Search

Mengdie Chen,1 Ping Feng,1 Yao Liang,2 Xun Ye,3 Yiyun Wang,2 Qiao Liu,1 Chaoyin Lu,1 Qidong Zheng,2 Lijing Wu2 1Department of Endocrinology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, People’s Republic of China; 2Department of Internal Medicine, Yuhuan Second People’s Hospital, Yuhuan, Zhejiang, People’s Republic of China; 3Department of Endocrinology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Lijing Wu, Department of Internal Medicine, Yuhuan Second People’s Hospital, No.77, Environmental Protection Middle Road, Chu Men Town, Yuhuan, Zhejiang, 317600, People’s Republic of China, Tel: +86-13777603508, Email 13777603508@163.comPurpose: This study was developed with the goal of clarifying whether there is any relationship between type 2 diabetes mellitus (T2DM) age of onset and clinical outcomes for patients in National Metabolic Management Centers (MMC).Patients and Methods: From September 2017 - June 2022, 864 total T2DM patients were recruited in MMC and assigned to those with early-onset and late-onset diabetes (EOD and LOD) based on whether their age at disease onset was ≤ 40 or > 40 years. All patients received standardized management. Baseline and 1-year follow-up data from these two groups of patients were assessed. Associations between onset age and other factors were evaluated with a multivariate linear regression approach, adjusting for appropriate covariates. Outcomes in particular subgroups were also assessed in stratified analyses.Results: Markers of dysregulated glucose metabolism and BMI values were significantly higher among EOD patients as compared to LOD patients. Subjects in both groups exhibited significant improvements in several disease-related parameters on 1-year follow-up after undergoing metabolic management. EOD patients exhibited significantly greater percentage reductions in HbA1c levels (− 28.49 (− 44.26, − 6.45)% vs − 13.70 (− 30.15,-1.60)%, P =0.017) relative to LOD patients following adjustment for confounders. Significant differences were also detected between these groups when focused on subgroups of patients who were male, exhibited a BMI ≥ 25, an HbA1c ≥ 9, or had a follow-up frequency < 2.Conclusion: Data from a 1-year follow-up time point suggest that a standardized metabolic disease management model can promote effective metabolic control in newly diagnosed T2DM patients, particularly among individuals with EOD.Keywords: age of onset, disease management, type 2 diabetes

Qinliang Zheng,1– 3,&ast; Meng Chen,4,&ast; Jennifer Hu,5 Ting Zhou,5 Peipei Wang6 1Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China; 2Shandong Provincial Key Medical and Health Discipline of Pediatric Internal Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China; 3Jining Key Laboratory for Prevention and Treatment of Severe Infection in Children, Affiliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China; 4Department of Cardiology, Affiliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China; 5Department of Medical Psychology, School of Health Humanities, Peking University, Beijing, People’s Republic of China; 6Sleep and Psychosomatic Medicine Center, Sanya Central Hospital/The Third People’s Hospital of Hainan Province, Sanya, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ting Zhou, Department of Medical Psychology, School of Health Humanities, Peking University, N0.38 Xueyuan Road, Haidian District, Beijing, 100191, People’s Republic of China, Email zhouting.92@bjmu.edu.cn Peipei Wang, Sleep and Psychosomatic Medicine Center, Sanya Central Hospital/The Third People’s Hospital of Hainan Province, No. 1154 Jiefangsi Road, Sanya, Hainan, 572000, People’s Republic of China, Email peipeiwang@pku.edu.cnObjective: This study aimed to examine the association between appearance comparison and adolescent depressive symptoms, the mediating role of body appreciation, and the moderating roles of gender and body-mass index (BMI) among adolescents in different age groups.Methods: A cross-sectional sample of 2645 Chinese students aged 12– 16 years (44.7% girls) participated. The measurements included depressive symptoms, appearance comparison, body appreciation, weight, and height. Multigroup path analysis was used to examine the moderated mediation model.Results: Compared with boys, adolescent girls presented greater levels of appearance, which increased with age. Body appreciation mediated the association between appearance comparison and depressive symptoms in girls, whereas appearance comparison directly correlated with depressive symptoms in boys. Body appreciation decreased with increasing BMI in boys but remained relatively stable in girls. Similar patterns were observed among junior and senior high school students.Conclusion: This study underscores the significant relationship between appearance comparison and adolescent depressive symptoms, suggesting varied mechanisms based on gender and BMI levels.Keywords: appearance comparison, body appreciation, adolescent depressive symptoms, gender difference, age group difference, body-mass index

Yue Wang,1 Jie Chen,1 Han Dong,2 Rui-Lin Ma,1 Ying Zou,3 Wei Wang,4 Qingmei Zheng,5 Ying Feng,6 Zhangyun Tan,7 Xiaoqin Zeng,8 Yinqing Zhao,7 Yan Deng,1 Yanfang Wang,1 Bei Gu,9 Aijun Sun1,10 1National Clinical Research Center for Obstetric & Gynecologic Diseases Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of Obstetrics and Gynecology, Women and Children’s Hospital of Jinzhou, Jinzhou, Liaoning, 121000, People’s Republic of China; 3Department of Obstetrics and Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, 410008, People’s Republic of China; 4Department of Reproductive Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 5Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266500, People’s Republic of China; 6Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 7Department of Obstetrics and Gynecology, Xinhui Maternity and Children’s Hospital, Nanning, Guangxi, 529100, People’s Republic of China; 8Department of Gynecology, Guangzhou Women and Children’s Medical Center, Guangzhou, Guangdong, 510000, People’s Republic of China; 9Department of Obstetrics and Gynecology, Beijing Shijitan Hospital, Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing, 100038, People’s Republic of China; 10Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, 100010, People’s Republic of ChinaCorrespondence: Aijun Sun, Email saj@pumch.cnBackground: The basic medical education stage is not enough to support physicians to fully diagnose and evaluate polycystic ovary syndrome (PCOS). The study aims to discover the difference in treatment choice between participants with different annual consultation number of PCOS, to promote lifelong learning, and drive balanced development within healthcare.Methods: This is a multicenter cross-sectional survey. Participants’ basic information, knowledge of PCOS and treatment options were collected online. According to the annual consultation number of patients with PCOS, physicians were divided into three groups: 0– 50 people/yr, 50– 200 people/yr, and > 200 people/yr, and the results were derived from χ2 test, Fisher exact test, and multivariate logistic regression analysis.Results: The study analyzed 1689 questionnaires, and 1206 physicians (71.4%) received less than 50 women per year, 388 physicians (30.0%) with an annual number of 50– 200 women, and 95 physicians (5.6%) with patient turnover for more than 200 people. Reproductive endocrinologists generally have higher access to the clinic. As the number of visits increases, more and more physicians would perceive patients as more likely to have abnormal blood glucose and heavy weight. Physicians with large numbers of consultations are more likely to use Asian or Chinese standards to assess obesity. The multivariate analysis involved variables such as age, hospital level, specialty, and patient turnover annually, and more young doctors actively assessed lipid profile (odds ratio (OR) 1.56, 95% confidence interval (CI) (1.16, 2.16)), and primary hospitals (OR 0.65 CI (0.44, 0.89)) chose OGTT for blood glucose assessment less than tertiary hospitals. Physicians in secondary hospitals are more aggressive in evaluating androgens.Conclusion: Our survey found differences in endocrine assessment, metabolic screening, and treatment in PCOS women in terms of the number of obstetrician-gynecologists who received different patient consultation numbers. The importance of continuing education for physicians is emphasized, to promote lifelong learning.Keywords: polycystic ovary syndrome, consultation number, lifelong learning, insulin resistance, obesity, hyperandrogenemia, metformin

Shuaijun Cao,1,&ast; Xiaoying Jiang,2,&ast; Jinshan Suo,3 Yanyan Lu,2 Mohan Ju,2 Qixiang Zeng,1 Qingru Zheng,1 Zuoyan Zhang,1 Wenqi Tang1 1Department of Critical Care Medicine, Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zuoyan Zhang; Wenqi Tang, Department of Critical Care Medicine, Shanghai Sixth People’s Hospital, No. 600 Yishan Road, Shanghai, 200000, People’s Republic of China, Tel +86 021-24058331, Email 18930177049@189.cn; zhang_zy1969@163.comIntroduction: Carbapenem-Resistant Enterobacteriaceae (CRE) has posed a significant threat to humans.The aim of this study was to investigate the molecular characteristics of blaKPC-producing Escherichia coli in a university-affiliated tertiary hospital.Methods: Polymerase chain reaction (PCR) and BLAST+ software were used to detect the prevalence of blaKPC in E. coli and Klebsiella pneumoniae. Whole-genome sequencing was performed for the blaKPC-harboring clinical E. coli isolates. Antimicrobial resistance genes, MLSTs, KPC-carrying plasmid typing and genetic environment of blaKPC were analyzed. A maximum likelihood core single nucleotide polymorphism (SNP)-based phylogeny tree was constructed to determine the evolutionary relationships within this ST131 collection. Conjugation experiments were performed to determine the mobilization of blaKPC. The minimal inhibitory concentrations of the common antimicrobial agents were determined using the broth microdilution method.Results: The prevalence of blaKPC in 424 clinical E. coli isolates and 1636 E. coli strains from GenBank database were 2.2% (45/2060) whereas the detection rate of blaKPC in K. pneumoniae from the GenBank database was 29.8% (415/1394). The blaKPC-harboring conjugants exhibited resistance to multiple β-lactams, except for cefepime-zidebactam and ceftazidime-avibactam. All blaKPC-carring E. coli isolates were susceptible to tigecycline and polymyxin B. ST131 was the dominant sequence type of blaKPC-carring E. coli, accounting for 40.0% (18/45). Most of the blaKPC-producing ST131 E. coli (89.5%,17/19) belonged to clade C ST131 lineage. Genetic environment analysis revealed that 57.8% (26/45) of blaKPC gene was linked to Tn 4401-associated structure ISKpn6-blaKPC-ISKpn7. IncN was the most common plasmid type in KPC-producing E. coli whereas IncFII was the dominant plasmid type in KPC-producing K. pneumoniae.Conclusion: The detection rate of blaKPC was lower in E. coli compared with K. pneumoniae. The dominant sequence and plasmid types of blaKPC-harboring isolates differed between E. coli and K. pneumoniae. Further studies about the role of the defense system in acquisition of KPC-plasmids in E. coli will be performed to provide new insights into the low prevalence of blaKPC.Keywords: Escherichia coli, blaKPC, carbapenemases, plasmids typing

Qinzhou Zheng,1,&ast; Cuimin Chen,2,&ast; Yong Liu,3 Jie Gao,2,&ast; Luxin Li,1 Chuan Yin,4 Xiaohuan Yuan1 1College of Life Science, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 2Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China; 3Center for Comparative Medicine, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 4Department of Gastroenterology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuan Yin, Department of Gastroenterology, Shanghai Changzheng Hospital, Naval Medical, University, Shanghai, 200003, People’s Republic of China, Email ilse1225@163.com Xiaohuan Yuan, College of Life Science, Mudanjiang Medical University, Mudanjiang, 157001, Heilongjiang, People’s Republic of China, Tel/Fax +86-453-6984647, Email yuanxiaohuan@mdjmu.edu.cnAbstract: Diabetic wounds pose a significant challenge to public health, primarily due to insufficient blood vessel supply, bacterial infection, excessive oxidative stress, and impaired antioxidant defenses. The aforementioned condition not only places a significant physical burden on patients’ prognosis, but also amplifies the economic strain on the medical system in treating diabetic wounds. Currently, the effectiveness of available treatments for diabetic wounds is limited. However, there is hope in the potential of metal nanoparticles (MNPs) to address these issues. MNPs exhibit excellent anti-inflammatory, antioxidant, antibacterial and pro-angiogenic properties, making them a promising solution for diabetic wounds. In addition, MNPs stimulate the expression of proteins that promote wound healing and serve as drug delivery systems for small-molecule drugs. By combining MNPs with other biomaterials such as hydrogels and chitosan, novel dressings can be developed and revolutionize the treatment of diabetic wounds. The present article provides a comprehensive overview of the research progress on the utilization of MNPs for treating diabetic wounds. Building upon this foundation, we summarize the underlying mechanisms involved in diabetic wound healing and discuss the potential application of MNPs as biomaterials for drug delivery. Furthermore, we provide an extensive analysis and discussion on the clinical implementation of dressings, while also highlighting future prospects for utilizing MNPs in diabetic wound management. In conclusion, MNPs represent a promising strategy for the treatment of diabetic wound healing. Future directions include combining other biological nanomaterials to synthesize new biological dressings or utilizing the other physicochemical properties of MNPs to promote wound healing. Synthetic biomaterials that contain MNPs not only play a role in all stages of diabetic wound healing, but also provide a stable physiological environment for the wound-healing process.Keywords: metal nanoparticles, wound healing, diabetic wound, drug delivery, antibacterial activity

