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Background@#Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. @*Methods@#Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. @*Results@#The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. @*Conclusion@#The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.
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Background@#Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. @*Methods@#Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. @*Results@#The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. @*Conclusion@#The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.
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Objective To investigate the relationship between FGF23 and Klotho in GD patients. Methods From March 2016 to November 2016, forty-three newly diagnosed and untreated Grave disease patients (GD group) and 27 healthy subjects were selected. Meanwhile,Peripheral venous serum was collected to detect serum calcium, phosphorus and thyroid function in GD group. The levels of FGF23, Klotho protein and 1 in each group were detected by enzyme-linked immunosorbent assay ( ELISA ) . The expression levels of FGF23,Klotho protein and 1,25-dihydroxyvitamin D3 were detected by enzyme-linked immunosorbent assay ( ELISA ) . The differences of FGF23, Klotho protein, 1, 25-dihydroxyvitamin D3, serum calcium and phosphorus between GD group and normal control group were compared,and the correlation between each index was analyzed. The relationship between FGF23 and Klotho protein and the pathogenesis of GD was explored. Results ( 1) Thyrotropin in thyroid function was significantly lower in GD group than that in normal group,and the difference was statistically significant ( 0. 003 ( 0. 002, 0. 004 ) mU/L vs. 1. 650 ( 0. 81, 2. 14 ) mU/L, Z=- 7. 587,P<0. 05] . Thyrotropin receptor antibodies,free triiodothyronine and free thyroxine in GD group were significantly higher than those in normal group. There were [ thyroid stimulating hormone receptor antibodies:9. 03(3. 89,21. 29)) U/L vs. 0. 60(0. 38,0. 97)) U/L,free triiodothyronine:23. 36(11. 61,38. 00)) pmol/L vs. 4. 63(4. 03,4. 92)) pmol/L,free thyroxine:4. 34(33. 94,100. 00) pmol/Lvs. 17. 69(15. 80,20. 35) pmol/L;Z=-6. 694,-6. 878,-6. 836,P<0. 05];( 2) The serum levels of FGF23,Klotho and phosphorus in patients with hyperthyroidism were significantly higher than those in the normal group,and the difference was statistically significant [FGF23:(524. 2±66. 7) ng/L vs. (467. 2±64. 5) ng/L,Klotho:8. 29(6. 89,11. 37) pg/ml vs. 6. 69 (6. 36,7. 53) pg/ml,phosphorus:1. 33(1. 03,1. 52) mmol/L vs. 1. 02(0. 84,1. 20) mmol/L; t=3. 517,Z=-3. 936,-3. 795,P<0. 05]. The Results of correlation analysis showed that: (1) There was no correlation among FGF23 and Klotho,thyroid stimulating hormone receptor antibody,free thyroxine,1,25-dihydroxyvitamin D3,phosphorus and calcium a ( P>0. 05);( 2) There was no correlation among Klotho and thyroid stimulating hormone receptor antibody, free thyroxin, 1, 25-dihydroxyvitamin D3, phosphorus and calcium ( P>0. 05 ) . Conclusion The elevated expression of FGF23 in GD may be involved in the pathogenesis of GD, and the elevated expression of Klotho in GD may be due to the abnormal immune status in GD patients,which may play a protective role.
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Objective To investigate the clinical significant and the difference of predicting the risk of dysglycemia and dyslipidemia by body mass index (BMI),waist circumference (WC) and waist-to-hip ratio (WHR) in order to look for the best predicting index.Methods Five thousand and thirty residents were participated to this study who were from Jinshan New Area and nearby of Jinshan,Shanghai,including 2004 males and 3026 females.They were divided into obesity group and non-obesity group based on the index of BMI,WC and WHR respectively.The ROC was made based on the above indies in different gender groups.Results The ROC area of BMI was the biggest with 0.641 (P ＜0.05) for male and 0.617(P ＜0.05) for female.The cut off value was 24.67 or 23.88 based on the male or the female.The same trend was seen in terms of WC with 88.5 cm for the male and 84.5 cm for the female.The small cut off value was seen in terms of WHR and there was no significant between male and female.Among male people,the cut off values was 26.01 in terms of BMI and 88.5 cm in terms of WC,0.89 cm in terms of WHR.Among the female people,there was the less predicting significant in terms of WC or WHR.The area under the curve had no significant differences,and the BMI predicted abnormal blood glucose of no value,the area under the curve is only 0.513 (P ＞ 0.05).Conclusion BMI is proved the best predictor for the risk of dyslipidemia.There are significant among BMI,WC and WHR in terms of predicting dysglycemia in different gender.BMI is proved without significant regarding of predicting dysglycemia in females.
