Hypertension is a risk factor for adverse outcomes in patients with coronavirus disease 2019: a cohort study

Abstract

Background

Comorbidities are commonly seen in patients with coronavirus disease 2019 (COVID-19), but the clinical implication is not yet well-delineated. We aim to characterize the prevalence and clinical implications of comorbidities in patients with COVID-19.     

个体化假体复合组织工程技术修复兔下颌骨缺损

目的研究快速成型（RP）技术辅助下制作的个体化假体复合珊瑚羟基磷灰石（CHA）、重组人骨形成蛋白2（rhBMP-2）修复兔下颌骨缺损的成骨效果。 方法以27只新西兰大白兔为实验对象，随机数字表法平均分成3组（每组9只），全部建立下颌骨连续性缺损模型，并在兔下颌骨缺损区分别植入个体化假体+自体骨（A组）、个体化假体+CHA（B组）、个体化假体+CHA+rhBMP-2（C组）。分别于术后4、12、24周3个时间点处死动物取材，进行大体标本观察，以及骨钙素（OC）、Ⅰ型胶原（COL-1）的免疫组化观察，分别比较各组修复骨缺损的能力，并对实验数据进行重复测量设计资料的单因素方差分析。 结果术后24周各组实验兔外形均对称，通过OC及COL-1的吸光度检测，骨缺损区均有大量新骨形成，A组（0.537 ± 0.010）、C组（0.530 ± 0.010）可见大量骨小梁及编织骨结构，缺损区的新骨OC、COL-1的免疫组化观察基本一致，差异无统计学意义（t = 0.007，P>0.05）；但A组强于B组（0.415 ± 0.009，t = 0.122，P<0.001）；C组也强于B组（t = 0.121，P<0.001），差异均有统计学意义。 结论在兔下颌骨缺损修复中，通过RP技术和组织工程技术相结合，CHA复合rhBMP-2后成骨能力明显增强，成骨效能肯定，为后期的临床应用提供可靠的实验基础。     

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).     

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。     

Association of genetic variants at MYP10 and MYP15 with high myopia in a Han Chinese population

Background: Previous genome-wide association study (GWAS) has revealed the association between MYP10 at 8p23 and MYP15 at 10q21.1 and high myopia (HM) in a French population. This study is managed to discover the connection between some single nucleotide polymorphism (located at MYP10 and MYP15) and Han Chinese HM.

Methods and Results: This case-control association study contained 1673 samples, including 869 ophthalmic patients and 804 controls. Twelve tag SNPs have been selected from the MYP10 and MYP15 loci and genotyped by SNaPshot method. Among 12 SNPs, rs4840437 and rs6989782 in TNKS gene were found significant association with HM. Carriers of rs4840437G allele and rs4840437GG genotype created a low risk of high myopia (P = .036, OR = 0.81, 95%CI = 0.71–0.93; P = .016, OR = 0.73, 95%CI = 0.56–0.96; respectively). Carriers of rs6989782T allele and rs6989782TT+CT genotype also had a decreased risk of high myopia (P = .048, OR = 0.82, 95%CI = 0.71–0.94; P = .006, OR = 0.74, 95%CI = 0.59–0.92; respectively). Other 10 SNPs displaced nonsignificant association with HM. Additionally, the risk haplotype AC and the protective haplotype GT, generated by two SNPs in TNKS, were considerably more likely to be association with HM (for AC, P = .002 and OR = 1.26; for GT, P = .027 and OR = 0.84).

Conclusions: Our results demonstrated that some heritable variants in the TNKS gene are associated with HM in the Han population. The possible functions of TNKS in the development and pathogenesis of hereditary high myopia still require further researches to identify.     

