新型口服抗凝药的药物基因组学研究进展

新型口服抗凝药（NOAC）在心脑血管血栓疾病的防治中发挥了重要作用。由于参与NOAC体内过程的转运体和代谢酶的基因多态性,不同个体口服相同剂量的NOAC后,其体内药代动力学参数存在差异。相对于药物转运体,药物代谢酶的基因多态性对NOAC的药代动力学性质影响较大,但目前相关研究较少。本文分析总结了基因多态性对NOAC药代动力学性质的影响。     

Diagnostic efficacy of three suction techniques for endoscopic ultrasound-guided fine-needle biopsy of solid pancreatic lesions: protocol for a multicenter randomized cross-over clinical trial

BackgroundHow suction technique affects endoscopic ultrasound-guided tissue acquisition (EUS-TA) remains unclear. A standardized protocol is currently lacking, with most previous studies being restricted to EUS-guided fine-needle aspiration (EUS-FNA). The research related to EUS-guided fine-needle biopsy (EUS-FNB) is sparse.AimsThe aim of this study is to evaluate the diagnostic efficacy, cellularity, tissue acquisition, blood contamination and adverse event rate of three common suction techniques (standard suction, slow-pull, and wet suction) used for EUS-FNB of solid pancreatic masses.MethodsThis is a multicenter single-blind randomized cross-over superiority trial. A total of 300 patients with suspected pancreatic malignancy will be enrolled from digestive endoscopic centers at five large tertiary hospitals in China. All three suction techniques will be performed on each patient using a 25G ProCore needle, with the sequence of suction techniques determined by randomization. Cytological and histological specimens obtained with each of the three techniques will be assessed independently. Outcomes among the three suction techniques will be compared.DiscussionTo the best of our knowledge, this is the largest multicenter randomized cross-over trial designed to determine the optimal suction technique for the diagnosis of solid pancreatic masses. This study may contribute to standardizing the suction technique for EUS-FNB.     

Meta-analysis of the impact of the SPINK1 c.194 + 2T > C variant in chronic pancreatitis

Background and aimsThe SPINK1 c.194 + 2T > C variant has been increasingly recognized as an important risk factor for chronic pancreatitis (CP). However, there is no clear agreement on its contribution to different ethnicities and CP etiologies. To address this issue, a meta-analysis of literature was performed.MethodsStudies addressing the presence of the SPINK1 c.194 + 2T > C variant in CP patients and controls were retrieved from the PubMed, EMBASE and Cochrane databases. Initial analysis included all CP patients, followed by subgroup analyses for East Asian and non-East Asian patients, and for idiopathic CP (ICP) and non-ICP.ResultsA total of 13 studies were retrieved for analysis, comprising 2097 cases and 4019 controls. There were 126 cases (10.01%) carrying the SPINK1 c.194 + 2T > C variant in cases, while only two controls were carriers (0.05%). Overall, the variant was significantly associated with an increased risk of CP (OR = 25.73). In the subgroup, the variant was significantly associated with increased risk of CP in East Asians (OR = 73.16), and in non-East Asians (OR = 10.21). Further, the contribution of the variant in ICP (OR = 35.31) was found to be higher than in non-ICP (25.75).ConclusionsThe SPINK1 c.194 + 2T > C variant is a strong risk factor for CP, especially in East Asian patients with ICP.     

