Inhibiting MMP13 Attenuates Deep Vein Thrombosis in a Mouse Model by Reducing the Expression of Pdpn

Objective:Matrix metalloproteinase 13(MMP13)is an extracellular matrix protease that affects the progression of atherosclerotic plaques and arterial thrombi by degrading collagens,modifying protein structures and regulating inflammatory responses,but its role in deep vein thrombosis(DVT)has not been determined.The purpose of this study was to investigate the potential effects of MMP13 and MMP13-related genes on the formation of DVT.Methods:We altered the expression level of MMP13 in vivo and conducted a transcriptome study to examine the expression and relationship between MMP13 and MMP13-related genes in a mouse model of DVT.After screening genes possibly related to MMP13 in DVT mice,the expression levels of candidate genes in human umbilical vein endothelial cells(HUVECs)and the venous wall were evaluated.The effect of MMP13 on platelet aggregation in HUVECs was investigated in vitro.Results:Among the differentially expressed genes,interleukin 1 beta,podoplanin(Pdpn),and factor VIII von Willebrand factor(F8VWF)were selected for analysis in mice.When MMP13 was inhibited,the expression level of PDPN decreased significantly in vitro.In HUVECs,overexpression of MMP13 led to an increase in the expression level of PDPN and induced platelet aggregation,while transfection of PDPN-siRNA weakened the ability of MMP13 to increase platelet aggregation.Conclusions:Inhibiting the expression of MMP13 could reduce the burden of DVT in mice.The mechanism involves downregulating the expression of Pdpn through MMP13,which could provide a novel gene target for DVT diagnosis and treatment.

Research progress on the correlation between intestinal microflora disorder and liver disease

In recent years,the relationship between intestinal flora and liver disease has become an important research direction of liver diseases.A growing body of evidence indicates that gut bacteria play a key role in the pathophysiology of liver disease,this article combed the at home and abroad in recent years,the changes of intestinal flora and autoimmune liver disease,alcoholic liver disease,fatty liver disease related to metabolism,hepatitis b viral hepatitis,cirrhosis and liver cancer occurrence and progress of relationship of related research,And the new progress of regulating intestinal microecology in the treatment of liver diseases.Dysregulation of intestinal flora plays an important role in the occurrence and development of liver diseases.Regulating intestinal flora to improve the prognosis of liver diseases will be an important development direction in the future.

Umbilical blood flow ultrasound characteristics of perioperative fetal intrauterine hypoxia and their relationship with maternal and fetal oxidative stress injury

Objective:To study the relationship between umbilical blood flow ultrasound characteristics of perioperative fetal intrauterine hypoxia and maternal as well as fetal oxidative stress injury.Methods: 108 puerperae giving birth in our hospital between May 2014 and October 2016 were selected and divided into normal pregnancy group with neonatal Apgar score >7 points and intrauterine hypoxia group with neonatal Apgar score≤7 points, color Doppler diasonograph was used to determine umbilical blood flow ultrasound parameters, umbilical cord blood was collected to determine the levels of oxidative stress products, and the placenta was collected to determine the levels of oxidative stress products and related apoptosis molecules.Results: During 24–30 weeks, 31–36 weeks and 37–41 weeks of pregnancy, umbilical blood flow resistance index (RI), pulsatility index (PI) and diastolic velocity/systolic velocity (S/D) of intrauterine hypoxia group were significantly higher than those of normal pregnancy group (P<0.05);malondialdehyde (MDA), oxidized low-density lipoprotein (ox-LDL), 8-isoprostanes (8-iso), and heat shock protein 70 (HSP-70) levels in umbilical cord blood of intrauterine hypoxia group were significantly higher than those of normal pregnancy group (P<0.05), MDA, oxLDL, 8-ios, HSP-70, Fas, FasL and Bax levels in placenta tissue were significantly higher than those of normal pregnancy group (P<0.05), and Bcl-2 and XIAP levels were significantly lower than those of normal pregnancy group (P<0.05);RI, PI and S/D were positively correlated with MDA, oxLDL, 8-ios and HSP-70 levels in umbilical cord blood and placenta tissue, positively correlated with Fas, FasL and Bax levels in placenta tissue, and negatively correlated with Bcl-2 and XIAP levels in placental tissue.Conclusions:The increased umbilical blood flow resistance and decreased flow volume of fetal intrauterine hypoxia are closely related to maternal, fetal and placental oxidative stress injury.

