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).     

基于超声定位的火器贯穿伤标准化动物损伤模型的构建

目的:基于超声定位技术,构建一种模拟真实战场环境下的股动脉火器贯穿伤标准化动物损伤模型。方法:选择体质量指数与人体相当的10只长白猪作为实验对象,采用定制弹道步枪和欧盟制式子弹作为致伤武器,使用自制超声引导定位架作为辅助血管定位装置。采用超声探头定位实验动物左侧股动脉血管位置,利用超声引导定位架和致伤架将实验动物的股动脉血管中心调整至子弹弹道轨迹线上射击致伤。计算自由出血20 s实验动物体外失血量,测量实验动物体表弹道入口、出口处直径和体内弹道深度,并通过解剖观察股动脉受损情况。采用SPSS 26.0软件进行统计学分析。结果:采用自制的超声引导定位架可以构建相对稳定的股动脉火器贯穿伤标准化动物损伤模型,成功率约90%(9/10);实验动物体表弹道入口平均直径为(7.20±1.03)mm,出口平均直径为(93.30±33.06)mm,两者相比具有明显统计学差异(t=-8.16,P=0.000);实验动物体内弹道平均深度为(191.80±25.50)mm;致伤20 s后死亡实验动物和存活实验动物的平均失血量分别为(478.00±267.48)和(111.50±45.32)g,两者相比没有统计学差异(t= -2.75,P=0.070)。结论:采用自制的超声引导定位架构建的股动脉火器贯穿伤标准化动物损伤模型成功率高、重复性好,且实验动物伤情稳定,可以为新型止血材料和止血装置的研制提供可靠的模型依据。     

肺部超声与脉搏指示连续心排血量监测评价急性心力衰竭患者肺水肿程度

目的 对比肺部超声与脉搏指示连续心排血量监测（PiCCO）评价急性心力衰竭肺水肿的价值。方法 对11例急性心力衰竭患者先后行常规超声心动图、肺部超声及PiCCO,共获得26例/次数据,将其分为轻度组[血管外肺水指数（EVLWI）≤ 10 ml/kg,n=12]和重度组（EVLWI>10 ml/kg,n=14）,比较组间血清N末端B型脑钠肽前体（NT-proBNP）值、超声及PiCCO参数的差异。采用Spearman相关性分析各指标与EVLWI的相关性;绘制受试者工作特征（ROC）曲线,计算曲线下面积（AUC）,判断各指标评价肺水肿的效能。结果 轻度组舒张压及左心室射血分数（LVEF）明显高于重度组（P均<0.05）;NT-proBNP、心率、左心室舒张末期内径（LVEDD）、左心室收缩末期内径（LVESD）、肺动脉压（PAP）、下腔静脉直径（IVCD）、E/e''、B线总分、全心舒张末期容积指数（GEDVI）及EVLWI明显低于重度组（P均<0.05）。B线总分与EVLWI呈显著正相关（r=0.955,P<0.001）;其诊断EVLWI>10 ml/kg的AUC为0.95,截断值为15.00时,敏感度为92.90%,特异度为66.70%。结论 肺部超声可较准确地评价急性心力衰竭患者肺水肿程度;B线总分与EVLWI呈显著性相关。     

碘对比剂每秒注入量对64排螺旋CT冠脉成像质量的影响

 目的 探讨碘对比剂每秒注入量对心脏冠脉成像质量的影响。方法 选取2019-09至2020-01解放军总医院第一医学中心做冠脉CTA检查的患者60例,按对比剂每秒注入量不同(4.0 ml/s、5.0 ml/s),分为研究组和对照组,每组30例,由两位高年资医师测量主动脉根部和右冠主干、左前降支、回旋支血管的CT值,采用五分法对图像进行评分,并统计CT值300～450 Hu的比例。结果 对照组主动脉根部和右冠主干、左前降支、回旋支血管CT值均高于研究组,差异有统计学意义(P＜0.05)。研究组主动脉根部和右冠主干、左前降支、回旋支的CT值均介于300~450 Hu(100.0%),而对照组分别为63.3%、66.7%、83.3%及93.3%;研究组与对照组的冠脉图像主观评价得分,差异无统计学意义。结论 对比剂每秒注入量对冠脉CTA图像质量及CT值有影响,4 ml/s每秒注入量时血管CT值略低,但对影像诊断无影响。     