右美托咪定对心外科术后患者睡眠质量的改善作用

目的研究右美托咪定对心外科术后患者睡眠质量的影响。方法利用多导睡眠图对2018年1月至2018年12月长海医院心脏术后患者进行睡眠监测,选择最终符合条件的患者63例为研究对象,按随机数字表法分为试验组32例和对照组31例。试验组患者从晚上22:00试验开始时持续静脉注射右美托咪定,次日晨6:00停止注射,连续注射3晚。镇静目标为镇静程度评估表(richmond agitation-sedation scale,RASS)评分-1~2分,右美托咪定的负荷剂量为0.5μg/kg,时间不超过20 min,然后以0.2~0.7μg/(kg·h)持续静脉注射,期间不使用其他镇静剂。对照组患者晚间不注射右美托咪定以及其他镇静药物。此段时间用多导睡眠仪监测两组患者的睡眠。观察目标为两组患者睡眠总时间、睡眠效率、觉醒次数、睡眠各阶段时间。试验期间白天的睡眠由床旁护士记录患者睡眠次数。结果试验组与对照组比,有更少的觉醒次数[(3.1~3.61)次vs.(8.87~9.77)次,P<0.01],更高的睡眠效率(68%~71.29%vs.25.1%~28.87%,P<0.01),更长的睡眠第二阶段[(249.55~266.89)min vs.(59.12~71.59)min,P<0.01],差异有统计学意义。两组患者睡眠第一阶段比较,差异无统计学意义[(63.61~7.05)min vs.(56.37~63.33)min,P>0.05]。结论夜间持续输注右美托咪定显著提高了患者睡眠效率、减少睡眠觉醒次数、增加睡眠第二阶段的时间,在一定程度上改善了心外科术后患者的睡眠质量。     

日本血吸虫感染小鼠外周血CD4+T细胞亚群动态变化的研究

目的 了解日本血吸虫感染小鼠外周血CD4⁺T细胞亚群水平的动态变化情况,探讨感染进程中CD4⁺T细胞亚群的免疫调控作用。方法 通过日本血吸虫尾蚴腹贴法建立日本血吸虫感染小鼠模型,将18只6周龄C57BL/6J雄性小鼠随机分成正常对照组和日本血吸虫感染组,每组9只。 通过流式细胞染色计数的方法检测感染3周、5周及8周后小鼠外周血CD4⁺T细胞亚群中Th1、Th2、Th17、Treg细胞变化情况。结果 随着日本血吸虫感染进程,与正常对照小鼠相比,感染小鼠外周血CD4⁺T细胞亚群中Th1、Th2、Th17、Treg细胞比例均显著增加。不同细胞亚群比例增加的趋势不尽相同,其中Th1细胞在感染第3周占比较高但其增长较为缓慢,而感染前3周Th2、Treg细胞占比较低但其增加幅度较大,在第8周达到峰值;Th17细胞比例在感染前3周基本无变化,随后显著增加。结论 日本血吸虫感染引起宿主CD4⁺T细胞亚群比例发生变化,本研究发现感染显著增加小鼠外周血Th1、Th2、Th17、Treg细胞比例,感染后3周内小鼠外周血CD4⁺T细胞亚群以Th1细胞为主,5周后Th2、Th17、Treg细胞逐渐占主导地位。本结果为研究日本血吸虫病免疫病理机制和特征提供基础。     

心身医学在全科实践中的作用思考

随着心身医学的研究发展,当今大部分疾病可归属到心身疾病范畴,且处于高发状态。我国提出了“首诊在基层”的服务模式,但全科医学尚处于发展阶段,基层卫生服务中全科医生存在医疗水平参差不齐的问题,其岗位胜任能力有待提高,在心身疾病诊疗能力层面尤为明显。通过心身医学与全科医学相结合,可以提升全科医生对心身疾病的认知应对能力,改善全科医生的岗位胜任能力不足现状,同时促进社区居民精神卫生健康,充分体现全科医生“健康守门人”的作用。本文阐述了目前国内全科医学起步晚、需求高的发展现状,总结归纳了国内外对心身医学的认知,揭示出我国精神卫生资源供不应求的现象。笔者根据我国存在心身疾病临床诊断率低,全科医生缺乏相关的心理干预技术,缺乏适合中国国情的诊断评估标准等问题,认为应从多角度进行促进,从政府部门制定相关政策、完善全科医生的院校教育和培训体系及结合本土中医全科特色方面,提出了增强全科医生心身疾病诊疗能力的三点建议。心身医学和全科医学相结合符合当前我国医疗服务发展需求,通过强化全科医生在首诊中的心身疾病认知与应对能力,对于提升基层医疗卫生服务能力,控制医保费用,减少患者与社会的经济负担,具有显著的促进意义,从而更好实现“健康2030”的目标。      