膝痹宁对膝骨关节炎模型大鼠滑膜纤维化的影响

目的观察膝痹宁对膝骨关节炎(KOA)模型大鼠滑膜纤维化的影响。方法大鼠分为空白组、KOA组、膝痹宁组;KOA组、膝痹宁组造模。分别在膝痹宁灌胃治疗的第1、14、28、42、56天测量各组大鼠的膝关节横径;第56天处死大鼠提取滑膜组织,解剖学观察滑膜组织形态;天狼星红染色评估滑膜组织胶原沉积情况;WB和PCR检测纤维化标记物生长转化因子-β(TGF-β)、Ⅰ型胶原α1链(COL1α1)、金属蛋白酶抑制剂1(TIMP1)的蛋白和基因表达。结果膝痹宁用药14天,28天时,膝关节横径变化并不显著,但膝痹宁用药42天,56天时,膝关节横径则较KOA模型明显减小,差异具有统计学意义(P<0.05);用药56天后对大鼠进行膝关节解剖学观察,KOA大鼠滑膜组织较正常大鼠有一定程度的增厚、充血、欠规则;而上述表现在膝痹宁大鼠有所减轻;天狼星红染色显示膝痹宁用药大鼠滑膜组织胶原沉积较少;纤维化标记指标物TGF-β、COL1α1、TIMP1的基因和蛋白表达在膝痹宁组均较KOA组降低,差异具有统计学意义(P<0.05)。结论膝痹宁对能有效减轻KOA滑膜纤维化,以“温经活血”立法的中药复方对组织纤维化具有良性干预效应。     

保留足趾的自体复合第2足趾关节移植治疗手指关节炎

目的 探讨保留足趾的自体复合第2足趾关节移植治疗手指关节炎的临床疗效.方法 2016年2月至2018年6月,共收治创伤性手指关节炎9例,其中男7例,女2例;年龄19~53岁,平均31.7岁;示指3例,中指6例;掌指关节(MP)关节炎4例,近侧指骨间关节(PIP)关节炎5例;均为创伤后继发的手指关节炎.采用游离带血供的自体复合第2足趾跖趾或趾骨间关节移植进行治疗,同时将受区废弃关节(7例)或切取自体髂骨移植(2例)修复供区骨缺损保留足趾长度,供区创面均直接关闭.术后观察手指和足趾骨折愈合情况、外形、移植关节活动度(ROM)、术后供区愈合情况和行走功能及相关并发症.结果 本组术后9例移植关节全部成活,1例足部供区行髂骨植骨微型钢板固定,术后1周伤口不愈合,考虑为内固定物排异反应,予拆除钢板改克氏针交叉固定,2周后创口顺利愈合.术后随访6~30个月,平均16.3个月.手指骨折平均愈合时间7~10周,平均8.3周,手指外观及功能良好.移植后的MP活动度为50°~75°,平均65.3°,PIP活动度为10°~85°,平均60.6°.根据中华医学会手外科学分会上肢部分功能评定试用标准评价手指功能:优5例,良3例,可1例,优良率为88.9%.足趾骨折平均愈合时间9~12周,平均10.2周,所有患者足趾外形良好,行走功能正常.2例取髂骨患者供区仅残留一条线形瘢痕,无疼痛、麻木等不适.结论 游离带血供的自体复合第2足趾关节移植治疗手指关节炎,同时应用受区废弃关节或切取自体髂骨移植修复供区骨缺损保留足趾,不仅能恢复手指关节的正常结构,使关节具有良好的功能,而且能保留足趾外形与功能,减少供区损伤,具有良好的治疗效果.     

桃红四物汤联合银杏酮酯滴丸治疗老年出血性玻璃体混浊的临床疗效研究

目的:探究桃红四物汤联合银杏酮酯滴丸治疗老年出血性玻璃体混浊的临床疗效。方法:收集2016年12月-2018年12月我院收治的老年出血性玻璃体混浊患者67例,共67眼,根据随机对照表分为对照组和试验组,其中试验组34例,对照组33例,对照组予以银杏酮酯滴丸;试验组在对照组的基础上联用桃红四物汤。两组均服用30 d。治疗结束后对比分析两组患者临床疗效、出血吸收时间、血液流变学及视网膜中央动脉血流动力学。结果:治疗后两组患者高切全血粘度、低切全血粘度、纤维蛋白原、阻力指数(Resistance Index,RI)低于治疗前,收缩期峰值速度(Peak Systolic Velocity,PSV)、舒张末期血流速度(End Diastolic Velocity,EDV)高于治疗前,差异具有统计学意义(P<0.05);治疗后试验组临床总有效率、PSV、EDV高于对照组,出血吸收时间、高切全血粘度、低切全血粘度、纤维蛋白原、RI低于对照组,差异具有统计学意义(P<0.05)。结论:桃红四物汤联合银杏酮酯滴丸治疗老年出血性玻璃体混浊临床疗效显著,适宜临床应用推广。