Systematic review of Yougui pills combined with levothyroxine sodium in the treatment of hypothyroidism.

BACKGROUND: Yougui pills have long been used to treat hypothyroidism, usually in combination with levothyroxine sodium in clinical treatment, while their clinical efficacy and safety are still controversial when compared to levothyroxine treatment alone. AIM: To explore the clinical efficacy and safety of Yougui pills combined with levothyroxine sodium in the treatment of hypothyroidism. METHODS: This meta-analysis was performed in accordance with the PRISMA guidelines. Randomized controlled trials on Yougui pills in the treatment of hypothyroidism published from 2008 to May 2021 were searched in a total of 8 databases (4 databases in Chinese and 4 databases in English). The quality of the included studies was evaluated according to the Cochrane risk assessment tool. Weighted mean difference (WMD) was used for continuous variables, and relative risk (RR) was used for binary variables. Data were extracted, and the meta-analysis was conducted with the statistical software of Stata15.0 and RevMan5.0. RESULTS: A total of 140 articles were retrieved, and 9 of them were finally included, with a total sample size of 936 cases. The main meta-analysis results are as follows: (1) The group of Yougui pills combined with levothyroxine sodium had a significantly higher overall response rate than the group of levothyroxine sodium (RR = 1.20, 95%CI 1.12, 1.28, P < 0.00001); (2) Yougui pills combined with levothyroxine sodium achieved significantly better efficacy than levothyroxine sodium alone in alleviating adverse symptoms [standard mean difference (SMD) = -1.10, 95%CI: -1.37, -0.84, P < 0.00001]; (3) The level of thyrotropin stimulating hormone in the group of Yougui pills combined with levothyroxine sodium was significantly lower than in the control group of levothyroxine sodium (WMD = -1.38, 95%CI: -2.10, -0.67, P = 0.00001); (4) The level of free triiodothyronine in the group of Yougui pills combined with levothyroxine sodium was higher than that in the control group of levothyroxine sodium (WMD = 0.41, 95%CI: 0.03, 0.79, P = 0.03); (5) The level of free thyroxine in the group of Yougui pills combined with levothyroxine sodium was significantly higher than that in the control group of levothyroxine sodium (SMD = 0.83, 95%CI: 0.44, 1.22, P ≤ 0.0001); and (6) The adverse reactions in the group of Yougui pills combined with levothyroxine sodium were significantly less than those in the control group of levothyroxine sodium (RR = 0.33, 95%CI: 0.20, -0.53, P < 0.00001). CONCLUSION: In the treatment of hypothyroidism, the combination of Yougui pills with levothyroxine sodium may be better than levothyroxine sodium treatment alone.

Diagnostic accuracy of ≥ 16-slice spiral computed tomography for local staging of colon cancer: A systematic review and meta-analysis.

BACKGROUND: Colorectal cancer is one of the most common cancers worldwide with high mortality and is classified as a single entity, although colon cancer and rectal cancer have largely different diagnoses, treatments, surgical methods, and recurrence rates. ≥ 16-slice spiral computed tomography (SCT) is mostly applied to detect the local stage of colon cancer; however, its diagnostic accuracy and whether it is conducive to distinguishing between high-risk and low-risk colon cancer are unclear. AIM: To systematically review the diagnostic accuracy of ≥ 16-slice SCT for local staging of colon cancer. METHODS: Based on the PubMed, EMBASE, Cochrane Library, and Web of Science databases, computers were used to search the literature from the establishment of the database to April 2021, and the results of the diagnostic tests on ≥ 16-slice SCT for local staging of colon cancer were collected according to the inclusion criteria. The data were then extracted and assessed on the basis of the Quality Assessment Checklist of the Institute of Economics of Canada, Reference Citation Analysis (https://www.referencecitationanalysis.com/). Afterward, a meta-analysis was performed using the statistical software Meta-disc 14.0 and Stata 15.0. RESULTS: Eleven studies that provided data on 1613 subjects with computed tomography diagnostic tests were included in this study. Meta-analysis revealed that the pooled sensitivity, pooled specificity, pooled negative likelihood ratio (LR), pooled diagnostic odds ratio, and area under the fitted receiver operating characteristic (ROC) curve of ≥ 16-slice SCT for colon cancer T staging were 0.67 (95%CI: 0.65-0.70), 0.81 (95%CI: 0.80-0.83), 4.13 (95%CI: 2.66-6.41), 0.39 (95%CI: 0.31-0.49), 10.81 (95%CI: 7.33-15.94), and 0.829, respectively, while the specificity, negative LR, diagnostic odds ratio, and area under the fitted ROC curve of ≥ 16-slice SCT for N staging of colon cancer were 0.54 (95%CI: 0.49-0.59), 0.74 (95%CI: 0.70-0.77), 1.92 (95%CI: 1.36-2.70), 0.67 (95%CI: 0.51-0.87), 3.74 (95%CI: 1.76-7.94), and 0.829 respectively. The sensitivity and specificity of ≥ 16-slice SCT for colon cancer T staging were acceptable, while the sensitivity for colon cancer N staging was relatively low, though its specificity was acceptable. CONCLUSION: ≥ 16-slice SCT for local staging of colon cancer has good diagnostic value; however, the accuracy needs to be confirmed by further clinical practice.

