self-efficacy have significant positive effects on the creativity of science-technology talents. Digital thinking positively moderates the relationship between perceived organizational support and affective commitment, innovative self-efficacy. Affective commitment and innovative self-efficacy play a moderated mediation role between perceived organizational support and the creativity of science-technology talents.Conclusion: Perceived organizational support promotes the creativity of science-technology talents through affective commitment and innovative self-efficacy, which is moderated by digital thinking. These findings not only help deepen and expand the theoretical research on perceived organizational support and creativity, but also inspire managers to guide science-technology talents to work creatively from the aspects of affective commitment, innovative self-efficacy and digital thinking.Keywords: perceived organizational support, talent creativity, affective commitment, innovative self-efficacy, digital thinking

Diliqingna Dilimulati,&ast; Lei Du,&ast; Xiu Huang,&ast; Muthukumaran Jayachandran, Meili Cai, Yuqin Zhang, Donglei Zhou, Jiangfan Zhu, Lili Su, Manna Zhang, Shen Qu Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shen Qu; Manna Zhang, Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, 301 Middle Yanchang Road, Shanghai, 200072, People’s Republic of China, Tel +8602166301004 ; +8613774448495, Email qushencn@hotmail.com; mannazhang@126.comPurpose: Fibrinogen-like protein (FGL)-1 is an original hepatokine with a critical role in developing hepatic steatosis. This study intends to examine the pre- and postoperative serum FGL-1 levels in bariatric patients and identify its relationship with other clinical indicators.Patients and Methods: Ninety-two individuals (60 bariatric patients and 32 people with normal weight) were enrolled in this research between July 2018 and April 2021. All bariatric patients finished follow-up visits 6 months after laparoscopic sleeve gastrectomy (LSG). Clinical data, anthropometric parameters, biochemical variables, FibroScan, and serum FGL-1 levels were collected at baseline and 6 months after LSG.Results: FGL-1 levels in patients with obesity (44.66± 20.03 ng/mL) were higher than in individuals with normal weight (20.73± 9.73 ng/mL, p < 0.001). After LSG, FGL-1 levels were significantly decreased (27.53± 11.45 ng/mL, p < 0.001). Besides, body mass index (BMI), liver enzyme levels, glucose metabolism, lipid metabolism, uric acid (UA), controlled attenuation parameter (CAP), and liver stiffness measurement (LSM) were significantly improved. After adjusting possible confounders, FGL-1 levels at baseline were negatively associated with changes in LSM levels; changes in FGL-1 levels showed positive correlations with changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and UA levels at 6 months after surgery.Conclusion: Serum FGL-1 levels were significantly decreased following LSG in patients with obesity. The preoperative serum FGL-1 levels could be a predictor of postoperative liver fibrosis improvement. Furthermore, the decreased FGL-1 levels were associated with improved liver enzymes and UA but not with bodyweight or glucolipid metabolism.Keywords: obesity, fibrinogen-like protein 1, liver fibrosis, laparoscopic sleeve gastrectomy

Yiting Kong,1,&ast; Chuan Liu,2,&ast; Chenyu Zhang,1 Wo Wang,2 Yalan Li,2 Haitang Qiu,1 Gaomao Wang,2 Daqi Li,2 Xiaorong Chen,2 Zhen Lv,2 Dongdong Zhou,2 Liyang Wan,2 Ming Ai,1 Jianmei Chen,1 Liuyi Ran,2,&ast; Li Kuang1,2,&ast; 1Department of Psychiatry, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liuyi Ran, Mental Health Center, University-Town Hospital of Chongqing Medical University, Shapingba District, Chongqing, 401331, People’s Republic of China, Tel/Fax +86-023-65714061, Email ranliuyi@163.com Li Kuang, Department of Psychiatry, the First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel/Fax +86-023-89012696, Email kuangli0308@163.comPurpose: Uric acid (UA) is thought to exert neuroprotective roles. The purpose of this study was to examine the association of serum UA with suicide attempts (SA) in adolescents and young adults with major depressive disorder (MDD).Patients and Methods: We retrospectively recruited 533 participants with MDD aged 13 to 25 years, of which 168 had a history of SA in the past three months and 365 did not have a history of SA. Serum UA levels were measured using the uricase-peroxidase coupling method. In addition to overall serum UA level comparison in MDD individuals with and without SA, a stratified analysis by biological sex was carried out.Results: Compared to MDD individuals without a history of SA, serum UA levels were significantly lower in MDD individuals with SA (P < 0.001). Female MDD, but not male MDD individuals, with SA exhibited lower levels of UA than those without SA (P < 0.01). Importantly, serum UA remained significantly associated with SA in MDD individuals (OR = 0.996, 95% CI: 0.993∼ 0.999, P < 0.01) when controlling for possible confounding variables.Conclusion: This research identifies a relationship between serum UA levels and SA in adolescents and young adults with MDD. UA may represent a biological risk marker for SA, in particular for female MDD individuals.Keywords: suicide, MDD, uric acid, antioxidant, oxidative stress, biomarker

