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Na Li,1,* Yue-xiang Ren,2,* Heng-ming Ye,1,3 Ying Lin,4 Qiang Liu,5 Jiao Wang,1 Ze-fang Ren,1 Lin Xu1,6,7 1The School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Public Health Service Center of Bao’an District, Shenzhen, People’s Republic of China; 4The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 5Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 6School of Public Health, the University of Hong Kong, Hong Kong; 7Institute of Applied Health Research, University of Birmingham, Birmingham, UK*These authors contributed equally to this workCorrespondence: Ze-fang Ren; Lin Xu, School of Public Health, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou, 510080, People’s Republic of China, Tel +0086-20-87332577 ; Tel +0086-20- 87335523, Fax +011-86-20-87332577, Email renzef@mail.sysu.edu.cn; xulin27@mail.sysu.edu.cnPurpose: Chlamydia trachomatis (C. trachomatis) is associated with several gynecological tumors; yet its prognostic role in breast cancer remains unclear. Thus, we investigated the prognostic role of anti-C. trachomatis immunoglobulin G (IgG) in breast cancer patients and the modification effects of pro-inflammatory cytokines.Methods: The serum levels of C. trachomatis IgG and four pro-inflammatory cytokines were measured. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), including product terms to assess the modification effects of pro-inflammatory cytokines on the association between C. trachomatis IgG and breast cancer prognosis.Results: From 2008 to 2018, 1121 breast cancer patients were recruited and followed up until December 31, 2021, with a median follow-up time of 63.91 months (interquartile range: 39.16– 90.08 months). Patients positive for C. trachomatis IgG showed HRs of 1.09 (95% CI, 0.67– 1.78) for overall survival (OS) and 1.24 (0.87– 1.78) for progression-free survival (PFS), compared to those who were negative. These associations became statistically significant in women aged 50 years or younger (HR=1.43, 95% CI=0.79– 2.58 for OS; HR=1.79, 95% CI=1.16– 2.77 for PFS). Positive C. trachomatis IgG serology was associated with adverse prognostic effects among patients with higher levels of pro-inflammatory cytokines (IL-6, TNF-α, IL-8, and IL-1β), but with favorable prognostic effects for those with low levels. These interactions were particularly significant in those aged 50 years or younger.Conclusion: In breast cancer patients younger than 50 years of age or with higher levels of pro-inflammatory cytokines, C. trachomatis infection appeared to have a negative prognostic impact. These findings highlight the significance of C. trachomatis in predicting prognosis and personalized therapy for breast cancer patients.Keywords: Chlamydia trachomatis, breast cancer, prognosis, pro-inflammatory cytokines

Shuang Du,1,&ast; Ke Lin,2,&ast; Jing Li,3 Xin Zhou,4 Chaolan Wang,2 Jun Liu,3 Na Li,2 Jian Chen2 1Department of Rehabilitation Medicine, The First People’s Hospital of Jin Tang County, Chengdu, Sichuan, 610400, People’s Republic of China; 2Traditional Chinese Medicine Department, The First People’s Hospital of Jintang County, Chengdu, Sichuan, 610400, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Jintang County, Chengdu, Sichuan, 610400, People’s Republic of China; 4Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Chen, Traditional Chinese Medicine Department, The First People’s Hospital of Jintang County, Chengdu, Sichuan, 610400, People’s Republic of China, Tel +86-10-18908176456, Email chenjian792@163.comPurpose: COPD patients frequently have abnormal serum phosphorus levels. The objective of this study was to examine the correlation between serum phosphorus levels with hospital and 90-day mortality in critically ill patients with COPD.Patients and Methods: The MIMIC IV database was used for this retrospective cohort analysis. We extracted demographics, vital signs, laboratory tests, comorbidity, antibiotic usage, ventilation and scoring systems within the first 24 hours of ICU admission. Restricted cubic splines and multivariate cox regression analysis models were used to evaluate the connection between serum phosphorus with hospital and 90-day mortality. We assessed and classified various factors including gender, age, renal disease, severe liver disease, the utilization of antibiotics and congestive heart failure.Results: We included a total of 3611 patients with COPD, with a median age of 70.7 years. After adjusting for all other factors, we observed a significant positive association between serum phosphate levels with both hospital mortality (HR 1.19, 95% CI: 1.07– 1.31, p< 0.001) and 90-day mortality (HR 1.15, 95% CI: 1.06– 1.24, p< 0.001). Compared to the medium group (Q2 ≥ 3.15, < 4.0), the adjusted hazard ratios for hospital mortality were 1.47 (95% CI: 1.08– 2, p=0.013), and 1.31 (95% CI: 1.06– 1.61, p=0.013) for 90-day mortality in the high group (Q3≥ 4.0). Hospital mortality decreased at serum phosphate levels below 3.8 mg/dl (HR 0.664, 95% CI: 0.468– 0.943, p=0.022), but increased for both hospital (HR 1.312, 95% CI: 1.141– 1.509, p< 0.001) and 90-day mortality (HR 1.236, 95% CI: 1.102– 1.386, p< 0.001) when levels were above 3.8 mg/dl. Subgroup and sensitivity analyses yielded consistent results.Conclusion: In critical ill COPD patients, this study demonstrated a non-linear association between serum phosphate levels and both hospital and 90-day mortality. Notably, there was an inflection point at 3.8 mg/dl, indicating a significant shift in outcomes. Future prospective research is necessary to validate this correlation.Keywords: COPD, serum phosphate, mortality, MIMIC-IV, critically ill

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

Xingyuan Li,1,2,&ast; Fenghao Yang,3,&ast; Nan Li,4,&ast; Yong Xu,5 Fang Liu1,2 1Department of Nephrology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Laboratory of Diabetic Kidney Disease, Kidney Research Institute, Department of Nephrology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Department of Psychiatry, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Liu, West China Hospital, Sichuan University, &num;37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-18980601214, Fax +86-28-85422335, Email liufangfh@163.comBackground: Diabetic kidney disease (DKD) patients require comprehensive disease education and mutual support to cope with various challenges. Social media platforms provide opportunities for DKD patients to access information and interact with peers. However, qualitative analysis of DKD patients’ real-world concerns and needs on social media is lacking.Methods: A qualitative study was conducted to analyze DKD patients’ posts on Facebook and Baidu DKD-specific forums from June 2013 to June 2023. Posts were retrieved, and the forum with the most DKD-related posts from each platform was selected using stratified random sampling. Thematic analysis was performed to identify common themes, which were categorized and quantified.Results: In total, 746 DKD-related posts were analyzed, generating 203 keyword categories with 954 tags. Three main themes emerged: Diagnosis and Comorbidities (50.2%), Treatment and Prevention (29.7%), and Lifestyle and Psychology (20.1%). Patients were most concerned about DKD diagnosis, staging, comorbidities, and interpreting diagnostic indicators. They also sought information on treatment advancements, medications, renal replacement therapies, and traditional Chinese medicine. Diet, exercise, work-life balance, family planning, and mental well-being were key lifestyle and psychological concerns.Conclusion: This study reveals DKD patients’ primary needs and concerns on social media, which can guide healthcare professionals in providing targeted education and support. Meeting patients’ needs through comprehensive education and counseling can improve treatment adherence and prognosis, though challenges remain in addressing all issues in real-world practice.Keywords: diabetic kidney disease, qualitative research, patient education, social media

