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Objective: The aim of this study was to explore the effect of micro-ribonucleic acid (miR)-146a on acute gouty arthritis rats through Toll-like receptor-4/myeloid differentiation factor 88 (TLR4/MyD88) signal transduction pathway., Materials and Methods: A total of 30 clean-grade Sprague-Dawley rats were divided into three groups, including agomiR-146a group (n=10), antagomiR-146a group (n=10) and negative control group (NC, n=10). The model was successfully established via a one-time injection of sodium urate into ankle joint cavity. Subsequently, agomiR-146a (10 μL), antagomiR-146a (10 μL) and normal saline (10 μL) were intrathecally injected into rats in the three groups at 1 h before injection and 12 h, 24 h, 48 h and 72 h after injection, respectively. The ankle joint swelling index, joint dysfunction index and joint inflammation index of rats in the three groups were closely monitored. After 72 h of observation, the rats were euthanized, and synovial tissues were collected from the knee joint. The expression and distribution of nuclear factor-κB (NF-κB) in synovial tissues were detected using the immunohistochemical method. Meanwhile, the expression levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) were detected via enzyme-linked immunosorbent assay. Furthermore, the mRNA and protein expression levels of TLR4 and MyD88 were detected via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blotting, respectively., Results: No statistically significant differences in the joint swelling index, joint dysfunction index, joint inflammation index, TLR4 and MyD88 and related inflammatory factors were found between the NC group and antagomiR-146a group. Compared with the NC group, agomiR-146a group showed markedly reduced ankle joint swelling index (p<0.05). Meanwhile, joint landing behavior and inflammatory swelling were significantly relieved in the agomiR-146a group (p<0.05). The mRNA and protein expression levels of TLR4 and MyD88 were remarkably decreased as well (p<0.05). Furthermore, the expression and distribution of NF-κB in synovial tissues of agomiR-146a group was markedly reduced when compared with the NC group (p<0.05). In addition, agomiR-146a group exhibited significantly lower expression levels of inflammatory factors (TNF-α, IL-1 and IL-6) in synovial tissues (p<0.05)., Conclusions: MiR-146a alleviates joint inflammation of acute arthritis in rats through the TLR4/MyD88/NF-κB signaling pathway, which may become a new therapeutic target.

Objective: To investigate the correlation of serum vitamin A, D, and E levels with a recurrent respiratory infection (RRI) in children., Patients and Methods: The medical records of 422 children with RRI (a study group) in Cangzhou Central Hospital from January 2015 to December 2018 were retrospectively analyzed (the study group was divided into an active group and a stable group). Further 100 healthy children who underwent physical examination at the same time were enrolled as a control group. High-performance liquid chromatography (HPLC) was used to determine vitamin A, D, and E levels, so as to analyze their differences between the groups., Results: Vitamin A, D, and E in the active and stable groups were significantly lower than those in the control group (p < 0.001); in the active group they were significantly lower than those in the stable group (p < 0.001). According to partial correlation analysis, in children with active RRI, vitamin A was respectively positively correlated with vitamin D (r=0.945, p < 0.001), and vitamin E (r=0.988, p < 0.001). Moreover, vitamin E was positively correlated with vitamin D (r=0.959, p < 0.001)., Conclusions: The deficiency of vitamin A, D, and E is positively correlated with the disease activity of children with RRI. Therefore, the supplement of vitamin A, D, and E through dietary adjustment is beneficial to the rehabilitation of the children.