Qingcong Zheng,1,&ast; Du Wang,2,&ast; Rongjie Lin,3,&ast; Yuchao Chen,4 Zixing Xu,1 Weihong Xu1 1Department of Orthopedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Arthritis Clinical and Research Center, Peking University People’s Hospital, Beijing, People’s Republic of China; 3Department of Orthopedic Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 4Department of Paediatrics, Fujian Provincial Hospital South Branch, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zixing Xu; Weihong Xu, Email xuzixing@fjmu.edu.cn; xuweihong815@126.comBackground: Rheumatoid arthritis (RA) is one of the most common chronic inflammatory autoimmune diseases. However, the underlying molecular mechanisms of its pathogenesis are unknown. This study aimed to identify the common biomarkers of ferroptosis and pyroptosis in RA and screen potential drugs.Methods: The RA-related differentially expressed genes (DEGs) in GSE55235 were screened by R software and intersected with ferroptosis and pyroptosis gene libraries to obtain differentially expressed ferroptosis-related genes (DEFRGs) and differentially expressed pyroptosis-related genes (DEPRGs). We performed Gene Ontology (GO), Kyoto Encyclopedia of the Genome (KEGG), ClueGO, and Protein-Protein Interaction (PPI) analysis for DEFRGs and DEPRGs and validated them by machine learning. The microRNA/transcription factor (TF)-hub genes regulatory network was further constructed. The key gene was validated using the GSE77298 validation set, cellular validation was performed in in vitro experiments, and immune infiltration analysis was performed using CIBERSORT. Network pharmacology was used to find key gene-targeting drugs, followed by molecular docking and molecular dynamics simulations to analyze the binding stability between small-molecule drugs and large-molecule proteins.Results: Three hub genes (CASP8, PTGS2, and JUN) were screened via bioinformatics, and the key gene (CASP8) was validated and obtained through the validation set, and the diagnostic efficacy was verified to be excellent through the receiver operating characteristic (ROC) curves. The ferroptosis and pyroptosis phenotypes were constructed by fibroblast-like synoviocytes (FLS), and caspase-8 was detected and validated as a common biomarker for ferroptosis and pyroptosis in RA, and quercetin can reduce caspase-8 levels. Quercetin was found to be a potential target drug for caspase-8 by network pharmacology, and the stability of their binding was further verified using molecular docking and molecular dynamics simulations.Conclusion: Caspase-8 is an important biomarker for ferroptosis and pyroptosis in RA, and quercetin is a potential therapy for RA via targeting caspase-8 through ferroptosis and pyroptosis.Keywords: rheumatoid arthritis, ferroptosis, pyroptosis, caspase-8, quercetin

Xiang Li,1,&ast; Shanghua Xiao,2,&ast; Nina Filipczak,3 Satya Siva Kishan Yalamarty,3 Hongming Shang,4 Jing Zhang,2 Qin Zheng2 1National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China; 2Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China; 3Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USA; 4Department of Biochemistry & Chemical Biology, Vanderbilt University, Nashville, TN, USA&ast;These authors contributed equally to this workCorrespondence: Jing Zhang; Qin Zheng, Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, People’s Republic of China, Email jing.zhang@jxutcm.edu.cn; 20060903@jxutcm.edu.cnAbstract: Neutrophil extracellular traps (NETs) are large DNA reticular structures secreted by neutrophils and decorated with histones and antimicrobial proteins. As a key mechanism for neutrophils to resist microbial invasion, NETs play an important role in the killing of microorganisms (bacteria, fungi, and viruses). Although NETs are mostly known for mediating microbial killing, increasing evidence suggests that excessive NETs induced by stimulation of physical and chemical components, microorganisms, and pathological factors can exacerbate inflammation and organ damage. This review summarizes the induction and role of NETs in inflammation and focuses on the strategies of inhibiting NETosis and the mechanisms involved in pathogen evasion of NETs. Furthermore, herbal medicine inhibitors and nanodelivery strategies improve the efficiency of inhibition of excessive levels of NETs.Graphical Abstract: Keywords: neutrophil extracellular traps, inflammation, targeted inhibition, nanotherapy, herbal medicine

Fayang Ling,1,&ast; Wenchuan Qi,1,&ast; Xiao Li,1,&ast; Jun Zhou,1 Jian Xiong,1 Yi Zhao,1 Qianhua Zheng,1 Fanrong Liang2 1Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine/Clinical Research Center for Acupuncture and Moxibustion in Sichuan Province, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fanrong Liang, Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine/Clinical Research Center for Acupuncture and Moxibustion in Sichuan Province, Chengdu, People’s Republic of China, Tel +86 136 0805 8216, Fax +86-028-87683962, Email acuresearch@126.com Qianhua Zheng, Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China, Tel +86 189 0870 5127, Fax +86-028-87683962, Email zhengqianhua@cdutcm.edu.cnPurpose: Cancer pain is a common symptom of cancer patients and greatly affects quality of life. Acupuncture has certain curative effects on cancer pain. The aim of this study was to analyze and visualize the current status and research trend of acupuncture treatment for cancer pain over the last 10 years and provide directions for future development.Methods: A search of the Web of Science Core Collection from 2012– 01-01 to 2022– 08-20 was performed to collect studies related to acupuncture therapy for cancer pain. CiteSpace was used to conduct bibliometric analysis and visualization from the perspective of the volume of annual publications, journals, nations, institutions, authors, keywords, and references.Results: A total of 302 studies were included in the analysis. The number of publications increased steadily with some fluctuations over the past decade. Integrative Cancer Therapies was the journal with the most relevant publications, and the Journal of Clinical Oncology was the most frequently cited journal. China had the highest volume of publications, and the USA contributed most to international collaboration. The most prolific institution was Memorial Sloan Kettering Cancer Center. The most productive author was Mao JJ, and the most influential author was Lu WD. “Acupuncture” was the top keyword in frequency and centrality. The references with the highest frequency and centrality were published by HE, Y, and Ting Bao, respectively.Conclusion: A stable development trend has formed in this field. The overall collaborative network needs to be strengthened. Breast cancer and multiple myeloma, electroacupuncture and bee venom acupuncture, postoperative pain, peripheral neuropathic pain syndrome, and aromatase inhibitors-associated arthralgia syndrome are research hotspots in this field. Randomized controlled trials (RCTs), evidence-based evaluations and mechanisms (cancer-induced bone pain) are research trends and frontiers.Keywords: acupuncture analgesia, cancer, pain, bibliometric analysis, CiteSpace

Guangtao Fu,1,&ast; Rongjie Wu,1,2,&ast; Ruiying Zhang,1,&ast; Duanyong Chen,1 Haotao Li,1 Qiujian Zheng,1,3 Yuanchen Ma1 1Department of Orthopedics, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 2Shantou University Medical College, Shantou, People’s Republic of China; 3The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanchen Ma, Tel +86-18688889132, Email myc998@qq.com; Qiujian Zheng, Tel +86-13802740561, Email zhengqiujian@gdph.org.cnBackground: Vitamin D deficiency is a common comorbidity in geriatric hip fracture patients. However, there is still an ongoing debate regarding the influence of preoperative Vitamin D status on postoperative mortality in hip fracture patients.Methods: Elderly patients (≥ 60 years) who underwent surgical interventions for unilateral hip fracture from 2015 to 2020 in our center were included. We retrospectively retrieved the demographic data from the electronic medical database. Preoperative serum total 25-hydroxy-Vitamin D was set as the independent variable and patients were classified as the Vitamin D deficiency (< 20ng/mL) and the control groups consequently. Clinical outcomes include all-cause mortality, walking ability, and major postoperative complications in the first postoperative year. Propensity score matching (PSM) was performed in a ratio of 1:1 in the two groups for further comparison.Results: A total of 210 patients were included and 121 patients (57.6%) were diagnosed with Vitamin D deficiency. Patients in the Vitamin D deficiency group were much older and therefore preferred peripheral nerve block, and had significantly higher proportions of females, preoperative dementia, higher ASA grade, and lower baseline serum albumin level. Overall, 79 patients were identified in the Vitamin D deficiency and control groups after PSM, respectively. Patients diagnosed with Vitamin D deficiency showed a significantly higher one-year mortality (21.5% vs 6.3%, P=0.011) and a much lower one-year independent walking rate (67.1% vs.84.8%, P=0.016) after the matching. Regarding the dataset before PSM and after PSM, the AUC for serum Vitamin D for predicting one-year mortality was 0.656 (P=0.006) and 0.695 (P=0.002), respectively.Conclusion: Our retrospective PSM-design study provides new evidence that Vitamin D deficiency was associated with a significantly higher mortality and poor walking ability in the first year after surgical intervention based on southern Chinese populations.Keywords: vitamin D deficiency, mortality, hip fracture, propensity score match, Chinese population

Qi Zheng,1,&ast; Le Kuai,2,&ast; Wencheng Jiang,1,&ast; Yan Qiang,3 Lei Wei,2 Siting Chen,2 Bin Li,1 Ruiping Wang3,4 1Department of Traditional Chinese Medicine, Shanghai Skin Diseases Hospital, Tongji University, Shanghai, People’s Republic of China; 2Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Clinical Research and Innovation Transformation Center, Shanghai Skin Diseases Hospital, Tongji University, Shanghai, People’s Republic of China; 4School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Li; Ruiping Wang, Email 18930568129@163.com; w19830901@126.comBackground: Gender difference is prevalent in clinical feature, disease severity for noncommunicable diseases (NCD), but studies on gender disparity in clinical feature, disease severity and NCD comorbidity among psoriasis patients are limited. This cross-sectional study explores gender differences in clinical feature, lifestyle behavior and NCD comorbidity among psoriasis patients.Methods: Psoriasis patients were recruited through cluster survey method in two hospitals, and questionnaire interviews were applied to collect the demographic feature, lifestyle habits, clinical feature and NCD among patients.Results: A total of 2102 psoriasis patients included 1332 males (63.4%), 70% were over 35 years old and approximately 50% of them were overweight or obesity. The median value for psoriasis initiation age and disease duration was 33 years old (34 for male and 32 for female) and 9 years (10 for male and 7 for female), respectively. The psoriasis recurrence was mainly in winter (73.4%) and autumn (34.2%) both for patients. The prevalence of tobacco smoking and alcohol drinking was 31.2% and 12.6%. Male patients had higher prevalence of tobacco smoking (odds ratio (OR) = 13.26, 95% confidence interval (CI): 9.54– 18.44) and alcohol drinking (OR = 14.44, 95% CI: 7.90– 26.40). The prevalence of diabetes, hypertension, hyperlipidemia, and metabolic syndrome were 13.2%, 28.5%, 23.4% and 21.5%, respectively. Male patients had higher prevalence of diabetes (OR = 1.53, 95% CI: 1.16– 2.02), hypertension (OR = 1.87, 95% CI: 1.52– 2.30), hyperlipidemia (OR = 2.34, 95% CI: 1.85– 2.95) and metabolic syndrome (OR = 2.06, 95% CI: 1.63– 2.62) than female patients. The proportions for 4 types of NCDs diagnosed after psoriasis onset were over 58%, which were also higher in males than females.Conclusion: Female patients had shorter disease duration and with less NCD, and male patients had more body weight issue, with fewer sleep time and higher prevalence of tobacco smoking and alcohol drinking and NCDs. We recommend that dermatologist should notice the gender disparity in psoriasis patients, which is helpful for the disease diagnosis and treatment.Keywords: psoriasis, gender disparity, tobacco smoking, alcohol drinking, overweight, metabolic diseases, comorbidity

