Objective:To provide theoretical basis for the relevant mechanisms in diabetic retinopathy by bioinformatics methods.Methods:Proliferative diabetic retinopathy(PDR)datasets GSE60439 and GSE94019 were screened through GEO database.Expres-sion data of GSE60439 dataset was extracted using R language,and the differential genes were determined,with the screening condi-tions of P<0.05 and|log2FC|≥1;WGCNA was used to select the important modules related to PDR in GSE94019 dataset;key genes were obtained by intersecting differential genes and genes in important modules.Key genes were subjected to GO and KEGG enrich-ment analysis;PPI network was constructed to identify high-risk key proteins.Finally,CIBERSORTx was used to analyze the infiltra-tion of immune cells in PDR,and Pearson correlation analysis was used to screen key genes related to immune cells as core genes.Results:Three core genes were finally obtained,namely Col1a1,Col1a2 and Col3a1,their expressions were positively correlated with M2 macrophages,and the core genes were enriched in the AGEs-RAGE signaling pathway.Conclusion:Positive feedback may be formed between M2 macrophages,AGEs-RAGE signaling pathway and collagen genes(Col1a1,Col1a2,Col3a1),even without the stimulation of high glucose,this vicious circle may continue to damage retinal tissue.

Objective:To explore the molecular mechanism of clinical bleeding in a family with hereditary coagulation factor Ⅺ (FⅪ) deficiency caused by a novel mutation of the coagulation factor Ⅺ (FⅪ) gene.Methods:A male proband with hereditary coagulation factor XI deficiency who was admitted to Yuncheng Central Hospital Affiliated to Shanxi Medical University due to "adenoid hypertrophy" on February 23, 2023 and his family members (5 people in 3 generations) were selected as research subjects. The clinical data of the proband and family members were collected; the relevant coagulation indexes of all members were tested; those with abnormal coagulation indexes (prolonged activated partial thromboplastin time (APTT), normal thrombin time (PT) and fibrinogen (Fib)) were selected for APTT correction experiment; those with corrected Rosner index (RI) less than 10% were selected to detect FⅪ activity (FⅪ:C) by one-step method, FⅪ antigen (FⅪ:Ag) by ELISA method, and whole exon sequence by Illumina sequencing method. New mutation sites were rated according to the American College of Medical Genetics and Genomics (ACMG) related variation rating guidelines, and bioinformatics software was used to predict the impact of new mutations on protein structure and function.Results:The APTT of the proband, his father and his daughter were all prolonged and their RI were all less than 10%. Further tests revealed that FⅪ:C and FⅪ:Ag of the three were all decreased. Illumina sequencing revealed a new frameshift mutation c.1223dupC (P.Ser409Leufs*32) in exon 11 of FⅪ of the three people, and a missense mutation c.G1253T (p.Gly418Val) in exon 11 of FⅪ of the proband′s father. ACMG rated the new mutation as pathogenic, and c.G1253T was a reported possible pathogenic mutation.Conclusion:The heterozygous frameshift mutation c.1223dupC (P.Ser409Leufs*32) in exon 11 of FⅪ may be the main molecular mechanism of the disease in this family.

Objective To investigate the changes and formation mechanism of plasma endothelial microparticles (EMPs) in patients with acute pancreatitis (AP). Methods Blood samples were collected from 60 patients with AP who were treated in The First Affiliated Hospital of Anhui Medical University from August 2020 to June 2021, and these patients were divided into mild acute pancreatitis (MAP) group with 23 patients, moderate-severe acute pancreatitis (MSAP) group with 23 patients, and severe acute pancreatitis (SAP) group with 14 patients; 20 individuals who underwent physical examination were enrolled as control group.Differential centrifugation was used to obtain platelet-poor plasma, flow cytometry was used to measure the level of CD31 + CD41 - EMPs, and ELISA was used to measure the levels of endothelin-1(ET-1), von Willebrand factor (vWF), nitric oxide (NO), and vascular cell adhesion molecule-1(VCAM-1).HUVECs were stimulated by the plasma of AP patients, and then flow cytometry and qRT-PCR were used to measure the changes in EMPs, reactive oxygen species (ROS), and mitochondrial membrane potential and the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1(ICAM-1), VCAM-1, NADPH oxidase, and P-selectin.A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups and within each group.The chi-square test was used for comparison of categorical data between groups, and the Pearson correlation test was used for correlation analysis. Results Compared with the control group, the MAP, MSAP, and SAP groups had a significant increase in the level of EMPs (all P < 0.05).Compared with the MAP and MSAP groups, the SAP group had a significant increase in the level of EMPs (both P < 0.05).In the patients with AP, the level of EMPs was negatively correlated with Acute Physiology and Chronic Health Evaluation Ⅱ score, Bedside Index for Severity in Acute Pancreatitis, Ranson score, CT score, and C-reactive protein ( r =0.686 2, 0.777 3, 0.713 8, 0.771 8, and 0.473 9, all P < 0.01).Compared with the control group, the MAP, MSAP, and SAP groups had significant increases in the levels of ET-1, vWF, and VCAM-1 and a significant reduction in the level of NO (all P < 0.05).Compared with the control group, the MSAP and SAP groups had the plasma that promoted the release of a large amount of EMPs (both P < 0.05).Compared with the control group, all the other groups, except the MAP group in terms of VCAM-1 and eNOS, had significant increases in the mRNA expression levels of eNOS, iNOS, ICAM-1, P-selectin, VCAM-1, and NADPH oxidase (all P < 0.05).Compared with the HC group, the MAP, MSAP, and SAP groups and the LPS group had a significant increase in the level of ROS and a significant reduction in mitochondrial membrane potential in HUVECs (all P < 0.05). Conclusion There is a significant increase in the plasma level of EMPs in AP patients, which is correlated with the severity of pancreatitis.Meanwhile, the plasma of AP patients can promote the formation of EMPs in HUVECs in vitro, which may be associated with cell oxidative injury.

