补中益气汤对于肝再生线粒体能量代谢的研究概况＊

肝再生的机制非常复杂，线粒体功能障碍所引起的能量供给不足是影响因素之一，但其机理亟待研究。严重肝损害时肝细胞ATP供应减少、线粒体能量代谢异常，导致肝再生受到抑制。补中益气汤为李东垣所创，其具补中益气、升阳举陷之功，有实验证实补中益气汤具有保护线粒体功能、增加线粒体能量代谢的作用，从而促进肝再生。本文综述补中益气汤总方与其中各类中药对线粒体能量代谢的保护作用，从而为促进肝再生提供新的治疗手段并对改善病人预后有重要意义。     

红花化瘀汤熏洗治疗膝关节镜术后康复效果及对患者疼痛和膝关节功能的影响

目的:探讨红花化瘀汤熏洗在膝关节镜术后康复中的临床效果及对患者疼痛和膝关节功能的影响。方法:选择膝关节镜手术患者104例为研究对象,随机数字表分为对照组和观察组各52例。对照组术后给予常规方法治疗,观察组在对照组基础上联合红花化瘀汤熏洗治疗。治疗8周后,比较两组治疗效果、VAS评分、膝关节功能及炎症因子。结果:两组术后2周、4周、6周及8周膝关节肿胀度均小于术前(P<0.05); 但观察组术后以上时间点膝关节肿胀度小于对照组(P<0.05); 且观察组术后以上时间点VAS评分低于对照组(P<0.05); 观察组术后8周疼痛、功能、活动度、畸形、肌力和稳定性评分高于对照组(P<0.05); 观察组治疗后8周NO和IL-1β水平低于对照组(P<0.05),TGF-1β水平高于对照组(P<0.05)。结论:红花化瘀汤熏洗用于膝关节镜术后康复中能改善患者膝关节肿胀程度,减轻患者疼痛,提高患者膝关节功能,可降低炎症因子水平。     

活血利水法在骨伤科疾病中的应用

基于骨伤疾病瘀血内阻的重要病机和现代医家"治血重治水"的学术观点,探索概括了活血利水法在骨伤疾病中的应用现状,结合现代医学的认识,全方位分析了活血利水法的优势和缺点。活血利水法可应用于骨折、筋伤等骨伤科大部分疾病及骨伤科疾病的围手术期,能改善肢体肿胀,促进伤口愈合,便于患者早期功能康复,但目前的临床应用尚缺乏统一的规范和标准,且处方不良反应尚未完全阐明。     

以脾胃为中心的葛根相关配伍对糖尿病心肌病大鼠受损心肌线粒体的改善作用

目的:观察葛根及其配伍对糖尿病心肌病(DCM)大鼠心肌线粒体质量变化的影响,探寻治疗糖尿病心肌病的最优配伍及机制。方法:采用链脲佐菌素腹腔注射进行模型大鼠制备,并将60只成模大鼠随机分为模型组6.5 g/(kg·d)、达美康组16.7 mg/(kg·d)、葛根组1.04 g/(kg·d)、葛芪组2.6 g/(kg·d)、葛参组2.6 g/(kg·d)、葛蒌组4.48g/(kg·d)及葛芪参蒌组7.6 g/(kg·d)各8只,同时选取空白大鼠8只,为对照组6.5 g/(kg·d)。各组依据上述剂量,以相应药物持续灌胃9周后,对比各组心肌线粒体超微结构变化、心肌线粒体膜电位变化及心肌ATP变化情况。结果:电镜显示各药物干预组心肌线粒体超微结构较模型组均有不同程度的改善,其中葛芪参蒌组改善效果最为明显,与空白组无明显差异; 流式细胞仪检测显示:各干预组波峰均在模型组、空白组之间; 其中葛芪参蒌组、葛参组、葛根组波峰位于达美康组右侧; 葛芪组、葛蒌组则位于达美康组左侧; 以葛芪参蒌组波峰与空白组最为接近。心肌ATP浓度检测显示:各中药干预组心肌ATP浓度均较模型组有所提升(P<0.05),其中葛芪参蒌组ATP值较其余各干预组提升最为明显(P<0.05),但仍低于空白组(P>0.05)。结论:葛根相关配伍均能够对心肌线粒体结构、心肌线粒体膜电位进行正向调控,进而使因糖尿病心肌病导致的心肌线粒体受损得以恢复,其中以益气、化瘀、祛痰三法合用的组方原则进行配伍的葛芪参蒌方改善效果最优。可见其治疗机制可能是通过益气、化瘀、祛痰的协同作用,正向调控心肌线粒体质量而达到治疗目的。     

