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Liping Zou,1,* Wanli Kang,2,* Chunhui Guo,3,* Juan Du,4,* Qing Chen,1 Zhengyu Shi,1 Xianzhen Tang,1 Li Liang,1 Peijun Tang,5 Qing Pan,6 Qingdong Zhu,7 Song Yang,8 Zhanlin Chang,9 Zhouli Guo,1 Guihui Wu,1 Shenjie Tang2 1Department of Tuberculosis, Public Health Clinical Center of Chengdu, Chengdu, People’s Republic of China; 2Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 3Department of Tuberculosis, Harbin Chest Hospital, Harbin, People’s Republic of China; 4Department of Tuberculosis, Wuhan Pulmonary Hotel, Wuhan, People’s Republic of China; 5Department of Tuberculosis, the Fifth People’s Hospital of Suzhou, Suzhou, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Anqing Municipal Hospital, Anqing, People’s Republic of China; 7Department of Tuberculosis, the Fourth People’s Hospital of Nanning, Nanning, People’s Republic of China; 8General Internal Medicine Department, Chongqing Public Health Medical Center, Chongqing, People’s Republic of China; 9Department of Surgery, the Third People’s Hospital of Tibet Autonomous Region, Lasa, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guihui Wu, Department of Tuberculosis, Public Health Clinical Center of Chengdu, Jingjusi 18 Street, Jingjiang District, Chengdu, Sichuan, People’s Republic of China, Tel +86-28-8455-0573, Email wghwgh2584@sina.com Shenjie Tang, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China, Tel +86-13621028338, Email tangsj1106@vip.sina.comObjective: Rifampin-resistant tuberculosis (RR-TB) remains a serious global public health concern. We assessed treatment outcomes and associated influencing factors among RR-TB patients in China.Methods: This research enrolled 1339 patients who started RR-TB treatment between May 2018 and April 2020 in China retrospectively. Data were collected from the electronic medical records. Multivariable logistic regression analysis was used to identify the influencing factors related to unfavorable outcomes.Results: Of the 1339 RR-TB patients, 78.8% (1055/1339) achieved treatment success (cured or treatment completed), 5.1% (68/1339) experienced treatment failure, 1.1% (15/1339) died during treatment, 10.1% (135/1339) were lost to follow-up, and 4.9% (66/1339) were not evaluated. About 67.7% (907/1339) of patients experienced at least one adverse event (AE). The most common AE was hypohepatia (507/1339, 37.9%), followed by hyperuricemia (429/1339, 32.0%), anemia (368/1339, 27.5%), electrolyte disturbance (318/1339, 23.7%), peripheral neuritis (245/1339, 18.3%), and gastrointestinal reactions (203/1339, 15.2%). Multivariate analysis showed that age ≥ 60 years [adjusted odds ratio (aOR): 1.96, 95% confidence interval (CI): 1.39– 2.77], national minority (aOR: 2.36, 95% CI: 1.42– 3.93), smoking (aOR: 1.50, 95% CI: 1.10– 2.04), cardiopathy (aOR: 2.90, 95% CI: 1.33– 6.31), tumors (aOR: 9.84, 95% CI: 2.27– 42.67), immunocompromise (aOR: 2.17, 95% CI: 1.21– 3.91), re-treated TB (aOR: 1.46, 95% CI: 1.08– 1.97), and experienced gastrointestinal reactions (aOR: 2.27, 95% CI: 1.52– 3.40) were associated with unfavorable outcomes. Body mass index (BMI) ≥ 18.5 kg/m2, regimens containing bedaquiline and experienced adverse events (AEs) such as hypohepatia, leukopenia, peripheral neuritis, and optic neuritis were associated with favorable outcomes.Conclusion: High rates of treatment success were achieved for RR-TB patients at tertiary tuberculosis hospitals in China. Age ≥ 60 years, national minority, smoking status, comorbidities, re-treated TB, and experienced gastrointestinal reactions were independent prognostic factors for unfavorable treatment outcomes.Keywords: RR-TB, treatment outcomes, influencing factors, China

Ente Li,1,2,* Qingfeng Zhu,3,* Ziman Lv,1,2,* Songsong Xie,3 Chunju Zhang,4 Wei Li,5 Ligu Mi,1,2 Quan Liu,6 Yuanzhi Wang,1,2 Xiaobo Lu2 1Department of Basic Medicine, School of Medicine, Shihezi University, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 2Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, the Xinjiang Production and Construction Corps, Shihezi University, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 3The First Affiliated Hospital of Shihezi University Medical College, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 4Tumxuk Center for Disease Prevention and Control, Tumxuk City, Xinjiang Uygur Autonomous Region, 843806, People’s Republic of China; 5Department of Basic Medicine, School of Medicine, Tarim University, Alaer City, Xinjiang Uygur Autonomous Region, 843300, People’s Republic of China; 6Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, Key Laboratory of Zoonotic Diseases, The First Hospital of Jilin University, Changchun City, Jilin Province, 30061, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuanzhi Wang; Xiaobo Lu, Email wangyuanzhi621@126.com; xjykdluxiaobo@126.comAbstract: Visceral leishmaniasis (VL), also known as kala-azar. It is characterized by prolonged intermittent fever, anemia, splenomegaly, hepatomegaly, and skin darkening. VL is primarily endemic in regions, such as Brazil, East Africa, and India. However, Northern Xinjiang, which is located in northwestern China, is considered a low-incidence area for VL, contributing to its status as a neglected infectious disease. In this report, we present a case of VL caused by Leishmania donovani that was diagnosed using metagenomic next-generation sequencing (mNGS). This case underscores the diagnostic value of mNGS, particularly in regions with low incidence of VL. Keywords: Visceral leishmaniasis, Leishmania donovani, metagenomic next-generation sequencing, northwestern China

Jing Lin,1 Fenglu Wu,2 Yanwen Zhu,2 Qianqian Zhu,2 Tong Du,2 Jiaying Lin2 1Center for Reproductive Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Jiaying Lin; Tong Du, Department of Assisted Reproduction, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Zhizaoju Road No. 639, Shanghai, People’s Republic of China, Email lemon_1114@126.com; ocyte@qq.comObjective: Our objective was to investigate the efficacy of letrozole co-treatment in an antagonist protocol for infertile women with polycystic ovary syndrome (PCOS).Patients and Methods: This retrospective cohort study included infertile women with PCOS undergoing IVF/ICSI with and without letrozole co-treatment in an antagonist protocol from 2007– 2021 at Shanghai Ninth People’s Hospital (Shanghai, China). A total of 1559 participants were enrolled, with 1227 women in the antagonist group and 332 women in the letrozole co-treatment group. Propensity score-based patient-matching model was conducted to balance covariates between the groups. The primary outcome was the number of retrieved oocytes, with secondary outcomes including endocrine parameters, ovarian stimulation outcomes, pregnancy outcomes, and obstetrical and neonatal complications.Results: Letrozole co-treatment induced significant changes in hormonal regulation, increased the percentage of large follicles, and resulted in fewer retrieved oocytes (P < 0.05). However, there was no negative impact on the number of usable embryos or good-quality embryos (P > 0.05). The live birth rates following fresh embryo transfer were comparable between the letrozole and control groups (single embryo transfer: 28.9% vs 29.7%, P > 0.05; double embryo transfer: 37.3% vs 45.6%, P > 0.05). Additionally, there were no significant differences between the two groups in the live birth rate per patient after frozen embryo transfer and the cumulative live birth rate (P > 0.05). No significant differences in obstetrical and neonatal complications were observed between the groups (P > 0.05).Conclusion: The addition of letrozole to the antagonist protocol for women with PCOS undergoing IVF induces a higher percentage of large follicles during oocyte retrieval, while reducing the overall number of retrieved oocytes. Moreover, the use of letrozole demonstrates comparable clinical outcomes following embryo transfers. These findings highlight the potential application of letrozole in an antagonist protocol for women with PCOS.Keywords: letrozole, antagonist protocol, polycystic ovary syndrome, follicle, in vitro fertilization

Yue Han,1,&ast; Chao Guo,2,&ast; Qianmei Zhu,1 Zijia Liu,1 Yuelun Zhang,3 Shanqing Li,2 Le Shen1 1Department of Anesthesiology, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing, People’s Republic of China; 2Department of Thoracic Surgery, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3Department of Medical Research Center, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zijia Liu, Department of Anesthesiology, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China, Tel/Fax +861069155580, Email liu-zj02@126.comBackground: Atrial fibrillation (AF) has become the most common postoperative arrhythmia of thoracic surgery. This study aimed to investigate the risk factors and complications of perioperative atrial fibrillation (PoAF) in elderly patients who underwent video-assisted thoracoscopic surgery (VATS).Methods: Data were collected from patients who underwent VATS between January 2013 and December 2022 at Peking Union Medical College Hospital (PUMCH). Univariable analyses and multivariable logistic regression analyses were used to determine the factors correlated with PoAF. Receiver operating characteristic (ROC) curve was used to evaluate the discrimination of the indicators to predict PoAF.Results: The study enrolled 2920 patients, with a PoAF incidence of 5.2% (95% CI 4.4%-6.0%). In the logistic regression analyses, male sex (OR=1.496, 95% CI 1.056– 2.129, P=0.024), left atrial anteroposterior dimension (LAD) ≥ 40 mm (OR=2.154, 95% CI 1.235– 3.578, P=0.004), hypertension (HTN) without regular treatment (OR=2.044, 95% CI 0.961– 3.921, P=0.044), a history of hyperthyroidism (OR=4.443, 95% CI 0.947– 15.306, P=0.030), surgery of the left upper lobe (compared to other lung lobes) (OR=1.625, 95% CI 1.139– 2.297, P=0.007), postoperative high blood glucose (BG) (OR=2.482, 95% CI 0.912– 5.688, P=0.048), and the time of chest tube removal (per day postoperatively) (OR=1.116, 95% CI 1.038– 1.195, P=0.002) were found to be significantly associated with PoAF. The area under the ROC curve was 0.707 (95% CI 0.519– 0.799). 86.9% patients were successfully converted to sinus rhythm. Compared with the non-PoAF group, the PoAF group had significantly greater risks of prolonged air leakage, postoperative acute coronary syndrome, longer ICU stays, and longer hospital stays.Conclusion: Male sex, LAD≥ 40 mm, HTN without regular treatment, a history of hyperthyroidism, surgery of the left upper lobe, postoperative BG, and the time of chest tube removal were associated with PoAF. These findings may help clinicians identify high-risk patients and take preventive measures to minimize the incidence and adverse prognosis of PoAF.Keywords: video-assisted thoracoscopic surgery, aged, atrial fibrillation, risk factor

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

Qing Zhu,1,2,&ast; Yijia He,1,2,&ast; Sijia Chen,1,2 Guoqiang Zhang1,2 1Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Hebei Provincial Innovation Center of Dermatology and Medical Cosmetology Technology, Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoqiang Zhang, Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China, Email 57702800@hebmu.edu.cnAbstract: Vitiligo has been reported to occur in association with lupus erythematosus (LE) and other autoimmune diseases. However, it remains unclear whether this association occurs because of shared immunopathogenesis. We hereby describe a case of discoid lupus erythematosus (DLE) in a 51-year-old man with a 3 years history of skin lesions on his face, arms, and the V zone of the neck, and with the coexistence of vitiligo for 12 years, who developed from DLE to hypertrophic discoid lupus erythematosus (HDLE) after 10 months. We reviewed the previously reported cases to summarize the clinical characteristics of these patients and hope it may provide a reference for dermatologists.Keywords: hypertrophic discoid lupus erythematosus, lupus erythematosus, vitiligo, association

Sifan Ji,1,2,&ast; Hang Qi,1,2,&ast; Li Yan,1,2,&ast; Duo Zhang,1,2 Yang Wang,1,2 HaLiSai MuDanLiFu,1,2 Chuqing He,1,2 Wei Xia,1,2 Qian Zhu,1,2 Yan Liang,1,2 Jian Zhang1,2 1Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Zhang, Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China, Tel +86 18017316017, Email zhangjian_ipmch@sjtu.edu.cnIntroduction: Endometriosis (EM) is an estrogen-dependent benign gynecologic disease affecting approximately 10% of reproductive-age women with a high recurrence rate, but lacks reliable biomarkers. No previous studies have investigated the possible use of extracellular vesicle (EV)-associated micro RNAs (miRNAs) from menstrual blood (MB) as candidate diagnostic or prognostic markers of EM.Methods: Specimens were obtained from endometriosis and non-endometriosis patients at the International Peace Maternity and Child Health Hospital in Shanghai. Microarray was used to screen differentially expressed miRNAs among peritoneal fluid (PF), fallopian tube fluid (FF), and MB. Dual-luciferase reporter gene assay was carried out to verify the relationship between miR-4443 and ACSS2. Cell proliferation and Transwell invasion assays were performed in vitro after intervention on miR-4443 and ACSS2 in hEM15A human endometrial stromal cells and primary human endometrial stromal cells (hESCs). Spearman correlation analysis, receiver operating characteristic (ROC) curve analysis, and survival analysis were applied to clinical data, including severity of symptoms and relapse of EM among EM patients.Results: EV-associated miR-4443 was abundant in MB of endometriosis patients. ACSS2 knockdown and miR-4443 overexpression promoted cell proliferation and migration via the PI3K/AKT pathway. miR-4443 levels in MB-EVs were positively correlated with the degree of dyspareunia (r=0.64; P< 0.0001) and dysmenorrhea (r=0.42; P< 0.01) in the endometriosis group. ROC curve analyses showed an area under the curve (AUC) of 0.741 (95% CI 0.624– 0.858; P< 0.05) for miR-4443 and an AUC of 0.929 (95% CI 0.880– 0.978; P< 0.05) for the combination of miR-4443 and dysmenorrhea.Conclusion: MB-derived EV-associated miR-4443 might participate in endometriosis development, thus providing a new candidate biomarker for the noninvasive prediction of endometriosis recurrence. Keywords: endometriosis, menstrual blood, biomarker, extracellular vesicles, miR-4443

