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).     

Growth Hormone Induces Recurrence of Infantile Hemangiomas After Apparent Involution: Evidence of Growth Hormone Receptors in Infantile Hemangioma

Infantile hemangiomas (IHs) are the most common benign tumor of infancy, characterized by a natural history of early proliferation in the first months of life to eventual involution during childhood, often with residual fibrofatty tissue. Once involution has been achieved, IHs do not typically recur. We present two cases of exogenous growth hormone therapy resulting in the recurrence of IHs in late childhood, supported by radiological, immunohistochemical, in vitro, and in vivo evidence.     

针刺辅助治疗难治性肠易激综合征临床试验方案关键点设计的思考＊

肠易激综合征（Irritable bowel syndrome，IBS）是临床常见病、多发病，其治疗方法丰富，但部分患者疗效欠佳，发展成难治性IBS。目前国内外关于针灸治疗难治性IBS的临床随机对照试验尚不多见。本文立足试验方案设计的“PICOS”原则，从研究对象及诊断标准、干预措施、对照措施、结局指标四个方面入手，重点探讨针刺辅助治疗难治性肠易激综合征临床试验设计的关键要点。从选择特色优势病种、明确诊断标准、制定符合临床实际的干预方案、运用符合目标的安慰针刺、结合研究设计和目的选定结局指标几个角度，阐述试验相关环节设计的原因和思考。     

关节镜下TightRope治疗后交叉韧带撕脱骨折

目的探讨关节镜下使用TightRope治疗后交叉韧带(PCL)撕脱骨折的技术应用和临床疗效。方法 12例膝关节PCL撕脱骨折患者在关节镜下使用TightRope固定PCL撕脱骨块。术后1周开始在支具保护下被动活动膝关节,术后10个月评估膝关节功能恢复情况。结果 12例患者均获随访,时间10～14个月,平均12.6个月,骨折均Ⅰ期愈合。1例屈膝受限15°,无伸膝受限;2例后抽屉试验(+)。Lysholm膝关节功能评分术前(45.6±6.3)分,术后10个月(87.8±4.8)分,差异有统计学意义(P 0.05)。结论关节镜下使用TightRope治疗PCL撕脱骨折固定可靠,操作相对简单,疗效满意。     

A drug safety evaluation of mogamulizumab for the treatment of cutaneous T-Cell lymphoma

Introduction: Cutaneous T-cell lymphomas (CTCL) are rare non-Hodgkin lymphomas of skin-homing T-cells that initially or mainly manifest cutaneously. Treatment of CTCL is challenging given the disease states’ varying presentation and prognosis. Systemic treatment options often lack comparative evidence and have relatively low response rates and short duration of response. The recent Food and Drug Administration (FDA) approval of mogamulizumab in adult patients with relapsed or refractory (R/R) CTCL after at least one prior line of therapy provided a new treatment option to patients with advanced disease.

Areas covered: The authors discuss basic information about CTCL and mogamulizumab’s mechanism of action. Then, the authors discuss the agent’s efficacy. Finally, the authors evaluate the safety of mogamulizumab in comparison to other agents available in CTCL.

Expert opinion: Mogamulizumab has been shown to be an effective and well tolerated therapy for patients with relapsed and refractory MF/SS with excellent activity in the circulating component of the disease.     

幼儿不同跑步着地方式的生物力学特征

文题释义：跑：跑是双脚交替接触地面的周期性运动，但跑有一个双脚都离开地面的腾空期。幼儿在 1 岁多开始学习跑步，最初是走跑结合的移动方式，由于身体发育不完善，下肢力量弱，平衡能力差，容易摔倒；到 2.5岁，幼儿跑步的腾空阶段明显；到 6岁，早期跑步的特点基本消失。 着地方式：指的是人体在跑步着地阶段足部接触地面的方式，一般分为3种方式：分别为足跟着地(fore foot strike)，跟骨先接触地面；全足着地(mid foot strike)，全脚掌着地，即足跟与前足同时接触地面；前足着地(rear foot strike)：前足部首先接触地面。 背景：成年人跑步着地方式一直是国内外学者研究的重点，而幼儿跑步的着地方式也是不容忽视的内容。 目的：运用生物力学方法探究幼儿在跑步过程中，不同着地方式下的运动学和动力学指标的差异，为幼儿正确的跑步着地方式提供科学依据。 方法：在北京市海淀区某公立幼儿园中随机抽取幼儿74名，按年龄分为3岁组、4岁组、5岁组，采用BTS红外动作捕捉系统、Kistler三维测力台和VIXTA录像解析系统同步采集幼儿跑步过程中不同着地方式下的运动学、动力学数据；运用Anybody 5.2仿真建模软件计算下肢肌肉力量指标。试验前向受试者父母详细解释并签署知情同意书，试验方案符合北京师范大学的相关伦理要求。 结果与结论：①3岁组全足着地的比例最高，足跟着地的比例最低，5岁组全足着地的比例最低，足跟着地的比例最高；前足着地者的蹬伸时间大于足跟着地(P < 0.01)和全足着地(P < 0.05)；②着地时刻，踝屈曲角度足跟着地者大于前足着地(P < 0.01)和全足着地者(P < 0.05)，全足着地者大于前足着地(P < 0.05)；前足着地者髋内收-外展角度、最大髋内收-外展角、髋内-收外展的关节变化量及最大膝内收-外展角速度大于足跟着地(P < 0.01)和全足着地者(P < 0.05)；前足着地者的踝屈伸最小值大于足跟着地者(P < 0.05)，而最大髋内收-外展角速度小于足跟着地者(P < 0.05)；③足跟着地和全足着地者的腓骨短肌、腓骨长肌、第三腓骨肌的肌力大于前足着地者(P < 0.05)，前足着地者的股中间肌、股外侧肌下束、股外侧肌上束、股内侧肌下束、股内侧肌上束、股内侧肌中束肌力均大于足跟着地(P < 0.01)和全足着地者(P < 0.05)；④结果提示：在3-6岁阶段，幼儿多采用足跟或全足着地模式进行奔跑，以满足自己在跑步过程的稳定性，随着年龄的增长，逐渐出现前足着地方式的跑步模式；前足着地能够动用更多髋关节和膝关节额状面的运动来维持人体运动中的稳定，足跟着地和全足着地能够动用更多的小腿前侧和后侧的肌力，而前足着地动用更多的大腿前侧肌力。 ORCID: 0000-0002-8337-3931(赵盼超) 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程     

