Pharmacological doses of melatonin impede cognitive decline in tau‐related Alzheimer models,once tauopathy is initiated,by restoring the autophagic flux

Alterations in autophagy are increasingly being recognized in the pathogenesis of proteinopathies like Alzheimer's disease (AD). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects in an Alzheimer model related to tauopathy by improving the autophagic flux and, thereby, prevent cognitive decline. The injection of AAV‐hTau^P301L viral vectors and treatment/injection with okadaic acid were used to achieve mouse and human ex vivo, and in vivo tau‐related models. Melatonin (10 μmol/L) impeded oxidative stress, tau hyperphosphorylation, and cell death by restoring autophagy flux in the ex vivo models. In the in vivo studies, intracerebroventricular injection of AAV‐hTau^P301L increased oxidative stress, neuroinflammation, and tau hyperphosphorylation in the hippocampus 7 days after the injection, without inducing cognitive impairment; however, when animals were maintained for 28 days, cognitive decline was apparent. Interestingly, late melatonin treatment (10 mg/kg), starting once the alterations mentioned above were established (from day 7 to day 28), reduced oxidative stress, neuroinflammation, tau hyperphosphorylation, and caspase‐3 activation; these observations correlated with restoration of the autophagy flux and memory improvement. This study highlights the importance of autophagic dysregulation in tauopathy and how administration of pharmacological doses of melatonin, once tauopathy is initiated, can restore the autophagy flux, reduce proteinopathy, and prevent cognitive decline. We therefore propose exogenous melatonin supplementation or the development of melatonin derivatives to improve autophagy flux for the treatment of proteinopathies like AD.     

Electronic clinical records in primary care for estimating disease burden and management. An example of COPD

Chronic obstructive pulmonary disease (COPD) is a significant health problem in developed countries. We aimed to estimate the prevalence of COPD in a single Spanish healthcare area. We also aimed to assess if there are any differences in prevalence and spirometry use among primary care services by utilizing already registered information. We designed a cross-sectional study to determine the prevalence of COPD and the performance of spirometries in each primary care service. A total of 8,444 patients were diagnosed with COPD, with a prevalence of 2.6% for individuals older than 39 years. The prevalence increased with age and was much higher in men. Significant heterogeneity was found in the prevalence of COPD and spirometry use among primary care services. COPD was underdiagnosed and there was wide variability in spirometry use in our area. Greater efforts are needed to diagnose COPD in order to improve its clinical outcomes and to refine registries so that they can be used as reliable sources of information     

基于VOSviewer的2019新型冠状病毒病中医临床诊疗可视化分析＊

目的 通过对公开发表在网络和数据库的有关中医药治疗2019新型冠状病毒肺炎（corona virus disease 2019，COVID-19）的文献进行方、药、证的可视化分析，客观全面的对COVID-19的中医药治疗进行探讨，为现代中医临床诊疗提供参考。方法 本文选用运用文献计量学方法和VOSviewer可视化软件对纳入文献中的用药情况进行数据拆分、整理和分析。结果 本研究高质量数据的主要期刊来源是核心期刊《中医杂志》；新冠临床用方以解表清热剂、开窍补益剂、辟秽祛湿剂为主；临床用药以解表药、清热解毒药、化湿祛痰药以及补益药为主；临床治病思路以六经辨证、三焦辨证和卫气营血辨证理论为指导；临床常见证型为湿、热、寒、毒相关证型；重视新冠前期预防以及后期恢复调养；治疗过程用药考究，注重养阴与祛邪并进。结论 新冠的中医临床诊治考病全面，并注重养阴与祛邪并进，可为官方制定治疗方案提供参考。     

益气通脉饮联合西药治疗气虚血瘀型冠心病心绞痛90例临床疗效观察

目的:探讨益气通脉饮治疗气虚血瘀型冠心病心绞痛的临床疗效。方法:选取2017年10月—2019年2月烟台业达医院收治的气虚血瘀型冠心病心绞痛的患者90例作为研究对象,根据随机数字表法将所选患者均分为两组,每组各45例,两组的一般资料经统计学方法,差异无统计学意义(P>0.05),因此具有可比性。对照组给予常规西药进行治疗,观察组在对照组治疗基础上给予益气通脉饮治疗,1个月后比较两组临床的疗效,评估治疗前后中医证候、心绞痛症状分级和血脂水平。临床检测的数据通过统计产品与服务解决方案(Statistical Product and Service Solutions,SPSS) 19.0软件进行分析和处理,计量的数据使用平均数±标准差(x±s)表示,采用双侧t检验,计数的数据采用χ~2检验,以%表示,以P<0.05为差异有统计学意义。结果:治疗后,对照组和观察组都有一定疗效,但观察组的改善中医证候总有效率95.56%(43/45),高于对照组的82.22%(37/45),两组比较具有统计学意义(P<0.05);心绞痛的症状总有效率观察组为93.33%(42/45),对照组为77.78%(35/45),两组比较差异有统计学意义(P<0.05);与治疗前相比较,两组治疗后的三酰甘油(Triglyceride,TG)、血清总胆固醇(Serum Total Cholesterol,TC)、高密度脂蛋白胆固醇(High Density Liptein Cholesterol,HDL-C)水平均降低(P<0.05),且观察组治疗后低于对照组(P<0.05),两组治疗后的HDL-C升高(P<0.05),组间比较,差异无统计学意义(P>0.05)。结论:益气通脉饮治疗气虚血瘀型冠心病心绞痛的疗效显著,值得临床进一步研究与推广应用。     

Sentinel lymph node biopsy for 102 patients with primary cutaneous melanoma at a single Japanese institute