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

Peng Wu,1,&ast; Xiaoyong Wang,2,&ast; Min Yin,1,&ast; Wenjie Zhu,3,&ast; Zheng Chen,1 Yang Zhang,1 Ziyu Jiang,4 Longqing Shi,5 Qiang Zhu1 1Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2The People’s Hospital of Rugao, Nantong, People’s Republic of China; 3Kangda College of Nanjing Medical University, Nanjing, People’s Republic of China; 4Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China; 5Department of Hepatobiliary and Pancreatic Surgery, Third Affiliated Hospital of Soochow University, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Longqing Shi, Department of Hepatobiliary and Pancreatic Surgery, The Third Affiliated Hospital of Soochow University, Jiangsu, People’s Republic of China, Email 20204135017@stu.suda.edu.cn Qiang Zhu, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China, Email zhu20081023@yeah.netBackground: Liver cancer remains to be one of the leading causes of cancer worldwide. The treatment options face several challenges and nanomaterials have proven to improve the bioavailability of several drug candidates and their applications in nanomedicine. Specifically, chitosan nanoparticles (CNPs) are extremely biodegradable, pose enhanced biocompatibility and are considered safe for use in medicine.Methods: CNPs were synthesized by ionic gelation, loaded with rutin (rCNPs) and characterized by ultraviolet–visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and transmission electron microscopy (TEM). The rCNPs were tested for their cytotoxic effects on human hepatoma Hep3B cells, and experiments were conducted to determine the mechanism of such effects. Further, the biocompatibility of the rCNPs was tested on L929 fibroblasts, and their hemocompatibility was determined.Results: Initially, UV–vis and FTIR analyses indicated the possible loading of rutin on rCNPs. Further, the rutin load was quantitatively measured using Ultra-Performance Liquid Chromatography (UPLC) and the concentration was 88 μg/mL for 0.22 micron filtered rCNPs. The drug loading capacity (LC%) of the rCNPs was observed to be 13.29 ± 0.68%, and encapsulation efficiency (EE%) was 19.55 ± 1.01%. The drug release was pH-responsive as 88.58% of the drug was released after 24 hrs at the lysosomal pH 5.5, whereas 91.44% of the drug was released at physiological pH 7.4 after 102 hrs. The cytotoxic effects were prominent in 0.22 micron filtered samples of 5 mg/mL rutin precursor. The particle size for the rCNPs at this concentration was 144.1 nm and the polydispersity index (PDI) was 0.244, which is deemed to be ideal for tumor targeting. A zeta potential (ζ-potential) value of 16.4 mV indicated rCNPs with good stability. The IC50 value for the cytotoxic effects of rCNPs on human hepatoma Hep3B cells was 9.7 ± 0.19 μg/mL of rutin load. In addition, the increased production of reactive oxygen species (ROS) and changes in mitochondrial membrane potential (MMP) were observed. Gene expression studies indicated that the mechanism for cytotoxic effects of rCNPs on Hep3B cells was due to the activation of Unc-51-like autophagy-activating kinase (ULK1) mediated autophagy and nuclear factor kappa B (NF-κB) signaling besides inhibiting the epithelial–mesenchymal Transition (EMT). In addition, the rCNPs were less toxic on NCTC clone 929 (L929) fibroblasts in comparison to the Hep3B cells and possessed excellent hemocompatibility (less than 2% of hemolysis).Conclusion: The synthesized rCNPs were pH-responsive and possessed the physicochemical properties suitable for tumor targeting. The particles were effectively cytotoxic on Hep3B cells in comparison to normal cells and possessed excellent hemocompatibility. The very low hemolytic profile of rCNPs indicates that the drug could be administered intravenously for cancer therapy.Keywords: rCNPs, Hep3B, ROS, qPCR, mechanism

Jinyuan Ma,1,2,&ast; Zongguang Tai,1,2,&ast; Ying Li,1,2,&ast; Yang Li,3 Jiandong Wang,1,2 Tao Zhou,1,2 Min Shen,1,2 Rujuan Xin,1,2 Cuie Shen,1,2 Quangang Zhu,1,2 Zhongjian Chen1,2 1Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Shanghai Engineering Research Center for Topical Chinese Medicine, Shanghai, People’s Republic of China; 3CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Quangang Zhu; Zhongjian Chen, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 1278 Baode Road, Shanghai, 200443, People’s Republic of China, Tel/Fax +86 21 36803155 ; +86 21 36803007, Email qgzhu@126.com; aajian818@163.comPurpose: Photodynamic therapy (PDT) has been an attractive strategy for skin tumor treatment. However, the hypoxic microenvironment of solid tumors and further O2 consumption during PDT would diminish its therapeutic effect. Herein, we developed a strategy using the combination of PDT and hypoxia-activated bioreductive drug tirapazamine (TPZ).Methods: TPZ was linked to DSPE-PEG-NHS forming DSPE-PEG-TPZ to solve leakage of water-soluble TPZ and serve as an antitumor agent and monomer molecule further forming the micellar. Chlorin e6 (Ce6) was loaded in DSPE-PEG-TPZ forming DSPE-PEG-TPZ@Ce6 (DPTC). To further improve tumor infiltration and accumulation, hyaluronic acid was adopted to make DPTC-containing microneedles (DPTC-MNs).Results: Both in vitro and in vivo studies consistently demonstrated the synergistic antitumor effect of photodynamic therapy and TPZ achieved by DPTC-MNs. With laser irradiation, overexpressions of PDT tolerance factors NQO1 and HIF-1α were inhibited by this PDT process.Conclusion: The synergistic effect of PDT and TPZ significantly improved the performance of DPTC-MNs in the treatment of melanoma and cutaneous squamous cell carcinoma and has good biocompatibility.Keywords: photodynamic therapy, hypoxia activation, combination therapy, PDT enhancement

Chunkun Yang,1,&ast; Qinwei Zhu,2,&ast; Yanbo Chen,3,&ast; Kui Ji,2 Shuanghong Li,2 Qian Wu,1 Qingquan Pan,2 Jun Li1 1Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Department of Emergency, Weifang Hospital of Traditional Chinese Medicine, Weifang, Shandong, People’s Republic of China; 3Department of Arrhythmia, Weifang People’s Hospital, Weifang, Shandong, People’s Republic of China&ast;These authors contributed equally to this workThese authors contributed equally to this workCorrespondence: Jun Li, Email gamyylj@163.comAbstract: Cardiovascular diseases (CVDs) are the most common cause of death worldwide and has been the focus of research in the medical community. Curcumin is a polyphenolic compound extracted from the root of turmeric. Curcumin has been shown to have a variety of pharmacological properties over the past decades. Curcumin can significantly protect cardiomyocyte injury after ischemia and hypoxia, inhibit myocardial hypertrophy and fibrosis, improve ventricular remodeling, reduce drug-induced myocardial injury, improve diabetic cardiomyopathy(DCM), alleviate vascular endothelial dysfunction, inhibit foam cell formation, and reduce vascular smooth muscle cells(VSMCs) proliferation. Clinical studies have shown that curcumin has a protective effect on blood vessels. Toxicological studies have shown that curcumin is safe. But high doses of curcumin also have some side effects, such as liver damage and defects in embryonic heart development. This article reviews the mechanism of curcumin intervention on CVDs in recent years, in order to provide reference for the development of new drugs in the future.Keywords: curcumin, intima, endothelial cells, vascular smooth muscle cell, cardiovascular diseases, inflammation, apoptosis

Jiandong Wang,1– 3,&ast; Jinyuan Ma,1,4,&ast; Zongguang Tai,1,4,&ast; Lisha Li,1,4 Tingrui Zhang,1,4 Tingting Cheng,1– 3 Junxia Yu,1– 3 Quangang Zhu,1,4 Leilei Bao,2 Zhongjian Chen1,4 1Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, People’s Republic of China; 2Department of Pharmacy, Third Affiliated Hospital of Naval Medical University, Shanghai, People’s Republic of China; 3School of Pharmacy, Bengbu Medical College, Bengbu, Anhui, People’s Republic of China; 4Shanghai Engineering Research Center of External Chinese Medicine, Shanghai, 200443, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leilei Bao; Zhongjian Chen, Department of Pharmacy, Third Affiliated Hospital of Naval Medical University ; Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 1278 Baode Road, Shanghai, 200443, People’s Republic of China, Tel/Fax +86 21 81875571 ; +86 21 36803007, Email annabao212@126.com; aajian818@163.comAbstract: Melanoma, a highly aggressive skin tumor, exhibits notable features including heterogeneity, a high mutational load, and innate immune escape. Despite advancements in melanoma treatment, current immunotherapies fail to fully exploit the immune system’s maximum potential. Activating immunogenic cell death (ICD) holds promise in enhancing tumor cell immunogenicity, stimulating immune amplification response, improving drug sensitivity, and eliminating tumors. Nanotechnology-enabled ICD has emerged as a compelling therapeutic strategy for augmenting cancer immunotherapy. Nanoparticles possess versatile attributes, such as prolonged blood circulation, stability, and tumor-targeting capabilities, rendering them ideal for drug delivery. In this review, we elucidate the mechanisms underlying ICD induction and associated therapeutic strategies. Additionally, we provide a concise overview of the immune stress response associated with ICD and explore the potential synergistic benefits of combining ICD induction methods with the utilization of nanocarriers.Keywords: immunogenic cell death, melanoma, immunotherapy, damage associated molecular patterns, nanocarrier

Xin Chen,1,&ast; Yan-Qiu He,1,&ast; Ti-Wei Miao,1 Jie Yin,2 Jie Liu,1 Hong-Ping Zeng,1 Qi Zhu1 1Department of Integrated Traditional Chinese and Western Medicine, Zigong First People’s Hospital, Zigong, People’s Republic of China; 2School of Automation & Information Engineering, Sichuan University of Science & Engineering, Zigong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Chen, Department of Integrated Traditional Chinese and Western Medicine, Zigong First People’s Hospital, Zigong, People’s Republic of China, Email 4651740@qq.comPurpose: Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases. Immediate early response 5 like (IER5L) plays crucial roles in progression and prognosis for several tumors, but its role in NSCLC remains unclear.Patients and Methods: Gene expression and mutation profiles, DNA methylation data, and clinical information for cancers were downloaded from multiple databases. Relative expression, prognostic value, and correlation with disease progression of IER5L were analyzed in multiple cancers, including NSCLC. Upstream mechanisms were explored using a transcriptional network. Functional enrichment analysis, protein–protein interaction network, and gene set enrichment analysis were applied to study downstream mechanisms. Correlations of IER5L with immune infiltration, immune molecules, methylation status, and tumor mutation burden (TMB) were analyzed using R language. Finally, quantitative polymerase chain reaction (qPCR) and single-cell RNA sequencing (scRNA seq) analysis were performed to validate IER5L expression in NSCLC.Results: Pan-cancer analysis displayed that IER5L expression was upregulated in multiple cancers and was associated with disease prognosis and progression, including NSCLC, which was validated using qPCR. scRNA seq analysis showed that multiple cells had increased IER5L expression. An EGR1-hsa-miR-8075-IER5L network was constructed for NSCLC. A total of 191 DEGs were identified between the two IER5L groups, which were significantly enriched in biological process of action potential, sodium ion transport, and regulation of membrane potential. Increased IER5L expression was primarily enriched in cell cycle, NOTCH signaling pathway, and oxidative phosphorylation pathway, and was correlated with increased regulatory T cells and neutrophils, elevated levels of immune molecules, and higher TMB.Conclusion: Our findings show that increased IER5L expression was correlated with progression and prognosis in multiple cancers as well as with immune infiltration and immune molecules in NSCLC. Thus, IER5L is a prognostic biomarker in multiple cancers and may correlate with immunotherapeutic response in NSCLC.Keywords: immediate early response 5 like, non-small cell lung cancer, pan-cancer, prognosis, immune infiltration

