新型冠状病毒肺炎免疫治疗药物托珠单抗的作用机制及安全性风险分析

目的分析托珠单抗的安全性风险,为临床合理用药提供参考。方法对世界卫生组织药品不良反应监测数据库、我国药品不良反应监测数据库、国内文献数据库中的不良反应报告情况及国外药监机构风险控制措施等相关资料进行整理与分析。结果应重视托珠单抗临床使用中可能发生的肝功能异常、皮肤损害、过敏反应、胃肠道损害、感染、血液系统损害等不良反应。结论托珠单抗临床使用中,应加强对严重感染及肝功能损害等严重不良反应的安全性监测,促进药品的临床合理使用。     

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).     

抑郁症康复技能训练程式在基层医院推广应用的价值研究

背景　抑郁症的康复技能训练是一种很好的辅助治疗方法，本课题通过引进成熟的抑郁症康复技术，使基层医务人员熟练掌握，为辖区内广大抑郁症患者开展康复训练，以期提高抑郁症患者的疗效，降低自杀风险。目的　探讨抑郁症康复技能训练程式在基层医院推广应用的价值。方法　选取门头沟区龙泉医院2018年1-9月门诊就诊的65例抑郁症患者为研究对象。入选患者全部接受康复训练，分别于训练前和训练结束3个月后采用汉密尔顿抑郁量表（HAMD）、社会功能缺陷筛选量表（SDSS）、服药依从性、自杀风险评估量表（nurses' global assessment of suicide risk，NGASR）和自杀风险问卷对患者进行评估。结果　共61例患者完成研究，与训练前比较，训练结束3个月后患者HAMD、SDSS评分明显降低，服药依从性除自行停药外均明显提高，自杀风险明显降低，差异有统计学意义（P<0.05）。结论　抑郁症康复训练程式能有效提高患者服药依从性，改善抑郁症状，减少自杀观念，在基层医院有推广价值。     

OSAHS患儿扁桃体和腺样体术后免疫功能的变化

目的 阻塞性睡眠呼吸暂停低通气综合征(OSAHS)是耳鼻咽喉科的一种常见病，儿童发病率呈上升趋势，调查显示儿童OSAHS发生率为4%~5%，2~6岁是发病的高峰期。OSAHS不仅严重影响儿童的睡眠质量，还会引起儿童生长发育迟缓、智力缺陷等一系列不良反应，OSAHS患儿的主要病因是扁桃体和/或腺样体肥大，因此最有效的治疗方法是扁桃体切除术和腺样体切除术。而扁桃体和腺样体是儿童淋巴组织系统的重要组成部分，在机体的防御和保护功能中发挥着重要作用。手术治疗OSAHS是否影响儿童的免疫功能目前存在争议。一些学者认为扁桃体切除和腺样体切除后儿童的免疫力降低，而另一些学者认为OSAHS儿童的免疫力在手术后保持不变，甚至比手术前有所提高。本文就儿童OSAHS手术前后免疫指标的变化作一综述。     

Comparison of the practicability of ultrasound and spiral computed tomography in the diagnosis of colon cancer: A protocol for systematic review and meta-analysis

Background:Colon cancer is a common malignant tumor of the gastrointestinal tract. Therefore, a clear diagnosis is particularly important for the treatment of colon cancer. Ultrasound and spiral computed tomography (CT) can both be used in the diagnosis, but each has its own advantages and disadvantages, which could cause confusion in clinical choice. The purpose of this study was to systematically evaluate the practicability of spiral CT and ultrasound in the diagnosis of colon cancer.Methods:A systematic search was performed by retrieving on English databases (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese databases (CNKI, Wanfang, Weipu [VIP], CBM). Besides, manually search for Google and Baidu academic of diagnostic experimental study of ultrasound and spiral CT in the diagnosis of Colon Cancer. The retrieval time limit was from the establishment of the database to October 2020. Two researchers independently extracted and evaluated the quality of the data in the included study. A meta-analysis was performed using Meta Disc1.4 and RevMan5.3 software.Results:Sensitivity, specificity, positive Likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were used to determine the diagnostic efficacy of ultrasonography and helical CT in colorectal cancer.Conclusions:This study will compare the practicability of CT and ultrasound in the diagnosis of colon cancer and provide reliable evidence-based basis for clinicians to choose the appropriate or best evidence-based basis.Ethics and dissemination:The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.OSF Registration number:DOI 10.17605/OSF.IO/WAJHQ     