Objective To investigate the endoscopic ultrasound (EUS) features of distal biliary stricture (DBS), and to provide a clinical basis for the evaluation of DBS by EUS. Methods Related clinical data were collected from 175 patients with DBS who underwent EUS examination in The First Affiliated Hospital of Anhui Medical University from April 2016 to March 2020 to analyze their clinical manifestation, laboratory examination results, imaging findings, and EUS findings, and the patients were followed up to summarize the EUS features of DBS. The chi-square test was used for comparison of categorical data between groups, and the t -test was used for comparison of continuous data between groups. Results Among the 175 patients with DBS, 85(48.57%) had benign DBS and 90(51.43%) had malignant DBS. Compared with the patients with benign DBS, the patients with malignant DBS had a significantly longer length of stricture on EUS (14.1±3.0 mm vs 7.9±3.0 mm, t =13.358, P < 0.001) and significantly higher incidence rates of the characteristic changes on EUS such as hypoechoic space-occupying lesions in lumen (57.8% vs 34.1%, χ 2 =9.843, P =0.002), peripheral lymph node enlargement (26.7% vs 12.9%, χ 2 =5.147, P =0.023), and pancreatic duct dilatation (51.1% vs 28.2%, χ 2 =9.532, P =0.002). EUS combined with magnetic resonance cholangiopancreatography had a sensitivity of 70.6% in the diagnosis of benign DBS and a sensitivity of 92.2% in the diagnosis of malignant DBS. Conclusion The characteristic EUS features of DBS, such as long length of stricture, hypoechoic lesion, peripheral lymph node enlargement, and pancreatic duct dilatation, may help with the differential diagnosis of DBS in clinical practice.

Objective To explore the characteristics of the effect of echinacoside on lipid metabolism in type 2 diabetic mice,and to investigate the content of growth factor 21 in liver tissue of diabetic mice,providing further insight into the possible way of regulating blood lipid metabolism in type 2 diabetic mice with Echinacea.Methods Twenty db/db mice (6-week-old) were randomly divided into two groups:experimental group and model group;while six db/m mice (SPF) (6-week-old) were control group.We detected the fasting blood glucose after 2 weeks that was higher than 16.7mmol/L in experiment.Each group was given sterilized distilled water,echinaco side,sterilized distilled water.The serum total,cholesterol,triglyceride,high density lipoprotein,low density lipoprotein,alanine aminotransferase level,aspartate,aminotransferase level,and the liver tissue measurement of fibroblast growth factor 21 levels were detected after eight weeks.Results The model group serum TG,TC and LDL were significantly higher than the control group (P ＜ 0.01).The content of serum HDL was significantly lower than the control group (P ＜ 0.01).Experimental group of serum TG,TC and LDL levels were significantly lower than the model group (P ＜ 0.01).The content of serum HDL was significantly higher than that in the model group (P ＜ 0.01).The expression of FGF21 in model group in liver were significantly lower than that of control group (P ＜ 0.01).The experimental group the expression of FGF21 in mouse liver was significantly higher than that in the model group (P ＜ 0.01).The content of ALT and AST in serum of model group was significantly higher than the control group (P ＜ 0.01).Experimental group serum ALT,AST were significantly lower than the experimental group (P ＜ 0.01).Conclusion After 8 weeks of administration,the serum lipid metabolism disorder of db/db diabetic mice was significantly improved,and the liver function damage was not increased.The mechanism of FGF21 may be related to the improvement of the expression level of liver tissue.

