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Dongmei Huang,1 Caizhong Zhou,2 Caili Li,3 Huiqiao Huang,4 Xiao Pan,3 Yanfei Pan,3 Qini Pan,3 Lichong Lai3 1Department of Rehabilitation Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Internal Medicine, Second People’s Hospital of Teng County, Wuzhou, Guangxi, People’s Republic of China; 3Nursing Department, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Party Committee Office, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Huiqiao Huang, Email hhq@sr.gxmu.edu.cnObjective: To investigate the current status of elderly health services in medical institutions at all levels within Guangxi Province, China.Methods: Using a purposeful sampling method, a questionnaire survey was conducted from July 24, 2023 to October 24, 2023 on the general situation, human resources, rehabilitation medicine, nursing services, and the development of hospice care at 1305 medical institutions in Guangxi.Results: Among the surveyed 1305 medical institutions in Guangxi, 172 (13.18%) had established departments of geriatrics, while 293 (22.45%) boasted departments of rehabilitation medicine. Furthermore, 909 (69.66%) of these institutions offered annual free physical examination services to individuals aged 65 and above. Notably, a total of 362 medical institutions, encompassing both comprehensive hospitals and grassroots hospitals, were recognized as elderly-friendly institutions, accounting for 31.4% of the surveyed sample.The highest demand for talents in medical institutions at all levels included specialized physicians/general practitioners (74.6%), traditional Chinese medicine practitioners (63.1%), rehabilitation therapists (56.1%), and specialized nurses for the elderly (41.7%). A total of 1038 medical institutions conducted popular science activities on elderly health, accounting for 79.5% of the total, focusing mainly on disease prevention (89.21%), nutritional diets (84.68%), rational medication use (79.77%), physical exercise (68.21%), and mental health (60.79%). Only 88 medical institutions provided hospice care services, accounting for 6.7% of the total.Conclusion: Guangxi medical institutions’ elderly services are inadequate. Geriatrics and rehab departments are scarce, talent is lacking, and hospice care is underdeveloped. As aging accelerates, the country and society must support elderly care. Governments should introduce talent incentives, and medical institutions should enhance services, foster a positive work environment, and advance Guangxi’s elderly health agenda.Keywords: medical institutions, elderly health services, elderly care, hospice care, current status

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

Xiuqi Qiao,1,2 Xiaoxia Wang,1 Lixin Guo,1,2 Qi Pan1,2 1Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 2Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of ChinaCorrespondence: Lixin Guo; Qi Pan, Email glx1218@163.com; panqi621@126.comBackground: Prior research based on observations has furnished evidence that supports a connection between daytime napping and the prevalence of non-alcoholic fatty liver disease (NAFLD). Nevertheless, the question of whether this correlation is indicative of a causal link has not been definitively answered.Methods: We used meta-analysis and Mendelian randomization (MR) to synthesize genetic and observational data. A two-sample MR analysis was conducted, leveraging 105 single-nucleotide polymorphisms (SNPs) known to be associated with daytime napping patterns. Additionally, summary-level data pertaining to NAFLD outcomes were acquired from the comprehensive UK Biobank study. Network meta-analyses were employed to investigate the relationship between excessive daytime napping and NAFLD, while subgroup was also performed.Results: Significant associations were observed between daytime napping and NAFLD. The systematic review/meta-analysis uncovered a heightened risk of NAFLD development among individuals who engaged in daytime naps exceeding 30 minutes, when compared to those who did not nap(odds ratio [OR] = 1.32, 95% confidence interval [CI]: 1.05 to 1.66). Furthermore, MR analysis indicated that a genetic propensity towards longer daytime napping was significantly linked to an increased likelihood of NAFLD (OR = 2.26, 95% CI: 1.38 to 3.73).Conclusion: Daytime napping has been found to be causally related to a higher risk of NAFLD. Furthermore, across all participants, napping for an average duration over 30 minutes was linked to an elevated likelihood of NAFLD.Keywords: daytime napping, non-alcoholic fatty liver disease, genetic variants, Mendelian randomization, network meta-analysis

Longyin Zhu,* Juan Cai,* Jia Fang, Lingyu Ran, Huan Chang, Huhai Zhang, Jiamin Zeng, Qin Yang, Chunxiao Fu, Qingping Li, Qianguang Pan, Hongwen Zhao Department of Nephrology, the First Hospital Affiliated to Army Military Medical University (Southwest Hospital), Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongwen Zhao; Qianguang Pan, Email zhaohw212@126.com; panqianguang@163.comObjective: Analyze risk factors for cardiac surgery-associated acute kidney injury (CSA-AKI) in adults and establish a nomogram model for CSA-AKI based on plasma soluble urokinase-type plasminogen activator receptor (suPAR) and clinical characteristics.Methods: In a study of 170 patients undergoing cardiac surgery with cardiopulmonary bypass, enzyme-linked immunosorbent assay (ELISA) measured plasma suPAR levels. Multivariable logistic regression analysis identified risk factors associated with CSA-AKI. Subsequently, the CSA-AKI nomogram model was developed using R software. Predictive performance was evaluated using a receiver operating characteristic (ROC) curve and the area under the curve (AUC). Internal validation was performed through the Bootstrap method with 1000 repeated samples. Additionally, decision curve analysis (DCA) assessed the clinical applicability of the model.Results: Multivariable logistic regression analysis revealed that being male, age ≥ 50 years, operation time ≥ 290 minutes, postoperative plasma suPAR at 2 hours, and preoperative left ventricular ejection fraction (LVEF) were independent risk factors for CSA-AKI. Employing these variables as predictive factors, a nomogram model was constructed, an ROC curve was generated, and the AUC was computed as 0.817 (95% CI 0.726– 0.907). The calibration curve indicated the accuracy of the model, and the results of DCA demonstrated that the model could benefit the majority of patients.Conclusion: Being male, age ≥ 50 years, operation time ≥ 290 minutes, low preoperative LVEF, and elevated plasma suPAR at 2 hours are independent risk factors for CSA-AKI. The nomogram model established based on these risk factors has high accuracy and clinical value, serving as a predictive tool for assessing the risk of CSA-AKI.Keywords: nomogram, acute kidney injury, prediction model, risk factors, cardiac surgery

