中医药干预新型冠状病毒肺炎临床研究方案分析

对中医药防治新型冠状病毒肺炎临床研究方案注册情况进行分析,为提高相关研究设计质量提供参考和建议。检索中国临床试验注册中心网站(www.chictr.org.cn)以及美国临床试验注册中心网站(clinicaltrials.gov),以新型冠状病毒肺炎、2019-nCoV等为检索词,检索新型冠状病毒肺炎中医药相关临床研究方案。按照纳入排除标准筛选文献,并提取研究注册时间、研究目的、研究类型、申办单位、研究对象、样本量、干预措施、评价指标等数据,采用描述性分析方法。共纳入新型冠状病毒肺炎中医药相关研究方案49个,研究负责单位以湖北、北京、浙江等地医院或高等院校为主。研究具体实施单位属地集中在湖北、广东、浙江、河南等地医院。研究设计以干预性试验研究为主(共40个),其中随机平行对照研究30个,非随机对照试验7个,单臂研究2个,连续入组1个;观察性研究6个;卫生服务研究2个;预防性研究1个。总样本量30562例,单个研究样本量最大20000例,最小30例。49个方案的研究对象包括健康人群(3个)、隔离观察人群(1个)、疑似病例(10个)、确诊病例(31个)、康复期病例(4个)。31个拟纳入确诊病例的研究方案中,有16个研究未明确病情分级,3个研究明确排除危重症,4个研究纳入普通型,2个研究纳入轻型、普通型或重型,1个研究纳入轻型和普通型,1个研究纳入普通型或重型,3个研究纳入重型,1个研究纳入重症或危重症。评价的干预措施包括中成药(连花清瘟胶囊/颗粒、藿香正气滴丸/口服液、八宝丹、固表解毒灵、金蒿解热颗粒、复方鱼腥草合剂、金叶败毒颗粒、疏风解毒胶囊、双黄连口服液、痰热清注射液、血必净注射液、热毒宁注射液、喜炎平注射液)、汤药、太极拳疗法。主要疗效指标以退热时间、临床症状缓解、新型冠状病毒核酸转阴、重症转化率、胸部CT影像为主。结果表明中医药防治新冠肺炎的临床研究响应快速,当前注册方案涵盖了疾病预防、治疗和康复全过程。但存在人群定义不清,研究目标不明确,干预方案需要细化,疗效评价指标需要优化等问题;另外,需要考虑疫情救治的实际困难和工作负担,在符合医学伦理条件下,优化流程,提高研究方案的可操作性。     

12-year survival analysis of 322 Hintegra total ankle arthroplasties from an independent center

Background and purpose — Total ankle arthroplasties (TAAs) have larger revision rates than hip and knee implants. We examined the survival rates of our primary TAAs, and what different factors, including the cause of arthritis, affect the success and/or revision rate.Patients and methods — From 2004 to 2016, 322 primary Hintegra TAAs were implanted: the 2nd generation implant from 2004 until mid-2007 and the 3rd generation from late 2007 to 2016. A Cox proportional hazards model evaluated sex, age, primary diagnosis, and implant generation, pre- and postoperative angles and implant position as risk factors for revision.Results — 60 implants (19%) were revised, the majority (n = 34) due to loosening. The 5-year survival rate (95% CI) was 75% (69–82) and the 10-year survival rate was 68% (60–77). There was a reduced risk of revision, per degree of increased postoperative medial distal tibial angle at 0.84 (0.72–0.98) and preoperative talus angle at 0.95 (0.90–1.00), indicating that varus ankles may have a larger revision rate. Generation of implant, sex, primary diagnosis, and most pre- and postoperative radiological angles did not statistically affect revision risk.Interpretation — Our revision rates are slightly above registry rates and well above those of the developer. Most were revised due to loosening; no difference was demonstrated with the 2 generations of implant used. Learning curve and a low threshold for revision could explain the high revision rate.

Arthritis in the ankle often develops earlier than in the hip or knee, and 70% have a traumatic etiology (Saltzman et al. 2005, Brown et al. 2006). Total ankle arthroplasty (TAA) can be indicated for severe arthritis in the ankle joint, but the anatomical preconditions, like a small surface area and high stress from compression and torque (Bouguecha et al. 2011, Kakkar and Siddique 2011), makes it less durable than hip and knee prosthetics. The Hintegra TAA, a 3-component mobile bearing, uncemented implant (Hintermann et al. 2004) is widely used and results from the development center demonstrate survival rates of 94% and 84% after 5 and 10 years’ follow-up (Barg et al. 2013). This is considerably more than the survival rates from national registries. Labek et al. (2011) demonstrated that development centers report only half of the revision rate that can be found in the few existing national registers. In a systematic review of primary Agility total ankle arthroplasty (DePuy Synthes Orthopedics, Warsaw, IN, USA), the author (Roukis 2012) found that the incidence of complications increased from 7% to 12%, in studies where the inventor was excluded. Similar results were found by Prissel and Roukis (2013), who found an increased incidence of complications from 6% to 13% in studies where the inventor or faculty consultants were excluded. These studies indicated the risk of selection (inventor) and publication (conflict of interest) bias.Planning and surgical technique, including significant experience, are mandatory for a successful outcome. The better result from development centers may reflect, besides the above-mentioned bias, that there is a long learning curve and that the indication for revision surgery varies.We examined the survival rates of primary Hintegra TAAs performed at Hvidovre Hospital, with revision rate as outcome. We report primary diagnosis for primary TAA and examine whether sex, generation of the implant, preoperative angles and implant position affect the revision rate.     

Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis

Ferroptosis is an iron-dependent novel cell death pathway. Deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition represents the mechanism of action of Deferoxamine on spinal cord injury recovery. A rat model of Deferoxamine at thoracic 10 segment was established using a modified Allen's method. Ninety 8-week-old female Wistar rats were used. Rats in the Deferoxamine group were intraperitoneally injected with 100 mg/kg Deferoxamine 30 minutes before injury. Simultaneously, the Sham and Deferoxamine groups served as controls. Drug administration was conducted for 7 consecutive days. The results were as follows:(1) Electron microscopy revealed shrunken mitochondria in the spinal cord injury group.(2) The Basso, Beattie and Bresnahan locomotor rating score showed that recovery of the hindlimb was remarkably better in the Deferoxamine group than in the spinal cord injury group.(3) The iron concentration was lower in the Deferoxamine group than in the spinal cord injury group after injury.(4) Western blot assay revealed that, compared with the spinal cord injury group, GPX4, xCT, and glutathione expression was markedly increased in the Deferoxamine group.(5) Real-time polymerase chain reaction revealed that, compared with the Deferoxamine group, mRNA levels of ferroptosis-related genes Acyl-CoA synthetase family member 2(ACSF2) and iron-responsive element-binding protein 2(IREB2) were up-regulated in the Deferoxamine group.(6) Deferoxamine increased survival of neurons and inhibited gliosis. These findings confirm that Deferoxamine can repair spinal cord injury by inhibiting ferroptosis. Targeting ferroptosis is therefore a promising therapeutic approach for spinal cord injury.     

加强型鼻咽通气道应用于鼻腔手术后气道管理临床研究

目的研制加强型鼻咽通气道应用于五官科鼻腔手术后的气道管理。方法选取2014年1月至2015年3月行五官科鼻腔手术的患者60例,将其分为A组和B组,各30例。A组作为加强型鼻咽通气道组,术毕在膨胀止血海绵中放置加强型鼻咽通气道保留鼻腔通气;B组作为对照组,术毕采用传统单纯填塞膨胀止血海绵。通过术后24、48 h随访,对两组患者进行疼痛、睡眠质量、口干程度评分,并对其进行对比分析。结果加强型鼻咽通气道具有良好的抗压抗折性;A组患者24、48 h睡眠质量、口干程度评分均明显优于B组,差异均有统计学意义(P<0.05)。结论加强型鼻咽通气道用于五官科鼻腔手术后气道管理可增强气道管理安全性及患者舒适度。     

基于子宫内膜异位症与恶性肿瘤的相关性探析补肾化瘀法作用机制及中医理论依据

子宫内膜异位症其异位内膜组织虽然在形态学上呈良性表现，却具有类似恶性肿瘤的生物学特性。中医学一般认为，“正虚伏邪”为恶性肿瘤的病机特点；那么，肾虚血瘀既属于“正虚伏邪”的范畴，又体现了EMs发病学和疾病发生、发展过程中的主要特点。在“病证相应”的中医治则之下，补肾化瘀法的临床疗效主要表现为：缓解痛经症状、提高受孕率，以及调整月经周期。本文基于EMs与恶性肿瘤的相关性，通过分析补肾化瘀法治疗EMs的理论依据及其抑制异位内膜侵袭的调控机制，主要包括解除免疫抑制、阻断局部微血管新生等，旨在阐明其疗效显著的原因，为临床推广提供可靠的基础研究证据。     

皮质发育障碍模型的建立及其致痫敏感性的研究

目的:建立皮质发育障碍模型,探讨皮质发育障碍模型的敏感性。方法:在SD大鼠孕17d腹腔注入1,3-二氯乙烯-亚硝基脲(BCNU)制作皮质发育障碍模型;Nissl染色观察P60d仔鼠病理变化;选取P60d雄性仔鼠,腹腔注射氯化锂-毛果芸香碱,分别比较两组大鼠癫发生的潜伏期、持续状态时间和死亡率。结果:同龄仔鼠脑组织湿重实验组比对照组显著减轻(P<0.01);Nissl染色显示皮质变薄、皮质层次紊乱、海马区域异位细胞异常聚集;有皮质发育障碍的仔鼠注射氯化锂-毛果芸香碱后,癫发生的潜伏期显著缩短(P<0.01),癫持续状态时间延长(P<0.01),死亡率显著升高(P<0.05)。结论:BCNU致皮质发育障碍模型具有癫易感性。     

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.     

2004年和2005年鲁东大学女教职工妇科查体结果分析

目的通过2004年和2005年本校女教职工妇科查体结果的分析，发现女教职工中未被识别的疾病与致病因子，从而达到防病、治病的目的。通过两年查体结果的分析比较，进一步说明高校女教职工定期进行妇科查体的必要性。方法收集、整理2004年和2005年两年的妇科查体结果，并对不同年龄组的患病率进行分析、比较，查找原因。结果两年的查体结果表明，2005年各年龄段妇科疾病的发病率明显较2004年低，经卡方比较，差异有显著性。结论对女教职工实施定期的妇科查体，对及旱发现妇科疾病、及时进行适当的治疗、保障女教职工的身体健康起了重要作用。