Ping Shao,1 Danyang Dong,1 Yong Huang,2 Yan Wang,1 Lian Pan,3 Qunshan Zhu,2 Zheng Wu,2 Fengjuan Jiang,4 Wei Wei2 1Department of Spleen and Stomach Diseases, Yixing Traditional Chinese Medicine Hospital, Wuxi, 214200, People’s Republic of China; 2Department of General Surgery, Jiangdu People’s Hospital Affiliated to Yangzhou University, Yangzhou, 225200, People’s Republic of China; 3Pathology Department, Yixing Traditional Chinese Medicine Hospital, Wuxi, 214200, People’s Republic of China; 4Department of Gastroenterology, Jiangdu People’s Hospital Affiliated to Yangzhou University, Yangzhou, 225200, People’s Republic of ChinaCorrespondence: Wei Wei, Email 18952531159@yzu.edu.cnBackground: Gastric cancer (GC) as is the second deadliest malignancy still lacks rapid, simple and economical detection and early clinical screening techniques. Surface-enhanced Raman spectroscopy (SERS) is a spectroscopic technique based on the surface plasmon resonance of precious metal nanoparticles, which can effectively detect low-abundance tumor markers. Combining SERS technology with sensors has high potential in the diagnosis and screening of GC.Methods: A novel Au/Si nano-umbrella array (Au/SiNUA) was prepared as a SERS substrate and the substrate was functionalized using the corresponding tumor marker aptamers for the detection of clinical biological samples using a one-step recognition release mechanism. Optimization of aptamer and complementary chain concentrations and detection time for optimal sensor preparation.Results: Au/SiNUA were tested to have good SERS enhancement activity. The proposed aptamer biosensor has good specificity and stability, with a low detection time of 18 min and a limit of detection (LOD) at the fM level, which is superior to most of the methods reported so far; and the accuracy of the clinical assay is comparable to that of the ELISA method. The expression levels of PDGF-B and thrombin in the serum of GC patients and healthy individuals can be effectively detected and differentiated.Conclusion: The ultrasensitive and specific aptamer biosensor is highly feasible for the diagnosis and screening of GC and has good application prospects.Keywords: surface-enhanced Raman scattering, gastric cancer, aptamer, biosensor, Au/SiNUA

Jiajin Di,1 Qingxian Zhu,2 Lei Wu,2 Jiali Tan,2 Yi Gao,1 Jun Liu2 1Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, People’s Republic of China; 2The Affiliated Maternity and Child Health Hospital of Jiangnan University, Wuxi, Jiangsu, People’s Republic of ChinaCorrespondence: Jun Liu, The Affiliated Maternity and Child Health Hospital of Jiangnan University, No. 48, Samuel Lane, Liangxi District, Wuxi, Jiangsu, People’s Republic of China, Tel +86 180 6836 0717, Email 6212807010@stu.jiangnan.edu.cnPurpose: The maintenance of stable blood glucose levels in gestational diabetes patients depends on their ability to make scientific decisions. Decision-making ability is influenced by factors such as preferences, knowledge acquisition, and risk perceptions. At present, problems such as irrational dietary structure, difficulties in decision-making, and poor adherence still exist in clinical practice. The key to guiding gestational diabetes patients in developing their scientific decision-making abilities lies in identifying the weak key points that affect their decision-making abilities. There is a lack of validated tools to assess these patients’ perceptions of dietary intake. In this study, we aimed to develop and validate the Dietary Intake Perceived Motivation Questionnaire for Patients with Gestational Diabetes Mellitus with the purpose of accurately identifying the obstacles encountered by gestational diabetes mellitus patients in the development of their scientific decision-making abilities.Patients and Methods: In this study, 304 individuals with gestational diabetes were recruited from a public hospital in Wuxi, China. The questionnaire was developed in 3 stages, consisting of questionnaire development, a pilot study, and a formal test, and the validity and reliability of the questionnaire were tested and confirmed. The content validity index and exploratory factor analysis were completed by expert correspondence to indicate the validity of the content and structure. In addition, Cronbach’s α was used to evaluate the internal consistency of each item of the questionnaire, and Spearman-Brown analysis was used to analyze the split-half reliability. In addition to the questionnaire, the study participants were asked to complete a general information questionnaire that included items on various demographic factors such as age, week of gestation, and mode of conception.Results: The questionnaire was validated through principal component analysis, resulting in a 31-item questionnaire named the Dietary Intake Perceived Motivation Questionnaire for Patients with Gestational Diabetes Mellitus. This questionnaire explained 86.267% of the variance and demonstrated good internal consistency (Cronbach’s α= 0.929).Conclusion: Our study determined that the questionnaire serves as a valuable tool in evaluating the motivation behind dietary intake in gestational diabetes patients.Keywords: questionnaire, gestational diabetes, pregnancy, validation

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

Qitao Chen, Qiuwei Tao, Qilin Zhu, Jing Zhu, Xufeng Du Department of Dermatology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of ChinaCorrespondence: Xufeng Du, Department of Dermatology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, No. 299 Qingyang Road, Wuxi, People’s Republic of China, Tel +86 19952290906, Email docdxf@126.comPurpose: Androgenetic alopecia (AGA) is a common dermatological condition, with reported associations between serum vitamin D and sex hormone levels. However, the relationship between these factors and the severity of hair loss remains unclear.Patients and Methods: Our cross-sectional study included 310 AGA patients who visited the dermatology clinic and underwent trichoscopy examinations throughout 2021. We collected data on serum sex hormones and 25(OH)D levels during their consultations. TrichoScan analysis was used to characterize and quantify AGA severity based on hair density and vellus hair proportions in the central scalp area, which were then correlated with the collected indicators.Results: The study findings reflect the basic demographic characteristics of AGA patients in the Chinese population. We discovered a significant negative correlation between serum SHBG levels and AGA severity in women, but no association was found in men. Serum testosterone, estradiol, dehydroepiandrosterone sulfate, and 25(OH)D levels showed no significant correlation with the severity of androgenetic alopecia, regardless of gender.Conclusion: To our knowledge, this is the first study to investigate the relationship between serum sex hormones, vitamin D, and AGA severity using trichoscopic scalp hair features.Keywords: androgenetic alopecia, TrichoScan, vitamin D, sex hormones

Yi Guo,1 Qiujin Zhu,2 Silu Shrestha2 1Institute of Educational Sciences, Hubei University of Education, Wuhan, People’s Republic of China; 2School of Philosophy, Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Silu Shrestha, Department of Psychology, School of Philosophy, Wuhan University, Bayi Road, Wuhan, Hubei Province, 430072, People’s Republic of China, Tel +86 18627015179, Email silushrestha@whu.edu.cnBackground: China is comprehensively promoting the construction of social psychological service system. Social organizations provide psychosocial care services to migrant children in China and hold important information and perspectives different from educators and parents on children’s mental health. This study aims to analyze mental health service delivery to migrant adolescents for their psychological well-being, to explore how society responds effectively to their psychological needs and to support in better program implementation of mental health services for migrant children.Methods: Following qualitative approach semi-structured interviews were conducted with community mental health service providers experienced in working with migrant children. The 15 individual interviews were conducted in Hubei province and Guangdong province, including professionals working with different social organization and social psychological service program in communities. The data were analysed through coding, comparing fragments, constant comparison and recognizing patterns.Results: The analysis yielded 3 categories (Stimulate the internal strength, Reconstruct the support systems, Understanding and participate in social activities) and 6 sub-categories (Improve the understanding of “me” and explore excellent qualities, Clearly envision “my” future and clear career planning, Improve the parent-child relationship and understand the family environment, Improve subjective support and actively develop support system, Acquire reasonable cognition and behavior and interact with surrounding ecology, Take greater responsibility and cultivate a sense of ownership). The results found that individual traits, family, communities and multiple factors affect the mental health of migrant children and identified the urgent needs, and ways to improve mental health service in efficiently and economically. Social psychological service providers contribute in strengthening the psychological well-being of the migrant children.Conclusion: Social psychological service sectors need to be strengthened to enhance the psychological well-being of the migrant children. The inherent gaps between the service required and service provided needs to be addressed through further studies on mental health needs of the migrant children.Keywords: urban setting, adaptation, mental health, content analysis, ecological systems theory

Wen Song,1 Xiaochao Song,2 Yinting Zhu,1 Yalu Ren,1 Jie Xu,1 Qiongfang Zhu1 1Center of Clinical Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China; 2Department of Infection Management, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of ChinaCorrespondence: Qiongfang Zhu; Jie Xu, Email zhuqiongfang1987@suda.edu.cn; xjddzyx163@163.comPurpose: Patients after hematopoietic stem cell transplantation (HSCT) are often followed by bloodstream infections (BSIs). BSI is an important cause of non-relapse mortality (NRM) in HSCT patients.Methods: We conducted a retrospective cohort study of patients (aged > 14 years) who underwent HSCT at our hospital from 2017 to 2021. Population characteristics, BSI microbiology, resistance to common antibiotics, and 30-day all-cause mortality were analyzed.Results: Of 3054 patients, 169 (5.5%) had BSIs after HSCT. Male, not in complete remission at transplantation and longer duration of neutropenia were risk factors for the development of BSI after HSCT. These BSIs were Gram-negative bacterial (n=123, 69.49%), Gram-positive bacterial (n=27, 15.25%), fungal (n=11, 6.36%), and polymicrobial (n=16, 9.25%). Among the Gram-negative bacteria, the proportions of isolates resistant to ceftazidime, cefepime, and piperacillin-tazobactam were similar (72.93%, 74.80%, and 77.42%, respectively). The overall drug resistance rates of amikacin and imipenem were 16.13% and 43.90%, respectively. Staphylococcus isolates were methicillin-resistant. In Enterococcus isolates, the penicillin resistance rate was 84.62%. Eleven isolates of Candida tropicalis were resistant to fluconazole and were sensitive to amphotericin B and flucytosine. The 30-day all-cause mortality rate of the 169 patients with BSIs was 8.88%. The 30-day all-cause mortality of patients with Gram-negative bacterial BSIs was 7.32%, 25.00% for polymicrobial BSIs, and 36.36% for fungal BSIs. The 30-day all-cause mortality of patients with fungal BSIs was significantly higher than that of patients with Gram-negative (P=0.0023) and Gram-positive bacteria (P=0.0023). Fungal BSI and non-Hodgkin’s lymphoma (NHL) were associated with higher 30-day mortality.Conclusion: Our study reveals the microbiological characteristics and 30-day all-cause mortality in patients with bloodstream infections after HSCT. Our data provides strong support for empirical antimicrobial therapy and infection prevention strategies for patients with BSIs after HSCT.Keywords: blood infections, hematopoietic stem cell transplantation, antibiotic resistance

Ziting Qu,1,&ast; Yanxun Han,2,&ast; Qingbo Zhu,1,&ast; Wenxi Ding,1 Yuyan Wang,1 Yan Zhang,1 Wei Wei,1 Yu Lei,1 Min Li,1 Yang Jiao,1 Kangsheng Gu,1,&ast; Yiyin Zhang1,&ast; 1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kangsheng Gu; Yiyin Zhang, Department of Oncology, The First Affiliated Hospital of Anhui Medical University, 218th Jixi Road, Hefei, Anhui, 230022, People’s Republic of China, Email gukangsheng@ahmu.edu.cn; zhangyiyin@ahmu.edu.cnBackground: Neutrophil extracellular traps (NETs) released by neutrophils are crucial for cancer development, metastasis, and can indicate gastric cancer (GC) patients’ prognosis. This study reveals the relevance of NETs-related genes to GC through transcriptome analysis.Methods: We obtained transcriptome sequencing data of GC from UCSC Xena and screened prognostic NETs-related genes by GEPIA2 database. The signature for NETs was subsequently created using the LASSO–Cox regression. The clinical value of model was further explored using the nomogram and was externally validated by the GEO database. After that, we employed GO, KEGG, and GSEA enrichment analyses to evaluate the bio-functional enrichment and related pathways. Additionally, ESTIMATE, MCP counter, and ssGSEA scores were used to investigate the immunological microenvironment of GC patients. Finally, in the external cohort, neutrophil elastase (NE)-DNA complexes were measured by ELISA, and the prognostic value of NE-DNA in GC was investigated using Cox analysis.Results: Seven NETs-associated genes (PDE4B, CD93, CTSG, IL6, ELANE, KCNJ15, and CRISPLD2) were filtered to establish the signature and participated in building the nomogram. In comparison to the high-risk group, the overall survival (OS) was much longer in the low-risk group (P=0.005). The validation cohort demonstrated the acceptable predictive ability of the nomogram. The signature was enriched in biological features such as extracellular matrix organization, epithelial-mesenchymal transition and inflammatory response. Moreover, there were substantial differences in immune cell infiltration across the different risk groups (p< 0.001), especially the high-risk group having more immune cells that are engaged in the antigen presentation process and associated functions. Finally, in the external cohort, NE-DNA levels were shown to be an independent factor affecting OS prognosis (p=0.006).Conclusion: Overall, this research identified a novel signature based on seven NETs-associated genes to predict prognosis and identify tumor microenvironment of GC. And high NE-DNA level may be a critical factor in the poor OS associated with NETs.Keywords: NETs, gastric cancer, gene signature, tumor microenvironment, prognosis