Zhao-Ting Gong,1 Yu-Yan Xiong,1,2 Yu Ning,1 Rui-Jie Tang,1 Jun-Yan Xu,3 Wen-Yang Jiang,1 Xiao-Song Li,1 Li-Li Zhang,1 Cheng Chen,1 Qi Pan,1 Meng-Jin Hu,1 Jing Xu,1 Yue-Jin Yang1 1State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100037, People’s Republic of China; 2Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of ChinaCorrespondence: Yue-Jin Yang, Email yangyjfw@126.comBackground: Exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) have been considered as a promising cell-free therapeutic strategy for ischemic heart disease. Cardioprotective drug pretreatment could be an effective approach to improve the efficacy of MSC-exo. Nicorandil has long been used in clinical practice for cardioprotection. This study aimed to investigate whether the effects of exosomes derived from nicorandil pretreated MSC (MSCNIC-exo) could be enhanced in facilitating cardiac repair after acute myocardial infarction (AMI).Methods: MSCNIC-exo and MSC-exo were collected and injected into the border zone of infarcted hearts 30 minutes after coronary ligation in rats. Macrophage polarization was detected 3 days post-infarction, cardiac function as well as histological pathology were measured on the 28th day after AMI. Macrophages were separated from the bone marrow of rats for in vitro model. Exosomal miRNA sequencing was conducted to identify differentially expressed miRNAs between MSCNIC-exo and MSC-exo. MiRNA mimics and inhibitors were transfected to MSCs or macrophages to explore the specific mechanism.Results: Compared to MSC-exo, MSCNIC-exo showed superior therapeutic effects on cardiac functional and structural recovery after AMI and markedly elevated the ratio of CD68+ CD206+/ CD68+cells in infarcted hearts 3 days post-infarction. The notable ability of MSCNIC-exo to promote macrophage M2 polarization was also confirmed in vitro. Exosomal miRNA sequencing and both in vivo and in vitro experiments identified and verified that miR-125a-5p was an effector of the roles of MSCNIC-exo in vivo and in vitro. Furthermore, we found miR-125a-5p promoted macrophage M2 polarization by inhibiting TRAF6/IRF5 signaling pathway.Conclusion: This study suggested that MSCNIC-exo could markedly facilitate cardiac repair post-infarction by promoting macrophage M2 polarization by upregulating miR-125a-5p targeting TRAF6/IRF5 signaling pathway, which has great potential for clinical translation. Keywords: mesenchymal stem cell, exosomes, nicorandil, macrophage polarization, myocardial infarction

Lin Chen,1,* Qini Pan,2,* Xiaohong Li,3 Shuangli Luo,4 Xiao Pan,2 Huiqiao Huang2 1Department of Cardiology, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of nursing, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3College of Life Sciences, Chongqing Normal University, Chongqing, People’s Republic of China; 4Department of nursing, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guxngxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huiqiao Huang; Xiao Pan, Email huangedugx@126.com; 1910026304@qq.comPurpose: Practitioners in China who implement hospice care services include doctors, nurses, and care workers. These individuals play an important role in the holistic care of patients at the end of life and their families. This study aimed to provide baseline data to develop hospice care services and improve relevant policies by investigating the knowledge and attitudes of hospice care practitioners (HCPs) and analyzing influencing factors.Methods: This cross-sectional descriptive study used stratified sampling and quota sampling. The HCPs were from nursing homes, medical institutions, integrated medical and nursing institutions, and community health service centers in Guangxi Zhuang Autonomous Region. We examined HCPs’ demographic characteristics and scores on a self-designed Chinese scale to measure their knowledge and attitudes(K&A scale). A total of 1821 HCPs completed surveys from May 2022 to July 2022. The data were analyzed using descriptive statistics, univariate analysis and multiple linear regression.Results: The standard score of the K&A scale of 1821 HCPs was 61.62 (SD=9.78), and the individual mean scores of knowledge and attitudes were 76.42 (SD=28.13) and 58.69 (SD=11.31), respectively. The final multiple linear regression analysis indicated that the main factors that influenced the K&A score were monthly income, job satisfaction, and the hospice care-related system (HCS).Conclusion: The HCPs in this study displayed moderate mean scores for knowledge and a less favorable attitude toward hospice care. Monthly income, job satisfaction and the HCS were the common factors that influenced HCPs’ K&A. The results suggest the need to strengthen targeted and professional training for HCPs, increase their welfare and benefits, and improve indigenous policies of hospice care.Keywords: attitudes, hospice care practitioners, hospice care-related system, knowledge

Chunkun Yang,1,* Qinwei Zhu,2,* Yanbo Chen,3,* 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*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

