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Mingmin Guo,1,2 Yi Wu,2,3 Maijiao Peng,1,2 Nenqun Xiao,1,2 Zhijun Lei,1,2 Zhoujin Tan2,3 1School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 2Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, Changsha, People’s Republic of China; 3School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Zhijun Lei, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China, Email lzj-707@163.com Zhoujin Tan, School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China, Email tanzhjin@sohu.comBackground: Sishen Pill (SSP) is a traditional Chinese medicine prescription commonly used to treat diarrhea with kidney-yang deficiency syndrome. The aim was to investigate the underlying mechanisms of SSP’s therapeutic effects, providing experimental evidence for its mechanism of action.Methods: A mouse model of diarrhea with kidney-yang deficiency syndrome was induced using adenine combined with Folium sennae. After successful model replication, SSP decoction was administered. CutC activity, TMAO, IL-6, TNF-α levels, and cecal content microbiota were measured.Results: SSP significantly improved the general behavioral characteristics of diarrhea mice, and reduced CutC activity, TMAO and IL-6 levels. Sequencing results indicated significant changes at the phylum and genus levels. Correlation analysis revealed a positive correlation between CutC activity and Faecalibaculum (p< 0.05) and Chryseobacterium (p< 0.05), and a significant negative correlation with Prevotellaceae UCG− 001, Rikenella (p< 0.05), Acinetobacter (p< 0.05), Parasutterella (p< 0.05), and Lacticaseibacillus (p< 0.05). TNF-α levels showed a significant negative correlation with Lacticaseibacillus (p< 0.05), Prevotellaceae UCG− 001 (p< 0.01), Parasutterella (p< 0.05), and Candidatus Saccharimonas (p< 0.05). IL-6 levels exhibited a significant negative correlation with Rikenella (p< 0.05), Acinetobacter (p< 0.05), Prevotellaceae UCG− 001 (p< 0.05), Lacticaseibacillus (p< 0.01), and Parasutterella (p< 0.05), and a significant positive correlation with Faecalibaculum (p< 0.05), Chryseobacterium (p< 0.01), and A2. Serum TMAO levels showed a significant positive correlation with Faecalibaculum (p< 0.05) and Chryseobacterium (p< 0.01), and hepatic TMAO levels exhibited a significant positive correlation with Chryseobacterium (p< 0.05).Conclusion: SSP significantly alleviated the symptoms of diarrhea with kidney-yang deficiency syndrome by modulating the cecal microbiota, downregulating CutC activity, and reducing TMAO and inflammatory factor levels. The cecal microbiota-CutC-TMAO-inflammatory cytokine axis may be a key mechanism underlying the therapeutic effects of SSP.Keywords: Diarrhea, Kidney-Yang Deficiency Syndrome, Sishen Pill, CutC, Cecal microbiota, TMAO, Inflammation

Xiang Zhang,1,&ast; Yu Zhou,2,3,&ast; Lu Fu,4,&ast; Lu Zhou,5 Xiangjun Cheng,6 Wei Zhang,2,3 Zhongming Tan5 1Department of Infection Management, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, People’s Republic of China; 3Sanya Institute of Nanjing Agricultural University, Sanya, Hainan Province, People’s Republic of China; 4Department of Nosocomial Infection Management, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, Jiangsu Province, People’s Republic of China; 5NHC Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, People’s Republic of China; 6Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongming Tan, NHC Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, No. 172 Jiangsu Road, Gulou District, Nanjing, Jiangsu Province, 210009, People’s Republic of China, Tel +862583759339, Email jstzm@jscdc.cn Wei Zhang, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, No. 1 Tongwei Road, Nanjing, Jiangsu Province, 210095, People’s Republic of China, Tel +862584396517, Email vszw@njau.edu.cnPurpose: Staphylococcus warneri is an opportunistic pathogen responsible for hospital-acquired infections (HAIs). The aim of this study was to describe an outbreak caused by S. warneri infection in a neonatal intensive care unit (NICU) and provide investigation, prevention and control strategies for this outbreak.Methods: We conducted an epidemiological investigation of the NICU S. warneri outbreak, involving seven neonates, staff, and environmental screening, to identify the source of infection. WGS analyses were performed on S. warneri isolates, including species identification, core genome single-nucleotide polymorphism (cgSNP) analysis, pan-genome analysis, and genetic characterization assessment of the prevalence of specific antibiotic resistance and virulence genes.Results: Eight S. warneri strains were isolated from this outbreak, with seven from neonates and one from environment. Six clinical cases within three days in 2021 were linked to one strain isolated from environmental samples; isolates varied by 0– 69 SNPs and were confirmed to be from an outbreak through WGS. Multiple infection prevention measures were implemented, including comprehensive environmental disinfection and stringent protocols, and all affected neonates were transferred to the isolation wards. Following these interventions, no further cases of S. warneri infections were observed. Furthermore, pan-genome analysis results suggested that in human S. warneri may exhibit host specificity.Conclusion: The investigation has revealed that the outbreak was linked to the milk preparation workbench by the WGS. It is recommended that there be a stronger focus on environmental disinfection management in order to raise awareness, improve identification, and prevention of healthcare-associated infections that are associated with the hospital environment.Keywords: Staphylococcus warneri, neonatal intensive care unit, whole-genome sequencing, pan-genome

Xiang Huo,1 Zhongming Tan,1,2 Huimin Qian,1,2 Yuanfang Qin,1,2 Chen Dong,1,2 Chuchu Li,1,2 Xiaoxiao Kong,1,2 Jie Hong1,2 1National Health Commission (NHC) Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People’s Republic of China; 2Department of Acute Infectious Disease Control and Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People’s Republic of ChinaCorrespondence: Jie Hong, Department of Acute Infectious Disease Control and Prevention, Jiangsu Provincial Center for Disease Control and Prevention, 172 Jiangsu Road, Gulou Distrct, Nanjing, People’s Republic of China, Email hongjie@jscdc.cnBackground: Streptococcus pneumoniae is a significant etiological agent of infection and commonly inhabits the human nasopharynx, alongside other potentially pathogenic bacteria. In this study, S. pneumoniae strains were obtained from a community population and subjected to investigation of their phenotypes, genotypes, and vaccine coverage.Methods: S. pneumoniae was isolated from nasopharyngeal swab samples of a healthy population in the Guangfu Community. Capsular serotypes and genotypes were identified using Quellung reaction and multilocus sequence typing (MLST), respectively. The antimicrobial susceptibility was tested using minimum inhibitory concentrations.Results: In total, 500 unvaccinated people were sampled. Ninety-four S. pneumoniae strains were identified. Common serotypes were 19F, 6A, and 9V. The strain coverages of PCV13 and PPV23 were 61.7% and 58.5%, respectively. About 27.6% isolates were non-susceptible to penicillin, and over 80% were resistant to erythromycin and doxycycline. Among 27 novel sequence types (STs) identified in all strains, the most common STs were ST236 (6/94, 6.4%) and ST12669 (6/94, 6.4%). Nearly half of the strains were grouped into four clone complexes (CC12665, CC271, CC6011, and CC180), of which CC271 showed the highest resistance to PEN.Conclusion: In our study, various drug-resistant clone complexes of Streptococcus pneumoniae were found in the healthy population, the elderly, and children. Consequently, pneumococcal vaccines should be included in the national immunization schedule to prevent disease spread.Keywords: vaccine, Streptococcus pneumonia, serotype, antibiotics, STs

