Mechanical and hypoxia stress can cause chondrocytes apoptosis through over-activation of endoplasmic reticulum stress

ObjectiveTo examine the role of mechanical force and hypoxia on chondrocytes apoptosis and osteoarthritis (OA)-liked pathological change on mandibular cartilage through over-activation of endoplasmic reticulum stress (ERS).MethodsWe used two in vitro models to examine the effect of mechanical force and hypoxia on chondrocytes apoptosis separately. The mandibular condylar chondrocytes were obtained from three-week-old male Sprague–Dawley rats. Flexcell 5000T apparatus was used to produce mechanical forces (12%, 0.5 Hz, 24 h vs 20%, 0.5 Hz, 24 h) on chondrocytes. For hypoxia experiment, the concentration of O₂ was down regulated to 5% or 1%. Cell apoptosis rates were quantified by annexin V and propidium iodide (PI) double staining and FACS analysis. Quantitative real-time PCR and western blot were performed to evaluate the activation of ERS and cellular hypoxia. Then we used a mechanical stress loading rat model to verify the involvement of ERS in OA-liked mandibular cartilage pathological change. Histological changes in mandibular condylar cartilage were assessed via hematoxylin & eosin (HE) staining. Immunohistochemistry of GRP78, GRP94, HIF-1α, and HIF-2α were performed to evaluate activation of the ERS and existence of hypoxia. Apoptotic cells were detected by the TUNEL method.ResultsTunicamycin, 20% mechanical forces and hypoxia (1% O₂) all significantly increased chondrocytes apoptosis rates and expression of ERS markers (GRP78, GRP94 and Caspase 12). However, 12% mechanical forces can only increase the apoptotic sensitivity of chondrocytes. Mechanical stress resulted in OA-liked pathological change on rat mandibular condylar cartilage which included thinning cartilage and bone erosion. The number of apoptotic cells increased. ERS and hypoxia markers expressions were also enhanced. Salubrinal, an ERS inhibitor, can reverse these effects in vitro and in vivo through the down-regulation of ERS markers and hypoxia markers.ConclusionWe confirmed that mechanical stress and local hypoxia both contributed to the chondrocytes apoptosis. Mechanical stress can cause OA-like pathological change in rat mandibular condylar cartilage via ERS activation and hypoxia existed in the meantime. Both mechanical forces and hypoxia can induce ERS and cause chondrocytes apoptosis only if the stimulate was in higher level. Salubrinal can protect chondrocytes from apoptosis, and relieve OA-liked pathological change on mandibular condylar cartilage under mechanical stress stimulation.     

经动脉新辅助化疗治疗局部晚期宫颈癌的临床价值

目的评价经动脉新辅助化疗（neoadjuvant intra—arterial chemotherapy,NAIC）治疗宫颈癌的临床疗效。方法选择2000年2月至2003年2月在本院确诊为局部晚期宫颈癌Ⅰb2～Ⅱb期,并符合经动脉新辅助化疗＋手术治疗适应证的患者86例为研究对象。将其随机分为NAIC组（n=43）和单纯手术组（n=43）（本研究疗程符合南充市中心医院人体试验委员会制定的伦理学标准,得到该委员会批准,且分组征得受试对象的知情同意,并与之签署临床研究知情同意书）。对NAIC组和单纯手术组的手术时间,术中出血量、术后并发症及5年生存率等进行对比分析。结果经动脉新辅助化疗＋手术治疗较单纯手术具有手术时间短、术中出血量少、术后并发症低、术后5年生存率高[（148．0±17．8）min vs．（182．0±20．1）min;（350．0±21．5）mL vs．（480．0±23．6）mL;2．3％ vs ;18．6％;79％vs．58％）]等优点,两组比较,差异有显著意义（P〈0．05）。结论经动脉新辅助化疗＋手术治疗局部晚期宫颈癌,可控制肿瘤微小浸润,减小肿瘤体积,提高手术切除率及患者5年生存率。     