Objective: This study aimed to investigate the predictive value of joint detection of serum amyloid A (SAA), plasma procalcitonin (PCT), and whole blood hypersensitive C-reactive protein (hs-CRP) in the diagnosis and efficacy of neonatal septicemia., Patients and Methods: A total of 195 cases of neonatal septicemia patients admitted to our hospital from March 2013 to May 2017 were selected as observation group, and 100 healthy newborns in the same period were selected as control group. Before treatment, all newborns were detected with enzyme-linked immunosorbent assay (ELISA) for serum SAA, PCT, and hs-CRP three indicators respectively, and differences between expressions of PCT, HS-CRP, SAA in the serum of children (effective group) who improved after treatment and patients in ineffective group were observed., Results: Three indexes of SAA, PCT, and hs-CRP in study group were significantly higher than those in control group before treatment, while three indexes of SAA, PCT, and hs-CRP in effective group were significantly lower than those in ineffective group after treatment, with statistical significance (p<0.05). By drawing the ROC curve, it was found that the AUC area, specificity, and sensitivity of joint detection were better than those of the single item detection., Conclusions: Joint detection of SAA, PCT, and hs-CRP has high diagnostic value in neonatal septicemia and is worthy of clinical application.

SUMOylation regulates diverse cellular processes including transcription, cell cycle, protein stability, and apoptosis. A recent research has now revealed the role of SUMO1 in cardiac disorders. Studies have evidenced that failing heart induces SUMO2/3 conjugation. Moreover, increased SUMO2/3- dependent modification has been observed to result in congestive heart disease such as cardiac hypertrophy by promoting cardiac cell death. Also, few recent studies have confirmed the role of SUMOylation in cardiac protein degradation. On the other hand, over-expression of SENP5, SUMO2/3-specific deconjugation enzyme has been observed to result in dilated cardiomyopathy or cardiac failure. So, the present review article would enlighten the latest updates about SUMOylation and associated factors during cardiac disorders.

Objective: To explore the correlation between GDF15, MMP7 and gastric cancer and its prognosis., Patients and Methods: Thirty-six cases of gastric cancer admitted to our hospital from February 2014 to February 2015 were included in the observation group. Thirty-two healthy people were selected during the same period as the control group. The levels of MMP7 and GDF15 mRNA in the observation group before and after treatment and in the control group were detected by fluorescence quantitative PCR. The expressions of GDF15 and MMP7 proteins were detected by enzyme-linked immunosorbent assay and Western-blotting analysis. The expression of GDF15 and MMP7 in gastric carcinoma were tested by immunohistochemistry assay., Results: Compared with the control group, the levels of GDF15 and MMP7mRNA in the observation group were significantly increased in gastric cancer tissue before treatment (p<0.05). After treatment, there was no significant difference in the expressions of GDF15 and MMP7 mRNA in patients with significant improvement and the control group (p>0.05). Immunohistochemistry and Western blot results found that levels of GDF15 and MMP7 proteins in the observation group before treatment (14.28±1.03: 9.06±0.82 g/l) were significantly higher than that in the control group (1.05±0.21; 0.94±0.12 g/l). And there were no significant differences between patients with significant improvement (1.64±0.18; 1.03±0.22 mg/l) and the control group (p>0.05), while the levels in patients with no significant improvement (12.04±1.01; 8.21±0.65 mg/l) were significantly higher than that in the control group. Immunohistochemical results showed that the number of GDF15 and MMP7 positive cells in patients with significant improvement (10.32%; 9.01%) were significantly lower than that before treatment or in patients with no significant improvement (85.43%; 90.27%)., Conclusions: There were significant correlations between GDF15, MMP7 and the incidence of gastric cancer. Levels of GDF15 and MMP7 in patients were significantly correlated with the degree of rehabilitation after treatment.

Cardiovascular disease (CVD) is the leading cause of death, irrespective of socioeconomic status, ethnic background and sex. Despite the considerable progress in the treatment, the complex pathophysiology underlying CVD is still not clear. In past few years, genetic approaches including epigenetics and personalized medicine initiated a new way of treating CVD. Epigenetics refers to the non-DNA sequence related heritable changes in gene expression and its role in understanding and treating coronary artery disease, heart failure, and cardiac hypertrophy is currently recognized as an important player. Histone acetylation, deactylation, DNA methylation and histone methylation are different mechanisms of epigenetic modifications. Cardiac Hypertrophy is linked with histone acetylation and the activity of histone acetyltransferases (HATs) has a positive role in cardiac hypertrophy. Altered DNA methylation, miRNA activity have been shown to be associated with atherosclerosis. It is documented that re-expression of certain fetal genes in the adult heart contributes to the development of heart failure syndrome, which is often associated with pathological cardiac remodeling comprising of changes in heart mass, size and shape. Thus, it appears that approaches that counteract epigenetic changes occurring in CVD can prove to have significant therapeutic impact. However, there are no major clinical practice or therapeutics reports of epigenetics contribution in CVD, even though deacetylase inhibitors like trichostatin A were shown to have some positive effects. In this review we will present an overview of various epigenetic mechanisms such as DNA methylation, histone modifications, and microRNA-dependent mechanisms in CVD and the novel epigenetics-based therapeutic approaches.