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

Guojun Tong,1,2 Hai Qian,1 Dongli Li,2 Jing Li,2 Jing Chen,2 Xiongfeng Li,3 Zhenhua Tan1 1General Surgery, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Huzhou, People’s Republic of China; 2Central Laboratory, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Huzhou, People’s Republic of China; 3Orthopedic Surgery, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Huzhou, People’s Republic of ChinaCorrespondence: Zhenhua Tan, General Surgery, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Sanhuan North Road 1558&num;, Huzhou, People’s Republic of China, Email Tanzh99@163.comAim: This study aims to explore the effect of different doses of antibiotics on rats in order to observe alterations in their fecal microbiota, inflammatory changes in the colonic mucosa and four types of inflammatory markers in blood serum.Methods: Our methodology involved separating 84 female Sprague Dawley rats into groups A-G, with each group consisting of 12 rats. We collected the rat feces for analysis, using a distinct medium for bacterial cultivation and counting colonies under a microscope. On the 11th and 15th days of the experiment, half of the rats from each group were euthanized and 5 mL of abdominal aortic blood and colon tissues were collected. Inflammations changes of colon were observed and assessed by pathological Hematoxylin Eosin (HE) staining. Enzyme-linked immune sorbent assay (ELISA) was adopted for detecting C-reactive protein (CRP), IL-6, IL1-β and TNF-α.Results: Our findings revealed that the initial average weight of the rats did not differ between groups (p> 0.05); but significant differences were observed between stool samples, water intake, food intake and weight (p=0.009, < 0.001, 0.016 and 0.04, respectively) within two hours after the experiment. Additionally, there were notable differences among the groups in nine tested microbiota before and after weighting methods (all p< 0.001). There were no difference in nine microbiota at day 1 (all p> 0.05); at day 4 A/B (p=0.044), A/D (p< 0.001), A/E (p=0.029); at day 8, all p< 0.01, at day 11, only A/F exist significant difference (p< 0.001); at day 14 only A/D has difference (p=0.045). Inflammation changes of colon were observed between groups A-G at days 11 and 15. Significant differences between all groups can be observed for CRP, IL-6, IL1-β and TNF-α (p< 0.001).Conclusion: This study suggests that antibiotics administration can disrupt the balance of bacteria in the rat gut ecosystem, resulting in an inflammatory response in their bloodstream and inducing inflammation changes of colon. Keywords: antibiotics, imbalance of intestinal flora, Sprague Dawley rats, inflammatory bowel disease, IBD, colitis model

Wenpei Wu,1,2,&ast; Zhi Geng,3– 5,&ast; Aimei Wu,2,&ast; Xinyi Chen,6,7 Xiaoying Meng,2 Qianyun Zhang,2 Zheng Tan,2 Hong Yue,2 Juncang Wu1,2 1Department of Neurology, Hefei Second People’s Hospital Affiliated to Bengbu Medical University, Hefei, Anhui, 230011, People’s Republic of China; 2Department of Neurology, Hefei Second People’s Hospital, Hefei, Anhui, 230011, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, People’s Republic of China; 5Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, 230000, People’s Republic of China; 6Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, Anhui, 230011, People’s Republic of China; 7The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juncang Wu; Hong Yue, Intersection of Guangde Road and Leshui Road, Hefei, Anhui, 230011, People’s Republic of China, Tel/Fax +86 551 13956076148 ; +86 551 18949855780, Email wujuncang126@126.com; yuehong01@foxmail.comBackground and Purpose: The role of serum uric acid (UA) level in patients suffering from stroke remains controversial. Our aim was to investigate the effect of UA level on clinical outcomes in patients with intracerebral hemorrhage (ICH).Methods: In the retrospective cohort study, we analyzed data from 250 patients with intracerebral hemorrhage (85 women and 165 men) to investigate the difference in UA levels between patients with a good prognosis and those with a poor prognosis. Additionally, we analyzed the impact of UA levels on the risk of short-time prognosis of ICH patients.Results: Patients with a good prognosis presented with significantly lower levels of UA (348.71 ± 84.97 μmol/L) than those with poor prognosis (393.06 ± 148.46 μmol/L). Furthermore, multivariate logistic regression model demonstrated that a high UA level was a likely risk factor for worse prognosis among patients suffering in ICH (odds ratio [95% confidence interval], 1.006 [1.0012, 1.0108]; P = 0.015). Additionally, UA has a threshold effect value of 363.9 μmol/L and was presented in levels that were in a nonlinear relationship with incidence rate of short-time prognosis outcome of ICH patients.Conclusion: Our findings indicate that higher UA levels can increase the risk of poor clinical prognosis in patients with ICH and high UA levels are not conductive to the clinical prognosis of patients with ICH. These findings provide a new perspective on the treatment and prevention of ICH.Keywords: intracerebral hemorrhage, uric acid, oxidative stress, follow-up, nonlinear relationship, prognosis

Zongbiao Tan,&ast; Chuan Liu,&ast; Pengzhan He,&ast; Yanrui Wu, Jiao Li, Jixiang Zhang, Weiguo Dong Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiguo Dong, Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Tel +86 027-88041911, Email dongweiguo@whu.edu.cnPurpose: Immune infiltration plays a pivotal role in the pathogenesis of mucosal damage in ulcerative colitis (UC). The objective of this study was to systematically analyze and identify genetic characteristics associated with immune infiltration in UC.Patients and Methods: Gene expression data from three independent datasets obtained from the Gene Expression Omnibus (GEO) were utilized. By employing the ssGSEA and CIBERSORT algorithms, we estimated the extent of immune cell infiltration in UC samples. Subsequently, Weighted Correlation Network Analysis (WGCNA) was performed to identify gene modules exhibiting significant associations with immune infiltration, and further identification of hub genes associated with immune infiltration was accomplished using least absolute shrinkage and selection operator (LASSO) regression analysis. The relationship between the identified hub genes and clinical information was subsequently investigated.Results: Our findings revealed significant activation of both innate and adaptive immune cells in UC. Notably, the expression levels of CD44, IL1B, LYN, and ITGA5 displayed strong correlations with immune cell infiltration within the mucosa of UC patients. Immunohistochemical analysis confirmed the significant upregulation of CD44, LYN, and ITGA5 in UC samples, and their expression levels were found to be significantly associated with common inflammatory markers, including the systemic immune inflammation indices, C-reactive protein, and erythrocyte sedimentation rate.Conclusion: CD44, LYN, and ITGA5 are involved in the immune infiltration pathogenesis of UC and may be potential therapeutic targets for UC.Keywords: Ulcerative colitis, Immune infiltration, WGCNA, CIBERSORT, LASSO