Yue Li,&ast; Dalei Zhou,&ast; Qing Liu, Weijie Zhu, Zulu Ye, Caiyun He Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Caiyun He; Zulu Ye, Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, No. 651, Dongfeng Road, Yuexiu District, Guangzhou, 510060, People’s Republic of China, Tel +86-18665593050 ; +86-15017590433, Fax +20-87340921, Email hecy@sysucc.org.cn; yezl@sysucc.org.cnPurpose: Fat mass and obesity-associated protein (FTO) and AlkB homolog 1 (ALKBH1) are m6A demethylases that have been demonstrated to be associated with the overall survival of patients with gastric cancer (GC). This study investigates the influence of genetic variants of FTO and ALKBH1 on susceptibility to GC.Patients and Methods: Potentially functional single nucleotide polymorphisms (SNPs) of FTO and ALKBH1 were genotyped in 419 patients with GC and 569 healthy controls by Kompetitive allele-specific PCR.Results: The AG and AG/AA variants of FTO rs2287142 were significantly associated with a decreased GC risk (for AG/AA vs GG: adjusted OR = 0.73, p = 0.020). The GA and GA/GG variants of ALKBH1 rs1076496 were closely correlated with an increased risk of GC in people aged ≥ 55 years (for GA/GG vs AA: adjusted OR = 1.51, p = 0.041) but showed a decreasing tendency of risk of GC in people aged < 55 years (adjusted OR = 0.85, p = 0.444). FTO rs2287142 and ALKBH1 rs1076496 conformed to the principle of a dominant model. FTO haplotype rs1421091-rs1421092-rs2287142-rs9939609 CTAT was closely associated with a lower risk of total GC (adjusted OR = 0.62, p = 0.023), while CTGA was linked with an increased risk of intestinal GC (adjusted OR = 2.51, p = 0.005). ALKBH1 rs1048147-rs1076496-rs11159286 CAC haplotype was significantly associated with a decreased risk of GC in people aged ≥ 55 years (adjusted OR = 0.41, p = 0.008). The FTO rs2287142-rs9939609 AG/AA-TT combination was associated with a decreased risk of GC only in the presence of rs1421091 TC/TT (adjusted OR = 0.70, p = 0.047), demonstrating that these FTO SNPs might have a cooperative effect on susceptibility to GC.Conclusion: FTO and ALKBH1 SNPs may have predictive value in evaluating susceptibility to GC with differing age or Lauren classification.Keywords: FTO, ALKBH1, gastric cancer, susceptibility, Lauren classification

Jiayao Guan,1,&ast; Chunmei Bao,2,&ast; Peng Wang,3 Ying Jing,3 Lingling Wang,3 Xinyue Li,3 Xiaofei Mu,3 Boan Li,2 Dongsheng Zhou,3 Xuejun Guo,1 Zhe Yin3 1Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin, 130122, People’s Republic of China; 2Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China; 3State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhe Yin, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, People’s Republic of China, Tel +86-10-66948557, Email jerry9yin@163.com Xuejun Guo, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin, 130122, People’s Republic of China, Tel +86-431-86985931, Email xuejung2021@163.comPurpose: The aim of this study was to gain a deeper genomics and bioinformatics understanding of diversification of accessory genetic elements (AGEs) in Providencia.Methods: Herein, the complete genome sequences of five Providencia isolates from China were determined, and seven AGEs were identified from the chromosomes. Detailed genetic dissection and sequence comparison were applied to these seven AGEs, together with additional 10 chromosomal ones from GenBank (nine of them came from Providencia).Results: These 17 AGEs were divided into four groups: Tn 6512 and its six derivatives, Tn 6872 and its two derivatives, Tn 6875 and its one derivative, and Tn 7 and its four derivatives. These AGEs display high-level diversification in modular structures that had complex mosaic natures, and particularly different multidrug resistance (MDR) regions were presented in these AGEs. At least 52 drug resistance genes, involved in resistance to 15 different categories of antimicrobials and heavy metal, were found in 15 of these 17 AGEs.Conclusion: Integration of these AGEs into the Providencia chromosomes would contribute to the accumulation and distribution of drug resistance genes and enhance the ability of Providencia isolates to survive under drug selection pressure.Keywords: Providencia, integrative and conjugative elements, integrative and mobilizable elements, unit transposons, multidrug resistance