Retrospective analysis of a TMJ ankylosis protocol with a 9 year follow up

ObjectiveTemporomandibular joint ankylosis (TMJa) is a debilitating condition that causes difficulty in mastication, speech and mouth opening. Its treatment poses surgical and rehabilitative challenges along with a high incidence of reankylosis. This study was designed to assess the long-term outcomes with a new two phase physiotherapy protocol following conservative resection of the ankylotic mass.Materials and methods143 patients who were treated for TMJa were initially recruited, among whom 98 were inducted into the study and retrospectively evaluated using clinical records and 3-dimensional computed tomography. All the patients underwent a minimal pre auricular incision and conservative interpositional gap arthroplasty with collagen membrane. This was followed by the new two phase physiotherapy protocol with the use of a bite block. The primary outcome measures were the maximum interincisal distance, vertical ramus height and complications. The patients were followed up at monthly intervals during the first year, quarterly intervals during the second year, and at intervals of 6 months during subsequent follow-up years. The mean follow up period was 6.38 ± 2.36 years after ankylotic release. Paired student t test was used for statistical analysis.ResultsThe mean scores for mouth opening at T1, T2 and T3 were statistically significantly different at all intervals (p < 0.0005). The mean scores for ramal length were statistically significantly different at T1 and T2 interval (p < 0.0005) and insignificant at T2 and T3 interval. No reankylosis was observed in patients who followed the physiotherapy protocol.ConclusionsIn the management of TMJa, the success of the conservative surgical technique with interpositional arthroplasty is less dependent on the longevity and rigidity of the interpositional material but more indebted to the patient compliance in following the proposed physiotherapy protocol.     

Residual excessive daytime sleepiness in patients with obstructive sleep apnea treated with positive airway pressure therapy

Sleep and Breathing - Patients with obstructive sleep apnea (OSA) commonly report residual excessive daytime sleepiness (EDS) despite treatment with positive airway pressure (PAP). The present...     

激光照射频次和单次照射时长对眼部组织的损伤作用评估

目的探讨激光照射频次和单次照射时长对泪液分泌、晶状体以及视网膜形态和功能的影响。方法选取36只健康豚鼠进行眼部激光照射实验,采用随机数字表法并依据激光照射频次和单次照射持续时间的不同将豚鼠随机分为高频短时(HFST)组、高频长时(HFLT)组、中频短时(MFST)组、中频长时(HFLT)组、低频短时(LFST)组和低频长时(LFLT)组,每组6只。各组豚鼠右眼进行500 lx的激光照射作为实验眼,左眼不接受任何干预作为对照眼。高频激光照射为15次,中频照射为10次,低频照射为5次,每次照射时间间隔为10 min;短时照射为30 s/次,长时照射为60 s/次。采用基础泪液分泌试验(SⅠt)对各组豚鼠实验眼与对照眼间泪液分泌量进行测定和比较;采用裂隙灯显微镜斜照法评估各组豚鼠晶状体透明性变化情况;采用眼底照相法评估豚鼠眼底和视盘大致形态;采用视网膜电图(ERG)记录法评价各组豚鼠视网膜功能变化;采用常规组织病理学方法检查视网膜外核层厚度变化。结果HFST组、HFLT组、MFST组、MFLT组、LFST组和LFLT组实验眼泪液分泌量分别为8.00(7.37,9.00)、8.75(8.25,9.00)、8.50(7.75,9.50)、9.00(8.50,9.50)、8.00(7.37,8.75)和8.25(7.75,8.75)mm/5 min,总体比较差异无统计学意义(χ²=5.502,P=0.240);各组豚鼠实验眼泪液分泌量与对照眼比较差异均无统计学意义(均P>0.05)。各组豚鼠双眼晶状体均透明,实验前后眼底均未见出血和渗出;HFST组实验眼ERG暗适应3.0 a波振幅值低于LFST组,差异有统计学意义(P<0.05),各组间实验眼ERG暗适应3.0 b波振幅总体比较差异无统计学意义(F=1.358,P=0.268);各组豚鼠实验眼与对照眼间ERG a、b波振幅比较差异均无统计学意义(均P>0.05);各组间豚鼠实验眼视网膜外核层厚度总体比较差异无统计学意义(F=0.952,P=0.463)。结论500 lx激光照射对眼表组织和晶状体无明显损伤,但一定程度上造成视网膜功能损害,损伤程度主要与激光照射频次有关。