Yajing You,1,&ast; Tao Yang,2,&ast; Shuhang Wei,1 Zongxin Liu,1 Chenxi Liu,1 Zijian Shen,3 Yinuo Yang,1 Yuemin Feng,1 Ping Yao,2 Qiang Zhu1,2 1Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China; 2Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China; 3Department of Radiology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Zhu, Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China, Email zhuqiang@sdu.edu.cn Ping Yao, Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China, Email pingyaozh@sina.comPurpose: Metabolic associated fatty liver disease is a novel concept defined as fatty liver associated with metabolic disorders. We investigated the effect of metabolic associated fatty liver disease on hepatocellular carcinoma patient mortality.Patients and Methods: A total of 624 patients with hepatocellular carcinoma between 2012 and 2020 were enrolled in this retrospective study. Hepatic steatosis was diagnosed using computed tomography or magnetic resonance imaging. Metabolic associated fatty liver disease was defined based on the proposed criteria in 2020. Propensity score matching was performed for patients with metabolic associated fatty liver disease and those without the condition. A Cox proportional hazards regression model was used to evaluate the association between metabolic associated fatty liver disease and hepatocellular carcinoma patient outcomes.Results: Patients with hepatocellular carcinoma and metabolic associated fatty liver disease tended to achieve better outcomes than did those without metabolic associated fatty liver disease after matching (p< 0.001). Metabolic associated fatty liver disease was significantly associated with better prognosis in patients with concurrent hepatitis B infection (p< 0.001). Moreover, high levels of hepatitis B viral DNA in serum samples was associated with a significantly increased risk of death in patients without non-metabolic associated fatty liver disease (p=0.045). Additionally, the association between metabolic associated fatty liver disease and survival in hepatitis B virus-related hepatocellular carcinoma was similar in all subgroups based on metabolic traits.Conclusion: Metabolic associated fatty liver disease increases the survival rate of patients with hepatocellular carcinoma and hepatitis B virus infection. The potential interaction of steatosis and virus replication should be considered for future research and clinical treatment strategies.Keywords: steatosis, diabetes, obesity, HBe Ag

Xianqiang Yu,1,2 Qian Zhu3 1Women and Children’s Hospital Affiliated to Qingdao University, Qingdao, People’s Republic of China; 2University of California, Los Angeles, Department of Cardiology, Los Angeles, CA, USA; 3Department of Hepatobiliary Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Qian Zhu, Department of Hepatobiliary and Pancreatic Surgery, Pancreatic Surgery Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, People’s Republic of China, Email zhuqian@whu.edu.cnAbstract: Acute pancreatitis (AP) is a common acute abdomen and the number one cause of acute digestive hospitalizations in the United States. Abdominal pain is the main clinical manifestation of abdominal symptoms, so reducing the abdominal symptoms caused by inflammation is very important to alleviate the pain of patients. Electroacupuncture (EA) as a traditional Chinese medicine (TCM) therapy has significant conditioning effects on various inflammatory diseases including AP. Continuous studies in recent years have shown that EA conditioning has significant effects on reducing inflammation and regulating gastrointestinal symptoms in AP. At the same time, there is sufficient evidence to further elucidate the mechanism of EA. In this review, we will summarize the effect of EA on AP and its mechanism, so as to better serve clinical practice in the treatment of AP in the future.Keywords: electroacupuncture, acute pancreatitis, traditional Chinese medicine, TCM

Chunkun Yang,1,&ast; Jiawen Cheng,1,&ast; Qinwei Zhu,2 Qingquan Pan,2 Kui Ji,2 Jun Li1 1Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Department of Emergency, Weifang Hospital of Traditional Chinese Medicine, Weifang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Li, Email gamyylj@163.comAbstract: Cardiovascular disease (CVD) is one of the leading causes of death in the world. Paeonol(Pae) is a phenolic component extracted from peony bark, peony root and Xu Changqing. Studies have shown that Pae can protect cardiomyocytes by inhibiting oxidative stress, promoting mitochondrial fusion, regulating mitochondrial autophagy and inhibiting inflammation. In addition, Pae improves ventricular remodeling by inhibiting myocardial apoptosis, hypertrophy and fibrosis. Pae also has a good protective effect on blood vessels by inhibiting vascular inflammation, reducing the expression of adhesion molecules, inhibiting vascular proliferation, and inhibiting oxidative stress and endoplasmic reticulum stress(ERS). Pae also has the effect of anti-endothelial cell senescence, promoting thrombus recanalization and vasodilating. In conclusion, the molecular targets of Pae are very complex, and the relationship between different targets and signaling pathways cannot be clearly explained, which requires us to use systems biology methods to further study specific molecular targets of Pae. It has to be mentioned that the bioavailability of Pae is poor, and some nanotechnology-assisted drug delivery systems improve the therapeutic effect of Pae. We reviewed the protective mechanism of paeonol on the cardiovascular system, hoping to provide help for drug development in the treatment of CVD.Keywords: paeonol, oxidative stress, inflammation, mitochondrial fusion, adhesion, autophagy

Lulu Xv,&ast; Bin Wang,&ast; Qing Zhu, Guoqiang Zhang&ast; The First Hospital of Hebei Medical University, Shijiazhuang, China&ast;These authors contributed equally to this workCorrespondence: Guoqiang Zhang, No. 89, DongGang Road, Shijiazhuang, Hebei Province, People’s Republic of China, Tel +8618633888122, Email zlx090702@163.comAbstract: This is a 58-year-old woman who has had itching on her right back for 10 days; a month ago she developed blisters on her right back with no apparent cause and pain, and was diagnosed with “herpes zoster”. Erythema and blisters with itching reappeared 10 days ago on the right side of the back, where the original blisters had subsided. The histopathological manifestations of the lesions were: mild hyperkeratosis of the epidermis, pustules within the stratum corneum, irregular proliferation of the spinous layer, spongiosis, local destruction of the basal layer, infiltration of eosinophils, neutrophils, histiocytes and scattered plasma cells in the dermis and subcutis. According to the medical history, clinical manifestations and histopathology of the lesions, the diagnosis was Wolf’s isotopic response after herpes zoster.Keywords: Wolf’s isotopic response, herpes zoster, eosinophilic pustular folliculitis

Junli Hu,1– 5,&ast; Xintian Cai,1– 6,&ast; Qing Zhu,1– 6 Mulalibieke Heizhati,1– 5 Wen Wen,1– 6 Qin Luo,1– 5 Jing Hong,1– 5 Yujie Dang,1– 6 Wenbo Yang,1– 5 Nanfang Li1– 5 1Hypertension Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 2Xinjiang Hypertension Institute, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 3NHC Key Laboratory of Hypertension Clinical Research, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 4Key Laboratory of Xinjiang Uygur Autonomous Region, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 5Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 6Graduate School, Xinjiang Medical University, Urumqi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center, People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumuqi, Xinjiang, 830001, People’s Republic of China, Tel +86 8564818, Email lnanfang2016@sina.comObjective: To investigate the association between plasma aldosterone concentration (PAC) and non-alcoholic fatty liver disease (NAFLD) diagnosis in Chinese hypertensive patients.Methods: We conducted a retrospective study of all patients diagnosed with hypertension between January 1, 2010, and December 31, 2021. We included 3713 hypertensive patients based on the criteria for inclusion and exclusion. PAC measurement was performed using a radioimmunoassay. NAFLD was diagnosed using abdominal ultrasonography. Cox regression analysis was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for univariable and multivariable models. A generalized additive model was used to identify nonlinear relationships between PAC and NAFLD diagnosis.Results: A total of 3713 participants were included in the analysis. Over a median follow-up of 30 months, 1572 hypertensive individuals developed new-onset NAFLD. When PAC was used as a continuous variable, the risk of NAFLD increased by 1.04 and 1.24-fold for each 1 ng/dL and 5 ng/dL increase in PAC, respectively. When PAC was considered a categorical variable, the HR for tertile 3 was 1.71 (95% CI, 1.47– 1.98, P < 0.001) compared to tertile 1. Overall, there was a J-shaped relationship between PAC and new-onset NAFLD. By fitting a two-piecewise linear regression model and using a recursive algorithm, we identified a PAC inflection point at 13 ng/dL (log-likelihood ratio test, P = 0.005). In adjusted model 3, for PAC ≥ 13 ng/dL, a 5 ng/dL increase in PAC was associated with a 30% increase in the risk of new-onset NAFLD (95% CI, 1.25– 1.35, P < 0.001).Conclusion: The study revealed a non-linear relationship between elevated PAC levels and the incidence of NAFLD in hypertensive patients. Notably, the risk of new-onset NAFLD was significantly increased when PAC levels were ≥ 13 ng/dL. Larger, prospective studies are necessary to confirm these findings.Keywords: plasma aldosterone concentration, non-alcoholic fatty liver disease, hypertension, cohort study

Qiao Zhu,1,&ast; Qingkai Zhao,2,&ast; Ping Ping,3,&ast; Qian Zhang,4,&ast; Li Gong,5 Long Feng,6 Yali Zhao,1 Shihui Fu7,8 1Central Laboratory, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 2Department of Health Medicine, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 3General Station for Drug Instrument Supervision and Control, Joint Logistic Support Force of Chinese People’s Liberation Army, Beijing, People’s Republic of China; 4Department of Neurology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 5Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, People’s Republic of China; 6Department of Anesthesiology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 7Department of Cardiology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 8Department of Geriatric Cardiology, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shihui Fu, Department of Cardiology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, Hainan, 572013, People’s Republic of China, Email xiaoxiao0915@126.com Yali Zhao, Central Laboratory, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, Hainan, 572013, People’s Republic of China, Email zhaoyl301@163.comBackground: Hair chemical elements reflect physical condition over time. Collection, transporting, and storing hair is more convenient than handling blood. Hair elements show higher levels for a long time, which allows for more accurate and sensitive results than using blood. Studies explored the relationships between elements and age, without full consideration of nutritional status, in older people. This study explored the relationships between hair chemical elements and Geriatric Nutritional Risk Index (GNRI) in oldest-old and centenarian populations to provide an updated reference for nutritional evaluation of older people.Methods: A total of 152 participants over 80 years old underwent home interviews and physical examinations. An inductively coupled plasma mass spectrometer was used to detect hair chemical elements.Results: Women accounted for 77.0% of participants. Women had lower levels of zinc, and higher levels of selenium, manganese, lead, iron, and copper than men (P< 0.05 for all). Ninety-two participants formed the 80– 99 year group, and 60 participants formed the 100+ year group. Centenarians had lower levels of selenium, lead, iron, and copper than those aged 80– 99 years (P< 0.05 for all). Hair selenium levels were positively associated with GNRI (odds ratio: 11.55, 95% confidence interval: 3.42– 19.68, P < 0.05) based on a multivariate linear regression analysis. Other chemical elements had no significant associations with GNRI based on a multivariate linear regression analysis.Conclusion: Chemical elements and nutrient status were altered based on age and gender, and an association existed between hair selenium and nutritional status in older people. Chemical elements may influence and indicate nutritional status in older people.Keywords: centenarian, oldest-old, hair chemical elements, nutritional status, selenium

