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.     

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).     

中国县级及以上医疗机构青光眼诊疗服务 现状分析

目的：统计分析中国县级及以上医疗机构青光眼亚专科建设、诊疗设备配备和服务提供情况，为进 一步推动我国青光眼防治工作提供理论依据。方法：调查研究。2015年对全国提供眼科服务的县级 及以上医疗机构通过网上填报的方式进行普查，采用描述性统计方法，对我国县级及以上医疗机构 青光眼亚专科建设、诊疗设备配备和服务提供情况进行系统整理和统计分析。结果：本次调查覆盖 全国6 341家县级及以上医疗机构，其中设立青光眼亚专科的医疗机构有672家（10.60%）。在青光眼 检查和治疗相关设备中，视力表配置率最高（99.30%），平均每家医疗机构配置3.28台；超声生物显 微镜配置率最低（11.50%），平均每家医疗机构配置0.13台。眼压测量、白内障手术和小梁切开术是 青光眼主要的诊疗服务类型。结论：我国县级及以上医疗机构青光眼亚专科建设亟待加强，诊疗设 备配备不全，诊疗服务能力需要全面提升。     

延安地区泌尿系结石成分分析的研究

目的利用红外光谱法测定延安大学附属医院泌尿外科手术获得的泌尿系结石成分,探讨延安地区泌尿系结石成分与年龄、性别等关系,比较上、下尿路结石成分特点,分析延安地区泌尿系结石发生的流行病学情况,为临床制定有效的个体化治疗及预防措施提供参考依据。方法收集2013年1月至2017年1月在延安大学附属医院泌尿外科治疗1984例尿路结石患者的年龄、性别、结石部位等临床资料,对比分析延安地区泌尿系结石在不同年龄、不同性别、不同解剖部位的分布特点。结果在1984例泌尿系结石的患者中,按每10岁年龄大小分组排序,统计各年龄阶段泌尿系结石发病情况,男性患者有1346例,女性患者有638例,男性年龄(50.23±14.48)岁,女性年龄(47.87±14.51)岁,男、女患者比例约2.11∶1。在66~75岁年龄段,尿路结石发病率性别差异具有统计学意义(P<0.05)。结石成分以混合性结石为主,以混合性结石为主,共1582例,占79.76%。其中1665例(83.92%)为上尿路结石,上、下尿路结石的比例为5.22∶1,其余为肾结石合并膀胱结石。上尿路结石中男性1062例,女性603例,男女比例为1.76∶1;下尿路结石中男性284例,女性35例,男女比例为8.11∶1。青壮年(年龄≤45岁)泌尿系结石患者草酸钙为主结石、感染性结石多见;中老年(年龄>45岁)泌尿系结石者草酸钙为主结石、尿酸类结石多见。感染性结石患者性别差异具有统计学意义(P<0.05)。结论在延安地区男性较女性更容易患泌尿系结石。同时,不同年龄段结石构成成分具有差异。对于年龄≤45岁患者,主要以草酸钙为主结石、感染性结石多见,这与结石整体发病率基本一致;而对于年龄>45岁患者,主要以草酸钙为主结石、尿酸性结石多见。表明对于不同年龄段的结石患者,可以根据上述结果在结石的预防和治疗上综合考量,给予明确而更加合理的治疗。     

2016至2018年某医院真菌血流感染者流行病学特征及耐药性分析

目的分析真菌性血流感染的病原菌分布以及耐药特征，为真菌血流感染的早期合理用药提供理论依据。 方法回顾性分析武汉大学人民医院2016年1月至2018年12月收治的真菌性血流感染者的菌群、科室分布以及耐药性。 结果入组192例真菌血流感染者的血培养样本中共分离192株真菌，其中白色念珠菌检出率为31.77%（61/192），其次热带念珠菌检出率为18.75%（36/192）；重症医学科检出率最高为33.85%（65/192）。所有菌株均对两性霉素B敏感，对其他抗菌药物耐药率分别为5-氟胞嘧啶4.49%（9/192）、伊曲康唑5.73%（11/192）、氟康唑10.94%（21/192）和伏立康唑11.46%（22/192）；除两性霉素B外，2016至2018年真菌对其他抗菌药物的耐药率均逐年上升，其中2018年所分离192株光滑念珠菌对伊曲康唑耐药菌率达46.7%。 结论真菌血流感染病原菌以念珠菌属为主，对目前抗真菌药物具有较高敏感性，但耐药率逐年上升，加强监测血培养病原菌变化及耐药趋势对指导临床用药至关重要。     

生殖专科机构预防新型冠状病毒肺炎感染的措施

新型冠状病毒肺炎(简称新冠肺炎, COVID-19)是近期流行的一种新发传染病,已造成大量人员感染,其中包括医务人员。为预防生殖医学的医院感染,有效降低新冠肺炎在生殖专科机构传播的风险,通过查询相关文献、指南和规范等,并结合生殖医学特点,制定生殖医学有关的临床区、手术室和实验室及相关人员预防新冠肺炎的措施。     

聪耳通窍汤联合耳针对老年神经性耳鸣近远期疗效观察

目的探讨聪耳通窍汤联合耳针治疗老年神经性耳鸣患者的近远期疗效。方法选取耳鼻喉科门诊收治的老年神经性耳鸣患者136例,按随机数字表法分组,对照组68例予以耳针治疗,研究组68例在对照组基础上予以聪耳通窍汤治疗。检测比较两组间近、远期临床疗效、甲襞微循环指标、血液流变学指标以及不良反应发生率。结果治疗后,对照组总有效率为67.64%(46/68)低于研究组总有效率83.82%(57/68),具有统计学意义(P<0.05);随访6个月后,对照组总有效率64.71%(44/68)低于研究组总有效率89.71%(61/68),具有统计学意义(P<0.05);与对照组比较,研究组治疗后甲襞微循环襻周积分、管襻积分、流态积分及总积分较低,治疗后血浆黏度、高切全血黏度、低切全血黏度及红细胞压积较低,差异具有统计学意义(P<0.05);治疗中出现的不良反应为恶心、腹胀、针刺部位疼痛,两组间不良反应发生率无统计学差异(P>0.05)。结论聪耳通窍汤联合耳针治疗老年神经性耳鸣患者的近远期疗效均较好,能明显改善患者微循环状态及血液流变学指标,减轻内耳循环障碍,具有较高安全性。