Qiuyu Pan,1,2,* Jun Hu,1,3,* Yangzong,1 Xiuling Zhang,4 Zhaxidawa1 1Medical College of Tibet University, Lhasa, Tibet, 850000, People’s Republic of China; 2School of Public Health, North Sichuan Medical College, Nanchong, Sichuan, 610037, People’s Republic of China; 3School of Management, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, People’s Republic of China; 4The Hospital of Shandong Normal University, Jinan, Shandong, 250014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhaxidawa, Medical College of Tibet University, Lhasa, Tibet, 850000, People’s Republic of China, Email zhaxi0891@qq.comBackground: Aging and its consequences are receiving considerable global attention in developed and developing countries. The health-related quality of life (HRQoL) of elderly individuals is crucial for public health and social welfare. Despite advances in understanding the health status of the elderly population in Tibet, a region located on China’s southwest border, a significant research gap remains regarding their HRQoL.Methods: We conducted a cross-sectional study in Tibet, China, in 2018, which thoroughly examined HRQoL and its determinants in individuals aged 60 and above. The EQ-5D-VAS instrument, consisting of two standardized scales (EQ-5D-3L and EQ-VAS), was utilized to measure HRQoL. We based the selection of potential determinants on a novel health ecological model encompassing various environmental and personal factors. We employed the Least Absolute Shrinkage and Selection Operator regression to systematically pinpoint key predictive factors for dimensionality reduction. The Tobit regression analysis further elucidated the relationship between these factors and the EQ-VAS and EQ-5D-index scores.Results: Our study encompassed 1604 elderly participants. They presented varying severity levels across all five dimensions of the EQ-5D-3L. The most commonly observed issue was pain/discomfort, with a prevalence of 40.27%. The average EQ-VAS score was 56.15 (SD=21.15), and the mean EQ-5D-index score was 0.78 (SD=0.25). Our multivariate analysis revealed that determinants such as age, sex, number of chronic illnesses, vision problems, hearing problems, physical activity, employment status, social participation, place of residence, and insurance type were significantly associated with HRQoL.Conclusion: The HRQoL of Tibet’s elderly population presents significant concerns, especially given the region’s challenging natural conditions. This underscores the urgent need for focused policy interventions at the socio-economic strata to extend vital support and aid.Keywords: HRQoL, the elderly, ecological model, Tibet, high altitude

Longyin Zhu,1,* Huhai Zhang,1,* Jia Fang,1 Shuang Xiao,2 Fu Xiong,3 Caixia Deng,3 Qin Yang,1 Chunxiao Fu,1 Qianguang Pan,1 Hongwen Zhao1 1Department of Nephrology, the First Hospital Affiliated to Army Military Medical University (Southwest Hospital), Chongqing, 400038, People’s Republic of China; 2Department of Infectious Disease, the First Hospital Affiliated to Army Military Medical University (Southwest Hospital), Chongqing, 400038, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, the First Hospital Affiliated to Army Military Medical University (Southwest Hospital), Chongqing, 400038, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongwen Zhao; Qianguang Pan, Email zhaohw212@126.com; panqianguang@163.comIntroduction: We report a fatal case of massive airway bleeding caused by pulmonary strongyloidiasis in a patient with a transplanted kidney.Case Presentation: A 47-year-old male, regularly taking immunosuppressants post-kidney transplant, visited our hospital with symptoms of abdominal bloating, nausea, and emesis persisting for three days. After hospitalization, he developed a cough, hemoptysis, and respiratory failure. Sputum analysis confirmed an infestation with Strongyloides stercoralis. Despite receiving albendazole therapy and bronchoscopic management for bronchial hemorrhage, the patient ultimately died due to acute respiratory and circulatory collapse triggered by severe airway bleeding.Conclusion: Patients undergoing immunosuppressive therapy following kidney transplantation are at increased risk for disseminated strongyloidiasis. Consequently, infectious disease screening prior to transplantation, along with essential preventive pharmacotherapy, is of paramount importance.Keywords: strongyloides stercoralis, kidney transplantation, airway bleeding, disseminated infection

Longyin Zhu,1 Huan Xu,2 Youmin Pu,1 Chunxiao Fu,1 Qianguang Pan,1,* Hongwen Zhao1,* 1Department of Nephrology, The First Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China; 2Department of Scientific Affairs, Vision Medicals Center for Infection Diseases, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongwen Zhao; Qianguang Pan, Department of Nephrology, The First Affiliated Hospital of Army Medical University, 30 Gaotanyanzheng Street, Shapingba District, Chongqing, 400038, People’s Republic of China, Tel/Fax +8613983360655 ; +86 18584651157, Email zhaohw212@126.com; panqianguang@163.comAbstract: We report a case of pneumocystis jiroveci pneumonia (PJP) in a 46-year-old woman, who previously underwent kidney transplant for chronic renal failure. She did not receive PJP prophylaxis treatment for the history of sulfonamide allergies. Four months after renal transplantation, the patient had cough, chest tightness, and shortness of breath. Procalcitonin (PCT) (0.06 ng/mL) and C-reactive protein (CRP) (5.33 mg/L) were normal, but the level of 1, 3-β-D-glucan test (G test, 193.89 pg/mL) were elevated. Metagenomics next-generation sequencing (mNGS) using bronchoalveolar lavage fluid (BALF) rapidly and accurately identified P. jiroveci. Through sulfonamide desensitization and sulfamethoxazole-trimethoprim (TMP-SMX) combined with caspofungin (CAS) treatment, PJP was controlled. However, the patients’ conditions were worsen for the hospital-acquired secondary pulmonary infection. A second BALF mNGS identified Enterobacter cloacae complex and Pseudomonas aeruginosa carrying carbapenem drug resistance genes, which were confirmed by subsequent culture and antimicrobial susceptibility test within 3 days. Finally, symptoms, such as chest tightness, cough, and shortness of breath, were improved and she was discharged after combined treatment with meropenem (MEM), polymyxin B (PMB), CAS, and TMP-SMX. In this case, mNGS, culture, and drug susceptibility testing were combined to monitor pathogenic microbial and adjust medication. At present, there are no case reports of mNGS use and sulfonamide desensitization in a kidney transplant recipient with sulfonamide allergies.Keywords: metagenomics next-generation sequencing, mNGS, Pneumocystis jiroveci pneumonia, PJP, sulfonamide allergies, SA, kidney transplant, KT, multiple drug-resistant Enterobacter cloacae complex, MDR-ECC, multiple drug-resistant Pseudomonas aeruginosa, MDR-PA