Enhui Guo,1,2,&ast; Chengqian Li,2,3,&ast; Yanjiao Hu,4 Kongyuan Zhao,1,2 Qingmei Zheng,1,&ast; Liming Wang1,&ast; 1Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Qingdao Medical College, Qingdao University, Qingdao, People’s Republic of China; 3Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 4Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingmei Zheng; Liming Wang, Department of Gynecology, The Affiliated Hospital of Qingdao University, No. 1677, Wutaishan Road, Huangdao District, Qingdao, Shandong, 266000, People’s Republic of China, Tel +86-18661806725 ; +86-18661807912, Email zhengqingmei0532@126.com; wlmqingyi@163.comAbstract: Leiomyoma with bizarre nuclei (LBN), also known as symplastic leiomyoma, is a histological subtype of benign leiomyoma with bizarre cells and nuclear atypia. Differentiating LBN from other benign leiomyoma subtypes, uterine smooth muscle tumors of uncertain malignant potential (STUMP), or leiomyosarcoma (LMS) can be diagnostically challenging owing to overlapping features in clinical presentation and pathologic morphological analysis. The difficulty of distinguishing LBN from other lesions, especially from LMS, and the potential of LBN for subsequent malignant transformation make LBN an important topic of research. Herein, we review the definition, diagnosis, treatment, and prognosis of LBN. Histopathological examination is essential for distinguishing LBN from other diseases. Pathology sampling and morphological examination remain the key to diagnosis. The newly established ancillary immunohistochemical (IHC) and molecular genetic analysis can be useful tools for differential diagnosis. Furthermore, serum biomarkers and imaging examination may also be useful diagnostic tools. Attention should be paid to the differentiation between LBN and LMS because morphological diagnosis may still be challenging in some cases. Some IHC markers of LBN have been identified, which may be helpful for differential diagnosis. Furthermore, the use of IHC panels as diagnostic markers may be advocated. Molecular genetic studies suggest that some genes can aid with the differential diagnosis between LBN and LMS. However, increasing evidence support the idea that LBN and LMS are molecularly related, indicating that LBN may represent a potentially malignant stage of precancerous progression. At present, conservative treatment is recommended for primary LBN, especially for patients desiring to retain fertility, but close follow-up with imaging examinations is required.Keywords: diagnosis, histopathology, molecular genetics, imaging examination, treatment, prognosis

Hanbi Wang,1 Zhiyuan Zhang,2 Jie Chen,1 Han Dong,3 Ying Zou,4 Wei Wang,5 Qingmei Zheng,6 Ying Feng,7 Zhangyun Tan,8 Xiaoqin Zeng,9 Yinqing Zhao,8 Yanfang Wang,1 Aijun Sun1 1Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of International Medical Service, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Obstetrics and Gynecology, Women and Children’s Hospital of Jinzhou, Jinzhou, Liaoning, People’s Republic of China; 4Department of Obstetrics and Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, People’s Republic of China; 5Department of Reproductive Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 6Department of Gynecology, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 7Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 8Department of Obstetrics and Gynecology, Xinhui Maternity and Children’s Hospital, Nanning, People’s Republic of China; 9Department of Gynecology, Guangzhou Women and Children’s Medical Center, Guangzhou, People’s Republic of ChinaCorrespondence: Aijun Sun, Email saj@pumch.cnObjective: To explore the needs of obstetricians and gynecologists with different working years for the contents and forms of CME.Methods: The online questionnaire was distributed on the largest academic training platform for obstetrics and gynecology in China from April 2020 to May 2020. The survey contents mainly included the training forms and training contents of CME, as well as the mastery of diseases by doctors with different working years.Results: 4458 questionnaires were returned, of which 3954 questionnaires were included in the study. There was a significant (p < 0.001) positive correlation between the mastery of 19 diseases by obstetricians and gynecologists with different working years. After adjusting for specialist departments, hospital grades, nature of units and ages, it was found that there was no statistically significant difference between the groups in gynecological endocrine-related diseases, such as precocious puberty/delayed puberty, and there was also no statistically significant difference between the groups of shorter working years in infertility, menopausal syndrome, hyperprolactinemia and premature ovarian failure.Conclusion: The most popular training content for obstetricians and gynecologists with different working years is common gynecological endocrine diseases, of which abnormal uterine bleeding, menopausal syndrome, polycystic ovarian syndrome and cervical lesions are the most selected diseases, and the most popular form of training is online.Keywords: continuing medical education, working years, internet, obstetrics and gynecology

Shiqi Wang,1 Chao Xia,2 Qirui Zheng,3 Aiping Wang,4 Qian Tan1 1Department of Burns and Plastic Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China; 2Department of Orthopedics, Air Force Hospital of Eastern Theater Command, Nanjing, People’s Republic of China; 3Software Institute, Nanjing University, Nanjing, People’s Republic of China; 4Department of Endocrinology, Air Force Hospital of Eastern Theater Command, Nanjing, People’s Republic of ChinaCorrespondence: Qian Tan, Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China, Tel +86 25 83106666, Email smmutanqian@sina.com Aiping Wang, Department of Endocrinology, Air Force Hospital of Eastern Theater Command, Nanjing, 210002, People’s Republic of China, Email wap454hospital@163.comBackground: Early detection of hard-to-heal diabetic foot ulcers (DFUs) is vital to prevent a poor prognosis. The purpose of this work was to employ clinical characteristics to create an optimal predictive model of hard-to-heal DFUs (failing to decrease by > 50% at 4 weeks) based on machine learning algorithms.Methods: A total of 362 DFU patients hospitalized in two tertiary hospitals in eastern China were enrolled in this study. The training dataset and validation dataset were split at a ratio of 7:3. Univariate logistic analysis and clinical experience were utilized to screen clinical characteristics as predictive features. The following six machine learning algorithms were used to build prediction models for differentiating hard-to-heal DFUs: support vector machine, the naïve Bayesian (NB) model, k-nearest neighbor, general linear regression, adaptive boosting, and random forest. Five cross-validations were employed to realize the model’s parameters. Accuracy, precision, recall, F1-scores, and AUCs were utilized to compare and evaluate the models’ efficacy. On the basis of the best model identified, the significance of each characteristic was evaluated, and then an online calculator was developed.Results: Independent predictors for model establishment included sex, insulin use, random blood glucose, wound area, diabetic retinopathy, peripheral arterial disease, smoking history, serum albumin, serum creatinine, and C-reactive protein. After evaluation, the NB model was identified as the most generalizable model, with an AUC of 0.864, a recall of 0.907, and an F1-score of 0.744. Random blood glucose, C-reactive protein, and wound area were determined to be the three most important influencing factors. A corresponding online calculator was created (https://predicthardtoheal.azurewebsites.net/).Conclusion: Based on clinical characteristics, machine learning algorithms can achieve acceptable predictions of hard-to-heal DFUs, with the NB model performing the best. Our online calculator can assist doctors in identifying the possibility of hard-to-heal DFUs at the time of admission to reduce the likelihood of a dismal prognosis.Keywords: hard-to-heal, diabetic foot ulcers, machine learning, classification

Wenhao Liao,1,&ast; Yuchen Li,1,2,&ast; Jing Wang,3,&ast; Maoyuan Zhao,1 Nianzhi Chen,1 Qiao Zheng,1 Lina Wan,1 Yu Mou,1 Jianyuan Tang,1,4 Zhilei Wang1,4 1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Department of Obstetrics and Gynecology, Bishan Hospital of Traditional Chinese Medicine, Chongqing, People’s Republic of China; 4TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianyuan Tang; Zhilei Wang, Email tangjy@cdutcm.edu.cn; wangzl1993@outlook.comAbstract: Cancer stem cells (CSCs) lead to the occurrence and progression of cancer due to their strong tumorigenic, self-renewal, and multidirectional differentiation abilities. Existing cancer treatment methods cannot effectively kill or inhibit CSCs but instead enrich them and produce stronger proliferation, invasion, and metastasis capabilities, resulting in cancer recurrence and treatment resistance, which has become a difficult problem in clinical treatment. Therefore, targeting CSCs may be the most promising approach for comprehensive cancer therapy in the future. A variety of natural products (NP) have significant antitumor effects and have been identified to target and inhibit CSCs. However, pharmacokinetic defects and off-target effects have greatly hindered their clinical translation. NP-based nanoformulations (NPNs) have tremendous potential to overcome the disadvantages of NP against CSCs through site-specific delivery and by improving their pharmacokinetic parameters. In this review, we summarize the recent progress of NPNs targeting CSCs in cancer therapy, looking forward to transforming preclinical research results into clinical applications and bringing new prospects for cancer treatment.Keywords: cancer, cancer stem cells, nanoformulations, natural products, targeted therapy

Xiting Wang, Hao Wang, Qin Zheng, Hui Geng, Jing Zhang, Yan Fan, Xueru Feng, Xiahuan Chen, Meilin Liu Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Meilin Liu, Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China, Email liumeilin@hotmail.comPurpose: Although aspirin can effectively reduce the occurrence of atherothrombosis, it is significantly associated with increased bleeding, with elderly individuals being at increased risk of cardiovascular diseases (CVD) and hemorrhage. This study aims to evaluate the efficacy and safety of aspirin 50 mg/d and 100 mg/d for the prevention and management of CVD in Chinese elderly.Patients and Methods: The Low-dose Aspirin for Primary and Secondary Prevention of Cardiovascular Disease in the Elderly Study (LAPIS) is a multicenter, prospective, observational cohort study, this study was a single-center interim analysis of LAPIS. Patients aged ≥ 60 and required long-term aspirin for primary and secondary prevention of CVD were eligible. From Apr 1, 2019 to Feb 28, 2022, 165 patients who received 50 mg/d aspirin and 261 patients who received 100 mg/d aspirin were included in the study. The incidence of major cardiovascular events (MACEs), bleeding events, and gastrointestinal adverse events were compared between two groups.Results: After adjusting for patient characteristics using propensity score matching, aspirin 100 mg/d was associated with increased incidence rates of total bleeding events (28.34 vs.17.25 events/100 patient-years, HR 1.671, 95% CI 1.024– 2.712, P = 0.040) and minor bleeding events (27.63 vs.15.92 events/100 patient-years, HR 1.738, 95% CI 1.056– 2.861, P = 0.031), whereas the incidence of MACE (6.35 vs 6.65 events/100 patient-years, HR 0.921, 95% CI 0.399– 2.127, P = 0.848) and gastrointestinal adverse events (12.73 vs.10.42 events/100 patient-years, HR 1.206, 95% CI 0.623– 2.337, P = 0.578) were similar between the two groups. Multivariate Cox analysis identified that aspirin dose (100 mg/d vs. 50 mg/d, HR 1.918, 95% CI 1.137– 3.235, P = 0.015), concomitant use of other antiplatelets (HR 1.748, 95% CI 1.009– 3.028, P = 0.046) and anticoagulants (HR 2.501, 95% CI 1.287– 4.862, P = 0.007) were independently associated with bleeding events.Conclusion: 50 mg/d aspirin may be preferred to balance the safety and effectiveness in Chinese individuals over 60 years of age who need long-term aspirin for the prevention and management of CVD.Trial Registration: ChiCTR1900021980 (chictr.org.cn). Registered on 19 March 2019.Keywords: low-dose aspirin, effectiveness outcome, safety outcome, Chinese elderly

Yuhui Yang,1,&ast; Guangtao Fu,1,&ast; Qingtian Li,1,&ast; Ruiying Zhang,1 Weihong Liao,1,2 Yuanchen Ma,1 Qiujian Zheng1,2 1Department of Orthopedics, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 2The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanchen Ma; Qiujian Zheng, Email mayuanchen@gdph.org.cn; zhengqiujian@gdph.org.cnObjective: This study aimed to investigate the risk factors associated with dislocation and dissociation following bipolar hemiarthroplasty (HA) for the treatment of patients with femoral neck fractures.Methods: We retrospectively reviewed 462 patients (479 hips) treated with bipolar HA from January 2010 to January 2020. All patients received posterolateral approaches and a minimum follow-up of at least 2 years regularly. A case–control study was performed to analyze the risk factors of dislocation regarding patient demographics, coexisting diseases, surgical and morphologic features. Multivariable logistic regression analysis for independent risk factors affecting dislocation and dissociation was also performed.Results: The dislocation rate was 5.01%, and the mean time from HA to the first incident of dislocation was 38.75 days. Patient-related factors, including operation side, prosthesis type, and neuromuscular disease, did not differ significantly. Regarding the morphological factors, a significant difference was observed in center-edge (CE) angle, abduction angle, acetabular depth, depth/width ratio, rotation center (RC) to greater trochanter tip (GTT) vertical distance, RC to GTT vertical distance difference, RC to GTT horizontal distance, RC to GTT horizontal distance difference, offset difference, and offset discrepancy. Further, decreased CE angle, increased abduction angle, decreased RC to GTT vertical distance, decreased offset difference and increased offset discrepancy were determined to be independent risk factors of dislocation. The proportion of patients experiencing dissociation was 1.04%. All the implanted femoral heads were smaller than 43 mm, which was determined to be the risk factor of dissociation.Conclusion: Decreased CE angle, RC to GTT vertical distance, offset difference, and increased abduction angle, offset discrepancy were determined to be independent risk factors of HA dislocation. Once dislocation risk was detected by simulated templating, THA or changing surgical approach should be considered to avoid evitable perioperative complications.Keywords: bipolar hemiarthroplasty, dislocation, morphological evaluation, greater trochanter tip, offset

