Brain neuropeptides in progressive supranuclear palsy

No significant alterations in the levels of Met-enkephalin-, Leu-enkephalin-, cholecystokinin- and substance P-like immunoreactive materials were found in 10 areas of postmortem brains from patients with progressive supranuclear palsy (PSP) when compared to controls. These results are at difference with the marked decrease in the levels of enkephalin-, cholecystokinin- and substance P-like immunoreactive materials previously reported in the basal ganglia of parkinsonian patients. Since PSP and Parkinson's disease are both characterized by a severe dopamine nigrostriatal deficit, these results suggest that the decreased brain peptide concentrations found in Parkinson's disease do not simply result from a dopaminergic neuronal loss.     

Newer variants of progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of disorders characterized by defects in bile secretion and presentation with intrahepatic cholestasis in infancy or childhood. The most common types include PFIC 1 (deficiency of FIC1 protein, ATP8B1 gene mutation), PFIC 2 (bile salt export pump deficiency, ABCB11 gene mutation), and PFIC 3 (multidrug resistance protein-3 deficiency, ABCB4 gene mutation). Mutational analysis of subjects with normal gamma-glutamyl transferase cholestasis of unknown etiology has led to the identification of newer variants of PFIC, known as PFIC 4, 5, and MYO5B related (sometimes known as PFIC 6). PFIC 4 is caused by the loss of function of tight junction protein 2 (TJP2) and PFIC 5 is due to NR1H4 mutation causing Farnesoid X receptor deficiency. MYO5B gene mutation causes microvillous inclusion disease (MVID) and is also associated with isolated cholestasis. Children with TJP2 related cholestasis (PFIC-4) have a variable spectrum of presentation. Some have a self-limiting disease, while others have progressive liver disease with an increased risk of hepatocellular carcinoma. Hence, frequent surveillance for hepatocellular carcinoma is recommended from infancy. PFIC-5 patients usually have rapidly progressive liver disease with early onset coagulopathy, high alpha-fetoprotein and ultimately require a liver transplant. Subjects with MYO5 B-related disease can present with isolated cholestasis or cholestasis with intractable diarrhea (MVID). These children are at risk of worsening cholestasis post intestinal transplant (IT) for MVID, hence combined intestinal and liver transplant or IT with biliary diversion is preferred. Immunohistochemistry can differentiate most of the variants of PFIC but confirmation requires genetic analysis.     

替罗非班联合奥扎格雷治疗进展性脑梗死的疗效及对血小板功能的影响

目的：观察替罗非班联合奥扎格雷治疗进展性脑梗死（PIS）的疗效及对血小板功能的影响。方法：将2017年1~12月我院治疗的114例PIS患者作为研究对象,应用随机数表法分为两组,各57例。观察组接受替罗非班、奥扎格雷治疗,对照组接受奥扎格雷治疗。观察两组临床疗效、治疗前后神经功能及血小板功能变化情况等。结果：较对照组相比,观察组总有效率（92.98%）相对较高,差异有统计学意义（P＜0.05）;治疗前按照美国国立卫生研究院卒中量表(NIHSS)评分、P选择素(P-selectin)、血小板聚集率对比,差异无统计学意义（P＞0.05）;治疗后较对照组相比,观察组NIHSS评分（6.22±1.17）分、P-selectin（10.19±2.31）μg·L-1、血小板聚集率（27.98±3.26）%相对较低,差异有统计学意义（P＜0.05）。结论：替罗非班联合奥扎格雷是PIS治疗中较为安全且有效的用药方案,利于促进患者神经功能恢复,改善血小板功能。     

处理后前向运动精子总数对宫腔内人工授精妊娠率的影响

目的:探讨精液处理后前向运动精子总数(post-wash total mobile sperm count,PTMC)对单纯以少、弱精子症为病因引起不孕不育症患者的夫精宫腔内人工授精(intrauterine insemination,IUI)妊娠率的影响。方法:分析2015年3月至2016年3月单纯以少、弱精子症为适应症接受IUI治疗的125个周期的临床资料,按处理后前向运动精子数进行分组,A组19个周期:10×10~6、B组71个周期:10×10~6~20×10~6、C组35个周期:20×10~6,比较各组临床妊娠率。结果:周期总临床妊娠率15.20%,A组周期妊娠率10.53%,B组周期妊娠率16.90%,C组周期妊娠率14.29%,各组妊娠率比较差异无统计学意义(P0.05)。结论:(1)由少、弱精子症引起不育的患者行IUI治疗,即使PTMC10×10~6也能获得一定的妊娠率。(2)精液处理后前向运动精子数对IUI的妊娠率有一定影响,但妊娠率并非一定随着PTMC的增多而提高。     