上海市黄浦区社会办医疗美容机构《医疗美容管理办法》知晓情况调查

目的了解上海市黄浦区社会办医疗美容机构的管理人员和医师对《医疗美容管理办法》相关内容的掌握情况,发现存在的问题并提出改善建议.方法采用现场调查与现场问卷调查相结合的方式,对在上海市黄浦区开展医疗美容科目的所有社会办医疗机构(共计38家)进行全覆盖现场调查,并对其中的管理人员41人、相关医师31人进行问卷调查.结果38家社会办医疗美容机构中,美容外科和美容皮肤科的开展率较高,分别为96.8%和97.2%,而美容牙科开展率为52.4%,美容中医科开展率最低(25.0%).管理人员关于非主诊医师可在主诊医师指导下工作的知晓率仅68.3%.关于美容外科、皮肤科、中医科、牙科主诊医师应具备的工作年限,管理人员答对率为90.2%,医师答对率为72.0%,二者有显著性差异(P<0.05).结论社会办医疗美容机构中的二级科目设置需进一步优化,以减少资源空置.应加强对医疗机构管理人员和医师的法律培训,改变经营模式,制定明确的准入与退出机制,从而减少违法违规行为的发生.     

基础医学综合实验与实验设计课程教学改革实践

本着以课程为中心的原则，研究组在基础医学综合实验课程建设、运行方式、教学方法改革等方面积极探索；以联系疾病、联系应用为导向，广泛开展基于疾病动物模型制备及干预过程的实验教学；增加"创新性"实验项目，确保课程内容体现出前沿性和时代性；以生物医学前沿方法训练引领课程建设，着力培养学员的学习能力、实践能力和创新能力。此外，在优化以实践应用、创新性为导向的课程内容建设的基础上，打造虚拟仿真实验项目，尝试线上线下混合式教学，全方位提升学员的实践运用能力。     

大椎刮痧治疗小儿外感发热(风热型)的临床疗效观察

【目的】观察大椎刮痧结合布洛芬口服对小儿外感发热(风热型)的疗效。【方法】将100例风热型外感发热患儿随机分为治疗组和对照组,每组各50例。对照组给予布洛芬口服治疗,治疗组给予大椎刮痧结合布洛芬口服治疗。观察2组患儿治疗前及治疗后30 min、60 min、120 min的体温变化情况,评价2组患儿治疗后120 min的降温疗效、中医证候疗效和安全性。【结果】(1)观察过程中,治疗组脱落1例,其余49例完成试验;对照组无脱落病例,50例全部完成试验。(2)治疗后30、60、120 min,2组患儿的体温均逐渐降低,与治疗前及前1个观察时点比较,差异均有统计学意义(P0.05);且治疗组在治疗后60、120 min的体温均明显低于对照组,差异均有统计学意义(P0.05)。(3)治疗后120 min,2组患儿的中医证候积分均较治疗前降低(P0.05),且治疗组的中医证候积分明显低于对照组,差异有统计学意义(P0.05)。(4)降温疗效方面,治疗后120 min,治疗组的总有效率为100.0%(49/49),对照组为96.0%(48/50),治疗组的降温疗效优于对照组,差异有统计学意义(P0.05)。(5)中医证候疗效方面,治疗后120 min,治疗组的有效率为61.2%(30/49),对照组为18.0%(9/50),治疗组的中医证候疗效优于对照组,差异有统计学意义(P0.05)。(6)治疗过程中,2组患儿均无明显不良反应发生。【结论】大椎刮痧结合布洛芬口服治疗风热型外感发热患儿疗效显著,相比单纯布洛芬口服治疗,可更好地降低患儿体温,改善患儿临床症状。