Iridoid glycosides (mainly geniposide) and crocetin derivatives (crocins) are the two major active constituents in Gardenia jasminoides Ellis. In the present study, geniposide, crocins, crocin-1 and crocetin were separated from gardenia chromatographically. Then, mice were orally administrated with geniposide (400 mg/kg b.w.), crocins (400 mg/kg b.w.), crocin-1 (400 mg/kg b.w.) and crocetin (140 mg/kg b.w.) once daily for 7 days with CCl4. Hepatoprotective properties were evaluated by biochemical parameters: Administration of geniposide, crocins, crocin-1and crocetin significantly lowered serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) levels in CCl4-treated mice. The reduced glutathione (GSH) levels and antioxidant enzymes (SOD and CAT) activities were also increased by geniposide, crocins, crocin-1 and crocetin. Histopathological examination of livers showed that these components reduced deformability, irregular arrangement and rupture of hepatocyte in CCl4-treated mice. These biochemical results and liver histopathological assessment demonstrated that geniposide, crocetin derivatives and crocetin show comparative beneficial effects on CCl4-induced liver damage via induction of antioxidant defense. Therefore, contents of geniposide and crocetin derivatives should be both considered for hepatoprotective efficacy of Gardenia jasminoides Ellis.
Alanine Transaminase ; Alkaline Phosphatase ; Animals ; Aspartate Aminotransferases ; Gardenia ; Glutathione ; Hepatocytes ; Iridoid Glycosides ; Liver* ; Mice* ; Rupture

Objective:To evaluate therapeutic effect and safety of Firebird stent combined tirofiban on acute myocar‐dial infarction (AMI) .Methods :A total of 86 AMI patients treated in our hospital from Aug 2011 to Aug 2013 were selected .According to random number table method ,patients were divided into combined treatment group (n=50 , received Firebird stenting combined tirofiban treatment ) and routine treatment group (n=36 ,received bare metal stenting) .Patients were followed up for 12~18 months ,therapeutic effects ,incidence rates of clinical events were compared between two groups .Results:After PCI ,compared with routine treatment group ,there were significant reductions in percentage of TIMI class 1~2 (13.9% vs .4.0% ) and corrected TIMI frame [ (29.2 ± 4.4) vs .(21.4 ± 5.1)] ,significant rise in percentage of TIMI class 3~4 (86.1% vs .96.0% ) in combined treatment group , P<0.05 all;on six months after PCI ,compared with routine treatment group ,there were significant reductions in inci‐dence rates of subacute thrombosis (2.8% vs .0% ) and myocardial infarction (2.8% vs . 0% ) in combined treat‐ment group (P<0.05 both);on 12 months after operation ,compared with routine treatment group ,there were sig‐nificant reductions in incidence rates of angina pectoris (16.7% vs .6.0% ) ,subacute thrombosis rate (11.1% vs . 0% ) ,myocardial infarction (8.3% vs .0% ) ,heart failure (2.8% vs .0% ) and rehospitalization rate (11.1% vs . 0% ) in combined treatment group , P<0.05 or <0.01 .Conclusion:Firebird stent combined tirofiban possesses sig‐nificant therapeutic effect on acute myocardial infarction ,and it's safe and reliable ,which is worth extending .

