Objective To observe the effect of angiotensin Ⅱ receptor blockers(ARBs)on peroxisome proliferator-activated receptor gamma(PPAR-γ)and to explore its mechanism for improving glucose and lipids metabolism.Methods Dual-luciferase gene reporting system was used to reflect PPAR-γ promoter activation by irbesartan and telmisartan.RT-PCR was used to reflect PPAR-γ mRNA by activation of irbesartan and telmisartan.Results Irbesartan and telmisartan may increase COS-7 cells PPAR-γ promoter expression and increase 3T3-L1 cells PPAR-γ mRNA expression in dose and time-dependent manners.Conclusions ARB may activate PPARs system to play a role in improving the glucose and lipids metabolism

Objective To explorer the effect of angiotensin type 1 receptor blockers (ARB) on activating peroxisome proliferator-activated receptor (PPAR) ? and ?.MethodsLuciferase gene reporters of PPAR? and PPAR? were constructed in COS-7 cells.The cells were then cultured with various concentrations (0,0.01,0.1,1,10 and 100 ?mol/L) of valsartan,losartan,irbesartan or telmisartan for 12,24,36,48 and 60 hours;or co-cultured with PPAR? antagonist GW9662 (10,30?mol/L) for 1 hour,and then cultured with various concentrations (0,1 and 10?mol/L) of irbesartan or telmisartan for 12,24,36,48 and 60 hours.The peroxisome proliferator-response element (PPRE) luciferase activity was determined by Dual-Luciferase Reporter Gene Assay system.3T3-L1 cells were induced to differentiate into adipocytes,and then co-cultured with 10?mol/L of valsartan,losartan,irbesartan or telmisartan for 24 hours,and the expressions of PPAR? and PPAR? mRNA and protein were detected by RT-PCR and Western blotting respectively.ResultsStimulation of valsartan and losartan didn't increase the transcriptional activities of PPAR? and PPAR? in COS-7 cells,while of irbesartan and telmisartan significantly increased the transcriptional activity of PPAR? and PPAR? in COS-7 cells.After co-cultured with 100 ?mol/L of irbesartan or telmisartan for 48 hours,the PPAR? transcriptional activities reached their peak values (43.3?13.0 and 47.8?11.8 respectively),and were significantly higher than that of control group (4.3?0.5,P

Objective To investigate the effect of telmisartan and irbesartan on PPARα transcriptional activity, and to clarify their molecular mechanisms in improving glucose and lipid metabolism. Methods The structural expression vectors, including pCMV-PPARα, pGL3-PPRE and the internal control vector pRL-TK, were transiently eo-transfected into COS-7 cells using SuperFect, the cells were eontinously cultured with various concentrations of telmisartan and irbesartan, and then the PPRE controlled luciferase activity was determined by using a dual-luciferase reporter gene assay system. PPARα mRNA and protein expression levels were detected by RT-PCR and Western blot after 3T3-L1 adipoeytes were treated with various concentrations of telmisartan or irbesartan. Results (1) Both telmisartan and irbesartan stimulated PPARα transcriptional activity in concentration-and time-dependent manners in cultured COS-7 cells with the maximal effect at 60 h, with the results increased by 3.8 and 2.6 folds respectively at the concentration of 100 μmol/L compared with control group (both P<0.01). (2) The PPARγ antagonist GW9662 did not inhibit fenofibrate, telmisartan and irbesartan-stimulated PPARα transcriptional activities. (3) Both telmisartan and irbesartan increased PPARα mRNA and protein expression levels in a dose-dependent manner in 3T3-L1 adipocytes. Conclusion Angiotensin type 1 receptor blockers, telmisartan and irbesartan, can both increase PPARα transcriptional activity, which may contribute to their metabolic effects.

Objective To investigate the effect of continuous subcutaneous insulin injection(CSII)and multiple subcutaneous insulin injection(MSII)on islet b cell function at the onset of type 2 diabetes.Method 64 patients were randomly divided into CSII(f/m=18/20)and MSII groups(f/m=14/12).There was no significant difference in age,fasting C peptide level,fasting blood glucose level,BMI and HbA1c.The patients of both groups were given intensive insulin therapy.Once the total dosage of daily insulin was kept less than 30U and the fast blood glucose was 3.6-6.0 mmol/L,intensive insulin therapy was changed to oral administration of hypoglycin A(OHA),otherwise the intensive insulin therapy was continued.The number of patients who were switched over to oral drug was compared after one month after the intensive therapy.Result 31 patients in CSII group and 8 patients in MSII group were changed to OHA one month after intensive therapy.A significant difference existed between the two groups(?2=3.37,P

