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。     

A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model

Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.     

中药穴位敷贴联合中药汤剂治疗糖尿病周围神经病变临床观察

目的探究糖尿病周围神经病变患者开展中药穴位敷贴联合中药汤剂治疗的效果。方法研究时限为2017年8月—2018年11月,研究对象为此期间收治的糖尿病周围神经病变患者42例,将其随机分为常规组(21例)、中药组(21例),分别开展常规治疗、中药穴位敷贴+中药汤剂治疗,比较治疗结果。结果2组患者治疗前中医证候积分、TCSS(多伦多临床评分)相近(P>0.05),治疗后中药组患者以上评分均较常规组具鲜明优势(P<0.05);常规组患者不良反应发生率为14.3%,与中药组0.0%相比,未见鲜明差异(P>0.05)。结论予糖尿病周围神经病变患者开展中药穴位敷贴联合中药汤剂治疗,效果安全有效。     

MBP对PBMC产生IFN-γ和NO的影响

目的探讨T细胞非特异性活化在CNS脱髓鞘性疾病中的作用。方法分离实验性自身免疫性脑脊髓炎(EAE)易感性BALB/c小鼠外周血单个核细胞(PBMC),采用体外细胞培养方法在体外与碱性髓鞘蛋白(MBP)共培养,测定培养上清液中IFN-γ、NO水平。结果经MBP刺激的PBMC产生IFN-γ[(43.83±6.06)pg/mL]和NO[(180.76±20.75)μmol/L]明显增加,与对照组产生的IFN-γ[(28.52±2.18)pg/mL]和NO[(95.61±13.09)μmol/L]相比差异有统计学意义(P<0.01)。结论在CNS脱髓鞘性疾病发病过程中,活化的T细胞、单核细胞等分泌致炎细胞因子和其他有害物质增多。     

The difference in blood pressure between upper arm and finger during physical exercise

Summary. A new apparatus which measures the blood pressure in the finger continuously and yet not invasively was tested for its usefulness during exercise. It was compared with upper arm measurements in 23 volunteers during prolonged bicycle ergometry. Simultaneously, a pulse plethysmogram was recorded from another finger of the same arm, whereas in six additional volunteers Doppler measurements were carried out on the radial artery. The results show that finger systolic pressure ceased to rise at about 40% of maximal exercise; the difference with the continuously rising systolic pressure in the upper arm becoming significant at 140 W. At the same time the amplitude of the finger plethysmogram became significantly higher than its initial value, indicating distinct cutaneous vasodilation, whereas the volunteers also became hot and started to perspire. However, the radial artery ‘flow’, deduced from the Doppler measurements, did not change significantly during exercise. It increased sharply and markedly in the cooling down period. Simultaneously with this increase in flow, HR and both systolic blood pressures fell drastically whereas the plethysmography amplitude remained about stable at its raised level. The results fit in with the idea that a compromise is achieved between the need for muscle activity and the need for temperature regulation. It is concluded that the Finapres functions well during exercise, but that the systolic pressure in the finger is not representative for its more central counterpart during cutaneous vasodilation. It is argued that opening up of AVAs may contribute to this pressure effect.     

应用射频技术阻断神经纤维的研究

目的　探讨应用射频技术行选择性脊神经后根切断术和验证其阻断神经纤维的可行性。方法　将 4 5只大鼠随机分成 3组 ,以实验确定的射频技术、苯酚注射、切断 3种方法阻断其坐骨神经 ,对阻断前和阻断后不同时间内坐骨神经功能进行评价 ,评价方法采用坐骨神经功能指数和神经组织形态学的轴突通过率。结果　射频组、切断组 2组大鼠的坐骨神经功能指数、轴突通过率差异均无显著性 (P >0 .0 5 ) ,而苯酚注射组的上述指标与前述 2组差异均有显著性 (P <0 .0 5 )。结论　直视下应用射频阻断神经 ,可以取得与切断神经相同的效果     

自体大隐静脉移植治疗周围血管损伤22例分析

目的：探讨周围血管损伤自全大隐静脉移植治疗的方法。适应证和治疗效果。方法：回顾性分析22例周围血管损伤自体大隐静脉移植治疗的临床资料，并阐述了术中注意事项，提出最佳手术时机及预后情况。结果：22例均采用自体大隐静脉移植，痊愈19例（86.4%)。截肢3例（13.6%），22例患者无死亡，随访2-9年，20例肢体功能恢复满意，2例移植段狭窄，但肢体功能良好。结论：自体大隐静脉移植是治疗周围血管损伤行之有效的方法之一。血管吻合的时间应在24h以内，最佳为8h以内。