Qingfei Chu,&ast; Xinyu Gu,&ast; Qiuxian Zheng, Jing Wang, Haihong Zhu State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haihong Zhu Tel +86-13656632056Email zhuhh72@zju.edu.cnBackground: PPAT (phosphoribosyl pyrophosphate amido transferase) catalyzes the first committed step of de novo purine biosynthesis and is a key regulatory point in the biosynthesis of nascent purine nucleotides. However, the clinical significance and biologic role of PPAT in hepatocellular carcinoma (HCC) remain unknown.Methods: We compared the expression of PPAT in carcinomatous and precancerous hepatocellular carcinoma tissues by immunohistochemistry in 90 cases of HCC. Correlation analysis was also made on clinical data, survival, classification, and staging.Results: The expression of PPAT in HCC tumor tissues is significantly higher than that in adjacent normal tissues. The results of the Kaplan–Meier analysis showed that HCC patients with high PPAT expression survived shorter than those with low PPAT expression. Moreover, the expression of PPAT was significantly associated with the tumor grade (P=0.014), PD-L1 (P< 0.001), and CTLA4 (P=0.003). The later grade of the tumor, the higher the expression of PPAT. In the PD-L1 high expression group, PPAT is also highly expressed.Conclusion: Our study demonstrated that PPAT expression might be included in the process of carcinogenesis and prognosis. Hence, PPAT could be served as a new prognostic biomarker for patients of HCC.Keywords: PPAT, HCC, prognosis, biomarker, metabolism

Zhiqiang Yang, Xinglang Wu, Junbo Li, Qiang Zheng, Junwei Niu, Shengwei Li Department of Hepatobiliary Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Shengwei Li Tel/Fax +8618780728917Email lishengwei@hospital.cqmu.edu.cnBackground: Hepatocellular carcinoma (HCC) is a highly malignant, recurrent and drug-resistant tumor, and patients often lose the opportunity for surgery when they are diagnosed. Abnormal gene expression is closely related to the occurrence of HCC. The aim of the present study was to identify the differentially expressed genes (DEGs) between tumor tissue and non-tumor tissue of HCC samples in order to investigate the mechanisms of liver cancer.Methods: The gene expression profile (GSE62232, GSE89377, and GSE112790) was downloaded from the Gene Expression Omnibus (GEO) and analyzed using the online tool GEO2R to identify differentially expressed genes (DEGs). Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery. Protein–protein interaction (PPI) of these DEGs was analyzed based on the Search Tool for the Retrieval of Interacting Genes database and visualized by Cytoscape software. In addition, we used the online Kaplan–Meier plotter survival analysis tool to evaluate the prognostic value of hub genes expression. HPA database was used to reveal the differences in protein level of hub genes.Results: A total of 50 upregulated DEGs and 122 downregulated DEGs were identified. Among them, ten hub genes with a high degree of connectivity were picked out. Overexpression of these hub genes was associated with unfavorable prognosis of HCC.Conclusion: Our study suggests that CCNB2, CDC20, AURKA, TOP2A, MELK, NCAPG, KIF20A, UBE2C, PRC1, and ASPM were overexpressed in HCC compared with normal liver tissue. Overexpression of these genes was an unfavorable prognostic factor of HCC patients. Further study is needed to explore the value of them in the diagnosis and treatment of HCC.Keywords: hepatocellular carcinoma, hub genes, expression profiling data, protein–protein interaction network

Dong-qi Lin,1 Jin-guo Zhu,1 Xiao-hua Xu,1 Ke Xiao,1 Xu-qing Wen,1 Qi-fa Zheng,1 Yu-hua Zhou,2 Xin-ying Cai3 1Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 2Nursing Department, Shantou Central Hospital, Shantou, Guangdong, People’s Republic of China; 3Clinical Research Center, Shantou Central Hospital, Shantou, Guangdong, People’s Republic of ChinaCorrespondence: Xin-ying CaiClinical Research Center, Shantou Central Hospital, Wai-ma Road 114, Shantou, Guangdong, People’s Republic of ChinaTel +86 754-88903584Fax +86 754-88548117Email cxy305527@yeah.netPurpose: The association between the process of postoperative pneumonia and lung cancer recurrence remains elusive in lung cancer surgery. Herein, the association between postoperative pneumonia and lung cancer recurrence was investigated, emphasizing the warning role of postoperative specific pneumonia in primary lung cancer resection patients.Methods: The occurrence of postoperative pneumonia was assessed in 4– 6 months (PPFS), 7– 12 months (PPST), and lung cancer recurrence within 1 year (LRO) in 332 patients. The primary outcome was the development of PPST and LRO according to PPFS occurrence. The relevant risk factors of PPFS, PPST, and LRO were identified through multivariable regression analysis.Results: During follow-up, 151 (45.48%) participants experienced PPFS. Irrespective of the existing postoperative pneumonia in 1– 3 months (PPOT), PPFS significantly increased the risk of PPST (P < 0.01) and LRO (P < 0.01), and persistent PPST further increased the risk of LRO (P < 0.001). The generalized estimating equation identified chemotherapy as an independent risk factor for PPFS and PPST.Conclusion: PPFS was associated with the increased risk of PPST and LRO. Postoperative pulmonary inflammation assessed 4 months post-surgery also significantly influenced LRO development, indicating a need for close follow-up of lung inflammatory conditions to improve patient outcomes.Keywords: chemotherapy, targeted therapy, inflammatory environment, risk factors

Mulin Liu,1 Siyi Chen,2 Aihui Zhang,2 Qin Zheng,2 Juan Fu3 1Department of Clinical Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Dalian Medical University, Dalian, Liaoning Province, 116044, People’s Republic of China; 3Department of Obstetrics and Gynecology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, People’s Republic of ChinaCorrespondence: Qin ZhengDepartment of Biochemistry and Molecular Biology, Liaoning Provincial Core Laboratory of Glycobiology and Glycoengineering, College of Basic Medical Science, Dalian Medical University, 9 West Section, Lvshun South Road, Dalian, Liaoning Province, 116044, People’s Republic of ChinaTel/ Fax +86 411-86110308Email zhengqin90@126.comJuan FuDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Dalian, Liaoning Province, 116011, People’s Republic of ChinaTel +86 411-83635963 ext. 3589Fax +86 411-83622844Email fujuan@firsthosp-dmu.comBackground: Bladder urothelial carcinoma (BLCA) is one of the most lethal and aggressive malignancies of genitourinary system that affects human health. The urokinase plasminogen activator receptor (PLAUR) plays essential roles in tumorigenesis and immune modulation, and its aberrant expression is closely correlated with cancer progression. However, whether PLAUR has the potential to be one promising biomarker or immunotherapy target for BLCA is unknown.Methodology: Various online databases were applied to assess the expression profile and prognostic value of PLAUR, as well as its correlation with immune infiltration in BLCA, including Oncomine, PrognoScan, TCGA, cBioPortal, TIMER, TISIDB, UALCAN, and MethSurv. The expression of PLAUR in BLCA was confirmed with ELISA assay for serum samples and immunohistochemistry for tissue samples.Results: The results showed that the expression of PLAUR was elevated in BLCA, which was further confirmed by ELISA and immunohistochemistry. Patients with higher PLAUR level were predicted to have lower overall survival and disease specific survival rates, which were not impacted by the genetic alterations of PLAUR. In addition, the expression of PLAUR was positively associated with immune infiltration, and also the expression levels of gene markers of various immune cells. The negative correlation between PLAUR expression and PLAUR methylation level was observed, among which PLAUR expression was positively correlated with the abundance of 28 kinds of tumor-infiltrating lymphocytes, while PLAUR methylation level was negatively correlated with the abundance of 11 types of tumor-infiltrating lymphocytes. Moreover, the methylation level of PLAUR was closely correlated with patients’ clinicopathological features, and hypomethylation of PLAUR was associated with better outcomes of BLCA patients.Conclusion: These findings suggested that PLAUR had the potential to serve as a valuable detection and prognostic biomarker or immunotherapeutic target for BLCA.Keywords: bladder urothelial carcinoma, PLAUR, biomarker, prognosis, immune infiltration, DNA methylation

Bin Zhu,1 Junrong Zhang,2 Qingzhu Zheng,1 Binhua Dong,3 Meihua Wang,1 Jin Liu,1 Yingping Cao1 1Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China; 2Department of Emergency Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China; 3Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, People’s Republic of ChinaCorrespondence: Yingping CaoDepartment of Clinical Laboratory, Fujian Medical University Union Hospital, No. 29, Xinquan Road, Fuzhou City, Fujian Province, People’s Republic of ChinaEmail caoyingping918@sina.comPurpose: The aim of our study was to identify the diagnostic ability of free fatty acids (FFAs) in younger colorectal cancer (CRC) patients by comparing carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9).Methods: Patients screened for CRC at Fujian Medical University Union Hospital from January 2011 to December 2014 were recruited. Patients pathologically diagnosed with CRC or colorectal adenoma (CA) and healthy control participants were included. The enzyme endpoint method was applied to measure FFA levels. Receiver operating characteristic (ROC) curve analysis was performed to further evaluate the diagnostic ability of FFAs.Results: FFA levels in late-stage patients (tumour-node-metastasis (TNM) stages III–IV) were higher than those in early-stage patients (TNM stages I–II) (P=0.02). The FFA levels in CRC patients were higher than those in controls of all ages, those younger than 50 years, males and females (P< 0.001), and this difference was larger for patients younger than 50 years and females than for the all ages group. There was no significant difference in the FFA level between CA patients and healthy participants (P=0.53). The area under the curve (AUC) values of FFA, CEA, CA19-9, FFA+CEA, FFA+CA19-9 and FFA+CEA+CA19-9 distinguished CRC patients from controls at all ages, with values of 0.604, 0.731, 0.640, 0.754, 0.678 and 0.758, respectively; however, in the younger CRC patients (age≤ 50), the AUC values were 0.701, 0.735, 0.669, 0.798, 0.749, and 0.801. The AUC in female patients younger than 50 years was larger than that in males (0.769 vs 0.660), and this value was greater than the value for CEA in males (0.739) and females (0.729).Conclusion: The FFA level not only can complement the predictive ability of the CEA and CA19-9 levels but also has a superior predictive ability in female and younger patients with CRC. FFA levels may have a potential role in triage screening of early CRC.Keywords: free fatty acid, colorectal cancer, colorectal adenoma, sex, younger patients

Guangtao Fu,1,* Haotao Li,1,2,* Hao Wang,1 Ruiying Zhang,1 Mengyuan Li,1 Junxing Liao,1 Yuanchen Ma,1 Qiujian Zheng,1 Qingtian Li1 1Department of Orthopedics, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, People’s Republic of China; 2College of Clinical Medicine, Shantou University, Shantou, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingtian LiDepartment of Orthopedics, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 106, Zhongshan 2nd Road, Yuexiu District, Guangzhou, Guangdong Province, People’s Republic of ChinaTel +86-18820109789Email 398619503@qq.comPurpose: To compare the effects of peripheral nerve block (PNB) and spinal anesthesia (SA) on one-year mortality and walking ability of elderly hip fracture patients after hip arthroplasty.Methods: Patients ≥ 65 years who underwent unilateral hip arthroplasty due to femoral neck fracture, using either PNB or SA from 2014 to 2019, were included. Demographic data, comorbidities, and results of preoperative screening were retrospectively collected. Propensity score matching (PSM) was performed in a ratio of 1:1 for PNB and SA groups. The primary outcomes were 30-day, 90-day, and one-year mortality. Secondary outcomes included walking ability in the first postoperative year, major complications, length of stay, and the cost of hospitalization. Survival analysis was performed using Kaplan–Meier method.Results: Three hundred and sixteen patients were included, of whom 200 received SA and 116 received PNB. Eighty-nine patients in each group were matched after PSM. Patients in the PNB group showed significantly lower risks of death in 30 days (2.2% vs 10.1%, P=0.029) and 90 days (3.4% vs 12.4%, P=0.026) after hip arthroplasty, when compared to the SA group. There was no significant difference in one-year mortality, walking ability, major complications, and length of stay. Higher hospitalization cost was found in the PNB group (53,828.21 CNY vs 59,278.83 CNY, P=0.024). One-year accumulated survival rate was higher in the PNB group without reaching a significant level.Conclusion: PNB was related to lower 30- and 90-day mortality but higher hospitalization cost in elderly hip fracture patients after hip arthroplasty. However, the anesthesia types were not associated with one-year mortality, one-year walking ability, major complications, and length of stay.Keywords: elderly hip fracture, 30-day mortality, walking ability, peripheral nerve block, propensity score matching