复方利福平胶囊致急性肾衰竭

1例29岁男性患者,因肺结核服用复方利福平胶囊（每粒含利福平600mg,异烟肼600mg）,1粒/次,隔日1次。治疗3个月后症状好转自行停药。1年后患者再次出现咳嗽、盗汗等症状,遂按原治疗剂量自行服用复方利福平胶囊。服药8d后,出现恶心、呕吐,腰痛,颜面及双下肢水肿,少尿、茶色尿。实验室检查：BUN21.2mmol/L,SCr877.8μmol/L,尿蛋白（＋）,尿潜血（＋＋＋）;ECT检查示左肾和右肾GFR值分别为21.11ml/min和20.98ml/min。停用复方利福平胶囊,行血液透析,同时给予对症、支持治疗,25d后症状好转。     

Nucleus pulposus explant culture model

Many of the therapeutic interventions for intervertebral disc degeneration attempt to repopulate the nucleus pulposus (NP) tissue; however, NP cells are heterogeneous and not well characterized. To address this, we have investigated the morphology, extracellular gene and protein expression, and apoptosis changes in NP explants cultured in vitro with or without chondrogenic reagents for different periods. We also compared the susceptibility of the explants to different treatments by comparing: treatment of NP explants with GDF5 protein, transfection of NP explants with GDF5 plasmid, and infection of NP explants with GDF5 adenovirus vector. We found that expression levels of two of the major extracellular proteins found in NP tissue, that is, collagen II and aggrecan, could be maintained in an NP explant culture model with a chondrogenic medium up to 7 days, and were significantly higher than that of fresh NP tissue after 14 days of culture in vitro, whether or not chondrogenic medium was used. In addition, the NP explant responded to treatment with growth factor, and could be infected by virus and transfected by plasmid for further evaluation of growth factor gene therapy. NP explant culture could therefore provide an easy in vitro culture model to characterize NP cells and evaluate potential therapeutic reagents. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 814–819, 2009     

Fatal heat stroke in a child entrapped in a confined space

We report the case of a child succumbing to heatstroke caused by confinement in an icebox. The post mortem examination found cyanosis and hematomas indicating that the child had tried to get out of the container. The temperature of the body was higher than it should have been considering the rigor and delay before post mortem examination. The autopsy showed no significant injury and toxicological tests were negative. A physiological study etablished that death resulted from heatstroke, not a lack of oxygen or CO₂ poisoning. We conclude that heat stroke should be considered as a possible mechanism of death even in the absence of context of environmental hyperthermia. We recommend that in these situations involving confinement, establishing the mechanism of death should be done not only on the basis of a detailed post-mortem examination to rule out other causes of death, but also based on complete physiological investigations.     

胃肠道间质瘤的诊治现状与进展

目的总结胃肠道间质瘤（GIST）的发病机制及流行病学特点,探讨其诊断及治疗并分析其预后。方法复习与GIST的发病机制、流行病学、诊断、治疗及预后方面有关的文献并对其进行综述。结果 GIST为非上皮源性肿瘤,起源于Cajal间叶细胞,是消化道最常见的间叶性肿瘤,约占消化道肿瘤的1%～3%,中位发病年龄为40～60岁,胃为最好发部位。目前认为,GIST的发病机制与原癌基因c-kit或血小板源性生长因子受体α（PDGFRα）基因突变有密切关系,但PDGFRα和c-kit基因突变不会同时出现在同一患者中。GIST的临床表现缺乏特异性,临床诊断主要依靠内镜及影像学技术,最终确诊依靠病理学检查。目前对GIST的治疗以手术与分子靶向药物治疗为主,其预后与肿瘤危险度分级及治疗干预密切相关。结论 GIST是具有恶性潜能的肿瘤,其危险度分级是指导临床治疗及预后评估的重要指标,GIST的预防、诊断、治疗及复发的预防有待进一步研究。     

胃肠道肿瘤患者术后早期肠内营养支持的临床分析

目的：探讨早期肠内营养在胃肠道肿瘤患者的术后治疗中的应用价值。方法：对照组术后早期通过使用静脉置管输入营养液进行肠外营养支持,待患者状况改善后改为肠内营养支持,观察组全程使用鼻置管输入营养液进行肠内营养支持,比较两组患者手术前和治疗后体重等各项生理指标水平和术后恢复情况。结果：经过营养支持,观察组体重、白蛋白和前白蛋白水平均较对照组有明显的提升。观察组肠道蠕动和肛门排气恢复时间均短于对照组,且住院时间明显缩短,差异有统计学意义（P〈0.05）。结论：在术后早期对患者行肠内营养支持可以明显改善患者的营养状况,提高患者免疫力,有效减少并发症的发生,有利于预后。     

