Warfarin, a classic oral anticoagulant, is characterized by a narrow therapeutic window and considerable interindividual variability in dosing requirements. This makes precise dose adjustment challenging in clinical practice and increases the risk of bleeding or thrombosis. To improve dose prediction, this study developed a streamlined multilayer perceptron (MLP) model using real-world data from the International Warfarin Pharmacogenomics Consortium (IWPC) database. The LASSO-proj algorithm was applied for high-precision feature selection prior to model construction. The resulting model demonstrated strong predictive performance on the test set, achieving a coefficient of determination (R2) of 0.456, a mean absolute error (MAE) of 8.92 mg/week, and 48.522% of its predictions falling within ±20% of the actual stable therapeutic dose. Through SHAP-based interpretation using DeepExplainer, key features influencing warfarin dosing were identified, including the VKORC1 genotype, body weight, age, and ethnicity. The interpretable MLP framework incorporating LASSO-proj not only maintains high predictive accuracy, but also significantly enhances model transparency, providing a valuable tool for guiding warfarin therapy.
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.
This article reviews Chinese nomenclature of renal replacement therapy and extracorporeal blood purification currently utilized to manage acute kidney injury and other organ dysfunction syndromes in critically ill patients, based on the recent reports of a consensus expert conference of Nomenclature Standardization Initiative Alliance. We provide a detailed description of the performance characteristics of membranes, filters, transmembrane transport of solutes and fluid, flows, and methods of measurement of delivered treatment, common definitions, components, techniques, and operations of the machines and platforms as well as the renal replacement therapy techniques in detail with the relevant technologies, procedures, operations, and recent developments in other extracorporeal therapies, including therapeutic plasma exchange, multiple organ support therapy, liver support, lung support, and blood purification in sepsis. We believe this nomenclature review will serve future use of terminology in publications, research, clinical operations and therapy platforms to enable consistent data collection and comparison.
Objective To evaluate the effectiveness and safety of different doses of interferon alfa (INF-α) in the treatment of chronic hepatitis C (CHC). Methods Such databases as MEDLINE, EMbase, CENTRAL, CBM, CNKI, VIP and WanFang Data were searched to collect the randomized controlled trials (RCTs) on different doses of INF-α in the treatment of CHC published before August, 2012. According to the inclusion and exclusion criteria, two reviewers independently screened literature, extracted data and evaluated the quality of the included studies, and then meta-analysis was performed using RevMan 5.0 software. Results A total of 13 RCTs involving 1 442 patients were included. The results of meta-analysis on different doses of INF-α showed that, a) There was no significant difference in the complete response rate between the 3 MU dose group and the 1 MU dose group (RR=0.83, 95%CI 0.52 to 1.32, P=0.43), but there was significant difference in the sustained response rate between those 2 groups (RR=1.89, 95%CI 1.00 to 3.59, P=0.05); and b) No significant differences were found in the complete response rate among the 3 MU dose group, the 6 MU dose group, and the 1 MU dose group. Conclusion INF-α in dose of 3 MU, 3 times daily, is effective in treating CHC, but it would not rule out that higher dose takes more effective action. When INF-α is used to treat CHC, an individualized medication should be applied according to patients’ tolerance and economic status.
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 systematically evaluate the dose-response relationship between coffee consumption and liver cancer risk. MethodsThe PubMed, Web of Science, Cochrane Library, EMbase, CNKI, VIP, WanFang Data, and CBM databases were searched from inception to December 2022. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using Stata 17.0 software. ResultsFifteen studies (11 cohort studies and 4 case-control studies) involving 557 259 participants were included. The results of meta-analysis showed that coffee consumption was significantly negatively associated with the risk of liver cancer (RR=0.39, 95%CI 0.27 to 0.57, P<0.01). The dose-response meta-analysis showed a non-linear dose-response relationship between coffee consumption and the risk of liver cancer (P<0.01). Compared with people who did not drink coffee, people who drank 1 cup of coffee a day had a 25% lower risk of liver cancer (RR=0.75, 95%CI 0.67 to 0.83), and people who drank 2 cups of coffee a day had a 38% lower risk of liver cancer (RR=0.62, 95%CI 0.56 to 0.70). The risk of liver cancer decreased by 45% (RR=0.55, 95%CI 0.48 to 0.62) for 3 cups of coffee and by 51% (RR=0.49, 95%CI 0.43 to 0.56) for 4 cups of coffee. ConclusionCurrent evidence suggests that there is a nonlinear dose-response relationship between coffee consumption and the risk of liver cancer. These results indicate that habitual coffee consumption is a protective factor for liver cancer. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
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)
Dose-response relationship model has been widely used in epidemiology studies, as well as in evidence-based medicine area. In dose-response meta-analysis, the results are highly depended on the raw data. However, many primary studies did not provide sufficient data and led the difficulties in data analysis. The efficiency and response rate of collecting the raw data from original authors were always low, thus, evaluating and transforming the missing data is very important. In this paper, we summarized several types of missing data, and introduced how to estimate the missing data and transform the effect measure using the existed information.
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.