Gastroprotection induced by capsaicin in healthy human subjects

AIM： To evaluate the gastro-protective effect of capsaicin against the ethanol- and indomethacin （IND）-induced gastric mucosal damage in healthy human subjects. METHODS： The effects of small doses （1-8 μg/mL, 100 mL） of capsaicin on the gastric acid secretion basal acid output （BAO） and its electrolyte concentration, gastric transmucosal potential difference （GTPD）, ethanol- （5 mL 300 mL/L i.g.） and IND- （3×25 mg/d） induced gastric mucosal damage were tested in a randomized, prospective study of 84 healthy human subjects. The possible role of desensitization of capsaicin-sensitive afferents was tested by repeated exposures and during a prolonged treatment. RESULTS： Intragastric application of capsaicin decreased the BAO and enhanced “non-parietal” component, GTPD in a dose-dependent manner. The decrease of GTPD evoked by ethanol was inhibited by the capsaicin application, which was reproducible. Gastric microbleeding induced by IND was inhibited by co-administration with capsaicin, but was not influenced by two weeks pretreatment with a daily capsaicin dose of 3×400μg i.g. CONCLUSION： Capsaicin in low concentration range protects against gastric injuries induced by ethanol or IND, which is attributed to stimulation of the sensory nerve endings.

Comparison of point and two-dimensional shear wave elastography of the spleen in healthy subjects

BACKGROUND Few systematic comparative studies of the different methods of physical elastography of the spleen are currently available.AIM To compare point shear wave and two-dimensional elastography of the spleen considering the anatomical location(upper,hilar,and lower pole).METHODS As part of a prospective clinical study,healthy volunteers were examined for splenic elasticity using four different ultrasound devices between May 2015 and April 2017.The devices used for point shear wave elastography were from Siemens(S 3000)and Philips(Epiq 7),and those used for two-dimensional shear wave elastography were from GE(Logiq E9)and Toshiba(Aplio 500).In addition,two different software versions(5.0 and 6.0)were evaluated for the Toshiba ultrasound device(Aplio 500).The study consisted of three arms:A,B,and C.RESULTS In study arm A,200 subjects were evaluated(78 males and 122 females,mean age 27.9±8.1 years).In study arm B,113 subjects were evaluated(38 men and 75 women,mean age 26.0±6.3 years).In study arm C,44 subjects were enrolled.A significant correlation of the shear wave velocities at the upper third of the spleen(r=0.33088,P<0.0001)was demonstrated only for the Philips Epiq 7 device compared to the Siemens Acuson S 3000.In comparisons of the other ultrasound devices(GE,Siemens,Toshiba),no comparable results could be obtained for any anatomical position of the spleen.The influencing factors age,gender,and body mass index did not show a clear correlation with the measured shear wave velocities.CONCLUSION The absolute values of the shear wave elastography measurements of the spleen and the two different elastography methods are not comparable between different manufacturers or models.

Safety, Tolerability, and Pharmacokinetics of E3030, a Novel Peroxisome Proliferator-Activated Receptor <i>α/γ</i>Dual Agonist, in Healthy Japanese Male Subjects

Objective: The objectives of the present study were to evaluate the safety of single oral dose E3030 in healthy Japanese male subjects, and to evaluate pharmacokinetics after single oral dose E3030 and food effect on pharmacokinetic profiles. Methods: This study was conducted in a randomized, double-blind, placebo-controlled, ascending single-dose study in 56 healthy Japanese male subjects. Subjects were orally administered E3030 (0.5-40 mg) or placebo. Results: Six of 42 (14%) subjects’ administered E3030 experienced adverse events;however, all adverse events were mild and transient, and there was no dose-dependent increase in any adverse event. Plasma samples were collected over 96 hours after dosing. After administration in the fasted state, Cmax of E3030 was achieved between 1.00 and 1.75 hours, indicating rapid absorption. Both Cmax and AUC were dose-proportional in the range of 0.5 to 40 mg. The average range of elimination half-life was 18.4-23.8 hr. CL/F and Vz/F also remained nearly constant regardless of dose levels. In addition, food effect was exploratorily evaluated in five subjects of administered E3030 (10 mg) in both fasted and fed states. The fed/fasted ratios for the geometric mean of the Cmax and AUC were 0.803 and 0.913, respectively. Conclusion: E3030 was safe and well tolerated at single doses up to 40 mg. The pharmacokinetic profile showed good linearity, and food effect on pharmacokinetics of E3030 was not significant.

