ObjectiveTo further evaluate the relation between usage of proton pump inhibitor (PPI) and the risk of pancreatic cancer. MethodThe observational studies were systematically searched in the databases of PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, CNKI, Wanfang, and VIP. The combined odds ratio (OR) and 95% confidence interval (CI) of pancreatic cancer risk were estimated by the corresponding effect model according to the heterogeneous results, and the subgroup analysis, meta-regression, and sensitivity analysis were performed. In addition, the relation between the defined daily dose (DDD) and usage time of PPI and the pancreatic cancer risk were studied by using restricted cubic spline. ResultsA total of 14 studies were included, including 1 601 430 subjects. The meta-analysis result showed that usage of PPI was positively correlated with the risk of pancreatic cancer [I2=98.9%, OR (95%CI)=1.60 (1.21, 2.11), P<0.001]. The subgroup analysis results showed that usage of PPI would increase the risk of pancreatic cancer in the subgroups of literature published before 2018 [OR (95%CI)=1.88 (1.05, 3.38), P=0.034], non-Asian regions [OR (95%CI)=1.37 (1.04, 1.82), P=0.028], case-control studies [OR (95%CI)=1.59 (1.16, 2.18), P=0.004], cohort studies [OR (95%CI)=1.65 (1.13, 2.39), P=0.009], and high-quality studies [OR (95%CI)=1.62 (1.19, 2.20), P=0.002]. The dose-response curve showed that there was a nonlinear relation between the usage of PPI and the risk of pancreatic cancer (χ2linear=2.27, P=0.132; Pnonlinear=0.039). When the usage of PPI was 800 DDD or less, usage of PPI would increase the risk of pancreatic cancer, but there was no statistical significance when the usage of PPI was more than 800 DDD. The time-effect curve showed that there was a linear relation between the usage time of PPI and the risk of pancreatic cancer (χ2linear=6.92, P=0.009), and the risk of pancreatic cancer would increase by 2.3% if the usage of PPI increased by one month [OR=1.02, 95%CI (1.01, 1.04), P=0.009]. The sensitivity analysis confirmed that the results were stable by gradually eliminating each study, the OR (95%CI) of the risk of pancreatic cancer was 1.37 (1.08, 1.74) to 1.66 (1.22, 2.27), and the publication bias was not found by Egger test (P=0.594).ConclusionsFrom the results of this meta-analysis, usage of PPI will increase the risk of pancreatic cancer, and the dosage of PPI and usage time of PPI may be related to the risk of pancreatic cancer. The clinical usage of PPI should be strictly controlled, and the dosage and usage time should also be carefully considered.
目的 分析上海市奉贤区中心医院2008年－2010年门、急诊麻醉药品的使用情况，促进麻醉药品使用的合理化和规范化。 方法 对2008年－2010年门急诊麻醉药品处方共5 461张进行统计分析，包括不合理处方比例及存在的问题、各年度处方总数、临床使用分布、各类麻醉药品的用药总量、各类麻醉药品的处方比例和等。对非癌痛处方以用药频率、药物利用指数为指标，癌症处方以用药天数和平均日剂量为指标进行分析、评价。 结果 门急诊的麻醉药品有9种，盐酸吗啡缓释片的总用量居首位，盐酸吗啡针在急诊处方中比例最高，药物利用指数＜1，不合理处方共770张，占14.10%。 结论 该院门急诊麻醉药品使用基本合理，但需对部分医师加强麻醉药品使用培训。
Objective To investigate the dose-dependent relationship of bone marrow mesenchymal stem cells(MSCs) transplantation in improving ischemic myocardial dysfunction? in a rat ischemic heart model. Methods Myocardial infarction was induced in 32 inbred F344 rats by acute ligation of the left anterior descending(LAD) coronary artery. One week after ligation, the ratswere randomized? into four equal groups, with eight rats in each group. Equal volume Iscove’s modified Dulbecco’s medium was injected in the control group, 1×103(group 1), 1×105(group 2), and 1×107(group 3) 5-bromodeoxyuridine (BrdU) labeled bone marrow MSCs were injected into the infarcted myocardium. Cardiac function was evaluated by ultrasound before the ligation of the LAD, before the transplantation and the 4th week after transplantation. The expressions of BrdU,Connexin43,Myosin heavy chain β(MHC), and smooth muscle actin α(α-SMA) were detected by immunofluorescence and immunohistochemistry at the 4th week after transplantation. The amount of functional vessels stained by α-SMA was counted simultaneously. Results At the 4th week? after transplantation, the ejection fraction(EF) in goup 2 was more significantly improved than that in group1(0.54±0.20 vs. 0.34±0.16, P＝0.004) and EF in group 3 was more significantly improved than that in group 2(0.71±0.24 vs. 0.54±0.20,P＝0.018), whereas no significant difference between group 1 and control group was detected (0.34±0.16 vs. 0.36±0.15,Pgt;0.05). The BrdU labeled MSCs could be found in host myocardium. The number of cells in group 2 by double staining both for BrdU and for MHC observed in ischemic myocardium were significantly more than that in group 1? (323.20±91.62 n/HP vs. 51.75±27.58 n/HP,P＝0.049) and the same was true between group 3 and group 2(409.75±106.65 n/HP vs. 323.20±91.62 n/HP,Plt;0.001), whereas the result of control group was negative.The majority of transplanted cells were found positive staining both for MHC and for Connexin43 in all groups. There were lots of positive staining of α-SMA whose form were partly irregular in ischemic myocardium indicating that there was neovascularization in group1 and control group. More neovascularization in group2 was found than that in group 1 (28.38±12.79 n/HP vs. 22.75±9.07 n/HP, P＝0015) and more neovascularization in group 3 was found? than that in group 2 (35.63±13.27 n/HP vs. 28.38±12.79 n/HP, P＝0.002) . Conclusion Transplanted into infarcted myocardium, bone marrow MSCs may have significant and dose-dependent potential for cardiomyogenesis with functional recovery from myocardial ischemia.