UNLABELLED: In the Diabetes Prevention Program Outcome Study (DPPOS), a cohort at high risk of diabetes, randomization to intensive lifestyle intervention or metformin, both associated with weight loss, did not have long-term negative effects on BMD compared with the placebo group. Potential positive effects of metformin on bone warrant further investigation. INTRODUCTION: Randomization to lifestyle intervention (ILS) or metformin in the Diabetes Prevention Program (DPP) resulted in weight loss and reduced progression to diabetes. Weight loss is associated with reduced bone mineral density (BMD), but the long-term effects of these interventions on BMD are unknown. In the DPP Outcome Study (DPPOS), we determined if randomization to ILS or metformin, compared with placebo, was associated with differences in BMD approximately 16 years later. METHODS: Of 3234 DPP participants, 2779 continued in DPPOS and were offered ILS in group format. Those randomized to metformin were offered unmasked metformin. At DPPOS year 12, 1367 participants had dual-energy X-ray absorptiometry scans. BMD in metformin and ILS groups was compared to placebo using sex-specific linear regression models, adjusted for age, race/ethnicity, and weight and weight-bearing activity at DPP baseline. RESULTS: At DPPOS year 12, mean age was 66.5 (±9.5) years. Femoral neck BMD was similar in the ILS and placebo groups in men (difference = -0.021 g/cm2, 95%CI (-0.063, 0.021)) and in women (+0.014 g/cm2, 95%CI (-0.014, 0.042)). Femoral neck BMD was higher in the metformin compared to placebo group although not statistically different in men (+0.017 g/cm2, 95% CI (-0.023, 0.058)) and in women (+0.019 g/cm2, 95% CI (-0.009, 0.047)). Prevalence of osteoporosis was low and similar across treatment groups in men (0.9%; p=0.745) and women (2.4%; p=0.466). CONCLUSION: In a cohort at high risk of diabetes, lifestyle intervention or metformin did not appear to have long-term negative effects on BMD. Potential positive effects of metformin on bone warrant further research.

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

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

Qianqian Pan,1,2 Mingjing Wei,1,3,4 Mengyi Lu,5 Yaping Xu,6 Xing Xie,1,3,4 Xiao Li1,3,4 1Department of Gynecologic Oncology, Women’s Hospital, School of Medicine Zhejiang University, Hangzhou, Zhejiang, 310006, People’s Republic of China; 2Zhejiang Financial College, Hangzhou, Zhejiang, People’s Republic of China; 3Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Hangzhou, Zhejiang, 310006, People’s Republic of China; 4Zhejiang University Cancer Center, Hangzhou, Zhejiang, 310058, People’s Republic of China; 5Wenzhou Central Hospital, Wenzhou, Zhejiang, People’s Republic of China; 6Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, 310003, People’s Republic of ChinaCorrespondence: Xiao Li, Women’s Hospital, Zhejiang University School of Medicine, No. 1 Xueshi Road, Hangzhou, Zhejiang, People’s Republic of China, 310006, Tel +86-0571-89998891, Fax +86-0571-89998891, Email 5198008@zju.edu.cnBackground: Increasing epidemiological evidence supported that chronic inflammatory factors might be involved in the carcinogenesis and progression of various cancers. The present study tried to investigate the prognostic value of perioperative C-reactive protein (CRP) in prognosis of patients with epithelial ovarian carcinoma (EOC) from a tertiary university teaching hospital.Methods: The cutoff value of CRP was calculated according to receiver operating characteristic (ROC) curve. Variables were compared using Chi-square test. Progress-free survival (PFS) and overall survival (OS) time were assessed by Kaplan–Meier (KM) survival analysis and Log rank test based on serum CRP level. Univariate and multivariate Cox regression analyses were applied for assessing the relationship between clinicopathological parameters and survival.Results: Higher perioperative CRP levels (preoperative ≥ 5.15 mg/L and postoperative ≥ 72.45 mg/L) were significantly associated with serous tumor, high-grade, advanced stage, elevated preoperative CA125, suboptimal surgery, chemotherapy resistance, recurrence and death in EOC (P < 0.01). KM analysis suggested patients with elevated preoperative, postoperative and perioperative CRP had shorter survival (P < 0.01). Elevated perioperative CRP was an independent risk factor for PFS (HR 1.510, 95% CI 1.124– 2.028; P = 0.006) and OS (HR 1.580, 95% CI 1.109– 2.251; P = 0.011). Similar results were obtained for elevated preoperative CRP. Subgroup analysis further suggested that elevated perioperative CRP was also an independent risk factor for prognosis in advanced stage and serous EOC.Conclusion: Elevated perioperative CRP was an independent risk factor for poorer prognosis of EOC, particularly in advanced stage and serous patients.Keywords: epithelial ovarian carcinoma, perioperative C-reactive protein, prognosis