Development and validation of biomarkers related to anoikis in liver cirrhosis based on bioinformatics analysis

BACKGROUND According to study,anoikis-related genes(ARGs)have been demonstrated to play a significant impact in cirrhosis,a major disease threatening human health worldwide.AIM To investigate the relationship between ARGs and cirrhosis development to provide insights into the clinical treatment of cirrhosis.METHODS RNA-sequencing data related to cirrhosis were obtained from the Gene Expression Omnibus database.Differentially expressed genes(DEGs)between cirrhotic and normal tissues were intersected with ARGs to derive differentially expressed ARGs(DEARGs).The DEARGs were filtered using the least absolute shrinkage and selection operator,support vector machine recursive feature elimination,and random forest algorithms to identify biomarkers for cirrhosis.These biomarkers were used to create a nomogram for predicting the prognosis of cirrhosis.The proportions of diverse immune cell subsets in cirrhotic vs normal tissues were compared using the CIBERSORT computational method.In addition,the linkage between immune cells and biomarkers was assessed,and a regulatory network of mRNA,miRNA,and transcription factors was constructed relying on the biomarkers.RESULTS The comparison of cirrhotic and normal tissue samples led to the identification of 635 DEGs.Subsequent intersection of the DEGs with ARGs produced a set of 26 DEARGs.Subsequently,three DEARGs,namely,ACTG1,STAT1,and CCR7,were identified as biomarkers using three machine-learning algorithms.The proportions of M1 and M2 macrophages,resting CD4 memory T cells,resting mast cells,and plasma cells significantly differed between cirrhotic and normal tissue samples.The proportions of M1 and M2 macrophages,resting CD4 memory T cells,and resting mast cells were significantly correlated with the expression of the three biomarkers.The mRNA–miRNA–TF network showed that ACTG1,CCR7,and STAT1 were regulated by 28,42,and 35 miRNAs,respectively.Moreover,AR,MAX,EP300,and FOXA1 were found to regulate four miRNAs related to the biomarkers.CONCLUSION This study revealed ACTG1,STAT1,and CCR7 as biomarkers of cirrhosis,providing a reference for developing novel diagnostic and therapeutic strategies for cirrhosis.

Analysis of alkaline phosphatase and γ-glutamyltransferase after radiofrequency ablation of primary liver cancer: A retrospective study

BACKGROUND Changes in alkaline phosphatase(ALP)andγ-glutamyltransferase(GGT)levels in patients with primary liver cancer(PLC)after radiofrequency ablation(RFA).Hepatocellular carcinoma is a malignant tumor with high incidence worldwide.As a common local treatment,RFA has attracted much attention for its efficacy and influence on liver function.AIM To investigate the effect of serum ALP and GGT levels on the prognosis of patients with PLC treated by RFA.METHODS The preoperative clinical data of 165 patients who were pathologically or clinically diagnosed with PLC and who received RFA in our hospital between October 2018 and June 2023 were collected.The chi-square test was used to compare the data between groups.The Kaplan-Meier method and Cox regression were used to analyze the associ-ations between serum ALP and GGT levels and overall survival,progression-free survival(PFS)and clinical characteristics of patients before treatment.RESULTS The 1-year survival rates of patients with normal(≤135 U/L)and abnormal(>135 U/L)serum ALP before treatment were 91%and 79%,respectively;the 2-year survival rates were 90%and 68%,respectively;and the 5-year survival rates were 35%and 18%,respectively.The difference between the two groups was statistically significant(P=0.01).Before treatment,the 1-year survival rates of patients with normal serum GGT levels(≤45 U/L)and abnormal serum GGT levels(>45 U/L)were 95%and 87%,the 2-year survival rates were 85%and 71%,and the 5-year survival rates were 37%and 21%,respectively.The difference between the two groups was statist-ically significant(P<0.001).Serum ALP[hazard ratio(HR)=1.766,95%confidence interval(95%CI):1.068-2.921,P=0.027]and GGT(HR=2.312,95%CI:1.367-3.912,P=0.002)is closely related to the overall survival of PLC patients after RF ablation and is an independent prognostic factor.The 1-year PFS rates were 72%and 50%,the 2-year PFS rates were 52%and 21%,and the 5-year PFS rates were 14%and 3%,respectively.The difference between the two groups was statistically significant(P<0001).The 1-year PFS rates were 81%and 56%in patients with normal and abnormal serum GGT levels before treatment,respectively;the 2-year PFS rates were 62%and 35%,respectively;and the 5-year PFS rates were 18%and 7%,respectively,with statistical significance between the two groups(P<0.001).The serum ALP concentration(HR=1.653,95%CI:1.001-2.729,P=0.049)and GGT(HR=1.949,95%CI:1.296-2.930,P=0.001)was closely associated with PFS after RFA in patients with PLC.The proportion of male patients with abnormal ALP levels is high,the Child-Pugh grade of liver function is poor,and the incidence of ascites is high.Among GGT-abnormal patients,the Child-Pugh grade of liver function was poor,the tumor stage was late,the proportion of patients with tumors≥5 cm was high,and the incidence of hepatic encephalopathy was high.CONCLUSION Serum ALP and GGT levels before treatment can be used to predict the prognosis of patients with PLC after RFA,and they have certain guiding significance for the long-term survival of patients with PLC after radiofrequency therapy.

