Objective The study was to investigate the relationship among angiotensin 1-converting enzyme(ACE), plasminogen activator inhibitor-1 (PAI-1)gene polymorphisms and the common carotid artery (CCA-IMT), and the predicting effects of them on CCA-IMT in newly diagnosed type 2 diabetes (T2DM). Methods The polymorphisms of ACE (I/D) gene and PAI-I (4G/5G) gene were deter-mined by polymemse chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific polymerase chain reaction (AS-PCR) method in 308 cases with T2DM. CCA-IMT was compared among the groups with different genotypes of ACE and PAI-1. The in-dependent or synergistic effects of the ACE I/D and PAI-1 40/5G polymorphisms on CCA-IMT in 308 patients with T2DM were analyzed with multivariate linear regression. Then the 156 newly diagnosed type 2 diabetics (durations< I year) without AS received the maltifactorial targeted intervention, including taking aspirin and controlling blood glucose, blood pressure, blood lipid and body weight. The differences of metabolic control, ACE (I/D) and PAId (40/5G) gene polymorphisms were analyzed. Logistic regression analysis was used to analyze the eorrelation among the CCA-IMT, ACE (I/D) and PAI-1 (4G/5G) polymorphisms. Results Patients with ACE DD genotypes had higher CCA-IMT than those with ACE-Ⅱ or ACE ID genotypes. Patients with both ACE DD and PAI-1 404G genotypes had a higher CCA-IMT than those with any other pairs of genotypes. Multivariate linear regression analysis showed that ACE DD and PAI-1 4G4G gene polymorphisms had synergistic effect on the CCA-IMT in T2DM patients. After 2 years multifactorial intervention, the frequencies of PAI-1 4G alleles and 404G genotypas were lower than those in the CCA-IMT non-inereasing group. Conclusions These findings indicate that the ACE-DD geno-type and its synergistic effects with the PAI-1 4G/4G genotype are independent risk factors for the CCA-IMT in T2DM patients. Under multi-factorial intervention for 2 years, PAI-1 4G/4G genotype may be a negative predictor for the progression of CCA-IMT in T2DM patients.

OBJECTIVETo investigate the mechanism underlying sodium butyrate (NaB)-induced apoptosis of a human colon cancer cell line HCT-116.

METHODSThe apoptosis of HCT-116 cells induced by NaB was confirmed by hoechst33342 staining and AnnexinV+ PI assay. The changes in the intracellular localization of stromal interaction molecule (STIM1) and Orai1 following NaB treatment were detected by immunofluorescence technique. Western blotting was used to investigate the protein expression levels of STIM1 and Orai1.

RESULTSNaB induced apoptosis and caused translocation and colocalization of STIM1 and Orai1 in HCT-116 cells.

CONCLUSIONThe apoptosis of human colon cancer cells induced by NaB is correlated to the redistribution of STIM1 and Orai1.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Butyrates ; pharmacology ; Calcium Channels ; metabolism ; HCT116 Cells ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Membrane Proteins ; metabolism ; Neoplasm Proteins ; metabolism ; ORAI1 Protein ; Stromal Interaction Molecule 1

Objective:To explore the mechanism by which Pien Tze Huang improves liver Kupffer cell damage induced by lipopolysaccharide (LPS) by regulating the expression of miR-155.Methods:LPS induced liver Kupffer cells to establish a cell injury model to simulate septic liver injury. RT-qPCR was used to detect the expression of miR-155 in damaged cells, and RT-qPCR, Western Blot, ELISA and flow cytometry were used to evaluate the inflammatory response and apoptosis of damaged cells. Then we treated LPS-induced Kupffer cells with Pien Tze Huang at different concentrations (0 mg/L, 5 mg/L, 10 mg/L and 15 mg/L), and detected the expression of miR-155 in the cells, the inflammatory response of the cells and Apoptosis rate. MiR-155 was silenced in the cell injury model, and RT-qPCR, Western Blot, ELISA and flow cytometry were used to evaluate the effect of miR-155 on inflammatory response and apoptosis of model cells. Overexpression of miR-155 in damaged cells treated with Pien Tze Huang was used to detect changes in cellular inflammatory response and apoptosis. Data are expressed in the form of mean ± standard deviation, and each group of data is analyzed using t test or one-way analysis of variance.Results:In the LPS-induced liver Kupffer cell injury model, the expression of miR-155 was significantly increased ( P<0.05), the expression levels of pro-inflammatory factors IL-6 and TNF-α were significantly increased, and the anti-inflammatory factor IL-10 was significantly increased. was inhibited ( P<0.05), and the cell apoptosis rate was significantly increased ( P<0.05). After Pien Tze Huang treatment, the expression of miR-155 in damaged liver cells was inhibited ( P<0.05), the levels of cellular inflammatory factors IL-6 and TNF-α were inhibited, and the expression of anti-inflammatory factor IL-10 was promoted ( P<0.05). Inhibit cell apoptosis ( P<0.05). Silencing miR-155 reduced the inflammatory response and apoptosis rate of cells ( P<0.05). Overexpression of miR-155 can reverse the effect of Pien Tze Huang on liver cell injury ( P<0.05). Conclusions:In the model of LPS-induced liver Kupffer cell injury, Pien Tze Huang can inhibite the inflammatory response and apoptosis of cells by inhibiting the expression of miR-155.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Type 2 diabetes (T2D) is characterized by the malfunction of pancreatic β cells. Susceptibility and pathogenesis of T2D can be affected by multiple factors, including sex differences. However, the mechanisms underlying sex differences in T2D susceptibility and pathogenesis remain unclear. Using single-cell RNA sequencing (scRNA-seq), we demonstrate the presence of sexually dimorphic transcriptomes in mouse β cells. Using a high-fat diet-induced T2D mouse model, we identified sex-dependent T2D altered genes, suggesting sex-based differences in the pathological mechanisms of T2D. Furthermore, based on islet transplantation experiments, we found that compared to mice with sex-matched islet transplants, sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway of β cells. Moreover, the diabetic mice with sex-mismatched islet transplants showed impaired glucose tolerance. These data suggest sexual dimorphism in T2D pathogenicity, indicating that sex should be considered when treating T2D. We hope that our findings could provide new insights for the development of precision medicine in T2D.