A case of sudden cardiac death due to mitochondrial disease

A 25-year-old, emaciated man without medical treatment was found to have died suddenly at home by his mother. At autopsy, there were no injuries to his body, but significant circulatory insufficiency was observed. Electron microscopy revealed abnormal mitochondria in cells of the cardiac conduction system. The conduction system was filled with mitochondrial size abnormalities and mitochondrial cristae abnormalities. No notable abnormal findings were observed in other organs. Genetic examination of the blood revealed the mitochondrial pathogenetic variant m.3243A>G. Epileptic seizures, diabetic ketoacidosis, and hyperosmolar hyperglycemic state were unlikely to be the cause of sudden death. The cause of death was diagnosed as arrhythmia possibly induced by the failure of the cardiac conduction system due to mitochondrial disease. This is a rare case of sudden death caused by an accumulation of abnormal mitochondria in the cardiac conduction system.     

COX20基因变异线粒体复合物Ⅳ缺乏症相关的遗传性周围神经病4例病例系列报告及文献复习

背景：原发性线粒体病具有高度的临床和遗传异质性，其中周围神经是线粒体病的常见受累器官之一。 目的：总结COX20基因变异相关周围神经病的临床表型及遗传学特征。 设计：病例系列报告。 方法：回顾性收集2018年5月至2020年5月复旦大学附属儿科医院诊治的COX20基因变异相关周围神经病患儿的临床资料，总结其临床表现、基因检测结果及治疗效果，并以“COX20”、“线粒体复合物Ⅳ缺乏症（Complex Ⅳ deficiency）”为关键词检索中英文数据库。检索时间均为从建库至2021年12月。总结已报道COX20基因变异与临床表型的关系。 主要结局指标：临床表型和COX20基因变异位点。 结果：4例患儿纳入分析，男、女各2例，其中3例自幼运动发育落后。4例均在儿童期起病，均以行走不稳为首发症状。肌电图均提示多发性周围神经损害改变，感觉神经轴索受累为主。4例患儿均携带COX20基因复合杂合变异，包括错义变异2个，无义变异和移码变异各1个，其中移码变异c.262delG(p.E88Kfs*35)尚未见报道。文献复习目前共报道COX基因变异18个家系22例患儿（包括本文病例）,起病中位年龄为5（1.0~17）岁，22例均以行走困难或步态不稳起病，11例（50.0%）有精神运动发育迟滞，病程中14例(63.6%)出现构音障碍，14例(63.6%)出现肌力下降和/或足部畸形，8例（36.4%）出现共济失调，6例(27.3%)出现肌张力障碍，5例（22.7%）存在认知倒退等。21例患儿行神经传导及肌电图检查，19例(90.5%)提示多发性周围神经病变。头颅（18例）及脊髓（10例）MR检查提示，脊髓萎缩4例（40%），小脑萎缩4例（22.2%）。9例患儿已无法独立行走，丧失独立行走能力中位年龄为10（7~21）岁。目前共报道9个变异位点，4种变异类型，其中错义变异5个，剪切变异2个，无义变异和移码变异各1个。 结论：COX20基因变异患者多早期起病，以周围神经系统病变为主要表现，可合并构音障碍、共济失调、肌张力障碍、认知倒退等，病情逐渐进展，致残率高。COX20基因变异类型以错义变异最常见。     

Photon versus proton neurotoxicity: Impact on mitochondrial function and 8-OHdG base-excision repair mechanism in human astrocytes

