Interleukin-1alpha polymorphism -889C/T related to obesity in Korean Taeumin women

Interleukin-1 (IL-1), a cytokine produced predominantly by cells from the macrophage lineage, can affect multiple neuroendocrine and metabolic functions. IL-1alpha production by cultured peripheral blood mononuclear cells from an obese group was significantly elevated in comparison to a control group. The aim of this study was to investigate whether the IL-1alpha polymorphism and Sasang constitution, a major branch in Korean traditional medicine, were related to obesity. Genotyping was done in 182 healthy females with a marked variation in body mass index (BMI) by a PCR-restriction fragment length polymorphism assay. The T allele was associated with decreased BMI (p = 0.020). In a subgroup with BMI values ranging from 27 approximately 29 kg/m(2), the frequency of the T allele was significantly decreased (p = 0.004, odds ratio, OR = 0.141 compared to a subgroup with a BMI values less than 25 Kg/m(2)). In addition, in Taeumin female subjects, the frequency of the IL-1alpha T allele was markedly decreased in a subgroup with BMI values in the range of 27 approximately 29 kg/m(2) compared to a lean group with BMI values less than 25 kg/m(2) (p = 0.004, OR = 0.139). In Korean women, an association was found between -889C/T polymorphism in the regulatory region of the IL-1alpha gene and BMI values. In addition, an association was found among IL-1alpha polymorphism, obesity, and the Sasang constitution.     

Antioxidative and hepatoprotective effect of CGX, an herbal medicine, against toxic acute injury in mice

Aim

CGX, a modified traditional Chinese herbal drug whose name means “liver cleaning,” is used to treat various liver disorders. This study investigated the protective effects of CGX and its mechanisms.

Material and methods

After pretreating ICR mice twice daily with CGX (po, 50 or 100 mg/kg) or distilled water for three consecutive days, acute liver injury was induced by a single injection of CCl₄ (ip, 10 mL/kg of 0.2% in olive oil) (n = 8 per group).

Results

Pretreatment with CGX significantly attenuated the elevation in biochemical parameters, such as alanine transaminase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) in serum, and the malondialdehyde concentrations in liver tissue. Pretreatment with CGX significantly restored the reduction of catalase activity and glutathione (GSH) content, but not superoxide dismutase (SOD) activity, and it inhibited the CCl₄-induced high expression of iNOS and TNF-α in hepatic tissue.

Conclusion

This study showed that CGX has hepatoprotective effects against free radical-induced acute injury via primarily antioxidative properties.     

Machine Learning Model for Classifying the Results of Fetal Cardiotocography Conducted in High-Risk Pregnancies

PurposeFetal well-being is usually assessed via fetal heart rate (FHR) monitoring during the antepartum period. However, the interpretation of FHR is a complex and subjective process with low reliability. This study developed a machine learning model that can classify fetal cardiotocography results as normal or abnormal.Materials and MethodsIn total, 17492 fetal cardiotocography results were obtained from Ajou University Hospital and 100 fetal cardiotocography results from Czech Technical University and University Hospital in Brno. Board-certified physicians then reviewed the fetal cardiotocography results and labeled 1456 of them as gold-standard; these results were used to train and validate the model. The remaining results were used to validate the clinical effectiveness of the model with the actual outcome.ResultsIn a test dataset, our model achieved an area under the receiver operating characteristic curve (AUROC) of 0.89 and area under the precision-recall curve (AUPRC) of 0.73 in an internal validation dataset. An average AUROC of 0.73 and average AUPRC of 0.40 were achieved in the external validation dataset. Fetus abnormality score, as calculated from the continuous fetal cardiotocography results, was significantly associated with actual clinical outcomes [intrauterine growth restriction: odds ratio, 3.626 (p=0.031); Apgar score 1 min: odds ratio, 9.523 (p<0.001), Apgar score 5 min: odds ratio, 11.49 (p=0.001), and fetal distress: odds ratio, 23.09 (p<0.001)].ConclusionThe machine learning model developed in this study showed precision in classifying FHR signals. This suggests that the model can be applied to medical devices as a screening tool for monitoring fetal status.     