Objective:This study aimed to investigate the relationships between anthropometric parameters and carotid elasticity by real-time vascular quantification stiffness technique (R-VQS), and to identify the predictive value of anthropometric parameters for cardiovascular disease risk.Methods:A total of 563 adults were recruited for this study and were divided into two groups by gender. The anthropometric indices [body mass index (BMI), waist circumference (WC), a body shape index (ABSI), body round index (BRI), and visceral adiposity index (VAI)] were calculated. R-VQS technique was used to assess the parameters of carotid elasticity: pulse wave velocity (PWV). The correlations between the anthropometric indices and PWV were analyzed. Linear regression was used to analyze the predictive factors of PWV.Results:⑴ The BMI, WC, ABSI, BRI, VAI and PWV were higher in men than those in women ( P<0.05); ⑵ In men and women, all the anthropometric parameters positively correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglycerides (TG), and negatively correlated with high-density lipoprotein (HDL) ( P<0.05); ⑶ diabetes mellitus (DM) and hypertension history were predictors of PWV in men ( β=0.110, 0.101, respectively, P<0.05); DM, hypertension history and smoking status were predictors of PWV in women ( β=0.061, 0.095, 0.067, respectively, P<0.05); ⑷ After adjusting for diabetes, hypertension and smoking, ABSI and VAI were predictors of PWV in men ( β=0.078, 0.068, P<0.05); BMI, WC, ABSI, BRI and VAI were predictive factors of carotid PWV in women ( β=0.131, 0.123, 0.204, 0.153, 0.196, P<0.05). Conclusions:Among the anthropometric indexes, ABSI and VAI have good correlations with carotid elasticity in wen and women, represented by PWV. These results suggest that ABSI and VAI may be convenient, highly cost-effective and simple parameters for obesity and are associated with cardiovascular disease (CVD) risk in clinical practice. R-VQS is a convenient, real-time and rapid technique for the early assessment of the carotid elasticity.

Objective To investigate the metabolomics characteristic of neuromyelities optica spectrum disorder (NMOSD) in plasma and cerebrospinal fluid.Methods Ultra high performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to identify plasma metabolites in 16 patients with NMOSD and 8 healthy controls.At the same time,the identification of metabolites in cerebrospinal fluid of 8 NMOSD patients and 5 healthy controls was completed.Differential metabolites screening and metabolomic pathway analysis were performed by diversified data analysis methods.Results Compared with healthy control group,the content of 8 substances such as Cis.8.11.14.Eicosatrienoic acid in the plasma of NMOSD patients was increased.The content of 8 substances such as L-glutamine acid were decreased.There was no significant difference in the metabolites between Aquaporin 4 (AQP-4) antibody positive and negative NMOSD plasma.The content of 6 substances such as 3-hydroxybutyric acid in cerebrospinal fluid of patients with NMOSD was reduced.Conclusions The distribution of metabolites in plasma between NMOSD patients and healthy controls was significantly different.There was no significant difference in metabolites between AQP-4 antibody positive and negative NMOSD plasma.There are some differences in metabolites between cerebrospinal fluid of NMOSD patients and healthy controls.A variety of amino acid abnormalities,sphingomyelin dysfunction,energy metabolism and mitochondrial dysfunction were involved in the pathogenesis of NMOSD.

Background::Reperfusion therapy is fundamental for ST-segment elevation myocardial infarction (STEMI). However, the details of contemporary practice and factors associated with reperfusion therapy in China are largely unknown. Therefore, this study aimed to explore reperfusion practice and its associated factors among hospitalized patients with STEMI in China.Methods::Patients with STEMI who were admitted to 159 tertiary hospitals from 30 provinces in China were included in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project from November 2014 to December 2019. The associations of the characteristics of patients and hospitals with reperfusion were examined using hierarchical logistic regression. The associations between therapies and in-hospital major adverse cardiovascular events were examined with a mixed effects Cox regression model.Results::Among the 59,447 patients, 37,485 (63.1%) underwent reperfusion, including 4556 (7.7%) receiving fibrinolysis and 32,929 (55.4%) receiving primary percutaneous coronary intervention (PCI). The reperfusion rate varied across geographical regions (48.0%-73.5%). The overall rate increased from 60.0% to 69.7% from 2014 to 2019, mainly due to an increase in primary PCI within 12 h of symptom onset. Timely PCI, but not fibrinolysis alone, was associated with a decreased risk of in-hospital major adverse cardiovascular events compared with no reperfusion, with an adjusted hazard ratio (95% confidence interval) of 0.64 (0.54,0.76) for primary PCI at <12 h, 0.53 (0.37,0.74) for primary PCI at 12 to 24 h, 0.46 (0.25,0.82) for the pharmaco-invasive strategy, and 0.79 (0.54,1.15) for fibrinolysis alone.Conclusions::Nationwide quality improvement initiatives should be strengthened to increase the reperfusion rate and reduce inequality in China.Trial registration::www.ClinicalTrials.gov, NCT02306616

OBJECTIVEDiagnosis and prenatal diagnosis to a family of hemoglobin variant with α-thalassemia.