Zhiyong Tan,1– 3,&ast; Xiaorong Chen,4,&ast; Jieming Zuo,1– 3,&ast; Shi Fu,1– 3,&ast; Jiansong Wang,1– 3 Haifeng Wang1– 3 1Department of Urology, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Urological Disease Clinical Medical Center of Yunnan Province, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 3Scientific and Technological Innovation Team of Basic and Clinical Research of Bladder Cancer in Yunnan Universities, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 4Department of Kidney Transplantation, the Third Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiansong Wang; Haifeng Wang, Department of Urology, the Second Affiliated Hospital of Kunming Medical University, Yunnan Institute of Urology, Kunming, 650101, People’s Republic of China, Email wangjiansong@kmmu.edu.cn; t13085348360@163.comBackground: As known abnormal sialylation exerts crucial roles in the growth, metastasis, and immune evasion of cancers, but the molecular characteristics and roles in bladder cancer (BLCA) remain unclear. This study intends to establish BLCA risk stratification based on sialylation-related genes and elucidate its role in prognosis, tumor microenvironment, and immunotherapy of BLCA.Methods: Bulk RNA-seq and scRNA-seq data were downloaded from open-access databases. The scRNA-seq data were processed using the R package “Seurat” to identify the core cell types. The tumor sub-typing of BLCA samples was performed by the R package “ConsensusClusterPlus” in the bulk RNA-seq data. Signature genes were identified by the R package “limma” and univariate regression analysis to calculate risk scores using the R package “GSVA” and establish risk stratification of BLCA patients. Finally, the differences in clinicopathological characteristics, tumor microenvironment, and immunotherapy efficacy between the different groups were investigated.Results: 5 core cell types were identified in the scRNA-seq dataset, with monocytes and macrophages presenting the greatest percentage, sialylation-related gene expression, and sialylation scores. The bulk RNA-seq samples were classified into 3 tumor subtypes based on 19 prognosis-related sialylation genes. The 10 differential expressed genes (DEGs) with the smallest p-values were collected as signature genes, and the risk score was calculated, with the samples divided into high and low-risk score groups. The results showed that patients in the high-risk score group exhibited worse survival outcomes, higher tumor grade, more advanced stage, more frequency of gene mutations, higher expression levels of immune checkpoints, and lower immunotherapy response.Conclusion: We established a novel risk stratification of BLCA from a glycomics perspective, which demonstrated good accuracy in determining the prognostic outcome, clinicopathological characteristics, immune microenvironment, and immunotherapy efficacy of patients, and we are proposing to apply it to direct the choice of clinical treatment options for patients.Keywords: bladder cancer, bulk RNA-seq, scRNA-seq, sialylation, tumor microenvironment, immunotherapy

Chan Dai,1 Huoying Chen,2 Mengya Jiao,1 Na Zhang,1 Xuhuan Tang,1 Anqi Fan,3 Shiwang Liu,1 Zhigang Qian,1 Chenchen Wang,1 Yong Xu,1 Zheng Tan,1,4 Fanfan Zeng,5 Fang Zheng1,4 1Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guizhou, People’s Republic of China; 3College of Life Science, Yangtze University, Jingzhou, Hubei, People’s Republic of China; 4Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, Hubei, People’s Republic of China; 5Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Fang Zheng, Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, Hubei, People’s Republic of China, Email zhengfangtj@hust.edu.cn Fanfan Zeng, Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, Hubei, People’s Republic of China, Email zengfanfan@126.comPurpose: IL-33 is constitutively expressed in skin tissues. Alopecia, a T cells-driven disorder of the hair follicles (HFs), is a common complication in the development of psoriasis. However, the role of IL-33 in psoriatic alopecia remains uncovered. Here, we investigated the roles of IL-33 in inducing pathological changes of hair follicles in psoriasis.Patients and Methods: Clinical samples and imiquimod (IMQ)-induced psoriatic mice samples were used to investigate the pathological changes and T-cell infiltration of HFs. By using immunohistochemistry staining, the distribution and expression alteration of IL-33 in HFs were determined. Next, by using IL-33 and ST2 knockout mice, we investigated the role of IL-33/ST2 axis in the pathological changes of HFs in psoriasis. Meanwhile, recombinant IL-33 protein was subcutaneous injected to confirm its effect. Finally, RNA sequencing was used to clarify the genes and signaling pathways that involved in this process. Differentially expressed genes were further verified by RT-PCR in cultured HFs in vitro.Results: We found that the pathological changes of HFs and T cells infiltration in imiquimod-induced psoriatic mice were similar to that in psoriasis patients. The IL-33 positive keratinocytes in the outer root sheath of HFs were increased in both psoriasis patients and psoriatic model mice compared with the controls. By using gene knockout mice, we found that the pathological changes and T cell infiltration were attenuated in IL-33−/− and ST2−/− psoriatic model mice. In addition, subcutaneous injection of recombinant IL-33 exacerbated the pathological changes of HFs and T cell infiltration. RNA sequencing and RT-RCR revealed that IL-33 upregulated the transcription of genes related to keratinocytes proliferation and T lymphocytes chemotaxis.Conclusion: Our study identifies that IL-33 promotes the pathological changes of HFs in psoriasis, which contributes to psoriatic alopecia. Inhibition of IL-33 may be a potential therapeutic approach for psoriatic alopecia.Keywords: IL-33, psoriatic alopecia, hair follicle, keratinocytes

Sassafras tzumu is one of the most valuable tree species in southern China. However, the dormancy of the seed limits its seedling quality. In order to improve the germination percentage of seeds, characteristics, causes of dormancy, changes in endogenous hormones and nutrients during storage were investigated. The results showed that seed viability was 78.11%, and the highest water absorption rate was 26.09%. The germination percentage of the embryo without cotyledon was 21.13%, but intact seed and embryo could not germinate on hormone-free medium. Seed embryo and coat extracts were found to have a significant inhibitory effect on seed germination. Germination percentage were significantly positively correlated to free amino content (p < 0.01) and negatively correlated to soluble sugar content (p < 0.05) during storage. The levels of GA3 and GA3/ABA had significant effects on the germination percentage of S. tzumu seed storage at 4°C. The results suggest that S. tzumu seeds are in intermediate physiological dormancy at maturity and are mainly caused by the presence of inhibitory substances in the seed tissues. Furthermore, changes in endogenous hormones and metabolism of nutrients at 4°C can significantly promote the release from dormancy of S. tzumu seeds.