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Objective:To establish the method for determining nimesulide in thermo-sensitive hydrogels and study the stability of the preparation. Methods:An HPLC method was adopted with a Shim-Pack C18-ODS (150 mm × 4. 6 mm,5 μm) column, the mobile phase was composed of menthol-water-acetic acid (65∶35∶0. 8) with the flow rate of 1. 0 ml·min-1 at 30℃, the detection wavelength was at 299 nm, and the injection volume was 10 μl. Results:The separation of nimesulide, impurities and degradation products was good. The linear range of nimesulide was 2. 43-24. 37μg·ml-1(r=0. 999 8), the average recovery was 100. 02%(RSD=1. 12%, n=5). The lowest detectable limit and the lowest quantitation limit was 0. 098μg·ml-1 and 0. 25μg·ml-1, respectively. The stabil-ity results of hard-light exposure, destructive testing and long-term testing showed that the preparation was basically stable at room tem-perature, while under high temperature with hard light, strong basicity, acidicity or oxidation solution, the preparation was unstable. Conclusion:The method is accurate and reliable in the determination and stability study of nimesulide thermo-sensitive hydrogels. The hydrogels should be stored in shady, cool and dark place.
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Objective: To establish an HPLC method for the simultaneous determination of chloromycetin and metronidazole in chlortalidone and metronidazole spirits. Method:The HPLC method was performed on an NOV-pak C18 (150 mm × 4. 6 mm, 5 μm) column and the mobile phase consisted of methanol and water (75∶25). The flow rate was 1. 0 ml·ml-1, the detection wavelength was 297nm, the temperature of column was 30℃ and the sample size was 20 μl. Result: The calibration curve of metronidazole was linear within the range of 5-80μg·ml-1(r=0. 999 7), and the average recovery was 100. 83% with RSD of 1. 82%(n=6). The cal-ibration curve of chlortalidone was linear within the range of 50-800μg·ml-1(r=0.999 7), and the average recovery was 100.2%with RSD of 0. 55%(n=6). Conclusion: The method is simple, rapid, accurate and reproducible, and can be used in the quality control of chlortalidone and metronidazole spirits.
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Objective To investigate the therapeutic effect of CTLA4Ig gene on experimental autoimmune thyroiditis (EAT) by the use of portable synthetic costimulatory molecules of cytotoxic T lymphocyte antigen 4 (CTLA-4) antagonist (CTLA4Ig) eukaryotic expression vector.Methods Thirty C57BL/6J female mice were divided into three groups,named EAT model group (EAT,n =10),CTLA4Ig-treatment group (CTLA4Ig-EAT,n =10) and control group(n =10).At 28 day after first immunization,plasmids mixture with pCI or pCI/CTLA4Ig were injected into thyroid tissues of EAT and CTLA4Ig-EAT by surgery,respectively.Serum,thyroid tissues and spleens were collected as samples.Thyroid autoantibody and expression of interleukin (Th)1,Th2 related cytokinesby were measured by real-time quantitative PCR and ELISA.Results Compared with EAT group,the expression of CTLA-4 in thyroid of CTLA4Ig-EAT group was elevated double folds (P =0.038),and the expression of Th1 cytokine interferon γ and intercellular adhesion molecule-1 decreased significantly (P =0.016,0.042).Meanwhile,Th2 cytokine IL-4 was increased after CTLA4Ig treatment (P =0.044).The same changes were seen in spleen tissues and serum.There was no significant difference in terms of TPOAb between EAT and treated group.Conclusion Local thyroid injection of CTLA4Ig gene shows the therapeutic effect to same degree on EAT through adjusting the underlying Th1/Th2 imbalance.