Glycemic Index of a Diabetes-Specific Nutritional Powder: An Open-Label Study in Healthy Indian Adults

Background: A balanced diet with a low glycemic index (GI) plays an important role in controlling and managing type 2 diabetes mellitus (T2DM). Here, we compared the GI of 2 flavors (vanilla and chocolate) of diabetes-specific nutritional (DSN) supplements to its comparator in healthy Indian adults under fasting conditions. Methods: This study was a 39-day open-label, non-comparative, single-center trial involving healthy adults aged between 18 to 45 years. The subjects received equal doses of 2 DSN powder (Treatments A and B), the comparator product (Treatment C), and dextrose monohydrate as a reference (Treatment R). Doses were administered as per the dosing schedule, after an overnight fast for 10 hours, with 2 intervening non-dosing days. Blood samples were collected on the dosing days to assess changes in capillary blood glucose levels. The primary endpoint of the study was the mean GI of Treatments A, B, and C (Defined as low: GI ≤ 55;medium: 55 GI ≤ 70;High: GI > 70), generated using the incremental area under the curve (AUCi) methodology. Safety was assessed throughout the study. Values of all study parameters were represented in ±SD or standard deviation. Results: Fourteen adult male subjects with a mean age of 29.42 ± 4.46 years, and a body mass index of 22.0 ± 1.95 Kg/m2, were enrolled in the study. The mean AUCi for treatments A, B, and C were 104 ± 10, 111 ± 12, and 87 ± 12 mmol min/L, respectively and for Treatment R it was 276 ± 16, 319 ± 28 and 338 ± 25 mmol min/L for Days 1, 6 and 8, respectively. The mean GI of Treatment A was 33 ± 3, Treatment B was 35 ± 3 and Treatment C was 29 ± 5;all GI means were ≤55. Mild adverse events were reported in 2 (14.3%) subjects. No serious adverse events or deaths were reported in the study. All treatments were well tolerated by the subjects. Conclusion: The glycemic index of both test products and comparator was low (i.e., GI 55) as per ISO 26642:2010 standard.

吡嘧司特钾片在中国健康志愿者空腹/餐后的生物等效性研究

目的比较单次空腹与餐后条件下吡嘧司特钾片在中国健康受试者体内的药代动力学,评价受试制剂(T)和参比制剂(R)的生物等效性。方法采用随机、开放、单剂量、两周期、双交叉生物等效性试验设计,空腹组与餐后组各入组26名与30名受试者,每周期在空腹状态或餐后状态下服用受试制剂与参比制剂10 mg,在给药周期前后按设计的时间点采集静脉血。用高效液相质谱联用法(LC-MS/MS)测定血浆中的吡嘧司特钾浓度,用Phoenix TM WinNonlin(8.3)软件计算药代动力学参数,对两制剂进行生物等效性分析。结果空腹单次口服给药受试制剂和参比制剂的t 1/2分别为(4.44±0.91)h和(4.49±0.93)h,t max中位数分别为(1.96±1.29)h和(2.18±1.25)h,C max分别为(867.12±205.56)μg·L^(-1)和(863.35±172.03)μg·L^(-1),AUC 0-t分别为(5513.23±1463.67)h·μg·L^(-1)和(5661.32±1628.65)h·μg·L^(-1),AUC 0-∞分别为(5699.81±1477.68)h·μg·L^(-1)和(5849.44±1644.75)h·μg·L^(-1);受试者的主要药代动力学参数C max、AUC 0-t、AUC 0-∞的90%置信区间的统计结果分别为92.49%~107.53%、94.71%~100.67%和95.28%~100.27%,均在80.00%~125.00%范围内,空腹口服受试制剂与参比制剂安全性良好;餐后单次口服给药受试制剂和参比制剂的t 1/2分别为(4.46±0.78)h和(4.51±0.84)h,t max中位数分别为(3.08±1.36)h和(3.28±1.28)h,C max分别为(683.83±111.87)μg·L^(-1)和(689.77±110.24)μg·L^(-1),AUC 0-t分别为(5695.99±1566.05)h·μg·L^(-1)和(5773.60±1551.04)h·μg·L^(-1),AUC 0-∞分别为(5914.06±1551.86)h·μg·L^(-1)和(5967.30±1552.89)h·μg·L^(-1);C max、AUC 0-t、AUC 0-∞的90%置信区间统计结果分别为93.56%~104.69%、96.43%~100.83%和97.29%~101.14%,均在80.00%~125.00%范围内,餐后口服受试制剂与参比制剂安全性良好。结论在空腹与餐后的单次口服给药条件下,两种吡嘧司特钾片具有较好的生物等效性。