Fei Gao,1,&ast; Yang Zhou,2,3,&ast; Xiaoming Yan,4,&ast; Haozhang Huang,2,3,5 Guoxiao Liang,2,3 Yongyi Xie,6 Qijiong Zhu,7 Ziming Chen,8 Bo Wang,2,3 Huanqiang Li,2,3 Ziling Mai,2,3,9 Ming Ying,2,3 Jin Liu,2,3 Shiqun Chen,2,3 Jiyan Chen2,3,10 1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 3Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 4Department of Information Technology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 5The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 6School of Pharmacy, Guangdong Medical University, Dongguan, People’s Republic of China; 7School of Public Health, Guangdong Medical University, Dongguan, People’s Republic of China; 8School of Foreign Studies, Southern Medical University, Guangzhou, People’s Republic of China; 9School of Biology and Biological Engineering, South China University of Technology, Guangzhou, People’s Republic of China; 10Guangdong Provincial People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiqun Chen, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China, Email shiqunchen@126.com Jiyan Chen, Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China, Tel +86 2083827812-10528, Fax +86 2083851483, Email chenjiyandr@126.comBackground: Diabetes mellitus (DM) patients with increased urinary albumin creatinine ratio (uACR) have higher risk of mortality, while it is unclear in DM patients with atherosclerotic cardiovascular disease (ASCVD).Methods: We analysed 2832 DM patients with ASCVD in this multi-center registry cohort study Cardiorenal ImprovemeNt II (CIN-II) in 5 Chinese tertiary hospitals from 2007 to 2020. Patients were divided into 3 groups according to their uACR level (normal group: uACR < 30mg/g, moderately increased group: 30mg/g≤ uACR < 300mg/g, severely increased group: 300mg/g≤ uACR). The main outcome of the study was cardiovascular mortality and all-cause mortality.Results: During a median follow-up of 2.1 years, among 2832 patients (mean age: 63.3 ± 9.9 years, 29.1% women), 434 patients (15.3%) had moderately increased uACR, and 203 patients (7.2%) had severely increased uACR. Compared to patients in normal group, patients had higher cardiovascular mortality in moderately increased group and severely increased group (2.5% vs 9.9% vs 16.7%, P < 0.001), as well as all-cause mortality. After adjusting confounders, the risk of cardiovascular mortality remained higher in moderately increased group (adjusted hazard ratio [aHR]: 3.13; 95% confidence interval [CI]: 2.04– 4.81) and severely increased group (aHR: 4.54; 95% CI: 2.58– 8.01) than in normal group, as well as all-cause mortality.Conclusion: In our study, we found nearly a quarter of DM patients with ASCVD had increased uACR, and they have over 2- or 3-fold risk of cardiovascular mortality than those with normal uACR. UACR is a helpful indicator for risk stratification and treatment target for DM patients with ASCVD.Keywords: diabetes mellitus, atherosclerotic cardiovascular disease, urinary albumin creatinine ratio, cardiovascular mortality

Yiran Chen,1,2,&ast; Xiaoling Wu,3,&ast; Xi Chen,1,2 Deliang Guo,1,2 Weijie Ma,1,2 Yonghua Guo,1,2 Kequan Xu,1,2 Shuxian Ma,1,2 Yufeng Yuan,1,2,4 Qian Zhu1,2 1Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 2Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, Hubei, 430071, People’s Republic of China; 3Department of Liver Surgery, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 4TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yufeng Yuan; Qian Zhu, Email yuanyf1971@whu.edu.cn; zhuqian@whu.edu.cnIntroduction: Hepatocellular carcinoma (HCC) was the sixth most prevalent cancer worldwide. Long non-coding RNA TGFB2-OT1 has been proven to mediate inflammation and autophagy in vascular endothelial cells. However, its function in HCC is still unknown.Methods: We analyzed the relationship between TGFB2-OT1 expression and the clinicopathological features of 202 HCC patients. RT-qPCR was used to analyze the TGFB2-OT1 expression in HCC cell lines and tissues. In vitro and in vivo assays were conducted to verify the effect of TGFB2-OT1 on the phenotype of HCC. RNA pull-down assays were applied to reveal the proteins binding to the TGFB2-OT1. Western-blot assays were conducted to analyze the protein expression in HCC cell lines.Results: TGFB2-OT1 was found to be highly expressed in HCC samples and hepatoma cells. TGFB2-OT1 expression was significantly associated with age (P = 0.001), cirrhosis (P = 0.003), tumor size (P < 0.001), tumor encapsulation (P = 0.029), tumor protruding from the liver surface (P = 0.040), and alpha fetoprotein (AFP, P < 0.001) levels. TGFB2-OT1 promoted proliferation, migration, invasion, and angiogenesis in HCC cells, both in vitro and in vivo. TGFB2-OT1 binds to β-catenin and competitively impaired the binding of β-catenin to GSK3β, thus suppressing the phosphorylation of β-catenin at Ser33, Ser37, and Thr41.Conclusion: TGFB2-OT1 is overexpressed in HCC and predicts the poor prognosis of HCC patients. TGFB2-OT1 impedes the phosphorylation of β-catenin and acts as an alternative activator of the Wnt/β-catenin pathway to promote the progression and angiogenesis of HCC.Keywords: TGFB2-OT1, HCC, β-catenin, angiogenesis, phosphorylation

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

Yihang Ma,1,&ast; Boyin Zhang,1,&ast; Huifeng Sun,2 Dandan Liu,1 Yuhang Zhu,1 Qingsan Zhu,1 Xiangji Liu3 1Department of Spine Surgery, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Respiratory Medicine, No.964 Hospital of People’s Liberation Army, Changchun, People’s Republic of China; 3Department of Spine Surgery, The Second Hospital of Dalian Medical University, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangji Liu, Email 13174462143@163.comAbstract: Bone tumors, including primary bone tumors, invasive bone tumors, metastatic bone tumors, and others, are one of the most clinical difficulties in orthopedics. Once these tumors have grown and developed in the bone system, they will interact with osteocytes and other environmental cells in the bone system’s microenvironment, leading to the eventual damage of the bone’s physical structure. Surgical procedures for bone tumors may result in permanent defects. The dual-efficacy of tissue regeneration and tumor treatment has made biomaterial scaffolds frequently used in treating bone tumors. 3D printing technology, also known as additive manufacturing or rapid printing prototype, is the transformation of 3D computer models into physical models through deposition, curing, and material fusion of successive layers. Adjustable shape, porosity/pore size, and other mechanical properties are an advantage of 3D-printed objects, unlike natural and synthetic material with fixed qualities. Researchers have demonstrated the significant role of diverse 3D-printed biological scaffolds in the treatment for bone tumors and the regeneration of bone tissue, and that they enhanced various performance of the products. Based on the characteristics of bone tumors, this review synthesized the findings of current researchers on the application of various 3D-printed biological scaffolds including bioceramic scaffold, metal alloy scaffold and nano-scaffold, in bone tumors and discussed the advantages, disadvantages, and future application prospects of various types of 3D-printed biological scaffolds. Finally, the future development trend of 3D-printed biological scaffolds in bone tumor is summarized, providing a theoretical foundation and a larger outlook for the use of biological scaffolds in the treatment of patients with bone tumors.Graphic Abstract: Keywords: 3D-printed, scaffolds, bone tumors, nanomaterials

Mengru Wang,1,&ast; Menghui Wang,1,&ast; Qing Zhu,1,2 Xiaoguang Yao,1 Mulalibieke Heizhati,1 Xintian Cai,1,2 Yue Ma,1 Run Wang,1 Jing Hong,1 Ling Yao,1 Le Sun,1 Na Yue,1 Yingli Ren,1 Nanfang Li1 1Hypertension Center, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 2Graduate School, Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China, Email lnanfang2016@sina.comPurpose: To develop and validate a risk prediction model for coronary heart disease (CHD) in snorers with hypertension, including traditional and new risk factors.Patients and Methods: Twenty factors were evaluated in the records of 2810 snorers with hypertension. Training (70%) and validation (30%) sets were created by random allocation of data, and a new nomogram model was developed. The model’s discrimination and calibration were measured by calculating the area under the receiver operating curve (AUC) and creating calibration charts. The performance of the nomogram model was compared with that of the Prediction for ASCVD Risk in China (China-PAR) and Framingham models by decision curve analysis. An optimal cutoff point for the risk score in the training set was computed to stratify patients.Results: In the nomogram model, the AUCs for predicting CHD at 5, 7 and 9 years in the training set were 0.706 (95% confidence interval [CI] 0.649– 0.763), 0.703 (95% CI 0.655– 0.751) and 0.669 (95% CI 0.593– 0.744), respectively. The respective AUCs were 0.682 (95% CI 0.607– 0.758), 0.689 (95% CI 0.618– 0.760) and 0.664 (95% CI 0.539– 0.789) in the validation set. The calibration chart showed that the predicted events from the nomogram score were close to the observed events. Decision curve analysis indicated that the nomogram score was slightly better than the Prediction for ASCVD Risk in China (China-PAR) and Framingham models for predicting the risk of CHD in snorers with hypertension. A cutoff point was identified for being CHD-free (a nomogram score of ≤ 121), which could be helpful for the early identification of individuals at high-risk of CHD.Conclusion: The nomogram score predicts the risk probability of CHD in snorers with hypertension at 5, 7 and 9 years, and shows good capability in terms of discrimination and calibration. It may be a useful tool for identifying individuals at high risk of CHD.Keywords: snorer, hypertension, coronary heart disease, prediction model

Qiannan Zhu,1 Jue Wang,1 Yuenian Shi,2 Xiaoming Zha,1 Shui Wang1 1The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of ChinaCorrespondence: Shui Wang; Xiaoming Zha, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, 210000, People’s Republic of China, Email ws0801@hotmail.com; njzhaxm@njmu.edu.cnPurpose: Solute carrier family 7, member 5 (SLC7A5) is reportedly a key gene in various tumors. However, the relationship between SLC7A5 and immune cell infiltration in breast cancer remains elusive. In this study, we investigated the expression levels and clinical value of SLC7A5 using the R package in breast cancer through the TCGA database.Methods: Public transcript data and clinical information of patients were downloaded from the TCGA database. Prognosis analysis was performed to explore the clinical value of SLC7A5 as well as drug sensitivity prediction and Gene Set Enrichment Analysis (GSEA). We also explored the correlations between SLC7A5 and immune infiltration as well as immune markers.Results: We observed that high SLC7A5 expression levels were related to poor survival. Our GSEA demonstrated that G protein-coupled receptor-ligand binding, interleukin signaling, neutrophil degranulation, amino acid and derivative metabolism, and Rho GTPase signaling were differentially enriched in the SLC7A5 high-expression phenotype. Patients in the low SLC7A5 expression group showed sensitivity to paclitaxel and doxorubicin.Conclusion: SLC7A5 could serve as a biomarker for breast cancer prognosis.Keywords: SLC7A5, breast cancer, immune cell infiltration, chemosensitivity

Qiaoyu Zhu,1 Jianming Zhu,2 Xing Wang,3 Qiong Xu4 1School of Physical Education, Shanghai University, Shanghai, 200444, People’s Republic of China; 2Sports Department, East China University of Political Science and Law, Shanghai, 200042, People’s Republic of China; 3School of Kinesiology, Shanghai University of Sport, Shanghai, 200438, People’s Republic of China; 4School of Physical Health, Shanghai Business School, Shanghai, 201400, People’s Republic of ChinaCorrespondence: Qiong Xu, Email susxuqiong@163.comObjective: This paper aims to perform a systematic assessment of the influence of physical exercise on asthma patients and discuss the intervention effects of different exercises on the lung function FEV1 (%pred) and quality of life among asthma patients so as to lay a scientific foundation for improving asthma symptoms.Methods: Both Chinese and English databases were retrieved, including PubMed, Web of Science, Embase, The Cochrane Library, CBM, CNKI, Wan Fang Data, and VIP, whose retrieval period started from the founding date of each database to 1st, November 2021. Randomized controlled trials (RCT) studying the symptom indicators of asthma patients were collected. Those collected papers were screened according to the Inclusion Criteria and Exclusion Criteria. Then, methodological quality assessments were conducted on the included papers, and combined effect sizes were analyzed by using software ReMan 5.3.5.Results: The meta analysis showed that physical exercise could significantly improve lung function FEV1 (%pred) and quality of life score. Trails containing breathing exercise are the main source of heterogeneity, and the subgroup of breathing exercise may have better performance than the subgroup of aerobic exercise in improving FEV1 (%pred).Conclusion: Physical exercise can significantly improve the symptoms and quality of life of asthma patients. Except the breathing exercise that showed heterogeneity, the subgroup of aerobic exercise could improve the capacity of FEV1 (%pred) more effectively, which led to a significant difference in the influence of quality of life. However, with regard to the gymnastic exercise including breathing exercise, there are limited same intervention methods and insufficient same outcome indicators. Therefore, more precise and high-quality researches are needed to make deeper verification in the future.Keywords: physical exercise, asthma, lung function, quality of life, meta analysis

