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).     

Outcomes of Early Decompressive Craniectomy Versus Conventional Medical Management After Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis

This meta-analysis examined whether early decompressive craniectomy (DC) can improve control of intracranial pressure (ICP) and mortality in patients with traumatic brain injury (TBI).Medline, Cochrane, EMBASE, and Google Scholar databases were searched until May 14, 2015, using the following terms: traumatic brain injury, refractory intracranial hypertension, high intracranial pressure, craniectomy, standard care, and medical management. Randomized controlled trials in which patients with TBI received DC and non-DC medical treatments were included.Of the 84 articles identified, 8 studies were selected for review, with 3 randomized controlled trials s having a total of 256 patients (123 DCs, 133 non-DCs) included in the meta-analysis. Patients receiving DC had a significantly greater reduction of ICP and shorter hospital stay. They also seemed to have lower odds of death than patients receiving only medical management, but the P value did not reach significance (pooled odds ratio 0.531, 95% confidence interval 0.209–1.350, Z = 1.95, P = 0.183) with respect to the effect on overall mortality; a separate analysis of 3 retrospective studies yielded a similar result.Whereas DC might effectively reduce ICP and shorten hospital stay in patients with TBI, its effect in decreasing mortality has not reached statistical significance.     

Exploration of D022-Type Al3TM(TM = Sc,Ti, V,Zr, Nb,Hf, Ta): Elastic Anisotropy,Electronic Structures,Work Function and Experimental Design

The structural properties, elastic anisotropy, electronic structures and work function of D0₂₂-type Al₃TM (TM = Sc, Ti, V, Y, Zr, Nb, La, Hf, Ta) are studied using the first-principles calculations. The results indicate that the obtained formation enthalpy and cohesive energy of these compounds are in accordance with the other calculated values. It is found that the Al₃Zr is the most thermodynamic stable compound. The mechanical property indexes, such as elastic constants, bulk modulus, shear modulus, Young’s modulus, Poisson’s ratio, and Vickers hardness are systematically explored. Moreover, the calculated universal anisotropic index, percent anisotropy and shear anisotropic factors of D0₂₂-type Al₃TM are analyzed carefully. It demonstrates that the shear modulus anisotropy of Al₃La is the strongest, while that of Al₃Ta is the weakest. In particular, the density of states at Fermi level is not zero, suggesting that these phases have metal properties and electrical conductivity. More importantly, the mechanisms of correlation between hardness and Young’s modulus are further explained by the work function. Finally, the experimental design proves that D0₂₂-Al₃Ta has an excellent strengthening effect.     

中华传统文化视角下疾病终末期患者尊严模型解析

目的:解析加拿大Chochinov疾病终末期患者尊严模型在中华文化情境下的适用性,并基于此对模型进行调适。方法:采用内容分析法,按照选定分析范围、抽取样本、确定分析单位和分析框架、资料分析四步完成。首先检索中、英文数据库中以中华文化背景下临终尊严为主题的文献,然后以尊严模型为框架对文献内容进行编码、归纳和分析。结果:尊严模型包含的多数主题符合我国临终患者的认知,如身体功能、医疗不确定性、死亡焦虑、隐私界限、照护要旨、他人负担、后事担忧等。但也出现了矛盾的主题,如忍受痛苦、自主性等,以及新的主题,包括家庭支持、病耻感和财务担忧。结论:加拿大版疾病终末期患者尊严模型并不完全符合中国文化,调适后的尊严模型更具我国文化特色,但仍需实证研究对模型进行验证。     

肛肠疾病手术前后肛管直肠压力测定的应用

目的:探讨肛肠疾病手术前后肛管直肠压力测定的应用。方法:将2018年5月-2019年5月在上海市松江区方塔中医医院及上海中医药大学附属曙光医院肛肠科行手术治疗的826例肛肠疾病患者作为研究对象,其中,选择性痔上黏膜吻合术246例、单纯外剥内扎术115例、外剥内扎结合内痔套扎术(Automatic Ligation of Hemorrhoids,RPH)153例、低位肛瘘切除术177例、高位肛瘘切开挂线术135例,分别于术前及术后1个月测定肛管直肠压力。结果:选择性痔上黏膜吻合术后直肠静息压、肛管静息压明显低于术前,肛管舒张压高于术前(P<0.05),但肛管最大收缩压与术前相比无明显差异(P>0.05);单纯外剥内扎术术后直肠静息压、肛管静息压明显低于术前,肛管舒张压、肛管最大收缩压明显高于术前(P<0.05);外剥内扎结合内痔套扎术术后直肠静息压、肛管静息压明显低于术前,肛管舒张压、肛管最大收缩压明显高于术前(P<0.05);低位肛瘘切除术术后直肠静息压、肛管静息压、肛管舒张压均高于术前(P<0.05),而肛管最大收缩压与术前相比无明显差异(P>0.05);高位肛瘘切开挂线术术后直肠静息压高于术前,肛管静息压、肛管舒张压低于术前(P<0.05),而与肛管最大收缩压术前相比无明显差异(P>0.05)。结论:肛肠疾病手术前后肛管直肠压力测定的应用效果显著,能准确判断手术效果及患者恢复情况,为医师的进一步诊治奠定了良好基础。     

营养风险与腹膜后肿瘤患者住院时间的相关性研究

目的 探讨营养风险与腹膜后肿瘤患者住院时间的相关性。方法 采用回顾性研究，选取2012年1月至2018年12月四川大学华西医院血管外科新入院腹膜后肿瘤患者60例，采用营养风险筛查表评估患者营养风险，收集患者体质指数、围术期血红蛋白和白蛋白水平、住院天数、术后恶心呕吐发生情况、术后排气、排便时间和首次进食时间。采用单因素分析比较不同患者住院时间，采用多重线性逐步回归分析患者住院时间的影响因素。结果 纳入的60例腹膜后肿瘤患者中，40例患者（66.7%）术前存在营养风险，52例患者（86.7%）术后存在营养风险；单因素分析显示，患者术前、术后营养风险 （术前P<0.001，术后P=0.043）、术前白蛋白 （P=0.019）、术后血红蛋白 （P=0.019）、术后白蛋白（P=0.025） 水平以及术后恶心呕吐 （P=0.001） 均会影响患者的住院时间；患者住院时间与围术期营养风险筛查工具评分、术后首次进食时间、术后排气时间和排便时间具有相关性，且相关性强（r=0.759~0.770； P<0.01）；多因素分析显示术前营养风险是腹膜后肿瘤患者住院时间的重要预测因素（β=0.399）。结论 术前营养风险是腹膜后肿瘤患者住院时间的预测因子。     

VEGF在膀胱移行细胞癌中的表达研究

目的研究血管内皮生长因子（VEGF）在膀胱移行细胞癌（TCC）中的表达。方法应用免疫组织化学染色方法观察62例TCC标本VEGF的表达情况。结果TCC组中VEGF的阳性表达率为56．5％（35，62），而8例正常膀胱粘膜组织VEGF表达均为阴性，两组比较差异有高度显著性p〈0．01（x^2=9．032）；VEGF表达与膀胱肿瘤病理分级、临床分期、复发密切相关。结论VEGF的异常表达在TCC的发生、发展过两组比较差异有程中起重要作用；该指标的检测有助于预后判断。