METHODSWhole blood cell analysis, hemoglobin analysis by capillary zone electrophoresis (CZE), Gap-PCR, polymerase chain reaction-reverse dot blot (PCR-RDB) assay and DNA sequencing.

RESULTSHb Zurich Albisrieden with α°-thalassemia lead to severe anemia. The genotype of fetus is also Hb Zurich Albisrieden with α°-thalassemia.

CONCLUSIONAbnormal hemoglobin with α-thalassemia may lead to severe anemia, Prenatal diagnosis of thalassemia has the vital significance for eugenic birth.

Adult ; Base Sequence ; Child, Preschool ; Female ; Fetal Diseases ; blood ; diagnosis ; genetics ; Hemoglobins, Abnormal ; genetics ; metabolism ; Humans ; Male ; Molecular Sequence Data ; Pregnancy ; Prenatal Diagnosis ; Young Adult ; alpha-Thalassemia ; blood ; diagnosis ; embryology ; genetics

Objective:To investigate the application of post-mortem tissue sampling under ultrasonography guidance in the autopsy of COVID-19 cases.Methods:Ultrasound-guided post-mortem tissue sampling of heart, lungs, liver, kidneys, and spleen were performed in 24 confirmed COVID-19 cases in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from Feb 20 to Mar 28, 2020. Seventeen males and seven females aged 39-91(66.6±10.6) years old were enrolled. The total time required for each post-mortem sampling was recorded, and the size of the samples collected from each organ was measured. The success rate of ultrasound-guided post-mortem tissue sampling for each organ was calculated.Results:Ultrasound images could clearly show the needle path and enabled accurate placement of the needle within the target organs, including heart, lung, liver, kidney, and spleen. The total time required for sampling was about 32-54 (39.8±5.7)min. The lengths of heart, lung, liver, kidney, and spleen tissues collected by ultrasound-guided sampling were 10(8, 14)mm, 13(12, 15)mm, 14(13, 15)mm, 13(11, 15)mm, 14(13, 15)mm, respectively. The success rates of heart, lung, liver, kidney, and spleen tissue sampling under ultrasound guidance were 87.5% (21/24), 91.7%(44/48), 100%(24/24), 89.6%(43/48) and 83.3%(20/24), respectively.Conclusions:Post-mortem sampling under ultrasonography guidance may be a rapid and reliable method for collecting of heart, lung, liver, kidney, and spleen tissues in the autopsy of COVID-19 cases.

Objective:To investigate the clinical features and prognosis of prolonged cytopenia (PC) in patients with large B-cell lymphoma (LBCL) undergoing anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy.Methods:A retrospective case series study was conducted on LBCL patients who received CAR-T cell therapy with a survival time of over one month at the Hematology Department of Peking Union Medical College Hospital from March 2019 to December 2023. Statistical analyses were performed on hematologic changes at 1, 3, 6, and 12 months post-CAR-T infusion, as well as on the progression-free survival (PFS) and post-treatment adverse events, including infections. Patients were categorized into the PC and non-PC groups based on the occurrence of cytopenia at 90 days post-infusion. Differences between groups were compared, and univariate logistic regression analysis was used to identify risk factors.Results:The median age of 27 LBCL patients receiving CAR-T cell therapy was 58 years (range 27-69 years), with 18 males. Among the 27 LBCL patients who received CAR-T cell therapy, PC was observed in 19 patients (70.4%), with instances of neutropenia (48.1%, 13 cases), anemia (37.0%, 10 cases), and thrombocytopenia (22.2%, 6 cases). Univariate logistic regression analysis revealed that prior chemotherapy sensitivity ( OR=18.00, 95% CI 1.56-207.45, P=0.020) and bone marrow suppression ( OR=18.00, 95% CI 1.38-235.69, P=0.028) were associated with PC. The median follow-up time was 13.5 months. The PC group exhibited a higher risk of infection within 3 months (9/19 vs. 1/8) and a shorter mean PFS (19.3 months vs. 24.4 months), although the difference was not statistically significant (both P>0.05). Conclusions:PC is common following CAR-T cell therapy and is associated with an increased risk of infection and poorer prognosis. Prior treatment sensitivity and bone marrow suppression may serve as indicators of PC.