Yi Tang,1,&ast; Zemin Wei,1,&ast; Ning Li,2 Chao Jiang,2 Chen Liang,1 Lulu Sun,2 Lufeng Tian,3 Zhengyu Jin,4 Zhe Wu,2,&ast; Hao Sun4,&ast; 1Department of Endocrinology, Fushun Central Hospital, Fushun, Liaoning Province, People’s Republic of China; 2Department of Radiology, Fushun Central Hospital, Fushun, Liaoning Province, People’s Republic of China; 3Department of Internal Medicine, Fushun Central Hospital, Fushun, Liaoning Province, People’s Republic of China; 4Department of Radiology, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Sun, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-10-69159537, Email sunhao_robert@126.com Zhe Wu, Fushun Central Hospital, Xincheng Road, Shuncheng District, Fushun, Liaoning Province, 113006, People’s Republic of China, Tel +86-156-42018778, Email wuzhe0306@163.comPurpose: To examine the risk of type 2 diabetes mellitus in non-obese patients with pancreatic fatty infiltration through abdominal computed tomography (CT) quantitation.Patients and Methods: We carried out a retrospective analysis of abdominal CT and inpatient medical records of 238 inpatients from July 2019 to April 2021. The patients were divided into a normal non-obese group (BMI < 25, n = 135) and diabetic non-obese group (BMI < 25, n = 103). Abdominal CT-related parameters included body width; mean CT values of the pancreas, liver, and spleen; difference between pancreas and spleen CT values (P−S); pancreas-to-spleen attenuation ratio (P/S); and liver-to-spleen attenuation ratio (L/S). Logistic regression was used to estimate the risk factors for comorbid diabetes in a non-obese population.Results: The P-values of the pancreas CT value, P−S, P/S, body width, and L/S were all < 0.05 and correlated to comorbid diabetes in non-obese patients. Worsening pancreatic fatty infiltration increased the risk of developing diabetes. Using a P/S of 1.0 as reference, every successive decrease in this ratio by 0.1 increases patient risk by 3.981, 4.452, 6.037, and 12.937 times.Conclusion: The risk of developing type 2 diabetes mellitus in non-obese patients increases with the degree of pancreatic fatty infiltration as assessed by CT.Keywords: computed tomography, non-obese patients, pancreatic fatty infiltration, type 2 diabetes mellitus

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

Naijing Li,1,&ast; Weiying Zhang,2,&ast; Siyuan Wu,3,&ast; Muhammad Shafiq,4 Peihan Xie,3 Lixiang Zhang,5 Shichao Jiang,3 Yue Bi1 1Department of Orthopedic Oncology, Yantai Shan Hospital, Yantai, People’s Republic of China; 2Health Management Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 4Innovation Center of Nanomedicines, Kawasaki Institute of Industrial Promotion, Kawasaki, Japan; 5Department of Health Management, Characteristic Medical Center of Chinese People’s Armed Police Force, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Bi; Shichao Jiang, Email dr_yuebi@126.com; mailjsc@163.comPurpose: Functional inorganic nanomaterials (NMs) are widely exploited as bioactive materials and drug depots. The lack of a stable form of application of NMs at the site of skin injury, may impede the removal of the debridement, elevate pH, induce tissue toxicity, and limit their use in skin repair. This necessitates the advent of innovative wound dressings that overcome the above limitations. The overarching objective of this study was to exploit strontium-doped mesoporous silicon particles (PSiSr) to impart multifunctionality to poly(lactic-co-glycolic acid)/gelatin (PG)-based fibrous dressings (PG@PSiSr) for excisional wound management.Methods: Mesoporous silicon particles (PSi) and PSiSr were synthesized using a chemo-synthetic approach. Both PSi and PSiSr were incorporated into PG fibers using electrospinning. A series of structure, morphology, pore size distribution, and cumulative pH studies on the PG@PSi and PG@PSiSr membranes were performed. Cytocompatibility, hemocompatibility, transwell migration, scratch wound healing, and delineated angiogenic properties of these composite dressings were tested in vitro. The biocompatibility of composite dressings in vivo was assessed by a subcutaneous implantation model of rats, while their potential for wound healing was discerned by implantation in a full-thickness excisional defect model of rats.Results: The PG@PSiSr membranes can afford the sustained release of silicon ions (Si4+) and strontium ions (Sr2+) for up to 192 h as well as remarkably promote human umbilical vein endothelial cells (HUVECs) and NIH-3T3 fibroblasts migration. The PG@PSiSr membranes also showed better cytocompatibility, hemocompatibility, and significant formation of tubule-like networks of HUVECs in vitro. Moreover, PG@PSiSr membranes also facilitated the infiltration of host cells and promoted the deposition of collagen while reducing the accumulation of inflammatory cells in a subcutaneous implantation model in rats as assessed for up to day 14. Further evaluation of membranes transplanted in a full-thickness excisional wound model in rats showed rapid wound closure (PG@SiSr vs control, 96.1% vs 71.7%), re-epithelialization, and less inflammatory response alongside skin appendages formation (eg, blood vessels, glands, hair follicles, etc.).Conclusion: To sum up, we successfully fabricated PSiSr particles and prepared PG@PSiSr dressings using electrospinning. The PSiSr-mediated release of therapeutic ions, such as Si4+ and Sr2+, may improve the functionality of PLGA/Gel dressings for an effective wound repair, which may also have implications for the other soft tissue repair disciplines.Keywords: electrospinning, nanofiber membrane, wound healing, mesoporous silicon, strontium

