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。     

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.     

热疗对肿瘤免疫微环境中免疫细胞及免疫相关细胞因子的影响

随着对肿瘤热疗和肿瘤免疫微环境(TIME)的深入研究,近年来热疗对TIME的作用越来越受到学者们的重视。本文就目前国内外研究进展,对热疗与TIME中几类主要免疫细胞和免疫相关细胞因子的影响及作用机制作一综述。全面而透彻的了解热疗对TIME的调控作用,有助于为肿瘤治疗提供新的思路和方法。     

Characterization of membrane occupation and recognition nexus repeat containing 3, meiosis expressed gene 1 binding partner,in mouse male germ cells

Mammalian spermatogenesis is a well-organized process of cell development and differentiation. Meiosis expressed gene 1 (MEIG1) plays an essential role in the regulation of spermiogenesis. To explore potential mechanisms of MEIG1''s action, a yeast two-hybrid screen was conducted, and several potential binding partners were identified; one of them was membrane occupation and recognition nexus repeat containing 3 (MORN3). MORN3 mRNA is only abundant in mouse testis. In the testis, Morn3 mRNA is highly expressed in the spermiogenesis stage. Specific anti-MORN3 polyclonal antibody was generated against N-terminus of the full-length MORN3 protein, and MORN3 expression and localization was examined in vitro and in vivo. In transfected Chinese hamster ovary cells, the antibody specifically crossed-reacted the full-length MORN3 protein, and immunofluorescence staining revealed that MORN3 was localized throughout the cytoplasm. Among multiple mouse tissues, about 25 kDa protein, was identified only in the testis. The protein was highly expressed after day 20 of birth. Immunofluorescence staining on mixed testicular cells isolated from adult wild-type mice demonstrated that MORN3 was expressed in the acrosome in germ cells throughout spermiogenesis. The protein was also present in the manchette of elongating spermatids. The total MORN3 expression and acrosome localization were not changed in the Meig 1-deficient mice. However, its expression in manchette was dramatically reduced in the mutant mice. Our studies suggest that MORN3 is another regulator for spermatogenesis, probably together with MEIG1.