BackgroundStudies of angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and the risks of knee osteoarthritis (OA) have yielded conflicting results.ObjectiveTo determine the association between ACE I/D and knee OA, we conducted a combined case-control study and meta-analysis.MethodsFor the case-control study, 447 knee OA cases and 423 healthy controls were recruited between March 2010 and July 2011. Knee OA cases were defined using the Kellgren-Lawrence grading system, and the ACE I/D genotype was determined using a standard polymerase chain reaction. The association between ACE I/D and knee OA was detected using allele, genotype, dominant, and recessive models. For the meta-analysis, PubMed and Embase databases were systematically searched for prospective observational studies published up until August 2015. Studies of ACE I/D and knee OA with sufficient data were selected. Pooled results were expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for the D versus I allele with regard to knee OA risk.ResultsWe found no significant association between the D allele and knee OA [OR: 1.09 (95% CI: 0.76–1.89)] in the present case-control study, and the results of other genetic models were also nonsignificant. Five current studies were included, and there were a total of six study populations after including our case-control study (1165 cases and 1029 controls). In the meta-analysis, the allele model also yielded nonsignificant results [OR: 1.37 (95% CI: 0.95–1.99)] and a high heterogeneity (I2: 87.2%).ConclusionsThe association between ACE I/D and knee OA tended to yield negative results. High heterogeneity suggests a complex, multifactorial mechanism, and an epistasis analysis of ACE I/D and knee OA should therefore be conducted.
Purpose: Oxidative stress and erythropoietin (EPO) levels are increased following high altitude exposure. We hypothesized that the altitude-oxidative stress and EPO response would be associated with the presence or absence of acute mountain sickness (AMS) in subjects exposed at high altitude. Methods: The study enrolled 29 healthy volunteers exposed at altitudes without strenuous physical exercise. Oxidative stress was determined by the spectrophotometric measurement of the colour occurring during the reaction of malondialdehyde (MDA) with thiobarbituric acid (TBA) on blood samples. Ferritin and EPO were also measured simultaneously. Results: During a rise in altitude at 2000 and 3000 m, there were no changes in plasma ferritin level in either of the 2 groups with or without AMS. In contrast, EPO increased at an altitude of 3000 m and after returning to sea level (28.2±2.7, 26.9±3.3 vs 12.2±1.4 and 17.1±1.6, P < 0.05, in group without AMS; 29.3±4.5, 22.8±2.7 vs 10.6±1.0 and 16.1±1.5, # P < 0.05, in group with AMS; compared with the baseline level and at the height of 2000 meters). At a height of 3000 m, plasma MDA level was elevated compared with that at the altitude of baseline and 2000 m in both groups of subjects with and without AMS (3.77±0.29 vs 1.14±0.17, and 1.64±0.22, P < 0.001, in subjects with AMS; 3.65±0.39 vs 1.71±0.21, and 1.73±0.21, P < 0.001, in subjects without AMS) . After returning to sea level, subjects without AMS had lower MDA oxidative stress compared with those with AMS (2.58±0.26 vs 3.51±0.24, P = 0.0223). Along with a rise in altitude, the oxidative stress in these both groups was not correlated with the changes in EPO (r2 = 0.0728, P = 0.1096). Conclusion: High altitude-induced oxidative stress, detected by MDA assay, is not different between the two groups of subjects with and without AMS. Upon return to sea level, subjects without AMS had lower MDA oxidative stress burden and higher EPO level than those with AMS. Whether the subjects with altitude illness had delayed recovery from oxidative stress merits further investigation.
PurposeGenome-wide association studies have identified numerous genetic variants that are associated with osteoporosis risk; however, most of them are present in the non-coding regions of the genome and the functional mechanisms are unknown. In this study, we aimed to investigate the potential variation in runt domain transcription factor 2 (RUNX2), which is an osteoblast-specific transcription factor that normally stimulates bone formation and osteoblast differentiation, regarding variants within RUNX2 binding sites and risk of osteoporosis in postmenopausal osteoporosis (PMOP).MethodsWe performed bioinformatics-based prediction by combining whole genome sequencing and chromatin immunoprecipitation sequencing to screen functional SNPs in the RUNX2 binding site using data from the database of Taiwan Biobank; Case-control studies with 651 postmenopausal women comprising 107 osteoporosis patients, 290 osteopenia patients, and 254 controls at Tri-Service General Hospital between 2015 and 2019 were included. The subjects were examined for bone mass density and classified into normal and those with osteopenia or osteoporosis by T-scoring with dual-energy X-ray absorptiometry. Furthermore, mRNA expression and luciferase reporter assay were used to provide additional evidence regarding the associations identified in the association analyses. Chi-square tests and logistic regression were mainly used for statistical assessment.ResultsThrough candidate gene approaches, 3 SNPs in the RUNX2 binding site were selected. A novel SNP rs6086746 in the PLCB4 promoter was identified to be associated with osteoporosis in Chinese populations. Patients with AA allele had higher risk of osteoporosis than those with GG+AG (adjusted OR = 6.89; 95% confidence intervals: 2.23–21.31, p = 0.001). Moreover, the AA genotype exhibited lower bone mass density (p < 0.05). Regarding mRNA expression, there were large differences in the correlation between PLCB4 and different RUNX2 alleles (Cohen’s q = 0.91). Functionally, the rs6086746 A allele reduces the RUNX2 binding affinity, thus enhancing the suppression of PLCB4 expression (p < 0.05).ConclusionsOur results provide further evidence to support the important role of the SNP rs6086746 in the etiology of osteopenia/osteoporosis, thereby enhancing the current understanding of the susceptibility to osteoporosis. We further studied the mechanism underlying osteoporosis regulation by PLCB4.
