Neuroactive gonadal drugs for neuroprotection in male and female models of Parkinson's disease

The existence of sex differences in Parkinson's disease (PD) incidence is well documented with greater prevalence and earlier age at onset in men than in women. These reported sex differences could be related to estrogen exposure. In PD animal models, estrogen is well documented to be neuroprotective against dopaminergic neuron loss induced by neurotoxins. Using the 1-methyl 4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) mouse model, we showed that several compounds are neuroprotective on dopaminergic neurons including estrogen, the selective estrogen receptor modulator raloxifene, progesterone, dehydroepiandrosterone, the estrogen receptor alpha (ERα) agonist PPT as well as the G protein-coupled membrane estrogen receptor (GPER1) specific agonist G1. Accumulating evidence suggests that GPER1 could be implicated in the neuroprotective effects of estrogen, raloxifene and G1 in collaboration with ERα. We recently reported that the 5α-reductase inhibitor Dutasteride is also neuroprotective and could bring an alternative to estrogens for therapy in male. Additional studies are needed to optimize therapies with these gonadal drugs into safe personalized treatments according to sex for treatment of PD.     

Identification of genetic loci simultaneously associated with multiple cardiometabolic traits

Background and aimsCardiometabolic disorders (CMD) arise from a constellation of features such as increased adiposity, hyperlipidemia, hypertension and compromised glucose control. Many genetic loci have shown associations with individual CMD-related traits, but no investigations have focused on simultaneously identifying loci showing associations across all domains. We therefore sought to identify loci associated with risk across seven continuous CMD-related traits.Methods and resultsWe conducted separate genome-wide association studies (GWAS) for systolic and diastolic blood pressure (SBP/DBP), hemoglobin A1c (HbA1c), low- and high- density lipoprotein cholesterol (LDL-C/HDL-C), waist-to-hip-ratio (WHR), and triglycerides (TGs) in the UK Biobank (N = 356,574–456,823). Multiple loci reached genome-wide levels of significance (N = 145–333) for each trait, but only four loci (in/near VEGFA, GRB14-COBLL1, KLF14, and RGS19-OPRL1) were associated with risk across all seven traits (P < 5 × 10^?8). We sought replication of these four loci in an independent set of seven trait-specific GWAS meta-analyses. GRB14-COBLL1 showed the most consistent replication, revealing nominally significant associations (P < 0.05) with all traits except DBP.ConclusionsOur analyses suggest that very few loci are associated in the same direction of risk with traits representing the full spectrum of CMD features. We identified four such loci, and an understanding of the pathways between these loci and CMD risk may eventually identify factors that can be used to identify pathologic disturbances that represent broadly beneficial therapeutic targets.     

Drug resistance profile of Mycobacterium kansasii clinical isolates before and after 2-month empirical antimycobacterial treatment

ObjectivesMycobacterium kansasii pulmonary disease is frequently misdiagnosed and treated as tuberculosis, especially in countries with high tuberculosis burden. This study aimed to investigate the drug resistance profile of M. kansasii in patients with M. kansasii pulmonary disease in Shanghai and to determine the variations in drug resistance after 2 months of antimycobacterial treatment.MethodsAll patients with a diagnosis of M. kansasii pulmonary disease from 2017 to 2019 in Shanghai were retrospectively analysed. Whole-genome sequencing was performed, and the minimum inhibitory concentration (MIC) to antimycobacterial drugs was measured using the broth microdilution method.ResultsIn total, 191 patients had a diagnosis of M. kansasii pulmonary disease. Of them, 24.1% (46/191) had persistent positive culture after 2 months of antimycobacterial treatment. Whole-genome sequencing revealed that the 46 paired isolates had a difference of <17 single nucleotide polymorphisms, thus excluding the possibility of exogenous reinfection. More than 90% of the baseline isolates were sensitive to rifampin, clarithromycin, moxifloxacin, or amikacin, whereas a high resistance to ethambutol (118/191, 61.8%) and 4 μg/mL of isoniazid (32/191, 16.8%) were observed. Two isolates presented high resistance to rifamycin (i.e. a rifampin MIC of >8 μg/mL and a rifabutin MIC of 8 μg/mL) both containing the rpoB mutation (S454L). The increase of MIC to rifampin, ethambutol, and/or isoniazid was identified in 50.0% (23/46) of the patients.DiscussionA high prevalence of innate resistance to ethambutol and isoniazid was observed among circulating M. kansasii clinical strains in Shanghai. The increase in drug resistance under empirical antimycobacterial treatment highlighted the urgency of definitive species identification before initiating treatment.     