Yanan Xu,1,&ast; Ying Jing,2,&ast; Lingfei Hu,2 Qiaoxiang Cheng,1 Huixia Gao,3 Zhi Zhang,3 Huiying Yang,2 Yuee Zhao,2 Dongsheng Zhou,2 Zhe Yin,2 Erhei Dai1,3 1Department of Clinical Laboratory Medicine, Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 2State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, People’s Republic of China; 3Department of Laboratory Medicine, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, Hebei, 050021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Erhei Dai; Zhe Yin, Tel +86-311-85814612 ; +86-10-66948557, Email daieh2008@126.com; jerry9yin@163.comPurpose: To establish a typing scheme for IncFIB replicon and to dissect genomic features of IncFIB-4.1/4.2 single-replicon plasmids.Methods: A total of 146 representative fully sequenced IncFIB-replicon-containing plasmids were selected to construct a phylogenetic tree of repBIncFIB sequences. A collection of nine IncFIB-4.1/4.2 single-replicon plasmids from China were fully sequenced here and compared with the first sequenced IncFIB-4.1/4.2 single-replicon plasmids from GenBank to dissect their genomic diversity.Results: In this study, a repB sequence-based scheme was proposed for grouping IncFIB replicon into seven primary types and further into 70 subtypes. A collection of nine IncFIB-4.1/4.2 single-replicon plasmids were fully sequenced here and compared with the first sequenced IncFIB-4.1/4.2 single-replicon plasmids from GenBank. These 11 plasmids had small backbones and shared only three key backbone markers repB together with its iterons, parABC, and stbD. Each plasmid contained one large accessory region (LAR) inserted into the backbone, and these 11 LARs had significantly distinct profiles of mobile genetic elements (MGEs) and resistance/metabolism gene loci. Antibiotic resistance regions (ARRs; the antibiotic resistance gene-containing genetic elements) were found in seven of these 11 LARs. Besides resistance genes, ARRs carried unit or composite transposons, integrons, and putative resistance units. IncFIB-4.1/4.2 single-replicon plasmids were important vectors of drug resistance genes. This was the first report of three novel MGEs: In1776, Tn 6755, and Tn 6857.Conclusion: Data presented here provided a deeper insight into diversity and evolution of IncFIB replicon and IncFIB-4.1/4.2 single-replicon plasmids.Keywords: IncFIB, IncFIB-4 single-replicon plasmids, large accessory regions, antibiotic resistance regions, In1776, Tn 6755, Tn 6857

Dan Zhou,1 Mengqi Yan,1 Songtao Tang,2 Yingqing Feng1 1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 2Department of Internal Medicine, Community Health Center of Liaobu Community, Dongguan, People’s Republic of ChinaCorrespondence: Yingqing Feng, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Two Road, Yuexiu District, Guangzhou, 510080, People’s Republic of China, Email 1250780250@qq.comBackground: Diabetes is most commonly associated with aortic stiffness, but the importance of nondiabetic glucometabolic status for aortic stiffness (AS) in hypertension patients is unclear.Methods: We included 1065 hypertension patients without diabetes in a cohort study. Carotid–femoral pulse wave velocity (cfPWV) > 10 m/s can broadly be defined as AS. Pearson correlation analysis and multiple regression analysis are used to reveal the relationship between elevated fasting blood glucose (FBG) and AS.Results: The 1065 hypertension patients (mean age 60 years) included 48% male, 22% smokers, 94.3% with anti-hypertensive drugs, 17.9% with AS, 80% with abdominal obesity, 42% with elevated triglycerides (TG), and 27% with elevated FBG. The mean values for office systolic blood pressure (SBP)/diastolic blood pressure (DBP) and central SBP/DBP were 130/85mmHg and 132/86mmHg. Mean cfPWV was 8.7m/s. Multiple regression analysis revealed that age, office SBP, and elevated FBG were independently related to AS in the whole hypertension. Elevated FBG had 1.6-fold risk of AS in hypertension patients compared with below the cutoff. In subgroup analysis, elevated FBG increased 2.68-fold risk for AS in those without metabolic syndrome (MS), not in MS. The area under curve (AUC) of office SBP was higher than central SBP for AS in receiver operating characteristic (ROC) analysis.Conclusion: We found that elevated FBG was an independent risk factor for AS in hypertension patients without MS, although there was a high proportion of abdominal obesity. Office SBP was better than central SBP to assess AS in community hypertension.Keywords: aortic stiffness, hypertension, elevated plasma blood glucose, carotid–femoral pulse wave velocity