Cardiovascular disease (CVD), the leading cause of death, is mostly precipitated by cardiometabolic risk and chronic kidney disease (CKD). CVD and kidney disease are closely interrelated and disease of one organ cause dysfunction of the other, ultimately leading to the failure of both organs. Patients with end-stage renal disease (ESRD) are at much higher risk of mortality due to CVD. Traditional CVD risk factors viz., hypertension, hyperlipidemia, and diabetes do not account for the high cardiovascular risk in CKD patients and also standard clinical interventions for managing CVD that are successful in the general population, are ineffective to lower the death rate in CKD patients. Nontraditional factors, related to disturbed mineral and vitamin D metabolism were able to provide some explanation in terms of vascular calcification, for the increased risk of CVD in CKD. Fibroblast Growth Factor 23, a bone-derived hormone that regulates vitamin D synthesis in renal proximal tubules and renal phosphate reabsorption, has been suggested to be the missing link between CKD and CVD. Acute Kidney Injury (AKI) is strongly related to the progress of CVD and its early diagnosis and treatment has significant positive effect on the outcomes of CVD in the affected patients. Besides this, non-dialysable protein-bound uraemic toxins such as indoxyl sulfate and p-cresyl sulfate, produced by colonic microbes from dietary amino acids, appear to cause renal dysfunction. Thus, therapeutic approaches targeting colonic microbiota, have led to new prospects in early intervention for CKD patients. Intervention targets for preventing CVD events in CKD patients ideally should include control of blood pressure and dyslipidemia, diabetes mellitus, lowering proteinuria, correction of anemia, management of mineral metabolism abnormalities and life style changes including smoking cessation, decreased consumption of salt, and achievement of normal body mass index. Use of β-blockers, renin-angiotensin blockers, diuretics, statins, and aspirin are helpful in the early stages of CKD. In this review, we will address the biological, pathological and clinical relationship between CVD and CKD and their therapeutic management.

Heart failure (HF) results from the impaired ability of heart to fill or pump out blood. HF is a common health problem with a multitude of causes and affects ~30 million people worldwide. Since ageing is a major risk factor for HF and as several treatment options are currently available to prolong the patients' survival, the number of affected patients is expected to grow. Even though traditional methods of assessment have been in use for managing HF, these are limited by time consuming and costly subjective interpretation and also by their invasive nature. Comparatively, biomarkers offer an objective and biologically relevant information that in conjunction with the patients' clinical findings provides optimal picture regarding the status of the HF patient and thus helps in diagnosis and prognosis. The current gold standard biomarkers for the diagnosis and prognosis of HF are B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP). Additional novel biomarkers (e.g., mid-regional pro atrial natriuretic peptide (MR-proANP), mid-regional pro adrenomedullin (MR-proADM), troponins, soluble ST2 (sST2), growth differentiation factor (GDF)-15 and galectin-3) can potentially identify different pathophysiological processes such as myocardial insult, inflammation and remodeling as the causes for the development and progression of HF. Different biomarkers of HF not only reflect the underlying mechanisms/pathways of HF and also its progression and also point specific therapy options. A multi-biomarker approach for personalized medical care is not too far fetched and such approach can greatly enhance diagnosis, prognostication, and therapy guidance for HF. In this review we describe the current status of HF biomarkers in clinical use and in laboratory research and the efforts aimed at the identification of novel biomarkers for HF.