Oscillation-specific nodal alterations in early to middle stages Parkinsons disease.

Background: Different oscillations of brain networks could carry different dimensions of brain integration. We aimed to investigate oscillation-specific nodal alterations in patients with Parkinsons disease (PD) across early stage to middle stage by using graph theory-based analysis. Methods: Eighty-eight PD patients including 39 PD patients in the early stage (EPD) and 49 patients in the middle stage (MPD) and 36 controls were recruited in the present study. Graph theory-based network analyses from three oscillation frequencies (slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.073 Hz; slow-3: 0.073-0.198 Hz) were analyzed. Nodal metrics (e.g. nodal degree centrality, betweenness centrality and nodal efficiency) were calculated. Results: Our results showed that (1) a divergent effect of oscillation frequencies on nodal metrics, especially on nodal degree centrality and nodal efficiency, that the anteroventral neocortex and subcortex had high nodal metrics within low oscillation frequencies while the posterolateral neocortex had high values within the relative high oscillation frequency was observed, which visually showed that network was perturbed in PD; (2) PD patients in early stage relatively preserved nodal properties while MPD patients showed widespread abnormalities, which was consistently detected within all three oscillation frequencies; (3) the involvement of basal ganglia could be specifically observed within slow-5 oscillation frequency in MPD patients; (4) logistic regression and receiver operating characteristic curve analyses demonstrated that some of those oscillation-specific nodal alterations had the ability to well discriminate PD patients from controls or MPD from EPD patients at the individual level; (5) occipital disruption within high frequency (slow-3) made a significant influence on motor impairment which was dominated by akinesia and rigidity. Conclusions: Coupling various oscillations could provide potentially useful information for large-scale network and progressive oscillation-specific nodal alterations were observed in PD patients across early to middle stages

MicroRNA-646 inhibits the proliferation of ovarian granulosa cells via insulin-like growth factor 1 (IGF-1) in polycystic ovarian syndrome (PCOS)

Introduction: Polycystic ovarian syndrome (PCOS) is a common endocrinopathy in women. MicroRNAs (miRNAs) have been proven to play a crucial role in balancing the proliferation and apoptosis of granulosa cells (GCs) in PCOS. Material and methods: The miRNA of PCOS was screened by bioinformatics analysis, and microRNA 646 (miR-646) was found to be involved in insulin-related pathways by enrichment analysis. The cell counting kit-8 (CCK-8), cell colony formation, and the 5-ethynyl-2’-deoxyuridine (EdU) assays were used to explore the effect of miR-646 on proliferation of GCs, flow cytometry was used to measure the cell cycle and apoptosis, and Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to explore the biological mechanism of miR-646. The human ovarian granulosa cells KGN were selected by measuring the miR-646 and via insulin-like growth factor 1 (IGF-1) levels and used for cell transfection. Results: Overexpressed miR-646 inhibited KGN cell proliferation, and silenced miR-646 advanced it. Most cells were arrested in the S phase of cell cycle with overexpressed-miR-646, while after silencing miR-646, cells were arrested in the G2/M phase. And the miR-646 mimic raised apoptosis in KGN cells. Also, a dual-luciferase reporter proved the regulation effect of miR-646 on IGF-1, miR-646 mimic inhibited IGF-1, and miR-646 inhibitor advanced IGF-1. The cyclin D1, cyclin-dependent kinase 2 (CDK2), and B-cell CLL/lymphoma 2 (Bcl-2) levels were inhibited with overexpressed-miR-646, while silenced-miR-646 promoted their expression, and the bcl-2-like protein 4 (Bax) level was the opposite. This study found that silenced-IGF1 antagonized the promotive effect of the miR-646 inhibitor on cell proliferation. Conclusions: MiR-646 inhibitor treatment can promote the proliferation of GCs by regulating the cell cycle and inhibiting apoptosis, while silenced-IGF-1 antagonizes it

Work-family conflict and its related factors among emergency department physicians in China: A national cross-sectional study

BackgroundWork-family conflict is common among emergency department physicians. Identifying the factors associated with work-family conflict is key to reducing its negative impact on mental health and work attitudes. However, the work-family conflict of Chinese emergency department physicians and the related factors have been scarcely studied.ObjectiveThis study aimed to investigate the current status and related factors of work-family conflict among Chinese emergency department physicians.MethodsA national cross-sectional study was conducted among emergency department physicians in China from June 2018 to August 2018. A standard questionnaire was used to investigate the demographic characteristics, work-related factors, and work-family conflict of emergency department physicians. The generalized linear regression analysis was used to identify the related factors of work-family conflict.ResultsA total of 10,457 licensed emergency department physicians participated in the study. The average score of work-family conflict among the enrolled emergency department physicians was 19.27 ± 3.94, and the prevalence of high levels of work-family conflict was 69.19%. The multivariable regression analysis showed that emergency physicians who were female (linear regression coefficient, −0.25; SE, 0.08; P = 0.002), older than 40 years (linear regression coefficient,−0.53; SE, 0.14; P < 0.001), and earning more than 4,000 CNY per month (e.g., 4,001~6,000 vs. ≤4,000 CNY: linear regression coefficient, −0.17; SE, 0.09; P = 0.04) had lower work-family conflicts. However, emergency department physicians who were married (linear regression coefficient, 0.37; SE, 0.11; P < 0.001), highly educated (linear regression coefficient, 0.46; SE, 0.10; P < 0.001), had a high technical title (e.g., intermediate vs. junior technical title: linear regression coefficient, 0.61; SE, 0.09; P < 0.001), worked in a high-grade hospital (e.g., tertiary hospital vs. emergency center: linear regression coefficient, 0.38; SE, 0.11; P < 0.001), had a higher frequency of night shifts (e.g., 6~10 night shifts per month vs. 0~5 night shifts per month: linear regression coefficient, 0.43; SE, 0.10; P < 0.001), self-perceived shortage of physicians in the department (linear regression coefficient, 2.22; SE, 0.08; P < 0.001), and experienced verbal abuse (linear regression coefficient, 1.48; SE, 0.10; P < 0.001) and physical violence (linear regression coefficient, 0.84; SE, 0.08; P < 0.001) in the workplace had higher work-family conflict scores.ConclusionMost emergency department physicians in China experience a high-level work-family conflict. Hospital administrations are recommended to develop family-friendly workplace policies, establish a scientific shift system, and keep the number of emergency department physicians to meet the demand to reduce work-family conflict

