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.     

骨形态发生蛋白2及碱性成纤维生长因子2对大鼠骨髓间充质干细胞膜片增殖和成骨分化的影响

文题释义： 细胞膜片技术：是在体外接种培养高密度的细胞，使其相互融合生长至100%而形成的透明致密膜状物。该技术不需要胰酶消化即可收集细胞，因此保留了大量的胞外基质、细胞间连接以及细胞-基质连接等结构。目前细胞膜片技术已成为组织工程领域的研究热点，已被推广应用于牙周膜、角膜、心脏、软骨、食管等多种组织器官修复。 成骨细胞：主要由内外骨膜和间充质始祖细胞分化而来，在复杂的骨形成过程中发挥着主要的功能，承担着骨基质的合成、分泌和矿化。骨髓间充质干细胞具有多向分化潜能，能定向分化为成骨细胞，其成骨分化过程可受多种因素的影响，如细胞因子的调控、遗传因素和激素水平等。背景：现阶段骨形态发生蛋白2和碱性成纤维生长因子2对骨髓间充质干细胞膜片增殖、成骨分化的影响和作用机制还尚未可知，如何将生长因子与组织工程细胞膜片技术相整合，最终将其用于骨缺损修复具有重要意义。 目的：探讨单独及联合应用骨形态发生蛋白2和碱性成纤维生长因子2对骨髓间充质干细胞膜片增殖和成骨分化的影响。 方法：体外分离培养鉴定SD大鼠骨髓间充质干细胞并构建细胞膜片，选用不同质量浓度的骨形态发生蛋白2和碱性成纤维生长因子2单独及联合诱导骨髓间充质干细胞膜片，CCK-8法结合碱性磷酸酶活性检测确定2种因子促进膜片增殖和成骨分化的最佳有效质量浓度；然后对骨髓间充质干细胞膜片进行成骨诱导，通过大体及显微镜观察、Vonkossa染色、茜素红染色、RT-PCR检测相关成骨标志物来评估诱导效果。 结果与结论：单独应用骨形态发生蛋白2可增强骨髓间充质干细胞膜片的碱性磷酸酶活性，最佳质量浓度为100 μg/L(P < 0.001)，单独应用碱性成纤维生长因子2能加速骨髓间充质干细胞膜片的增殖，最佳质量浓度为20 μg/L(P < 0.001)，而联合应用既可以促进膜片增殖又能提高其碱性磷酸酶活性(P < 0.001)；经成骨诱导后，4组膜片在形态学上无明显差异，均能诱导骨髓间充质干细胞膜片的成骨分化，其中联合组钙结节最明显(P < 0.001)，可显著促进膜片晚期成骨分化并抑制其早期成骨分化，具有明显的协同促进作用(P < 0.001)。结果表明，骨形态发生蛋白2和碱性成纤维生长因子2联合应用时具有协同作用，既可以促进骨髓间充质干细胞膜片增殖，又能显著增强其成骨诱导能力。ORCID: 0000-0003-1918-579X(何惠宇) 中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程     

Hypocholesterolaemic mechanism of bitter melon aqueous extracts via inhibition of pancreatic cholesterol esterase and reduction of cholesterol micellar solubility

This study investigated the hypocholesterolaemic effects of bitter melon aqueous extracts (BMAE) in vitro, the inhibitory effects of BMAE on pancreatic cholesterol esterase (CEase) and incorporation of cholesterol into micelles were investigated. BMAE decreased the in vitro micellar solubility of cholesterol in a dose-dependent manner. The conformation of CEase was investigated by means of circular dichroism (CD) and fluorescence. The result revealed the decrease of α-helix contents, increase of β-sheet and exposure of aromatic amino acid residuals. The incorporation of cholesterol into micelles was inhibited by BMAE. A complex was observed by transmission electron microscopy (TEM), which indicated interaction between cholesterol and BMAE. The result revealed that BMAE can play a role in decreased intestinal cholesterol absorption via inhibition of CEase, and of micelle formation.     

