全视网膜光凝治疗糖尿病视网膜病变对视野影响的研究进展

糖尿病视网膜病变(DR)早期视野改变往往比视力更能及时反映病情进展。而全视网膜光凝(PRP)治疗DR在延缓病情进展的同时也造成了患眼视力下降和视野缩小等副作用。有研究表明,PRP治疗后的DR患者可因中心20°范围内的视野缺损而导致驾驶测试失败。为保证PRP疗效同时达到降低并发症的目的,激光技术不断改进与发展,通过调整激光参数、使用新型激光系统、与抗血管内皮生长因子(VEGF)药物联合、中西医结合治疗等方式可一定程度改善患眼视野,实现更佳疗效。未来可考虑在缺血指数(ISI)量化分析下,对视网膜缺血程度进行分级,依据ISI指标和视网膜无灌注区分布探索PRP治疗建议的最佳阈值及光凝范围,从而为DR患者提供更及时、更合理的个性化治疗方案。文章就PRP治疗DR对视野的影响进行简要综述。     

缬沙坦对颈动脉不稳定斑块患者血清炎症介质及缺血性脑卒中复发的影响

目的探讨缬沙坦对颈动脉不稳定斑块患者血清C-反应蛋白(CRP)、可溶性血管内皮细胞黏附分子-1(sVCAM-1)、白细胞介素-6(IL-6)的影响及对缺血性脑卒中复发干预的临床研究。方法不稳定斑块65例,缬沙坦治疗组33例,缬沙坦胶囊,80 mg,每日1次,口服,其他治疗措施与对照组基本相同。对照组32例,利尿降压药,口服。治疗前、1个月、2个月、38个月抽空腹静脉血共计5 ml,检测CRP、sVCAM-1、IL-6、血糖,同时监测血压。38个月时统计两组脑梗死复发和死亡情况,以CT或磁共振成像(MRI)出现新的梗塞灶为准。结果在1、2、38个月后治疗组血清CRP、sVCAM-1I、L-6浓度逐渐降低,组内相比差异有统计学意义(P<0.05),对照组除转变为硬斑者外其余变化不大。治疗组和对照组组间相比变化较大,差异有统计学意义(P<0.05)。终点38个月时,治疗组、对照组经CT或MRI证实脑梗死复发为7例(21.2%)和15例(46.9%)例,死亡为2例(6.1%)和5例(15.6%)例,治疗组复发率和病死率明显低于对照组(P<0.05)。结论缬沙坦稳定颈动脉斑块与血清中CRP、sVCAM-1I、L-6炎症介质的降低密切相关,降低不稳定斑块的破裂,从而减少了缺血性脑卒中的复发和死亡。     

L-Serine Treatment is Associated with Improvements in Behavior,EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants

Pathogenic missense variants in GRIN2A and GRIN2B may result in gain or loss of function (GoF/LoF) of the N-methyl-D-aspartate receptor (NMDAR). This observation gave rise to the hypothesis of successfully treating GRIN-related disorders due to LoF variants with co-agonists of the NMDAR. In this respect, we describe a retrospectively collected series of ten individuals with GRIN2A- or GRIN2B-related disorders who were treated with L-serine, each within an independent n-of-1 trial. Our cohort comprises one individual with a LoF missense variant with clinical improvements confirming the above hypothesis and replicating a previous n-of-1 trial. A second individual with a GoF missense variant was erroneously treated with L-serine and experienced immediate temporary behavioral deterioration further supporting the supposed functional pathomechanism. Eight additional individuals with null variants (that had been interpreted as loss-of-function variants despite not being missense) again showed clinical improvements. Among all nine individuals with LoF missense or null variants, L-serine treatment was associated with improvements in behavior in eight (89%), in development in four (44%), and/or in EEG or seizure frequency in four (44%). None of these nine individuals experienced side effects or adverse findings in the context of L-serine treatment. In summary, we describe the first evidence that L-serine treatment may not only be associated with clinical improvements in GRIN-related disorders due to LoF missense but particularly also null variants.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01173-9.     

A Young Patient with Microscopic Polyangiitis Requiring Hemodialysis with Complications of Repeated Episodes of Posterior Reversible Encephalopathy Syndrome Probably Due to Different Etiologies

A young woman with microscopic polyangiitis (MPA) requiring hemodialysis showed repeated posterior reversible encephalopathy syndrome (PRES) with spatiotemporal multiple lesions over a period of two months. The first PRES episode with confusion and the second PRES episode with vertigo and nausea were caused by MPA, hypertension and renal failure. These symptoms were improved by the reinforcement of MPA treatment and blood pressure management. The third PRES episode with nausea, headache, seizure and visual changes was induced by rituximab infusion and hypertension. The PRES was improved with blood pressure and convulsant management. These conditions are challenging to diagnose and treat.     