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

Shun Yu Sun,1 Wei Yi Yang,2 Zhuo Tan,2 Xing Yu Zhang,1 Yi Lin Shen,1 Qi Wei Guo,1 Guo Ming Su,1 Xu Chen,1 Jia Lin,1 Ding Zhi Fang1 1Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Preventive Medicine, West China School of Public health, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Ding Zhi FangDepartment of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, People’s Republic of China, Tel +86 28 85503410, Fax +86 28 85503204, Email dzfang@scu.edu.cnPurpose: To investigate serum levels of free fatty acids (FFAs) and their associations with routine serum lipids in diet-induced obese mice, which have been scantily reported before.Methods: Male C57BL/6 J mice were fed high-fat diets for 12 weeks to induce obesity. Levels of serum FFAs were measured by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.Results: Obese mice had higher serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), but lower triglycerides (TG) than control mice. A total of 30 FFAs were found, and 3 saturated fatty acids (SFAs), all 8 monounsaturated fatty acids (MUFAs) and 7 polyunsaturated fatty acids (PUFAs) decreased in obese mice, but one SFA (C4:0) increased. Differences in the relative levels of individual FFAs to total FFAs, SFAs, MUFAs or PUFAs between obese and control mice were different from each other and from those evaluated by concrete levels except C4:0, C16:1, C19:1 and C18:4. Only the concrete levels of C4:0, C22:3 and C18:4 were associated with routine serum lipids, including C22:3 negatively with TG in control mice, and C4:0 and C18:4 positively with LDL-C in obese mice, although the relative levels of C4:0 to total MUFAs negatively with TC, and C23:3 to total SFAs or MUFAs negatively with TG in control mice. Different relative levels of the remaining FFAs were differently associated with different routine serum lipids in obese and/or control mice.Conclusion: Obesity may influence serum FFAs profiles. The relationship of individual FFAs and their relative levels to other FFAs with routine serum lipids in obese and control mice suggests that individual FFAs may interact with others and obesity on levels of routine serum lipids. Once confirmed, the interactions may be novel perspectives when fatty acids are used to improve hyperlipidemia in the subjects with obesity.Keywords: free fatty acid, obesity, triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein

In this research, the characteristics of nickel-titanium (NiTi) powders produced by electrode induction melting inert gas atomization (EIGA) technique for additive manufacturing (AM) technology are investigated using various powder characterization technologies. The results show that the particle size distribution (PSD) of pre-alloyed NiTi powders prepared by EIGA has the range of 10 μm to 180 μm. The mean particle size distribution (D50) of the powder is 75 μm. The oxygen increase of the powder is only 0.005% compared to the raw rod. According to the requirements of the characteristics of the metal powder material used for AM, the powders are sieved into three categories, P1 (15-63 μm), P2 (63-150 μm), and P3 (>150 μm), respectively. The flow rates of P1 and P2 are 19.3 and 17.5 s·(50 g)-1, respectively. The surface, crosssectional microstructure, phase structure, and martensitic transformation temperature of the pre-alloyed NiTi powders with different particle sizes are investigated. The results show that powders of different particle sizes are primarily spherical or nearly spherical. The grain size of powders reduces with the decreasing of particle size. Both the bar stock and the powders of P1, P2, and P3 mainly exhibit the B2 phase. Comparing the powders P1, P2, and P3, the transformation temperature reduces with the decrease of particle size. A high density (99.55%) pre-alloyed NiTi specimen is successfully produced by selective laser melting (SLM) technology using P1 powders. The results indicate that the pre-alloyed NiTi alloy powder is appropriate for AM, which also has a good reference value for researchers producing AM powders.

Peng Yu, Ke Wei, Taimin Zhang, Zhenzong Tan, Hezhao Zhao, Hao Sun Chongqing University Cancer Hospital Gastrointestinal Department, Chongqing, 400000, People’s Republic of ChinaCorrespondence: Hao Sun; Hezhao ZhaoChongqing University Cancer Hospital, Gastrointestinal Department, Chongqing, 400000, People’s Republic of ChinaEmail sunhao68@hotmail.com; zhzalee@hotmail.comBackground: Growing evidence indicated that circRNAs played major roles in the progression of human cancer. Nevertheless, the molecular mechanism and effects of circTMCO3 in GC are still unclear.Methods: First, qRT-PCR was used to evaluate the levels of circTMCO3 from GC tissues, GC cells, normal tissues and gastric epithelial cells. Then, the GC cells were transfected to analyze the proliferation, migration and invasion of GC cells by MTT, colony formation and transwell assays. Next, the expressions of miR-577 and RAB14 in GC tissues and cells were examined by qRT-PCR following transfection. The target interaction of circTMCO3-miR-577 and miR-577-RAB14 was explored by the dual-luciferase reporter and RNA pull-down assays. In the end, the growth and viability of GC cells were detected by MTT, colony formation and transwell assays, respectively, following the transfection of GC cells.Results: In this research, we found circTMCO3 expressions are significantly up-regulated in GC tissues and cells compared with the normal tissues and gastric epithelial cells. We discovered that the knockdown of circTMCO3 remarkably inhibits the proliferation, migration and invasion of GC cells. Besides, through the prediction of binding sites between circTMCO3, miR-577 and RAB14, we discovered miR-577 is a target of circTMCO3 while RAB14 is a target gene of miR-577. Finally, the results demonstrate the overexpression of miR-577 and the silence of RAB14 could inhibit the effects of circTMCO3 on proliferation, migration and invasion in GC cells.Conclusion: circTMCO3 accelerated the growth and migration of GC cells by regulating miR-577/RAB14 axis.Keywords: gastric cancer, circTMCO3, miR-577, RAB14, KATO III, HGC-27

Miaomiao Liu,1,&ast; Hua Jiang,1,&ast; Yujuan Li,1 Chunmei Li,1 Zhijun Tan,2 Faguang Jin,1 Tao Zhang,1 Yandong Nan1 1Department of Respiratory and Critical Care Medicine, Tangdu Hospital, Air Force Military Medical University, Xi’an, 710038, People’s Republic of China; 2Department of Health Statistics, Air Force Military Medical University, Xi’an, 710032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yandong Nan; Tao Zhang Email 13709205538@163.com; zhangft@fmmu.edu.cnObjective: To identify the risk factors for predicting the dynamic progression of COVID-19.Methods: A total of 2321 eligible patients were included in this study from February 4 to April 15, 2020. Two illness conditions, including mild/moderate (M/M) subtype to severe/critical (S/C) and S/C to fatality, were classified. Clinical message was collected and compared, respectively. Kaplan–Meier method, Cox regression model and risk score system were used to predict disease progression in S/C COVID-19.Results: A total of 112 of 1761 patients with M/M subtype were progressors (P) and 1649 non-progressors (NP). Increasing disease progression associated with higher levels of neutrophils count (HR=1.958, 95% CI=1.253– 3.059, P=0.003), CK (HR=2.203, 95% CI=1.048– 4.632, P=0.037), LDH (HR=3.309, 95% CI=2.083– 5.256, P< 0.001) and CRP (HR=2.575, 95% CI=1.638– 4.049, P< 0.001), and lower level of lymphocytes count (HR=1.549, 95% CI=1.018– 2.355, P=0.041), as well as total lesion volume ratio greater than ≥ 10% (HR=2.286, 95% CI=1.451– 3.601, P< 0.001) on admission. In progression to fatality, 56 of the 672 S/C cases died and 616 survived. Increasing fatality associated with lower level of lymphocytes count (HR:2.060, 95% CI:1.000– 4.242, P=0.050), higher levels of BUN (HR:2.715, 95% CI:1.539– 4.790, P< 0.001), CK-MB (HR:3.412, 95% CI:1.760– 6.616, P< 0.001), LDH (HR:5.578, 95% CI:2.317– 13.427, P< 0.001), and PT (HR:3.619, 95% CI:2.102– 6.231, P< 0.001). Furthermore, high risk of neutrophils count, lymphocytes count, CK, LDH, CRP, and total lesion volume ratio was powerfully correlated with the incidence of progression to S/C in patients with NS COVID-19 and high odds of lymphocytes count, BUN, CK-MB, LDH, and PT were significantly associated with death in patients with S/C COVID-19. In addition, the progression and mortality rates increased with increasing risk scores.Conclusion: Elevated LDH level and lymphopenia were independent predictors for COVID-19 sustainable management in classifying non-severe patients who progressed to severe condition and identifying S/C patients who deteriorated to fatal outcomes as well. Total lesion volume ratio ≥ 10% may provide early predictive evidence with COVID-19 patients at high risk of developing into S/C to improve prognosis.Keywords: COVID-19, mild/moderate, severe/critical, progression, fatality, risk factors