早发型子痫前期应用低分子肝素期待治疗的临床效果分析

目的分析早发型子痫前期应用低分子肝素期待治疗的临床效果。方法回顾分析2017-01—2018-12间在郑州大学第一附属医院产科终止妊娠的95例早发型子痫前期患者的临床资料。按终止妊娠前是否应用低分子肝素分为2组。对照组(47例)给予降压、解痉等治疗;观察组(48例)在对照组基础上加用低分子肝素。结果2组分娩孕周、妊娠延长时间、妊娠并发症发生率、新生儿出生体质量、新生儿窒息及胎儿宫内窘迫发生率、新生儿Apgar评分等,差异均无统计学意义(P>0.05)。结论对早发型子痫前期患者在常规治疗基础上短期应用低分子肝素,不能延长妊娠时间,不改善母婴结局。     

竹林区村庄白纹伊蚊孳生特点的调查

白纹伊蚊在竹林里孳生的阳性比为75.4%;而在竹林包围的居民区阳性比为15.3%。白纹伊蚊在居民区孳生密度布雷图指数为19.4,容器指数为6.2%。居民区孳生蚊虫的主要场所是泡菜坛,泡菜坛主要孳生蚊种是骚扰阿蚊,阳性比为73.7%,其次是淡色库蚊为20.2%,贪食库蚊为14.0%,白纹伊蚊最低,为9.1%。     

Changes in T .lymphocyte subsets after severe traumatic brain inJury

BACKGROUND： Besides local changes of cranial parenchymal cells, hemorrhage, etc., severe traumatic brain injuries also cause the changes of total body fluid and various functions, and the changes of lymphocytes and T lymphocyte subsets should be paid more attention to. OBJECTIVE： To reveal the changing laws of T lymphocyte subsets after severe traumatic brain injury, and compare with mild to moderate brain injury. DESIGN： A comparative observation. SETTINGS： Department of Neurosurgery, Longgang District Buji People＇s Hospital of Shenzhen City; Central Laboratory of Shenzhen Hospital of Prevention and Cure for Chronic Disease. PARTICIPANTS： All the subjects were selected from the Department of Neurosurgery, Longgang District Buji People＇s Hospital of Shenzhen City from August 2002 to August 2005. Thirty patients with severe brain injury, whose Glasgow coma score （GCS） was ≤ 8 points, were taken as the experimental group, including 21 males and 9 females, aging 16 - 62 years. Meanwhile, 30 patients with mild traumatic brain injury were taken as the control group （GCS ranged 14- 15 points）, including 18 males and 12 females, aging 15 -58 years. All the subjects were in admission at 6 hours after injury, without disease of major organs before injury Informed consents were obtained from all the patients or their relatives. METHODS： （1） The T lymphocytes and the subsets in peripheral blood were detected with immunofluorescent tricolor flow cytometry at l, 3, 7 and 14 days after injury in both groups. （2） The conditions of pulmonary infections were observed at 4 days after injury. The differences of measurement data were compared with the t test. MAIN OUTCOME MEASURES： Changes of T lymphocytes subsets at 1 - 14 days after severe and mild or moderate traumatic injury. RESULTS： Finally, 28 and 25 patients with mild to moderate traumatic brain injury, whereas 25 and 21 patients with severe traumatic brain injury were analyzed at 7 and 14 days respectively, and the missed ones died due to the development of disease. （1） Changes of T lymphocyte subsets： At 1 and 3 days after injury, CD3, CD4, CD8, CD4/CD8 began to decrease, whereas CD8 increased in the experimental group, which were very significantly different from those in the control group （t =2.77 - 3.26, P 〈 0.01）, and began to recover at 7 days, which were significantly different from those in the control group （t = 2.06 - 2.24, P 〈 0.05）, and generally recovered to the normal levels at 14 days （P 〉 0.05）. （2） Conditions of pulmonary infections： At 4 days after injury, the rate of pulmonary infection was significantly different between the experimental group and control group [73% （22/30）, 0, x2=37.29, P 〈 0.01]. CONCLUSION： Patients with severe traumatic brain injury suffer from damages of cellular immune function at early period （within 7 days）, and they are easily to be accompanied by pulmonary infections.     

Liposome-mediated transfer of vascular endothelial growth factor cDNA augments survival of random-pattern skin flaps in the rat.

Tissue engineering is an application for gene therapy that is in its infancy. We show that simple liposomal-mediated gene transfer could result in a potentially useful biological effect in the field of wound healing. cDNA encoding the 165 amino acid form of vascular endothelial growth factor complexed to commercially available liposomes was injected into rat skin 1 week before raising a random pattern 3 x 10 cm flap. The flap survival was enhanced by 14 percent, and was accomplished without accessing the arterial inflow of the territory. These results were statistically significant (p<0.002) and reproducible. No adverse effects were seen. Histological analysis of the angiogenesis localized much of the new vessel formation to the area around the hair follicles. Polymerase chain reaction amplification of extracted flap tissue confirmed the presence of the transgene.