The attenuation effect of potassium 2‐(1‐hydroxypentyl)‐benzoate in a mouse model of diabetes‐associated cognitive decline: The protein expression in the brain

Aims dl‐PHPB (potassium 2‐(1‐hydroxypentyl)‐benzoate) has been shown to have neuroprotective effects against acute cerebral ischemia, vascular dementia, and Alzheimer''s disease. The aim of this study was to investigate the effects of dl‐PHPB on memory deficits and preliminarily explore the underlying molecular mechanism.MethodsBlood glucose and behavioral performance were evaluated in the KK‐A^y diabetic mouse model before and after dl‐PHPB administration. Two‐dimensional difference gel electrophoresis (2D‐DIGE)‐based proteomics was used to identify differentially expressed proteins in brain tissue. Western blotting was used to study the molecular mechanism of the related signaling pathways.ResultsThree‐month‐old KK‐A^y mice were given 150 mg/kg dl‐PHPB by oral gavage for 2 months, which produced no effect on the level of serum glucose. In the Morris water maze test, KK‐A^y mice treated with dl‐PHPB showed significant improvements in spatial learning and memory deficits compared with vehicle‐treated KK‐A^y mice. Additionally, we performed 2D‐DIGE to compare brain proteomes of 5‐month KK‐A^y mice treated with and without dl‐PHPB. We found 14 altered proteins in the cortex and 11 in the hippocampus; two of the 25 altered proteins and another four proteins that were identified in a previous study on KK‐A^y mice were then validated by western blot to further confirm whether dl‐PHPB can reverse the expression levels of these proteins. The phosphoinositide 3‐kinase/protein kinase B/glycogen synthase kinase‐3β (PI3K/Akt/GSK‐3β) signaling pathway was also changed in KK‐A^y mice and dl‐PHPB treatment could reverse it.ConclusionsThese results indicate that dl‐PHPB may play a potential role in diabetes‐associated cognitive impairment through PI3K/Akt/GSK‐3β signaling pathway and the differentially expressed proteins may become putative therapeutic targets.     

Proteomic analysis of the effects of caffeine in a neonatal rat model of hypoxic‐ischemic white matter damage

AimWhite matter damage (WMD) is the main cause of cerebral palsy and cognitive impairment in premature infants. Although caffeine has been shown to possess neuroprotective effects in neonatal rats with hypoxic‐ischemic WMD, the mechanisms underlying these protective effects are unclear. Herein, proteins modulated by caffeine in neonatal rats with hypoxic‐ischemic WMD were evaluated.MethodsWe identified differential proteins and performed functional enrichment analyses between the Sham, hypoxic‐ischemic WMD (HI), and HI+caffeine‐treated WMD (Caffeine) groups. Confirmed the changes and effect of proteins in animal models and determined cognitive impairment via water maze experiments.ResultsIn paraventricular tissue, 47 differential proteins were identified between the Sham, HI, and Caffeine groups. Functional enrichment analyses showed that these proteins were related to myelination and axon formation. In particular, the myelin basic protein (MBP), proteolipid protein, myelin‐associated glycoprotein precursor, and sirtiun 2 (SIRT2) levels were reduced in the hypoxic‐ischemic WMD group, and this effect could be prevented by caffeine. Caffeine alleviated the hypoxic‐ischemic WMD‐induced cognitive impairment and improved MBP, synaptophysin, and postsynaptic density protein 95 protein levels after hypoxic‐ischemic WMD by preventing the HI‐induced downregulation of SIRT2; these effects were subsequently attenuated by the SIRT2 inhibitor AK‐7.ConclusionCaffeine may have clinical applications in the management of prophylactic hypoxic‐ischemic WMD; its effects may be mediated by proteins related to myelin development and synapse formation through SIRT2.     

急性一氧化碳中毒后迟发性脑病患者血清白介素水平的变化及其临床意义

目的 探讨急性一氧化碳（CO）中毒后迟发性脑病（DEACMP）患者血清白介素（IL）水平变化及其临床意义。方法 采用酶联免疫吸附法检测34例DEACMP患者治疗前、后血中IL-2、4、6的水平,并与30名健康人和30例急性CO中毒（ACMP）患者进行比较。结果 （1）DEACMP组治疗后血中IL-2、4、6的含量显著高于治疗前（均P〈0．01）,但仍显著低于ACMP组和健康对照组（均P〈0．01）;（2）ACMP组血IL-2、4、6的含量明显高于健康对照组（均P〈0．01）。结论 DEACMP的发生与神经免疫病理损伤有关,血中IL-2、4、6的水平可以反映DEACMP患者机体的免疫状态。     

手十二井穴刺络放血法对MCAO模型大鼠大脑皮层c-fos蛋白表达的影响

目的 从脑内c-fos蛋白表达的角度观察井穴放血法对急性缺血性脑损伤的脑保护作用。方法 以凝结法阻断大鼠一侧大脑中动脉造成急性局灶性缺血性脑损伤模型(MCAO)，用免疫组织化学法观察缺血区皮层脑组织c-fos阳性细胞的表达变化及施加手十二井穴放血法后对其的干预治疗作用。结果 急性缺血性脑损伤可快速诱导c-fos蛋白在皮层缺血区脑组织的表达，其表达有随缺血时间延长逐渐增多的趋势，而缺血后即刻施加井穴放血的干预治疗．在1h、3h、6h、24h各缺血时间段均可明显上调缺血区皮层脑组织c-fos蛋白的表达水平。结论 c-fos蛋白表达既与缺血的严重程度有关．也反应神经元的应激反应能力，脑缺血能诱导c-fos蛋白的逐渐表达，提示脑的缺血性损伤可应激性地增强神经细胞对缺血、缺氧的耐受和适应能力。而早期施加井穴刺络放血疗法能进一步增强c-fos蛋白表达，提高神经细胞的应激能力，从而提高缺血区脑组织的抗损伤修复能力，减缓神经细胞凋亡，抵抗缺血性脑损害的进一步发展，产生有效的脑保护作用，表明井穴放血法对中风早期有一定的急救作用。