Objective To investigate the clinical significance of interleukin-6 (IL-6) and leukotriene B4 (LTB4) in the early diagnosis of allergic purpura(HSP) in children and its effect on prognosis.Methods A total of 68 children with Henoch-Schonlein purpura enrolled in our hospital from May 2014 to May 2016 were selected.The levels of IL-6 and LTB4 in the early stage and early recovery stage of children were detected.The significance of early diagnosis and the impact on prognosis were analyzed.Results Compared with the control group,the levels of IL-6 and LTB4 in acute and early recovery stage of children with Henoch-Schonlein purpura were significantly higher(P＜0.05),and those in the acute stage of children were higher than those in the early recovery stage(P＜0.05).The higher the level of IL-6 and LTB4 in the serum,the greater the possibility of renal damage in patients,and the difference was statistically significant (P＜0.05).The higher the level of serum IL-6 and LTB4,the higher the cure rate(P＜0.05) and the lower the recurrence rate(P＜0.05).The AUC of the combined detection of HSP was 0.894 and the sensitivity was 0.811,which were better than those of IL-6 and LTB4(P＜0.05).Conclusion Combined detection of IL-6 and LTB4 is of great clinical significance in the early diagnosis and prognosis of HSP.

Aim To investigate the effect of colchicine on lipopolysaccharide (LPS) induced endothelial to mesenchymal transition (EndMT) in human umbilical vein vascular endothelial cells (HUVECs) and its related mechanisms. Methods The EndMT model was established by treating HUVECs with LPS. Cell proliferation rate was detected by CCK-8 assay, cytotoxicity was detected by LDH assay, and the optimal drug concentration was screened. The cells were divided into the normal control group, the normal control + colchicine (10 nmol • L) group, the LPS (10 mg • L) model group, and the LPS + colchicine (10 nmol • L) group. The morphologic changes of the cells were observed under an inverted microscope, the cell migration ability was detected by Transwell assay, and the ability of tube formation was analyzed by tube formation assay. The expression of endothelial markers (CD31/ VE-cadherin) and mesenchymal cell markers (a-SMA/FSP-1) were detected by Western blot. NF-KB inhibitor was used to detect the changes in related signaling pathways. Results CCK-8 and LDH experiments showed that 10 nmol • L colchicine was the optimal concentration. LPS could induce morphological changes in HUVECs, and colchicine could reverse morphological changes in HUVECs to a certain extent. Transwell experiment showed that the migration ability of HUVECs in the LPS treatment group was significantly enhanced (P < 0. 05), and colchicine could significantly reverse this phenomenon (P < 0. 05) . Tube formation experiment showed that LPS decreased the endothelial tube formation ability of HUVECs (P < 0. 05), while colchicine treatment markedly improved LPS-induced tube formation defects (P < 0. 05) . Western blot assay showed that after colchicine co-cultured with LPS, the expression levels of CD31 and VE-cadherin significantly increased compared with the model group (P < 0. 05), while the expression levels of a-SMA and FSP-1 significantly decreased compared with the model group (P < 0. 05) . During the induction of EndMT by LPS, colchicine could inhibit the activation of the NF-KB/Snail signaling pathway. Conclusions Colchicine can effectively inhibit EndMT induced by LPS, and the mechanism may be related to the regulation of the NF-KB/Snail signaling pathway.

Objective To investigate the effect and mechanism of AngⅡ on collagen in hepatic stellate cell. Methods HSCs were isolated and cultured, 3H-pro incorporation method was used to evaluate the effects of different doses of AngⅡ on the proline syntheses. RT-PCR assay were used to assess changes in mRNA expression levels of type Ⅰ and Ⅲ procollagen. PDGFR-β mRNA and protein were determined by in situ hybridization and immunocytochemistry. Results 10-8~ 10-5 mol/L AngⅡ could significantly increase the 3H-pro incorporation rate of HSC in a dose-dependent style, 10-6 mol/L AngⅡis the most effective dose. The cultured HSC showed a little expression of type Ⅰ and Ⅲ procollagen mRNAs, while 10-6 mol/L AngⅡwas able to enhance the expression for type Ⅰ and Ⅲ procollagen mRNAs significantly(P < 0.01). AngⅡalso could enhance both mRNA and protein expression of PDGFR-β on HSC(P < 0.01). Conclusion These results suggest that AngⅡ could promote HSC collagen synthesis by enhancing the expressions of PDGFR-β.