OBJECTIVE: To investigate the serum levels of microRNA-155 (miR-155) and interleukin-6 (IL-6) in uremic dialysis patients and to evaluate the effect of alprostadil (A) on them.
 METHODS: A total of 81 chronic kidney disease (CKD) uremic patients were divided into 4 groups: the peritoneal dialysis group (PD group, n=20), the peritoneal dialysis plus alprostadil group (PD+A group, n=20), the hemodialysis group (HD group, n=21), the hemodialysis plus alprostadil group (HD+A group, n=20). Sixteen healthy people were taken as the normal control (NC) group. The peripheral blood of all objects were collected for serum preparation. The expression of miRNA-155 was determined by real-time qPCR and the serum level of IL-6 was measured by ELISA. Experimental and clinical data of all the objects were collected.
 RESULTS: Serum levels of miRNA-155 and IL-6 were increased in all dialysis patients groups compared with NC group (P<0.05); miRNA-155 expression in PD+A group was down-regulated compared with PD group or HD group (P<0.05); the levels of IL-6 in PD+A and HD+A group were significantly decreased compared with PD group or HD group (P<0.05). Correlation analysis showed that serum level of miR-155 was positively correlated with the level of IL-6 as well as high-sensitivity C-reactive protein (hs-CRP), while miR-155 was negatively correlated with HDL and albumin (P<0.01). Linear stepwise regression analysis indicated that serum miR-155 was independently associated with albumin and hs-CRP.
 CONCLUSION Serum miRNA-155 and IL-6 in uremic dialysis patients were remarkably increased compared to healthy objects. Serum miRNA-155 was positively correlated with the level of IL-6 as well as hs-CRP, while miR-155 was negatively correlated with HDL and albumin. Alprostadil could ameliorate the inflammatory conditions of uremic dialysis patients by inhibition of the IL-6 expression. Serum miRNA-155 may be a novel target for the treatment of uremic dialysis patients.
Alprostadil ; therapeutic use ; C-Reactive Protein ; metabolism ; Case-Control Studies ; Humans ; Interleukin-6 ; blood ; MicroRNAs ; blood ; Peritoneal Dialysis ; Regression Analysis ; Renal Dialysis ; Renal Insufficiency, Chronic ; therapy ; Uremia ; blood ; drug therapy

OBJECTIVETo investigate MUC2 expression in rat colons induced by probiotics and its effects on the inhibition of E.coli K1 (E44) penetration of the intestinal barrier by probiotics.

METHODSSD rats were subjected to intragastric administration of probiotics, E44, or probiotics +E44 on a daily basis for 7 days, and MUC2 expression in the colons was determined by RT-PCR. MUC2-targeted shRNA (shRNA MUC2) and scrambled shRNA plasmids (shRNA NC) were respectively transfected into Lovo cells, and the efficiency of MUC2 knockdown was determined using qRT-PCR. Competitive exclusion assay was used to evaluate the effects of the probiotics against E44 adhesion and invasion.

RESULTSIntestinal MUC2 mRNA expression was up-regulated in the rats after intragastric administration of probiotics, while E44 administration caused significantly lowered MUC2 expression. MUC2 expression was down-regulated (by 66.7%) by transfection with shRNA MUC2 in Lovo cells as compared with the negative control and mock control cells. The inhibition of E44 adherence and invasion by probiotics was significantly attenuated in transfected Lovo cell culture (in which the relative adhesion and invasion rates of E44 were 56.64% and 66.64%, respectively) as compared with those in the control group.

CONCLUSIONThe up-regulation of MUC2 in rat colons can be one of the mechanisms of the probiotics in antagonizing the translocation of the pathogenic bacteria. Silencing MUC2 expression causes attenuated inhibitory effect of the probiotics on E. coli K1 penetration across human intestinal epithelial cells.

Animals ; Animals, Newborn ; Cell Line, Tumor ; Colon ; drug effects ; metabolism ; microbiology ; Escherichia coli ; pathogenicity ; Escherichia coli Infections ; genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Mucin-2 ; genetics ; Probiotics ; pharmacology ; RNA, Messenger ; genetics ; RNA, Small Interfering ; Rats ; Rats, Sprague-Dawley ; Transfection

Objective To improve self-management of diabetics with role lack.Methods A total of 121 diabetics with role lack were enrolled and received mass education and individual counseling.Serum levels of glucose and lipid profiles and body mass index (BMI) were assessed and compared before and after intervention by using paired t test.Results Knowledge on diabetes ( 79.37 ± 12.45 vs 31.69 ± 9.36,t =2.860,P ＜ 0.05) and self-management skills ( 9.21 ± 2.85 vs 4.43 ± 1.72,t =2.812,P ＜ 0.05 ) were significantly improved after receiving health education,although fasting plasma glucose [ ( 6.3 ± 1.8 ) vs (8.1 ±2.1) mmol/L,t =2.736,P ＜0.05],2-h postprandial blood glucose [(8.1 ±3.7) vs (12.8 ±4.1)mmol/L,t =3.549,P ＜ 0.05 ],glycosylated hemoglobin Alc [ (6.4 ± 2.5 ) ％ vs (7.1 ± 2.7 ) ％,t =2.603,P ＜ 0.05 ],total cholesterol [ ( 5.2 ± 2.3 ) vs ( 6.3 ± 2.4 ) mmol/L,t =2.036,P ＜ 0.05 ],triglyceride [(1.7±0.7) vs (2.4±0.8) mmol/L,t=2.368,P＜0.05] and BMI [(25.6±6.2) vs (27.3±6.5)kg/m2,t =2.546,P ＜ 0.05 ] were largely decreased.Conclusion Health education could improve selfmanagement and cure of diabetic patient with role lack.