Objective To explore the effects of using proton pump inhibitors (PPIs) on the outcomes of hip fracture.Methods Searches were conducted through Medline,Embase,Cochrane Library and Chinese Biomedical Literature Database to identify the studies of the association between PPIs exposure and hip fracture.Quality of studies was assessed using the Newcastle-Ottawa Quality Assessment Scale.Pooled odds ratios (ORs) and 95％ confidence interval (CIs) were calculated for the risk of hip fracture associated with current exposure of PPIs.And several subgroups were analyzed by dosing duration,dose,osteoporosis and corticosteroid usage to explore potential study heterogeneities.All statistical analyses were performed with STATA software.Results Among 11 publications included for final analysis,there were a total of 1 107 577 subjects with an average age of over 60 years.A positive relationship existed between PPIs exposure and hip fracture with an OR of 1.46 (95％ CI:1.26-1.70,P =0.000) as compared with nonPPI-users,especially those on concurrent corticosteroid and PPIs.A significantly increased risk of hip fracture was found in the group of a short-term duration for under 1 year (OR =1.18,95％ CI:1.01-1.38,P =0.041),medium-term for 1-3 years (OR =1.23,95％ CI:1.01-1.49,P =0.038) and longer duration for over 6 years (OR =1.38,95％ CI:1.27-1.50,P =0.000).Furthermore,concurrent use of PPIs was not associated with an increased risk of hip fracture in a definite dose-response manner.As compared with non-PPI-users,no significantly increased risk of hip fracture was found in PPI-users with osteoporosis (P ＞ 0.05).Publication bias was not present.Conclusions Use of PPIs may be somewhat associated with an increased risk of hip fracture.Considering potential adverse effects,clinicians should prescribe cautiously PPIs for high-risk patients,especially elders.

BACKGROUND: Ultraviolet light (UVA) has a close relationship with photoaging, and mitochondrial damage is a basis of coil senescence and death.OBJECTIVE: To explore the influence of UVA on the mitochondrial deoxyribonucleic acid of human skin fibroblasts, in addition, to discuss whether transforming growth factor β1 (TGF-β1) could relieve mitochondrial DNA (mtDNA) deletion. DESIGN, TIME AND SETTING: The experiment was performed at Department of Plastic Surgery, the First Affiliated Hospital of Fourth Military Medical University from March 2007 to April 2008.MATERIALS: TGF-β1 was purchased from PerProtech Company; rnitochondrial DNA 4 977 bp primer was synthesized by Shanghai Sangon Biological Engineering Technology & Services Co., Ltd; UVA light was produced by Beijing Optical Instruments Factory; and the ultraviolet radiation meter was provided by Photoelectric Instrument Factory of Beijing Normal University.METHODS: Young adult's fibroblasts were obtained from 12 cases with posthectomy. Then the cells were divided into control,UVA irradiation (30, 60, 90 J/cm~2) groups. The mitochondrial DNA 4 977 bp deletion was detected by semi-quantitative PCR. After that, TGF-β1 with different doses (0.1, 1, 10 βg/L) were used to interfere the cells with UVA 90 J/cm~2 irradiation.MAIN OUTCOME MEASURES: DNA 4 977 bp deletion under different doses cumulative irradiation, as well as the effect of TGF-β1 on mtDNA 4 977bp deletion after irradiates UVA90 J/cm~2 were observed.RESULTS: Mitochondrial DNA 4 977 bp had deleted when irradiated with cumulative dose of 60 J/cm~2 UVA, the deletion was aggravated when the UVA dose arrived at 90 J/cm~2, The absorbance value, PCR electrophoresis and band scanning showed that the deletion of mitochondrial DNA 4 977 bp was reduced after adding TGF-β1 at 2 hours prior to irritation in the large dose (10 μg/L) group. However, the difference between the medium and small dose groups had no obviously significance.CONCLUSION: A certain dose of TGF-β1 (10 μg/L) has protective effect on mtDNA 4 977 bp deletion.

Objective To evaluate the effect of DHA on sevoflurane-induced activation of microglia.Methods N9 mouse microglia were seeded in culture plates (1 ml) or culture dishes (10 ml) at a density of 1 × 106 cells/ml and divided into 4 groups (n =18 each) using a random number table method:control group (C group),DHA group,sevoflurane group (Sevo group) and DHA plus sevoflurane group (DHA+Sevo group).Group C received no treatment.Cells were incubated in the culture medium containing 25 μmol/L DHA in DHA and DHA+Sevo groups.Cells were exposed to 2％ sevoflurane in Sevo and DHA +Sevo groups.At 24 h of culture,activated microglia were detected and counted by immunohistochemistry,the rate of CD11b positive cells was calculated,the expression of microglial biomarker CD1lb was detected by Western blot,and the concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin1 beta (IL-1β) were determined by enzyme-linked immunosorbent assay.Results Compared with C and DHA groups,the rate of C D 11 b positive cells was significantly increased,the expression of CD11 b was upregulated,and the concentrations of TNF-α and IL-1β were increased in Sevo group (P＜0.05).Compared with Sevo group,the rate of CD11b positive cells was significantly decreased,the expression of CD11b was down-regulated,and the concentrations of TNF-α and IL-1β were decreased in DHA + Sevo group (P＜0.05).Conclusion DHA can decrease inflammatory responses through reducing sevoflurane-induced activation of microglia.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.