Effect of Xuesaitong Combined with Autologous Platelet-rich Gel on Blood Glucose,AT-III,TNF-αand 24-h Urinary Protein Level in Patients with Diabetic Foot

[Objectives]To investigate the clinical effect of different doses of Xuesaitong combined with autologous platelet-rich gel(APG)on patients with diabetic foot(DF).[Methods]90 patients with diabetic foot admitted to our hospital from February 2017 to February 2019 were enrolled in the study.According to the random number table method,the subjects were divided into study group A and B and control group C.Group A was given a low dose of Xuesaitong combined with APG,while group B was given high-dose Xuesaitong combined with APG and group C was treated only with APG.Patients in the three groups were observed and the changes of related indexes were detected.[Results]After treatment,with regard to the three groups,the fasting blood glucose,2-h postprandial blood glucose level,HbA1c,TNF-α,Hcy,blood urea nitrogen(BUN),creatinine(Cr)and 24-h urine protein levels were all decreased,yet AT-III level was increased,and granulation tissue coverage and thickness,wound clearance rate were increased,while the repair time of ulcer surface was significantly reduced.The above indexes were all significantly different(P<0.05).Compared with the control group C,the changes of the indexes in the study group A and B were the same as above,and the difference was significant(P<0.05).Compared with the study group A,the level of AT-III in group B was significantly increased(P<0.05),while TNF-α,Hcy,BUN,Cr and 24-h urine protein levels were significantly decreased(P<0.05).There was no significant difference in the other indexes between groups A and B(P>0.05).[Conclusions]Xuesaitong combined with APG could effectively reduce the blood sugar level of DF patients,improve the clinical indexes,promote wound healing,and the high-dose group had more significant advantages and was worthy of promotion.

The stability of FKBP9 maintained by BiP is crucial for glioma progression

FK506-binding protein 9(FKBP9)is involved in tumor malignancy by resistance to endoplasmic reticulum(ER)stress,and the up-regulation of FKBP9 is associated with patients'poor prognosis.The current knowledge of the molecular mechanisms is still limited.One pre-vious study showed that FKBP9 could confer glioblastoma cell resistance to ER stress through ASK1-p38 signaling.However,the upstream regulatory mechanism of FKBP9 expression is still indistinct.In this study,we identified the FKBP9 binding proteins using co-immunoprecipitation followed by mass spectrometry.Results showed that FKBP9 interacted with the binding immu-noglobulin protein(BiP).BiP bound directly to FKBP9 with high affinity.BiP prolonged the half-life of the FKBP9 protein and stabilized the FKBP9 protein.BiP and FKBP9 protein levels were positively correlated in patients with glioma,and patients with high expression of BiP and FKBP9 showed a worse prognosis.Further studies showed that FKBP9 knockout in genetically engineered mice inhibited intracranial glioblastoma formation and prolonged survival by decreasing cellular proliferation and ER stress-induced CHOP-related apoptosis.Moreover,normal cells may depend less on FKBP9,as shown by the absence of apoptosis upon FKBP9 knockdown in a non-transformed human cell line and overall normal development in homozygous knockout mice.These findings suggest an important role of BiP-regulated FKBP9-associated signaling in glioma progression and the BiP-FKBP9 axis may be a potential therapeutic target forglioma.

Pathogenesis sequences in Gejiu miners with lung cancer： an introduction

Tin miners in Gejiu, Yunnan Province, China are at high risk of developing lung cancer with significant occupational characteristics. Tissue samples from these miners presented pathological characteristics, such as fibroplasia in carcinomas, peri-cancerous tissue in lung cancers, and hyperplasia and dysplasia of epithelial cells in peri-cancerous tissue. Carcinomas induced by Yunnan tin mine dust in the animal experiment underwent inflammation, fibroplasia, hyperplasia, dysplasia, and carcinogenesis of epithelial ceils. A correlated and synergistic relationship was observed between bronchial epithelial cell transformation and fibroblast activation in vitro induced by mine dust. Fibroblast hyperplasia and activation are important factors that promote the transformation and carcinogenesis of epithelial cells. Our findings suggested that pulmonary fibrosis may increase the risk and promote the occurrence of lung cancer, which can lead to lun~ fiber hyperplasia.