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

Na Li,1 Liufu Cui,1 Gary Tse,2,3 Panagiotis Korantzopoulos,4 Konstantinos P Letsas,5 George Bazoukis,6,7 Shuohua Chen,8 Nan Zhang,2 Xuemei Yang,9 Peipei Liu,10 Lili Wu,11 Gan-Xin Yan,12,13 Gregory Yoke Hong Lip,14,15 Shouling Wu,8 Tong Liu2 1Department of Rheumatology and Immunology, Kailuan General Hospital, Tangshan, Hebei Province, People’s Republic of China; 2Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 3School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, People’s Republic of China; 4First Department of Cardiology, University of Ioannina Medical School, Ioannina, Greece; 5Arrhythmia Unit, Laboratory of Cardiac Pacing and Electrophysiology, Onassis Cardiac Surgery Center, Athens, Greece; 6Department of Cardiology, Larnaca General Hospital, Larnaca, Cyprus; 7European University Cyprus, Medical School, Nicosia, Cyprus; 8Department of Cardiology, Kailuan General Hospital, Tangshan, Hebei Province, People’s Republic of China; 9School of Clinical Medicine, North China University of Science and Technology, Tangshan, Hebei Province, People’s Republic of China; 10School of Public Health, North China University of Science and Technology, Tangshan, Hebei Province, People’s Republic of China; 11Department of Cardiology, Shanghai Songjiang District Central Hospital, Shanghai, People’s Republic of China; 12Lankenau Medical Center and Lankenau Institute for Medical Research, Wynnewood, PA, USA; 13Department of Cardiology, Fuwai Huazhong Hospital, Zhengzhou, Henan Province, People’s Republic of China; 14Liverpool Centre for Cardiovascular Sciences, University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK; 15Danish Center for Clinical Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkCorrespondence: Tong Liu, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China, Email liutong@tmu.edu.cn; liutongdoc@126.com Shouling Wu, Department of Cardiology, Kailuan General Hospital, Tangshan, Hebei Province, People’s Republic of China, Email drwusl@163.comObjective: This study aimed to explore the impact of a combination of hyperuricemia (HUA) and excessive high-sensitivity C-reactive protein (hs-CRP) levels on the likelihood of developing cardiac conduction block (CCB). Additionally, it sought to assess whether the influence of uric acid (UA) on CCB is mediated by hs-CRP.Methods: A prospective study was executed utilizing data from the Kailuan cohort, including 81,896 individuals initially free from CCB. The participants were categorized into four groups depending on the existence of HUA and low-grade inflammation (hs-CRP> 3 mg/L). Cox regression analysis was employed to ascertain hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of incident CCB. A mediation analysis was performed to determine if hs-CRP functioned as a mediator in the connection between UA levels and the incidence of CCB.Results: During a median observation period of 11.8 years, we identified 3160 cases of newly occurring CCB. Compared with the low UA/low CRP group, the combination of HUA and low-grade inflammation elevated the CCB risks (HR:1.56, 95% CI:1.22– 1.99), atrioventricular block (AVB) (HR:1.88, 95% CI:1.27– 2.77), and right bundle branch block (HR:1.47, 95% CI:1.02– 2.12), respectively. Mediation analysis revealed that in the HUA group, compared with the non-HUA group, the risk of CCB elevated by 14.0%, with 10.3% of the increase mediated through hs-CRP.Conclusion: HUA combined with elevated hs-CRP increased the risk of CCB, especially AVB. The connection between UA and the CCB risk was partly mediated by hs-CRP. Keywords: hyperuricemia, inflammation, cardiac conduction block, combined exposure, risk factors, mediation

Mingyue Fu,1,2,&ast; Diliaremu Aihemaiti,1,2,&ast; Haowen Fu,1,2,&ast; Na Li,1,2 Yifan Yuan,3 Mei Ye1,2 1Department of Gastroenterology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Hubei Clinical Centre and Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yifan Yuan; Mei Ye, Email yifanyuan95@163.com; wumeiye08@163.comBackground: Crohn’s disease (CD) is a persistent inflammatory condition that impacts the gastrointestinal system and is characterized by a multifaceted pathogenesis involving genetic, immune, and environmental components. This study primarily investigates the relationship between gene expression and immune cell infiltration in CD, focusing on disulfidptosis—a novel form of cell death caused by abnormal disulfide accumulation—and its impact on various immune cell populations. By identifying key disulfidptosis-related genes (DRGs) and exploring their association with distinct gene expression subtypes, this research aims to enhance our understanding of CD and potentially other autoimmune diseases.Methods: Gene expression data from intestinal biopsy samples were collected from both individuals with CD and healthy controls, and these data were retrieved from the GEO database. Through gene expression level comparisons, various differentially expressed genes (DEGs) were identified. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to reveal the biological processes and pathways linked to these DEGs. Later, immune cell infiltration was evaluated. Hub candidate DRGs were identified using machine learning algorithms. Validation of the expression of hub DRGs was carried out using quantitative real-time polymerase chain reaction. The hub DRGs were subjected to unsupervised hierarchical clustering to classify CD patients into subtypes. The characteristics of each subtype were then analyzed.Results: Two hub DRGs (NDUFA11 and LRPPRC) were identified. NDUFA11 showed a significantly positive association with the abundance of Th17 cells. Conversely, higher expression levels of LRPPRC were associated with a reduced abundance of various immune cells, particularly monocytes. CD patients were classified into two disulfidptosis-related subtypes. Cluster B patients exhibited lower immune infiltration and milder clinical presentation.Conclusion: LRPPRC and NDUFA11 are identified as hub DRGs in CD, with potential roles in disulfidptosis and immune regulation. The disulfidptosis subtypes provide new insights into disease progression.Keywords: Crohn’s disease, disulfidptosis, machine learning, expression pattern, immune cell infiltration

Ning Li,&ast; Jia-Min Shao,&ast; Ye Jiang, Chu-Han Wang, Si-Bo Li, De-Chao Wang, Wei-Ying Di Department of Neurology, Affiliated Hospital of Hebei University, Baoding, Hebei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei-Ying Di, Email diweiying@126.comBackground: This study addresses the predictive modeling of Enlarged Perivascular Spaces (EPVS) in neuroradiology and neurology, focusing on their impact on Cerebral Small Vessel Disease (CSVD) and neurodegenerative disorders.Methods: A retrospective analysis was conducted on 587 neurology inpatients, utilizing LASSO regression for variable selection and logistic regression for model development. The study included comprehensive demographic, medical history, and laboratory data analyses.Results: The model identified key predictors of EPVS, including Age, Hypertension, Stroke, Lipoprotein a, Platelet Large Cell Ratio, Uric Acid, and Albumin to Globulin Ratio. The predictive nomogram demonstrated strong efficacy in EPVS risk assessment, validated through ROC curve analysis, calibration plots, and Decision Curve Analysis.Conclusion: The study presents a novel, robust EPVS predictive model, providing deeper insights into EPVS mechanisms and risk factors. It underscores the potential for early diagnosis and improved management strategies in neuro-radiology and neurology, highlighting the need for future research in diverse populations and longitudinal settings.Keywords: Enlarged Perivascular Spaces, cerebral small vessel disease, predictive model, risk factors, neuro-radiology, LASSO regression

