1.Efficacy and safety of sequential or combined therapy with tenofovir alafenamide fumarate in entecavir-treated patients with low-level viremia
Yijing ZHANG ; Lingying HUANG ; Bowu CHEN ; Wanchun ZHU ; Man LI ; Jie SHEN ; Yueqiu GAO
Journal of Clinical Hepatology 2026;42(1):66-73
ObjectiveTo investigate the efficacy of sequential tenofovir alafenamide fumarate (TAF) therapy versus the regimen of entecavir (ETV) combined with TAF in chronic hepatitis B (CHB) patients experiencing low-level viremia (LLV) after ETV therapy, as well as their impact on virologic response, liver and renal function, and blood lipid levels. MethodsA total of 217 CHB patients with LLV after ETV treatment who were admitted to Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 2020 to December 2023 were enrolled, and according to the treatment regimen, they were divided into TAF group (180 patients receiving sequential TAF therapy) and combined group (37 patients receiving ETV+TAF therapy). The propensity score matching (PSM) method was used to match the patients at a ratio of 1∶1, and finally 37 patients were included in each group to balance the baseline confounding factors. The two groups were compared in terms of hepatitis B virus DNA (HBV DNA) clearance rate, hepatitis B envelope antigen (HBeAg) clearance rate, liver and renal function parameters (liver stiffness measurement [LSM], platelet count [PLT], aspartate aminotransferase [AST], alanine aminotransferase [ALT], and creatinine [Cr]), blood lipid levels (total cholesterol [TC], triglyceride [TG], high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol [LDL-C]), and the incidence rate of adverse reactions. The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the paired t-test was used for comparison within each group; the chi-square test was used for comparison of categorical data between groups. ResultsAfter 48 weeks of treatment, compared with the TAF group, the combined group had significantly higher HBV DNA clearance rate (86.49% vs 59.46%, χ²=6.852, P=0.009) and HBeAg clearance rate (59.46% vs 35.14%, χ²=4.391, P=0.036). After treatment, compared with the TAF group, the combined group had significantly lower levels of LSM (7.01±1.50 kPa vs 7.90±1.68 kPa, t=2.404, P=0.019), AST (18.02±2.28 U/L vs 21.12±2.85 U/L, t=5.166, P<0.001), and ALT (19.85±3.86 U/L vs 22.00±3.90 U/L, t=2.383, P=0.020) and significantly higher levels of PLT [(218.35±42.60)×109/L vs (192.82±44.13)×109/L, t=2.532, P=0.014] and Cr (70.92±6.54 μmoL/L vs 67.60±6.13 μmoL/L, t=2.253, P=0.027). After treatment, there was a slight increase in the level of TC in both the TAF group (5.60±0.89 mmol/L vs 5.18±0.85 mmol/L, t=2.076, P=0.041) and the combined group (5.45±0.80 mmol/L vs 5.02±0.83 mmol/L, t=2.269, P=0.026). There was no significant difference in the incidence rate of adverse reactions between the TAF group and the combined group (21.62% vs 18.92%, χ²=0.084, P=0.772). ConclusionFor ETV-treated CHB patients experiencing LLV, compared with sequential TAF therapy, the ETV+TAF combined therapy can effectively increase virologic response rate, alleviate liver fibrosis, and improve liver function, whereas sequential TAF therapy has less impact on renal function. Sequential or combined therapy with TAF may induce a slight increase in the level of TC, which should be taken seriously in clinical practice.
2.Influence of virologic response on disease progression in patients with compensated hepatitis B cirrhosis
Bowu CHEN ; Xiaojun ZHU ; Xin ZHANG ; Xuehua SUN ; Man LI ; Yueqiu GAO
Journal of Clinical Hepatology 2021;37(8):1811-1816.