一起介入治疗意外照射导致背部大面积放射性皮肤损伤的调查及分析

目的 通过调查分析1例由于介入治疗意外照射致背部大面积放射性损伤的病例,探讨该事件发生过程中存在的问题,为今后避免类似事件发生提供建议。方法 询问受照患者详细病史,收集分析患者临床诊疗资料,追踪观察患者临床表现和体征。采集患者外周血估算生物剂量,现场采集介入治疗医院照射设备数据等。结果 患者全身生物剂量估算为0.95 Gy。测得介入设备减影模式和透视模式下透视受检者入射体表空气比释动能率典型值分别为373.5和47.8 mGy/min。该介入医生习惯长时间曝光操作,其年有效剂量为20.51 mSv,高于同科室其他工作量相近的介入医生（3.09 mSv）。患者全身及局部临床表现均符合放射损伤,辗转多家医院未予明确诊断,局部损伤治疗效果不明显。结论 结合生物剂量估算结果及临床表现,该病例被诊断为放射性皮肤损伤Ⅳ度。放射性损伤与是否按规范操作及X射线机输出剂量等因素密切相关,非专科医院在辐射损伤的临床诊断及治疗有待加强。     

苏州市吴江区消除碘缺乏病后2001～2011年监测结果分析

目的 分析苏州市吴江区2001～2011年碘缺乏病监测情况,掌握动态变化趋势,评价防治效果,为持续消除碘缺乏病提供科学依据.方法 根据省市有关碘盐监测和调查评估方案,采用碘盐监测、病情监测及综合监测方法.结果 2008～2011年的碘盐覆盖率≥95％,差异无统计学意义（P＞o.05）,2007年以后碘盐合格率呈上升趋势,差异有统计学意义（P ＜0.05）;8～10周岁儿童甲状腺肿大率为0.83％（均＜5％）,2007年、2009年出现降低趋势,差异有统计学意义（P ＜0.05）;8～10周岁儿童尿碘100 μg/L以下的比率在6.25％～16.66％（＜50％）、尿碘50μg/L以下的比率在0～3.00％（＜20％）;特需人群的孕妇和哺乳期妇女尿碘中位数为181.40μgL,尿碘150 μg/L以下的比率占42.86％.结论 吴江区盐碘、尿碘及甲状腺肿大率3项指标均达到国家消除碘缺乏病的标准.11年的监测结果显示,全区碘缺乏病的防治成果得到了进一步巩固.今后应加强特需人群的碘营养监测.     

Knowledge,attitudes and practices related to the influenza virus and vaccine among older adults in Eastern China

BackgroundThis study aims to assess the association between socio-demographic and health characteristics of older adults in Eastern China and knowledge, attitudes, and practices (KAP) about the influenza virus and vaccine.MethodsA prospective cohort of 1506 older adults (aged ≥60 years) was enrolled from November to December 2015 in Jiangsu Province. We examined the association between demographics, health and functional status, and cognitive impairment at enrollment with awareness of influenza virus and vaccine and KAP items focused on five Health Belief Model domains. At a 12-month follow-up interview we assessed change in awareness and readiness to be vaccinated.ResultsOne in five older adults was aware of the influenza virus (21%) or vaccine (20%); even fewer reported having at least “a little” knowledge of the virus and vaccine (7% and 4%, respectively); less than 1% reported ever receiving an influenza vaccine. Retirement, higher education and income, and normal cognitive status were consistently associated with both awareness and knowledge of influenza virus. The odds of having at least “a little” knowledge of the vaccine was 2.9-fold (95% CI = 1.6–5.3) higher among older adults with at least some secondary schooling. Among the 108 with knowledge of the virus, 55% said they “worry about getting the flu this season.” Among the 73 with knowledge of the vaccine, 92% believed the vaccine was at least somewhat effective and less than half (43%) thought that influenza vaccination was safe. At a 12-month follow-up interview, 33% (442/1333) increased from no knowledge to at least “a little”.ConclusionsIf and when influenza vaccines become widely available to older adults in China, our results indicate that influenza vaccination campaigns with basic information on the virus and vaccine could be beneficial for all older adults, especially those with less education and/or more cognitive impairment.     

苏州市婴幼儿轮状病毒腹泻分子流行病学研究

目的 研究苏州市5岁以下婴幼儿轮状病毒腹泻分子流行病学特征。方法 对2001年9月～2002年8月期间在苏州大学附属儿童医院就诊的5岁以下腹泻患儿进行调查。收集腹泻患儿粪便标本检测轮状病毒并对轮状病毒阳性标本用ELISA、PCR法进行分型研究。结果 共检测标本775份，轮状病毒阳性274份，检出率35．35％；血清分型发现，轮状病毒腹泻G分型以G3(40．15％)和G1(28．42％)为主要流行株，基因P分型结果以P[4](39．68％)为主，尚发现较多不常见G／P组合和未分型病毒株。结论 苏州市婴幼儿轮状病毒腹泻，以G3和P[4]最多见，但有较多未分型病毒株，应继续进行轮状病毒腹泻的监测。     

2009-2011年苏州市吴中区托幼机构的消毒质量

目的 了解吴中区托幼机构消毒卫生现状,分析存在的问题,为托幼机构卫生管理工作提供科学依据.方法 依据卫生部消毒技术规范和江苏省托幼机构消毒卫生标准,对全区26家托幼机构2009-2011年的监测采样结果进行评价和分析.结果 共采集样本644份,合格551份,合格率为85.6％.餐具合格率最高,工作人员手合格率最低.城乡托幼机构消毒质量间的差异有统计学意义(P＜0.01).结论 吴中区托幼机构合格率不高,应不断加强对托幼机构消毒卫生质量监督管理.     

Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in gastric cancer

Background and objective

The underlying molecular mechanisms of gastric cancer (GC) have yet not been investigated clearly. In this study, we aimed to identify hub genes involved in the pathogenesis and prognosis of GC.