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Yu-Yan Qin,1,* Hui Yu,1,2,* Yong Huang,1,* Xiaoyi Yang,1 Songpei Li,1 Ao Shen,1 Yinshan Lin,1 Mei Zhang,1 Qiulian Zhu,1 Jingwei Zhang,1 Lingmin Zhang,1 Xi-Yong Yu1 1Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China; 2Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Co., Ltd, Guangzhou, Guangdong, 510515, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xi-Yong Yu; Lingmin Zhang, School of Pharmaceutical Sciences, Guangzhou Medical University, Xinzao Road, Panyu District, Guangzhou, 511436, People’s Republic of China, Email yuxycn@gzhmu.edu.cn; zhanglm@gzhmu.edu.cnBackground: Acute lung injury (ALI) leads to diffuse pulmonary interstitial and alveolar edema, further developing into acute respiratory distress syndrome (ARDS). The present therapeutic approaches showed limited effects with poor clinical efficacy or severe side effects. This study aims to develop novel pharmaceutical agents to reduce lung damage with acceptable side effects for ALI.Methods: Naked gene delivery system based on epigallocatechin 3-gallate (EGCG) was synthesized to deliver plasmid expressing DNA damage regulated autophagy modulator 1 (DRAM1), designated as EGCG/DRAM1 (ED). ED was characterized by dynamic light scattering analysis and transmission electron microscope. The biodistribution of ED in mice was measured by an in vivo small animal imaging system. The therapeutic potentials of ED were evaluated in MLE12 cells and LPS-induced ALI mice.Results: Our results showed that ED was nearly spherical with a diameter of ~100 nm and increased the stability of DRAM1 plasmid that encapsulated. The synthesized ED showed negligible toxicity at the selected experimental concentration in MLE12 cells. ED could be taken up by MLE12 cells with high efficiency and escape from the lysosome. In ALI mice, ED facilitated the accumulation and retention of DRAM1 plasmid in lung, and attenuated pulmonary edema and pulmonary vascular permeability. The therapeutic effects of ED on ALI were associated with increased autophagy and reduced oxidative stress in lung.Conclusion: In summary, ED attenuated pulmonary edema and pulmonary vascular permeability, and improved pulmonary dysfunction in ALI mice. This naked gene delivery system for autophagy enhancement may serve as a potential therapeutic strategy to attenuate ALI. Keywords: acute lung injury, EGCG, DRAM1, autophagy, oxidative stress

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

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

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

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

Zhan T, Zhu Q, Han Z, et al. Cancer Manag Res. 2020;12:1483–1492. The authors have advised Figure 4C on page 1490 is incorrect. Due to an error at the time of figure assembly Figure 4D and Figure 4C were inadvertently duplicated. The correct Figure 4 is shown below. Figure 4 miR-455-3p restrains Wnt/β-catenin signaling via TAZ. (A and B) Expression of β-catenin, Cyclin D and C-myc in pancreatic cancer cells transfected with miR-455-3p mimic or miR-455-3p mimic plus TAZ expression vector was detected by qPCR. (C and D) Western blot analysis of β-catenin, Cyclin D and C-myc in PANC1 and MIAPaCa2 cells transfected with miR-455-3p mimic or miR-455-3p mimic plus TAZ expression vector β-actin is used as loading control vs miR-455-3p mimics/mimic control group, miR-455-3p mimics/miR-455-3p mimics+TAZ group. *p

