Identification of key immune-related genes and immune infiltration in diabetic nephropathy based on machine learning algorithms.

BACKGROUND: Diabetic nephropathy (DN) is a complication of diabetes. This study aimed to identify potential diagnostic markers of DN and explore the significance of immune cell infiltration in this pathology. METHODS: The GSE30528, GSE96804, and GSE1009 datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified by merging the GSE30528 and GSE96804 datasets. Enrichment analyses of the DEGs were performed. A LASSO regression model, support vector machine recursive feature elimination analysis and random forest analysis methods were performed to identify candidate biomarkers. The CIBERSORT algorithm was utilised to compare immune infiltration between DN and normal controls. RESULTS: In total, 115 DEGs were obtained. The enrichment analysis showed that the DEGs were prominent in immune and inflammatory responses. The DEGs were closely related to kidney disease, urinary system disease, kidney cancer etc. CXCR2, DUSP1, and LPL were recognised as diagnostic markers of DN. The immune cell infiltration analysis indicated that DN patients contained a higher ratio of memory B cells, gamma delta T cells, M1 macrophages, M2 macrophages etc. cells than normal people. CONCLUSION: Immune cell infiltration is important for the occurrence of DN. CXCR2, DUSP1, and LPL may become novel diagnostic markers of DN.

Safety and Efficacy of High Power Shorter Duration Ablation Guided by Ablation Index or Lesion Size Index in Atrial Fibrillation Ablation: A Systematic Review and Meta-Analysis.

BACKGROUND: High power shorter duration (HPSD) ablation may lead to safe and rapid lesion formation. However, the optimal radio frequency power to achieve the desired ablation index (AI) or lesion size index (LSI) is insubstantial. This analysis aimed to appraise the clinical safety and efficacy of HPSD guided by AI or LSI (HPSD-AI or LSI) in patients with atrial fibrillation (AF). METHODS: The Medline, PubMed, Embase, Web of Science, and the Cochrane Library databases from inception to November 2020 were searched for studies comparing HPSD-AI or LSI and low power longer duration (LPLD) ablation. RESULTS: Seven trials with 1013 patients were included in the analysis. The analyses verified that HPSD-AI or LSI revealed benefits of first-pass pulmonary vein isolation (PVI) (RR: 1.28; 95% CI: 1.05-1.56, P = 0.01) and acute pulmonary vein reconnection (PVR) (RR: 0.65; 95% CI: 0.48-0.88, P = 0.005) compared with LPLD. HPSD-AI or LSI showed higher freedom from atrial tachyarrhythmia (AT) (RR = 1.32, 95% CI: 1.14-1.53, P = 0.0002) in the subgroup analysis of studies with PVI ± (with or without additional ablation beyond PVI). HPSD-AI or LSI could short procedural time (WMD: -22.81; 95% CI, -35.03 to -10.60, P = 0.0003), ablation time (WMD: -10.80; 95% CI: -13.14 to -8.46, P < .00001), and fluoroscopy time (WMD: -7.71; 95% CI: -13.71 to -1.71, P = 0.01). Major complications and esophageal lesion in HPSD-AI or LSI group were no more than LDLP group (RR: 0.58; 95% CI: 0.20-1.69, P = 0.32) and (RR: 0.84; 95% CI: 0.43-1.61, P = 0.59). CONCLUSIONS: HPSD-AI or LSI was efficient for treating AF with shorting procedural, ablation, and fluoroscopy time, higher first-pass PVI, and reducing acute PVR and may increase freedom from AT for patients with additional ablation beyond PVI compared with LPLD. Moreover, complications and esophageal lesion were low and no different between two groups.

Impaired Mitophagy: A New Potential Mechanism of Human Chronic Atrial Fibrillation.