Mulin Liu,1,* Qin Zheng,2,* Siyi Chen,2 Jiwei Liu,3 Shijun Li1 1Department of Clinical Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, Liaoning Province, 116044, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shijun LiDirector of Department of Clinical Laboratory, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Dalian, Liaoning Province, 116011, People’s Republic of ChinaTel +86-0411-83635963-2232Fax +86-0411-83622844Email lishijun@dmu.edu.cnJiwei LiuDirector of Department of Oncology, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Dalian, Liaoning Province, 116011, People’s Republic of ChinaTel +86-0411-83635963-2232Fax +86-0411-83622844Email liujiwei451@126.comBackground: Bladder urothelial carcinoma (BLCA) is one of the most frequently appearing, lethal and aggressive malignancies of the genitourinary system with growing morbidity and mortality, which affects human health seriously. Protein glycosylation, catalyzed by specific glycosyltransferase, has been found to be abnormal in several diseases, especially cancer. Fucosyltransferase VII (FUT7), one of the fucosyltransferases, was observed abnormally expressed in various cancers, however, the role of FUT7 in BLCA, and the association between its expression and clinical outcomes or immune infiltration remains unclear.Methodology: FUT7 expression in BLCA was analyzed in Oncomine database, which was further confirmed with immunohistochemistry and ELISA. The prognostic value of FUT7 for BLCA was evaluated with PrognoScan database, and its genetic alteration was examined in cBioPortal database. The proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) changes of bladder cancer cells after FUT7 siRNA or cDNA transfection were determined by CCK8, colony formation, transwell and Western blot, respectively. The correlation between FUT7 expression and immune infiltration levels was analyzed in TIMER and TISIDB databases, and the methylation level of FUT7 was detected in UALCAN database.Results: The results showed that the expression of FUT7 was increased in BLCA, and patients with high FUT7 level were predicted to have lower overall survival and disease-specific survival rates, which were not influenced by FUT7 genetic alterations. Downregulation FUT7 inhibited the proliferation, migration, invasion and EMT of bladder cancer cells, whereas upregulation of FUT7 showed the opposite effects. We found that FUT7 was positively correlated with immune cell infiltration levels (CD8+ T cells, CD4+T cells, macrophage, neutrophil and dendritic cells), and also the expression of gene markers of immune cells. The negative correlation between FUT7 expression and FUT7 methylation level was observed, among which FUT7 expression was positively correlated with the abundance of 28 kinds of tumor-infiltrating lymphocytes (TILs), while FUT7 methylation level was negatively correlated with TILs.Conclusion: Altogether, these findings suggested that FUT7 possessed the potential to serve as a detection biomarker or immunotherapeutic target for BLCA.Keywords: bladder urothelial carcinoma, FUT7, EMT, diagnosis, prognosis, immune infiltration

Jianyan Long,1,* Ruiming Liang,1,* Qiuyi Zheng,1,2 Gang Yuan,3 Ziyi Xin,4 Xinwen Chen,2 Fenghua Lai,2 Yihao Liu1,2 1Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, People’s Republic of China; 3Phase I Clinical Trial Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, People’s Republic of China; 4Department of Medical Records, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yihao LiuClinical Trials Unit, Department of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58, ZhongShan Road 2, Guangzhou, Guangdong 510080, People’s Republic of ChinaTel +86-20-87755766Email liuyih3@mail2.sysu.edu.cnFenghua LaiDepartment of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58, ZhongShan Road 2, Guangzhou, Guangdong 510080, People’s Republic of ChinaTel +86-20- 87332200Email laifh@mail2.sysu.edu.cnPurpose: A better understanding of the current features of type 2 diabetes mellitus (T2DM)-related clinical trials is important for improving designs of clinical trials and identifying neglected areas of research. It was hypothesized that the trial registration policy promoted the designs of T2DM-related trials over the years. Therefore, this study aimed to present a comprehensive overview of T2DM-related clinical trials registered in the ClinicalTrials.gov database.Methods: T2DM-related clinical trials registered in the ClinicalTrials.gov database were searched and assessed the characteristics of the relevant trials. We searched PubMed and Google Scholar for the publication statuses of the primary completed trials.Results: Overall, 5117 T2DM-related trials were identified for analysis. Of the interventional trials, 71.5% had a primary treatment purpose while only 8.9% were prevention or health service. There were more interventional trials registered prior to patient recruitment between 2012 and 2019 than between 2004 and 2011 (44.6% vs 19.9%, P< 0.001). The period between 2012 and 2019 also had more trials that enrolled < 100 participants (59.2% vs 50.9%), were single-center studies (60.7% vs 50.6%), had non-randomized allocations (11.3% vs 6.3%), were open-label (49.2% vs 45.6%), and had smaller sample sizes than the period between 2004 and 2011 (all P< 0.001). The five-year cumulative publication rates after primary completion of the trials were < 40%.Conclusion: Although the ClinicalTrials.gov database did not include all clinical trials, the trials registered in the ClinicalTrials.gov database still accounted for most of the clinical studies. Encouragingly, more interventional trials were registered prior to patient recruitment over the years. The majority of T2DM-related clinical trials focused on drug-related treatment, and trials regarding prevention in T2DM should be promoted. More attention should be paid to improve the publication and dissemination of clinical trials results.Keywords: clinical trials, type 2 diabetes mellitus, ClinicalTrials.gov, publication status

Yingchong Chen,1 Yuling Liu,2 Jin Xie,1 Qin Zheng,1 Pengfei Yue,1 Liru Chen,3 Pengyi Hu,1 Ming Yang1 1Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, People’s Republic of China; 2Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, People’s Republic of China; 3Beijing Hospital, Beijing 100730, People’s Republic of ChinaCorrespondence: Pengfei Yue; Ming YangKey Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, 1688 Meilingdadao Road, Nanchang 330004, People’s Republic of ChinaTel/ Fax +86 791 8711 8658Email ypfpharm@126.com; yangming_215@163.comPurpose: Nose-to-brain drug delivery is an effective approach for poorly soluble drugs to bypass the blood–brain barrier. A new drug intranasal delivery system, a nanosuspension-based in situ gel, was developed and evaluated to improve the solubility and bioavailability of the drug and to prolong its retention time in the nasal cavity.Materials and Methods: Breviscapine (BRE) was chosen as the model drug. BRE nanosuspensions (BRE-NS) were converted into BRE nanosuspension powders (BRE-NP). A BRE nanosuspension in situ gelling system (BRE-NG) was prepared by mixing BRE-NP and 0.5% gellan gum (m/v). First, the BRE-NP were evaluated in terms of particle size and by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Subsequently, the critical ionic concentration of the gellan gum phase transition, influence of the deacetylated gellan gum (DGG) concentration on the expansion coefficient (S%), water-holding capacity, rheological properties and in vitro release behaviour of the BRE-NG were investigated. The pharmacokinetics and brain distribution of the BRE-NG after intranasal administration were compared with those of the intravenously injected BRE-NP nanosuspensions in rats.Results: The rheology results demonstrated that BRE-NG was a non-Newtonian fluid with good spreadability and bioadhesion performance. Moreover, the absolute bioavailability estimated for BRE-NG after intranasal administration was 57.12%. The drug targeting efficiency (DTE%) of BRE in the cerebrum, cerebellum and olfactory bulb was 4006, 999 and 3290, respectively. The nose-to-brain direct transport percentage (DTP%) of the cerebrum, cerebellum and olfactory bulb was 0.975, 0.950 and 0.970, respectively.Conclusion: It was concluded that the in situ gel significantly increased the drug retention time at the administration site. Therefore, the nanosuspension-based in situ gel could be a convenient and effective intranasal formulation for the administration of BRE.Keywords: nose-to-brain, nanosuspensions, in situ gel, breviscapine, brain distribution

Bin Zhu,1 Binhua Dong,2 Simei Hong,3 Meihua Wang,1 Weichao Dai,4 Qingzhu Zheng,1 Dan Wu,5 Yingping Cao1 1Department of Clinical Laboratorial Examination, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 2Department of Gynecology, Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Pathology, Fujian Provincial Cancer Hospital, Fuzhou, People’s Republic of China; 4Department of Gynecology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 5Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of ChinaCorrespondence: Yingping CaoDepartment of Clinical Laboratorial Examination, Fujian Medical University Union Hospital, NO. 29, Xinquan Road, Fuzhou City, Fujian Province, People’s Republic of ChinaTel +86-591-86218678Email caoyingping@aliyun.comBinhua DongDepartment of Gynecology, Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, NO. 18, Daoshan Road, Fuzhou, Fujian 350001, People’s Republic of ChinaTel +86-591-87558732Fax +86-591-87551247Email dbh18-jy@126.comPurpose: Cervical cancer (CC) is a common malignancy in women. Squamous cell carcinoma antigen (SCC-Ag) and cancer antigen (CA)-125 are widely used to help diagnose CC, but novel tumour markers with superior sensitivity and specificity are needed. α-Actinin 4(ACTN4) is overexpressed in CC, though its diagnostic value for CC is unclear. This study examined the diagnostic value of ACTN4 and SCC-Ag as biomarkers for cervical intraepithelial neoplasia (CIN) 3 or worse.Methods: Women screened for CC at Fujian Medical University Union Hospital were recruited from 2017.1 to 2018.5. Cervical tissues and blood were collected at the same time. Patients pathologically diagnosed as CIN3+ or NILM/CIN1/CIN2 were classified into the case and control groups, respectively. ACTN4 mRNA and protein levels were detected through quantitative PCR and immunohistochemistry, respectively, and ACTN4 and SCC-Ag concentrations were analysed by ELISA. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood rate (PLR), negative likelihood rate (NLR), and Youden index (YI) of ACTN4 and SCC-Ag were evaluated. The optimum cut-off points for ACTN4 and SCC-Ag were determined by receiver operating characteristic (ROC) curve analysis, and accuracy was evaluated by the area under the ROC curve.Results: In total, 105 patients were classified as CIN3+ cases and 106 as controls. The median ACTN4 levels in case and control tissues were 10.6 and 4.15, respectively. The ACTN4 and SCC-Ag concentrations were significantly higher in cases than controls (PACTN4=0.0007; PSCC-Ag=0.0067). The sensitivity, specificity, PPV, NPV, PLR, NLR and YI of ACTN4 were 68.6%, 76.3%, 76.3%, 72.5%, 2.89, 0.41 and 44.9, respectively; SCC-Ag had a similar diagnostic value (P> 0.05), and ACTN4 combined with SCC-Ag had a superior diagnostic value (75.6%, 87.5%, 88.6%, 73.7%, 6.05, 0.28, and 63.1, respectively).Conclusion: Combined ACTN4 and SCC-Ag detection is a promising serological biomarker for patients with CIN3 or worse.Keywords: ACTN4, SCC-Ag, CIN3 or worse, serological biomarker