Objective To explore the ^“contribution^” of different exposures to cardiovascular diseases at the population level and to construct a risk prediction model for the effective allocation of prevention resources. Methods The CHNS (China Health and Nutrition Survey) database was used. In 2009, 2011 and 2015, 9 899 permanent residents aged 35 to 75 years in 10 provinces and cities in the central and eastern regions (Beijing, Liaoning, Heilongjiang, Shanghai, Shandong, Henan, Hubei, Hunan, Guangxi and Jiangsu) were selected as the research subjects. A single-factor analysis was conducted to examine the risk factors including sex, age, BMI, marital status, urban/rural area, sleep time, smoking, alcohol consumption, diabetes, education, and health insurance. The multifactor-adjusted population-attributable risk of certain risk factors was also estimated based on logistic regression analysis. The cardiovascular disease (CVD) risk prediction model was developed using a modeling group of 6 927 randomly selected individuals (70%) and a validation group of 2 974 individuals (30%). The model's differentiation and calibration were assessed using the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow goodness-of-fit test. Results The results showed that the adjusted population attributable risk and 95% confidence interval for BMI, sleep time, smoking, drinking and diabetes were 32.20% (27.67%-36.89%), 7.90% (1.68%-16.58%), 18.56% (11.35%-26.24%), 6.47% (0.11%-13.25%) and 5.73% (4.42%-7.03%). The results of multivariate adjusted population attributable risk percentage showed that BMI was the dominant cause of cardiovascular diseases, followed by smoking, sleep time, drinking and diabetes. The low-risk prevalence rate was 18.44%, the higher-risk prevalence rate was 14.19%, and the high-risk prevalence rate was 42.52%. The area under ROC curve AUC was 0.711, P<0.001, and Hosmer-Lemeshow goodness of fit test showed P=0.257. Conclusion In the future, it is important to focus on high-risk groups , control body mass index to the normal range, and reduce smoking , which is of great significance for the prevention of cardiovascular diseases. The risk prediction model has the value of good differentiation and practicability , and can provide certain prediction ability for the prevention of cardiovascular diseases.

BACKGROUNDNumerous studies have demonstrated that the peroxisome proliferator-activated receptor-γ (PPARγ) plays an important role in regulating endothelial progenitor cells (EPC) function. Telmisartan, as a partial agonist of PPARγ, may have an effect on the regulation of EPC functions. The purpose of this study was to investigate the effects of telmisartan on EPC proliferation and differentiation.

METHODSPeripheral blood derived mononuclear cells containing EPC were isolated from healthy volunteers and then cultured on fibronectin-coated dishes in the presence or absence of telmisartan. The proliferative activity of EPC was determined by colony forming units (CFU) and MTT assay. The migratory activity of EPC was assessed by transwell assay. The expression of endothelial cells (EC) markers, including vascular endothelial cadherin (VE-cadherin), von Willebrand factor (vWF) and endothelial nitric oxide synthase (eNOS), were measured by Western blotting analysis.

RESULTSMorphological analysis revealed that telmisartan significantly increased the proliferation of EPC and the number of endothelial cell colony forming units. Telmisartan could enhance the expression of the makers of mature EC, including VE-cadherin, vWF, and eNOS, which indicated telmisartan could stimulate EPC to differentiate into mature EC. Telmisartan increased the phosphorylation of Akt in EPC. The inhibition of Akt activation significantly attenuated the effect of telmisartan on EPC functions, suggesting that Akt is involved in the stimulatory effect of telmisartan on EPC differentiation.

CONCLUSIONSThe results of this study demonstrate that telmisartan promotes EPC functions via activation of Akt.

Benzimidazoles ; pharmacology ; Benzoates ; pharmacology ; Cell Differentiation ; drug effects ; genetics ; Cell Proliferation ; drug effects ; Cells, Cultured ; Endothelial Cells ; cytology ; Humans ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Stem Cells ; cytology ; drug effects

Objective: To examine the correlation between the promoter methylation of Sterol regulatory-element binding protein-2 (SREBP-2) and miR-33a expression as well as serum markers in patients with coronary artery disease (CAD). Methods: The case-control study. 100 participants who underwent coronary angiography from August 2017 to April 2018 in TaiheHospital, Hubei University of Medicine, were recruited in this study.The methylation level of two fragments, including 12 CpG sites in the promoter region of SREBP-2, have been detected by pyrosequencing in 50 patients with coronary artery disease (CAD) and 50 non-CAD controls. Serum miR-33a level and a panel of 15 CAD related biomarkers were examined by qPCR and routine biochemistry methods. Results: Methylation level of one CpG site (F1-4 loci) in SREBP-2 promoter region were significant higher in CAD patients than in controls(4.56%±0.70% vs 3.54%±0.72%, t=-3.864, P<0.001); methylation level of F1-4 site was negatively correlates with the serum miR-33a levels and high-density lipoprotein cholesterol (HDL-C) levels(r=-0.318, P=0.001; r=-0.225, P=0.024, respectively). Furthermore, F1-4 hypermethylation was an independent risk factor of CAD, independent of age, gender, histories of hypertension, hyperlipidemia, and diabetes(OR=2.452, 95%CI=1.398-4.299, P=0.002). Conclusion These results suggest that DNA methylation and miRNA might cooperate to regulate the lipid metabolism in CAD.

