Correlation of macrophage-related cytokines and silent information regulator 1 and forkhead box protein O3 levels in peripheral blood mononuclear cells in patients with active pulmonary tuberculosis / 中国热带医学

@#Abstract: Objective　To explore the correlation between the levels of silent information regulator 1 (SIRT1) and forkhead box protein O3 (FOXO3) in peripheral blood mononuclear cells of patients with active pulmonary tuberculosis (APTB) and macrophage-related cytokines-inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1). Methods　A total of 64 APTB patients who were treated in Yubei Hospital, the First Affiliated Hospital of Chongqing Medical University from January 2020 to December 2021 were gathered as the APTB group, 59 people with latent tuberculosis infection (LTBI) were gathered as the LTBI group, and 62 healthy people were gathered as the control group. Quantitative real-time PCR (qPCR) method was performed to measure the levels of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells. The enzyme-linked immunosorbent assay (ELISA) was performed to measure serum iNOS and Arg-1 levels; ROC curve was used to analyze the value of SIRT1 mRNA and FOXO3 mRNA levels in the differential diagnosis of LTBI and APTB; Pearson correlation was performed to analyze the correlation of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells of APTB patients with serum iNOS and Arg-1 levels. Results　The levels of SIRT1 mRNA, FOXO3 mRNA and serum iNOS in peripheral blood mononuclear cells decreased in control group, LTBI group and APTB group, and the level of serum Arg-1 increased in turn (P<0.05). The AUCs of SIRT1 mRNA and FOXO3 mRNA in differential diagnosis of LTBI and APTB were 0.876 and 0.887, respectively, the sensitivity was 71.2% and 76.3%, and the specificity was 96.9% and 90.6% respectively. The levels of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells of APTB patients were positively correlated (r=0.500, P<0.05), and they were positively correlated with serum iNOS and negatively correlated with serum Arg-1 (P<0.05). The SIRT1 mRNA, FOXO3 mRNA and serum iNOS in peripheral blood mononuclear cells of APTB patients after 6 months of treatment were higher than those before treatment, and serum Arg-1 was lower than before treatment (P<0.05). Conclusions　The levels of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells of APTB patients are low, and they are positively correlated with macrophage-related cytokine iNOS and negatively correlated with Arg-1.

Effects of 16 week aerobic exercise on baPWV and ABI of middle-aged and elderly patients / 中国应用生理学杂志

OBJECTIVES@#To investigate the interventional effects of 16-week aerobic exercises on the elderly's arteriosclerosis and its mechanism.@*METHODS@#Twenty-seven elderly people with the average age of 62. 70 ±3. 26 joined a 16-week square dance/taijiquan exercise program that conducted 60 minutes each time, six times per week. Arterial stiffness and its related indexes such as systolic pressure(SBP), diastolic pressure(DBP), left brachial-ankle pulse wave velocity (L-baPWV), right brachial-ankle pulse wave velocity(R-baPWV), left ankle brachial index (L-ABI), right ankle brachial index(R-ABI), serum triglyceride(TG), total cholesterol(TC), high density lipoprotein cholesterol(HDL-c), low density lipoprotein cholesterol(LDL-c), superoxide dismutase(SOD), malondialdehyde(MDA) and glutathione peroxidase (GSH-Px) were detected at 3 time points including before exercise program, by the end of exercise for 8 weeks and 16 weeks.@*RESULTS@#① Compared with pre-exercise, the R-baPWV and R-ABI of the elderly people were decreased at the end of the 8 week, and the L-baPWV, RbaPWV, R-ABI and L-ABI were decreased significantly at the end of the 16 week. ②Compared with pre-exercise, SBP and DBP were declined markedly (<0.01, <0.05) at the end of the 8 week, SBP, DBP and pulse pressure were decreased significantly (<0.01, <0.05) at the end of the 16 week. ③Compared with pre-exercise, TC and LDL-c were declined markedly (<0.01) at the end of the 8 and the 16 week, and there was no difference of the level of TG and LDL-c between pre-exercise and post-exercise. ④There was no evident difference of serum level of SOD, GSH-Px, MDA between pre-exercise and post-exercise at the end of the 8 week. Compared with pre-exercise, the level of serum SOD, GSH-Px was increased evidently while the content of serum MDA was decreased significantly (<0.01).@*CONCLUSIONS@#Sixteen-week aerobic exercises could reduce baPWV and ABI levels, regulate blood pressure, blood lipids and lipid peroxides levels of the elderly evidently, thus improve the controlling quality of atherosclerosis.