Syringic acid mitigates myocardial ischemia reperfusion injury by activating the PI3K/Akt/GSK-3ß signaling pathway.

Syringic acid is an abundant phenolic acid compound that possesses anti-oxidant, anti-microbial, anti-inflammatory, and anti-endotoxic properties. However, the research of pretreatment with syringic acid against myocardial ischemia reperfusion is still limited. Thus, our research revealed the protective effect of syringic acid in the rat model with myocardial ischemia reperfusion injury. Histological analysis was performed by hematoxylin and eosin (H&E). The myocardial systolic function was detected by echocardiographic. Myocardial infarct size was measured by Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC) double staining. The apoptosis index was recorded by Terminal deoxynucleotidyl transferase dUTP nick end labeling staining (TUNEL). The contents of creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH) in the serum were determined by a commercial kit. The expression of the PI3K/Akt/GSK-3ß signaling pathway-related molecules and apoptosis-associated indicators was detected by western blotting or real-time PCR. We found that pretreatment with syringic acid obviously increased the myocardial systolic function (LVEF and LVFS) and decreased the infarct size, the apoptosis index as well as the serum level of CK-MB and LDH. Meanwhile, syringic acid also remarkably augmented the contents of p-PI3K, p-Akt, p-GSK-3ß, Bcl-2 and mitochondria cytochrome c. However, the expression of caspase-3, -9 and Bax significantly reduced. Interestingly, co-treatment with PI3K inhibitor of LY294002 counteracted those effects induced by syringic acid. In conclusion, pretreatment with syringic acid can mitigate myocardial ischemia reperfusion injury by inhibiting mitochondria-induced apoptosis which is regulated by the PI3K/Akt/GSK-3ß signaling pathway.

LncRNA H19 ameliorates myocardial infarction-induced myocardial injury and maladaptive cardiac remodelling by regulating KDM3A.

Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide, and novel therapeutic targets still need to be investigated to alleviate myocardial injury and the ensuing maladaptive cardiac remodelling. Accumulating studies have indicated that lncRNA H19 might exert a crucial regulatory effect on cardiovascular disease. In this study, we aimed to explore the biological function and molecular mechanism of H19 in MI. To investigate the biological functions of H19, miRNA-22-3p and KDM3A, gain- and loss-of-function experiments were performed. In addition, bioinformatics analysis, dual-luciferase reporter assays, RNA immunoprecipitation (RIP) assays, RNA pull-down assays, quantitative RT-PCR and Western blot analyses as well as rescue experiments were conducted to reveal an underlying competitive endogenous RNA (ceRNA) mechanism. We found that H19 was significantly down-regulated after MI. Functionally, enforced H19 expression dramatically reduced infarct size, improved cardiac performance and alleviated cardiac fibrosis by mitigating myocardial apoptosis and decreasing inflammation. However, H19 knockdown resulted in the opposite effects. Bioinformatics analysis and dual-luciferase assays revealed that, mechanistically, miR-22-3p was a direct target of H19, which was also confirmed by RIP and RNA pull-down assays in primary cardiomyocytes. In addition, bioinformatics analysis and dual-luciferase reporter assays also demonstrated that miRNA-22-3p directly targeted the KDM3A gene. Moreover, subsequent rescue experiments further verified that H19 regulated the expression of KDM3A to ameliorate MI-induced myocardial injury in a miR-22-3p-dependent manner. The present study revealed the critical role of the lncRNAH19/miR-22-3p/KDM3A pathway in MI. These findings suggest that H19 may act as a potential biomarker and therapeutic target for MI.