Fimasartan Ameliorates Deteriorations in Glucose Metabolism in a High Glucose State by Regulating Skeletal Muscle and Liver Cells

PurposeSince diabetes and hypertension frequently occur together, it is thought that these conditions may have a common pathogenesis. This study was designed to evaluate the anti-diabetic function of the anti-hypertensive drug fimasartan on C2C12 mouse skeletal muscle and HepG2 human liver cells in a high glucose state.Materials and MethodsThe anti-diabetic effects and mechanism of fimasartan were identified using Western blot, glucose uptake tests, oxygen consumption rate (OCR) analysis, adenosine 5′-triphosphate (ATP) enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining for diabetic biomarkers in C2C12 cells. Protein biomarkers for glycogenolysis and glycogenesis were evaluated by Western blotting and ELISA in HepG2 cells.ResultsThe protein levels of phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK), p-AKT, insulin receptor substrate-1 (IRS-1), and glucose transporter type 4 (Glut4) were elevated in C2C12 cells treated with fimasartan. These increases were reversed by peroxisome proliferator-activated receptor delta (PPARδ) antagonist. ATP, OCR, and glucose uptake were increased in cells treated with 200 µM fimasartan. Protein levels of glycogen phosphorylase, glucose synthase, phosphorylated glycogen synthase, and glycogen synthase kinase-3 (GSK-3) were decreased in HepG2 cells treated with fimasartan. However, these effects were reversed following the addition of the PPARδ antagonist GSK0660.ConclusionIn conclusion, fimasartan ameliorates deteriorations in glucose metabolism as a result of a high glucose state by regulating PPARδ in skeletal muscle and liver cells.     

Significant accumulation of KRAS mutations in bronchiolar metaplasia-associated honeycomb lesions of interstitial pneumonia

Interstitial pneumonia (IP) is a major risk factor for lung adenocarcinoma (LADC). IP-related LADC predominantly develops in the bronchiolar metaplasia lining in honeycomb lesions. Kirsten rat sarcoma virus (KRAS) is the most common oncogene mutated in IP-related LADC. The present study examined the metaplastic epithelia in honeycomb lesions for KRAS mutations using digital droplet polymerase chain reaction (ddPCR), a sensitive method used to detect infrequent mutations. Significantly higher KRAS mutation variant allele frequencies (VAFs) were detected in the metaplastic lung epithelia from 13 patients with IP compared with those in 46 non-lesioned lung samples from patients without IP (G12V, P=0.0004, G12C, P=0.0181, and G12A, P=0.0234; Mann Whitney U test). Multivariate analyses revealed that higher KRAS G12V (logistic regression model; P=0.0133, odds ratio=7.11) and G12C (P=0.0191, odds ratio=5.81) VAFs in patients with IP were independent of confounding variables, such as smoking and age. In patients with IP, metaplastic epithelia exhibited significantly higher KRAS G12V and G12C VAFs compared with the non-lesioned counterparts (paired t-test; G12V, P=0.0158, G12C, P=0.0465). These results suggested that IP could increase KRAS mutations and supported the hypothesis that bronchiolar metaplasia could be a precursor for IP-related LADC.     

失效模式与效应分析改善消毒供应中心感染手术器械处理效果的研究

目的：研究失效模式与效应分析改善消毒供应中心感染手术器械处理的临床效果。方法组建失效模式与效应分析(FMEA)小组,根据之前存在的问题重新设计、完善消毒供应中心感染手术器械的处理流程,应用FMEA方法评估并分析感染手术器械处理流程中有可能出现的失效模式,并且制定改进措施,同时予以评估。结果消毒供应中心感染手术器械处理流程中有未彻底清洗(危机值=504)、清洗步骤紊乱(危机值=336)、未初步消毒(危机值=210)、精密仪器发生损耗(危机值=120)、医疗器械生锈(危机值=96)等高风险失效模式,经FMEA方法分析后采取了措施改进,上述存在的高风险失效模式的危机值均显著下降。结论失效模式与效应分析改善消毒供应中心感染手术器械处理的临床效果显著,可以保障规范的顺利实施,值得临床推广。