Xu Zhu,1,&ast; Ting Yin,1,&ast; Ting Zhang,1 Qingqing Zhu,1 Xinyi Lu,1 Luyang Wang,1 Shengen Liao,1 Wenming Yao,1 Yanli Zhou,1 Haifeng Zhang,1,2 Xinli Li1 1Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, People’s Republic of China; 2Department of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinli Li, Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, People’s Republic of China, Email xinli3267@njmu.edu.cnObjective: This study aimed to analyze immune-related genes and immune cell components in the peripheral blood of patients with acute myocardial infarction (AMI).Methods: Six datasets were obtained from the GEO repository comprising 88 healthy samples and 215 AMI samples. We performed the weighted gene co-expression analysis (WGCNA) and five machine learning (ML) methods to identify immune-related genes and construct diagnostic models. CIBERSORT algorithm was adopted for the assessment of the degree of immune infiltration. Finally, RT-PCR, immunofluorescence double and immunohistochemistry were conducted to analyze the expression level of the identification of featured immune-related genes and localization relationship in heart tissue of AMI mouse model.Results: A total of 496 immune-related DEGs were obtained between AMI and normal samples. WGCNA finally determined the co-expression modules that showed the most significantly positively associated with AMI (r=0.41; P< 0.001). Among the five ML models, XGBoost had the highest AUC (0.849) and accuracy (0.812) to discriminate patients with AMI from normal in the validation sets. Furthermore, we found that the proportion of chemokine receptor (CCR), macrophages, neutrophils, and Treg cells in the AMI groups was significantly higher than that in the normal groups. In vitro RT-PCR verification revealed that SOCS3, MMP9, and AQP9 expression increased significantly in the AMI mouse model. Among the 22 immune cells, AQP9, MMP9, and SOCS3 displayed the strongest positive correlation with neutrophils. In MI-mice, MPO stained strongly along the lateral cardiomyocytes, whereas it was weaker in sham mice. Combined immunofluorescence was observed in same parts of the cytoplasm of cardiomyocytes in myocardial infarction area, indicating co-localization of MPO with MMP9 and SOCS3 in these areas, respectively.Conclusion: Immune-related genes and immune cells are intimately related to AMI. Constructing different ML models based on these biomarkers could be a valuable approach to diagnosing AMI in clinical practice.Keywords: acute myocardial infarction, immune-related genes, immune infiltration, machine learning, diagnostic model

Yaqin Shi,1,&ast; Meng Shen,1,&ast; Mengdan Xu,1 Min Tao,1 Kai Chen,1 Qingqing Zhu2 1Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingqing Zhu, Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Email athena_zqq@126.com Kai Chen, Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Email cky9920@163.comPurpose: The RAD51 family of genes, including RAD51 and the five RAD51-like paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3), are known to be crucially associated with DNA damage repair pathway. Increasing evidence indicated that RAD51 family members were implicated in breast cancer tumorigenesis. However, their biological roles and prognostic values in breast cancer have yet to be clarified.Methods: In this study, by using the Oncomine and GEPIA databases, we explored the transcriptional levels of RAD51 family members in breast cancer. Besides, the associations between RAD51 family expression and clinical features were evaluated by using the UALCAN database and Kaplan–Meier (KM) Plotter. We also analyzed the mutations of the RAD51 family and differentially altered genes from the cBioPortal database.Results: We found that RAD51 mRNA was significantly elevated in breast cancer samples than in normal tissues, while XRCC2 mRNA was downregulated. Besides, a remarkable correlation was detected between the expression of RAD51/RAD51B/XRCC2 genes and the breast cancer stage. Survival analysis utilizing the KM Plotter indicated that high RAD51 and XRCC3 mRNA was associated with a poor prognosis. Conversely, RFS data suggested that high levels of RAD51B/RAD51C/RAD51D/XRCC2 were associated with a favorable prognosis. Moreover, a high genetic variation rate of RAD51C (7%) was detected in breast cancer patients.Conclusion: Conclusively, we implied that RAD51 and XRCC3 might be potential targets for precision therapy in breast cancer and the RAD51B/RAD51C/RAD51D/XRCC2 genes have significant values for breast cancer prognosis.Keywords: RAD51, breast, cancer, expression, gene, prognosis

Junli Hu,1– 5,&ast; Xintian Cai,1– 5,&ast; Nanfang Li,1– 5 Qing Zhu,1– 5 Wen Wen,1– 5 Jing Hong,1– 5 Delian Zhang,1– 5 Xiaoguang Yao,1– 5 Qin Luo,1 Le Sun1– 5 1Hypertension Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 2Xinjiang Hypertension Institute, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 3National Health Committee Key Laboratory of Hypertension Clinical Research, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 4Key Laboratory of Xinjiang Uygur Autonomous Region, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 5Xinjiang Clinical Medical Research Center for Hypertension Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China, Tel/Fax +86 991-8564818, Email lnanfang2016@sina.comPurpose: This study aimed to investigate the association between triglyceride glucose index-waist circumference (TyG-WC) and the risk of first myocardial infarction (MI) in Chinese hypertensive patients with obstructive sleep apnoea (OSA).Methods: This study was an observational cohort study. A total of 2224 Chinese hypertensive patients with OSA without a history of MI were included in this study. Hazard ratio (HR) and 95% confidence interval (CI) were estimated using multivariable Cox proportion hazard models. A generalized additive model was used to identify nonlinear relationships. Additionally, we performed hierarchical analysis and test for interaction.Results: During a median follow-up of 7.15 years, 85 incidents of MI developed. Overall, there was a positive association between TyG-WC and the risk of first MI. In the multivariable-adjusted model, the risk of MI increased with quartiles of the TyG-WC, the HR in quartile 4 versus quartile 1 was 4.29. A generalized additive model and a smooth curve fitting showed that there existed a similar J-shaped association between TyG-WC and the risk of first MI, with an inflection point at about 785.Conclusion: Elevated levels of the baseline TyG-WC are associated with an increased risk of first MI. This finding indicates that the TyG-WC might be useful to identify the high risk of first MI in Chinese hypertensive patients with OSA.Keywords: triglyceride glucose index-waist circumference, myocardial infarction, hypertension, obstructive sleep apnoea, cohort study

Ning Liu,1 Min Ye,2 Qinya Zhu,2 Dingchao Chen,3 Mingmin Xu,4 Jia He,5 Qian Li,4 Jie Li6 1Outpatient Department, Zhejiang Rongjun Hospital, Jiaxing, Zhejiang Province, 314000, People’s Republic of China; 2Nursing Department, Zhejiang Rongjun Hospital, Jiaxing, Zhejiang Province, 314000, People’s Republic of China; 3Medical Department, Zhejiang Rongjun Hospital, Jiaxing, Zhejiang Province, 314000, People’s Republic of China; 4Ultrasonic Department, Zhejiang Rongjun Hospital, Jiaxing, Zhejiang Province, 314000, People’s Republic of China; 5Department of Urology, Zhejiang Rongjun Hospital, Jiaxing, Zhejiang Province, 314000, People’s Republic of China; 6The Health Administration Center, Zhejiang Rongjun Hospital, Jiaxing, Zhejiang Province, 314000, People’s Republic of ChinaCorrespondence: Jie Li, The Health Administration Center, Zhejiang Rongjun Hospital, Jiaxing, Zhejiang Province, 314000, People’s Republic of China, Email 65017341@qq.comBackground: Coronavirus disease 2019 (COVID-19) has developed into a worldwide pandemic, which presents several challenges for frontline health-care workers (HCWs). HCWs are highly prone to various skin diseases due to prolonged use of personal protective equipment (PPE). The most frequently used type of PPE is facemasks. To effectively control adverse skin reactions, there is an urgent need for a range of preventive practices.Methods: This cross-sectional study was conducted at 12 hospitals in Zhejiang province, China. HCWs were invited to participate in the web survey. Data were extracted by two independent reviewers using a predesigned data collection form and analyzed with SPSS 20.0.Results: A total of 1147 questionnaires were collected, and of these, 1090 (95.03%) were valid and returned. The incidence of chest tightness and shortness of breath and face eczema was significantly higher in HCWs wearing N95 facemasks (41.91%; 31.62%) than in the HCWs wearing medical facemasks (38.05%, P = 0.010; 21.91%, P = 0.012). The incidence of ear pain and indentation was significantly higher in HCWs wearing hang-facemasks (83.81%) than in HCWs wearing strains-facemasks (61.19%, P < 0.001). The incidence of ear pain and indentation was significantly higher in HCWs wearing undiscriminating size code facemasks (79.88%) than in the HCWs wearing discriminating size code facemasks (67.86%, P = 0.031). There was a significant reduction (P < 0.001) in the incidence of HCWs without adverse reactions (ADRs) with increasing time wearing facemasks.Conclusion: Incidence of ADRs does not significantly increase with the durations of mask wear where wearing mask time exceeded 4 hours per day. The medical staff generally wore masks for more than 4 hours per day; therefore, we recommend taking 15 min of rest after 2 hours of mask-wearing. Results in this study support the conclusion that the type of strain-facemasks and discriminating size code facemasks has a lower incidence of ADRs than other type of medical facemasks.Keywords: facemask, health care, COVID-19, coronavirus, dermatitis, skin care, protective equipment

Kaixuan Li,1 Meihong Yu,2,3 Haozhen Li,1 Quan Zhu,1 Ziqiang Wu,1 Zhao Wang,1,4 Zhengyan Tang1,5 1Department of Urology, Xiangya Hospital of Central South University, Changsha, 410008, People’s Republic of China; 2Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Research Center of Digestive Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 4National Clinical Research Center for Geriatric Disorders, Changsha, 410008, People’s Republic of China; 5Provincial Laboratory for Diagnosis and Treatment of Genitourinary System Disease, Changsha, 410000, People’s Republic of ChinaCorrespondence: Zhao Wang, Department of Urology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, People’s Republic of China, Tel +86-15116358241, Email xywangz07@163.com Meihong Yu, Department of Gastroenterology, The Second Xiangya Hospital of Central South University, No. 139 Middle Renmin Road, Changsha, Hunan, 410011, People’s Republic of China, Tel +86-15243646849, Fax +86-731-85533525, Email 2204130510@csu.edu.cnPurpose: Venous thromboembolism (VTE) comprises deep venous thrombosis (DVT) and pulmonary embolism (PE), which can lead to death. VTE is an insidious disease with no specific symptoms and overlooked readily. We aimed to establish prediction models for VTE in non-oncological urological inpatients to aid urologists to better identify VTE patients.Patients and Methods: A retrospective analysis of 1453 inpatients was carried out. The risk factors for VTE had been clarified in our previous study. A stepwise regression method was used to screen the relevant influencing factors for VTE and construct a logistic regression prediction model to predict VTE. To validate the accuracy of the model, data from 291 patients from another cohort were used for external validation.Results: A total of 1453 inpatients were enrolled. Five potential risk factors (previous VTE; treatment with anticoagulants or anti-platelet agents before hospital admission; D-dimer ≥ 0.89 μg/mL; lower-extremity swelling; chest symptoms) were selected by multivariable analysis with p < 0.05. These five risk factors were used to build a logistic regression prediction model. When p < 0.1 in the multivariable logistic regression model, two additional risk factors were added: Caprini score ≥ 5 and complications, and all seven risk factors were used to build another prediction model. Internal verification showed the cutoff values, sensitivity, and specificity of the two models to be 0.02474, 0.941, 0.816 (model 1) and 0.03824, 0.941, and 0.820 (model 2), respectively. Both models had good predictive ability, but prediction accuracy was 43.0% for both when using the data of the additional 291 inpatients in the two models.Conclusion: Two novel prediction models were built to predict VTE in non-oncological urological inpatients. This is a new method for VTE screening, and internal validation showed a good performance. External validation results were suboptimal but may provide clues for subsequent VTE screening.Keywords: non-oncological surgery, prediction model, urology, venous thromboembolism

Xintian Cai,1,2 Nanfang Li,1 Junli Hu,1 Wen Wen,1,2 Xiaoguang Yao,1 Qing Zhu,1,2 Mulalibieke Heizhati,1 Jing Hong,1 Le Sun,1 Guzailinuer Tuerxun,1 Delian Zhang,1 Qin Luo1 1Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, Urumqi, Xinjiang, People’s Republic of China; 2Graduate School, Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of ChinaCorrespondence: Nanfang LiHypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, Urumqi, Xinjiang, People’s Republic of China, Email lnanfang2016@sina.comPurpose: We aimed to investigate the relationship between the Chinese visceral adiposity index (CVAI) and the risk of new-onset myocardial infarction (MI) in patients with hypertension and obstructive sleep apnoea (OSA) and to inspect possible modifiers of the effect.Methods: The Cox regression model was used to evaluate the relationship between baseline CVAI and risk of new-onset MI. A generalized additive model was used to identify the nonlinear relationship. Besides, we conducted subgroup analyses and interaction tests.Results: A total of 2177 patients with hypertension and OSA undergoing polysomnography were enrolled in this study. During a median follow-up period of 87 months, 82 participants developed new-onset MI. Overall, CVAI was positively related to the risk of new-onset MI (per 1 SD increase; HR = 1.54, 95% CI: 1.28– 1.85). In multivariable-adjusted models, the risk of new-onset MI increased with quartiles of CVAI, with an HR of 3.64 (95% CI: 1.94– 6.83) for quartile 4 compared with quartile 1. The generalized additive model and smoothed curve fit revealed a nonlinear relationship between CVAI and risk of new-onset MI with an inflection point of approximately 112. None of the stratification variables had a significant effect on the relationship between CVAI and new-onset MI. Similar outcomes were observed in the sensitivity analysis. The addition of CVAI significantly improved reclassification and discrimination over the conventional model, with a category-free NRI of 0.132 (95% CI 0.021 to 0.236, P = 0.021) and an IDI of 0.012 (95% CI 0.005 to 0.023, P < 0.001).Conclusion: This study demonstrated a nonlinear relationship between CVAI and the risk of new-onset MI in patients with hypertension and OSA. Higher CVAI was significantly associated with the risk of new-onset MI when CVAI was ≥ 112.Keywords: Chinese visceral adiposity index, myocardial infarction, hypertension, obstructive sleep apnoea, cohort study

