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51.
Xue Yao Yan Zhang Jian Hao Hui-Quan Duan Chen-Xi Zhao Chao Sun Bo Li Bao-You Fan Xu Wang Wen-Xiang Li Xuan-Hao Fu Yong Hu Chang Liu Xiao-Hong Kong Shi-Qing Feng 《中国神经再生研究》2019,(3)
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. 相似文献
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Feng He Yuanjun Ma Shi Li Haozhe Ren Qian Liu Xiaohua Chen Hui Miao Tao Ye Qian Lu Zuge Yang Tianle Li Xin Tong Hongxu Yang Mian Zhang Helin Wang Yazhou Wang Shibin Yu 《Journal of bone and mineral research》2022,37(5):1044-1055
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). 相似文献
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Yu Fan Xiaoling Liao Yuesong Pan Kehui Dong Yilong Wang Yongjun Wang 《Journal of stroke and cerebrovascular diseases》2019,28(1):220-226
Background
The intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) therapy is safe and efficient during the treatment of acute ischemic stroke. Nonetheless, the different outcomes among various stroke subgroups have limited data with regard to the safety and efficacy of cryptogenic stroke (CS). The present study compared the safety and efficacy when IVT with rt-PA was used for the treatment of CS and the other stroke subtypes.Methods
This study classified the IVT with rt-PA patients within 4.5 hours after stroke onset, based on the trial of ORG 10172 in acute stroke treatment criteria in terms of diagnostic evaluation. The data were obtained from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China database, a large multicenter prospective registry. A multivariable logistic regression model was employed to compare the differences between the subtypes in symptomatic intracerebral hemorrhage (sICH) within 7 days and studied the mortality and the outcome during 90 days.Results
In total, 1118 patients were recruited; of these, 131 (11.7%) suffered from CS and 987 (88.3%) with the other etiology. In the CS group, patients were younger than those in the other etiology groups (P < .001). Moreover, it had a lower prevalence of previous stroke (P?=?.0117), receiving antiplatelet drug in 24 hours prior to thrombolysis (P?=?.0017), and functional independence (mRS > 1 before stroke, P?=?.003). The CS group had lower blood pressure (systolic blood pressure P?=?.0001; diastolic blood pressure; P?=?.0212) before thrombolysis, atrial fibrillation (P < .001), and diabetes mellitus (P?=?.0005). Transient ischemic attack, hypertension, hyperlipidemia, blood glucose, receiving anticoagulants in 24 hours prior to thrombolysis, and standard dosage of rt-PA were equally distributed in both groups. After the adjustment of confounders between the CS and the other subgroups, no obvious differences were observed in sICH rate and mortality (P > .05) The CS patients exhibited excellent recovery (mRS, 0-1; 63.78%) and functional independence (mRS, 0-2; 74.8%) than the large artery atherosclerosis patients.Conclusions
IVT with rt-PA is a safe and effective method for the treatment of CS patients. 相似文献56.
57.
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。 相似文献
58.
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。 相似文献
59.
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。 相似文献
60.