Fuyan Shi,1 Chen Wang,2 Yujia Kong,1 Liping Yang,3 Juan Li,1 Gaopei Zhu,1 Jing Guo,4 Qingfeng Zheng,5 Bo Zhang,6 Suzhen Wang1 1Department of Health Statistics, School of Public Health, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of China; 2Department of Computer Science, Rutgers University, Piscataway, NJ 08854, USA; 3Center for Health and Medicine, Xijing Hospital, an Affiliated Hospital of Air Force Military Medical University, Xi’an, Shannxi 710032, People’s Republic of China; 4Department of Health Policy and Management, School of Public Health, Peking University, Beijing 100191, People’s Republic of China; 5Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 6Department of Neurology and ICCTR Biostatistics and Research Design Center, Boston Children’s Hospital and Harvard Medical School, Boston, MA, 02115, USACorrespondence: Bo Zhang; Suzhen Wang Email bo.zhang@childrens.harvard.edu; wangsz@wfmc.edu.cnObjective: To evaluate the survival benefit of surgery and radiation for hepatocellular carcinoma (HCC) after adjusting for patient-specific and tumor-specific factors.Methods: This study analyzed HCC patients who enrolled in the Surveillance, Epidemiology, and End Results (SEER) registry between January 2004 and December 2013. Of the 5552 HCC patients, 4597 received surgery and 955 received radiation. Patients who received radiation were further divided into 3 subgroups: 541 who received beam radiation (BR), 197 who received radioactive implants (RI), and 217 who received radioisotopes (RIT). Propensity score weighting analysis derived from generalized boosted models (GBMs) was performed to ensure well-balanced characteristics in all comparison groups.Results: Overall survival rates and HCC-specific survival rates were higher in those receiving surgery compared with those receiving radiotherapy. This was confirmed by Cox proportional hazard regression both before and after inverse probability of treatment weighting (IPTW). Before IPTW, the RIT group had a better outcome than the BR group in terms of overall and HCC-specific survival rates, but there was no significant difference between the RI and BR groups. After IPTW, Cox proportional hazard regression demonstrated that both the RIT and RI groups had higher survival rates than the BR group.Conclusion: In HCC patients, surgery was associated with higher survival rates compared with radiotherapy while adjusting for other factors. Among those who received radiotherapy, RIT and RI granted survival benefits.Keywords: hepatocellular carcinoma, survival analysis, propensity score, generalized boosted models, inverse probability of treatment weighting, Cox proportional hazard models

Xu Jia,1,* Ziren Luo,2,* Ying Gao,3 Hua Liu,3 Xinghai Liu,3 Wenli Mai,3 Hong Liu,3 Qian Zheng3 1Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, People’s Republic of China; 2School of Pharmacy, North Sichuan Medical College, Nanchong 637000, People’s Republic of China; 3Department of Physiology, North Sichuan Medical College, Nanchong 637007, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian ZhengDepartment of Physiology, North Sichuan Medical College, Nanchong, 637007, People’s Republic of ChinaEmail 373969568@qq.comObjective: The protective effects of epigallocatechin gallate (EGCG) on interleukin-1β (IL-1β)-induced apoptosis were investigated in murine MIN6 pancreatic β-cells. The role of uncoupling protein-3 (UCP3) signaling in this process was also explored.Methods: After treatment with IL-1β and EGCG, cells were collected and analyzed. Cell viability was measured using the CCK8 assay and the function of β-cells was evaluated by analyzing insulin secretion. Detection of mitochondrial function in cells was performed by measuring mitochondrial membrane potential, the concentration of ATP and activity of ROS. Apoptosis was analyzed by Hochest33258 staining and flow cytometry. Expression levels of UCP3 were interrogated using immunohistochemistry, RT-PCR and Western blotting.Results: Compared with the control group, IL-1β treatment (20nM) for 24 h significantly decreased cell viability and insulin secretion, damaged mitochondrial function and increased ROS activity. Results also showed increased apoptosis and a decrease in UCP3 expression levels (p< 0.01). However, treatment with low (1mM) or high (5mM) concentrations of EGCG significantly decreased IL-1β-induced apoptosis (p< 0.01), restored mitochondrial function and subsequently increased UCP3 levels in IL-1β-induced β-cells (p< 0.01).Conclusion: These results suggest that EGCG protects against IL-1β-induced mitochondrial injury and apoptosis in β-cells through the up-regulation of UCP3.Keywords: EGCG, pancreatic β-cells, apoptosis, UCP3

Xiang Li,1,* Qian Zou,1,* Jing Zhang,2 Peng Zhang,2 Xiong Zhou,1 Satya Siva Kishan Yalamarty,3 Xinli Liang,2 Yali Liu,4 Qin Zheng,2 Jianqing Gao5 1State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, Jiangxi, People’s Republic of China; 2Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi, People’s Republic of China; 3Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA; 4College of Science and Technology, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi, People’s Republic of China; 5Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing ZhangKey Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi, People’s Republic of ChinaTel/Fax +86 791 87118658Email 20101036@jxutcm.edu.cnPurpose: Folic acid and cyclic arginylglycylaspartic acid peptides were introduced to the surface of negatively charged lipid-coated hybrid polydopamine-cysteine cores for the delivery of epirubicin (EPI) (E/PCF-NPs). The combined chemo-photothermal therapy using E/PCF-NPs for triple-negative breast cancer was evaluated.Materials and Methods: The temperature elevation and thermal toxicity of nanoparticles were studied. The morphology and properties of E/PCF-NPs were characterized by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. Physicochemical properties, including particle size, zeta potential, drug loading, entrapment efficiency (EE%), stability and in vitro release, were determined. The cell viability, reactive oxygen species (ROS) levels, ratios of oxidized nicotinamide adenine dinucleotide to its reduced form (NAD+/NADH), apoptosis assays, and cellular uptake of E/PCF-NPs were determined on 4T1 cells. Pharmacokinetic studies and tissue distributions were performed and detected by an ultra-high performance liquid chromatography/mass spectrometry system. The antitumor effects of E/PCF-NPs under near-infrared (NIR) laser irradiation were also evaluated.Results: The sphere-like morphology of E/PCF-NPs showed a high EE%, uniform size of 106.7 nm, remarkable stability, and highly improved cytotoxicity under NIR laser, when compared to that of photothermal treatment alone. In vitro release of EPI from E/PCF-NPs was pH sensitive, and a greater response was achieved under NIR laser irradiation. Compared to chemotherapy or photothermal treatment alone, the combined treatment in vitro significantly inhibited the survival rate of 4T1 cells to 17.7%, induced ROS generation, and reduced NAD+/NADH significantly. Treatment with E/PCF-NPs under irradiation induced 4T1 cell apoptosis in approximately 93.6% cells. In vitro cellular uptake of E/PCF-NPs was time-dependent. The long-circulating and higher tumor accumulation of E/PCF-NPs resulted in complete ablation of breast tumor tissue through the enhanced photothermal effect by NIR laser irradiation-mediated cell apoptosis.Conclusion: E/PCF-NPs show enhanced anti-cancer effects due to synergistic effects of chemotherapy with photothermal therapy and may be potential therapeutic agents for cancer treatment.Keywords: polydopamine nanoparticles, L-cysteine, epirubicin, pharmacokinetics, triple-negative breast cancer

Qiaomei Zheng, Jinhua Wang, Wenwen Li, Xiaoyun Chen, Shaozhan Chen, Lihong Chen Department of Obstetrics and Gynecology, The First Affiliated Hospital of Fujian Medical University, Fujian Medical University, Fuzhou, Fujian 350001, People’s Republic of ChinaCorrespondence: Lihong ChenDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Fujian Medical University, Fujian Medical University, 20 Chazhong Road, Fuzhou, Fujian 350001, People’s Republic of ChinaTel +86-059187982061Fax +86-059187981028Email chenlihong_0102@126.comPurpose: To explore the exact mechanism through which emodin down-regulates the migration and invasion abilities of endometrial stromal cells. Moreover, to explore the theoretical basis of emodin in the treatment of endometriosis.Patients and Methods: Endometriosis endometrial stromal cells (EESs) were cultured from 15 women with endometriosis and control endometrial stromal cells (CESs) were cultured from 12 women without endometriosis. The levels of proteins were evaluated by Western blot. The migration and invasion abilities of cells were detected by transwell assays.Results: The abilities of migration and invasion of EESs were much stronger than those of CESs. After treated with emodin, the migration and invasion abilities of EESs and CESs were significantly down-regulated, and the levels of integrin-linked kinase (ILK) and p-GSK-3β were statistically down-regulated in EESs. Besides that, the expression of keratin was up-regulated while the expression of vimentin, β-catenin and slug were all down-regulated by emodin in a dose- and time-dependent manner. Silencing of ILK gene in EESs also achieved the above effects, which were strengthened by emodin. Conversely, exogenous expression of ILK in CESs increased the expression of p-GSK-3β, which were abrogated by emodin. Furthermore, SB216763 increased migration and invasion abilities of CESs by facilitating the epithelial–mesenchymal transition (EMT) through up-regulating levels of p-GSK-3β, β-catenin and slug, which were also abrogated by emodin.Conclusion: Emodin inhibits the migration and invasion abilities of human endometrial stromal cells by reversing the EMT via ILK/GSK-3β pathway. So, emodin may be considered as a promising targeted therapy for endometriosis.Keywords: emodin, endometriosis, EMT, ILK, GSK-3β

Fuyan Shi,1 Changlan Yu,2 Liping Yang,3 Fangyou Li,2 Jiangtao Lun,4 Wenfeng Gao,5 Yongyong Xu,6 Yufei Xiao,1 Sravya B Shankara,7 Qingfeng Zheng,8 Bo Zhang,9 Suzhen Wang1 1Department of Health Statistics, School of Public Health and Management, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2Anqiu City Center for Disease Control and Prevention, Anqiu, Shandong, People’s Republic of China; 3Health and Medical Center, Xijing Hospital, Air Force Military Medical University, Xi’an, Shannxi, People’s Republic of China; 4Anqiu Meteorological Bureau, Anqiu, Shandong, People’s Republic of China; 5Department of Immunology and Rheumatology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, People’s Republic of China; 6Department of Health Statistics, School of Military Preventive Medicine, Air Force Military Medical University, Xi’an, Shannxi, People’s Republic of China; 7Program in Health: Science, Society, and Policy, Brandeis University, Waltham, MA, USA; 8Institute for Hospital Management of Tsinghua University, Tsinghua Campus, Shenzhen, People’s Republic of China; 9Department of Neurology and ICCTR Biostatistics and Research Design Center, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USACorrespondence: Bo Zhang; Suzhen Wang Email bo.zhang@childrens.harvard.edu; wangsz@wfmc.edu.cnObjective: The purpose of this study was to explore the dynamics of incidence of hemorrhagic fever with renal syndrome (HFRS) from 2000 to 2017 in Anqiu City, a city located in East China, and find the potential factors leading to the incidence of HFRS.Methods: Monthly reported cases of HFRS and climatic data from 2000 to 2017 in the city were obtained. Seasonal autoregressive integrated moving average (SARIMA) models were used to fit the HFRS incidence and predict the epidemic trend in Anqiu City. Univariate and multivariate generalized additive models were fit to identify and characterize the association between the HFRS incidence and meteorological factors during the study period.Results: Statistical analysis results indicate that the annualized average incidence at the town level ranged from 1.68 to 6.31 per 100,000 population among 14 towns in the city, and the western towns exhibit high endemic levels during the study periods. With high validity, the optimal SARIMA(0,1,1,)(0,1,1)12 model may be used to predict the HFRS incidence. Multivariate generalized additive model (GAM) results show that the HFRS incidence increases as sunshine time and humidity increases and decreases as precipitation increases. In addition, the HFRS incidence is associated with temperature, precipitation, atmospheric pressure, and wind speed. Those are identified as the key climatic factors contributing to the transmission of HFRS.Conclusion: This study provides evidence that the SARIMA models can be used to characterize the fluctuations in HFRS incidence. Our findings add to the knowledge of the role played by climate factors in HFRS transmission and can assist local health authorities in the development and refinement of a better strategy to prevent HFRS transmission.Keywords: hemorrhagic fever with renal syndrome, meteorological factors, autoregressive integrated moving average model, generalized additive model, prediction