矿泉对人体某些生理作用的研究进展

目的探讨矿泉对人体的生理机能影响。方法汇集国内外近年来关于矿泉对人体生理作用的研究进行分析归纳。结果矿泉对人体各部位、各系统均有影响。结论开发利用矿泉这一自然疗养因子，在疗养、康复及医疗方面具有良好的发展前景。     

Antibody Therapies for Progressive Multiple Sclerosis and for Promoting Repair

Progressive multiple sclerosis (PMS) is clinically distinct from relapsing–remitting MS (RRMS). In PMS, clinical disability progression occurs independently of relapse activity. Furthermore, there is increasing evidence that the pathological mechanisms of PMS and RRMS are different. Current therapeutic options for the treatment of PMS remain inadequate, although ocrelizumab, a B-cell-depleting antibody, is now available as the first approved therapeutic option for primary progressive MS. Recent advances in understanding the pathophysiology of PMS provide hope for new innovative therapeutic options: these include antibody therapies with anti-inflammatory, neuroprotective, and/or remyelination-fostering effects. In this review, we summarize the relevant trial data relating to antibody therapy and consider future antibody options for treating PMS.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-022-01214-x.     

一个进行性肌营养不良症家系的研究

目的寻找由DNA损伤(如突变)引起的人类表型缺陷,为人类遗传资源的收集与保藏以及人类基因结构与功能的研究打下基础。方法通过实地调查得到表型缺陷家系,然后进行系谱分析。结果得到一进行性肌营养不良家系,4代41位成员中有12例患者。结论进行性肌营养不良是由DNA损伤引起的人类表型缺陷;该病症符合常染色体显性遗传;该病的发生具有一定的外显率和表现度。     

Auditory development in progressive motor neuronopathy mouse mutants

The present study was performed to elucidate the hearing development in the progressive motor neuronopathy (pmn) mouse mutant. This mouse has been used as a model for human motoneuron disease. A missense mutation in the tubulin-specific chaperon E (Tbce) gene on mouse chromosome 13 was localized as the underlying genetic defect. The protein encoded by the Tbce gene is essential for the formation of primary tubulin complexes. Studies on motoneurons show disorganization in microtubules and disturbed axonal transport, followed by retrograde degeneration of the motoneurons. A similar pathomechanism is also possible for hearing disorders where disrupted microtubules could cause functional deficits in spiral ganglion neurons or in cochlear hair cells. Click auditory brainstem response (ABR) audiometry in homozygous pmn mutants showed a normal onset of hearing, but an increasing hearing threshold from postnatal day 26 (P26) on to death, compared to heterozygous mutants and wild-type mice. Histological sections of the cochlea at different ages showed a regular morphology. Additionally, spiral ganglion explants from mutant and wild-type mice were cultured. The neurite length from pmn mutants was shorter than in wild-type mice, and the neurite number/explant was significantly decreased in pmn mutants. We show that the pmn mouse mutant is a model for a progressive rapid hearing loss from P26 on, after initially normal hearing development. Heterozygous mice are not affected by this defect. With the knowledge of the well-known pathomechanism of this defect in motoneurons, a dysfunction of cellular mechanisms regulating tubulin assembling suggests that tubulin assembling plays an essential role in hearing function and maintenance.     

Novel mutation in potassium channel related gene KCTD7 and progressive myoclonic epilepsy

Progressive myoclonic epilepsy (PME) is a heterogeneous group of epilepsies characterized by myoclonus, seizures and progressive neurological symptoms. The index patient was a 6-year old boy showing early-onset therapy resistant PME and severe developmental delay. Genome-wide linkage analysis identified several candidate regions. The potassium channel tetramerization domain containing 7 gene (KCTD7) in the 7q11.21 linkage region emerged as a suitable candidate. Sequence analysis revealed a novel homozygous missense mutation (p.R94W) in a highly conserved segment of exon 2. This is the second family with PME caused by KCTD7 mutations, hence KCTD7 mutations might be a recurrent cause of PME.