Shagufta Naz,1,2 Fawad Ali Shah,1 Humaira Nadeem,1 Sadia Sarwar,1 Zhen Tan,3 Muhammad Imran,1 Tahir Ali,2 Jing Bo Li,2 Shupeng Li4 1Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, 44000, Pakistan; 2Shenzhen University Clinical Research Center for Neurological Diseases, Health Management Center, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, People’s Republic of China; 3Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 4State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, People’s Republic of ChinaCorrespondence: Humaira NadeemRiphah Institute of Pharmaceutical Sciences, Riphah International University, G-7/4, 7th Avenue, Islamabad, 44000, PakistanTel +92 51-2891835Fax +92 51-8350180Email humaira.nadeem@riphah.edu.pkShupeng LiState Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, People’s Republic of ChinaEmail lisp@pku.edu.cnPurpose: The development of resistance to available anticancer drugs is increasingly becoming a major challenge and new chemical entities could be unveiled to compensate this therapeutic failure. The current study demonstrated the synthesis of 2-aminothiazole [S3(a-d) and S5(a-d)] and 2-aminopyridine [S4(a-d) and S6(a-d)] derivatives that can target multiple cellular networks implicated in cancer development.Methods: Biological assays were performed to investigate the antioxidant and anticancer potential of synthesized compounds. Redox imbalance and oxidative stress are hallmarks of cancer, therefore, synthesized compounds were preliminarily screened for their antioxidant activity using DPPH assay, and further five derivatives S3b, S3c, S4c, S5b, and S6c, with significant antioxidant potential, were selected for investigation of in vitro anticancer potential. The cytotoxic activities were evaluated against the parent (A2780) and cisplatin-resistant (A2780CISR) ovarian cancer cell lines. Further, Molecular docking studies of active compounds were performed to determine binding affinities.Results: Results revealed that S3c, S5b, and S6c displayed promising inhibition in cisplatin-resistant cell lines in comparison to parent cells in terms of both resistance factor (RF) and IC50 values. Moreover, S3c proved to be most active compound in both parent and resistant cell lines with IC50 values 15.57 μM and 11.52 μM respectively. Our docking studies demonstrated that compounds S3c, S5b, and S6c exhibited significant binding affinity with multiple protein targets of the signaling cascade.Conclusion: Anticancer activities of compounds S3c, S5b, and S6c in cisplatin-resistant cell lines suggested that these ligands may contribute as lead compounds for the development of new anticancer drugs.Keywords: thiazole, pyridine, antioxidant activity, anticancer activity, molecular docking

Xiao Xiao,1 Zhiwen Tan,2 Min Jia,3 Xiaoli Zhou,1 Kemei Wu,3 Yanbing Ding,1 Wenjing Li3 1Department of Encephalopathy, Hubei Provincial Hospital of Traditional Chinese Medicine (Affiliated Hospital of Hubei University of Traditional Chinese Medicine, Hubei Institute of Traditional Chinese Medicine), Wuhan City, Hubei Province, People’s Republic of China; 2Department of Encephalopathy, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, Hubei Province, People’s Republic of China; 3Department of Neurology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, Hubei Province, People’s Republic of ChinaCorrespondence: Wenjing LiDepartment of Neurology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, No. 158 Wuyang Avenue, Enshi, 445000, Hubei Province, People’s Republic of ChinaTel +86 13597789520Fax +86 718 8263395Email 13597789520@163.comBackground: Parkinson’s disease (PD) is a prevalent neurodegenerative disease. Long noncoding RNA small molecule RNA host gene 1 (SNHG1) has been reported to play critical roles in Parkinson’s disease (PD) progression. The study aimed to further elucidate the mechanism of SNHG1 in PD pathogenesis.Methods: The levels of SNHG1, miR-125b-5p and mitogen-activated protein kinase 1 (MAPK1) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. Cell viability and apoptosis were evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. The activity of Caspase-3 or Caspase-9 was measured using a Caspase-3 or Caspase-9 Assay Kit. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, lactic dehydrogenase (LDH) activity, reactive oxygen species (ROS) generation and superoxide dismutase (SOD) activity were gauged by enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assay was performed to identify the relationship between miR-125b-5p and SNHG1 or MAPK1. The MPTP-induced PD mouse was used as an in vivo model of PD and MPP+-treated SK-N-SH and MN9D cells were used as in vitro models of PD.Results: SNHG1 and MAPK1 were significantly up-regulated while miR-125b-5p was down-regulated in the MPTP-induced PD mouse model and MPP+-induced PD cell models. SNHG1 silence or miR-125b-5p overexpression protected against MPP+-evoked apoptosis, oxidative stress and inflammation in SK-N-SH and MN9D cells. Moreover, SNHG1 acted as a molecular sponge of miR-125b-5p, and the protective impact of SNHG1 silence on MPP+-evoked cell damage was reversed by miR-125b-5p inhibition. Furthermore, MAPK1 was a functional target of miR-125b-5p and its overexpression attenuated the effects of miR-125b-5p restoration in MPP+-triggered cell injury. In addition, the behavioral changes in MPTP-induced PD mouse in vivo model were relieved by SNHG1 silence.Conclusion: SNHG1 knockdown exerted neuroprotective effects in MPP+-evoked cytotoxicity through regulating the miR-125b-5p/MAPK1 axis both in human and mouse PD cell models, highlighting a possible target for PD therapy.Keywords: Parkinson’s disease, SNHG1, miR-125b-5p, MAPK1, cytotoxicity

Jiaoying Jia, Yan Cui, Zhigang Tan, Wenjia Ma, Yugang Jiang Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha City, Hunan Province 410011, People’s Republic of ChinaCorrespondence: Yugang JiangDepartment of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha City, Hunan Province 410011, People’s Republic of ChinaTel +8673185295880Email jiangyugang123@csu.edu.cnBackground/Aims: Multiple studies have found that microRNAs (miRNAs) are involved in the development of cerebral ischemia. MiR-579-3p can inhibit inflammatory responses and apoptosis, leading to ischemia/reperfusion (I/R) damage. However, the mechanism of how miR-579-3p actions in brain I/R injury remains unclear. This study aimed to investigate the mechanism of the role of miR-579-3p in brain I/R injury.Methods: A rat model of cerebral ischemia–reperfusion injury was established by suture method. The effects of miR-579-3p on cerebral infarction size, brain water content, and neurological symptoms were evaluated. Flow cytometry was used to detect apoptosis. ELISA was used to detect the level of inflammatory factors. Western blot was used to detect the expression of P65, NCOA1, Bcl-2 and Bax. The relationship between miR-579-3p and NCOA1 was analyzed by bioinformatics analysis and luciferase assay.Results: Overexpression of miR-579-3p reduced infarct volume, brain water content and neurological deficits. Overexpression of miR-579-3p inhibited the expression level of the inflammatory cytokines, such as TNF-α, IL-6, COX-2 and iNOS, and increased the expression level of IL-10. MiR-579-3p overexpression inhibited NF-кB activity by reducing NRIP1. In addition, miR-579-3p could reduce the apoptotic rate of cortical neurons. Overexpression of miR-579-3p inhibited the activity of caspase-3, increased the expression level of anti-apoptotic gene Bcl-2 in neurons, and decreased the expression level of apoptotic gene Bax.Conclusion: miR-579-3p can be used to treat brain I/R injury, and its neuroprotective effect may be ascribed to the reduction of inflammation and apoptosis.Keywords: ischemia/reperfusion, miR-579-3p, inflammation, apoptosis