Risk factors associated with acute respiratory distress syndrome in COVID-19 patients outside Wuhan: A double-center retrospective cohort study of 197 cases in Hunan,China

BACKGROUNDThere have been few reports on the risk factors for acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19), and there were obvious differences regarding the incidence of ADRS between Wuhan and outside Wuhan in China.AIMTo investigate the risk factors associated with ARDS in COVID-19, and compare the characteristics of ARDS between Wuhan and outside Wuhan in China.METHODSPatients were enrolled from two medical centers in Hunan Province. A total of 197 patients with confirmed COVID-19, who had either been discharged or had died by March 15, 2020, were included in this study. We retrospectively collected the patients’ clinical data, and the factors associated with ARDS were compared by the χ² test, Fisher’s exact test, and Mann-Whitney U test. Significant variables were chosen for the univariate and multivariate logistic regression analyses. In addition, literature in the PubMed database was reviewed, and the characteristics of ARDS, mortality, and biomarkers of COVID-19 severity were compared between Wuhan and outside Wuhan in China.RESULTSCompared with the non-ARDS group, patients in the ARDS group were significantly older, had more coexisting diseases, dyspnea, higher D-dimer, lactate dehydrogenase (LDH), and C-reactive protein. In univariate logistic analysis, risk factors associated with the development of ARDS included older age [odds ratio (OR) = 1.04), coexisting diseases (OR = 3.94), dyspnea (OR = 17.82), dry/moist rales (OR = 9.06), consolidative/mixed opacities (OR = 2.93), lymphocytes (OR = 0.68 for high lymphocytes compared to low lymphocytes), D-dimer (OR = 1.41), albumin (OR = 0.69 for high albumin compared to low albumin), alanine aminotransferase (OR = 1.03), aspartate aminotransferase (OR = 1.02), LDH (OR = 1.02), C-reactive protein (OR = 1.04) and procalcitonin (OR = 17.01). In logistic multivariate analysis, dyspnea (adjusted OR = 27.10), dry/moist rales (adjusted OR = 9.46), and higher LDH (adjusted OR = 1.02) were independent risk factors. The literature review showed that patients in Wuhan had a higher incidence of ARDS, higher mortality rate, and higher levels of biomarkers associated with COVID-19 severity than those outside Wuhan in China.CONCLUSIONDyspnea, dry/moist rales and higher LDH are independent risk factors for ARDS in COVID-19. The incidence of ARDS in Wuhan seems to be overestimated compared with outside Wuhan in China.     

Sox2基因在眼部疾病中的研究进展

Sox2基因是SRY(sex determination region of Y chromosome)相关基因家族中的一员,是维持胚胎干细胞多能性和自我更新特性的关键转录因子之一。Sox2参与多种生物学过程,如调节细胞增殖和凋亡、参与肿瘤的形成和发展等。但关于Sox2基因在眼部疾病中作用研究的综述较少,为此,本文从Sox2基因的表达水平、相关信号通路及临床应用潜能等方面进行综述,以便于读者对Sox2基因在眼部疾病中的作用有更全面的认识和了解,开展更深入的研究。     

重组牛碱性成纤维细胞生长因子与胰岛素联合应用治疗压疮创面：随机对照○

背景：长期卧床可导致压疮,促进压疮创面的愈合,缩短压疮的治愈时间是压疮治疗的关键。 目的：观察胰岛素对重组牛碱性成纤维细胞生长因子治疗压疮创面愈合的影响。 方法：选择2009-01/2010-05四川省南充市中心医院收治的压疮病例34例共45处压疮,采用单盲随机分组原则分为实验组和对照组。TDP-L-1-2特定电磁波理疗后,实验组创面加入重组牛碱性成纤维细胞生长因子外用溶液1~3 mL(轻度1 mL,中度2 mL,重度3 mL)+生理盐水3~5 mL(轻度3 mL,中度4 mL,重度5 mL)+胰岛素;对照组不加胰岛素。记录两组治疗两周显效情况和创面愈合时间,并进行对比分析。 结果与结论：实验组治疗有效率、压疮创面治愈时间明显高于对照组(P < 0.05),但两组患者治疗前血糖浓度差异无显著性意义(P > 0.05)。提示胰岛素的加入可以促进压疮的愈合,而不引起患者血糖浓度的改变。