药物临床试验健康受试者筛选及给药后安全性评价吉林共识(2023版)

受试者筛选和安全性评价均是药物临床试验质量保证的重要环节,是否能筛选到足够符合要求的受试者并对受试者进行客观、科学的安全性评价与分析是关系到临床试验能否顺利进行,并得出科学结论的关键影响因素。目前,两者均在实际工作中面临较大挑战。一是在纳入健康受试者的临床试验中,健康受试者并无明确入排标准界定,各家判断不一。二是受试者的安全性评价及分析存在尺度不一、主观性大等问题,缺乏指导性的规则和方法。为规范和帮助药物临床试验中对受试者筛选及给药后安全性评价与分析工作,吉林省药理学会临床药理学专业委员会撰写了本共识,旨在更好地指导纳入受试者和评价分析药物对受试者的安全性。

早期药物临床试验中健康受试者管理的 常见问题与对策

早期药物临床试验常以健康受试者为试验对象,与患者参与试验动机不同,健康受试者多以快速获得报酬为目的,且年龄、背景均与患者群体存在较大差异,因此试验期间对健康受试者的管理工作与患者也存在明显不同。本研究以健康受试者参加早期药物临床试验的全流程为主线,罗列从筛选、住院、出院等各个环节发现的真实问题,结合同行在该领域期刊公开发表的论文及笔者实际工作经验,分析探讨具体的原因及应对方法,为早期药物临床试验中健康受试者的管理工作提供参考,以更好地遵守药物临床试验质量管理规范,保障受试者的权益和安全、保证数据和结果的科学、真实,促进试验顺利进行。

北京某三甲医院2012—2023年健康体检人群空腹血糖变化趋势分析

目的分析2012—2023年北京某三甲医院健康体检人群空腹血糖(FPG)的变化趋势。方法收集2012—2023年中国人民解放军总医院第二医学中心33600名健康体检者的FPG检测结果。以FPG≥6.1 mmol·L^(–1)为异常。按年龄(18~30岁、31~40岁、41~50岁和51~60岁)和性别分别分组。采用线性回归分析评估FPG与年份之间的关系,采用趋势χ2检验分析FPG异常率与年份之间的关系。结果2012—2023年,18~30岁组、31~40岁组、51~60岁组FPG水平和异常率均与年份呈线性关系(P<0.05),随年份呈上升趋势。除2022年和2023年18~30岁组FPG水平和异常率稍高于31~40岁组(P>0.05)外,其他年份各年龄组之间FPG水平和异常率差异均有统计学意义(P<0.05),且随年龄的增高,FPG水平和异常率均逐渐升高。相对于2012年,2023年各年龄组FPG异常人数和异常率增长情况为51~60岁组>18~30岁组>31~40岁组>41~50岁组。各年龄组男性FPG水平和异常率均高于同年龄组女性(P<0.01),且男性、女性FPG水平和异常率均随年龄的增加而升高。结论2012—2023年中国人民解放军总医院第二医学中心健康体检人群FPG水平和异常率均呈上升趋势,且男性高于女性,呈现年轻化趋势。