Mitophagy is an autophagic response and plays essential roles in survival, development, and homeostasis of cells. It has been reported that mitophagic dysfunction is involved in several cardiovascular diseases. However, the effect of mitophagy on atrial fibrillation (AF) is still unknown. Therefore, we investigated the exact role of mitophagy in human chronic AF. Western blot was used to detect the protein abundance. The mitochondrial morphology and structure were observed by transmission electron microscopy. Immunofluorescent stainings were performed to analyze colocalization of mitochondria with autophagosomes or lysosomes. Totally, 43 patients with valvular heart disease undergoing cardiac surgery were selected, including 21 patients with chronic AF. Comparing with the sinus rhythm (SR) group, we found the size and number of mitochondria in atrial myocytes of patients with AF increased significantly. In addition, expression of LC3B II and LC3B II/LC3B I ratio was significantly decreased in the AF group. Moreover, the expression of p62 was markedly elevated in the AF group compared with that in the SR group. The results of immunofluorescence staining and western blot showed an enhanced expression of Cox IV in the AF group. Dual immunofluorescent stainings revealed that mitophagy defect in atrial myocytes of patients with AF resulted from dysfunction in the process of delivery of mitochondria into autophagosomes. For the first time, impaired mitophagy, during the phagocytosis of mitochondria, is associated with human chronic AF. Mitophagy could be a potential therapeutic target for AF.

Impact of Age on the Prognosis of Papillary Thyroid Carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is a common subtype of thyroid carcinoma with a rising incidence rate. The purpose of this study was to provide a better understanding of age and PTC using the Surveillance, Epidemiology, and End Results (SEER) Program. METHODS: The study derived patients' information from the SEER Program (2010-2015). Chi-square or Fisher exact tests, and Kaplan-Meier method were used to analyze survival. Prognostic factors associated with survival were analyzed by Cox multivariate regression. RESULTS: A total of 1738 records were included from SEER, with 1079 PTC in the age group <55 years, and 659 PTC in the age group ≥55 years. The 5-year survival rate was 94% and the overall survival (OS) curve in different age groups indicated that patients younger than 55yr have a longer survival time (P < 0.05). In multivariate Cox regression, age, M stage and surgery treatment were independent risk factors (P < 0.05). Regarding PTC-specific survival, age and surgery treatment were the two main independent prognostic factors in multivariate regression. However, AJCC and M stage were not in the disease specific survival. CONCLUSION: Age is a prognostic factor in OS and PCT specific survival. AJCC I stage and surgery treatment are also significant in predicting prognosis.

A Network Pharmacology Approach to Estimate the Active Ingredients and Potential Targets of Cuscutae semen in the Treatment of Osteoporosis.

BACKGROUND Osteoporosis is a metabolic osteopathy characterized by abnormal bone mass and microstructure that has become a public health problem worldwide. Cuscutae semen (CS) is a traditional Chinese medicine (TCM) that has a positive effect on the prevention and treatment of osteoporosis. However, the mechanism of CS is unclear. Therefore, this study aimed to reveal the possible molecular mechanism involved in the effects of CS on osteoporosis based on a network pharmacology approach. MATERIAL AND METHODS The inactive and active ingredients of CS were identified by searching the pharmacology analysis platform of the Chinese medicine system (TCMSP), and the targets of osteoporosis were screened in the relevant databases, such as GeneCards, PubMed, and the Comparative Toxicogenomics Database (CTD). The network of "medicine-ingredients-disease-targets (M-I-D-T)" was established by means of network pharmacology, and the key targets and core pathways were determined by R analysis. Molecular docking methods were used to evaluate the binding activity between the target and the active ingredients of CS. RESULTS Eleven active ingredients were identified in CS, and 175 potential targets of the active ingredients were also identified from the TCMSP. Moreover, we revealed 22 539 targets related to osteoporosis in the 3 well-established databases, and we determined the intersection of the disease targets and the potential targets of the active ingredients; 107 common targets were identified and used in further analysis. Additionally, biological processes and signaling pathways involved in target action, such as fluid shear stress, atherosclerosis, cancer pathways, and the TNF signaling pathway, were determined. Finally, we chose the top 5 common targets, CCND1, EGFR, IL6, MAPK8, and VEGFA, for molecular docking with the 11 active ingredients of CS. CONCLUSIONS This study suggested that CS has multiple ingredients and multiple targets relevant to the treatment of osteoporosis. We determined that the active ingredient, sesamin, may be the most crucial ingredient of CS for the treatment of osteoporosis. Additionally, the network pharmacology method provided a novel research approach to analyze the function of complex ingredients.