Xiaoye Duan,1,2 Qi Pan,1 Lixin Guo1,2 1Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Lixin Guo, Email glx1218@163.comBackground: This study aimed to assess the effects of chronic sleep deprivation (CSD) on bone metabolism in growing rats and the likely underlying mechanism.Methods: Twenty 5-week-old male Wistar rats and randomly divided into the CSD and normal control (NC) groups after one-week acclimatization. After a 6-week intervention of sleep deprivation, the distal femurs of both groups were harvested for micro-computed tomography scans and histological analysis. Meanwhile, the femur tissues were measured the mRNA and protein expression via RNA sequencing and immunohistochemical analysis. Serum bone turnover markers were evaluated at 0, 2, 4, and 6 weeks.Results: CSD impaired the bone growth, showing an imbalance of bone turnover status, dysphasia in the metaphysis growth plate, and deterioration of bone microarchitecture. Further, CSD suppressed bone formation, showing that the expression of osteogenesis-related proteins (col1α 1 and osteocalcin) and mRNA (igf1, bglap, runx2, col1α 1, pth1r) are down-regulated. Differentially expressed genes were detected, and functional enrichment analyses revealed that the PI3K/AKT pathway was significantly down-regulated in the CSD group.Conclusion: These results suggest that CSD can significantly impaire bone health, and it may exert these effects in part by suppressing bone formation and osteoblast differentiation, and inactivating the PI3K/AKT signaling pathway.Keywords: chronic sleep deprivation, sleep loss, growth, bone formation, RNA sequencing, PI3K/AKT pathway

Hangbin Hu,1,&ast; Yifeng Lou,1,2,&ast; Haiting Feng,3 Jingjing Tao,1 Weixiao Shi,1 Shuangling Ni,4 Qunying Pan,3 Tianxiang Ge,3 Ping Shen,1 Zifeng Zhong,3 Yonghong Xiao,1 Tingting Qu1,3 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Infectious Disease Department, Sanmen People’s Hospital, Taizhou, Zhejiang, People’s Republic of China; 3Infection Control Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 4Infectious Disease Department, Lishui People’s Hospital, Lishui, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tingting Qu; Yonghong Xiao, Tel +86 571 87236673, Email qutingting@zju.edu.cn; yonghong@163.comObjective: Critical patients in intensive care unit (ICU) are highly susceptible to acquiring carbapenem-resistant Acinetobacter baumannii (CRAB) infection. To investigate the relationship between nosocomial infections and environmental health, we studied the distribution and homology of CRAB isolates from patients and environment and evaluated the effectiveness of infection control measures.Methods: In the 4-month study, we conducted a monthly CRAB screening of the ICU environment prior to disinfection in a Chinese teaching hospital. The ICU underwent routine disinfection procedures twice a day. We collected samples from the environment around the patients before disinfection. Clinical specimens from patients were also screened. The samples obtained were studied for phenotype and homology via antibiotic susceptibility testing, pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing (WGS).Results: Ten specimens were sampled from ICU environments. Five were obtained in May 2020, and sputums from patient a in bed A at this time were cultured for CRAB isolates; in June 2020 another 5 environmental specimens were obtained from the same bed unit for CRAB, and sputums from patient b in bed A at this time were also cultured for CRAB isolates. Following intensive infection control measures, environmental sampling was negative in July and August. These 18 CRAB isolates all carried OXA-66 and OXA-23 genes and showed a similar resistance phenotype. WGS showed a close relationship among specimens from patients’ sputum and their surroundings, but no homology between patients.Conclusion: The analysis of cgMLST and SNPs is more accurate for strain homology analysis. Our data confirm that CRAB isolates spread from patient to environment in ICU; however, contact isolation and disinfection measures are effective in avoiding transmission, highlighting the importance of continued education and surveillance of CRAB. WGS could provide rich information on antimicrobial resistance, which is of great value in scientific research and clinical diagnosis.Keywords: carbapenem-resistant Acinetobacter baumannii, intensive care unit, whole genome sequencing, cgMLST, PFGE

Apatites record crucial information on the origin, composition, and chemical evolution of volatiles on terrestrial planets. As a martian intrusive rock, the gabbroic shergottite Northwest Africa (NWA) 13581 provides key information on the volatile evolution related to magmatic processes in the interior, shedding light on the intricate volatile circulation on Mars. The textural and chemical characteristics of the phosphates in NWA 13581 indicate a complex formation history involving fractional crystallization, degassing, and fluid interaction. Degassing of the NWA 13581 parent melt is capable of exsolving chlorine‐rich fluids, resulting in the formation of notably fluorine‐rich apatite with a high x‐site occupancy of fluorine up to 90%. The degassed/exsolved volatile‐rich fluids could subsequently continue to migrate and interact with surrounding magmatic suites, leading to highly heterogeneous compositions of active fluids. The crystallization of apatite is initiated by the interaction of fluids with merrillite at the late stage of the magmatic process, leading to the formation of phosphate intergrowths. Influenced by the composition and chemical evolution of volatiles in fluids and melts, apatite exhibits notable variability in chlorine compositions both within individual grains and among different grains. Moreover, the presence of magnetite associated with phosphate intergrowth highlights the transportation of metallic components in addition to volatiles from deep layers to shallower depths or to the surface of Mars. This process, which is observed in young shergottites, indicates the persistent presence of hydrothermal systems until recent geological periods, contributing to the generation and circulation of volatiles within the martian interior and on the surface. Plain Language Summary: Understanding the volatile composition of Mars is crucial for assessing its potential habitability. Apatite in the intrusive gabbroic martian meteorite Northwest Africa (NWA) 13581 provides valuable insights into the presence and evolution of halogens in martian magma. The textural and chemical features of phosphates suggest a complex formation process involving fractional crystallization, degassing and fluid interaction. In the case of cumulates such as NWA 13581, degassing could result in the exsolution of fluids, potentially serving as a brine source for the martian surface. Subsequent interaction with chlorine‐rich fluids further modifies the composition of apatite. Moreover, the presence of secondary magnetite indicates that elements like Fe can be extracted from the melt and transported by fluids, implying potential mining resources with a magmatic origin on Mars. The processes observed in NWA 13581 are likely common among different subtypes of shergottites. The diverse composition of apatite in shergottites that have undergone fluid interaction indicates localized and heterogeneous compositions of active fluids. The formation history preserved in NWA 13581 phosphate highlights the ongoing generation and circulation of volatiles on Mars, even in recent geological periods. Key Points: Phosphates in martian meteorite NWA 13581 support the magmatic origin of halogen fluids related to the magmatic process of shergottitesThe presence of magnetite indicates that hydrothermal fluids enable iron transportation and aggregation from the mantle to a shallower depthHydrothermal systems may have been common and active in recent geological periods, contributing to martian volatile generation and circulation [ABSTRACT FROM AUTHOR]