Shao-Wei Xue,1,2 Donglin Wang,1,2 Zhonglin Tan,3 Yan Wang,1,2 Zhenzhen Lian,1,2 Yunkai Sun,1,2 Xiaojiao Hu,1,2 Xiaole Wang,1,2 Xin Zhou1,2 1Center for Cognition and Brain Disorders, Institutes of Psychological Sciences and the Affiliated Hospital, Hangzhou Normal University, Hangzhou 311121, People’s Republic of China; 2Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou 311121, People’s Republic of China; 3Department of Psychiatry, Hangzhou Seventh People’s Hospital, Hangzhou 310013, People’s Republic of ChinaCorrespondence: Donglin WangCenter for Cognition and Brain Disorders, Institutes of Psychological Sciences and the Affiliated Hospital, Hangzhou Normal University, 2318 Yuhangtang road, Hangzhou, Zhejiang 311121, People’s Republic of ChinaTel +86 571 28867717Fax +86 571 28867717Email wangdl@hznu.edu.cnPurpose: Entropy analysis of resting-state functional magnetic resonance imaging (R-fMRI) has recently been adopted to characterize brain temporal dynamics in some neuropsychological or psychiatric diseases. Thalamus-related dysfunction might be a potential trait marker of major depressive disorder (MDD), but the abnormal changes in the thalamus based on R-fMRI are still unclear from the perspective of brain temporal dynamics. The aim of this study was to identify local entropy changes and subregional connectivity patterns of the thalamus in MDD patients.Patients and methods: We measured the sample entropy of the R-fMRI data from 46 MDD patients and 32 matched healthy controls. We employed the Louvain method for the module detection algorithm to automatically identify a functional parcellation of the thalamus and then examined the whole-brain subregional connectivity patterns.Results: The results indicated that the MDD patients had decreased entropy in the bilateral thalami compared with healthy controls. Increased functional connectivity between the thalamic subregions and the medial part of the superior frontal gyrus (mSFG) was found in MDD patients.Conclusion: This study showed new evidence about sample entropy changes in MDD patients. The functional connectivity alterations that were widely distributed across almost all the thalamic subregions with the mSFG in MDD suggest a general involvement independent of the location and function of the subregions.Keywords: major depressive disorder, entropy, thalamus, functional connectivity, superior frontal gyrus

Xiuli Zhang,* Zhen Tan,* Ting Kang, Chuanying Zhu, Siyu ChenDepartment of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaCorrespondence: Siyu ChenDepartment of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai 200092, People’s Republic of ChinaTel +86 21 2507 7642Email siyu.chen@shsmu.edu.cn*These authors contributed equally to this workPurpose: Gastric carcinogenesis is a multistep process and is the second-highest cause of cancer death worldwide with a high incidence of invasion and metastasis. MicroRNAs (miRNAs) engage in complex interactions with the machinery that controls the transcriptome and concurrently target multiple mRNAs. Recent evidence has shown that miRNAs are involved in the cancer progression, including promoting cell-cycle, conferring resistance to apoptosis, and enhancing invasiveness and metastasis. Here, we aim to elucidate the roles of miRNAs, especially microRNA-4665-3p (miR-4665-3p), in the inhibitory effect of arsenic sulfide in gastric cancer (GC).Methods: The arsenic sulfide-induced miRNA expression alterations in AGS cells was determined by miRNA microarray. RT-PCR was used to further verify the arsenic sulfide-regulated miRNAs in GC tissues. The inhibition of miR-4665-3p on the migration and invasion of GC cells were determined by wound healing assay and transwell assay. Western blot analysis was used to detect the expression of EMT related proteins and the putative target of miR-4665-3p.Results: The miR-4665-3p was up-regulated by arsenic sulfide and showed inhibition upon the migration and invasion of GC cells. MiRBase and Western blotting indicated that miR-4665-3p directly down-regulated the oncoprotein GSE1. Morphological observation also indicated that the up-regulation of miR-4665-3p inhibits the EMT in GC cells.Conclusion: Our data demonstrates that the increased expression of miR-4665-3p induced by arsenic sulfide suppresses the cell invasion, metastasis and EMT of GC cells, and has the potential to be a novel therapeutic target in GC.Keywords: arsenic sulfide, miR-4665-3p, gastric cancer, invasion, migration

Cuiling Zhang,1 Weigang Ren,1 Qingxin Liu,2 Zhikai Tan,3 Junwei Li,1 Chunyi Tong3 1College of Veterinary Medicine, Qingdao Agricultural University, Qingdao 266109, People’s Republic of China; 2Jiangsu Vocational College of Agriculture and Forestry, Jurong 212400, People’s Republic of China; 3Hunan Province Key Laboratory of Plant Functional Genomics and Developmental Regulation, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Hunan University, Changsha 410082, People’s Republic of China Introduction: In this study, we report on the development of an effective delivery system for siRNAs; a novel cell-penetrating peptide (CPP), T9(dR), obtained from transportan (TP), was used for in vivo and in vitro testing. Methods: In this study, toxicity of T9(dR) and TP and efficient delivery of siRNA were tested in 293T, MDCK, RAW, and A549 cells. Furthermore, T9(dR)- and TP-delivered siRNAs against nucleoprotein (NP) gene segment of influenza virus (siNP) were studied in both cell lines and mice. Results: Gel retardation showed that T9(dR) effectively condensed siRNA into nanoparticles sized between 350 and 550 nm when the mole ratio of T9(dR) to siRNA was ≥4:1. In vitro studies demonstrated that T9(dR) successfully delivered siRNA with low cellular toxicity into several cell lines. It was also observed that T9(dR)-delivered siRNAs inhibited replication of influenza virus more efficiently as compared to that delivered by TP into the MDCK and A549 cells. It was also noticed that when given a combined tail vein injection of siNP and T9(dR) or TP, all mice in the 50 nmol siNP group infected with PR8 influenza virus survived and showed weight recovery at 2 weeks post-infection. Conclusion: This study indicates that T9(dR) is a promising siRNA delivery tool with potential application for nucleotide drug delivery. Keywords: cell-penetrating peptide, CPP, siRNA, inhibition, influenza virus, IV, transportan, nucleoprotein, NP

A fully coupled thermo-mechanical model is established to simulate the temperature variations and the material deformations in friction stir welding (FSW) of Ti-6Al-4V. The extracted data are used for further simulation on microstructural evolutions. A multi scale model, which consists of the grain growth model in grain cluster scale and the phase transformation model in one grain scale, is proposed. The nuclei of α and β phases, the recrystallizations and the grain growths are systematically investigated. Comparisons with experimental data and experimental observations can validate the newly proposed microstructural evolution model for Ti-6Al-4V. Results indicate that the volume fractions of α and β phases can be directly determined by the cooling rates in FSW process. With the increase of the rotating speed, the volume fraction of α phase is increased and β phase decreased due to the increase of welding temperature. With the decrease of the translational speed, the volume fraction of α phase gets bigger and β phase smaller. The acicular α grain can be generated on the β grain boundaries and grows along direction on β substrate. The average length of α grain can be increased with longer cooling time and decreased with lower rotating speed or higher translational speed.