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Objective To investigate the clinical application of alpha lipoic acid on early diabetic nephropathy(DN).Methods Seventy patients with early diabetic nephropathy were randomly divided into two groups.Patients in control group were treated with regular glycemic control methods,while patients in treatment group were received alpha lipoic acid 300 mg static drop treatment for two weeks beside regular treatment.High sensitivity C reaction protein,microalbuminuria and urine creatinine were measured before and after the treatment.Microalbuminuria and urine creatinine were re-measured three months later.Results At the end of two weeks treatment,the levels of high sensitivity C reaction protein in the treatment group decreased from (3.92 ± 4.56) mg/L to (2.24 ± 2.49) mg/L,and there was significant difference (t =2.803,P ＜ 0.05).Microalbuminuria decreased from (127.18 ± 76.91) mg/L to (84.50 ± 122.87) mg/L,and there was significant difference (t =2.501,P ＜ 0.05).The ratio of microalbuminuria and urine creatinine in treatment group decreased from(28.95 ± 30.49) mg/mmol to(13.76 ± 20.83) mg/mmol,and there was significant difference (t =3.616,P ＜ 0.05).While there was no significant difference in the control group before and after regular waglycemic control.At three months after treatment,there were no significant difference regarding of microalbuminuria,the ratio of microalbuminuria and urine creatinine between treatment and control groups (P ＞ 0.05).Conclusion Alpha lipoic acid might be with ability of decreasing the levels of microalbuminuria of diabetic nephropathy in the short term,but further study is needed to verify whether alpha lipoic acid can decrease the level of microalbuminuria in the long term.
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Objective To investigate the potential role of T follicular helper cells (Tfh) in the pathogenesis of autoimmune thyroid diseases by comparing the expression of C-X-C chemokine teceptor type 5 (CXCR5) and CD57 in Hashimoto's thyroiditis (HT) and Graves' disease (GD) thyroid tissues.Methods The expression of CXCR5 and CD57 proteins was determined by immunohistochemical analysis in 15 HT thyroid samples,18 GD samples and 10 normal thyroid samples.Results Immunohistochemical staining showed that CXCR5 and CD57 were mainly positive in cytomembrane and cytoplasm of the infiltrated lymphocytes both in HT and GD tissues,with much higher levels than that of normal thyroid tissues ( P ＜ 0.05 ).Both CXCR5 and CD57 were not significantly different between the HT and GD tissues.Conclusion CXCR5 and CD57 expressions were increased with a similar expression pattern in both of the two main autoimmune thyroid diseases( AITD),indicating that Tfh may participate inthe development and progression of AITD.
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To identify association between the presence of previously reported four single nucleotide polymorphisms(SNPs) at exon 10, 12 and 33 of thyroglobulin(Tg) gene with autoimmune thyroid disease(AITD) patients whose TgAb is positive. In this case-control association study, the Tg gene polymorphisms at exon 10, 12, and 33 were determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)method in 222 patients with AITD. According to the titers of the Tg autoantibodies(TgAb) in serum, they were divided into two subgroups: TgAb positive group and TgAb negtive group. And a haplotype case-control analysis was also done in two groups.The difference of their frequencies was analyzed by Chi-square test. No differences in alleles and genotypes frequencies were observed in all patients whose TgAb iseither positive or negative(P＞0.05). But there was a significant association of G-C-A-C haplotype with the patients whose TgAb was positive(P=0.028,OR=3.34). There is association of thyroglobulin gene polymorphisms with TgAb in patients with AITD.