Effect of TGF-b1 siRNA-mediated silencing on Smad proteins in hepatic fibrosis rats / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the changes in Smad 2, 3, 4 and 7 of the transforming growth factor-beta 1 (TGF-b1)/Smad signaling pathways in carbon tetrachloride (CCL4)-induced hepatic fibrosis rats treated with TGF-b1 small interfering (si)RNA.</p><p><b>METHODS</b>Rats were randomly divided among five groups: non-fibrotic (normal); fibrosis-induced (model); fibrotic treated with 0.125 mg/kg TGF-b1 siRNA; fibrotic treated with 0.250 mg/kg TGF-b1 siRNA; and fibrotic treated with negative control TGF-b1 siRNA. The expression of Smad 2, 3, 4 and 7 was detected by real-time polymerase chain reaction (for mRNA), immunohistochemistry and Western blotting (for protein).</p><p><b>RESULTS</b>The mRNA and protein levels of Smad 2, 3 and 4 were significantly lower in the the fibrotic rats treated with either 0.250 mg/kg or 0.125 mg/kg TGF-b1 siRNA than in the fibrotic model or the negative control TGF-b1 siRNA rats (P less than 0.01). Moreover, the mRNA and protein expression levels of Smad 2, 3 and 4 were significantly lower in the 0.250 mg/kg TGF-b1 siRNA group than in the 0.125 mg/kg group (P less than 0.05). Comparing the 0.250 mg/kg and 0.125 mg/kg TGF-b1 siRNA groups to the model group and the TGF-b1 siRNA negative control group showed significantly increased levels of mRNA and protein expression of Smad 7 (P less than 0.01). In addition, the expression levels of Smad 7 were significantly higher in the 0.250 mg/kg TGF-b1 siRNA group than in the 0.125 mg/kg group (P less than 0.05).</p><p><b>CONCLUSION</b>siRNA-mediated silencing of TGF-b1 in rats led to significantly reduced expression of Smad 2, 3 and 4, but significantly increased expression of Smad 7. TGF-b1 regulation of Smad signaling molecules may contribute to hepatic fibrosis in rats and represent a target of future therapeutic intervention.</p>

Efficacy of lamivudine on acute-on-chronic liver failure in patients with chronic hepatitis B / 中华肝脏病杂志

To observe the therapeutic effects of lamivudine treatment in patients with early- to mid-stage hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Clinical data of 73 hospitalized patients with HBV-ACLF were retrospectively analyzed. Prothrombin time (PT, active coagulation), HBV DNA, and model for end-stage liver disease (MELD) score data from treatment weeks 4, 8, 24, and 48 were collected and analyzed using the statistical t-test. During the treatment duration, the complete virologic response rates were 57.5% (42/73) at 4 weeks, 71.0% (44/62) at 8 weeks, 83.1% (49/59) at 24 weeks, and 86.5% (45/52) at 48 weeks. The partial virologic response rates were 30.1% (22/73) at 4 weeks, 25.8% (16/62) at 8 weeks, 17.0% (10/59) at 24 weeks, and 13.5% (7/52) at 48 weeks. At week 48, the survival rate was 71.2% (52/73) and the probability of survival was higher in the complete virological response rate (VRR) group than in the partial VRR group [45/73 (61.6%) vs. 7/73 (30.1%), respectively; P = 0.000]. In addition, there were significant improvements in the serum normalization rate of HBV DNA, alanine aminotransferase, aspartate aminotransferase, albumin, total bilirubin, PT and MELD score in surviving patients compared to baseline (P less than 0.05) and in the complete VRR group compared to the partial VRR group (P less than 0.05). Antiviral therapy using lamivudine may be an effective therapeutic option for patients with HBV-ACLF.

Construction and identification of siRNA eukaryotic expression vectors targeting on TGFβ1, TIMP-1 and TIMP-2 genes in vitro / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To construct the siRNA eukaryotic expression vectors targeting on TGFβ1, TIMP-1 and TIMP-2 and to investigate the inhibitory efficiency of target genes expression on rat hepatic stellate cell in vitro.</p><p><b>METHODS</b>The siRNA cDNA sequences of TGFβ1, TIMP-1 and TIMP-2 were designed, synthesized and inserted into plasmid pGenesil-1 respectively to generate eukaryotic expression plasmids. The plasmids were transfected into HSC T6 cells in vitro and the inhibitory efficiency of target genes expression was observed with real-time PCR and Western blot.</p><p><b>RESULTS</b>The eukaryotic expression vectors were constructed successfully. The expressions of TGFβ1 mRNA, TIMP-1 mRNA and TIMP-2mRNA in siRNA-transfected groups were decreased by 63.4% ± 8.0%, 64.5% ± 9.0% and 55.0% ± 17.0% respectively and the expressions of TGFβ1 protein, TIMP-1 protein and TIMP-2 protein were decreased by 57.8% ± 3.0%, 55.1% ± 5.0%, 49.3% ± 1.0% respectively as compared to the control groups.</p><p><b>CONCLUSIONS</b>The siRNA eukaryotic expression vectors constructed targeting on TGFβ1, TIMP-1 and TIMP-2 could reduce the expressions of target genes and they might be able to used for the exploration of new anti-fibrosis drugs genetically.</p>