中老年人5年内主观认知下降进展的危险因素:一项基于CHARLS的病例对照研究

目的探讨中老年人5 a内主观认知下降(SCD)进展的影响因素。方法选取2011—2018年中国健康与退休纵向研究(CHARLS)数据库中SCD人群为研究对象,根据5 a随访后的自身前后认知评分改变评估分为SCD进展组和SCD非进展组,使用1∶1倾向性评分匹配方法控制一般资料,匹配后的人群采用Logistic回归模型,分析SCD进展的影响因素。结果基线检查时报告3864例SCD中,258例SCD进展(6.68%);匹配前2组性别、BMI、教育水平、吸烟、CES-D 10得分、就餐模式、舒张压、平衡测试、握力、CRP水平差异有统计学意义;将匹配后2组比较中P<0.1的变量纳入Logistic回归分析,纳入CES-D 10得分(χ^(2)=2.494,P=0.01)、舒张压(Z=11.946,P=0.10)、平衡测试(Z=3.853,P=0.06)、CRP水平(Z=-1.646,P=0.10),结果显示CES-D 10得分(P=0.01,OR=1.092,95%CI:1.019~1.171)以及平衡测试(P=0.03,OR=0.643,95%CI:0.427~0.967)可能是SCD人群5 a后进展的危险因素。结论更高的CES-D 10得分及不能完成平衡测试对SCD人群短期发生认知障碍进展有不利影响。

老年人小腿围、HCAR与认知障碍的因果中介分析--基于CLHLS2014数据

目的探究小腿围与认知障碍的关系及超敏C反应蛋白/白蛋白比值(hypersensitive C-reactive protein/albumin ratio,HCAR)的中介作用。方法筛选2014年CLHLS数据库中的1784例老年人数据。通过中文版简易精神状态量表(Chinese version of the brief mental state examination,cMMSE)评估认知功能。使用R软件进行数据处理和分析,Bootstrap抽样法验证中介效应。结果校正多种协变量后,小腿围与认知障碍呈显著负相关(OR=0.951,95%CI:0.933~0.970),HCAR在其中起到中介作用(中介效应比例为0.022,95%CI:0.002~0.060)。结论小腿围与认知障碍之间存在负关联,HCAR起中介作用。该发现对预防和干预认知障碍有重要意义。

The Prevalence of Metabolic Syndrome in an Apparently Healthy, Normotensive and Non-Diabetic Population in Saudi Arabia by Two Definitions: Implications for Local Practice

Objectives: We aimed to 1) investigate the prevalence of MS in apparently healthy, non-hypertensive non-diabetic individuals living in Jeddah using the IDF and the NCEP-ATP III criteria to test for agreement in classification, and to determine the characteristics of subjects identified by either definition, and 2) examine the significance of family medical history and life style habits. Methods: 557 apparently healthy individuals aged 18 - 50 y were randomly approached in Jeddah health centres. 412 agreed to participate, while 55 were excluded because they were found to be frankly hypertensive and/or diabetic. Finally, 357 apparently healthy subjects with no hypertension or diabetes were fully studied. Anthropometric and demographic information were collected. Insulin, glucose, and lipid profile were obtained in fasting blood samples. Individuals were identified using the two definitions of metabolic syndrome, and their characteristics were compared statistically to the rest of the population. Results: Of the 233 subjects fulfilling the inclusion criteria, 44 and 39 (18.9% and 16.7%) were identified as having MS by the IDF or ATPIII definitions, respectively. The most common characteristic was central obesity using the IDF definition, and low HDL-cholesterol using the NCEP-ATP III definition. As expected from our exclusion criteria, the least common feature was high blood pressure in both cases. There was no significant difference between subgroups with and without MS with regard to smoking, exercise, and family history of disease. Regression analysis indicated the strongest predictors of MS were: blood glucose, LDL-C/HDL-C ratio and plasma insulin using the NCEP-ATPIII definition, and blood glucose, Waist /Hip ratio and plasma atherogenic index (PAI) using the IDF definition. Conclusions: In the absence of local cut-off thresholds for waist circumference, subjects might escape diagnosis using the IDF definition. The use of waist/Hip ratio, LDL-C: HDL-C, PAI and circulating insulin help with the diagnosis.