Haoxiang Chen,* Juchang Zhong,* Jian Wang, Ruiying Huang, Xiaoyin Qiao, Honghui Wang, Zhikai Tan College of Biology, Hunan University, Changsha, Hunan 410082, China *These authors contributed equally to this work Background: Skeletal muscle tissue engineering often involves the prefabrication of muscle tissues in vitro by differentiation and maturation of muscle precursor cells on a platform which provides an environment that facilitates the myogenic differentiation of the seeded cells.Methods: Poly lactic-co-glycolic acid (PLGA) 3D printed scaffolds, which simulate the highly complex structure of extracellular matrix (ECM), were fabricated by E-jet 3D printing in this study. The scaffolds were used as platforms, providing environment that aids in growth, differentiation and other properties of C2C12 myoblast cells.Results: The C2C12 myoblast cells grown on the PLGA 3D printed platforms had enhanced cell adhesion and proliferation. Moreover, the platforms were able to induce myogenic differentiation of the myoblast cells by promoting the formation of myotubes and up-regulating the expressions of myogenic genes (MyHC and MyOG).Conclusion: The fabricated 3D printed platforms have excellent biocompatibility, thereby can potentially be used as functional cell culture platforms in skeletal tissue engineering and regeneration. Keywords: myoblast, myogenic differentiation, 3D printing, 3D cell culture, skeletal muscle regeneration

Zhen Tan,* Xiuli Zhang,* Ting Kang, Lian Zhang, Siyu Chen Department of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China *These authors contributed equally to this work Purpose: Gastric and colon cancers have been the leading causes of cancer mortality in the world with limited therapy. Small molecules binding to bromodomains of bromodomain-containing protein 4 (BRD4) exert strong antitumor activities against hematological malignancies, while generally have limited efficacy in advanced solid tumors. Here, we found that the bromodomain and extra-terminal (BET)-bromodomain inhibitor JQ1, when combined with arsenic sulfide (As4S4, abbreviated as AS), synergistically decreased the expression of nuclear factor of activated T-cells (NFATs) as well as the downstream oncogene c-Myc and largely induced cell apoptosis via mitochondrial pathway in gastric and colon cancer cell lines.Methods: The synergistic cytotoxicity of AS and JQ1 in gastric and colon cancer cells was determined by MTT assay and verified by FACS assay. Western blot analysis and quantitative real-time PCR (qPCR) assay were used to detect the expression of NFATs and downstream apoptotic proteins. The mitochondrial transmembrane potential was determined by FACS assay, and the metastasis of cancer cells was detected by the wound-healing assay.Results: AS and JQ1 synergistically induced cell apoptosis in gastric and colon cancer cells by downregulating NFATs and upregulating apoptotic proteins. Combination of AS and JQ1 was associated with the decreased mitochondrial transmembrane potential, the cytochrome c release, and the subsequent caspase-3 activation.Conclusion: Thus, our data indicate that AS can effectively enhance the cytotoxicity of BET inhibitors in gastric and colon cancer cells through mitochondrial-mediated apoptosis induction. Keywords: arsenic sulfide, JQ1, NFAT, apoptosis, mitochondria

Jia J, Cui Y, Tan Z, Ma W, Jiang Y. Neuropsychiatr Dis Treat. 2020;16:1229–1238.The Editor and Publisher of Neuropsychiatric Disease and Treatment wish to retract the published article.The journal was notified by the Editor of Metabolic Brain Disease of a submission they received from another author group which had significant overlap with the paper published in Neuropsychiatric Disease and Treatment. The authors of the Neuropsychiatric Disease and Treatment paper could not be contacted for an explanation.The Editor has determined the findings are no longer valid and has requested for the paper to be retracted.Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.This retraction relates to this paper

Net primary production (NPP) is a central and fundamental carbon-related term in global change studies. We proposed a top-down method to quantifying forest NPP which overcomes the deficits of the traditional bottom-up method. The new top-down method combines eddy flux data, climate variables, tree inventory and metabolic theory. Our method was tested in six forests and provides reliable annual NPP estimations which are consistent with bottom-up results. Carbon use efficiency also supports this new method. Taking advantage of fine temporal resolution of our top-down method, we examined whether and confirmed NPP was well correlated with leaf area index at a seasonal scale, as suggested by past studies. The potential value of our new method as a standard NPP method is high because of the world-wide network on eddy tower and inventory plot, however further data of performance of the new method is needed to fully evaluate its performance under different conditions.

Rianne M Blom,1 Nienke C Vulink,1 Sija J van der Wal,1 Takashi Nakamae,1–3 Zhonglin Tan,1,4 Eske M Derks,1 Damiaan Denys1,5 1Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 2Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 3Department of Neural Computation for Decision-Making, ATR Brain Information Communication Research Laboratory Group, Kyoto, Japan; 4Department of Psychiatry, Hangzhou Mental Health Center, Hangzhou, People’s Republic of China; 5Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands Abstract: Body integrity identity disorder (BIID) is a condition in which people do not perceive a part of their body as their own, which results in a strong desire for amputation or paralyzation. The disorder is likely to be congenital due to its very early onset. The English literature describes only Western patients with BIID, suggesting that the disorder might be merely prevalent in the West. To scrutinize this assumption, and to extend our knowledge of the etiology of BIID, it is important to trace cases with BIID in non-Western populations. Our objective was to review Chinese and Japanese literature on BIID to learn about its presence in populations with a different genetic background. A systematic literature search was performed in databases containing Japanese and Chinese research, published in the respective languages. Five Japanese articles of BIID were identified which described two cases of BIID, whereas in the Chinese databases only BIID-related conditions were found. This article reports some preliminary evidence that BIID is also present in non-Western countries. However, making general statements about the biological background of the disorder is hampered by the extremely low number of cases found. This low number possibly resulted from the extreme secrecy associated with the disorder, perhaps even more so in Asian countries. Keywords: amputation, cross-cultural comparison, apotemnophilia, treatment, phenomenology, genetics

Zhang F, Li M, Wu X, et al. Drug Des Devel Ther. 2015;9:3969–3987. On page 3976, Figure 3B should be presented as follows: Following a review of the data post-publication, the authors found two identical cell cycle images in two different groups were placed for 200μM and 400μM. We have replaced the image for 400μM in this corrigendum. The authors confirmed that this error does not affect any statistical results or any relevant conclusions about Figure 3B. The authors apologize for this oversight. Read the original article here