Silica-coated magnetic nanoparticles labeled endothelial progenitor cells alleviate ischemic myocardial injury and improve long-term cardiac function with magnetic field guidance in rats with myocardial infarction.

Low retention of endothelial progenitor cells (EPCs) in the infarct area has been suggested to be responsible for the poor clinical efficacy of EPC therapy for myocardial infarction (MI). This study aimed to evaluate whether magnetized EPCs guided through an external magnetic field could augment the aggregation of EPCs in an ischemia area, thereby enhancing therapeutic efficacy. EPCs from male rats were isolated and labeled with silica-coated magnetic iron oxide nanoparticles to form magnetized EPCs. Then, the proliferation, migration, vascularization, and cytophenotypic markers of magnetized EPCs were analyzed. Afterward, the magnetized EPCs (1 × 106 ) were transplanted into a female rat model of MI via the tail vein at 7 days after MI with or without the guidance of an external magnet above the infarct area. Cardiac function, myocardial fibrosis, and the apoptosis of cardiomyocytes were observed at 4 weeks after treatment. In addition, EPC retention and the angiogenesis of ischemic myocardium were evaluated. Labeling with magnetic nanoparticles exhibited minimal influence to the biological functions of EPCs. The transplantation of magnetized EPCs guided by an external magnet significantly improved the cardiac function, decreased infarction size, and reduced myocardial apoptosis in MI rats. Moreover, enhanced aggregations of magnetized EPCs in the infarcted border zone were observed in rats with external magnet-guided transplantation, accompanied by the significantly increased density of microvessels and upregulated the expression of proangiogenic factors, when compared with non-external-magnet-guided rats. The magnetic field-guided transplantation of magnetized EPCs was associated with the enhanced aggregation of EPCs in the infarcted border zone, thereby improving the therapeutic efficacy of MI.

Long noncoding RNA UCA1 inhibits ischaemia/reperfusion injury induced cardiomyocytes apoptosis via suppression of endoplasmic reticulum stress.

BACKGROUND: Ischemia heart disease is one of the major causes of death worldwide which often associated with tissue infarction and limit the recovery of function. Multiple factors involved in the I/R-induced cardiomyocyte dysfunction which were consistent with a role of oxidative stress and altered endothelium-dependent responses. However, the pathogenic mechanisms in I/R injury remain unclear. MATERIALS AND METHODS: The H9C2 cells were in the ischaemia/reperfusion (I/R) condition. After I/R, the cells were transfected with or without adenovirus-urothelial carcinoma associated 1(Ad-UCA1). Then qRT-PCR analysis was performed to quantify mRNA expression of different treatment groups. Cell apoptosis rate was assessed using flow cytometry and ER stress biomarker expression were measured by immunoblotting. Intracellular and mitochondrial ROS generation were assayed by fluorescence microscope after staining with the DCFDA or MitoSOX. RESULTS: I/R conditions trigger lncRNAs UCA1 expression, cellular and mitochondria ROS production, resulting in cell apoptosis through the induction of oxidative and ER stress. Overexpression of UCA1 protects H9C2 cells from I/R-induced ER stress and cell apoptosis. Moreover, UCA1 might be a potential regulator in the protective effect of I/R­induced oxidative stress and mitochondria dysfunction. Subsequently, ER stress inhibitor attenuated the effect of siUCA1 induced injury in H9C2 cells. CONCLUSION: The expression of UCA1 against I/R induced oxidative stress and mitochondria dysfunction via suppression of endoplasmic reticulum stress. UCA1 might be a biomarker to improved diagnosis of I/R injury.