Objective To analyze the effect of moistening room mirror combined with pranoprofen eye drops on dry eye and its effect on serum MMP-2 and STRA6 levels. Methods 100 cases with dry eye disease treated in our hospital from January 2016 to August 2017 were randomly divided into the observation group and the control group. The control and observation group were treated with pranoprofen eye drops and moisturizing room mirror combined with pranoprofen eye drops. The clinical efficacy of the patients was evaluated, and the symptoms and the survival quality, MMP-2 and STRA6 of the patients were analyzed. Results Significant clinical efficiency was significantly higher in the observation group than in the control group (P < 0.05). BUT, SIt, visual related quality of life scores in the observation group were significantly higher than the control group (P < 0.05). Symptom score, MMP-2 and STRA6 levels in the observation group were significantly lower than the control group (P < 0.05).Conclusions The combination of moisturizing chamber mirror and pralofen eye drops in the treatment of dry eye can effectively improve the clinical efficacy and reduce the levels of MMP-2 and STRA6.

BACKGROUND: Sweat secreted by eccrine sweat glands is transported to the skin surface through the lumen. The eccrine sweat gland develops from the initial solid bud to the final gland structure with a lumen, but how the lumen is formed and the mechanism of lumen formation have not yet been fully elucidated. This study aimed to investigate the mechanism of lumen formation of eccrine gland organoids (EGOs). METHODS: Human eccrine sweat glands were isolated from the skin for tissue culture, and the primary cultured cells were collected and cultured in Matrigel for 14 days in vitro. EGOs at different development days were collected for hematoxylin and eosin (H&E) staining to observe morphological changes and for immunofluorescence staining of proliferation marker Ki67, cellular motility marker filamentous actin (F-actin), and autophagy marker LC3B. Western blotting was used to detect the expression of Ki67, F-actin, and LC3B. Moreover, apoptosis was detected using a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay kit, and the expression of poly (ADP-ribose) polymerase and Caspase-3 was detected by Western blot. In addition, 3-methyladenine (3MA) was used as an autophagy inhibitor to detect whether the formation of sweat glands can be effectively inhibited. RESULTS: The results showed that a single gland cell proliferated rapidly and formed EGOs on day 4. The earliest lumen formation was observed on day 6. From day 8 to day 14, the rate of lumen formation in EGOs increased significantly. The immunofluorescence and Western blot analyses showed that the expression of Ki67 gradually decreased with the increase in days, while the F-actin expression level did not change. Notably, the expression of autophagy marker LC3B was detected in the interior cells of EGOs as the apoptosis signal of EGOs was negative. Compared with the control group, the autophagy inhibitor 3MA can effectively limit the formation rate of the lumen and reduce the inner diameter of EGOs. CONCLUSION Using our model of eccrine gland 3D-reconstruction in Matrigel, we determined that autophagy rather than apoptosis plays a role in the lumen formation of EGOs.
Apoptosis ; Autophagy ; Eccrine Glands ; Epithelial Cells ; Humans ; Organoids

Traditional Chinese medicine (TCM) network pharmacology and molecular docking technology were applied to explore the mechanism of anti-coronavirus pneumonia (coronavirus disease 2019, COVID-19) of Qingfei Paidu decoction. The Chinese Pharmacopoeia (2015 edition) and Traditional Chinese Medicine Systems Pharmacology (TCMSP), OMIM (Online Mendelian Inheritance in Man), GeneCard, STRING, and others online databases are used for building a series of network, and selecting the core target and analyzing the signal pathway. Finally, we make molecular docking predictions for the important compounds. The results showed that the Qingfei Paidu decoction compound-pneumonia target network contained 292 compounds and 214 corresponding targets, and the core targets involved AKT1 (AKT serine/threonine kinase 1), IL6 (interleukin 6), MAPK8 (mitogen-activated protein kinase 8), MAPK1 (mitogen-activated protein kinase 1), and JUN (jun proto-oncogene). GO (Gene Ontology) function enrichment analysis yielded 858 GO entries, and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment screening yielded 122 related pathways, including hypoxia inducible factor-1 (HIF-1) and Toll-like receptor (TLRs) signaling pathways related to pneumonia, as well as T-cell receptor (TCR) signaling pathway related to lung injury protection. The molecular docking results showed that some core compounds of the Chinese herbal medicine of Qingfei Paidu decoction have a certain degree of affinity for 2019-novel coronavirus (2019-nCoV) main protease (3C-like protease, 3CLpro) and angiotensin-converting enzyme 2 (ACE2). In this paper, we preliminarily explored the potential therapeutic mechanism for Qingfei Paidu decoction to against COVID-19 and predicted the active ingredients. We hope that the results will help to the further study on the active ingredients and mechanism of Qingfei Paidu decoction to COVID-19.

Humans ; East Asian People ; Surveys and Questionnaires ; Vitiligo/epidemiology*