Ⅰ期临床试验中健康受试者筛选失败原因及影响因素分析

目的分析Ⅰ期临床试验(PhaseⅠclinical trial,PⅠCT)中健康受试者(healthy subject,HS)筛选失败(screening failure,SF)的原因及影响因素,为今后PⅠCT中HS筛选提供参考。方法对上海市公共卫生临床中心在2016年6月—2020年9月期间完成的PⅠCT的HS筛选进行回顾性研究,统计不合格例次构成比及发生率,分析人口学信息及筛选步骤设置对筛选合格率(eligibility rate,ER)的影响。结果共纳入58项PⅠCT,从12028例受试者中筛选出3315例合格HS,ER 27.6%;不合格例次占比最高的是实验室检查(47.2%),其次是生命体征(vital sign,VS)、辅助检查和人口学信息。筛选过程中纳入烟碱测试(P=0.003)、胸片(P=0.025)或腹部B超检查(P=0.002)对ER有显著影响。结论PⅠCT中HS筛选失败的主要原因是实验室检查,其次是VS、辅助检查和人口学信息不合格;HS筛选过程中增加烟碱测试、胸片或腹部B超可使ER降低。

健康中国建设背景下我国居民进行体育锻炼影响其主观幸福感的实证研究:基于CGSS的相关数据分析

在健康中国建设背景下,采用2012—2018年中国综合社会调查项目的相关数据,探究了我国居民体育锻炼、未来医疗支付保障对其主观幸福感的作用机制及对其健康水平的调节作用,并从城乡、学历、性别等层面进行了异质性分析。经研究发现:受访居民进行体育锻炼能显著增强自身的主观幸福感。受访居民进行体育锻炼可以通过减少对未来医疗支出风险的担忧和消除预防性储蓄动机增强主观幸福感。受访居民当前的健康水平影响其对未来医疗支出的判断,能强化其进行体育锻炼对自身主观幸福感的影响。体育锻炼对乡村受访居民、低学历受访居民及女性受访居民的主观幸福感的增强作用更为显著。

对健康人、冠心病与缺血性中风病人的血液滞后环、触变性与黏弹性的研究

这是一篇源自英文文献[1]、[2]的译文,拟介绍了血液滞后环、触变性与黏弹性的研究方法,并对健康人、冠心病与缺血性中风病人的研究结果作了比较。

健康老龄化理念下老年人幸福感的影响因素及其实现途径——基于CHARLS数据的实证分析

根据中国健康与养老追踪调查(CHARLS)2018年全国基线调查数据,通过二项logistic回归模型对被解释变量进行回归分析发现,老年人主观幸福感受多种因素的影响,其中婚姻状况、健康状况、身体疼痛程度、年经济收入、有无保险等因素对其的主观幸福感具有显著的正向或负向影响,性别、年龄、教育水平、慢性病情况对其的主观幸福感影响不显著。政府相关部门应在政策上向老年人倾斜,为其提供增加经济收入的工作机会及更多的社会保障与福利;相关社会组织应在健康、理财、生活等方面为老年人提供更多的关爱与支持等,这将有助于提升老年人的养老质量与幸福感,促进社会的和谐发展。

健康城市参与度在成人心理健康与主观幸福感间的中介效应分析

目的 探讨健康城市参与度在心理健康相关状况(包括失眠、焦虑和抑郁)与主观幸福感间的中介效应。方法 采用一般资料问卷、阿森斯失眠量表、广泛性焦虑量表、10项流调中心抑郁量表、健康城市参与度问卷以及世界卫生组织幸福感指数量表,于2020年9月对南京市溧水区1031例常住成年居民进行调查。运用回归模型和中介检验分析健康城市参与度在心理健康与主观幸福感间的中介效应。结果 失眠、焦虑和抑郁均与健康城市参与度、主观幸福感呈显著负相关(r<0,P<0.05),而健康城市参与度与主观幸福感则呈显著正相关(r=0.258,P<0.001)。健康城市参与度在失眠与主观幸福感间以及焦虑与主观幸福感间存在显著的中介效应,在控制所有潜在混杂变量后,其中介效应值分别为-0.036(95%CI:-0.057~-0.015)和-0.025(95%CI:-0.047~-0.004),中介效应占比分别为4.98%和3.65%。控制了性别、年龄、婚姻、教育、收入和职业后,健康城市参与度在抑郁与主观幸福感关系间的中介效应具有统计学意义(间接效应值=-0.022,P<0.05;中介占比3.58%)。结论 健康城市参与度在心理健康相关状况与主观幸福感间起部分中介效应。本研究提示促进居民心理健康水平和提升其健康城市参与度,对于改善个体主观幸福感具有现实意义。