Lingling Yuan,1 Ting Wang,1 Jinsheng Duan,2 Jing Zhou,1 Na Li,1 Guizhi Li,1 Hong Zhou1 1Department of Endocrinology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050004, People’s Republic of China; 2Department of Cardiology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050004, People’s Republic of ChinaCorrespondence: Hong Zhou, Department of Endocrinology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China, Tel +86-15130119625, Email zhoubs2013@hebmu.edu.cn; zhoubs2013@163.comIntroduction: Cardiac fibrosis is one of the important causes of heart failure and death in diabetic cardiomyopathy (DCM) patients. Circular RNAs (circRNAs) are covalently closed RNA molecules in eukaryotes and have high stability. Their role in myocardial fibrosis with diabetic cardiomyopathy (DCM) remain to be fully elucidated. This study aimed to understand the expression profiles of circRNAs in myocardial fibrosis with DCM, exploring the possible biomarkers and therapeutic targets for DCM.Methods: At 21 weeks of age, db/db mice established the type 2 DCM model measured by echocardiography, and the cardiac tissue was extracted for Hematoxylin–eosin, Masson’s trichrome staining, and transmission electron microscopy. Subsequently, the expression profile of circRNAs in myocardial fibrosis of db/db mice was constructed using microarray hybridization and verified by real‐time quantitative polymerase chain reaction. A circRNA–microRNA–messenger RNA coexpression network was constructed, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were done.Results: Compared with normal control mice, db/db mice had 77 upregulated circRNAs and 135 downregulated circRNAs in their chromosomes (fold change ≥ 1.5, P ≤ 0.05). Moreover, the enrichment analysis of circRNA host genes showed that these differentially expressed circRNAs were mainly involved in mitogen-activated protein kinase signaling pathways. CircPHF20L1, circCLASP1, and circSLC8A1 were the key circRNAs. Moreover, circCLASP1/miR-182-5p/Wnt7a, circSLC8A1/miR-29b-1-5p/Col12a1, and most especially circPHF20L1/miR-29a-3p/Col6a2 might be three novel axes in the development of myocardial fibrosis in DCM.Conclusion: The findings will provide some novel circRNAs and molecular pathways for the prevention or clinical treatment of DCM through intervention with specific circRNAs.Keywords: Circular RNAs, expression profile, diabetic cardiomyopathy, cardiac fibrosis, bioinformatic analysis

Yu Huang,1,&ast; Shuyang Wu,1,&ast; Jingjing Li,1,2 Chenglin He,1 Yanfen Cheng,3 Nan Li,1 Yitao Wang,1,4 Yihan Wu,1 Jinming Zhang1 1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, Hong Kong Polytechnic University, Hong Kong, SAR, People’s Republic of China; 3Chengdu University, Chengdu, People’s Republic of China; 4Macau Center for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinming Zhang; Yihan Wu, State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China, Email cdutcmzjm@126.com; yihanwuone@126.comBackground: Chemo-photodynamic combination therapy has demonstrated significant potential in the treatment of cancer. Triptolide (TPL), a naturally derived anticancer agent, when combined with the photosensitizer Chlorin e6 (Ce6), has shown to provide enhanced anti-tumor benefits. However, the development of stimuli-responsive nanovehicles for the co-delivery of TPL and Ce6 could further enhance the efficacy of this combination therapy.Methods: In this study, we synthesized a pH/ROS dual-responsive mPEG-TK-PBAE copolymer, which contains a pH-sensitive PBAE moiety and a ROS-sensitive thioketal (TK) linkage. Through a self-assembly process, TPL and Ce6 were successfully co-loaded into mPEG-TK-PBAE nanoparticles, hereafter referred to as TPL/Ce6 NPs. We evaluated the pH- and ROS-sensitive drug release and particle size changes. Furthermore, we investigated both the in vitro suppression of cellular proliferation and induction of apoptosis in HepG2 cells, as well as the in vivo anti-tumor efficacy of TPL/Ce6 NPs in H22 xenograft nude mice.Results: The mPEG-TK-PBAE copolymer was synthesized through a one-pot Michael-addition reaction and successfully co-encapsulated both TPL and Ce6 by self-assembly. Upon exposure to acid pH values and high ROS levels, the payloads in TPL/Ce6 NPs were rapidly released. Notably, the abundant ROS generated by the released Ce6 under laser irradiation further accelerated the degradation of the nanosystem, thereby amplifying the tumor microenvironment-responsive drug release and enhancing anticancer efficacy. Consequently, TPL/Ce6 NPs significantly increased PDT-induced oxidative stress and augmented TPL-induced apoptosis in HepG2 cells, leading to synergistic anticancer effects in vitro. Moreover, administering TPL/Ce6 NPs (containing 0.3 mg/kg of TPL and 4 mg/kg of Ce6) seven times, accompanied by 650 nm laser irradiation, efficiently inhibited tumor growth in H22 tumor-bearing mice, while exhibiting lower systemic toxicity.Conclusion: Overall, we have developed a tumor microenvironment-responsive nanosystem for the co-delivery of TPL and Ce6, demonstrating amplified synergistic effects of chemo-photodynamic therapy (chemo-PDT) for hepatocellular carcinoma (HCC) treatment.Keywords: triptolide, PDT, ROS, Ce6, pH responsive, hepatic carcinoma

Suqing Liu,1 Fengling Li,1 Qinghua Cao,2 Ning Li,1 Qian Gao1 1Department of Gynaecology and Obstetrics, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, People’s Republic of China; 2Department of Pathology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, People’s Republic of ChinaCorrespondence: Fengling Li, Department of Gynecology and Obstetrics, Yantai Affiliated Hospital of Binzhou Medical University, Muping District, Yantai, Shandong, People’s Republic of China, Email sdbzlsq1989@163.comAbstract: Gastric adenocarcinoma (GAS) is a rare subtype of mucinous adenocarcinoma characterized by gastric differentiation and is unrelated to human papillomavirus (HPV) infection. This report discusses a 40-year-old female who presented with abdominal distension accompanied by increased abdominal circumference. CT of the abdomen and pelvis showed a large 21.0&ast;12.7&ast;26.0 cm mass later diagnosed as GAS combined with squamous cell carcinoma on surgical pathology. Immunohistological staining of GAS was positive for CK7, MUC6, PAX-8 CEA, and P53 (wild type) and negative for CDX2, CK20, ER, PR, P16, and WT1. The proliferative index (Ki-67) was 20%. Immunohistochemical staining of squamous cell carcinoma was positive for P16 and P53 (wild type), and the proliferative index (Ki-67) was 90%. However, the pathogenesis and molecular mechanisms of GAS have not been fully elucidated. As more cases are identified and reported, additional targeted therapies can be developed and tested in these patients.Keywords: cervical cancer, gastric type, adenocarcinoma