Guanlie Li,1,&ast; Haiqing He,1,&ast; Guodong Zheng,1,&ast; Wenjing Jiang,1 Shuwen Du,1 Hua Tao,1 Tao Xiao,1 Dazhi Zhou,2 Shangwei Ding,2 Xi-Yong Yu,1 Yu Zhang,1 Ao Shen1 1Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Ultrasound, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ao Shen; Yu Zhang Tel +86 20 3110 0902; +86 20 3710 3275Email shenao@gzhmu.edu.cn; qianedyzy@163.comBackground: Pulmonary fibrosis (PF) is a fatal lung disease and affects over 5 million patients worldwide. Precise and early detection of PF is of pivotal importance to slow the disease progression. However, there are currently no effective tools to detect PF directly.Purpose: This study aimed to develop an imaging modality to detect PF directly. Excessive collagen deposition is the hallmark of PF. Herein, we developed a novel PF diagnostic agent, namely PVD (platelets-derived nanovesicles labeled with dye), by utilizing near-infrared (NIR)-responsive biomimetic platelets that specifically recognize collagen.Methods: In brief, platelets membrane was extracted from purified platelets by freeze/thaw and formed to PVD nanovesicles via sonication and extrusion, when loaded with DiR dye. Red blood cells membrane loaded with DiR was prepared in the same way as PVD to form RVD as control. Collagen self-assembled on microplates was used as an in vitro collagen fibrils model and monocrotaline-induced rats were used as an in vivo PF model.Results: We demonstrated that PVD, but not RVD nor other controls, could bind collagen both in vitro and in vivo, and directly detect pulmonary fibrosis in vivo and ex vivo at the early PF stage.Conclusion: Collectively, PVD is a versatile NIR-responsive probe for the direct visualization of collagen, and can be particularly helpful in direct detecting PF. To the best of our knowledge, PVD is the first report of a NIR probe for the direct detection of pulmonary fibrosis.Keywords: pulmonary fibrosis, collagen, platelets, imaging diagnosis, near-infrared

Lisha Li,1 Lianglu Wang,1 Kai Guan,1 Jun Liu,1 Daobin Zhou,2 Yanbin Zhang,2 Yan Zhang2 1Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment of Allergic Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, 100730, People’s Republic of China; 2Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaCorrespondence: Yan ZhangDepartment of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaTel +86-10-69151605Email zhangyan10659@pumch.cnObjective: This study aimed to evaluate the incidence and severity of immediate hypersensitivity reactions (HSRs) in the first exposure to rituximab with the adoption of skin testing screening and desensitization and investigate the value of skin testing as a predictive tool for immediate HSR to rituximab.Methods: This was a prospective intervention study. Patients with hematological malignancies who required rituximab were recruited. Skin testing screening with rituximab was conducted before the first infusion. Patients with positive skin testing results underwent desensitization, while those with negative results received rituximab at a standard infusion rate. All immediate HSRs were recorded, and the predictive value of positive skin testing results for immediate HSRs to rituximab was analyzed.Results: In the 19 patients who adopted the novel protocol, six patients (31.6%) had immediate HSRs during the first infusion, with three mild reactions (15.8%), two moderate reactions (10.5%), and only one severe reaction (5.3%). The positive predictive value of intradermal test (IDT) with 1 mg/mL rituximab solution for immediate HSR was 100%, and the negative predictive value was 84.6%.Conclusion: The protocol of skin testing screening and desensitization might have some potential to control the incidence and severity of immediate HSRs to rituximab during the first exposure. IDT result before the first infusion could become a useful predictor for immediate HSR to rituximab.Keywords: rituximab, hypersensitivity, skin testing, predictive value of tests, desensitization, lymphoma

