督脉灸联合香砂养胃丸治疗脾虚泄泻的临床观察

目的观察督脉灸联合香砂养胃丸治疗脾虚泄泻的临床疗效。方法将2018年3月—2019年3月在东营市垦利县人民医院确诊为脾虚泄泻的90例患者,按照随机数字表法分为对照组和观察组各45例。对照组采用香砂养胃丸治疗,观察组采用香砂养胃丸联合督脉灸治疗。两组治疗1个疗程后观察并比较疗效以及治疗前后各项中医证候积分变化情况。结果治疗后观察组总有效率为88.89%,高于对照组的57.87%,观察组各项中医证候积分均降低且低于对照组,两组各项指标差异均具有统计学意义(P<0.05)。结论督脉灸联合香砂养胃丸治疗脾虚泄泻疗效显著,能够有效改善患者临床症状。     

颈椎后路单开门微型钢板内固定术治疗颈椎管狭窄症

目的:探讨颈椎后路单开门微型钢板内固定术治疗颈椎管狭窄症的临床疗效和安全性。方法:2017年3月至2019年3月收治25例颈椎管狭窄症患者。男15例,女10例。年龄33~68岁,中位数45岁。C3~C5狭窄16例,C3~C6狭窄9例。发育型狭窄18例,退行性狭窄7例。病程1~7年,中位数4年。均采用颈椎后路单开门微型钢板内固定术治疗。测定患者的颈椎曲度和活动度,采用视觉模拟量表(visual analogue scale,VAS)和Oswestry功能障碍指数(Oswestry disability index,ODI)量表评价颈肩部疼痛情况,采用日本骨科学会(Japanese Orthopedic Association,JOA)脊髓型颈椎病评分量表(17分法)评价颈髓功能,采用Odom评级标准评价整体疗效,记录并发症发生情况。结果:所有患者均随访至术后12个月。与术前相比,术后3个月时患者的颈椎曲度和活动度均增大(5.25°±3.05°,8.02°±3.13°,t=3.169,P=0.003;38.48°±13.60°,56.12°±12.90°,t=4.705,P=0.000),颈肩部疼痛VAS评分和ODI均减小[(7.69±0.53)分,(3.14±0.21)分,t=39.906,P=0.000;(21.75±5.48)分,(10.13±2.12)分,t=9.888,P=0.000]。患者术前及术后3个月、6个月、12个月的JOA评分比较,总体差异有统计学意义[(8.22±1.51)分,(14.75±3.32)分,(16.53±3.52)分,(16.78±3.66)分,F=41.001,P=0.000];术后3个月、6个月、12个月的JOA评分均高于术前(P=0.000;P=0.000;P=0.000)。术后12个月时,按照Odom评级标准评定,优12例、良10例、一般2例、差1例;疗效评定为差的1例患者,经非手术治疗后病情控制。1例患者术后出现背部疼痛,服用非甾体抗炎止痛药后疼痛缓解;均未出现吞咽困难、脊髓损伤、内固定松动等并发症。结论:采用颈椎后路单开门微型钢板内固定术治疗颈椎管狭窄症,能有效改善患者的颈椎曲度和活动度、减轻颈肩部疼痛症状、改善颈髓功能,总体疗效较好,而且具有较高的安全性。     