Chao Lu,1– 3 Weiwei Jin,1,2 Yiping Mou,1,2 Hongliang Shao,4 Xiaosan Wu,4 Shaodong Li,5 Biwu Xu,4 Yuanyu Wang,1,2 Qicong Zhu,1,2 Tao Xia,1,2 Yucheng Zhou1– 3 1Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang Province, People’s Republic of China; 2Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, Zhejiang Province, People’s Republic of China; 3School of Medicine, Soochow University, Suzhou, Jiangsu Province, People’s Republic of China; 4School of Medicine, Bengbu Medical College, Bengbu, Anhui Province, People’s Republic of China; 5School of Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Yucheng Zhou; Yiping MouDepartment of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang Province, People’s Republic of ChinaEmail drzhouyc@163.com; yipingmou@126.comBackground: Gastrointestinal stromal tumors (GIST) of the duodenum are rarely reported and optimal minimally invasive management has not been well proposed. Pancreaticoduodenectomy and different types of pancreas-sparing duodenectomy can be chosen; however, which to choose and its corresponding clinical outcomes and oncological concerns remain controversial.Patients and Methods: Patients diagnosed with GIST of duodenum underwent laparoscopic pancreaticoduodenectomy (L-PD) or pancreas-sparing duodenectomy (L-PSD) in Zhejiang Provincial People’s Hospital were enrolled. All prospectively maintained data were analyzed retrospectively. Patients were grouped into the L-PD group or the L-PSD group, and the clinical outcomes and oncological outcomes were analyzed.Results: Between June 2013 and March 2019, a total of 22 patients (11 males/11 females) underwent surgical management, including 13 L-PDs and 9 L-PSDs. The average age was 58.2± 9.5 year-old (median 60.5 year-old). The most common presentations were GI bleeding (54.5%) and abdominal discomfort (27.2%), and the dominant lesion located in the second portion of duodenum (59.1%). Compared with L-PD group, L-PSD group showed much shorter operation time (364.2± 58.7min vs. 230.0± 12.3min, P< 0.001), less blood loss (176.9± 85.7mL vs. 61.1± 18.2min, P< 0.001), faster recovery to off-bed (2.6± 1.3d vs. 1.1± 0.3d, P=0.003), anus flatus (4.5± 1.0d vs. 2.4± 0.5d, P< 0.001) and liquid intake (4.9± 1.3d vs. 2.3± 0.5d, P< 0.001). Lymph node retrieval was much less in L-PSD, but no lymph node metastasis was observed in any patients. L-PSD had much Lower morbidity of both minor (Grade I/II) and major (III/IV/V) complications than that of L-PD (11.1% vs. 61.6%, P=0.02), resulting in shorter hospital stays (10.9± 3.8d vs. 20.6± 11.1d, P=0.021) and less total cost (76,972.4± 11,614.8yuan vs 125,628.7± 46,356.8yuan, P=0.006). The median follow-up was 42 months (range from 12 to 82months) without loss. Only 1 L-PD patient suffered hepatic metastasis 36months after surgery, and given sunitinib to stabilize the disease, none of the rest observed recurrence or metastasis.Conclusion: For GIST located opposite the major papilla, L-PSD showed comparable safety and oncological benefits when compared to L-PD, with shorter operation time, less blood loss and much faster recovery time, resulting in much less total cost. L-PSD should be applied in selected patients with experienced hands.Keywords: GIST, duodenum, pancreaticoduodenectomy, pancreas-sparing duodenectomy

Xiao Chen,1,2,* Qiaoyun Zhu,2,* Yanchao Liu,2 Ruonan Wang,2 Hongyi Xie,3 Jiayao Chen,4 Ying Cheng,5 Haiping Zhang,6 Lijun Cao,7 Yu Chen1,2 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Key Laboratory of Clinical in vitro Diagnostic Techniques of Zhejiang Province, Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Laboratory Medicine, Beilun People’s Hospital, Ningbo, Zhejiang, People’s Republic of China; 4Department of Laboratory Medicine, Zhoushan People’s Hospital, Zhoushan, Zhejiang, People’s Republic of China; 5Department of Laboratory Medicine, Quzhou People’s Hospital, Quzhou, Zhejiang, People’s Republic of China; 6Department of Laboratory Medicine, Yuhuan People’s Hospital, Yuhuan, Zhejiang, People’s Republic of China; 7Department of Laboratory Medicine, People’s Hospital of Zhenhai District, Ningbo, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu ChenState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of ChinaTel +86057187236383Email chenyuzy@zju.edu.cnObjective: Vibrio parahaemolyticus is a major diarrhoea-inducing pathogen in coastal areas. In this study, we analysed the pathogenic characteristics of and variation in V. parahaemolyticus isolated from acute diarrhoeal patients in seven hospitals in different areas of southeastern China from 2013 to 2017.Methods: The fecal specimens of patients with acute diarrhoea were collected. The routine microbiological test procedure combining with MALDI Biotyper microbial identification system was carried out to identify the V. parahaemolyticus. Serum agglutination tests, PCR for the detection of virulence-related genes and the Kirby-Bauer method to test for antimicrobial sensitivity were performed.Results: From 2013 to 2017 in southeastern China, a total of 1220 V. parahaemolyticus strains were isolated from 16,504 stool specimens collected from acute diarrhoeal patients, and the annual isolation rate fluctuated between 6.1% and 8.7%. In total, 96.7% of the V. parahaemolyticus isolates were isolated in summer and autumn, mainly in people aged 18– 44. Fifty-nine serotypes were identified, and the agglutination rate of the O antigen was 98.5%. From 2014 to 2016, the dominant serotype was O3:K6, while in 2013 and 2017, it was O4:KUT. The serotypes of O3:K6, O4:KUT, O4:K8, O3:KUT, O10:K60, O1:KUT and O1:K36 appeared every year from 2013 to 2017. O4:K6 and OUT:K6 began to appear after 2014 and 2015, respectively. A total of 49.5% of the strains belonged to the pandemic group, which consisted of 26 serotypes. Most isolates were sensitive to common antibiotics, excluding ampicillin.Conclusion: V. parahaemolyticus is still present at a high level in southeastern China. Although the pandemic O3:K6 serotype is predominant, new serotypes continue to emerge, especially the O4:KUT serotype, which exceeded O3:K6 in prevalence in some years. Long-term surveillance is necessary to prevent the outbreak or transmission of this pathogen.Keywords: Acute diarrhoea, Vibrio parahaemolyticus, serotypes, virulence genes, antimicrobial resistance

