中医药治疗糖尿病周围神经病变的研究进展

糖尿病渐以年轻化的趋势呈现,糖尿病周围神经病变(DPN)是糖尿病最常见的慢性并发症之一,因其高致残率严重影响病患的生活品质。本文简单阐述糖尿病周围神经病变的病因,并就中医药的角度对该病的治疗概况进行综述,以期为临床诊治提供新见解和新研究策略。     

Diabetic macular ischaemia- a new therapeutic target?

Diabetic macular ischaemia (DMI) is traditionally defined and graded based on the angiographic evidence of an enlarged and irregular foveal avascular zone. However, these anatomical changes are not surrogate markers for visual impairment. We postulate that there are vascular phenotypes of DMI based on the relative perfusion deficits of various retinal capillary plexuses and choriocapillaris. This review highlights several mechanistic pathways, including the role of hypoxia and the complex relation between neurons, glia, and microvasculature. The current animal models are reviewed, with shortcomings noted. Therefore, utilising the advancing technology of optical coherence tomography angiography (OCTA) to identify the reversible DMI phenotypes may be the key to successful therapeutic interventions for DMI. However, there is a need to standardise the nomenclature of OCTA perfusion status. Visual acuity is not an ideal endpoint for DMI clinical trials. New trial endpoints that represent disease progression need to be developed before irreversible vision loss in patients with DMI. Natural history studies are required to determine the course of each vascular and neuronal parameter to define the DMI phenotypes. These DMI phenotypes may also partly explain the development and recurrence of diabetic macular oedema. It is also currently unclear where and how DMI fits into the diabetic retinopathy severity scales, further highlighting the need to better define the progression of diabetic retinopathy and DMI based on both multimodal imaging and visual function. Finally, we discuss a complete set of proposed therapeutic pathways for DMI, including cell-based therapies that may provide restorative potential.     

Complete recovery of filler-induced visual loss following subcutaneous hyaluronidase injection

The rise in popularity of hyaluronic acid (HA) dermal filler injection has caused an exceptional increase in the number of cases of reported irreversible blindness. Here, we reported a case of ischemic optic neuropathy and ophthalmoplegia following subcutaneous HA filler injection with complete visual recovery. A 31-year-old Chinese woman presented with sudden onset of right monocular visual impairment associated with diplopia. Patient had received a hyaluronic acid-containing ?ller injection for nasal dorsum augmentation twelve hours prior to presentation. Visual acuity of the right eye was counting finger. A right relative afferent pupillary defect was demonstrated with ophthalmoplegia. Humphrey visual field test disclosed a right inferior altitudinal field defect with impairment of colour vision. Computed tomography of the orbit revealed mild enlargement of the right medial and inferior recti muscles. Our patient showed a tremendous improvement of vision after a subcutaneous hyaluronidase injection with complete visual recovery within 2 weeks.     

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.     

The neurobiology of chronic pain states

Plasticity enables alterations in transmission in nociceptive systems. It is this plasticity in the nervous system that can alter the linear relation between noxious stimuli and the perception of pain and is important in the switch from acute to chronic pain. In this way, a number of CNS mechanisms can alter neuronal activity, leading to abnormal ongoing and stimulus-evoked pains due to peripheral and central changes. Peripheral nerves can become sensitized, spinal cord neurons can be rendered hyperexcitable and ascending projections to higher centres can further trigger changes in descending controls from the midbrain and brainstem. Together, these changes, all of which appear to involve reversible physiological and pharmacological plasticity, can alter the relationship between an applied stimulus and the perceived response and so lead to persistent pain states.     

重灸中脘穴对脾胃虚寒型糖尿病胃轻瘫患者胃肠激素、胃动力学的影响

目的观察重灸中脘穴对脾胃虚寒型2型糖尿病胃轻瘫患者胃肠激素、胃动力学的影响。方法选取符合纳入标准的88例脾胃虚寒型糖尿病胃轻瘫患者,按随机数字表法分为治疗组和对照组,每组44例。对照组采用常规药物治疗,治疗组采用重灸中脘穴治疗。疗程结束后记录并对比分析两组临床疗效、胃肠激素[胃泌素(GAS)、胃动素(MTL)]、胃动力学(胃收缩频率、胃排空时间、胃排空率)、主要临床症状评分等变化。结果治疗组临床疗效明显优于对照组,差异具有统计学意义(P<0.05);两组治疗后GAS、MTL均明显优于治疗前(P<0.05),且治疗组明显优于对照组(P<0.05);两组治疗后胃收缩频率、胃排空时间、胃排空率均明显优于治疗前(P<0.05),且治疗组明显优于对照组(P<0.05);两组治疗后主要临床症状评分均明显优于治疗前(P<0.05),且治疗组明显优于对照组(P<0.05)。结论在常规药物治疗基础上重灸中脘穴治疗脾胃虚寒型2型糖尿病胃轻瘫,可调节胃肠激素,改善胃肠动力,促进胃肠功能恢复。     

抗PD-(L)1、抗CTLA-4免疫治疗标志物研究进展

免疫检查点抑制剂已经改变了包括肺癌、黑色素瘤等许多肿瘤的治疗情况，并且在一些难治性肿瘤中表现出持久的应答率，然而在部分接受治疗的患者中表现出无反应及严重免疫相关副作用。为了优化免疫疗法的使用，可能需要多种临床应答的预测性标志物。本研究回顾了几种潜在有效生物标志物的可用数据，通过免疫组化检测肿瘤细胞和免疫细胞中PD-L1的表达，提示其是一种临床疗效的良好预测标志物;且PD-L1表达阴性者经免疫治疗后仍可获益。PD-L1表达在肿瘤内是动态和异质性的:在原发性灶和转移灶之间或在穿刺标本和大体标本之间表达不一致。肿瘤突变负荷与新抗原的高比率可获得持久获益。外周血标志物也可作为潜在标志物，增加的绝对淋巴细胞计数（ALC）与疾病控制和生存显著相关。在这篇综述中，我们旨在讨论抗PD-（L）1与抗CTLA-4 免疫治疗相关标志物研究现状，为临床运用提供指导，以便能够准确筛选出从这些治疗中获益更多的患者。     

激光联合复方血栓通胶囊治疗糖尿病视网膜病变合并黄斑水肿的疗效观察

目的:分析糖尿病视网膜病变合并黄斑水肿联合采用激光与复方血栓通胶囊治疗的临床疗效。方法:选取我院2017年1月—2019年1月收治的200例糖尿病视网膜病变合并黄斑水肿患者为研究对象,随机分为两组。对照组单独行激光治疗,观察组于对照组基础上联合复方血栓通胶囊治疗,对比两组临床疗效、治疗前后IL-6(白介素-6)、VEGF(血管内皮生长因子)、NOS(血清一氧化氮合成酶)水平变化情况。结果:对照组总有效率(68.00%,68/100)较观察组总有效率(98.00%,98/100)更高(P<0.05);与对照组对比,观察组治疗后NOS水平更高,IL-6、VEGF水平更低(P<0.05)。结论:糖尿病视网膜病变合并黄斑水肿联合采用激光与复方血栓通胶囊治疗的临床疗效显著,值得推广。