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.     

Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep

Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.     

中西医结合治疗动眼神经麻痹疗效观察

目的了解中西医结合法治疗动眼神经麻痹的临床疗效。方法对我院2012-03—2014-03收治的动眼神经麻痹患者进行抽样,择取74例患者随机分成2组,对照组予以基础性西医疗法,实验组在对照组治疗基础上予以中医疗法(包括针刺及服用中药正容汤等),观察2组患者的临床治疗效果。结果实验组总有效率(94.60%)明显高于对照组(64.86%),差异具有统计学意义(P0.05)。结论中西医结合法治疗动眼神经麻痹临床疗效确切,安全系数高,值得临床大力推广使用。     

Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer

Although both surgery and radiation are potential curative options for men with clinically localized prostate cancer, a significant proportion of men with high-risk and locally advanced disease will demonstrate biochemical and potentially clinical progression of their disease. Neoadjuvant systemic therapy before radical prostatectomy (RP) is a logical strategy to improve treatment outcomes for men with clinically localized high-risk prostate cancer. Furthermore, delivery of chemotherapy and other systemic agents before RP affords an opportunity to explore the efficacy of these agents with pathologic end points.Neoadjuvant chemotherapy, primarily with docetaxel (with or without androgen deprivation therapy), has demonstrated feasibility and safety in men undergoing RP, but no study to date has established the efficacy of neoadjuvant chemotherapy or neoadjuvant chemohormonal therapies. Other novel agents, such as those targeting the vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, clusterin, and immunomodulatory therapeutics, are currently under investigation.     

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。     

经食管实时三维超声心动图评价房性心律失常对二尖瓣结构和功能的影响

目的:应用经食管实时三维超声心动图(RT-3D-TEE)技术,探讨房性心律失常对二尖瓣结构和功能的影响.方法:选取2018年6月~2019年6月本院收治的房性心律失常拟行射频消融的患者49例纳入观察组,另外选取21例正常窦性心律者作为对照组,所有患者均行经胸超声心电图(TTE)和经食管实时三维超声心动图(RT-3D-TEE)检查,将两组患者的瓣环投影面积(A2D)、瓣环周长(C3D)、瓣环高度(H)、瓣环前后径(DAP)、瓣环前外侧至后内侧直径(DAIPm)、左室射血分数(LVEF)、左心房前后径(Lad)等参数进行比较,并分别计算对合面积和对合指数,之后采取二项Logistic回归分析或逐步线性回归对各参数及临床因素与对合指数的相关性进行分析.结果:两组患者在LVEF和对合面积方面的比较无明显差异(P>0.05),在A2D、C3D、H、DA、PDAIPm、Lad方面的比较,房性心律失常组患者明显高于正常窦性心律组患者(P<0.05),且观察组患者的对合指数明显降低(P<0.05).将49例观察组患者以不同心律失常类型分为持续性房颤、阵发性房颤、房扑、混合型房性心律失常4个亚组,采用单因素方差分析,发现在LVEF、C3D、Lad、对合指数方面的比较,各亚组间无明显差异(P>0.05).采用二项Logistic回归分析发现,女性是导致对合指数低的危险因素,另外对合指数较低、房性心律失常是导致二尖瓣返流的重要因素.结论:房性心律失常对患者二尖瓣的A2D、C3D、H、DA、PDAIPm、Lad等都会造成较大影响,从而降低对合指数,影响二尖瓣的正常功能,导致二尖瓣返流的发生.     

左氧氟沙星为基础的三联疗法根除幽门螺旋杆菌的疗效探讨

目的：探讨左氧氟沙星为基础的三联疗法根除幽门螺旋杆菌的临床治疗效果。方法方便选择2013年9月—2015年3月期间该院收治的120例Hp感染者作为实验对象，随机数字表法将患者分为对照组（n=60例）和观察组（n=60例），对照组采用标准三联法治疗，观察组采用以左氧氟沙星为基础的三联疗法治疗，观察两组患者Hp根除情况及恶心呕吐、腹部不适等不良反应发生情况。结果观察组Hp根除率显著高于对照组，差异有统计学意义（P<0.05），观察组总不良反应发生率为8.33%（5/60)，对照组总不良反应发生率为13.33%（8/60)，观察组不良反应发生率低于对照组，差异不具有统计学意义（P>0.05）。结论 Hp患者采用以左氧氟沙星为基础的三联疗法治疗，临床疗效较好，能够有效提高Hp根除率，并且不良反应发生率低，安全可靠，值得临床推广使用。     

Assisting students with autism to cooperate with their peers to perform computer mouse collaborative pointing operation on a single display simultaneously

The purpose of this study was to provide students with autism spectrum disorder (ASD) the chance to cooperate with their peers to perform computer mouse collaborative pointing operation. In this study, we adopted the Single Display Groupware (SDG) concept to develop the Multiple Cursor Collaborative Operating Program (MCCOP) software, which allows multiple users to operate a single computer simultaneously without interfering with each other. With the implementation of MCCOP software, users control their own cursors to perform a function in their respective cursor moving areas on a single display. A collaborative pointing test software (CPTS) program was designed in this experiment to evaluate participants’ collaborative pointing performance. This study adopted an ABAB design, and the experimental results show that all participants significantly increased their collaborative pointing performance during the intervention phase, compared to the baseline phase. Practical and developmental implications of the findings are discussed.