Guanming Shao,&ast; Yonghui Ma,&ast; Chao Qu, Ruiqian Gao, Chengzhan Zhu, Linlin Qu, Kui Liu, Na Li, Peng Sun, Jingyu Cao Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Sun; Jingyu Cao, Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China, Email psun1@qdu.edu.cn; cjy7027@163.comBackground: Circulating eosinophils are associated with tumor development. An eosinophil-related index, the neutrophil to eosinophil ratio (NER), can be used to predict the prognosis of patients with tumors. However, there is still a lack of efficient prognostic biomarkers for HCC. In this study, we aimed to investigate the predictive value of the NER and develop an optimal machine learning model for the recurrence of HCC patients. Patients and methods: A retrospective collection of 562 patients who underwent hepatectomy with a pathologic diagnosis of HCC was performed. The relationship between NER and progression-free survival (PFS) was investigated. We developed a new machine learning framework with 10 machine learning algorithms and their 101 combinations to select the best model for predicting recurrence after hepatectomy. The performance of the model was assessed by the area under the curve (AUC) of characteristics and calibration curves, and clinical utility was evaluated by decision curve analysis (DCA).Results: Kaplan‒Meier curves showed that the PFS in the low NER group was significantly better than that in the high NER group. Multivariate Cox regression analysis showed that NER was an independent risk factor for recurrence after surgery. The random survival forests (RSF) model was selected as the best model that had good predictive efficacy and outperformed the TNM, BCLC, and CNLC staging systems.Conclusion: The NER has good predictive value for postoperative recurrence in patients with hepatocellular carcinoma. Machine learning model based on NER can be used for accurate predictions.Keywords: hepatocellular carcinoma, liver resection, recurrence, machine learning, neutrophil-to-eosinophil ratio

Xiaoxiao Zhao,1 Hanjun Zhao,1 Runzhen Chen,1 Jiannan Li,1 Jinying Zhou,1 Nan Li,1 Shaodi Yan,2 Chen Liu,1 Peng Zhou,1 Yi Chen,1 Li Song,1 Hongbing Yan2 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People’s Republic of China; 2Department of Cardiology, Fuwai Hospital Chinese Academy of Medical Sciences, ShenZhen, People’s Republic of ChinaCorrespondence: Hanjun Zhao, Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, No. 167, Beijing, 100037, People’s Republic of China, Tel +86-15210020808, Email 15210020808@163.com Hongbing Yan, Fuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Road, Shenzhen, 518000, People’s Republic of China, Tel +86-1301339287, Email hbyanfuwai2018@163.comBackground and Aim: An elevated triglyceride-glucose (TyG) level is associated with increased risk of mortality in patients with CAD. Trimethylamine N-oxide (TMAO) has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is correlated with adverse outcomes. However, the incremental prognostic value of TMAO and TyG in the cohort of optical coherence tomography (OCT)-defined high-risk ST-segment elevation myocardial infarction (STEMI) patients is unknown.Methods: We studied 274 consecutive aged ≥ 18 years patients with evidence of STEMI and detected on pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019.Outcomes: There were 22 (22.68%), 27 (27.84%), 26 (26.80%), and 22 (22.68%) patients in groups A-D, respectively. The baseline characteristics according to the level of TMAO and TyG showed that patients with higher level in both indicators were more likely to have higher triglycerides (p < 0.001), fasting glucose (p < 0.001) and higher incidence of diabetes (p = 0.008). The group with TMAO > median and TyG ≤ median was associated with higher rates of MACEs significantly (p = 0.009) in fully adjusted analyses. During a median follow-up of 2.027 years, 20 (20.6%) patients experienced MACEs. To evaluate the diagnostic value of the TyG index combined with TMAO, the area under the receiver operating characteristic curve for predicting MACEs after full adjustment was 0.815 (95% confidence interval, 0.723– 0.887; sensitivity, 85.00%; specificity, 72.73%; cut-off level, 0.577). Among the group of patients with TMAO > median and TyG ≤ median, there was a significantly higher incidence of MACEs (p= 0.033). A similar tendency was found in the cohort with hyperlipidemia (p= 0.016) and diabetes mellitus (p= 0.036).Conclusion: This study demonstrated the usefulness of combined measures of the TyG index and TMAO in enhancing risk stratification in STEMI patients with OCT-defined high-risk plaque characteristics.Trial Registration: This study was registered at ClinicalTrials.gov as NCT03593928.Keywords: optical coherence tomography, triglyceride glucose index, trimethylamine N-oxide, high risk plaque feature, major adverse cardiovascular events, prospective study