Fei Zhang,* Maolan Li,* Xiangsong Wu,* Yunping Hu, Yang Cao, Xu’an Wang, Shanshan Xiang, Huaifeng Li, Lin Jiang, Zhujun Tan, Wei Lu, Hao Weng, Yijun Shu, Wei Gong, Xuefeng Wang, Yong Zhang, Weibin Shi, Ping Dong,# Jun Gu,# Yingbin Liu#Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work #These authors jointly directed this work Abstract: Gallbladder cancer (GBC), the most frequent malignancy of the biliary tract, is associated with high mortality and extremely poor prognosis. 20(S)-ginsenoside Rg3 (20(S)-Rg3) is a steroidal saponin with high pharmacological activity. However, the anticancer effect of 20(S)-Rg3 in human GBC has not yet been determined. In this study, we primarily found that 20(S)-Rg3 exposure suppressed the survival of both NOZ and GBC-SD cell lines in a concentration-dependent manner. Moreover, induction of cellular senescence and G0/G1 arrest by 20(S)-Rg3 were accompanied by a large accumulation of p53 and p21 as a result of murine double minute 2 (MDM2) inhibition. 20(S)-Rg3 also caused a remarkable increase in apoptosis via the activation of the mitochondrial-mediated intrinsic caspase pathway. Furthermore, intraperitoneal injection of 20(S)-Rg3 (20 or 40 mg/kg) for 3 weeks markedly inhibited the growth of xenografts in nude mice. Our results demonstrated that 20(S)-Rg3 potently inhibited growth and survival of GBC cells both in vitro and in vivo. 20(S)-Rg3 attenuated GBC growth probably via activation of the p53 pathway, and subsequent induction of cellular senescence and mitochondrial-dependent apoptosis. Therefore, 20(S)-Rg3 may be a potential chemotherapeutic agent for GBC therapy.Keywords: gallbladder cancer, 20(S)-ginsenoside Rg3, senescence, apoptosis, p53 pathway

Qiang Fu, Hongyu Hu, Dezhao Wang, Wei Chen, Zhixu Tan, Qun Li, Buxing Chen Department of Cardiology, Beijing Titantan Hospital, Capital Medical University, Beijing, People’s Republic of China Background: Growing evidence suggests that the left radial approach (LRA) is related to decreased coronary procedure duration and fewer cerebrovascular complications as compared to the right radial approach (RRA) in elective percutaneous coronary intervention (PCI). However, the feasibility of LRA in primary PCI has yet to be studied further. Therefore, the aim of this study was to investigate the efficacy of LRA compared with RRA for primary PCI in ST-elevation myocardial infarction (STEMI) patients.Materials and methods: A total of 200 consecutive patients with STEMI who received primary PCI were randomized to LRA (number [n]=100) or RRA (n=100). The study endpoint was needle-to-balloon time, defined as the time from local anesthesia infiltration to the first balloon inflation. Radiation dose by measuring cumulative air kerma (CAK) and CAK dose area product, as well as fluoroscopy time and contrast volume were also investigated.Results: There were no significant differences in the baseline characteristics between the two groups. The coronary procedural success rate was similar between both radial approaches (98% for left versus 94% for right; P=0.28). Compared with RRA, LRA had significantly shorter needle-to-balloon time (16.0±4.8 minutes versus 18.0±6.5 minutes, respectively; P=0.02). Additionally, fluoroscopy time (7.4±3.4 minutes versus 8.8±3.5 minutes, respectively; P=0.01) and CAK dose area product (51.9±30.4 Gy cm2 versus 65.3±49.1 Gy cm2, respectively; P=0.04) were significantly lower with LRA than with RRA.Conclusion: Primary PCI can be performed via LRA with earlier blood flow restoration in the infarct-related artery and lower radiation exposure when compared with RRA; therefore, the LRA may become a feasible and attractive alternative to perform primary PCI for STEMI patients. Keywords: transradial approach, primary percutaneous coronary intervention, ST-segment elevation myocardial infarction

The regrowth of tropical secondary forests and plantations can not offset the carbon release caused by tropical deforestation, consequently determining net carbon losses on tropical lands. However, large uncertainties remain in relation to this assumption. Here, we used a biometric method to estimate the net dry matter production and net ecosystem production in a rubber forest, the most widespread plantation type in tropical Southeast Asia. According to biometric estimates made during the study, the ecosystem was a carbon sink (790 gC m-2 yr-1). Net ecosystem carbon fluxes were measured by the eddy covariance method. The carbon budget estimated using the FluxNet procedure (904 gC m-2 yr-1) was closer to the biometric estimates in comparison to a method based on data measured during neutral atmospheric conditions. Overall, when considering the whole life cycle, including deforestation of the prior-existing tropical forest, the hypothesis of plantations serving as large carbon sinks is not supported by our study.

Although numerous studies have been conducted to investigate ecosystem-scale soil respiration, our understanding of this process is still incomplete, especially with respect to the spatial variability and ecological factors that drive such variability in respiration. The present study was conducted to investigate the respiration, structural parameters and soil properties in a seasonal rainforest with complex topography. Specifically, we sampled a 20-ha plot in intervals of 20 m to measure the soil respiration. Based on the entire 20-ha plot, the spatial mean soil respiration rate was 4.09 µmol m-2 s-1 and 2.71 µmol m-2 s-1 during the rainy and dry season, respectively. Strong spatial heterogeneity was observed, with coefficients of variance of 42% and 38% being obtained for the rainy and dry season, respectively. The patch size of soil respiration was approximately 40 m, which was much smaller than that of the soil temperature and water content. Soil-respiration hot spots induced a right-skewed probability density function of soil respiration in space. However, termite mounds did not account for the respiration hot spots. The required number of sampling points in our studied forest was estimated to be 71 and 51 for the rainy and dry season, respectively.

Soil erosion delivers enormous amounts of macro-nutrients including nitrogen (N) and phosphorus (P) from land to rivers, potentially sustaining water column bioavailable nutrient levels for decades. In this study, we represent erosional N and P fluxes in the Energy Exascale Earth System Model (E3SM) and apply the model to the continental United States. We estimate that during 1991-2019 soil erosion delivers 775 Gg yr-1 (1 Gg = 109 g) of particulate N (PN) and 328 Gg yr-1 of particulate P (PP) on average to the drainage basins of the northern Gulf of Mexico, including the Mississippi/Atchafalaya River and other rivers draining to the Texas Gulf and the Eastern Gulf. Our model simulation shows that in these rivers PP is the dominant P constituent and over 55% of P exported by erosion comes from soil P pools that could become bioavailable within decades. More importantly, we find that during 1991-2019 erosional N and P fluxes increase at rates of about 15 Gg N yr-1 and 6 Gg P yr-1, respectively, due to increased extreme rains in the Mississippi/Atchafalaya river basin, and this intensification of erosional N and P fluxes drive the significant increase of riverine PN and PP yields to the northern Gulf of Mexico. With extreme rains projected to increase with warming, erosional nutrient fluxes in the region would likely continue to rise in the future, thus complicating the effort of reducing eutrophication in the inland and coastal waters.