Depu Zhou, Jie Wang, Xiaokun Li Department of Endocrinology, Yanbian University Hospital, Yanji City, Jilin Province, People’s Republic of ChinaCorrespondence: Xiaokun Li Email professerlxk@tom.comBackground: This study investigated patients with diabetes mellitus (DM) and the role of the platelet–lymphocyte ratio (PLR) in comorbid clinically relevant depression (CRD) in these individuals, so as to determine the association between PLR and depression.Material and Methods: All data used in this research is originally from the United States National Health and Nutrition Examination Survey (NHANES). CRD in DM patients was screened via a Patient Health Questionnaire-9 (PHQ-9). PLR was calculated by platelet and lymphocyte counts. The associations between PLR and CRD in DM patients were determined using multivariable logistic regression models, weighted generalized additive models, and receiver operating characteristic curve (ROC). The second outcome was the relationship between suicide tendency and PLR.Results: We selected 3537 DM patients from 2009 to 2016 in database. PLR was statistically significantly associated with risk of CRD in diabetic patients (p trend< 0.05 in non-adjusted and adjusted model) and had a predictive value (AUC = 0.559). We also found a U-shaped association between PLR and CRD in patients with DM. The break point was 69.2. To the right of 69.2, the OR (95% CI) was 1.00 (1.00, 1.01). To the left of it, the OR (95% CI) was 0.97 (0.95, 1.00). We have found that PLR is not related to suicidal tendencies.Conclusion: PLR is an independent risk factor for CRD in DM patients, and the relationship between them is nonlinear. When PLR was around 69.2, patients with diabetes had the lowest risk of depression. Further research is needed to clarify the nonlinear relationship between PLR and depression in DM patients.Keywords: diabetes mellitus, the platelet–lymphocyte ratio, depression, NHANES

Xinhui Wang, Xiaoli Liu, Peng Wang, Lihua Yu, Fengna Yan, Huiwen Yan, Dongdong Zhou, Zhiyun Yang Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of ChinaCorrespondence: Zhiyun YangCenter of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of ChinaTel/Fax +86-10-84322148Email yangzhiyun2016@163.comBackground and Aims: Although antiviral treatment has been shown to reduce mortality in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients with high HBV-DNA levels, it is still unclear whether it is useful in reducing mortality in patients with low HBV-DNA levels.Methods: A retrospective analysis of 756 HBV-associated HCC patients at the Beijing Ditan Hospital with HBV-DNA levels < 500 IU/mL was conducted between January 2008 and June 2017. Patients were divided into antiviral and non-antiviral groups based on whether they received nucleos(t)ide analogue (NA) treatment when they were diagnosed with HCC in our hospital for the first time. We used 1:4 frequency matching by age, gender, tumor size, Barcelona Clinic Liver Cancer (BCLC) staging, anti-tumor therapy, cirrhosis, diabetes, and hyperlipoidemia to compare the antiviral (n = 366) and non-antiviral (n = 100) groups. A Cox multivariate regression analysis was employed to evaluate the effects of NA therapy on the hazard ratio (HR), and the Kaplan–Meier survival curve was used to determine the mortality risk in patients with HCC. A Log rank test was performed to analyze the effects of NA therapy on the survival rate of patients with HCC.Results: After propensity score matching, the 1-, 3-, and 5-year overall survival (OS) rates for the antiviral and non-antiviral groups were 82.5%, 68.6%, and 52.2%, and 61.0%, 51.0%, and 38.0%, respectively. The l-year progression-free survival (PFS) rates for the two groups were 68.0% and 47.0%, respectively. The OS of the antiviral group was significantly higher than that of the control group (P < 0.001, P = 0.001, and P = 0.013, respectively). The 1-year PFS for the antiviral group was also significantly better than that for the non-antiviral groups (P = 0.005). After adjusting for confounding prognostic factors in the Cox model, the HR of 5-year death after antiviral treatment was 0.721 (95% confidence interval [CI], 0.530– 0.980, P = 0.037). Antiviral therapy is an independent protective factor for 5-year mortality in patients with HCC and low-level viremia.Conclusion: Antiviral therapy significantly reduced mortality in HCC patients with low HBV-DNA levels.Keywords: antiviral therapy, hepatitis B virus, low-level viremia, hepatocellular carcinoma, prognosis, nucleos(t)ide analog

