Objective To investigate the effects of QUE on proliferation and DNA synthesis of cultured retinal pigment epithelium(RPE) cells with or without EGF. Methods With or without EGF, cultured RPE cells were treated with QUE by various concentrations(200,100,50,1mu;mol/L) and with QUE 200mu;mol/L at different times(24-168 hr), cells proliferation and DNA synthesis were evaluated by cell count method and the uptake of thymidine. The viability of cells was determined by trypanblue exclusion. Results The best concentration of QUE which inhibits proliferation and DNA synthesis of PRE cells was 200mu;mol/L. The significant inhibition effect of QUE occurred at 48hr, and the best inhibition of QUE occurred at 96hr. QUE had more powerful effect of antiproliferation on RPE cells, and the viability of RPE cells was over85%. Conclusion The results suggested that QUE could inhibit the proliferation of RPE cells in a dose-dependent and time-dependent manner, especially inhibit the proliferation induced by EGF stimulating. QUE had no cyto-toxic effect on RPE cells cultured in vitro. (Chin J Ocul Fundus Dis,1999,15:27-29)
Objective To investigate the effect of the synthetic bone morphogenetic protein 2 (BMP-2)derived peptide on the osteogenic induction in the marrow mesenchymal stem cells (MSCs）and to evaluate the osteoinductivity and dosedependence of the BMP-2 derived peptide in vitro. Methods MSCs of 4-week old Wistar rats were separated and cultured. In the 3rd passage, the conditional culture medium was changed, in which the BMP-2-derived peptide in the following doses was added: 300,200, 100, 50, and 0 μg/ml, respectively (Groups A-E). The activity of alkaline phosphatase (ALP）and the amount of calciumdeposition were meassured at 5，10，15 and 20 days during the culture with the conditional culture medium. The real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) was performed to measure the mRNA expressions of collagen type Ⅰ, osteopontin (OPN), and osteocalcin（OCN）and to measure the osteoinductivity of the BMP-2-derived peptide in the different concentrations.Results Under the inverted phase contrast microscope, MSCs cultured in the conditional culture medium for 3-4 days were changed in shape, from long fusiform to short fusiform or polygon. As the concentration of the BMP-2-derived peptide increased, the time for MSCs to change into the osteoblasts decreased. There was a significantly greater level of the ALP activity and amount of the calcium deposition in Groups A and B than in the other groups（Plt;0.05）. However,there was no significant difference between Group A and Group B （Pgt;0.05）. Theresult of FQPCR showed that after MSCs were cultured in the different doses of theconditional culture medium for 14 days, the mRNA expressions of collagen type Ⅰ, OPN andOCN were at higher levels. An increasing order in the level of the cycle threshold (Ct) was found in the following groups: Agt;Bgt;Cgt;D. Almost no expression was found in Group E. The Ct levels were significantly greater in Groups A and B thanin Groups C and D（Plt;0.05）. However, there was no significant difference between Group A and Group B （Pgt;0.05）.ConclusionThe BMP-2-derived peptide can greatly promote differentiation of MSCs into the osteoblasts, the promotion of osteogenesis has a dosedependent pattern, and the best inducing dosage is 200 μg/ml.
Objective According to health technology assessment (HTA) methodology, to assess the efficacy and safety of different doses of metoprolol in the treatment of atrial fibrillation (AF). Methods Based on the principles of HTA, we searched some important medical databases including MEDLINE, EMBASE, The Cochrane Library and CMCC, as well as several national special heart disease databases and side effect centers. We selected eligible studies based on the inclusion and exclusion criteria and critically assessed their quality. Results Intravenous metoprolol 10 mg - 15 mg could control rapid ventricular rate in patients with chronic AF. On either rest or exercise, oral metoprolol 150 mg/d had a better control of rapid ventricular rate than 50 mg/d in patients with chronic AF. For preventing postoperative AF (POAF), the intravenous metoprolol 20 mg group and the 30 mg group could decrease the incidence of POAF compared to the 10 mg group. Oral metoprolol 150 mg/d was more effective than 100 mg/d in preventing POAF. In addition, intravenous metoprolol therapy was well-tolerated and more effective than oral metoprolol therapy in preventing atrial fibrillation after cardiac surgery. Results from several national side effect centers demonstrated that the incidence of adverse reactions associated with metoprolol was low. Conclusion Present evidence showed that high dose of metoprolol was superior to low dose in treating AF, however, the evidence available is insufficient. It is suggested that adequate evidence through further studies are needed. The safety profile of different doses of metoprolol is similar.
As a valid method in systematic review, dose-response meta-analysis is widely used in investigating the relationship between independent variable and dependent variable, and which usually based on observational studies. With large sample size, observational studies can provide a reasonable amount of statistical power for meta-analysis. However, due to the design defects of observational studies, they tend to introduce many kinds of biases, which may influence the final results that make them deviation from the truth. Given the dead zone of methodology, there is no any bias adjusting method in dose-response meta-analysis. In this article, we will introduce some bias adjusting methods from other observational-study-based meta-analysis and make them suit for dose-response meta-analysis, and then compare the advantages and disadvantages of these methods.
According to the heterogeneity between dose-response data across different studies and the potential nonlinear trend within the dose-response relationship, there are several models for trend estimation from summarized dose-response data, with applications to meta-analysis. However, up to now, there is no guideline of conducting a metaanalysis of dose-response data. After summarizing the previous papers, this paper focuses on how to select the right model for conducting a meta-analysis of dose-response data based on the heterogeneity across different studies, the goodness of fit, and the P value of overall association between exposure and event. Then a preliminary statistical process of conducting a meta-analysis of dose-response data is proposed.