Rui Jing,1 Hui Dong,1 Kun Huang,2 Zhong Liu,1 Ran Xue,1 Yiran Dong,1 Mei Jiao,3 Na Li,4 Yumei Guo,5 Yun Liu,6 Wenqian Zhang,1 Hongyun Sun1 1Institute for Tuberculosis Control, Jinan Center for Disease Control and Prevention, Jinan, People’s Republic of China; 2Tuberculosis Control Division, Licheng Center for Disease Control and Prevention, Jinan, People’s Republic of China; 3Department of Sexually Transmitted Diseases and AIDS Prevention and Control, Lixia Center for Disease Control and Prevention, Jinan, People’s Republic of China; 4Tuberculosis and Vector Control Division, Shizhong Center for Disease Control and Prevention, Jinan, People’s Republic of China; 5Department of Infectious Diseases and Endemic Disease Control, Huaiyin Center for Disease Control and Prevention, Jinan, People’s Republic of China; 6AIDS Prevention and Control Department, Tianqiao Center for Disease Control and Prevention, Jinan, People’s Republic of ChinaCorrespondence: Wenqian Zhang; Hongyun Sun, Institute for Tuberculosis Control, Jinan Center for Disease Control and Prevention, Jinan, People’s Republic of China, Tel +86 0531-81278897 ; +86 0531 81278873, Email wqzh618@gmail.com; jncdcxxtb@jn.shandong.cnPurpose: This study aimed to investigate awareness of tuberculosis control among post-treatment tuberculosis patients, in order to provide a basis for future preventive and control work in this population.Patients and Methods: A cross-sectional descriptive study was conducted on post-treatment patients with tuberculosis in seven districts of Jinan City between July 2021 and December 2022. A face-to-face or telephone interviews using structured questionnaires for the research subjects were conducted by data collectors. Analyses were carried out first for all subjects, and then separately for male and female subjects.Results: A total of 837 valid questionnaires were collected, of which 495 were males and 342 were females. The awareness rate of the core TB knowledge was 82.46%. The ≥ 65 year group in the total group (OR=0.43, 95% CI: (0.28, 0.68)), male (OR=0.47, 95% CI: (0.27, 0.83)) and female group (OR=0.40, 95% CI: (0.19, 0.86)) was lower than that of the control group. Educational level and monthly income are the main factors of TB cognition in total group. People with university or higher education (OR=2.05, 95% CI: (1.38, 3.05)) and with a monthly income of ≥ 6,000 (OR=1.89, 95% CI: (1.10, 3.25)) had a higher awareness rate. The group with current residence in the city was more aware than the reference group.Conclusion: In the future, the communication of the main transmission route, suspicious symptoms, and cure of TB needs to be strengthened for the post-treatment TB patients. The elderly, those with secondary school education or below, agricultural workers and low-income people are the groups with weak knowledge of TB, and they are also the groups that need to be focused on health education. The above information should be focused on the above groups of people in order to educate them in a way that is easily acceptable to them.Keywords: pulmonary tuberculosis, awareness rate, completed treatment patients, layered analysis

Chuanhao Xiong,1,&ast; Jingzhu Wu,1,&ast; Yuhang Ma,1,&ast; Na Li,1 Xuejiao Wang,1 Yao Li,2 Xiaoying Ding1 1Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoying Ding, Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Hongkou District, Shanghai, 200080, People’s Republic of China, Email xiaoyingding@126.com Yao Li, Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, People’s Republic of China, Email yao.li@shsmu.edu.cnPurpose: Polycystic ovary syndrome (PCOS) is a frequent cause of infertility in reproductive-age women. Our work aims to evaluate the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on gut microbiota, with metabolic parameters including body weight and the hormone profile in PCOS.Patients and Methods: Dehydroepiandrosterone (DHEA)-induced PCOS mice were established and then treated with two GLP-1RAs: liraglutide and novel form semaglutide for four weeks. Changes in body weight and metabolic parameters were measured. Fecal samples were collected and analyzed using metagenomic sequencing.Results: Liraglutide and semaglutide modulated both alpha and beta diversity of the gut microbiota in PCOS. Liraglutide increased the Bacillota-to-Bacteroidota ratio through up-regulating the abundance of butyrate-producing members of Bacillota like Lachnospiraceae. Moreover, liraglutide showed the ability to reverse the altered microbial composition and the disrupted microbiota functions caused by PCOS. Semaglutide increased the abundance of Helicobacter in PCOS mice (p < 0.01) which was the only bacteria found negatively correlated with body weight. Moreover, pathways involving porphyrin and flavonoids were increased after semaglutide intervention.Conclusion: Liraglutide and semaglutide improved reproductive and metabolic disorders by modulating the whole structure of gut microbiota in PCOS. The greater efficacy in weight loss compared with liraglutide observed after semaglutide intervention was positively related with Helicobacter. The study may provide new ideas in the treatment and the underlying mechanisms of GLP-1RAs to improve PCOS.Keywords: PCOS, GLP-1 receptor agonists, gut microbiota, metabolism

Qiang Fu,1 Na Han,1 Na Li,2 Ling Gui,3 Chen Shi,4 Peipei Rong,5 Fan Zeng,1 He Rao,6 Yuan Chen1 On behalf of Cancer Rehabilitation and Palliative Treatment Professional Committee of Hubei Anti Cancer Association1Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Cancer Center, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of China; 3Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 4Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 5Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of China; 6Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of ChinaCorrespondence: Qiang Fu; Yuan Chen, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei, 430030, People’s Republic of China, Email fqiang2016@163.com; chenyuan008@163.comAbstract: Pain is one of the most common clinical symptoms of cancer patients, seriously affecting the quality of life of patients and bringing heavy mental and economic burden to families and society. The treatment of cancer pain in China is facing numerous challenges, one of which includes the irrational usage of analgesic drugs in clinical practice. As a strong opioid analgesic, transdermal fentanyl patch has been widely used due to its convenient clinical application and obvious therapeutic effect. Several basic-level hospitals and even general hospitals in China fail to appropriate the application of drugs in clinical application due to the lack of understanding of the pharmacological characteristics and clinical application of fentanyl transdermal patch by medical staff, seriously affecting the treatment quality. Therefore, it is imperative to strengthen the rational use and management of fentanyl transdermal patches. Accordingly, the initiation by the Cancer Rehabilitation and Palliative Treatment Professional Committee of the Hubei Anti-cancer Association launched the compilation of the “Guidelines for Rational Clinical Use of Fentanyl Transdermal Patch” (from now on referred to as the “Guidelines”) in Hubei Province, China. The experts in the preparation group are experts in many disciplines, such as medicine, pharmacy, and nursing. The expert group determines the outline, prepares the required regulations, and revises it repeatedly. Moreover, these experts put forward suggestions for revision to strictly control the accuracy and scientific authenticity of the contents of the “Guide”. Finally, all experts of the preparation team certify and finalize the draft. This “Guide” prepared by experts of the Cancer Rehabilitation and Palliative Treatment Professional Committee of the Hubei Anti-cancer Association and the expert advisory group with joint efforts, aims to play a positive role in promoting the rational clinical use of fentanyl transdermal patch, reducing the mental and economic burden of patients, and ensuring medical quality and medical safety.Keywords: fentanyl transdermal patch, reasonable application, medication guidelines