Guoying Zou,1 Qing Zhu,1 Biqiong Ren,1 Qi Guo,1 Yuanyuan Wu,1 Junyu He,1 Ying Wu,1 Zhihong Luo2 1Department of Clinical Laboratory, The Second People’s Hospital of Hunan Province, Changsha, Hunan, 410007, People’s Republic of China; 2Office of the Party Committee, The Second People’s Hospital of Hunan Province, Changsha, Hunan, 410007, People’s Republic of ChinaCorrespondence: Zhihong Luo, Office of the Party Committee, The Second People’s Hospital of Hunan Province, Furong Middle Road 427, Yuhua District, Changsha, Hunan, 410007, People’s Republic of China, Tel +86 19848029533, Email lzh3068@sina.comPurpose: To determine the levels of serum HDL-associated apolipoproteins (apoM and apoC) and HDL-binding receptor (scavenger receptor BI, SR-BI) in patients with gram-negative bacteria sepsis (G-sepsis) and to evaluate the value of lipoproteins in the diagnosis, severity and prognosis of G-sepsis.Patients and Methods: A total of 128 patients with sepsis, 40 patients with system inflammatory reaction syndrome (SIRS) and 40 healthy subjects were enrolled in the Second People’s Hospital of Hunan Province from September 2019 to September 2020. The levels and the correlation of lipoproteins were detected and dynamically monitored by enzyme-linked adsorption method, ROC curve for the diagnostic, severity and prognostic value of lipoproteins in G-sepsis.Results: The levels of serum HDL-associated lipoproteins in patients with G-sepsis were significantly decreased (P < 0.05), and the ROC curve showed that HDL-C, SR-BI, apoM and apoC had cut-off values of 0.915 mmol/L, 122.100 pg/mL, 102.400 ug/mL and 17.55 mg/mL, respectively, for the diagnosis of G-sepsis, with the sensitivity was 85.56%, 97.78%, 93.33% and 73.03%, and the specificity was 95.0%, 82.50%, 61.54% and 82.50%, respectively. There was a correlation between HDL-associated apolipoproteins. Changes in serum HDL-associated lipoproteins were more obvious in shock group than classic inflammation indicators, such as PCT, IL-6 and CRP. They showed a trend change on day 3, with the levels of SR-BI and apoC changing 2– 3 times, and the sensitivity of HDL-C, SR-BI, apoM and apoC for the diagnosis of G-septic shock were 32.43%, 72.97%, 65.75%, and 43.24%, and specificity of 94.34%, 81.13%, 83.07%, and 86.79%, respectively. The AUC, sensitivity and specificity of apoM combined with SR-BI were improved.Conclusion: HDL-associated lipoproteins were correlated with bacterial-infected types, and serum levels of HDL-associated lipoproteins can be used as potential biomarkers for early diagnosis and progress of G-sepsis. ApoM combined with SR-BI could improve the sensitivity and specificity of prognosis assessment.Keywords: apolipoprotein, high-density lipoprotein, gram-negative sepsis, biomarker, prognosis

Chenglong Sun,1 Wenhao Zheng,2 Qiang Zhu,1 Quan Du,1 Wenhua Yu1,3 1Department of Neurosurgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Neurosurgery, Hangzhou Ninth People’s Hospital, Hangzhou, People’s Republic of ChinaCorrespondence: Wenhua YuDepartment of Neurosurgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, No. 261, Huansha Road, Hangzhou, People’s Republic of ChinaEmail ywhsyyy@163.comBackground: The pear shape of an inflated balloon is thought to be a gold standard of successful percutaneous balloon compression (PBC). However, neither how nor why it changes in that way (the anatomic basis) has not yet been fully described.Aim: In this article, we try to describe how the balloon in Meckel’s cave (MC) should appear and why; and identify which shapes are good pear shapes, which shapes are not good pear shapes, and which shapes are intermediate.Methods: Radiographs from over 150 percutaneous balloon compression (PBC) cases were thoroughly evaluated. We proposed a model of changing balloon shape in MC and 70 cases were followed up over two years, in which therapeutic effect was measured.Results: We found that the balloon changed stereotypically in MC. The model that we proposed is consistent with the description of MC’s structures and its’ surroundings in the literature. The distinct pear (pear in MC) brought about a far better surgical result than other shapes (p < 0.01).Conclusion: Our study showed how and why the balloon shape changed during PBC surgery. The model provides clear guidance for PBC surgery.Keywords: percutaneous balloon compression, balloon shape transformation, trigeminal neuralgia, Meckel’s cave

Cong Zhang,1,2,&ast; Qingna Yan,1,&ast; Qiushuang Zhu,1,&ast; Jinxiao Liu,1,&ast; Yuanjie Dong,1 Yuqiao Li,1 Ruohua Wang,1 Xuanfeng Tang,1 Xinyi Lv,1 Xiaoqing Li,1 Yunjiang Cai,3 Yucun Niu1 1Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, 150086, People’s Republic of China; 2Center of Disease Control and Prevention of Xishan District, Wuxi, 214000, People’s Republic of China; 3Nursing College of Daqing Campus of Harbin Medical University, Daqing, 163319, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yucun NiuDepartment of Nutrition and Food Hygiene, College of Public Health, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, 150081, People’s Republic of ChinaTel +86-451-8750-2730Fax +86-451-8750-2885Email niuyucun@163.comPurpose: How to prolong life by diet has been widely concerned. There are many reports about the effects of different dietary patterns on life span, but the results are not consistent. The main reason may be that total energy intake has not been considered. This study aims to explore the effects of isocaloric different dietary patterns on population life span.Materials and Methods: From the data of the follow-up population, eligible participators were divided into normal control (NC) group (28.31% fat, 12.37% protein, 62.30% carbohydrate), isocaloric high-fat (IHF) group (38.39% fat, 12.21% protein, 51.32% carbohydrate), isocaloric high-protein (IHP) group (33.41% fat, 17.10% protein, 52.67% carbohydrate) and isocaloric high-carbohydrate (IHC) group (22.23% fat, 10.52% protein, 70.13% carbohydrate) according to the dietary structure and the age stratification. Global serum metabolic profiling analysis by UPLC−Q-TOF-MS/MS technology, fatty acid and amino acid profiles in serum were determined by GC-MS and UPLC-TQ-MS technology. One-way ANOVA followed by Dunnett post hoc test and receiver operating characteristic (ROC) curve analysis were used to statistical analysis.Results: Non-targeted metabolomics was to identify 18 potential metabolites related to longevity. ROC curve analysis to identify biomarkers indicated that the areas under the ROC (AUC) of the 12 of 18 biomarkers are above 0.9. The 12 biomarkers were mainly enriched in three metabolic pathways: lipid metabolism, amino acid metabolism and tricarboxylic acid cycle. Compared to control, 11 and 10 of 12 biomarkers showed the same trend with aging in IHP and IHC groups, respectively. Conversely, no differences were observed between IHF group and NC group.Conclusion: Without consideration of the nature of carbohydrates, fats and proteins, IHP and IHC diets might shorten life span by influencing amino acid metabolism, lipid metabolism and tricarboxylic acid cycle metabolism, while the isocaloric IHF diet has no effects on longevity.Keywords: amino acid, fatty acid, biomarkers, metabolomics

Xin-Tian Cai,1,2,&ast; Qing Zhu,1,2,&ast; Sha-Sha Liu,2 Meng-Ru Wang,2 Ting Wu,2 Jing Hong,2 Jun-Li Hu,2 Nanfang Li1,2 1Graduate School, Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang LiGraduate School, Xinjiang Medical University; Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, Urumqi, Xinjiang, People’s Republic of ChinaEmail lnanfang2016@sina.comPurpose: The metabolic score for insulin resistance (METS-IR) index is an emerging surrogate predictor of type 2 diabetes mellitus (T2DM). This study aimed to evaluate the association between the METS-IR index and the risk of T2DM in non-obese Japanese adults.Methods: A total of 12,290 non-obese participants were selected from the NAGALA prospective cohort study conducted from 2004 to 2015. Cox proportional hazards models were used to assess the association between the baseline METS-IR index and risk of T2DM. Generalized additive models were used to identify nonlinear relationships. In addition, we performed subgroup analyses and interaction tests. Results were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs).Results: During a median follow-up of 2050 days, 176 (1.43%) incident T2DM occurred. The fully adjusted HR (95% CI) for the incidence of T2DM in non-obese adults was 1.17 (HR=1.17, 95% CI: 1.09– 1.27, P< 0.001) for every 1-unit increase in the METS-IR index. The risk of developing T2DM increased with the quartile of change in the METS-IR index, after adjustment for multiple potential confounding, the HRs for the Q4 group versus the Q1 group was 4.01 (95% CI, 1.39– 11.57). Generalized additive models also showed a cumulative increase in the risk of T2DM with increasing the METS-IR index. Time-dependent receiver operating curve suggested helpful discriminative power of the METS-IR index for T2DM. The C-statistics by the clinical risk factors significantly improve with the addition of the METS-IR index (from 0.862 to 0.875, P = 0.035); the discriminatory power and risk reclassification also appeared to be substantially better, with the category-free NRI of 0.216, and the IDI of 0.011.Conclusion: The METS-IR index was a significant and independent predictor for future T2DM development in non-obese adults. The METS-IR index may have clinical significance in identifying groups at high risk of T2DM.Keywords: metabolic score for insulin resistance index, type 2 diabetes mellitus, non-obese, population-based cohort study

Yuanli Huang,1,2 Guanghui Zhang,1,2 Qing Zhu,1 Xia Wu,3 Ligao Wu1 1Department of Pathology, the First Affiliated Hospital of Bengbu Medical College, Bengbu City, Anhui Province, People’s Republic of China; 2Graduate School of Bengbu Medical College, Bengbu City, Anhui Province, People’s Republic of China; 3Department of Pathology, Fuyang Tumor Hospital, Fuyang City, Anhui Province, People’s Republic of ChinaCorrespondence: Ligao Wu Tel +86 15395225588Email wlgahbb@126.comPurpose: Pyroptosis is a recently discovered highly inflammatory form of programmed cell death, during which the N-terminus of the cleaved Gasdermin protein family forms pores in the cell membrane, leading to cell disintegration and the release of certain intracellular factors, including caspase3, gasdermin E (GSDME), and high mobility group proteins (HMGB1), which trigger a series of secondary inflammatory reactions. Specifically, caspase3 can lyse GSDME and induce pyrolysis, while HMGB1 is released passively after cell membrane destruction. In this study, the roles of these proteins in lung cancer tissues as well as their clinical significance were investigated.Patients and Methods: The expression levels of GSDME, caspase3, and HMGB1 proteins in lung cancer and paracancerous tissues were determined via immunohistochemical staining, and their relationship with the clinical stage, pathological grade, and survival prognosis of the patients was analyzed. Further, CD8+ T cell accumulation in the above-mentioned tissues was also determined, and differences between them with respect to CD8+T cell distribution were also investigated. Furthermore, the relationships between CD8+ T cell abundance and the expression levels of the above-mentioned proteins were determined via statistical analyses.Results: Lung cancer and paracancerous tissues showed significantly different GSDME, caspase3, and HMGB1 protein expression levels. GSDME expression level and the presence or absence of lymph node invasion were identified as prognostic indicators of survival in patients with lung cancer. Surprisingly, however, HMGB1, which showed a certain level of correlation with the presence or absence of lymph node metastasis, could not be used as a prognostic indicator of survival.Conclusion: GSDME may be an important prognostic indicator of survival in patients with lung cancer. However, the effects of HMGB1 expression level and CD8+ T cell abundance on the prognosis of patients with lung cancer still need further investigation.Keywords: cell pyroptosis, caspase3, GSDME, HMGB1, lung cancer, CD8+T