Effect of preoperative loading dose ticagrelor and clopidogrel on no-reflow phenomenon during intervention in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: Previous studies have shown that ticagrelor is more effective than clopidogrel in platelet inhibition. However, this conclusion remains controversial. Therefore, we performed this meta-analysis to assess the effect of preoperative loading dose ticagrelor and clopidogrel on no-reflow (NRF) during intervention in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (PPCI). MATERIALS AND METHODS: Randomized controlled trials and observational studies were reviewed. The retrieval time was limited from inception to October 1, 2017. The retrieved databases included PubMed, Embase, the Cochrane Library, Web of Science, CBM, CNKI, the VIP database, and the Wang Fang database. RevMan 5.3 software was used for data analysis. RESULTS: Fourteen randomized controlled trials and one observational study, including 4,162 patients, were included. In these articles, 1,521 patients were in the ticagrelor group (180 mg) and 2,641 patients were in the clopidogrel group (600 mg). The meta-analysis showed that compared with clopidogrel group, preoperative loading dose ticagrelor: 1) significantly reduced the incidence of NRF during PPCI (95% confidence interval [CI]: 0.15, 0.39, P<0.05) as well as the level of postoperative corrected thrombolysis in myocardial infarction frame count (95% CI: -8.89, -6.91, P<0.05); 2) significantly reduced the incidence of major adverse cardiovascular events during hospitalization, including 30 and 180 days after PPCI (95% CI: 0.41, 0.82, P<0.05; 95% CI: 0.15, 0.46, P<0.05, respectively); and 3) significantly improved thrombolysis in myocardial infarction flow after PPCI (95% CI: 1.40, 2.45, P<0.05). No significant difference was observed in terms of bleeding events within 30 and 180 days after PPCI (95% CI: 0.71, 1.54, P=0.82; 95% CI: 0.81, 3.19, P=0.18, respectively). CONCLUSION: Compared with clopidogrel, loading dose ticagrelor effectively reduced both the occurrence of NRF during PPCI and the incidence of major adverse cardiovascular event in patients with ST-segment elevation myocardial infarction undergoing PPCI. Furthermore, it did not increase the risk of bleeding after PPCI.

Clinical effect of trimetazidine on prevention of contrast-induced nephropathy in patients with renal insufficiency: An updated systematic review and meta-analysis.

BACKGROUND: With the continuous development of cardiac interventional medicine, the incidence of contrast-induced nephropathy (CIN) is increasing every year, which is a serious threat to people's physical and mental health. Trimetazidine (TMZ) is a type of anti-ischemic drug developed in recent years, which can significantly reduce the incidence of CIN. At present, a systematic review and meta-analysis was conducted to evaluate the clinical effect of TMZ on prevention of CIN in patients with renal insufficiency. However, the study did not include patients from other countries and speaking different languages. So we conducted this study to update the previous meta-analysis that investigated the effects of TMZ on prevention of CIN in patients with renal insufficiency, and provided some theoretical reference for clinical. METHODS: By searching PubMed, Embase, the Cochrane Library, Web of Science, CBM, CNKI, VIP database, and Wang Fang database for randomized controlled trial, which is comparing TMZ versus conventional hydration for prevention of CIN. Two researchers independently screened literature, and then evaluated the quality of literature and extracted the relevant data. Stata 11.0 software was used for statistical analysis. RESULTS: Finally, this updated review showed that 3 studies that were not included in the previous meta-analysis were included in our study (3 articles were published in the Chinese Journal, 1 study for CIN, 1 study for CIN, serum creatinine (Scr), and superoxide dismutase, 1 study for CIN and Scr), and 1 outcome (Scr) reflecting the change of renal function was additionally included in our study. Of the 932 studies, 6 randomized controlled trials met the criteria, including 377 patients in TMZ group and 387 patients in control group. This meta-analysis for all studies showed that TMZ can significantly reduce the incidence of CIN (relative risk 0.27, 95% confidence interval [CI] 0.16, 0.46, P = 0.000), and can decrease the level of Scr after operation, including Scr of postoperative 24 hours (standardized mean difference [SMD] -0.30, 95% CI -0.51, -0.09, P = 0.005), Scr of postoperative 48 hours (SMD -0.66, 95% CI -1.23, -0.10, P = 0.022), and Scr of postoperative 7 days (SMD -0.74, 95% CI -1.36, -0.11, P = 0.021). However, the Scr of postoperative 72 hours between TMZ group and control group has no statistical significance (P = 0.362). CONCLUSION: Our study showed that when comparing with conventional hydration, TMZ can significantly reduce the incidence of CIN and the level of postoperative Scr. Therefore, we could suggest that TMZ was superior to conventional hydration for the treatment of CIN in patients with renal insufficiency. However, due to the restriction of quality and number of included articles, it still needs to carry out multicenter, randomized, double-blind clinical trials to confirm this conclusion in the future.