Defeng Pan,1,&ast; Yufei Zhou,2,&ast; Shengjue Xiao,1,&ast; Yue Hu,3,&ast; Chunyan Huan,1 Qi Wu,1 Xiaotong Wang,1 Qinyuan Pan,1 Jie Liu,1 Hong Zhu1 1Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 2Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of General Practice, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Defeng PanDepartment of Cardiology, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai West Road, Xuzhou, 221004, Jiangsu, People’s Republic of ChinaTel +86 516-83262017Email xzdefengpan@xzhmu.edu.cnIntroduction: Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, but the molecular mechanisms underlying AF are not known. We aimed to identify the pivotal genes and pathways involved in AF pathogenesis because they could become potential biomarkers and therapeutic targets of AF.Methods: The microarray datasets of GSE31821 and GSE41177 were downloaded from the Gene Expression Omnibus database. After combining the two datasets, differentially expressed genes (DEGs) were screened by the Limma package. MicroRNAs (miRNAs) confirmed experimentally to have an interaction with AF were screened through the miRTarBase database. Target genes of miRNAs were predicted using the miRNet database, and the intersection between DEGs and target genes of miRNAs, which were defined as common genes (CGs), were analyzed. Functional and pathway-enrichment analyses of DEGs and CGs were performed using the databases DAVID and KOBAS. Protein–protein interaction (PPI) network, miRNA- messenger(m) RNA network, and drug-gene network was visualized. Finally, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to validate the expression of hub genes in the miRNA–mRNA network.Results: Thirty-three CGs were acquired from the intersection of 65 DEGs from the integrated dataset and 9777 target genes of miRNAs. Fifteen “hub” genes were selected from the PPI network, and the miRNA-mRNA network, including 82 miRNAs and 9 target mRNAs, was constructed. Furthermore, with the validation by RT-qPCR, macrophage migration inhibitory factor (MIF), MYC proto-oncogene, bHLH transcription factor (MYC), inhibitor of differentiation 1 (ID1), and C-X-C Motif Chemokine Receptor 4 (CXCR4) were upregulated and superoxide Dismutase 2 (SOD2) was downregulated in patients with AF compared with healthy controls. We also found MIF, MYC, and ID1 were enriched in the transforming growth factor (TGF)-β and Hippo signaling pathway.Conclusion: We identified several pivotal genes and pathways involved in AF pathogenesis. MIF, MYC, and ID1 might participate in AF progression through the TGF-β and Hippo signaling pathways. Our study provided new insights into the mechanisms of action of AF.Keywords: atrial fibrillation, bioinformatics analysis, differentially expressed genes, pathways, protein–protein interaction network

Yao Tong,&ast; Chengrong Bao,&ast; Yi-Qiong Xu,&ast; Lei Tao,&ast; Yao Zhou, Lei Zhuang, Ying Meng, Hui Zhang, Jingjing Xue, Weijun Wang, Lele Zhang, Qingbo Pan, Zhenzhen Shao, Tianran Hu, Qian Guo, Qingsheng Xue, Han Lu, Yan Luo Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Luo; Han Lu Email ly11087@rjh.com.cn; luhan0301@163.comBackground: Acute lung injury (ALI) is a severe respiratory disease with high rates of morbidity and mortality. Many mediators regarding endogenous or exogenous are involved in the pathophysiology of ALI. Here, we have uncovered the involvement of integrins and matrix metalloproteinases, as critical determinants of excessive inflammation and endothelial permeability, in the regulation of ALI.Methods: Inflammatory cytokines were measured by quantitative real-time PCR for mRNA levels and ELISA for secretion levels. Endothelial permeability assay was detected by the passage of rhodamine B isothiocyanate-dextran. Mice lung permeability was assayed by Evans blue albumin (EBA). Western blot was used for protein level measurements. The intracellular reactive oxygen species (ROS) were evaluated using a cell-permeable probe, DCFH-DA. Intratracheal injection of lipopolysaccharide (LPS) into mice was conducted to establish the lung injury model.Results: Exogenous MMP-9 significantly aggravated the inflammatory response and permeability in mouse pulmonary microvascular endothelial cells (PMVECs) treated by LPS, whereas knockdown of MMP-9 exhibited the opposite phenotypes. Knockdown of integrin β 3 or β 5 in LPS-treated PMVECs significantly downregulated MMP-9 expression and decreased inflammatory response and permeability in the presence or absence of exogenous MMP-9. Additionally, the interaction of MMP-9 and integrin β 5 was impaired by a ROS scavenger, which further decreased the pro-inflammatory cytokines production and endothelial leakage in PMVECs subjected to co-treatment (LPS with exogenous MMP-9). In vivo studies, exogenous MMP-9 treatment or knockdown β 3 integrin significantly decreased survival in ALI mice. Notably, knockdown of β 5 integrin alone had no remarkable effect on survival, but which combined with anti-MMP-9 treatment significantly improved the survival by ameliorating excessive lung inflammation and permeability in ALI mice.Conclusion: These findings support the β 3/5 integrin-MMP-9 axis as an endogenous signal that could play a pivotal role in regulating inflammatory response and alveolar-capillary permeability in ALI.Keywords: acute lung injury, endothelial cells, integrin, MMP-9