早期乳腺癌后续强化辅助内分泌治疗(MA-17研究结果解读)

1乳腺癌内分泌治疗:他莫昔芬的益处和局限性他莫昔芬(TAM)是最常用的乳腺癌内分泌治疗的药物,关于TAM在早期乳癌术后预防复发转移的辅助治疗阶段中应用,最为权威的结论来自发表在Lancet上、对5 5个临床试验共计37 000例患者的综合回顾报告,目前TAM在乳癌辅助治疗中应用的基本共识有:①辅助内分泌治疗的决定因素为激素受体(ER/PR)状况,ER阳性者效果最好,部分ER、阴性PR阳性的患者也可以使用TAM,但ER阴性患者辅助治疗用TAM不能改善生存;②目前认为TAM合适的服药时间为5年,可以显著降低复发风险12%,提高生存率9%。至于再延长用药…     

Additional bedtime H2‐receptor antagonist for the control of nocturnal gastric acid breakthrough: A Cochrane systematic review

OBJECTIVES: To assess the effectiveness and safety of additional bedtime H₂‐receptor antagonists (H₂RAs) in suppressing nocturnal gastric acid breakthrough (NAB) via a systematic review. METHODS: Eligible trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 2, 2004), MEDLINE (January 1966–June 2004), EMBASE (January 1980–June 2004) and CINAHL (January 1982–June 2004). Additional hand‐searching was conducted on the proceedings of correlated conferences, eight important Chinese journals and references of all included trials. All randomized controlled trials evaluating H₂RAs for the control of NAB were eligible for inclusion. The systematic review was conducted using methods recommended by The Cochrane Collaboration. RESULTS: Only two randomized crossover studies, comprising 32 participants, met the inclusion criteria. Because the design, dosage and duration of the treatments were different between the studies, it was not possible to conduct meta‐analysis. There were no consistent conclusions found between the two included studies in evaluating H₂RAs for the control of NAB. CONCLUSIONS: No implications for practice at this stage can be concluded. Appropriately designed large‐scale randomized controlled trials with long‐term follow up are needed to determine the effects of additional bedtime H₂RAs in suppressing NAB.     

还原型谷胱甘肽联合甘草酸二铵对腹部开放伤后海水浸泡犬肝功能损伤的治疗作用

Objective To investigate effect of reduced glutathione and diammonium glycyrrhizinate on the treatment of hepatic damage in experimental dogs following open abdominal injuries coupled with seawater immersion. Methods Twenty-four dogs with open abdominal injuries were randomly divided into 3 groups: the control group (given with simple observation after 1.5 h seawater immersion); the routine treatment group (given routine care and fluid transfusion after 1.5 h seawater immersion) ; the hepatic treatment group (given routine are, fluid transfusion and hepatic treatment as well, after 1.5 h seawater immersion). Each group consisted of 8 dogs. Blood samples were taken at different time points to measure total bilirubin (TB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), prothromin time (PT), endotoxin, tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), and pathological examination was also made at the same time. Results For the control group, contents of TB, ALT, AST and LDH increased significantly and survival time was less than 24 hours. Contents of TB, ALT, AST and LDH of the routine treatment group also increased significantly, but survival time of all the experimental animals was mere than 24 hours. Reduced glutathione and diammonium glycyrrhizinate could reduce the extent of lesion quite significantly 12～24 hours following open abdominal injuries. Conclusions Reduced glutathione and diammonium glycyrrhizinate seemed to have good effects on the treatment and prevention against hepatic damage induced by trauma coupled with seawater immersion. It could be used as a primary means for the treatment of such kind of hepatic damage.