The effect of alprostadil on preventing contrast-induced nephropathy for percutaneous coronary intervention in diabetic patients: A systematic review and meta-analysis.

BACKGROUND: At present, there are a lot of research about the effect of Alprostadil on preventing contrast-induced nephropathy for percutaneous coronary intervention (PCI) in diabetic patients, but the clinical efficacy is not consistent, so we conduct this study and therefore determine the dominant strategy for the treatment of PCI in diabetic patients based on the best evidence currently. METHODS: An electronic database search was conducted in MEDLINE, Embase, Cochrane library, CBM, CNKI, VIP, and WanFang to retrieve randomized controlled trial (RCT) comparing Alprostadil versus hydration on preventing CIN for PCI in diabetic patients. Reference lists of relevant articles were also screened manually to retrieve additional ones. Two investigators independently assessed the eligibility of retrieved articles using predefined inclusion and exclusion criteria. All characteristics as well as outcome variables including incidence of CIN, blood urea nitrogen (BUN), cystatin C (CysC), glomerular filtration rate (GFR), serum creatinine (Scr), serum beta 2-microspheres (ß2-MG) presented in each included study were extracted. Heterogeneity was thought to be significant when I > 50%. All of the meta-analytic procedures were performed by using Review Manager software, version 5.3. RESULTS: Finally, data from 8 articles including 969 patients were included into this meta-analysis, among them, 487 patients in the experience group, and 482 patients in the control group. Meta analysis showed that the incidence of CIN in the experimental group was significantly lower than that in the control group (OR = 0.28,95%CI[0.18,0.42]). The incidence of adverse reactions in the experimental group was significantly lower than that in the control group (OR = 0.46,95%CI[0.24,0.85]). The BUN of 24 hours, 48 hours, and 72 hours in the experimental group were significantly lower than that of control group (MD = -0.77, 95%CI [-1.22, -0.32]; MD = -1.38, 95%CI [-1.83,-0.92]; MD = -2.43, 95%CI [-2.68,-2.19], respectively). The CysC of 24 hours, 48 hours, and 72 hours in the experimental group were significantly lower than that of control group (MD = -0.30, 95%CI [-0.40, -0.21]; MD = -0.54, 95%CI [-0.68,-0.41]; MD = -0.49, 95%CI [-0.63, -0.35], respectively). The GFR of 24 hours, 48 hours, and 72 hours in the experimental group were significantly higher than that of control group (MD = 7.86, 95%CI [4.44, 11.29], MD = 18.23, 95%CI [13.76,22.69], MD = 12.81, 95%CI [8.51,17.11], respectively). The Scr of 24 hours, 48 hours, and 72 hours in the experimental group were significantly lower than that of control group (MD = -9.09, 95%CI [-12.67, -5.51], MD = -19.14, 95%CI [-23.61, -14.66], MD = -6.50, 95%CI [-8.29, -4.71], respectively). The ß2-MG of 24 hours, 48 hours, and 72 hours in the experimental group were significantly lower than that of control group (MD = -0.12, 95%CI [-0.27, 0.03], MD = -0.55, 95%CI [-0.71, -0.39], MD = -0.50, 95%CI [-0.60, -0.39], respectively). CONCLUSION: Our result suggested that comparing with conventional Hydration, Alprostadil can significantly reduce the incidence of CIN, adverse reaction, and protect renal function in PCI in diabetic patients. Due to the limitations of the quality and quantity of the articles, this conclusion still needs further research to confirm.