Kai Zhang,* Jiawei Li,* Qian Zhu, Cai Chang Department of Medical Ultrasound, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cai ChangFudan University Shanghai Cancer Center, No. 270, Dong’an Road, Shanghai, Xuhui District 200032, People’s Republic of ChinaTel +86 180 1731 2605Fax +86 21 6417 4774Email changc62@126.comPurpose: To compare the diagnostic performance for pathologic complete response (pCR) in breast cancer after neoadjuvant chemotherapy (NAC) between ultrasound (US) and magnetic resonance imaging (MRI).Patients and Methods: A total of 1,219 breast cancer patients with 1,232 tumors who accepted US and/or MRI examination after NAC and before breast surgery were included. The diagnostic performance of US, MRI, and US plus MRI in predicting pCR was compared.Results: The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of US for pCR were 36.2%, 90.2%, 71.0%, 67.3%, and 71.9%, respectively, while for MRI they were 44.4%, 92.9%, 75.6%, 77.7%, and 75.0%, respectively. The combination of US and MRI had increased specificity (98.0%) and PPV (86.8%), decreased sensitivity (22.5%) and NPV (68.8%), but similar accuracy (70.5%) in comparison with US or MRI alone. The prediction of pCR by imaging differed in different histological, molecular subtypes and primary tumor size.Conclusion: Neither US nor MRI could predict a pCR with sufficient accuracy. The combination of US and MRI could not predict a pCR reliably either. The explanation of imaging for pCR should take into account histological, molecular subtypes, and primary tumor size.Keywords: breast neoplasms, neoadjuvant therapy, pathologic complete response, ultrasonography, magnetic resonance imaging

Yuan Liu,1,2,* Jing-Jing Zhao,1,2,* Zi-Qi Zhou,1,2 Qiu-Zhong Pan,1,2 Qian Zhu,1,2 Yan Tang,1,2 Jian-Chuan Xia,1,2 De-Sheng Weng1,21State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workIntroduction: IL-37 is a cytokine of IL-1 family that plays an important role in innate immunity and inflammation, and has been studied as a tumor suppressor in many cancers. However, it remains unclear whether IL-37 plays a regulatory role in tumor-infiltrating dendritic cells (DCs) in hepatocellular carcinoma (HCC).Materials and methods: We evaluated the relationship between IL-37 expression and tumor infiltration by DCs in 155 HCC samples through immunohistochemical analysis and Kaplan–Meier survival analysis. The effects of IL-37 on the anti-tumor activity of DCs were investigated by ELISA, flow cytometry, real-time quantitative PCR, cytotoxicity assays and tumorigenicity assays.Results: The expression level of IL-37 in HCC samples was positively correlated with the degree of CD1a+ DCs infiltration. The survival rates of patients with both a high expression of IL-37 and a high infiltration by CD1a+ DCs were significantly higher than those of patients with a low expression of IL-37 and a low infiltration by CD1a+ DCs. In vitro chemotaxis analysis indicated that HCC cells overexpressing IL-37 recruited more DCs by secreting higher levels of specific chemokines (eg, CCL3 and CCL20). In addition, IL-37 indirectly up-regulated the expression of major histocompatibility class II molecules, CD86 and CD40 on DCs by acting on tumor cells; IL-37 also indirectly enhanced the anti-tumor effect of T lymphocytes by stimulating DCs to secrete cytokines such as IL-2, IL-12, IL-12p70, interferon-α (IFN-α) and IFN-γ. Finally, overexpression IL-37 in HCC cells significantly delayed tumor growth and increased recruitment of CD11c+ DCs to tumor tissues was also revealed in vivo mouse model.Conclusion: DCs play an important role in IL-37 mediated anti-tumor immune responses in HCC, which may contribute to the development of novel cancer immunotherapeutic strategies.Keywords: IL-37, dendritic cells, antitumor immunity, hepatocellular carcinoma

Sun J, Li Y, Ling B, Zhu Q, Hu Y, Tan D, Geng P, Xu J. Int J Chron Obstruct Pulmon Dis. 2019;14:1229–1237.The author has advised that an error occurred in the numbering of the second and third affiliations in the affiliations list. The correct affiliations list for this paper should appear as follows:Jiayan Sun,1 Yujie Li,1 Bingyu Ling,1 Qingcheng Zhu,1 Yingying Hu,2 Dingyu Tan,1 Ping Geng,1 Jun Xu31Department of Emergency, Clinical Medical College, Yangzhou University, Northern Jiangsu People’s Hospital, Yangzhou, People’s Republic of China; 2Department of Emergency, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, People’s Republic of China; 3Department of Emergency, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaRead the original article