“龙虎交战”针法针刺八脉交会穴对偏头痛患者头痛天数及血清CGRP表达的影响＊

目的 观察“龙虎交战”针法针刺八脉交会穴对无先兆偏头痛（Migraine without aura，MO）患者头痛天数及外周血降钙素基因相关肽（Calcitonin gene related peptide，CGRP）表达水平的影响。方法 按照头痛程度将90例MO受试者区层随机分为治疗Ⅰ组、治疗Ⅱ组和对照组各30例。治疗Ⅰ组施以“龙虎交战”针法针刺八脉交会穴（外关和足临泣），治疗Ⅱ组施以平补平泻针法针刺八脉交会穴（外关和足临泣），对照组施以平补平泻针法针刺非经非穴点，每次留针30分钟，5次/周，共治疗20次。于治疗前、治疗结束4周后的随访分别记录三组患者头痛天数的变化情况以判定疗效，并采集患者治疗前、治疗结束4周后随访的肘部静脉血用ELISA法检测血清中的CGRP含量的变化。结果 ①各组治疗前患者的头痛天数无显著差异（Ｐ > 0.05），治疗Ⅰ组、治疗Ⅱ组和对照组治疗结束4周后随访的头痛天数较治疗前均显著降低（Ｐ < 0.05）；治疗Ⅰ组头痛天数的降低显著优于治疗Ⅱ组和对照组（Ｐ < 0.001），治疗Ⅱ组头痛天数的降低显著优于对照组（Ｐ < 0.05）；②3组治疗前CGRP的表达无显著差异，治疗Ⅰ组、治疗Ⅱ组治疗结束4周后随访CGRP的表达较治疗前均显著下降（Ｐ < 0.001），对照组治疗结束4周后随访CGRP的表达较治疗前差异无显著性（Ｐ > 0.05）；治疗Ⅰ组CGRP治疗结束4周随访的表达较治疗Ⅱ组和对照组均显著下降（Ｐ < 0.01），治疗Ⅱ组CGRP的表达较对照组显著下降（P < 0.01）。结论 ①八脉交会穴施以“龙虎交战”针法针刺能明显改善MO患者的头痛天数，同时降低MO患者血清CGRP的表达水平，这可能是针刺八脉交会穴治疗MO的机制之一；②非经非穴点的针刺效应无持续性，而八脉交会穴的针刺效应具有持续性；③八脉交会穴可以充分发挥复式针刺手法的治疗效应，提示我们在临床上治疗疾病时不仅要注意腧穴配伍，恰当的针刺手法更是提高临床疗效、事半功倍的关键。     

Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis

Ferroptosis is an iron-dependent novel cell death pathway. Deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition represents the mechanism of action of Deferoxamine on spinal cord injury recovery. A rat model of Deferoxamine at thoracic 10 segment was established using a modified Allen's method. Ninety 8-week-old female Wistar rats were used. Rats in the Deferoxamine group were intraperitoneally injected with 100 mg/kg Deferoxamine 30 minutes before injury. Simultaneously, the Sham and Deferoxamine groups served as controls. Drug administration was conducted for 7 consecutive days. The results were as follows:(1) Electron microscopy revealed shrunken mitochondria in the spinal cord injury group.(2) The Basso, Beattie and Bresnahan locomotor rating score showed that recovery of the hindlimb was remarkably better in the Deferoxamine group than in the spinal cord injury group.(3) The iron concentration was lower in the Deferoxamine group than in the spinal cord injury group after injury.(4) Western blot assay revealed that, compared with the spinal cord injury group, GPX4, xCT, and glutathione expression was markedly increased in the Deferoxamine group.(5) Real-time polymerase chain reaction revealed that, compared with the Deferoxamine group, mRNA levels of ferroptosis-related genes Acyl-CoA synthetase family member 2(ACSF2) and iron-responsive element-binding protein 2(IREB2) were up-regulated in the Deferoxamine group.(6) Deferoxamine increased survival of neurons and inhibited gliosis. These findings confirm that Deferoxamine can repair spinal cord injury by inhibiting ferroptosis. Targeting ferroptosis is therefore a promising therapeutic approach for spinal cord injury.     

