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).     

液体复苏在高呼吸末正压通气导致的肺泡微循环障碍中的作用

目的明确高呼气末正压（PEEP）条件下肺泡微循环的变化情况以及液体复苏在高PEEP情况下对肺泡微循环的影响。 方法选用北京当地的15条健康成年杂种狗进行实验，分别观察基线（PEEP 5 cmH₂O，1 cmH₂O=0.098 kPa）、高PEEP（平均动脉压下降≥20 mmHg，1 mmHg=0.133 kPa）及液体复苏后的呼吸、系统循环及肺泡微循环情况，肺泡微循环利用旁流暗视野成像（SDF）技术进行观察、留取视频结果，线下利用AVA3.2软件进行分析，不同条件下的实验数据之间的差异利用Wilcoxon秩和检验进行分析。 结果高PEEP可导致中心静脉压（CVP）升高（P=0.001）及心输出量（CO）下降（P=0.002），肺泡微循环表现为总微血管数量（TVDa，P=0.036）、灌注血管数量（PVDa，P=0.002）、灌注血管比例（PPVa，P=0.003）、血流状态（MFIa，P=0.002）显著下降，肺泡周围毛细血管密度下降不明显（TVDs，P=0.319）；液体复苏恢复整体循环后，微循环参数均无显著改善。 结论过高的PEEP水平可导致肺泡微循环的显著恶化，通过液体复苏不能改善由此产生的微循环障碍。     

局部晚期食管鳞癌新辅助放疗剂量与病理完全缓解关系分析

目的 探讨接受新辅助放化疗的局部晚期食管鳞癌患者新辅助放疗剂量与病理完全缓解(pCR)的关系。方法 收集2017-2019年间在四川大学华西医院肿瘤中心经病理确诊为食管鳞癌并接受新辅助放化疗和手术的 116例局部晚期患者临床资料。116例患者中 40~45Gy组 80例,≥45Gy组 36例,分析两组术后pCR率。结果 全组患者的pCR率为38.8%(45/116),40~45Gy组与≥45Gy组的pCR率分别为44%(35/80)和28%(10/36)(P=0.105)。结论 术前新辅助采用较高的放疗剂量不增加局部晚期食管鳞癌的pCR率,有必要进行前瞻性的临床研究确定合适的新辅助放疗剂量。     

一种面向中医药数据的高效脱敏算法＊

目的 针对中医药大数据平台传统的加密方案效率不高的问题，提出一种高效的基于属性的内积加密的数据脱敏算法。方法 Hash（哈希）算法是应用广泛的高效的数据加密方法，但传统的哈希算法基于单一的控制策略，效率不高。本文提出一种基于属性的内积加密的数据脱敏算法，把批量的敏感数据分割为不同长度数据颗粒度，与特定密文的哈希进行内积处理。结果 在面对中医药大数据平台的海量数据加密的场景，与传统的哈希加密算法相比，本文提供的加密算法具有很好的性能。结论 为了保障个人隐私数据不被泄露，中医药大数据平台中的个人医疗数据需要加密脱敏后，才能进行分析处理或对外发布。本文提出的算法具备灵活的数据颗粒度、策略和高效的性能表现，适用于海量的中医药数据脱敏。     

MOB1A regulates glucose deprivation-induced autophagy via IL6-STAT3 pathway in gallbladder carcinoma

MOB kinase activator 1A (MOB1A) plays an important role in many diseases and cancers. Here, we observed that MOB1A was substantially overexpressed in gallbladder carcinoma (GBC) tissues compared with nontumor tissues. The high expression of MOB1A was closely associated with poor survival in patients with GBC at advanced TNM stages. Furthermore, our study indicated that MOB1A promoted autophagy by activating the IL6/STAT3 signaling pathway and regulating the chemosensitivity to gemcitabine under glucose deprivation conditions both in vitro and in vivo. In conclusion, these findings suggested that MOB1A is critical for the development of GBC via the MOB1A-IL6/STAT3-autophagy axis.     

Comparison of Laparoscopic-Assisted Operations and Laparotomy Operations for the Treatment of Hirschsprung Disease: Evidence From a Meta-Analysis

The purpose of this meta-analysis is to compare the relative merits among laparoscopic-assisted operations and laparotomy operations for patients with Hirschsprung disease.PubMed, Web of Science, and Wanfang databases were searched for the related articles. We analyzed dichotomous variables by estimating odds ratios (ORs) with their 95% confidence intervals (CIs) and continuous variables using the weighted mean difference (WMD) with the 95% CI. The random-effects model (REM) was used to combine the results. The outcome measures included operating time (OT), estimated blood loss (EBL), length of hospital stay (LOHS), mean first bowel movement (MFBM), and number of complications.Sixteen articles were included in the meta-analysis. These studies involved a total of 774 patients, 396 of whom underwent laparoscopic-assisted operations and 378 of whom underwent laparotomy operations. The EBL (WMD = −1.48, 95% CI = −1.82, −1.13), LOHS (WMD = −0.67, 95% CI = −0.86, −0.49), MFBM (WMD = −0.83, 95% CI = −1.05, −0.61), and number of complications (OR = 0.60, 95% CI = 0.40, 0.89) were significantly lower in laparoscopic-assisted operations than in laparotomy operations. The OT (WMD = 0.12, 95% CI = −0.05, 0.28) showed no significant differences between laparoscopic-assisted operations and laparotomy operations.Compared with laparotomy operations, laparoscopic-assisted operations are generally safer and more reliable for patients with Hirschsprung disease.