Depu Zhou, Jie Wang, Xiaokun Li Department of Endocrinology, Yanbian University Hospital, Yanji, Jilin Province, People’s Republic of ChinaCorrespondence: Xiaokun LiDepartment of Endocrinology, Yanbian University Hospital, No. 119, Shizi Street, Yanji City, Jilin Province, 133000, People’s Republic of ChinaTel +86 433-2660170Email professerlxk@tom.comBackground: The red blood cell distribution width (RDW)–albumin ratio (RA) is a new biomarker, which is d-efined as RDW divided by albumin. This study aimed at determining the prognostic values of RA for diabetic ketoacidosis (DKA).Methods: Data were obtained from Medical Information Mart for Intensive Care Database III V1.4 (MIMIC-III) and the RA calculated. Multivariate Cox regression analysis was performed to determine the correlation between RA and 90-day mortality or 365-day mortality. To further investigate the association with RA and mortality, the patients were divided into two groups. The second outcome was the association between the incidence of DKA-related infections and RA.Results: For DKA patients in the ICU, RA was significantly correlated with 90-day mortality (HR: 2.1, 95% CI: 1.5, 3.0, p

Wenqing Yu,1,&ast; Ningfei Ji,2,&ast; Chengjing Gu,3,&ast; Juan Yao,4 Mingdong Ding,1 Daming Zhou,1 Mao Huang,2 Mingshun Zhang5,6 1Department of Infectious Diseases, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, 225300, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 3Department of Pharmacy, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, 225300, People’s Republic of China; 4Department of Oncology, Huaian Hospital of Huaian City, Huaian, Jiangsu, 223200, People’s Republic of China; 5Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of China; 6NHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengjing GuDepartment of Pharmacy, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, 225300, People’s Republic of ChinaTel +86 0523-86606290Email chengjingyu706@163.comWenqing YuDepartment of Infectious Diseases, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, 225300, People’s Republic of ChinaEmail wenqinggu706@126.comBackground: RORγt+Foxp3+ (Th17-like) Tregs are a plastic Treg subset implicated in immune-related diseases; however, the mechanism of Treg phenotypic transformation in malignant pleural effusion (MPE) has not been elucidated.Methods: The percentage of CD4+CD25+Foxp3+Helios+ and RORγt+Foxp3+ Tregs from peripheral blood and pleural effusion mononuclear cells were measured. The level of interferon regulatory factor 4 (IRF4) mRNA expression was detected by quantitative real-time reverse transcription polymerase chain reaction. The effects of IRF4 on the induction of Tregs from patients with non-small cell lung cancer (NSCLC) were evaluated in vitro. Correlation assays between IRF4 expression and the frequency of RORγt+Foxp3+ Tregs were performed.Results: The frequency of CD4+CD25+Foxp3+Helios+ Tregs and CD4+RORγt+ Th17 cells was both increased in the MPE of NSCLC patients. The group of double-positive Foxp3+RORγt+ Treg phenotype were identified in the pleural effusion. A significant increase in the frequency of Foxp3+RORγt+ Tregs was found in MPE compared with the non-malignant pleural effusion (NPE). Compared to NPE, the relative level of IRF4 expression was increased in the MPE. IRF4 expression was positively associated with the frequency of Foxp3+RORγt+ Tregs in the PE. In vitro, the level of Helios mRNA and protein expression was reduced in induced Tregs following IRF4 over-expression. Additionally, the level of RORγt protein expression was substantially increased. However, ectopic Helios expression in induced Tregs reversed the effects induced by enhanced IRF4 expression.Conclusion: IRF4 may serve as a potential molecule that promotes the conversion of regulatory T cells from MPE to a Th17-like phenotype by modulating Helios.Keywords: malignant pleural effusion, lung cancer, IRF4, regulatory T cells, phenotypic transformation

Chong Wei, Lu Zhang, Wei Zhang, Daobin Zhou Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Daobin Zhou Email zhoudb@pumch.cnAbstract: A 56-year-old man complaining of blurred vision was referred to the ophthalmologist. He was initially diagnosed with uveitis and showed no response to steroid treatment. Diagnostic vitrectomy and skin lesion biopsy performed later confirmed the diagnosis of extranodal NK/T cell lymphoma (ENKTL), nasal type. Despite sufficient systemic chemotherapy, the patient developed central nervous system (CNS) relapse 3 months after achieving systemic remission. The diagnosis and treatment of this patient required multidisciplinary teamwork between ophthalmologists, pathologists, and hematologists. This report focused on the diagnostic planning and optimal treatment strategy for this patient.Keywords: extranodal NK/T-cell lymphoma, intraocular lymphoma, chemotherapy, central nervous system