Shang Gao,1 Chenmoji Wang,1 Lijie Qi,2 Songlin Liang,1 Xintian Qu,1 Wei Liu,3,&ast; Nianhu Li4,&ast; 1The First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China; 2Qilu Hospital of Shandong University, Jinan, Shandong Province, People’s Republic of China; 3Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China; 4Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nianhu Li; Wei Liu, Email tigerlee073@126.com; weiliu800109@163.comBackground: The method of action of Bushen Formula (BSHXF) in the treatment of intervertebral disc degeneration (IVDD) was uncovered in this work using in vivo and in vitro tests. To clarify the mechanism of action of BSHXF, we validated the rat intervertebral disc degeneration model and the nucleus pulposus cell degeneration model.Methods: In an in vivo model of IVDD the study explores the impact of BSHXF on mitochondrial function, pro-inflammatory cytokines, pro-apoptotic factors, and matrix metalloproteinases. Additionally, it evaluates the induced degeneration of nucleus pulposus (NP) cells in an in vitro model stimulated by interleukin-1 β (IL-1β). The study measures the effects of BSHXF on both the inflammatory response and mitochondrial function.Results: The MRI results showed that BSHXF reduced intervertebral disc volume reduction and degradation of NP tissue. HE, SO-FG and immunofluorescence further confirmed the protective effect of BSHXF on degenerative intervertebral discs. BSHXF reduced the inflammatory levels of IL-6 IL-1β and TNF-α in degenerative intervertebral disc tissue. Meanwhile, JC-1, mPTP and ROS detection revealed that BSHXF can restore mitochondrial function by regulating the expression of antioxidant proteins, playing a protective role in NP cells. Finally, the WB results showed that BSHXF can alleviate IL-1β mediate the degeneration of NP cells. BSHXF can alleviate NP cell apoptosis by inhibiting the expression of bax, cleaved caspase-3, caspase-3, and cyt-c, and increasing the expression of Bcl-2.Conclusion: This study reveals that BSHXF inhibits the development of inflammatory factors, which may play a significant role in intervertebral disc degeneration. This implies that BSHXF is a suitable herbal medication for future research into inflammatory cytokine treatment.Keywords: intervertebral disc degeneration, nucleus pulposus cell, BSHXF, apoptosis, inflammatory

Fengbo Liu,1 Yue Xi,2 Ning Li,3 Ming Wu4 1School of Physical Education, Zhengzhou University of Light Industry, Zhengzhou, Henan Province, People’s Republic of China; 2College of Physical Education and Health, East China Normal University, Shanghai, People’s Republic of China; 3School of Physical Education, Putian University, Putian, Fujian Province, People’s Republic of China; 4Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of ChinaCorrespondence: Fengbo Liu, School of Physical Education, Zhengzhou University of Light Industry, Zhengzhou, Henan Province, People’s Republic of China, Email lfbzzuli@126.comObjective: To explore the impact of brief mindfulness training on college students’ mobile phone addiction and the mediating effect of the sense of meaning in life between them.Methods: This study has employed the mixed experimental design of 2 (experimental conditions) × 2 (time points), randomly assigned 44 college students into a mindfulness training group and a control group (22 college students in each group), and selected the Freiburg Mindfulness Inventory (FMI), Mobile Phone Addiction Tendency Scale (MPATS), and Chinese Meaning in Life Questionnaire (C-MLQ) to conduct separate tests before and after mindfulness training.Results: The results show that: (1) in the pretest, the differences between the mindfulness training group and the control group in the level of mindfulness, the level of mobile phone addiction, and the sense of meaning in life are not statistically significant; (2) in the posttest, compared with those of the control group, both the FMI score (p=0.013) and the C-MLQ score (p< 0.001) of the mindfulness training group improve significantly, while the MPATS score (p=0.008) of the mindfulness training group declines significantly; and (3) the Bootstrap analysis of the mediating effect shows that after the change in C-MLQ (95% CI [0.537, 11.630]) enters the equation, the direct effect of mindfulness training is not significant (95% CI [− 3.254, 5.861]).Conclusion: The results of this study reveal the impact and mechanism of brief mindfulness training on college students’ mobile phone addiction, and provide an empirical basis for intervening on mobile phone addiction.Keywords: brief mindfulness, mobile phone addiction, sense of meaning in life, mediating effect

Chuling Hu,1,&ast; Yan Liu,2,&ast; Wei Cao,3,&ast; Na Li,4 Shen Gao,5 Zhuo Wang,5 Fenfen Gu2 1Department of Pharmacy, Jiaxing Maternity and Child Health Care Hospital, Affiliated Women and Children’s Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 2Department of Clinical Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Neurovascular Disease, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 4Department of Pathology, Jiaxing Maternity and Child Health Care Hospital, Affiliated Women and Children’s Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 5Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuo Wang; Fenfen Gu, Email wangzhou088@163.com; fenfen09@163.comIntroduction: Chemotherapy is still the treatment of choice for advanced triple-negative breast cancer. Chemotherapy combined with immunotherapy is being tried in patients with triple-negative breast cancer. As a kind of “cold tumor”, triple-negative breast cancer has a bottleneck in immunotherapy. Indoleamine 2, 3-dioxygenase-1 inhibitors can reverse the immunosuppressive state and enhance the immune response.Methods: In this study, mesoporous silica nanoparticles were coated with the chemotherapeutic drug doxorubicin and indoleamine 2, 3-dioxygenase 1 inhibitor 1-Methyl-DL-tryptophan (1-MT), and then encapsulate the surfaces of a triple-negative breast cancer cell membrane to construct the tumor dual-targeted delivery system CDIMSN for chemotherapy and immunotherapy, and to investigate the immunogenic death effect of CDIMSN.Results and discussion: The CDIMSN could target the tumor microenvironment. Doxorubicin induced tumor immunogenic death, while 1-MT reversed immunosuppression. In vivo findings showed that the tumor size in the CDIMSN group was 2.66-fold and 1.56-fold smaller than that in DOX and DIMSN groups, respectively. CDIMSN group was better than naked DIMSN in stimulating CD8+T cells, CD4+T cells and promoting Dendritic Cells(DC) maturation. In addition, blood analysis, biochemical analysis and Hematoxylin staining analysis of mice showed that the bionic nanoparticles had good biological safety. Keywords: immunogenic cell death, doxorubicin, bionic nanoparticle, IDO1 inhibitor, triple-negative breast cancer