两种3D打印导板在托槽间接粘接中的准确性比较

目的:评估两种3D打印导板在辅助托槽间接粘接时准确性的差异。方法:利用离体牙按照牙弓形态排牙,标记测量点建立实验模型备用。通过数字化扫描仪获取数字化模型,利用计算机软件设计3D打印整段式和单牙位导板。通过制作的间接粘接导板将托槽转移定位到实验模型,测量标记点与托槽特定位点间距离,对转移前后距离的变化进行统计学分析。结果:通过配对t检验分析,整段式和单牙式两种3D打印导板在托槽转移前后位置变化差值分别为（0.21±0.05） mm、（0.22±0.05） mm,两者无统计学差异（P>0.05）。结论:在上述实验条件下,两种3D打印导板在辅助托槽间接粘接过程中准确性无明显差异。     

中美临床执业医师资格考试中关于医学人文考核的比较研究

医师资格考试是大多数国家普遍采用的医师资格认证形式。医学人文的考核在医师资格考试中占有重要地位。以临床类别考试为例,通过文献分析、比较研究的方法,比较分析中美两国执业医师资格考试和医师资格分阶段考试实证研究考试中的医学人文考核,包括考试内容和形式、考试分值及比例。发现两国医学人文考核内容和比例基本相当,但我国现行考试医学人文考核站数较少,考试形式和呈现方式有待进一步改善,下一步应继续探索标准化病人应用于我国医师资格考试的可行性,充分发挥医师资格考试对医学教育的导向作用。     

Clinical characteristics,rates of blindness,and geographic features of PACD in China

ObjectiveTo analyze the rates of blindness with the demographics and clinical characteristics of patients with primary angle-closure disease (PACD) to provide a comprehensive epidemiologic reference in China.MethodsA retrospective analysis was conducted in the Chinese Glaucoma Study Consortium database, which is a national multicenter glaucoma research alliance of 111 hospitals participating between December 21, 2015 and September 9, 2018. The diagnosis of PACD was made by qualified physicians through examination. Comparison of sex, age, family history, subtypes of PACD, and blindness were analyzed.ResultsA total of 5762 glaucoma patients were included, of which 4588 (79.6%) had PACD. Of PACD patients, 72.1% were female with the sex ratio (F/M) of 2.6, and the average age of patients was 63.8±9.3 years with the majority between 60 and 70 years. Additionally, 30% of these patients had low vision in one eye, 8.8% had low vision in both eyes, 1.7% had blindness in one eye, and 0.3% had blindness in both eyes. There were statistical differences with regards to age between male and female patients with PACD, with male patients being older on average. Primary angle-closure glaucoma was more commonly diagnosed in males (60%) compared to females (35.9%), whereas acute primary angle closure (APAC) was more commonly diagnosed in females (54.3%) compared to males (37.7%). The visual acuity in APAC patients was lower and the rate of low vision and blindness was higher than other subtypes.ConclusionPACD was the major type of glaucoma in Chinese hospitals. There were more female patients with PACD, mostly between 60 and 70 years old, with higher rates of APAC in women. APAC resulted in the worst visual outcomes of all PACD subtypes.     