When investing the relationship between independent and dependent variables in dose-response meta-analysis, the common method is to fit a regression function. A well-established model should take both linear and non-linear relationship into consideration. Traditional linear dose-response meta-analysis model showed poor applicability since it was based on simple linear function. We introduced a piecewise linear function into dose-response meta-analysis model which overcame this problem. In this paper, we will give a detailed discussion on traditional linear and piecewise linear regression model in dose-response meta-analysis.
Objective To systematically review the dose-response relationship between cadmium exposure and the risk of stroke onset. Methods The PubMed, Web of Science, Cochrane Library, Embase, CNKI, VIP, WanFang Data, and CBM databases were electronically searched to collect studies related to objectives from inception to June 2024. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Meta-analysis was then performed using Stata 15.1 software. Results There were 10 studies that involved 28 250 participants, and 7 of them were prospective cohort studies and 3 were case-control studies. Meta-analysis results showed that cadmium exposure significantly increased the risk of stroke (RR=1.39, 95%CI 1.20 to 1.59, P<0.01), blood cadmium exposure significantly increased the risk of stroke (RR=1.79, 95%CI 1.34 to 2.25, P<0.01), urinary cadmium exposure significantly increased the risk of stroke (RR=1.30, 95%CI 1.09 to 1.52, P<0.01). Blood cadmium exposure had a significantly nonlinear dose-response relationship associated with an increased risk of stroke (χ2=8.56, P<0.05). The risk of stroke increased by 15% with the blood cadmium exposure concentration of 0.8 μg/L (RR=1.15, 95%CI 0.98 to 1.36), and 51% with the blood cadmium exposure concentration of 1.2 μg/L (RR=1.51, 95%CI 1.14 to 2.01) than those without blood cadmium exposure. Urinary cadmium exposure had significantly linear dose-response relationship associated with an increased risk of stroke (χ2=2.47, P=0.12). The risk of stroke increased by 26% with the urinary cadmium exposure concentration of 0.8 μg/g (RR=1.26, 95%CI 1.20 to 1.31), and 31% with the urinary cadmium exposure concentration of 1.2 μg/g (RR=1.31, 95%CI 1.27 to 1.36) than those without urinary cadmium exposure. Conclusion Cadmium exposure increases the risk of stroke. There was a significant dose-response relationship between cadmium exposure and the risk of stroke.
ObjectivesTo compare different formula calculated dosages with the actual doses of warfarin from patients in Beijing Hospital so as to investigate suitable warfarin dosing models for Chinese patients.MethodsOne hundred and three Chinese patients with long-term prescription of warfarin were randomly selected from Beijing Hospital from July 2012 to May 2013. The CYP2C9 and VKROC1 genotypes and basic statistical information were collected. SPSS 18.0 software was used to compare the differences between different formula calculated dosages and the actual dosages of warfarin.ResultsFive genotypes were found in 103 patients, including: CYP2C9 AA genotype + VKORC1 AA genotype (n=72, 69.9%), CYP2C9 AA genotype + VKORC1 AG genotype (n=17, 16.5%), CYP2C9 AC genotype + VKORC1 AA genotype (n=10, 9.7%), CYP2C9 AC genotype + VKORC1 AG genotype (n=3, 2.9%) and CYP2C9 AA genotype + VKORC1 GG genotype (n=1, 1%). Compared with the actual dosages of warfarin, the degree of coincidence was highest for dosages calculated by Jeffrey’s formula.Conclusions Using Jeffrey’s formula to calculate warfarin dosages may be more suitable for Chinese patients with using long-term warfarin. Due to limited sample size, prospective and large sample size studies are required to verify the above conclusion.
ObjectiveTo develop reporting guideline for dose-response meta-analysis (DMA), so as to help Chinese authors to understand DMA better and to promote the reporting quality of DMA conducted by them. MethodPubMed, EMbase, The Cochrane Library, CNKI, and WanFang Data were searched from Jan 1st 2011 to Dec 30th 2015 to collect DMA papers published by Chinese authors. The number of these publications by years, whether and what kind of reporting guideline was used, and whether the DMA method claimed in these publications was correct were analysed. Then we drafted a checklist of items for reporting DMA, and organized a discussion meeting with experts from the fields of DMA, evidence-based medicine, clinical epidemiology, and clinicians to collect suggestions for revising the draft reporting guideline for DMA. ResultsOnly 33.73% of the publications clarified it is a DMA on the title and 48.02% of them reported risk of bias. Almost 38.49% of the publications didn't use any reporting guidelines. Fourteen of them claimed an incorrect use of methodology. We primarily took account for 47 potential items related to DMA based on our literature analysis results and existing reporting guidelines for other types of meta-analyses. After the discussion meeting with 6 experts, we revised the items, and finally the G-Dose checklist with 43 items for reporting DMA was developed. ConclusionThere is a lack of attention on reporting guidelines in Chinese authors and evidence suggests these authors may be at risk of incomplete understanding on reporting guidelines. It is strongly recommended to use reporting guidelines for DMA and other types of meta-analyses in Chinese authors.
Dose-response meta-analysis, an important tool in investigating the relationship between a certain exposure and risk of disease, has been increasingly applied. Traditionally, the dose-response meta-analysis was only modelled as linearity. However, since the proposal of more powerful function models, which contains both linear, quadratic, cubic or more higher order term within the regression model, the non-linearity model of dose-response relationship is also available. The packages suit for R are available now. In this article, we introduced how to conduct a dose-response meta-analysis using dosresmeta and mvmeta packages in R.