Xuepan Chen,1,2,* Yuanchen Ma,1,* Zhantao Deng,1 Qingtian Li,1 JunXing Liao,1 Qiujian Zheng1 1Department of Orthopedics, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences;School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China; 2Shantou University Medical College, Shantou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiujian ZhengDepartment of Orthopedics, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, No. 106, Zhongshan Second Road, Yuexiu District, Guangzhou 510000, People’s Republic of ChinaEmail zqj106@126.comIntroduction: Transthoracic echocardiography (TTE) is a common cardiac screening test before hip fracture surgery. However, the general TTE test delays surgery, so it would be meaningful if we could simplify the TTE by only assessing cardiac abnormality specifically. Therefore, we aimed to establish the most clinically relevant abnormality by comparing the predictive value of each major cardiac abnormality in postoperative cardiac complications and mortality in elderly hip fracture patients.Patients and Methods: From January 2014 to January 2019, the medical records of all surgically treated elderly patients (> 65 years) with hip fracture were analyzed. The major TTE abnormalities were defined as left ventricular hypertrophy, systolic pulmonary arterial pressure > 25 mm Hg, moderate-severe valve abnormality, left ventricular ejection fraction (LVEF) < 50%, and pericardial effusion. The outcomes were postoperative cardiac complications and in-hospital mortality.Results: There were 354 patients involved finally. Postoperative cardiac complications were encountered in 7.6% (n=27) of patients. The mortality rate was 2.8% (n=10). History of coronary artery disease (CAD) (OR: 3.281, 95% CI: 1.332– 8.079, p=0.010) and presence of aortic stenosis (AS) (OR:5.656, 95% CI: 1.869– 17.117, p=0.002) were independent predictors of postoperative cardiac complications. In addition, age (OR: 1.264, 95% CI: 1.047– 1.527, p=0.015), history of CAD (OR: 19.290, 95% CI: 2.002– 185.885, p=0.010), presence of AS (OR:7.164, 95% CI: 1.988– 51.413, p=0.040) and LVEF < 50% (OR:8.803, 95% CI: 1.115– 69.472, p=0.039) were independent predictors of mortality. However, the rest of preoperative TTE abnormalities were not associated with postoperative cardiac complications or mortality.Conclusion: Among the TTE abnormalities presented by elderly patients with hip fracture, moderate-severe AS was the predictor of postoperative cardiac complications. Moreover, moderate-severe AS and LVEF < 50% were the predictors of in-hospital mortality. Therefore, we could simplify the TTE process by assessing aortic valve and LVEF specifically on focused echocardiography, which could avoid surgery delay.Keywords: aging, hip fracture surgery, mortality, postoperative cardiac complications, echocardiographic abnormality

Qing Tang,* Ping Hu,* Haibo Peng, Ning Zhang, Qiang Zheng, Yun He School of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, Chongqing 401331, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun HeSchool of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, 55 South Daxuecheng Road, Chongqing 401331, People’s Republic of ChinaTel +86 23 6567 8450Fax +86 23 65678455Email yun.he@cqu.edu.cnPurpose: Traditional chemotherapy is accompanied by significant side effects, which, in many aspects, limits its treatment efficacy and clinical applications. Herein, we report an oxidative responsive polymersome nanosystem mediated by near infrared (NIR) light which exhibited the combination effect of photodynamic therapy (PDT) and chemotherapy.Methods: In our study, poly (propylene sulfide) 20-bl-poly (ethylene glycol) 12 (PPS 20-b-PEG 12) block copolymer was synthesized and employed to prepare the polymersome. The hydrophobic photosensitizer zinc phthalocyanine (ZnPc) was loaded in the shell and the hydrophilic doxorubicin hydrochloride (DOX·HCl) in the inner aqueous space of the polymersome.Results: Under the irradiation of 660 nm NIR light, singlet oxygen 1O 2 molecules were generated from ZnPc to oxidize the neighbouring sulfur atoms on the PPS block which eventually ruptured the intact structure of polymersomes, leading to the release of encapsulated DOX·HCl. The released DOX and the 1O 2 could achieve a combination effect for cancer therapy if the laser activation and drug release occur at the tumoral sites. In vitro studies confirmed the generation of singlet oxygen and DOX release by NIR irradiation. In vivo studies showed that such a combined PDT-chemotherapy nanosystem could accumulate in A375 tumors efficiently, thus leading to significant inhibition on tumor growth as compared to PDT (PZ group) or chemotherapy alone (DOX group).Conclusion: In summary, this oxidation-sensitive nanosystem showed excellent anti-tumor effects by synergistic chemophotodynamic therapy, indicating that this novel drug delivery strategy could potentially provide a new means for cancer treatments in clinic.Keywords: near infrared laser, photodynamic therapy, oxidation-responsive, polymersome, combination therapy, cancer

Qingwei Wu, 1, 2 Lili Yu, 1, 2 Xiaoqing Lin, 1, 2 Qingzhu Zheng, 1, 2 Songgao Zhang, 1, 2 Dunyan Chen, 1, 2 Xiaojie Pan, 1, 3 Yi Huang 1, 2, 4 1Provincial Clinical College, Fujian Medical University, Fuzhou 350001, People’s Republic of China; 2Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou 350001, People’s Republic of China; 3Department of Thoracic Surgery, Fujian Provincial Hospital, Fuzhou 350001, People’s Republic of China; 4Center for Experimental Research in Clinical Medicine, Fujian Provincial Hospital, Fuzhou 350001, People’s Republic of ChinaCorrespondence: Yi HuangDepartment of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou 350001, People’s Republic of ChinaEmail hyi8070@126.comPurpose: Circulating microRNAs (miRNAs) have shown the potential for non-invasive diagnosis of various types of malignancies at an early stage. The aim of the study was to explore the feasibility of a combination of 8 serum miRNAs related to non-small-cell lung cancer (NSCLC) with the corresponding serum exosomal miRNAs in early diagnosis for the patients with NSCLC.Methods: We measured 8 serum miRNAs and the corresponding serum exosomal miRNAs including miR-21-5p, miR-126-3p, miR-141-3p, miR-146a-5p, miR-155-5p, miR-222-3p, miR-223-3p, and miR-486-5p in 48 patients with early NSCLC at stages I/II, 32 patients with lung benign lesion (LBL), and 48 healthy control (HC) by quantitative real-time polymerase chain reaction (qRT-PCR).Results: The expression levels of 4 serum miRNAs including miR-21-5p, miR-141-3p, miR-222-3p, and miR-486-5p, and 2 serum exosomal miRNAs including miR-146a-5p and miR-486-5p in the early NSCLC group were significantly different from that in the LBL group and the HC group (P < 0.01). The areas under the receiver operating characteristic curves (AUC) of the 4 serum miRNAs and 2 serum exosomal miRNAs in the early NSCLC group were ≥ 0.697, of which serum exosomal miR-146a-5p and miR-486-5p were 0.813 and 0.886, respectively, and higher than that of the 4 serum miRNAs. Additionally, a combination of 4 serum miRNAs with 2 serum exosomal miRNAs improved the AUC to 0.960 for the patients with NSCLC at early stages, with a sensitivity of 85.42% and a specificity of 92.50%.Conclusion: This study suggests that serum exosomal miRNAs other than serum miRNAs might be preferable biomarkers for the patients with NSCLC at early stages, and a combination of serum miRNAs with serum exosomal miRNAs contributes to the further improvement of early diagnosis for NSCLC.Keywords: serum, exosome, microRNA, non-small-cell lung cancer, early diagnosis

Chen Wang,1–3 Na Zhao,1–3 Qin Zheng,1–3 Di Zhang,1–3 Yang Liu1–31Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang 110122, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital, China Medical University, Shenyang 110001, People’s Republic of China; 3Department of Pathology, Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110122, People’s Republic of ChinaPurpose: The biological functions of BHLHE41 in the proliferation of glioblastoma remained unexplored. We aimed to investigate the biological roles and underlying molecular mechanisms of BHLHE41 in glioblastoma.Materials and methods: We used multiple methods, including Western blot analysis, soft agar colony-formation assay, CCK8 assay, and flow cytometry, to evaluate the changes in multiple cellular functions after BHLHE41 knockdown or overexpression in U87 and U251 cell lines. The TCGA database was then used to analyze the associations between BHLHE41 expression with clinicopathological factors and the overall survival (OS) of glioma patients.Results: This study determined that overexpression of BHLHE41 promoted glioma cell proliferation and colony formation. Besides, BHLHE41 upregulated cyclinD1, cyclinD3, and cyclinE1 expression and drove phase transition from G1 to S and G2 phases by upregulating these cyclins. In contrast, knockdown of BHLHE41 had an opposite effect on all of these parameters. However, BHLHE41 had no effect on apoptosis. Moreover, BHLHE41 activated MAPK/ERK signaling pathway to upregulate cyclinD1 expression. After the ERK signal pathway was blocked by a specific inhibitor, SCH772984, cyclinD1 upregulation was reversed. Furthermore, the median OS of low-grade glioma (LGG) patients with low to median level of BHLHE41 was 22.6 months, longer than that of the patients with high level of BHLHE41 (21.0 months).Conclusion: BHLHE41 has an important role in the proliferation of glioblastoma and could serve as a novel candidate for targeted therapy of glioblastoma.Keywords: BHLHE41, cyclinD1, ERK, cell cycle, proliferation, glioblastoma

Sheng Cheng, Qiming Zheng, Guoqing Ding, Gonghui LiDepartment of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaPurpose: The clinical impacts of serum lipid levels on prostate cancer recurrence after radical prostatectomy have been evaluated by several observational studies with conflicting results. We performed the present meta-analysis to summarize the evidence evaluating the role of serum lipid profile in prostate cancer patients.Methods: We comprehensively searched the PubMed database for potentially relevant studies through January 2019. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) for the highest versus the lowest level of serum lipid levels were calculated with the DerSimonian and Laird random-effects model.Results: A total of 12 eligible studies with 10,978 prostate cancer cases were included in this study. The pooled HRs of prostate cancer recurrence after racial prostatectomy were 0.92 (95% CI 0.73–1.16, P=0.462), 0.87 (95% CI 0.56–1.35, P=0.535), 1.09 (95% CI 0.92–1.30, P=0.320), and 1.01 (95% CI 0.78–1.31, P=0.938) for serum total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride, respectively. Sensitivity analysis was conducted by excluding each study sequentially and the results showed that all the summary risk estimates were stable and not influenced by any single study.Conclusion: The present meta-analysis indicated that serum lipid levels in patients undergoing radical prostatectomy were not associated with prostate cancer recurrence.Keywords: serum lipids, prostate cancer, recurrence, radical prostatectomy, meta-analysis

Jianyong Zhang,1,2,* Qiaoling Zheng,1,3,* Wenxiong Zhang,1 Nanpeng Wang,2 Jianjun Xu,1 Xiaoshu Cheng,1 Yiping Wei11Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China; 2Department of General surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550000, People’s Republic of China; 3Jiangxi Health Vocational College, Nanchang, Jiangxi 330000, People’s Republic of China*These authors contributed equally to this work Introduction: Lung cancer is one of the most common malignancies worldwide, and the main effective treatment is surgical operation to cure this disease. This study assessed the feasibility of surgical aerosol for identification of lung cancer and adjacent normal tissue in surgery.Methods: In vitro experiments, the surgical aerosol was released when the tissue sample was being cut using a standard electrosurgery handpiece. Surgical smoke was dissolved in methanol by negative-pressure suction and then get to the neutral sprayer for analysis. Multivariate analysis was performed using partial least squares (PLS) analysis in MatLab 2011.Results: A total of 208 surgical aerosol database entries were obtained from 26 patients. In the cancerous aerosol, relative abundance (760.61, 782.39, and 789.68 m/z) was increased, while relative abundances of (756.41 m/z) was decreased compared with normal-tissue aerosol. After PLS analysis, mass–spectrometry (MS) data for the cancer aerosol showed clear differentiation from normal. Four significant peaks were identified by collision-induced dissociation experiments. The cancerous aerosol showed overexpression of phosphatidylserine (34:2), phosphatidylcholine (36:4), and triacylglycerol (46:2), while phosphatidylcholine (34:3) was decreased. Coupling PLS and extractiveelectrospray-ionization MS analysis of the surgical aerosol data of lung cancer were clearly distinguished from normal.Conclusion: The surgical aerosol might contain biomarkers for identification of lung cancer and normal tissue.Keywords: lung cancer, biomarker, surgical aerosol, mass spectrometry