Qi Pan,1 Jing Xu,1 Cen-Jin Wen,2 Yu-Yan Xiong,1 Zhao-Ting Gong,1 Yue-Jin Yang1 1State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Yue-Jin YangState Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaEmail yangyjfw@126.comAbstract: Despite several recent advances, current therapy and prevention strategies for myocardial infarction are far from satisfactory, owing to limitations in their applicability and treatment effects. Nanoparticles (NPs) enable the targeted and stable delivery of therapeutic compounds, enhance tissue engineering processes, and regulate the behaviour of transplants such as stem cells. Thus, NPs may be more effective than other mechanisms, and may minimize potential adverse effects. This review provides evidence for the view that function-oriented systems are more practical than traditional material-based systems; it also summarizes the latest advances in NP-based strategies for the treatment and prevention of myocardial infarction.Keywords: nanoparticles, myocardial infarction, treatment, prevention

Jiaxin Bian,1,2 Hongyu Chen,1,2 Junhui Sun,1,2 Yuqing Cao,3 Jianhong An,3 Qing Pan,4 Ming Qi1,2,5– 8 1Department of Cell Biology and Medical Genetics, School of Medicine Zhejiang University, Hangzhou, 310000, People’s Republic of China; 2Center for Precision Medicine, Zhejiang-California International NanoSystems Institute, Hangzhou, 310000, People’s Republic of China; 3School of Optometry and Ophthalmology Wenzhou Medical College, Wenzhou, People’s Republic of China; 4Department of Ophthalmology, Zhejiang University Medical School First Affiliated Hospital, Hangzhou, 310000, People’s Republic of China; 5Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Department of Laboratory Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, 310000, People’s Republic of China; 6DIAN Diagnostics, Hangzhou, 310000, People’s Republic of China; 7Department of Pathology and Laboratory of Medicine, University of Rochester Medical Centre, Rochester, NY, 14609, USA; 8HVP-China, Hangzhou, 310000, People’s Republic of ChinaCorrespondence: Qing PanDepartment of Ophthalmology, Zhejiang University Medical School First Affiliated Hospital, 79 Qingchun Road, Hangzhou, People’s Republic of ChinaTel +86 13515814709Email panqing@hotmail.comMing QiDepartment of Cell Biology and Medical Genetics, School of Medicine Zhejiang University, Research Building A713, Yuhangtang Road 866, Hangzhou, People’s Republic of ChinaTel +86 13666686943Fax +86 57188208274Email mingqi@zju.edu.cn; ming_qi@urmc.Rochester.eduPurpose: The aim of study was to establish Rdh12-associated inherited retinal disease (Rdh12-IRD) mouse model and to identify the best timepoint for gene therapy.Methods: We induced retinal degeneration in Rdh12−/− mice using a bright light. We clarified the establishment of Rdh12-IRD mouse model by analyzing the thickness of retinal layers and electroretinography (ERG). Rdh12-IRD mice received a subretinal injection of adeno-associated virus 2/8-packaged Rdh12 cDNA for treatment. We evaluated the visual function and retinal structure in the treated and untreated eyes to identify the best timepoint for gene therapy.Results: Rdh12-IRD mice showed significant differences in ERG amplitudes and photoreceptor survival compared to Rdh12+/+ mice. Preventive gene therapy not only maintained normal visual function but also prevented photoreceptor loss. Salvage gene therapy could not reverse the retinal degeneration phenotype of Rdh12-IRD mice, but it could slow down the loss of visual function.Conclusion: The light-induced retinal degeneration in our Rdh12−/− mice indicated that a defect in Rdh12 alone was sufficient to cause visual dysfunction and photoreceptor degeneration, which reproduced the phenotypes observed in RDH12-IRD patients. This model is suitable for gene therapy studies. Early treatment of the primary Rdh12 defect helps to delay the later onset of photoreceptor degeneration and maintains visual function in Rdh12-IRD mice.Keywords: Rdh12, retinal diseases, mouse model, gene therapy