Hongfang Zeng,1– 3,&ast; Xiaoli Li,1– 3,&ast; Duanfang Zhou,1– 3 Ning Wang,4 Xiaoping Yu,1– 3 Liangyuan Long,1,3 Hao Cheng,5,6 Shuyu Zhou,5 Zhengze Shen,7 Weiying Zhou1– 3 1Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Drug Metabolism, Chongqing, People’s Republic of China; 3Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People’s Republic of China; 4West China Biopharm Research Institute, West China Hospital, Chengdu, Sichuan Province, 610041, People’s Republic of China; 5China Company 18th, College of Pharmacy, Army Medical University, Chongqing, 400038, People’s Republic of China; 6Department of Pharmacy, Medical Security Center, the 925 Hospital, Joint Logistic Support Force, Guiyang, Guizhou Province, 550005, People’s Republic of China; 7Department of Pharmacy, Yongchuan Hospital Affiliated to Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiying ZhouDepartment of Pharmacology, College of Pharmacy, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of ChinaTel/Fax +86 23 684 85161Email wyzhou0118@163.comPurpose: To examine the pharmacological effects of Qihu on type 2 diabetes mellitus using db/db mice.Materials and Methods: Thirty-seven db/db mice were randomly divided into the following 5 groups: diabetes model control group (DM group; n = 7), administered with the adjuvant 0.3% carboxymethyl cellulose-Na; positive control group (Met group; n = 8), administered with metformin (0.13 g/kg bodyweight); Qihu-L group (n = 7), administered with a low dose of Qihu (0.75 g/kg bodyweight), Qihu-M group (n = 7), administered with a medium dose of Qihu (1.5 g/kg bodyweight); Qihu-H group (n = 8), administered with a high dose of Qihu (3.0 g/kg bodyweight). BKS mice (n = 8) were used as the negative control group. The db/db mice were administered with drugs through oral gavage for 28 days. The random blood glucose levels, glucose tolerance test, bodyweight, food intake, and blood lipid levels of the mice were measured during the experimental period. The liver and pancreas tissues were collected for pathological, quantitative real-time polymerase chain reaction, and Western blotting analyses.Results: Compared with the DM group, the Qihu groups exhibited decreased bodyweight gain. The blood glucose levels in the Qihu-L, Qihu-M, and Qihu-H were 31.46%, 43.73%, and 51.83%, respectively, lower than those in the DM group. The triglyceride levels were significantly downregulated and the swelling and steatosis of the hepatocytes were significantly lower in the Qihu-M and Qihu-H groups than in the DM group. Qihu downregulated the expression of IL-1β, IL-6, and TXNIP and upregulated the AMP-activated protein kinase (AMPK) signaling pathway in the pancreas and liver tissues of db/db mice.Conclusion: The anti-diabetic effects of Qihu are mediated through the activation of the AMPK/Txnip signaling and the downregulation of the secretion of inflammatory factors in db/db mice.Keywords: type 2 diabetes mellitus, T2DM, Traditional Chinese medicine, TCM, TXNIP, anti-inflammatory

