Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.     

氧暴露剂量对人肺呼吸功能的影响

本文对８名受试者在０．２５～０．２７ＭＰａ下进行三种氧剂量暴露后的肺呼吸功能和Ｘ线胸片跟踪观察，目的在于验证整体实验功能结果对本室以往肺表面活性物质（ＰＳ）物理特性测定结果的符合性。结果表明，氧暴露剂量达到１０６０ＵＰＴＤ（肺型氧中毒剂量单位）时，对呼吸道粘膜、肺泡内皮细胞可产生一定程度影响，导致ＦＥＶ１、ＦＥＶ，％、ＭＭＦ、Ｖ１０（呼气流速）显著改变（Ｐ＜０．０５或Ｐ＜Ｏ．０１），但在停止暴露后４—１２ｈ内上述指标完全恢复。以上与本室以往ＰＳ物理特性测定结果相一致。本义肺活量降低程度较Ｗｒｉｇｈｔ（１９７２）报道的小，Ｘ线胸片无异常；因此，间断用氧要达到连续用氧的等效剂量，应对Ｗｒｉｇｈｔ计量法进行一些修正。     

呼气相胸片的识别研究

根据呼气相胸片中肺部区域灰度较高的特点，通过边缘提取和边缘跟踪确定胸部区域，运用最大类间方差方法确定图像分割的阈值．再提取出肺部区域，然后求出肺部的灰度均值。但这样的结果并不理想。于是在此基础上提出修正方案，即以肺部灰度均值和骨骼灰度均值的比值作为特征值．即比例法。此方法可以较客观的识别呼气相胸片。最后用类间距离对这两种方法进行了量化比较。     

复方苁蓉益智胶囊联合奥拉西坦治疗老年阿尔茨海默病的临床疗效

目的：分析复方苁蓉益智胶囊联合奥拉西坦治疗老年阿尔茨海默病的临床疗效。方法：选取2018年1月至2021年9月北京市隆福医院收治的148例老年阿尔茨海默病患者作为研究对象,采用随机数字表法简单随机化分为对照组和观察组,每组74例。对照组采用奥拉西坦胶囊进行治疗,观察组在对照组的基础上联合复方苁蓉益智胶囊治疗,均治疗3个月。比较2组患者临床疗效、氧化应激指标、炎症介质、病情严重程度、胆碱能神经递质水平、血液流变学指标及简易精神状态量表（MMSE）评分。结果：治疗后,观察组总有效率高于对照组（P<0.05）。与治疗前比较,治疗后2组患者血清超氧化物歧化酶（SOD）、乙酰胆碱（ACh）、胆碱酯酶（AChE）水平、MMSE及画钟试验评分、即刻记忆、回忆、注意力及计算力、地点定向力、时间定向力、语言评分升高,观察组高于对照组（均P<0.05）;2组患者血清丙二醛（MDA）、白细胞介素-1β（IL-1β）、核因子κB水平及临床痴呆量表（CDR）评分、全血高切黏度、全血低切黏度、红细胞聚集指数降低,观察组低于对照组（均P<0.05）。结论：复方苁蓉益智胶囊联合奥拉西坦可有效减轻老年阿尔茨海默病患者机体炎症反应和氧化应激反应,缓解患者病情进展,调节神经递质水平和血液流变学,改善其认知功能,具有较好的治疗效果。     

Direct Anterior Approach in Lateral Decubitus Position Versus Supine Position for Unilateral Total Hip Arthroplasty: A Comparative Study

ObjectiveTo compare the clinical efficacy of the direct anterior approach in lateral decubitus position (L‐DAA) and supine position (S‐DAA) for unilateral total hip arthroplasty.MethodsA retrospective study was conducted on 89 patients who underwent primary unilateral total hip arthroplasty in our department between August 2016 and December 2017. There were 46 patients who underwent L‐DAA and 43 patients who underwent S‐DAA. The body mass index (BMI), operation time, blood loss, preoperative Hb, first day and third day postoperative Hb, incision length, hospital stay, preoperative and postoperative Harris score, preoperative and postoperative visual analogue scale (VAS) score, radiological evaluation, intraoperative and postoperative complication, postoperative absolute length difference of lower extremity were recorded and analyzed. P < 0.05 was set as the significant difference.ResultsAll patients were followed up for 8–23 months, with an average of 15.6 months. No significant differences were found in preoperative and postoperative Harris scores, preoperative Hb, incision lengths, radiological evaluations, preoperative and postoperative VAS scores, and hospital stay (P > 0.05). However, significant differences were detected in BMI, blood loss, first day and third day postoperative Hb, and operation time (P < 0.05). There were no postoperative complications in the L‐DAA and S‐DAA groups. During the operation, two cases of proximal femoral fracture occurred in the L‐DAA group, four in the S‐DAA group, and the difference was statistically significant. There were significant differences found in the postoperative absolute length difference of lower extremity between the two groups.ConclusionCompared with the S‐DAA approach, the L‐DAA approach had the advantages of shorter operation time and less blood loss. Compared with S‐DAA, it was easier to expose the proximal femur, and lower BMI was required in L‐DAA. However, it was more difficult to compare the length of both lower extremities in the L‐DAA approach than in the S‐DAA approach.     