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BACKGROUND: Previous studies found that C57BL/6 mouse was susceptible to atherosclerosis, while BALB/c mouse was resistant to atherosclerosis. The stenosis of the culprit vessel and the severity of myocardial infarction were correlated to the levels of OX40L expression. Whether OX40L has differential expression between C57BL/6 and BALB/c mouse was not identified.OBJECTIVE: To observe the differential expression of OX40L mRNA and protein in C57BL/6 and BALB/c mouse.METHODS: Total RNA and protein were extracted by Trizol and RIPA Buffer from heart, brain, kidney, skeletal muscle and spleen tissues of C57BL/6 and BALB/c mice. RT-PCR and Western Blot were used to detect OX40L mRNA and protein expression in heart, brain, kidney, spleen and skeletal muscle of two kinds of mice. The differential expression of OX40L mRNA and protein between C57BL/6 and BALB/c mice was observed.RESULTS AND CONCLUSION: RT-PCR results showed that the mRNA expression level of OX40L in heart of C57BL/6 mice mouse was significantly higher than BALB/c mice (P ＜ 0.05); the mRNA expression level of OX40L in spleen of BALB/c mice was significantly higher than C57BL/6 mice (P ＜ 0.05). There were no significant differences in the brain, kidney and skeletal muscle between these two strains. The results of Western Blot showed that the protein expression level of OX40L in heart, brain and kidney of C57BL/6 mice were significantly higher than BALB/c mice (P ＜ 0.05). There were no significant differences in skeletal muscle and spleen between these two strains. The OX40L mRNA transcription level in heart was higher in C57BL/6 mouse than BALB/c mouse, while the expression in spleen was lower than the latter. The OX40L protein levels in C57BL/6 mouse heart, brainand kidney were higher than BALB/c mouse. The differences of OX40L expression between the two strains of mice indicated that OX40L may promote to C57BL/6 mouse susceptible to atherosclerosis.
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Objective To study the relationship between single nucleotide polymorphisms(SNPs)of thrombospondin-1 gene(TSP-1)and coronary artery disease(CAD).Methods Fragment 8831A→G of Exon thirteen in TSP-1 gene from 437 cases of CAD and 423 subjects without coronary heart disease from November 2003 to May 2007 in The First Affiliated Hospital of Nanjing Medical University and Affiliated Yueyang Hospital of Shanghai Traditional Chinese Medicine University were analysed by polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP),and sequence analysis for confirmation.Results The prevalence of the 8831G in the 860 subjects was rare.No association of the N700S polymorphism with an altered risk of ACS was found in our study (GA VS AA:OR=1.699;95%CI 0.309-9.348,P＞0.05).Conclusion The TSP-1 8831A→G polymorphism is rare and unrelated to CAD in the Chinese Han population.
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Objective To investigate the possible association between the thrombospandin-1(TSP-1) gene GI678A (Ala523Thr)polymorphism and acute coronary syndrome (ACS) in a Chinese Han population.Method he ease cohort studied was compsed of 412 hospitalized patients with ACS recruited from four participating hospitals between November 2003 and May 2006.The diagnosis of ACS was based on the criteria of AHA/ACC set in 2002.The eontrul group was consisted of 319 age- and sex-matched subjects from partiei pating hospitals,and they were free from coronary artery disease judged by history,clinical examination,electrocardiography,exercise test and angiography.The TSP-1 GI678A polymorphism was determined by polymerase ehain reaction and restriction fragment length polymurphism analysis(PCR-RFLP).Results The prevalence OfAA genotype of the G1678A polymorphismin patients with ACS was significantly higher than that in the control subjects (49.5%% vs.40.4%,P=0.015).The frequencies of GA and GG genotypes were not significantly different between patients with ACS and controls (CA:39.3% vs.46.1%,P=0.070;CA;11.2% vs.13.5%,P=0.340).The frequencies of A allele in the ACS group and control group were 69.2% and 63.5%,respectively (P=0.022).Furthermore,multiple logistic regression analysis showed that the AA genotype was a significant risk factor for ACS (OR=1.52;95% CI:1.11～2.08;P=0.010).Conclusions The present findings suggest that the AA genotype in TSP-1 gene GI678A polymorphism may be associated with a risk factor for ACS in the Hart nationality of China.The AA genotype may be a genetic marker of the liability to the inheritance of AC,S.