HBV infection-induced liver cirrhosis development in dual-humanized mice with human bone mesenchymal stem cell transplantation

疾病动物模型是现代医学发展的基石，尤其是重大、突发传染病暴发时，适宜的疾病动物模型可为及时发现病原体、制定防控策略提供强大保障，原创的疾病动物模型已成为衡量一个国家生物医药科研水平的标志。我校夏宁邵教授团队和浙江大学附属第一医院李君教授团队历经5年的协同攻关，终于建立了国际上首个高度模拟人类乙肝病毒（HBV）自然感染诱发的慢乙肝肝硬化小鼠模型。厦门大学公共卫生学院袁伦志博士生、浙江大学医学院附属第一医院江静博士和厦门大学公共卫生学院刘旋博士生为该论文共同第一作者。厦门大学夏宁邵教授、浙江大学附属第一医院李君教授和厦门大学程通副教授为该论文共同通讯作者。【Abstract】Objective： Developing a small animal model that accurately delineates the natural history of hepatitis B virus (HBV) infection and immunopathophysiology is necessary to clarify the mechanisms of host-virus interactions and to identify intervention strategies for HBV-related liver diseases. This study aimed to develop an HBV-induced chronic hepatitis and cirrhosis mouse model through transplantation of human bone marrow mesenchymal stem cells (hBMSCs). Design： Transplantation of hBMSCs into Fah -/- Rag2 -/- IL-2Rγc -/- SCID (FRGS) mice with fulminant hepatic failure (FHF) induced by hamster-anti-mouse CD95 antibody JO2 generated a liver and immune cell dual-humanized (hBMSC-FRGS) mouse. The generated hBMSC-FRGS mice were subjected to assessments of sustained viremia, specific immune and inflammatory responses and liver pathophysiological injury to characterize the progression of chronic hepatitis and cirrhosis after HBV infection. Results： The implantation of hBMSCs rescued FHF mice, as demonstrated by robust proliferation and transdifferentiation of functional human hepatocytes and multiple immune cell lineages, including B cells, T cells, NK cells, dendritic cells (DCs) and immune cell lineages, including B cells, T cells, NK cells, dendritic cells (DCs) and viremia and specific immune and inflammatory responses and showed progression to chronic hepatitis and liver cirrhosis at a frequency of 55% after 54 weeks. Conclusion： This new humanized mouse model recapitulates the liver cirrhosis induced by human HBV infection, thus providing research opportunities for understanding viral immune pathophysiology and testing antiviral therapies in vivo.this work was supported by the national Science and technology Major Project (grant nos. 2017ZX10304402, 2017ZX10203201 and 2018ZX09711003-005-003), the national natural Science Foundation of china(grant nos. 81672023, 81571818 and 81771996), the Scientific research Foundation of the State Key laboratory of Molecular Vaccinology and Molecular Diagnostics (grant no 2016ZY005), Zhejiang Province and State's Key Project of the research and Development Plan of china (grant nos 2017c01026 and 2016YFc1101304/3).该研究获得了传染病防治国家科技重大专项、新药创制国家科技重大专项和国家自然科学基金的资助

Hospitalization Costs of COVID-19 Cases and Their Associated Factors in Guangdong, China: A Cross-Sectional Study

Background: The ongoing COVID-19 pandemic has brought significant challenges to health system and consumed a lot of health resources. However, evidence on the hospitalization costs and their associated factors in COVID-19 cases is scarce.Objectives: To describe the total and components of hospitalization costs of COVID-19 cases, and investigate the associated factors of costs.Methods: We included 876 confirmed COVID-19 cases admitted to 33 designated hospitals from January 15th to April 27th, 2020 in Guangdong, China, and collected their demographic and clinical information. A multiple linear regression model was performed to estimate the associations of hospitalization costs with potential associated factors.Results: The median of total hospitalization costs of COVID-19 cases was $2,869.4 (IQR:$3,916.8). We found higher total costs in male (% difference: 29.7, 95% CI: 15.5, 45.6) than in female cases, in older cases than in younger ones, in severe cases (% difference: 344.8, 95% CI: 222.5, 513.6) than in mild ones, in cases with clinical aggravation than those without, in cases with clinical symptoms (% difference: 47.7, 95% CI: 26.2, 72.9) than those without, and in cases with comorbidities (% difference: 21.1%, 21.1, 95% CI: 4.4, 40.6) than those without. We also found lower non-pharmacologic therapy costs in cases treated with traditional Chinese medicine (TCM) therapy (% difference: −47.4, 95% CI: −64.5 to −22.0) than cases without.Conclusion: The hospitalization costs of COVID-19 cases in Guangdong were comparable to the national level. Factors associated with higher hospitalization costs included sex, older age, clinical severity and aggravation, clinical symptoms and comorbidities at admission. TCM therapy was found to be associated with lower costs for some non-pharmacologic therapies