IgG抗体亲和力试验判定麻疹病例的价值

目的评价麻疹IgG抗体亲和力试验对判定麻疹病例的价值。方法以中国疾病预防控制信息系统2013-2015年天津市麻疹实验室确诊病例和麻疹排除病例为研究对象。回顾性追溯保存的病例血清,开展麻疹IgG抗体亲和力试验,重新对麻疹排除病例进行归类。结果共收集到326例麻疹病例血标本,其中实验室确诊病例267例,排除病例59例,≥20岁病例占92.33%(301/326)。麻疹IgG抗体亲和力试验显示,确诊病例和排除病例中麻疹IgG高亲和力抗体的比例分别为66.95%(158/236)和91.23%(52/57),差异有统计学意义(χ²⁼13.33,P<0.001)。根据判定标准,15.25%(9/59)排除病例被重新判定为麻疹病例,其中8例是高亲和力抗体,有含麻疹成分疫苗(MCV)免疫史,判定为继发性免疫失败病例;1例为低亲和力抗体,有典型的麻疹临床症状,无MCV免疫史。结论麻疹IgG抗体亲和力试验能够提供有参考意义的血清学证据,可以减少麻疹急性期血清学诊断中由于IgM抗体假阴性而造成的错误排除。     

工厂两级计算机系统之间的通讯

论述了IBM-PC及其兼容机之间的点点通讯,加装调制解调器通讯距离可达数公里。采用该技术可完成厂部与车间两级计算机系统的分级管理与控制。     

细胞间黏附因子1(Ⅰ区)模拟肽的筛选及初步鉴定

目的 筛选表达细胞间黏附因子1（ICAM－1）（Ⅰ区）模拟肽的特异噬菌体克隆,为研制抗脑型疟黏附肽类药物奠定基础。方法 以抗ICAM－1（Ⅰ区）的单抗15．2为靶,采用亲和筛选法对噬菌体随机十二肽库进行3轮筛选,通过ELISA及竞争抑制试验初步鉴定了获得的噬菌体短肽与单抗15．2之间的结合特性。结果 从第3轮洗脱液中挑选20个噬菌体克隆进行夹心法ELISA检测,其中18个克隆OD值超过阴性对照2．1倍以上,阳性率达90％。竞争性ELISA试验表明多数阳性噬菌体与ICAM－1能竞争性地与15．2单抗结合。结论 阳性噬菌体表达的短肽可能是15．2单抗所识别的模拟表位。Ⅰ     

Profiling the Tox21 Chemical Collection for Acetylcholinesterase Inhibition

Background: Inhibition of acetylcholinesterase (AChE), a biomarker of organophosphorous and carbamate exposure in environmental and occupational human health, has been commonly used to identify potential safety liabilities. So far, many environmental chemicals, including drug candidates, food additives, and industrial chemicals, have not been thoroughly evaluated for their inhibitory effects on AChE activity. AChE inhibitors can have therapeutic applications (e.g., tacrine and donepezil) or neurotoxic consequences (e.g., insecticides and nerve agents).Objectives: The objective of the current study was to identify environmental chemicals that inhibit AChE activity using in vitro and in silico models.Methods: To identify AChE inhibitors rapidly and efficiently, we have screened the Toxicology in the 21st Century (Tox21) 10K compound library in a quantitative high-throughput screening (qHTS) platform by using the homogenous cell-based AChE inhibition assay and enzyme-based AChE inhibition assays (with or without microsomes). AChE inhibitors identified from the primary screening were further tested in monolayer or spheroid formed by SH-SY5Y and neural stem cell models. The inhibition and binding modes of these identified compounds were studied with time-dependent enzyme-based AChE inhibition assay and molecular docking, respectively.Results: A group of known AChE inhibitors, such as donepezil, ambenonium dichloride, and tacrine hydrochloride, as well as many previously unreported AChE inhibitors, such as chelerythrine chloride and cilostazol, were identified in this study. Many of these compounds, such as pyrazophos, phosalone, and triazophos, needed metabolic activation. This study identified both reversible (e.g., donepezil and tacrine) and irreversible inhibitors (e.g., chlorpyrifos and bromophos-ethyl). Molecular docking analyses were performed to explain the relative inhibitory potency of selected compounds.Conclusions: Our tiered qHTS approach allowed us to generate a robust and reliable data set to evaluate large sets of environmental compounds for their AChE inhibitory activity. https://doi.org/10.1289/EHP6993