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BACKGROUND: To apply mouse anti-human cTnI monoclonal antibody as the drug vector in the treatment and diagnosis of myocardial injury, it is important to degrade the immunity of murine antibody and overcome human anti-mouse reaction. Humanization has been applied as an attempt to resolve this problem.OBJECTIVE: To clone murine anti-cTnI Fab fragment and analyse the nucleotide and deduced amino acid sequences.DESIGN: Single sample study.SETTING: An institute of cardiovascular disease under a medical university-affiliated hospitalMATERIALS: The study was conducted in the Institute of Cardiovascular Diseases, First Affiliated Hospital of Nanjing Medical University from January 2003 to May 2004. The hybridoma cell line JS200202 which secrets the anti-cTnI monoclonal antibody was provided by Institute of Cardiovascular Disease, First Affiliated Hospital of Nanjing Medical University.METHODS: IgG heavy chain primers and κ light chain primers of amplified mouse were designed. Total RNA was extracted from hybridoma cells which secrete cTnI. Reverse transcription polymerase chain reaction(RT-PCR) was amplified. Cloning and subsequent sequence analysis of the Fab fragment was performed. The deduced amino acid sequence was compared and analysed with previously published sequences.MAIN OUTCOME MEASURES: Heavy chain Fd segment and κ light chain gene sequence and its subgroups.RESULTS: A band of approximate 700 and 800 base pairs were amplified using IgG heavy chain primers and κ light chain primers respectively. Sequence analysis indicated that the deduced amino acid sequences were in consistent with the characterization of the amino acid in the murine IgGl Fab fragment(GenBank accession NO AY484430, AY484431; Protein Bank accession NO AAR83243, AAR83244).CONCLUSION: A complete murine anti-cTnI Fab fragment was obtained in this study, which may provide basis for the production of the chimeric anti-cTnI antibody.
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Objective: To construct a recombinant adenovirus expression vector of the SD rat Lys184del mutant cardiac troponin I gene(cTnI Lys184del).Methods: The Lys184del mutant cardiac troponin I gene of SD rat was induced by PCR-based site-directed mutagenesis,the amplified fragment containing the mutation was then inserted into the cloning vector pMD18-T.After the addition of a sequence encoding a 6?His tag at the C-terminus by PCR,the coding region of cTnI Lys184del was subcloned into Adeno-X viral DNA to form a recombinant adenoviral plasmid,which was packed into infectious recombinant adenoviral particles(Ad-cTnI Lys184del) by transfecting HEK293 cells.Results: The DNA sequence of Ad-cTnI Lys184del was proved to be correct by PCR and sequencing,and its expression was identified by Western blot analysis.Conclusion: The successfully constructed recombinant adenovirus Ad-cTnI Lys184del has provided valuable data for further researches on its functional characteristics.
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Objective To investigate cardiac troponin I (cTnⅠ) for detecting minor myocardial damage and evaluating the prognostic value in unstable angina (UA) Methods Serum cTnⅠ, creatine kinase isoenzyme MB (CK MB) and a part in cardiac troponin T (cTnT) were measured in 106 (UA) and 44 stable angina (SA) patients as well as 68 cases with normal coronary angiography, 72 healthy subjects Relative risk factors and occurrence of heart events were analyzed Results 61 of 106 patients with UA had elevated cTnⅠ levels (57 5%), but 8 of 44 cases with SA had positive results (18 18%) Among them, only 3 cases had slightly elevated CK MB levels The incidences of heart events were significantly higher in patients with elevated cTnⅠ levels than in patients with normal one The higher cTnⅠ levels was and the more heart events occurred cTnT values was similarly found to be an indicator of increased risk of heart events Conclusion cTnⅠ is a higher sensitive and specific marker for assessing minor myocardial damage cTnⅠ is a strong independent indicator of risk stratification in UA
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Some kinetic characteristics of beta-adrenoceptor on circulating intact lymphocytes (CIL) in the combined renovasoeular hypertensive and diabetic (HD) rats were studied and the relation of betareceptos between CIL and cardium as well as the morphologic changes in the processe of dilated cardiomypathy (DCM) were observed. The results show that: the density of beta-adrenoceptor on CIL (Bmax) was going up 41.28%(P0.05), but the Kd was still 50.01%(P