ObjectiveTo investigate the effect of CYP2C9 and APOE on the dose of stable warfarin and model prediction in Hainan population.MethodsFrom August 2016 to July 2018, 368 patients who required heart valve replacement and agreed to take warfarin anticoagulation at the second department of cardiothoracic surgery in our hospital were enrolled, including 152 males aged 48.5–70.5 (60.03±10.18) years and 216 females aged 43.5–65.6 (54.24±11.35) years. CYP2C9 and APOE were amplified by polymerase chain reaction. The gene fragment was sequenced by the Single Nucleotide Polymorphisms (SNP) site. The patients' age, sex, weight, history of smoking and drinking, and the dose of stable warfarin were recorded. Regression analysis of these clinical data was made to construct a dose prediction model.ResultsAmong 368 patients, CYP2C9 genotype test results showed 301 patients (81.8%) with *1*1 genotype, and 67 patients (18.2%) with *1*3 type. For different CYP2C9 genotype patients, the difference was statistically significant in the dose of stable warfarin (P<0.05). The results of APOE genotype showed 93 patients (25.3%) with E2 genotype, 221 patients (60.1%) with E3 genotype, and 54 patients (14.7%) with E4 genotype; the dose of stable warfarin in patients with different APOE genotypes was statistically significant (P<0.05). Multiple regression analysis showed that patients' age, body weight, and CYP2C9 and APOE genotypes were correlated with the dose of stable warfarin. The correlation coefficient R2 was 0.572, and the prediction model was statistically significant (P<0.05).ConclusionCYP2C9 and APOE gene polymorphisms exist in Hainan population. There is significant difference in the dose of stable warfarin among different genotypes of patients. The model to predict stable warfarin can partly explain the difference of warfarin among different patients.
Dose-response meta-analysis serves an important role in investigating the dose-response relationship between independent variables (e.g. dosage) and disease outcomes. Traditional dose-response meta-analysis model is based on one independent variable to consider its own dose-specific effect on the outcome. However, for drug clinical trials, it generally involves two-dimensions of the treatment, such as dosage and course of treatment. These two-dimensions tend to be associated with each other. When neglecting their correlations, the results may be at risk of bias. Moreover, taking account of the "combined effect” of dosage and time on outcome has more clinical value. Therefore, in this article, based on traditional dose-response meta-analysis model, we propose a three-dimension model for dose-response meta-analysis which considers both the effect of dosage and time, to provide a solution for the above-mentioned problems in a traditional model.
Objective To investigate the retinal toxicity and verify the safe dose of intravitreal injection of nonsteroid anti-inflamatory drug,diclofenac sodium.Methods Twenty-eight healthy adult white rabbits were divided at random into 7 groups and received in every right eye the intravitreal injection of a single dose of diclofenac sodium solution ranging from 0.4-0.1 mg/0.1ml respectively ,the left eyes were regarded as conreol ones.Before injection and on the 1st,3rd,7th,14th,21st,and 28th day after injection the electroretinography on both eyes was examined.On the 28th day after injection the retinas of two rabbits of every group were examined by using light microscopy.On the 10th and 30th day after injection the retinal tissues around the optic nerve sisk of two eyes from every group at random were tested by using transmission electron microscopy.Results The retio of amplitude ofb wave of electroretinography in 0.4mg and 0.5mg groups had no sighnificant difference from groups before injection,the retinal tissues showed no structural changes in light and ecectron microscopy examination.The ratio of amplitude ofb wave of photoptic electroretinogrphy in 0.6mg groups in the early stage after injection was markedly reduced（P＜0.05）and returned to that before injection with time,reversible change of the edematou retina was discovered.The ratio of amplitude of b wave of electroretinography in 0.7-1.0mg groups was distinctly descreaded after injection（P＜0.05 or P＜0.01）,the cells of all the retinal layer revealed apparent and irreversible damage.Conclusion The largest dose of safety of intravitreal diclofenac sodium should be not more than 0.6mg.The toxic effect of intravitreal diclofenac sodium on retina is concerned mostly to cones and rods.
目的 了解2007年-2008年成都地区17家医院消化系统药物的使用状况。 方法 采用限定日剂量（DDD）的方法，对成都地区2007年-2008年17家医院消化系统用药的销售金额、用药频度（DDDs）等进行统计分析。 结果 2007-2008年成都地区17家医院消化系统用药总金额分别为12 527.89万元和16 446.21万元，居所有药物销售总额的第5位。在金额排序和用药频度排序中，抗溃疡药、肝病用药居于前列。 结论 消化系统药物的应用状态与同期的整体增长保持一致，相比上一年略有上涨。抗溃疡药中的质子泵抑制剂以其优异的性价比，引领着消化系统药物销售额的增长。