Fei-Fei Wang,1,&ast; Nan Li,1,&ast; Jing-Jing Wang,1 Nijiti Muyesai,1 Haiyan Fu2 1The People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Emergency Care Center, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China; 2Department of Gastroenterology, Urumqi Friendship Hospital, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiyan Fu, Department of Gastroenterology, Urumqi Friendship Hospital, 558, Shengli Road, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China, Tel/Fax +8618599026892, Email fuhaiyanfhu@126.com Nijiti Muyesai, The People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Emergency Care Center, the People’s Republic of China, No. 91, Tianchi Road, Tianshan District, Urumqi, 830000, People’s Republic of China, Tel/Fax +86 13899955322, Email nijiati0a@126.comObjective: The aim of this study is to examine the distribution and features of gastroscopy in northern Xinjiang, a province in China.Methods: We included a group of 895 patients diagnosed with digestive diseases at Urumqi Friendship Hospital and analyzed their gastroscopic results and baseline data.Results: Among patients aged 12 to 86 years in the specified region, females exhibited a heightened susceptibility to esophageal-gastrointestinal and intestinal disorders compared to males. The mean age for chronic gastritis onset was determined to be 54.79 years. In the context of esophageal-gastric-intestinal disorders, the distribution across various ethnic groups manifested as follows: the Han, Uygur, Hui, and Kazakh populations comprised 53.97%, 23.91%, 7.15%, and 3.46%, respectively. Through principal component-based dimension reduction analysis, we identified chronic non-atrophic gastritis with erosive gastritis, duodenal bulb inflammation, and chronic non-atrophic gastritis (predominantly in the gastric antrum) as pivotal factors contributing to differences in hiatal hernia. Multiple linear regression models were established for different ethnic groups, duodenal bulb inflammation, and hiatal hernia by age. The results revealed a heightened risk of duodenal bulb inflammation (P < 0.01) in Han, Kazakh, Hui, Mongolian, and Uygur women, while the risk of hiatal hernia exhibited a positive correlation with age (P = 0.001).Conclusion: Among patients undergoing gastrointestinal examinations in northern Xinjiang, the most prevalent pathological condition was identified as chronic gastritis. Notably, within this subgroup, the prevalence of duodenal bulb inflammation was found to be greater in women than in men. The ethnic composition within this context encompassed patients from the Han, Kazakh, Hui, and Mongolian ethnic groups. Furthermore, a positive correlation was identified between the incidence of esophageal hiatal hernia and age.Keywords: age, ethnicity, esophageal-gastric-intestinal disease, gastroscopy, gender, northern Xinjiang

Li N, Cheng C, Wang T. Onco Targets Ther. 2020;13:4495–4505. We, the Editor and Publisher of the journal OncoTargets and Therapy have retracted the published article. Following publication of the article, concerns were raised about the duplication of images from Figures 4 and 6 with images from unrelated articles. Specifically, Images for Figure 4B have been duplicated with images for Figure 3F from Zhang J, He H, Wang K, et al. miR-326 inhibits the cell proliferation and cancer stem cell-like property of cervical cancer in vitro and oncogenesis in vivo via targeting TCF4. Ann Transl Med. 2020;8(24):1638. https://doi.org/10.21037/atm-20-6830 and Figure 3D from Wu J, Zhang C, Chen L. MiR-511 Mimic Transfection Inhibits the Proliferation, Invasion of Osteosarcoma Cells and Reduces Metastatic Osteosarcoma Tumor Burden in Nude Mice via Targeting MAPK1. Cancer Biomark. 2019:26(3):343–351. The images for Figure 6A have been duplicated with images for Figure 1B from Bai J, Jiao WY. Down-Regulation of ZEB1 by miR-199a-3p Overexpression Restrains Tumor Stem-Like Properties and Mitochondrial Function of Non-Small Cell Lung Cancer. Onco Targets Ther. 2020;13:4607-4616. https://doi.org/10.2147/OTT.S244525. Images for Figure 6D have been duplicated with images for Figure 4C from Shi S, Hu X, Xu J, Liu H, Zou L. Retracted Article: MiR-320d suppresses the progression of breast cancer via lncRNA HNF1A-AS1 regulation and SOX4 inhibition. RSC Adv. 2018;8:19196-19207; Figure 5B from Lei K, Ma B, Shi P, et al. Icariin Mitigates the Growth and Invasion Ability of Human Oral Squamous Cell Carcinoma via Inhibiting Toll-Like Receptor 4 and Phosphorylation of NF-κB P65. Onco Targets Ther. 2020;13:299-307. https://doi.org/10.2147/OTT.S214514 and Figure 6C from Jiang Z, Mao Z. Retracted Article: Astragaloside IV (AS-IV) alleviates the malignant biological behavior of hepatocellular carcinoma via Wnt/β-catenin signaling pathway. RSC Adv. 2019;9: 35473-35482. The corresponding author did not respond to our queries and was unable to provide a satisfactory explanation for how the images came to be duplicated or provide satisfactory original data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain

Runzhen Chen,1,2,&ast; Jiannan Li,1,3,&ast; Zhaoxue Sheng,4 Jinying Zhou,1,3 Ying Wang,1 Xiaoxiao Zhao,1,3 Nan Li,1 Weida Liu,5 Chen Liu,1,3 Peng Zhou,1,3 Yi Chen,1,3 Shaodi Yan,2 Li Song,1– 3 Hongbing Yan,2,3 Hanjun Zhao1,3 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, People’s Republic of China; 3Coronary Heart Disease Center, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Cardiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 5Medical Research Center, Peking Union Medical College Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongbing Yan, Fuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Road, Nanshan District, Shenzhen, 510000, People’s Republic of China, Email hbyanfuwai2018@163.com; hbyanfuwai@aliyun.com Hanjun Zhao, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, 167 North Lishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Email 15210020808@163.comBackground: As a specialized pro-resolving lipid mediator, resolvin D1 (RvD1) inhibits atherosclerosis progression in vivo by reducing regional oxidative stress and chronic inflammation. However, it is unclear how RvD1 is involved in human coronary artery disease. This study aims to investigate the association between plasma levels of RvD1 and culprit-plaque characteristics in patients with ST-segment elevation myocardial infarction (STEMI).Methods: A total of 240 STEMI patients undergoing optical coherence tomography (OCT) examination were analyzed. RvD1 levels were measured in patient plasma samples using an enzyme-linked immunosorbent assay. Logistic regression was performed to assess the association between RvD1 levels and various culprit plaque morphologies, and the receiver operating curve was used to search for an optimal cutoff threshold to predict certain pathological features.Results: The median RvD1 level was 129.7 (56.6– 297.8) pg/mL. According to multivariable logistic regression, high RvD1 was associated with plaque rupture (≥ 111.5 pg/mL, odds ratio [OR]: 2.09, 95% confidence interval [CI]: 1.20– 3.66, P = 0.010), healed plaques (≥ 246.4 pg/mL, OR: 2.17, 95% CI: 1.11– 4.24, P = 0.023), and calcification (≥ 293.38 pg/mL, OR: 2.10, 95% CI: 1.21– 3.66, P = 0.008) at culprit lesions.Conclusion: Increased levels of RvD1 were associated with higher instability of coronary atherosclerotic plaques in STEMI patients.Keywords: resolvin D1, specialized pro-resolving lipid mediator, myocardial infarction, optical coherence tomography, atherosclerosis, inflammation