This study assesses and compares the neurotoxic effects of proton and photon radiation on mitochondrial function and DNA repair capabilities of human astrocytes. Human astrocytes received either proton (0.5 Gy and 3 Gy), photon (0.5 Gy and 3 Gy), or sham-radiation treatment. The mRNA expression level of the DNA repair protein OGG1 was determined via RT-qPCR. The levels of 8-OHdG in the cell media were measured via ELISA. Real-time kinetic analysis of extracellular oxygen consumption rates was performed to assess mitochondrial function. Radiation-induced changes in mitochondrial mass and oxidative activity were assessed using fluorescent imaging with MitoTracker™ Green FM and MitoTracker™ Orange CM-H₂TMRos dyes respectively. PCR was used to quantify the alteration in the mitochondrial DNA content, measured as the mitochondrial to nuclear DNA ratio. A significant increase in mitochondrial mass and levels of reactive oxygen species was observed after radiation treatment. Additionally, real-time PCR analysis indicated a significant depletion of mitochondrial DNA content in the irradiated cells when compared to the control. This was accompanied by a decreased gene expression of the DNA base-excision repair protein OGG1 and reduced clearance of 8-OHdG adducts from the genome. Photon radiation treatment was associated with a more detrimental cellular impact when compared to the same dose of proton radiation. These results are indicative of a radiation-induced dose-dependent decrease in mitochondrial function, an increase in senescence and astrogliosis, and impairment of the DNA repair capabilities in healthy glial cells. Photon irradiation was associated with a more significant disruption in mitochondrial function and base-excision repair mechanisms in vitro in comparison to proton treatment.     

C19orf12 mutation causing mitochondrial membrane-protein Associated Neurodegeneration masquerading as spastic paraplegia

Mitochondrial Membrane-protein Associated Neurodegeneration (MPAN) is a rare disease, caused by C19orf12 mutations and up to 29 different mutations have been described. We report a young woman presented with spastic paraparesis due to C19orf12 gene. MPAN presenting like Hereditary spastic paraplegia-43 is rare and the genetic mutation had been described only once in the literature.     

急性脑膨出预防模式在幕上重型颅脑外伤治疗中的应用及脑膨出危险因素分析

目的探讨急性脑膨出预防模式在幕上重型颅脑外伤（sTBI）大骨瓣减压术中的应用及脑膨出危险因素。 方法选取郴州市第一人民医院神经外科自2016年5月至2018年5月收治的行大骨瓣减压术治疗幕上sTBI的患者130例，根据随机数字表法分成对照组（65例）、观察组（65例）。对照组仅进行常规术前准备，观察组采用急性脑膨出预防模式。比较2组患者急性脑膨出发生率，术后随访6个月，利用GOS评分评价患者的预后。采用单因素与Logistic多因素分析急性脑膨出的危险因素。 结果观察组急性脑膨出发生率（9.23%）低于对照组（23.08%），差异有统计学意义（P<0.05）。观察组预后良好率（75.38%）显著高于对照组（56.92%），差异有统计学意义（P<0.05）。Logistic回归模型提示GCS评分（3~5分）、无急性脑膨出预防模式、迟发型出血、弥漫性脑肿胀、脑挫伤是急性脑膨出的危险因素（P<0.05）。采用急性脑膨出预防模式是预防急性脑膨出的保护性因素（P<0.05）。 结论急性脑膨出预防模式的应用能降低幕上sTBI患者急性脑膨出发生率，可提高预后良好率，且急性脑膨出的发生与GCS评分（3~5分）、无急性脑膨出预防模式、迟发型出血、弥漫性脑肿胀、脑挫伤有关。     

Evaluation of mitogenome sequence concordance,heteroplasmy detection,and haplogrouping in a worldwide lineage study using the Precision ID mtDNA Whole Genome Panel

The emergence of Massively Parallel Sequencing technologies enabled the analysis of full mitochondrial (mt)DNA sequences from forensically relevant samples that have, so far, only been typed in the control region or its hypervariable segments. In this study, we evaluated the performance of a commercially available multiplex-PCR-based assay, the Precision ID mtDNA Whole Genome Panel (Thermo Fisher Scientific), for the amplification and sequencing of the entire mitochondrial genome (mitogenome) from even degraded forensic specimens. For this purpose, more than 500 samples from 24 different populations were selected to cover the vast majority of established superhaplogroups. These are known to harbor different signature sequence motifs corresponding to their phylogenetic background that could have an effect on primer binding and, thus, could limit a broad application of this molecular genetic tool. The selected samples derived from various forensically relevant tissue sources and were DNA extracted using different methods. We evaluated sequence concordance and heteroplasmy detection and compared the findings to conventional Sanger sequencing as well as an orthogonal MPS platform. We discuss advantages and limitations of this approach with respect to forensic genetic workflow and analytical requirements.