胫骨侧个性化髓外定位技术行人工全膝关节置换术后胫骨假体冠状位力线的评价研究

目的探讨人工全膝关节置换术(total knee arthroplasty,TKA)中应用胫骨侧个性化髓外定位技术截骨后胫骨假体冠状位力线情况。方法回顾分析2020年1月—2021年6月接受初次TKA且符合选择标准的170例(210膝)患者临床资料。其中,77例(96膝)胫骨侧采用传统髓外定位技术(传统定位组);93例(114膝)采用个性化髓外定位技术(个性化定位组),即结合胫骨解剖形态特点,在胫骨平台关节面选择个性化定位点作为髓外近端定位点。两组性别、年龄、身体质量指数、侧别、骨关节炎病程及Kellgren-Lawrence分级等一般资料比较,差异均无统计学意义(P>0.05),具有可比性。测量个性化定位组术前胫骨冠状位近、远端解剖轴形成的侧弓角(tibial bowing angle,TBA)并对胫骨轴线分型,分析个性化定位点位置分布规律。比较两组手术前后髋-膝-踝角(hip-knee-ankle angle,HKA)、胫骨远端外侧角(lateral distal tibial angle,LDTA),术后冠状位胫骨假体角(tibia component angle,TCA)及胫骨假体冠状位力线优良率。结果个性化定位组胫骨轴线分为直线型58膝(50.88%)、内弓型35膝(30.70%)、外弓型21膝(18.42%)。直线型者胫骨个性化定位点多位于外侧髁间棘高点(62.07%),内弓型者多位于内、外侧髁间棘之间区域(51.43%),外弓型者多位于外侧髁间棘外侧坡(57.14%)。两组组内手术前后HKA比较,差异均有统计学意义(P<0.05);手术前后LDTA比较,差异均无统计学意义(P>0.05)。两组间术前LDTA、HKA及手术前后差值比较,差异均无统计学意义(P>0.05);术后TCA比较,差异有统计学意义(P<0.05)。传统定位组术后胫骨平台假体较个性化定位组更倾向于内翻。术后个性化髓外定位组胫骨假体冠状位力线优良率为96.5%(110/114),传统定位组为87.5%(84/96),差异有统计学意义(χ²=7.652,P=0.006)。结论 TKA胫骨侧冠状位截骨时采用个性化髓外定位技术可行,与传统髓外定位技术相比胫骨假体冠状位力线优良率更高。     

Risk-based,response-adapted therapy for early-stage extranodal nasal-type NK/T-cell lymphoma in the modern chemotherapy era: A China Lymphoma Collaborative Group study

We aimed to determine the survival benefits of chemotherapy (CT) added to radiotherapy (RT) in different risk groups of patients with early-stage extranodal nasal-type NK/T-cell lymphoma (ENKTCL), and to investigate the risk of postponing RT based on induction CT responses. A total of 1360 patients who received RT with or without new-regimen CT from 20 institutions were retrospectively reviewed. The patients had received RT alone, RT followed by CT (RT + CT), or CT followed by RT (CT + RT). The patients were stratified into different risk groups using the nomogram-revised risk index (NRI). A comparative study was performed using propensity score-matched (PSM) analysis. Adding new-regimen CT to RT (vs RT alone) significantly improved overall survival (OS, 73.2% vs 60.9%, P < .001) and progression-free survival (PFS, 63.5% vs 54.2%, P < .001) for intermediate-risk/high-risk patients, but not for low-risk patients. For intermediate-risk/high-risk patients, RT + CT and CT + RT resulted in non-significantly different OS (77.7% vs 72.4%; P = .290) and PFS (67.1% vs 63.1%; P = .592). For patients with complete response (CR) after induction CT, initiation of RT within or beyond three cycles of CT resulted in similar OS (78.2% vs 81.7%, P = .915) and PFS (68.2% vs 69.9%, P = .519). For patients without CR, early RT resulted in better PFS (63.4% vs 47.6%, P = .019) than late RT. Risk-based, response-adapted therapy involving early RT combined with CT is a viable, effective strategy for intermediate-risk/high-risk early-stage patients with ENKTCL in the modern treatment era.     

Pink1/Parkin-Mediated Mitophagy Regulated the Apoptosis of Dendritic Cells in Sepsis

Inflammation - Dendritic cells (DCs) are vital antigen-presenting cells (APCs) in the immune system, whose apoptosis is closely related to the development of sepsis. Mitophagy is one of the...