Sentinel lymph node biopsy (SLNB) is a widely accepted standard procedure for patients with clinically localized melanoma. Melanoma prevalence and Clark's subtype differ between Asians and Caucasians. Here, we evaluated our experience on SLNB for cutaneous melanoma in a Japanese population. SLNB was performed for patients with melanoma between July 2000 and June 2014. We retrospectively analyzed 102 patients regarding association of clinicopathological features with sentinel lymph node (SLN) status, melanoma‐specific survival (MSS) and disease‐free survival (DFS). A positive SLN was significantly associated with primary Breslow thickness. Compared with 43 patients with negative SLN, 59 patients with positive SLN had significantly shorter MSS (5‐year survival rate, 94.3% vs 63.2%; P = 0.0002) and DFS (5‐year survival rate, 92.7% vs 63.4%; P = 0.0004). According to our subgroup analyses, nine patients with positive non‐SLN had significantly shorter MSS compared with 32 patients with negative non‐SLN (5‐year survival rate, 32.4% vs 68.5%; P = 0.0273). The survival of 51 Japanese patients with acral lentiginous melanoma (ALM) was not inferior to the survival of patients with other Clark's subtype. Breslow thickness is an important factor for both MSS and DFS, and the status of SLN is the most predictive prognostic factor in Japanese patients with clinically localized melanomas, as in case of Caucasians. Features of ALM may be different between Asians and Caucasians.     

普通变异型免疫缺陷病合并肝硬化1例并文献复习

目的:讨论普通变异型免疫缺陷病(common variable immunodeficiency disease,CVID)的发病机制、临床表现及治疗方法。方法:报道1例普通变异型免疫缺陷病合并肝硬化患者并复习相关文献。结果:普通变异型免疫缺陷病是临床少见病,易误诊,病因不清,临床表现复杂,部分患者病程中可出现肝功能异常,甚至并发肝硬化。结论:临床反复感染的患者应考虑CVID的可能,须进一步作血浆免疫球蛋白的检测确诊。对已经确诊患者定期补充静脉丙种球蛋白,同时还应定期检查肝功能。     

Association of meibomian gland architecture and body mass index in a pediatric population

PurposeTo determine if meibomian gland architecture in a pediatric population is impacted by body mass index (BMI).MethodsProspective evaluation of 175 eyes of 175 pediatric patients from two clinics. Demographic and clinical information were reviewed. Symptoms of dry eye were assessed with the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. Meibography was performed and grading of images was performed by a masked rater using a previously validated 5-point meiboscale (0–4) for gland atrophy and a 3-point score (0–2) for gland tortuosity.Results175 eyes of 175 participants aged 4–17 years (11.6 ± 3.7 years) were imaged. The mean meiboscore was 0.82 ± 0.94 (range 0–4) and the mean gland tortuosity score was 0.53 ± 0.70 (range 0–2). Ninety-six patients (56%) showed evidence of gland atrophy (meiboscore greater than 0) and the majority of patients (n=50, 29%) had a gland tortuosity score of 1. The mean BMI was 20.5 ± 4.86 kg/m² with 39.4% of patients (n = 69) above the 85th percentile. BMI percentile was not found to be a significant predictor of a meiboscore greater than 0 (odds ratio (OR) 1.004 95% confidence interval (CI) (0.99–1.10, p = 0.41). However, BMI percentile was found to be a significant predictor of gland tortuosity score (OR 1.01 95% CI (1.00–1.02), p = 0.02). Patients with BMI percentiles between 41 and 60 were 3.79 times more likely to have a gland tortuosity score of greater than 0 than patients with BMI percentiles between 0 and 20 (OR 3.789 CI (1.17–12.24)). No significant associations were found between age, race, or sex and meiboscore or tortuosity. There was a trend towards reduction in lipid layer thickness with increasing BMI percentile (p = 0.028, r² = 0.04).ConclusionIn this pediatric population, there was an association between meibomian gland tortuosity and higher percentiles of BMI. Future studies are needed to elucidate the pathogenesis of meibomian gland tortuosity and atrophy in pediatric patients.     

Retinal disease in the C3 glomerulopathies and the risk of impaired vision

Background: Dense deposit disease and atypical hemolytic uremic syndrome are often caused by Complement Factor H (CFH) mutations. This study describes the retinal abnormalities in dense deposit disease and, for the first time, atypical haemolytic uremic syndrome. It also reviews our understanding of drusen pathogenesis and their relevance for glomerular disease. Methods: Six individuals with dense deposit disease and one with atypical haemolytic uremic syndrome were studied from 2 to 40 years after presentation. Five had renal transplants. All four who had genetic testing had CFH mutations. Individuals underwent ophthalmological review and retinal photography, and in some cases, optical coherence tomography, and further tests of retinal function. Results: All subjects with dense deposit disease had impaired night vision and retinal drusen or whitish-yellow deposits. Retinal atrophy, pigmentation, and hemorrhage were common. In late disease, peripheral vision was restricted, central vision was distorted, and there were scotoma from sub-retinal choroidal neovascular membranes and atypical serous retinopathy. Drusen were present but less prominent in the young person with atypical uremic syndrome due to a heterozygous CFH mutation. Conclusions: Drusen are common in forms of C3 glomerulopathy caused by compound heterozygous or heterozygous CFH mutations. They are useful diagnostically but also impair vision. Drusen have an identical composition to glomerular deposits. They are also identical to the drusen of age-related macular degeneration, and may respond to the same treatments. Individuals with a C3 glomerulopathy should be assessed ophthalmologically at diagnosis, and monitored regularly for vision-threatening complications.