Jianfei Pan,1,* Quanwei Zhu,1,* Xiaoqian Zhang,2 Jun Xu,1 Linlin Pan,1 Xiang Mao,3 Xiao Wu1,4,* 1Department of Emergency, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 3Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 4Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiang MaoDepartment of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of ChinaTel +86 65908477Email xiangmao1002@163.comPurpose: To explore the distribution of pathogenic bacteria in patients with intra-abdominal infection, to clarify the independent factors that affect the prognosis of patients with intra-abdominal infection and its evaluation value for prognosis.Patients and Methods: The pathogens, underlying diseases, and related clinical data of patients with intra-abdominal infection from January 2012 to December 2019 in our hospital were retrospectively collected and the APACHE II score was calculated. The patients were divided into survival group and death group according to the prognosis, and the index between the two groups was compared. Spearman correlation analysis was used to evaluate the correlation between each index and prognosis, multivariate logistic regression analysis was used to screen the independent prognostic factors.Results: Spearman correlation analysis showed that ALB level was negatively correlated with prognosis, age and APACHE II score were positively correlated with prognosis. Logistic regression analysis showed that age, ALB level, and APACHE II score were independent prognostic factors. The formula of age combined ALB level and APACHE II score was Y = X1-3.6X2 + 6.5X3 (X1 was the age, X2 was the ALB level and X3 was the APACHE II score), Y was positively correlated with poor prognosis, and the optimal cutoff value was Y = 40.96.Conclusion: Age, ALB level, and APACHE II score are independent factors that influencing the prognosis of patients with intra-abdominal infection, and the combination of age, ALB level, and APACHE II score can better assess the prognosis of patients with intra-abdominal infection.Keywords: intra-abdominal infection, formula, prognostic factors, the value of independent factors, single center

Yue Qiu,1,&ast; Daojiong Lin,2,&ast; Yi Xu,3,&ast; Yibing Cheng,4 Fang Wang,5 Qingxiong Zhu,6 Chunhui Zhu,6 Chaomin Wan,7 Yu Zhu,7 Jianning Tong,8 Rui Li,8 Qionghua Zhou,2 Minxia Chen,3 Qingwen Shan,9 Zhiqiang Zhuo,10 Caihong Wang,10 Shiyong Zhao,11 Wen Song,11 Mei Zeng1 1Department of Infectious Diseases, Children’s Hospital of Fudan University, ShangHai, People’s Republic of China; 2Department of Infectious Diseases, Hainan Women and Children’s Medical Center, Haikou, People’s Republic of China; 3Department of Infections Disease, Guangzhou Women and Children’s Medical Center, Guangzhou, People’s Republic of China; 4Department of Emergency, Children’s Hospital Affiliated to Zhengzhou University (Henan Children’s Hospital), Zhengzhou, People’s Republic of China; 5Department of Infections Disease, Children’s Hospital Affiliated to Zhengzhou University (Henan Children’s Hospital), Zhengzhou, People’s Republic of China; 6Department of Infection Diseases, Children’s hospital of Jiangxi Province, Nanchang, People’s Republic of China; 7Department of Pediatrics, West China Second Hospital, Sichuan University, Chengdu, People’s Republic of China; 8Department of Pediatric, Gastroenterology and Infectious Diseases, Qingdao Women and Children’s Hospital, Qingdao, People’s Republic of China; 9Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 10Department of Infectious Diseases, Xiamen Children’s Hospital, Xiamen, People’s Republic of China; 11Department of Infectious Diseases, Hangzhou Children’s Hospital, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei ZengDepartment of Infectious Diseases, Children’s Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, People’s Republic of ChinaTel +86-21-64931132Email zengmeigao@aliyun.comObjective: To assess clinical characteristics, outcomes and antimicrobial resistance of invasive Klebsiella pneumoniae (KP) infections in Chinese pediatric patients in hospital and community settings.Methods: This retrospective study was conducted in the nine tertiary hospitals during 2016– 2018. The 324 pediatric inpatients who had KP isolated from blood and cerebrospinal fluid and had complete medical records reviewed were included. We analyzed the risk factors, outcomes and antimicrobial resistance pattern of KP-infected patients based on comparison between healthcare-associated KP infections (HAI) and community-acquired infections.Results: Of the 324 enrolled patients, 275 (84.9%) were clinically defined as HAI, including 175 (63.6%) neonates and 100 (36.4%) aged > 28 days. The overall prevalence of CRKP was 38.2% (43.4% in HAI verse 8.7% in CAI, P < 0.05). Prematurity (odds ratio (OR): 37.07, 95% CI: 8.29– 165.84), hematologic malignancies (OR: 15.52, 95% CI: 1.89– 127.14) and invasive mechanical ventilation (OR: 13.09, 95% CI: 1.66– 103.56) were independent risk factors for HAI. Patients from rural area (OR: 1.94, 95% CI: 1.12– 3.35), invasive mechanical ventilation (OR: 2.33, 95% CI: 1.25– 4.33), antibiotic therapy prior to admission (OR: 2.33, 95% CI: 1.25– 4.33) and prior hospital stay in the past 30 days (OR: 3.46, 95% CI: 1.87– 6.41) were associated with healthcare-associated CRKP infections. Organ dysfunction was independently correlated with poor outcomes (OR: 2.92, 95% CI: 1.23– 6.95).Conclusion: Pediatric invasive KP infections and high prevalence of CRKP infections largely occurred in healthcare settings in China. The adequate and intensified infection control measures should be focused on high-risk hematologic patients, neonatal patients and intubated patients.Keywords: Klebsiella pneumoniae, healthcare-associated infections, children

Xinning Wang,1 Qiang Zu,1 Jinshan Lu,1 Lei Zhang,1 Qiang Zhu,1 Xuefeng Sun,2 Jun Dong1 1Department of Urology, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Nephrology, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xuefeng Sun; Jun Dong Email xfssun@126.com; jundong@vip.126.comIntroduction: Our previous study revealed that a young internal environment ameliorated kidney aging by virtue of an animal model of heterochronic parabiosis and a model of heterochronic renal transplantation. In this research, we used proteome to investigate the effects of donor-recipient age difference in clinical renal transplantation.Methods: This study included 10 pairs of renal transplantation donors and recipients with an age difference of greater than 20 years to their corresponding recipients/donors. All recipients have received transplantation more than 3 years ago. Renal function and the serum/urine proteomes of the donors and recipients were analyzed.Results: The renal function was similar between the young recipients and the old donors. In contrast, the renal function of the young donors was significantly superior to that of the old recipients. Furthermore, 497 and 975 proteins were identified in the serum and urine proteomes, respectively. The content of SLC3A2 in the blood was found to be related to aging, while the contents of SERPINA1 and SERPINA3 in the urine were related to immune functions after renal transplantation.Conclusion: This study demonstrated that, in the human body, a younger internal environment could ameliorate kidney aging and provided not only clinical evidence for increasing the age limit of kidney transplant donors but also new information for kidney aging research.Keywords: renal transplantation, aging, proteome, living donor transplantation

Honglei Zhao,1 Hongyan Wu,2 Meitao Duan,2 Ruixuan Liu,2 Quanhong Zhu,1 Kai Zhang,2 Lili Wang1 1Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, People’s Republic of China; 2Research Center for Biomedical Information Technology, Shenzhen Institutes of Advanced Technologies, Chinese Academy of Sciences, Shenzhen, People’s Republic of ChinaCorrespondence: Kai ZhangResearch Center for Biomedical Information Technology, Shenzhen Institutes of Advanced Technologies, Chinese Academy of Sciences, Shenzhen, People’s Republic of ChinaTel +86-13076878540Email kai.zhang@siat.ac.cnLili WangFuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, People’s Republic of ChinaEmail 1248532808@qq.comPurpose: The aim of the present study was to examine the protective effects of cinnamaldehyde (CA) on type 1 diabetes mellitus (T1DM) and explore the underlying molecular mechanisms by using multiple omics technology.Methods: T1DM was induced by streptozotocin in the mice. Immunostaining was performed to evaluate glycogen synthesis in the liver and morphological changes in the heart. Gut microbiota was analyzed using 16S rRNA gene amplification sequencing. The serum metabolomics were determined by liquid chromatography–mass spectrometry. The relevant gene expression levels were determined by quantitative real-time PCR.Results: CA treatment significantly improved the glucose metabolism and insulin sensitivity in T1DM mice. CA increased glycogen synthesis in the liver and protected myocardial injury in T1DM mice. CA affected the gut microbiota particularly by increasing the relative abundance of Lactobacillus johnsonii and decreasing the relative abundance of Lactobacillus murinus in T1DM mice. The glucose level was positively correlated with 88 functional pathways of gut microbiota and negatively correlated with 2 functional pathways of gut microbiota. Insulin resistance was positively correlated with 11 functional pathways. The analysis of serum metabolomics showed that CA treatment significantly increased the levels of taurochenodeoxycholic acid, tauroursodeoxycholic acid, tauro-α-muricholic acid and tauro-β-muricholic acid, taurodeoxycholic acid, taurocholic acid and taurohyodeoxycholic acid in T1DM mice. Taurohyodeoxycholic acid level was highly correlated with the blood glucose levels. Furthermore, the abundance of Faecalibacterium prausnitzii was positively correlated with AKT2, insulin like growth factor 1 receptor, E2F1 and insulin receptor substrate 1 mRNA expression levels, while taurohyodeoxycholic acid level was negatively correlated with IRS1 mRNA expression level.Conclusion: Our results indicated that CA may interfere with gut microbiota to affect host metabolomics, especially the bile acids, so as to directly or indirectly modulate the expression levels of glucose metabolism-related genes, thus subsequently reducing the blood glucose level in the T1DM mice.Keywords: cinnamaldehyde, type 1 diabetes, glucose, insulin, gut microbiota, serum metabolomics

Xin Tian, Qiuxia Zhu, Zhenyong Zhang Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110022, People’s Republic of ChinaCorrespondence: Zhenyong ZhangDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110022, People’s Republic of ChinaEmail zhangzhenyongvip@163.comAbstract: Synchronous occurrences of gastric cancer positive for human epidermal growth factor receptor 2 (HER2+) and bladder cancer are rarely encountered in clinical practice. When and how to effectively treat both tumors, without compounding adverse effects, must be addressed. Herein, we describe an elderly man who presented with both gastric cancer (HER2+) and bladder cancer. Due to enlarged and fused lymph nodal metastasis, he was ill-suited for stomach resection. After transurethral resection of the bladder tumor, we administered both chemotherapy and the targeted agent trastuzumab. Gastric cancer showed partial response however bladder cancer recurred following two cycles of this regimen, the adverse effects were prohibitive, prompting refusal of further chemotherapy and radiotherapy. He then received the immune checkpoint inhibitor (ICI) nivolumab and trastuzumab in combination. This particular regimen successfully controlled both cancers and substantially improved the patient’s quality of life. Its long-term use did not intensify adverse reactions, enabling a progression-free survival of 21 months to date. We have also reviewed other published clinical strategies applied in rare instances of multiple primary malignancies as a reference for treating such patients.Keywords: immunotherapy, targeted therapy, synchronous cancer, HER2-positive gastric cancer, bladder cancer

Fu He,1,2 Kangjian Song,1,2 Ge Guan,3 Junyu Huo,1,2 Yang Xin,1 Tianxiang Li,3 Chao Liu,1 Qingwei Zhu,1,2 Ning Fan,1 Yuan Guo,1 Liqun Wu1 1Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, People’s Republic of China; 2Department of Clinical Medicine, Qingdao University, Qingdao, 266071, Shandong, People’s Republic of China; 3Organ Transplant Center, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, People’s Republic of ChinaCorrespondence: Liqun WuLiver Disease Center, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, 266003, Shandong Province, People’s Republic of ChinaTel +86 18661809789Email wulq5810@126.comPurpose: Gene rearrangements (GRs) have been reported to be related to adverse prognosis in some tumours, but the relationship in hepatocellular carcinoma (HCC) remains less studied. The objective of our study was to explore the clinicopathological characteristics and prognosis of HCC patients (HCCs) with GRs (GR-HCCs).Patients and Methods: This retrospective study included 297 HCCs who underwent hepatectomy and had their tumours sequenced by next-generation sequencing. Categorical variables between groups were compared by the chi-square test. The impact of variables on disease-free survival (DFS) and survival after relapse (SAR) was analysed by the Kaplan–Meier method and Cox regression.Results: We observed four repetitive GR events in 297 HCCs: BRD9/TERT, ARID2/intergenic, CDKN2A/intergenic and OBSCN truncation. GR-HCCs frequently presented with low tumour differentiation, tumour necrosis, microvascular invasion, elevated AFP and gene mutations (TP53, NTRK3 and BRD9). The 1-, 2-, and 3-year cumulative DFS rates in GR-HCCs were 45.1%, 31.9%, 31.9%, respectively, which were significantly lower than those of GR-negative HCCs (NGR-HCCs) (72.5%, 57.9%, and 49.0%, respectively; P = 0.001). GR was identified as an independent risk factor for inferior DFS in HCCs (HR = 1.980, 95% CI = 1.246– 3.147; P = 0.004). However, there was no significant difference in SAR between GR-HCCs and NGR-HCCs receiving targeted therapy or immunotherapy.Conclusion: GR is frequently associated with TP53 mutations and significantly affects DFS following radical resection for HCC. We recommend that GR-HCCs should be closely followed up as a high-risk group for postoperative recurrence.Keywords: hepatocellular carcinoma, gene rearrangement, next-generation sequencing, prognosis, risk factors