Background: Ventilator weaning is one of the most significant challenges in the intensive care unit (ICU). Approximately 30% of patients fail to wean, resulting in prolonged use of ventilators and increased mortality. There are numerous high-performance prediction models available today, but they require a large number of parameters to predict and are thus impractical in clinical practice. Objectives: This study aims to create an artificial intelligence (AI) model for predicting weaning time and to identify the most simplified key predictors that will allow the model to achieve adequate accuracy with as few parameters as possible. Methods: This is a retrospective study of to-be-weaned patients (n = 1439) hospitalized in the cardiac ICU of Cheng Hsin General Hospital’s Department of Cardiac Surgery from November 2018 to August 2020. The patients were divided into two groups based on whether they could be weaned within 24 h (i.e., “patients weaned within 24 h” (n = 1042) and “patients not weaned within 24 h” (n = 397)). Twenty-eight variables were collected including demographic characteristics, arterial blood gas readings, and ventilation set parameters. We created a prediction model using logistic regression and compared it to other machine learning techniques such as decision tree, random forest, support vector machine (SVM), extreme gradient boosting, and artificial neural network. Forward, backward, and stepwise selection methods were used to identify significant variables, and the receiver operating characteristic curve was used to assess the accuracy of each AI model. Results: The SVM [receiver operating characteristic curve (ROC-AUC) = 88%], logistic regression (ROC-AUC = 86%), and XGBoost (ROC-AUC = 85%) models outperformed the other five machine learning models in predicting weaning time. The accuracies in predicting patient weaning within 24 h using seven variables (i.e., expiratory minute ventilation, expiratory tidal volume, ventilation rate set, heart rate, peak pressure, pH, and age) were close to those using 28 variables. Conclusions: The model developed in this research successfully predicted the weaning success of ICU patients using a few and easily accessible parameters such as age. Therefore, it can be used in clinical practice to identify difficult-to-wean patients to improve their treatment.
Background A chronic inflammatory state is a prominent feature in patients with end-stage renal disease (ESRD). Nuclear factor-kappa B (NF-κB) is a transcription factor that regulates the expression of genes involved in inflammation. Some genetic studies have demonstrated that the NF-κB genetic mutation could cause kidney injury and kidney disease progression. However, the association of a gene polymorphism in the transcription factor binding site of NF-κB with kidney disease is not clear. Methods We used the Taiwan Biobank database, the University of California, Santa Cruz, reference genome, and a chromatin immunoprecipitation sequencing database to find single nucleotide polymorphisms (SNPs) at potential binding sites of NF-κB. In addition, we performed a case–control study and genotyped 847 patients with ESRD and 846 healthy controls at Tri-Service General Hospital from 2015 to 2016. Furthermore, we used the ChIP assay to identify the binding activity of different genotypes and used Luciferase reporter assay to examine the function of the rs9395890 polymorphism. Result The results of biometric screening in the databases revealed 15 SNPs with the potential binding site of NF-κB. Genotype distributions of rs9395890 were significantly different in ESRD cases and healthy controls ( P = 0.049). The ChIP assay revealed an approximately 1.49-fold enrichment of NF-κB of the variant type TT when compared to that of the wild-type GG in rs9395890 ( P = 0.027; TT = 3.20 ± 0.16, GT = 2.81 ± 0.20, GG = 1.71 ± 0.18). The luciferase reporter assay showed that the NF-κB binding site activity in T allele was slightly higher than that in G allele, though it is not significant. Conclusions Our findings indicate that rs9395890 is associated with susceptibility to ESRD in Taiwan population. Electronic supplementary material The online version of this article (10.1186/s12882-019-1471-2) contains supplementary material, which is available to authorized users.
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