HIFα Regulates Developmental Myelination Independent of Autocrine Wnt Signaling

The developing CNS is exposed to physiological hypoxia, under which hypoxia-inducible factor α (HIFα) is stabilized and plays a crucial role in regulating neural development. The cellular and molecular mechanisms of HIFα in developmental myelination remain incompletely understood. A previous concept proposes that HIFα regulates CNS developmental myelination by activating the autocrine Wnt/β-catenin signaling in oligodendrocyte progenitor cells (OPCs). Here, by analyzing a battery of genetic mice of both sexes, we presented in vivo evidence supporting an alternative understanding of oligodendroglial HIFα-regulated developmental myelination. At the cellular level, we found that HIFα was required for developmental myelination by transiently controlling upstream OPC differentiation but not downstream oligodendrocyte maturation and that HIFα dysregulation in OPCs but not oligodendrocytes disturbed normal developmental myelination. We demonstrated that HIFα played a minor, if any, role in regulating canonical Wnt signaling in the oligodendroglial lineage or in the CNS. At the molecular level, blocking autocrine Wnt signaling did not affect HIFα-regulated OPC differentiation and myelination. We further identified HIFα–Sox9 regulatory axis as an underlying molecular mechanism in HIFα-regulated OPC differentiation. Our findings support a concept shift in our mechanistic understanding of HIFα-regulated CNS myelination from the previous Wnt-dependent view to a Wnt-independent one and unveil a previously unappreciated HIFα–Sox9 pathway in regulating OPC differentiation.SIGNIFICANCE STATEMENT Promoting disturbed developmental myelination is a promising option in treating diffuse white matter injury, previously called periventricular leukomalacia, a major form of brain injury affecting premature infants. In the developing CNS, hypoxia-inducible factor α (HIFα) is a key regulator that adapts neural cells to physiological and pathologic hypoxic cues. The role and mechanism of HIFα in oligodendroglial myelination, which is severely disturbed in preterm infants affected with diffuse white matter injury, is incompletely understood. Our findings presented here represent a concept shift in our mechanistic understanding of HIFα-regulated developmental myelination and suggest the potential of intervening with an oligodendroglial HIFα-mediated signaling pathway to mitigate disturbed myelination in premature white matter injury.     

Necroptotic TNFα-Syndecan 4-TNFα Vicious Cycle as a Therapeutic Target for Preventing Temporomandibular Joint Osteoarthritis

Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease for which the underlying mechanism still remains unclear. Compared with apoptosis and autophagy, necroptosis causes greater harm to tissue homeostasis by releasing damage-associated molecular patterns (DAMPs). However, the role of necroptosis and downstream key DAMPs in TMJOA is unknown. Here, rodent models of TMJOA were established by the unilateral anterior crossbite (UAC). Transmission electron microscopy (TEM) and immunohistochemistry of receptor interacting protein kinase 3 (RIPK3)/phosphorylation of mixed lineage kinase domain-like protein (pMLKL) were conducted to evaluate the occurrence of necroptosis in vivo. The therapeutic effects of blocking necroptosis were achieved by intra-articularly injecting RIPK3 or MLKL inhibitors and using RIPK3 or MLKL knockout mice. In vitro necroptosis of condylar chondrocyte was induced by combination of tumor necrosis factor alpha (TNFα), second mitochondria-derived activator of caspases (SMAC) mimetics and carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (z-VAD-fmk). The possible DAMPs released by necroptotic chondrocytes were screened by quantitative proteomics and blocked by specific antibody. Translucent cytosol, swollen organelles, and ruptured cell membranes, features of necroptosis, were frequently manifested in chondrocytes at the early stage of condylar cartilage degeneration in TMJOA, which was accompanied by upregulation of RIPK3/pMLKL. Inhibiting or knocking out RIPK3/MLKL significantly prevented cartilage degeneration. DAMPs released by necroptotic condylar chondrocytes, such as syndecan 4 (SDC4) and heat shock protein 90 (HSP90), were verified. Furthermore, blocking the function of SDC4 significantly attenuated the expression of TNFα in cartilage and synovium, and accordingly increased cartilage thickness and reduced synovial inflammation. Thus, the necroptotic vicious cycle of TNFα-SDC4-TNFα contributes to cartilage degeneration and synovitis, and can serve as a potential therapeutic target for treating TMJOA. © 2022 American Society for Bone and Mineral Research (ASBMR).