Changshun Chen,1 Chen Zhu,2 Xiang Hu,1 Qiuli Yu,3 Qianjin Zheng,1 Shengxiang Tao,1 Lihong Fan2 1Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China; 2School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, Hubei, China; 3School of Health Sciences, Wuhan University, Wuhan, Hubei, China Purpose: The aims of this research were to combine a-hemihydrate calcium sulfate/octacalcium phosphate (α-CSH/OCP) with sodium hyaluronate (SH) or SH sulfate (SHS) to determine whether these composites can be used as a new type of bone repair material. This study may provide a theoretical basis and new ideas for the construction of active bone repair materials and their clinical application.Methods: In this study, we combined α-CSH/OCP with SH or SHS. Scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), and the wettability test were performed, and porosity, setting time, in vitro degradation, and the mechanical properties of these composite materials were analyzed to evaluate the ultrastructural and physicochemical properties. We evaluated the histocompatibility of these composites by MTT assay, hemolysis, acute toxicity, and pyrogenic and intracutaneous stimulation tests. In addition, the osteogenic differentiation ability of these materials was detected in vitro using Western blot analysis and in vivo using an animal model of bone defect.Results: The α-CSH/OCP/SH composite had a compressive strength of 13.72 MPa, a porous rate of 27.45%, and the 28-day degradation rate of 64%. The MTT assay results showed that the relative proliferation rates of the α-CSH/OCP/SH group were greater than 90%. The results of the α-CSH/OCP/SH composite in the hemolysis, acute toxicity, pyrogenic, and intracutaneous stimulation tests were within the normal range. Western blot analysis indicated that the expression of bone extracellular matrix (ECM) proteins was notably upregulated and always higher in the α-CSH/OCP/SH group than in the other groups. XRD of the rabbit radius-defect model indicated that bone healing in the area implanted with α-CSH/OCP/SH was excellent approximately 9 weeks after repair.Conclusion: α-CSH/OCP/SH has very good biocompatibility and exhibits clear advantages in the induction of bone regeneration and self-repair, and this compound shows promise in the field of bone tissue engineering. Keywords: sodium hyaluronate, characterization, BMSCs, biocompatibility, osteogenic differentiation

Lihong Chen, Jinhua Wang, Jianbo Wu, Qiaomei Zheng, Jifen Hu Department of Obstetrics and Gynecology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China Background: Indirubin is the active component of Danggui Longhui Wan, a traditional Chinese medicine formulation. Due to its anti-inflammation and anti-tumor effects, indirubin has been widely used for the treatment of inflammation, cancer, and other chronic disease. Herein, we aimed to investigate the role and mechanism of indirubin in human ovarian cancer cell proliferation.Materials and methods: The cell viability was determined by Cell Counting Kit-8 and colony formation assays by treatment with different dosages of indirubin over 72 hours. Apoptosis was examined by flow cytometry with fluorescein isothiocyanate Annexin V Apoptosis Detection Kit. Western blot assay was finally applied to analyze the expression of cancer-related STAT3 pathway and its downstream proteins.Results: Indirubin was found to significantly inhibit cell viability and induce apoptosis in 2 human ovarian cancer cell lines. Mechanistic studies revealed that indirubin treatment led to reduced levels of phosphorylated-STAT3, thus repressing the downstream pro-survival proteins and elevating pro-apoptosis ones.Conclusion: Our study provided the evidence for anti-survival activity of indirubin by inhibiting cell viability and inducing apoptosis in human ovarian cancer cells, which involved impaired STAT3 signaling pathway. Our findings further support indirubin as a potential drug candidate against human ovarian cancer. Keywords: indirubin, ovarian cancer, cell viability, STAT3 signaling

Deting Xue,1,* Erman Chen,1,* Huiming Zhong,2,* Wei Zhang,1 Shengdong Wang,1 Muhammad Umar Joomun,1 Tianyi Yao,3 Yanbin Tan,1 ShiSheng Lin,3 Qiang Zheng,1 Zhijun Pan1 1Department of Orthopaedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, People’s Republic of China; 2Department of Emergency, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, People’s Republic of China; 3Department of Information Science and Electronic Engineering and State Key Laboratory of Modern Optical Instrumentation, Zhejiang University, Hangzhou 310027, People’s Republic of China *These authors contributed equally to this work Background: The osteo-immunomodulatory properties of biomaterials play an important role in the outcomes of bone regeneration. Graphene oxide (GO) has been widely applied in many research fields due to its unique properties. However, the immunomodulatory properties of GO as a biomaterial for bone tissue engineering are still unclear. Materials and methods: In this study, we evaluated the Inflammatory response of RAW264.7 cells influenced by GO. Then the osteogenic differentiation of BMSCs, and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) by stimulation with GO/RAW 264.7-conditioned culture medium were accessed. We also further investi­gated the possible mechanisms underlying the osteo- and angio-immunomodulatory effects of GO. Results: Our results showed that GO stimulates the secretion of oncostatin M, tumor necrosis factor alpha and other factors through the nuclear factor-κB pathway. GO/RAW264.7-conditioned medium promoted the osteogenic differentiation of BMSCs, stimulated upregulation of the HUVECs of vascular-related receptors, and promoted their tube formation in vitro. Conclusion: In conclusion, our research shows that GO, as a biomaterial, can induce the formation of a beneficial osteo-immunomodulatory environment and is a promising biomaterial for bone tissue engineering. Keywords: graphene oxide, osteo-immunomodulatory, bone marrow mesenchymal stem cells, osteogenesis, angiogenesis, RAW264.7 cells, HUVECs

Shu-Jun Lu, Xiao-Sheng Zhou, Qi Zheng, Hong-Liang Chen, Yan-Lei Geng Department of Neurology, Binzhou Medical University Hospital, Binzhou, People’s Republic of China Objectives: This study aimed to determine the relationship between the polymorphisms of the H1/H2 gene of platelet membrane receptor P2Y12 and cerebral infarction (CI) in a Han population in North Shandong Province, People’s Republic of China. Patients and methods: A case–control study, which involved 168 nonstoke subjects (contrast group) and 152 CI patients (CI group), was conducted. The state of subjects in the CI group was validated by computed tomography or MRI. The clinical data were categorized into two groups. The data included age, gender, smoking, drinking, shrinkage pressure, diastolic blood pressure, blood glucose, cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, serum uric acid, fibrinogen and homocysteine. The polymorphisms were genotyped with PCR and restriction fragment length polymorphism analysis. The distribution characteristics of nonstoke subjects and CI patients and the relationship between the polymorphisms of the H1/H2 gene of platelet membrane receptor P2Y12 and ischemic stroke were analyzed. Results: No significant difference was found between the contrast group and CI group (P>0.05) in terms of age, gender composition, smoking, alcohol consumption, blood glucose, cholesterol, triglyceride, low-density protein, high-density lipoprotein cholesterol, uric acid and homocysteine. In contrast, significant differences were found between these two groups (P

Kai Zhang,* Ruoxi Hong,* Fei Xu, Wen Xia, Lee Kaping, Ge Qin, Qiufan Zheng, Qianyi Lu, Yan Xia Shi, Zhong Yu Yuan, Shusen Wang Sun Yat-Sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China *These authors contributed equally to this work Background: The clinical implication of plasma ESR1 mutations in the estrogen receptor (ER)-positive metastatic breast cancer (MBC) patients who had progressed after prior aromatase inhibitor (AI)-based therapy remains controversial. We conducted the first meta-analysis to investigate the prognostic significance and predictive role of plasma ESR1 mutations in MBC patients with prior exposure to AI therapy. Materials and methods: We searched PubMed, Embase, and Cochrane Library databases for eligible studies. Meta-analysis was conducted to calculate combined hazard ratios (HRs) with 95% CIs for progression-free survival (PFS) and overall survival (OS). Subgroup and sensitivity analyses were also performed. Results: This study enrolled a total of 1,530 patients with ER-positive MBC cases from six articles, including 429 ESR1 mutation carriers (28.04%). Meta-analysis demonstrated that plasma ESR1 mutation carriers had significantly worse PFS (HR: 1.40, 95% CI: 1.17–1.66; P

Wei Chen, Jia You, Qi Zheng, Yue-Yong Zhu Center for Liver Diseases, The First Affiliated Hospital, Fujian Medicine University, Fuzhou 350005, Fujian Province, China Introduction: Increasing evidence demonstrates that long noncoding RNAs (lncRNAs) play important roles in the progression of hepatocellular carcinoma (HCC) by regulating gene expression. However, the identification of functional lncRNAs in HCC remains insufficient. Our study aimed to investigate the function of lncRNA OGFRP1, which has not been functionally researched before, in Hep3B and HepG2 cells. Methods: lncRNA OGFRP1 in HCC cells was down-regulated by using RNAi technology. Quantitative real-time polymerase chain reaction was used to determine the mRNA expression of lncRNA OGFRP1. Cell proliferation was examined by CCK8 and clone formation assays. Cell cycle and apoptosis were analyzed by flow cytometry. Cell migration and invasion were assessed by using Scratch assay and transwell assay, respectively. Protein expression of signaling pathways was determined by using Western blot. Results: Cell proliferation of Hep3B was significantly inhibited by down-regulation of lncRNA OGFRP1 (P

Yinyin Qu,1 Qing Zheng,1 Cheng Ni,1 Zhongqi Cui,2 Xiangyang Guo1 1Department of Anesthesiology, 2Department of Cardiac Surgery, Peking University Third Hospital, Beijing, People’s Republic of China Introduction: Lung metastasis of leiomyosarcoma that protrudes into the left atrium is an extremely rare condition. Severe complications may occur that prominently increase the mortality during the perioperative period. Currently, the anesthetic management reports are limited and there is no generally acknowledged algorithm available.Case presentation: A 67-year-old man presented with cough and dyspnea for 10 days. Workup revealed bilateral pulmonary effusion. Transthoracic echocardiography showed a large mass in the left atrium. Urgent surgical resection under cardiopulmonary bypass was performed. We focused on oxygenation improvement and cardiac function management by applying protective ventilation with low positive end expiratory pressure, low dose inotropic agents, and other methods to maintain stable homeostasis. Results of biopsy established a diagnosis of metastatic leiomyosarcoma.Conclusion: We reported a case of metastatic leiomyosarcoma presenting as a lung mass with left atrial extension and anesthetic management during surgical resection. Treating acute heart failure and refractory hypoxemia was the key focus perioperatively. Keywords: leiomyosarcoma, metastatic, anesthesia, acute heart failure, hypoxemia

Wenxin He, Qiming Zheng, Yutian Ji, Chanchan Shen, Qisha Zhu, Wei Wang Department of Clinical Psychology and Psychiatry, School of Public Health, Zhejiang University College of Medicine, Hangzhou, People’s Republic of China Background: The body dysmorphic disorder is prevalent in general population and in psychiatric, dermatological, and plastic-surgery patients, but there lacks a structure-validated, comprehensive self-report measure of body image concerns, which is established through both exploratory and confirmatory factor analyses. Methods: We have composed a 34-item matrix targeting the body image concerns and trialed it in 328 male and 365 female Chinese university students. Answers to the matrix dealt with treatments including exploratory factor analyses, reserve of qualified items, and confirmatory factor analyses of latent structures. Results: Six latent factors, namely the Social Avoidance, Appearance Dissatisfaction, Preoccupation with Reassurance, Perceived Distress/Discrimination, Defect Hiding, and Embarrassment in Public, were identified. The factors and their respective items have composed a 24-item questionnaire named as the Body Image Concern Scale. Each factor earned a satisfactory internal reliability, and the intercorrelations between these factors were in a median level. Women scored significantly higher than men did on the Appearance Dissatisfaction, Preoccupation with Reassurance, and Defect Hiding. Conclusion: The Body Image Concern Scale has displayed its structure validation and gender preponderance in Chinese university students. Keywords: body dysmorphic disorder, body image, factor analysis, questionnaire development

Trichophyton (T.) mentagrophytes is common tineas infection with high incidence in rabbits and also a classical zoonotic infection in people exposed to infected animals. However, many cases never got a correct diagnosis, let alone considerable management and treatment, which could cause certain economic losses in rabbit farms. An outbreak of a highly contagious skin disease infecting rabbits and accompanying all farm staff on a large scale rabbit farm in China was investigated. The disease was diagnosed by routine physical examinations, and the etiology of the disease was identified as T. mentagrophytes by fungal culture, sequence of ribosomal internal transcribed spacer (ITS+) and chitin synthase-1 gene (pchs-1). To date, there is no report of Dermatomycoses infection in rabbits accompanied by farm staff infection in mainland China. In this case, the etiology is identified by using advanced molecular techniques and clinical, microbiological aspects and the histological features of the infection are described.