中国健康受试者中特拉唑嗪的安全性分析

目的研究仿制盐酸特拉唑嗪胶囊与原研盐酸特拉唑嗪胶囊在中国健康受试者中的安全性,探讨用药后不良事件的影响因素。方法68例健康受试者,分为空腹、餐后各34例,分别于空腹、餐后状态下单次口服仿制药或原研药盐酸特拉唑嗪2 mg后进行随机、开放、两周期、双交叉试验。收集试验期间发生的所有不良事件(AE),分析与药物相关不良事件(CAE)的构成比与发生率,比较空腹或餐后状态下、服用仿制药或原研药受试者发生CAE的差异。结果有41例受试者(60.29%)发生100例次CAE。其中,33例受试者(48.53%)服用仿制药后发生50例次CAE,24例受试者(35.29%)服用原研药后发生50例次CAE。发生率≥10%的CAE依次为:低血压(38.24%)、头晕(16.18%)与脉搏增快(14.71%)。与原研药相比,仿制药空腹或餐后状态下给药后发生各类CAE的发生时间、持续时间比较,差异无统计学意义(P>0.05)。与空腹试验组相比,服用仿制药或原研药的受试者在餐后试验组发生低血压事件后的持续时间延长(P<0.05);服用仿制药的受试者在餐后试验组发生脉搏增快事件的时间缩短(P<0.05)。结论人体生物等效性试验中的不良事件主要来源于药物本身的安全性风险,食物可能影响特拉唑嗪的药物安全性。

我国城镇居民健康生活方式与主观幸福感的关系:体育锻炼和健康状态的链式中介作用

目的:探讨我国城镇居民健康生活方式、主观幸福感、体育锻炼及健康状态之间的关系。方法:基于2017年中国综合社会调查(CGSS)实证,累计对12582名城镇居民的调查数据进行分析。结果:我国居民健康生活方式与体育锻炼、健康状态、主观幸福感两两间均存在显著相关(r=0.020,0.022,0.286;P<0.01);体育锻炼和健康状态在健康生活方式与主观幸福感之间发挥中介作用(P<0.01);体育锻炼和健康状态在健康生活方式与主观幸福感之间发挥链式中介作用(P<0.01)。结论:健康生活方式不仅直接影响城镇居民的主观幸福感,而且还可以通过体育锻炼和健康状态间接影响居民的主观幸福感。

经口吸入制剂在中国健康受试者生物等效性试验中的安全性分析

目的:探讨无锡市人民医院Ⅰ期临床研究中心开展的经口吸入制剂(OIDPs)生物等效性试验的安全性。方法:收集2017-2022年在无锡人民医院参加20项OIDPs生物等效性试验的482例健康受试者的安全性数据,比较受试制剂和参比制剂发生不良事件(AE)的差异性,以及性别、年龄、作用机制、装置类型对AE的影响。结果:77例受试者(16.0%,77/482)共发生AE 102例次,与试验药物相关AE 87例次,均属于轻、中度,无严重不良事件发生。受试制剂和参比制剂的药物相关AE发生率并无差异,性别、年龄、药物作用机制和装置类型对AE发生也无明显影响。结论:在20项OIDPs生物等效性试验中,健康受试者用药后安全性、耐受性良好,且OIDPs仿制药和原研药的安全性特征基本相似。

社区建成环境对老年人身心健康的影响路径分析——基于江浙皖3个城市的比较研究

我国人口老龄化现象正在进一步加剧,老年群体的健康问题值得关注,而目前社区建成环境成为干预其健康的重要着力点。以江浙皖地区内3个典型城市为例,利用Arc GIS空间分析获取老年人日常生活圈内的客观建成环境并以此作为地理背景,以“客观建成环境—个体感知—体力/休闲活动—健康”为路径构建结构方程模型,分析3个城市老年人健康的受影响机制并比较异同。结果发现,3个城市有相同的影响路径和不同的影响机制。南京市客观建成环境通过影响老年人主观建成环境感知间接影响休闲活动强度,进而影响心理健康;合肥市客观建成环境通过影响老年人主观建成环境感知间接影响体力活动强度,进而影响生理健康;嘉兴市客观建成环境通过影响老年人主观建成环境感知间接影响休闲活动强度,进而影响生理健康。基于研究结果,进一步验证主观感知和个体活动强度起到的中介效应,以期为建设老年友好社区提供相关建议。