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Objective@#Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.@*Methods@#Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281.@*Results@#At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss.@*Conclusion@#Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.
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Objective To investigate the effect of miRNA-200b-specific inhibitor on hepatic stellate cells(HSCs) activation,proliferation,and extracellular matrix production.Methods The miRNA-200b-specific inhibitors were designed,synthesized,and transfected into HSCs with lipofectamine 2000.The supernatant and HSCs were collected after incubation for 48 h.The expression of miR-200b was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR).The expression ofα-smooth muscle actin (oα-SMA) protein in HSCs was detected by Western blotting.The cell proliferation was assayed by methyl thiazolyl tetrazolium (MTT) method.Contents of type Ⅲ procollagen and hyaluronic acid in supernatant were determined by radioimmunoassay.Results Compared to the control group,miRNA-200b expression was decreased in the miRNA-200b inhibitor group by 82％ (P ＜ 0.01),α-SMA protein expression was reduced in the miRNA-200b inhibitor group by (19 ± 3) ％ (P ＜ 0.05),and the activity of HSCs proliferation was reduced by(33 ± 5)％ (P ＜0.01),and the contents of type Ⅲ procollagen and hyaluronic acid in supernatant were reduced in miRNA-200b inhibitor group by (35 ± 4)％ and (31 ± 2)％,respectively(P ＜0.01).Conclusions The miRNA-200b-specific inhibitor could significantly reduce the expression of miRNA-200b,and inhibit HSC proliferation,activation,and extracellular matrix production.
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Objective To investigate the effect of microRNA-21 (miR-21) antisense oligonucleoti-de on collagen synthesis in the rat hepatic satellite cells ( HSCs) .Methods Rat hepatic stellate cells were isolated and cultured; the miR-21 antisense oligonucleotide was transfected into HSCs with lipofectamine 2000;after incubation 48 h, the HSCs were collected.The expression of miR-21 was detected with reverse transcription polymerase chain reaction ( RT-PCR) , andα-smooth muscle actin (α-SMA) protein in HSCs with Western blot.The cell proliferation was assayed with methyl thiazolyl tetrazolium ( MTT) method.Re-sults Compared to scrambled control group, the expression of miR-21 was reduced by 76%( P <0.01), the proliferation activity of HSCs was reduced by(26 ±3)%( P <0.01), the expressions of type I and III collagen proteins were reduced by(61 ±7)%and (48 ±6)%( P <0.01).Conclusions The miR-21 an-tisense oligonucleotide could reduce significantly the expression of miR-21, and inhibit HSC proliferation and extracellular matrix production.
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Objective To investigate the effect of TGFβ1 siRNA on hepatic satellite cells (HSCs) activation, proliferation and extracellular matrix production. Methods The TGFβ1, siRNA plasmid was transfected into HSCs with Lipofectamine 2000. The supernatant and HSCs were collected after incubation for 72h. The expression of TGFβ1, and a-SMA protein in HSCs was detected by. Western blotting. The expression of type Ⅰ and Ⅲ collagen mRNA was detected by RT-PCR. The cell proliferation was assayed by MTT method. Contents of typeⅣ collagen and hyaluronic acid in supernatant were determined by radioimmuno-assay.Results Compared with scrambled control group, the TGFβ1, and a-SMA protein expression,the activity of HSCs proliferation,the expression of typeⅠ and Ⅲ collagen mRNA,and the contents of type Ⅳ collagen and hyaluronic acid in supernatant were reduced in TGFβ1, siRNA group by (79±5)%,(55±4)%, (25±4)% ,(63±6)% ,(57±4)% ,(53±8)% ,(46±8)% ( P<0.01),respectively.Conclusion TGFβ1, siRNA could significantly reduce the expression of TGFβ1,inhibited HSC activation,proliferation and extracellular matrix production.
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Objective To study the diagnostic value of common inflammatory markers in patients with infectious diseases. Methods One hundred sepsis patients, 100 viral infection patients,100 pulmonary tuberculosis patients and 100 gonorrhea patients were analyzed retrospectively. The contents of procalcitonin (PCT), C-reactive protein (CRP), haptoglobin (HP), ceruloplasmin (CER), α1-acid glycoprotein (α1-AAG), α1-antitrypsin (α1-AAT), white blood cell count (WBC) and erythrocyte sedimetation rate (ESR) were measured. The receiver operating characteristic curve (ROC curve), sensitivity, specificity, positive predictive value, negative predictive value, Youden's index,positive and negative likelihood ratios and total coincidence rate were calculated respectively. Results The area under the ROC curve, sensitivity, specificity, Youden's index and positive likelihood ratios,positive predictive value and total coincidence rate of PCT in sepsis patients were 0. 895, 0.84, 0.92,0.76, 10.50, 0.91 and 0.88, respectively, which were superior to CRP, HP, CER, α1-AAG, α1-AAT, WBC and ESR. Conclusions PCT is a better inflammatory reactive parameter than other parameters currently applied in practice and may serve as a rapid and sensitive test in the early stage of severe bacterial infections.
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Objective To observe the early efficacy and safety of combined sequential administration of lamivudine and interferon alfa-2b in patients with hepatitis Be antigen (HBeAg)-positive chronic hepatitis B. Methods 71 patients were divided into combined therapy growp (23 eases),interferon group (27 cases) and lamivudine group (21 cases).patients in the first group were given sequential combination treatment with of lamivudine monotherapy for nine weeks followed by lamivudine plus interferon alfa-2b for 15 weeks while patients in the interferon group and Lamivudine group received interferon alfa-2b monotherapy and lamivudine respectively. Results At 24weeks, 43.37% of the patients who received sequential combination treatment and 33.33% of those who received interferon alfa-2b monotherapy had HBeAg seroconversion,which is higher than those who received lamivudine monotherapy(9.52%, P0.05). The normolization rates of ALT in combining group , interferon group and Lamivudine group were 60.87%, 51.85% and 19.04% respectively(P