Shengjue Xiao,1,&ast; Linyun Zhang,1,2,&ast; Qi Wu,1,&ast; Yue Hu,3 Xiaotong Wang,1 Qinyuan Pan,1 Ailin Liu,1 Qiaozhi Liu,1 Jie Liu,1 Hong Zhu,1 Yufei Zhou,4,5 Defeng Pan1 1Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 2Department of Cardiology, The People’s Hospital of Suzhou New District, Suzhou, Jiangsu, 215000, People’s Republic of China; 3Department of General Practice, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 4Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 5Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, 200030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Defeng PanDepartment of Cardiology, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai West Road, Xuzhou, 221004, Jiangsu, People’s Republic of ChinaTel +86 516-83262017Email xzdefengpan@xzhmu.edu.cnObjective: Percutaneous coronary intervention (PCI) is one of the most effective treatments for acute coronary syndrome (ACS). However, the need for postoperative revascularization remains a major problem in PCI. This study was to develop and validate a nomogram for prediction of revascularization after PCI in patients with ACS.Methods: A retrospective observational study was conducted using data from 1083 patients who underwent PCI (≥ 6 months) at a single center from June 2013 to December 2019. They were divided into training (70%; n = 758) and validation (30%; n = 325) sets. Multivariate logistic regression analysis was used to establish a predictive model represented by a nomogram. The nomogram was developed and evaluated based on discrimination, calibration, and clinical efficacy using the concordance statistic (C-statistic), calibration plot and decision curve analysis (DCA), respectively.Results: The nomogram was comprised of ten variables: follow-up time (odds ratio (OR): 1.01; 95% confidence interval (CI): 1.00– 1.03), history of diabetes mellitus (OR: 1.83; 95% CI: 1.25– 2.69), serum creatinine level on admission (OR: 0.99; 95% CI: 0.98– 1.00), serum uric acid level on admission (OR: 1.005; 95% CI: 1.002– 1.007), lipoprotein-a level on admission (OR: 1.0021; 95% CI: 1.0013– 1.0029), low density lipoprotein cholesterol level on re-admission (OR: 1.33; 95% CI: 0.10– 0.47), the presence of chronic total occlusion (OR: 3.30; 95% CI: 1.93– 5.80), the presence of multivessel disease (OR: 4.48; 95% CI: 2.85– 7.28), the presence of calcified lesions (OR: 1.63; 95% CI: 1.11– 2.39), and the presence of bifurcation lesions (OR: 1.82; 95% CI: 1.20– 2.77). The area under the receiver operating characteristic curve values for the training and validation sets were 0.765 (95% CI: 0.732– 0.799) and 0.791 (95% CI: 0.742– 0.830), respectively. The calibration plots showed good agreement between prediction and observation in both the training and validation sets. DCA also demonstrated that the nomogram was clinically useful.Conclusion: We developed an easy-to-use nomogram model to predict the risk of revascularization after PCI in patients with ACS. The nomogram may provide useful assessment of risk for subsequent treatment of ACS patients undergoing PCI.Keywords: acute coronary syndrome, percutaneous coronary intervention, revascularization, nomogram, prediction model

Yi-Jie Zhang,1,2 Qi Pan,1,2 Yang Yu,1,2 Xin-Ping Zhong1,2 1Department of Hepatobiliary and Organ Transplantation, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 2The Key Laboratory of Organ Transplantation of Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of ChinaCorrespondence: Xin-Ping ZhongDepartment of Hepatobiliary and Organ Transplantation, The First Affiliated Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang 110001, Liaoning Province, People’s Republic of ChinaTel +86-13309831481Email zhongxp2@yeah.netBackground and Aim: Hepatocellular carcinoma (HCC) is a type of cancer with high mortality rates. The overexpression of microRNA-519d (miR-519d) has been explored in different types of cancers, which could significantly help suppress cancer development. This study aimed to investigate the interaction of miR-519d with its target gene, Rab10, as well as its effects on cell proliferation and autophagy in HCC cells through modulation of the AMPK signaling pathway.Methods: Microarray analysis was used to analyze the differentially expressed genes in HCC, and the target genes of the screened-out miRNA were predicted and verified. The expression of miR-519d and Rab10, AMPK signaling pathway-related proteins, apoptosis- and autophagy-related proteins was determined by RT-qPCR and Western blot analysis in HCC tissues and cell lines. Lastly, the effects of miR-519d and Rab10 in HCC cell proliferation, apoptosis, and mouse tumour xenograft in vivo were examined through gain- and loss-of-function experiments.Results: MiR-519d was down-regulated and Rab10 was upregulated in HCC tissues and cell lines. Overexpression of miR-519d decreased the expression of Rab10, mTOR, and Bcl-2, but increased the expression of Bax, Beclin1, Atg5, and p53. Upregulated miR-519d and downregulated Rab10 expression suppressed cell proliferation and induced cell apoptosis and autophagy in HCC cells. Finally, upregulation of miR-519d inhibited tumour growth in vivo.Conclusion: The result obtained in this study indicates that up-regulation of miR-519d inhibits proliferation and promotes apoptosis and autophagy of HCC cells through activation of the AMPK signaling pathway via downregulating Rab10, which provides a potential target for the treatment of HCC.Keywords: microRNA-519, Rab10, Adenosine 5ʹ-monophosphate-activated protein signaling pathway, hepatocellular carcinoma, proliferation, autophagy

Objective: To construct a prediction model for fetal growth restriction (FGR) during the first trimester of pregnancy and evaluate its screening performance. Methods: This was a prospective cohort study of singleton pregnancies that underwent routine ultrasound screening at 11 to 13 + 6 weeks at the Affiliated Suzhou Hospital of Nanjing Medical University between January 2019 and April 2022. Basic clinical information, ultrasound indicators and serum biomarkers of pregnant women were collected. Fetal weight assessment was based on the fetal growth curve for the Southern Chinese population. FGR was diagnosed according to Delphi consensus criteria. Least absolute shrinkage and selection operator (lasso) regression was used to select variables for inclusion in the model. Discrimination, calibration and clinical effectiveness of the model were evaluated in training and validation cohorts. Results: A total of 1188 pregnant women were included, of whom 108 had FGR. Lasso regression identified seven predictive features, including history of maternal hypertension, maternal smoking or passive smoking, gravidity, uterine artery pulsatility index, ductus venosus pulsatility index and multiples of the median values of placental growth factor and soluble fms‐like tyrosine kinase‐1. The nomogram prediction model constructed from these seven variables accurately predicted FGR, and the area under the receiver‐operating‐characteristics curve in the validation cohort was 0.82 (95% CI, 0.74–0.90). The calibration curve and Hosmer–Lemeshow test demonstrated good calibration, and the clinical decision curve and clinical impact curve supported its practical value in a clinical setting. Conclusion: The multi‐index prediction model for FGR has good predictive value during the first trimester. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]