Objective To investigate the expression of PTEN and vascular endothelial growth factor (VEGF) in esophageal carcinoma and the relationship between their expression.Methods The expression of PTEN and VEGF were detected using immunohistochemical S-P method.Results Among 80 cases of esophageal carcino- ma,31 showed positive staining of PTEN (38.75%),while all 20 case of normal mucosa showed positiva staimng of PTEN.The expression level of PTEN in highly differentiated squamous carcinoma was higher than that low differ- entiated squamous carcinoma.Also,the expression of PTEN was significantly correlated with lymph node metastasis (r=0.61,P<0.01)and differentiation(r=0.57.P<0.05).In 80 cases of esophageal carcinoma,57(70.13%) were of positive staining of VEGF,while in 20 of normal esophageal mucosa,only 3 showed positive staining of VEGF.The expression of VEGF was markedly correlated with infiltrative deepness(r=0.49,P<0.05)and lymph node metastasis(r=0.55,P<0.05)and differentiation(r=0.48,P<0.05).Conclusion Combined detection of PTEN and VEGF maybe helpful to evaluate prognosis and infiltrative capability of esophageal carcinoma,with sig- nificant importance to the prediction of the prognosis of esophageal carcinoam.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

ObjectiveTo explore the mechanism of Buzhong Yiqitang on pyroptosis in autoimmune thyroiditis （AIT） mice based on the NOD-like receptor hot protein domain related protein 3 （NLRP3）/cysteinyl aspartate specific proteinase-1（Caspase-1）/Gasdermin D （GSDMD） pathway. MethodSixty NOD.H-2^h4 mice were divided into normal group， model group， low， medium， and high dose groups （4.10， 8.19， 16.38 g·kg^-1）of Buzhong Yiqitang， and selenium yeast tablet group （0.26 mg·kg^-1）， with 10 mice in each group. Except for the normal group， all other groups were given 0.05% NaI by gavage for eight weeks to establish a model and then received the drug treatment for eight weeks. The serum levels of thyroid peroxidase antibody （TPO-Ab） and thyroglobulin antibody （TgAb） were detected using enzyme-linked immunosorbent assay （ELISA） method. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in mouse thyroid tissue. The immunohistochemical method was used to detect the protein expression of NLRP3， Caspase-1， interleukin-1β （IL-1β）， and interleukin-18 （IL-18）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of NLRP3， Caspase-1， IL-1β， and IL-18. Western blot was used to detect the levels of pyroptosis-related proteins in thyroid tissue. ResultCompared with the normal group， the serum levels of TPO-Ab and TgAb in the model group were significantly increased （P<0.01）. Thyroid follicles either increased in a cubic shape or were damaged and atrophied， with a large number of lymphocytes infiltrating around the follicles. Compared with the model group， the levels of TPO-Ab and TgAb in other groups were significantly reduced （P<0.01）， and the morphology and structure of follicles were improved. The degree of lymphocyte infiltration was reduced. Among them， the medium dose group of Buzhong Yiqitang had the most significant reduction and improvement effect. Compared with the normal group， the positive products and mRNA expression of NLRP3， Caspase-1， IL-1β， and IL-18 proteins in the thyroid tissue of the model group significantly increased （P<0.01）， and the protein expression levels of NLRP3， cleaved Caspase-1， IL-1β， IL-18， and GSDMD-N were significantly increased （P<0.05， P<0.01）. Compared with the model group， the positive products and mRNA expression of NLRP3， Caspase-1， IL-1β， and IL-18 proteins in other groups were significantly reduced （P<0.05， P<0.01）， with the most significant reduction effect in the medium dose group of Buzhong Yiqitang. The protein expression levels of NLRP3， cleaved Caspase-1， IL-1β， IL-18， and GSDMD-N were significantly reduced （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can improve AIT， and its mechanism may be achieved by regulating the NLRP3/Caspase-1/GSDMD signaling pathway to inhibit pyroptosis.