Yao Zou,1,2 Owais M Bhat,2 Xinxu Yuan,2 Guangbi Li,2 Dandan Huang,2 Yi Guo,1,3 Dan Zhou,1,3 Pin-Lan Li2 1Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2Department of Pharmacology and Toxicology, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA; 3School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of ChinaCorrespondence: Pin-Lan LiDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, School of Medicine, 1220 East Broad Street, Richmond, VA, 23298-0613, USATel +1 804-828-4793Fax +1 804-828-4794Email pin-lan.li@vcuhealth.orgDan ZhouResearch Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, People’s Republic of ChinaTel/Fax +86 22-59596211Email acuzhoudan@163.comBackground: Exosomes have been reported to mediate activation of the inflammatory response by secretion of inflammasome products such as IL-1β or IL-18 and that changes in exosomes production or secretion may be a therapeutic target for treatment of a variety of different chronic diseases. The present study tested the hypothesis that exosome-mediated release of NLRP3 inflammasome products instigates the inflammatory response in the lung during emphysema, a type of chronic obstructive pulmonary disease (COPD) and that electroacupuncture (EA) may attenuate emphysema by inhibition of NLRP3 inflammasome activation and consequent inflammation.Methods: The COPD mice model was developed by injecting porcine pancreatic elastase (PPE) via puncture tracheotomy and instillation. EA (4 Hz/20 Hz, 1 to 3 mA) was applied to the bilateral BL13 and ST36 for 30 min, once every other day for 2 weeks. Micro computed tomography (micro-CT) was performed to measure lung function. Histopathological changes in the lungs were displayed by HE staining.Results: In a mouse model of porcine pancreatic elastase (PPE)-induced emphysema, the lung tissue was found to display several key features of emphysema, including alveolar septal thickening, enlarged alveoli, interstitial edema, and inflammatory cells infiltration. Lungs of mice receiving PPE exhibited substantially increased low attenuation area (LAA) in micro-CT images. The colocalization of NLRP3 vs ASC or caspase-1 detected by confocal microscopy was shown to increase in both bronchial and alveolar walls, indicating the increased formation of NLRP3 inflammasomes. IL-1β, a prototype NLRP3 inflammasome activating product, was also found to have increased in the lung during emphysema, which was colocalized with CD63 (an exosome marker), an indicative of inflammatory exosome formation. By nanoparticle tracking analysis (NTA), IL-1β-containing exosomes were shown to significantly increase in the bronchoalveolar lavage (BAL) from mice with emphysema. Therapeutically, IL-1β production in the lung during emphysema was significantly reduced by EA at the acupoint Feishu (BL13) and Zusanli (ST36), accompanied by decreased colocalization of NLRP3 vs ASC or caspase-1. Increased exosome release into BAL during emphysema was shown to be significantly attenuated in EA-treated mice compared to their controls. However, EA of non-specific BL23 together with ST36 acupoint had no effects on NLRP3 inflammasome activation, exosome release and associated lung pathology during emphysema.Conclusion: NLRP3 inflammasome activation in concert with increased release of exosomes containing IL-1β or other inflammasome products contributes to the development of lung inflammation and injury during PPE-induced emphysema and that EA of lung-specific acupoints attenuates inflammasome activation and exosome release, thereby reducing inflammatory response in the lung of mice with emphysema.Keywords: chronic lung disease, inflammation, acupoints, exosome

Fanxiao Liu, Jun Dong, Dongsheng Zhou, Qingyu Zhang Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Qingyu ZhangDepartment of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of ChinaTel/Fax +86-0531-68773201Email zqy2008512@126.comPurpose: This study aims to identify differentially expressed genes (DEGs) in macrophages exposed to ultra-high-molecular-weight polyethylene (UHMWPE) or vitamin E-blended UHMWPE (VE-UHMWPE) particles, thereby providing potential targets for the treatment of inflammatory osteolysis.Methods: The GSE104589 dataset of genome expression in macrophages exposed to UHMWPE and VE-UHMWPE was downloaded from the Gene Expression Omnibus database to identify DEGs. Functional enrichment analysis was performed using DAVID, and the corresponding protein–protein interaction (PPI) network was constructed from the STRING database. Important modules were selected using the molecular complex detection algorithm, and hub genes were identified in cytoHubba. MicroRNAs targeting these DEGs were obtained from the TarBase, miRTarBase, and miRecords databases, while transcription factors (TFs) targeting DEGs were predicted from the ENCODE database. Finally, the top five DEGs were validated by quantitative real‐time polymerase chain reaction (qRT-PCR).Results: A total of 112 DEGs (44 upregulated and 68 downregulated DEGs) were screened. Immune and inflammatory responses were significantly related in gene ontology analysis, and 18 signaling pathways were enriched according to Kyoto Encyclopedia of Genes and Genomes pathway analysis. The PPI network involving 85 nodes and 266 protein pairs indicated that IL1β, CXCL1, ICAM1, CCL5 and CCL4 showed higher degrees. qRT-PCR analysis of the top five DEGs revealed a decreasing trend in the VE-UHMWPE group compared with the UHMWPE group. Key microRNAs (hsa-miR-144, hsa-miR-21, and hsa-miR-221) and TFs (RELA and NFKB1) were predicted to be correlated with the pathogenesis of inflammatory osteolysis through microRNA-TF regulatory network analysis.Conclusion: The present study helps shed light on the molecular mechanisms underlying the changes in the wear-induced inflammatory process after blending vitamin E with UHMWPE. Hub genes including IL1β, CXCL1, ICAM1, CCL5, and CCL4, key microRNAs (hsa-miR-144, hsa-miR-21, and hsa-miR-221) and TFs (RELA and NFKB1) may serve as prognostic and therapeutic targets of inflammatory osteolysis.Keywords: inflammatory osteolysis, aseptic loosening, bioinformatics analysis, VE-UHMWPE, macrophages