ObjectiveTo investigate the effect of sustained virologic response on disease progression and the development of hepatocellular carcinoma (HCC) in patients with compensated hepatitis B cirrhosis receiving antiviral therapy with nucleos(t)ide analogues (NAs). MethodsA total of 542 patients with compensated hepatitis B cirrhosis who attended Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 1 to December 31, 2013, received antiviral therapy, and were followed up for more than 5 years were enrolled, and according to the status of virologic response during follow-up, they were divided into a sustained virologic response cohort with 496 cases and a non-sustained virologic response cohort with 46 cases. With disease progression as the outcome event, general information and examination data were collected during the 5-year follow-up period. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. A multivariate logistic regression analysis was performed; relative risk and 95% confidence interval (CI) were used to investigate the degree of correlation of factors measured with the progression of liver cirrhosis. The life-table method was used to calculate the 1-, 3-, and 5-year progression-free survival rates, and the Kaplan-Meier method was used to plot survival curves; the log-rank test was used for univariate analysis, and the Cox regression model was used for multivariate regression analysis. ResultsFor the 542 patients, the mean progression-free survival time was 62.50 months (95% CI: 61.01-63.92), and the 1-, 3-, and 5-year progression-free survival rates were 94%, 82%, and 71%, respectively. The sustained virologic response cohort had a significantly longer mean progression-free survival time than the non-sustained virologic response cohort [63.10 months (95% CI: 61.65-64.55) vs 55.95 months (95% CI: 50.19-61.71), χ2=12.058, P=0.001]. Compared with the non-sustained virologic response cohort, the sustained virologic response cohort had significantly lower 5-year cumulative incidence rate of HCC than (20.6% vs 34.8%, χ2=5.759, P=0.016) and 5-year cumulative incidence rate of decompensated cirrhosis (5.0% vs 15.2%, χ2=8.239, P=0.004). Virologic response was an independent risk factor for disease progression (hazard ratio=232, 95% CI: 1.45-3.72). ConclusionSustained virologic response can reduce the incidence rates of complications and HCC, improve long-term prognosis, and prolong survival time in patients with compensated hepatitis B cirrhosis.
3.Effect of jinmaitong capsule on inducible nitric oxide synthase and nitrotyrosine in diabetic rats.
Qing SUN ; Xiaochun LIANG ; Puyan WANG ; Bowu LI ; Li ZHAO ; Wenzhi HUANG ; Yandong ZHANG
China Journal of Chinese Materia Medica 2012;37(3):348-352
OBJECTIVETo observe the effect of Jinmaitong capsule (JMT), a compound traditional Chinese medicine, on expressions of inducible nitric oxide synthase (iNOS) and nitro tyrosine (NT) protein in streptozocin-induced diabetic (STZ-DM) rats.
METHODIntraperitoneal injection of streptozocin in rats to establish a model. STZ-DM rats were randomly divided into the model control group (distilled water), the small-dose JMT group (JMT at dose of 0.45 g x kg(-1) x d(-1)), the medium-dose JMT group (JMT at dose of 0.88 g x kg(-1) x d(-1)), the large-dose JMT group (JMT at dose of 1.75 g x kg(-1) x d(-1)) and Vitamin C group (VC at dose of 0.05 g x kg(-1) x d(-1)). Ten normal rats with matching weight and age were selected as the normal control group (distilled water). After intragastric administration for 16 weeks, the expressions of iNOS and NT in sciatic nerve were detected by the immunohistochemistry method.
RESULTThe expression levels of iNOS and NT protein in diabetic rats were higher than those in normal rats (P<0.05, P<0.01). Compared with the model group, the levels of iNOS and NT protein in JMT and VC groups were significantly decreased (P<0.05, P<0.01). Particularly, the medium-dose JMT group showed a better effect than the VC group (P<0.05, P<0.01).
CONCLUSIONJMT could down-regulate the expressions of iNOS and NT protein of sciatic nerve in diabetic rats.
Animals ; Blood Glucose ; Body Weight ; drug effects ; Capsules ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; pathology ; Diabetic Neuropathies ; drug therapy ; metabolism ; pathology ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Enzyme Activation ; drug effects ; Male ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; drug effects ; metabolism ; pathology ; Tyrosine ; analogs & derivatives ; metabolism
4.Cardiac electrophysiological characteristics after transplantation of differentiated bone marrow mesenchymal stem cells
Bowu LIU ; Anlin Lü ; Xuebo YAN ; Wei HUANG ; Jing HOU ; Yao LI
Chinese Journal of Tissue Engineering Research 2011;15(32):6072-6076
BACKGROUND: With the development of biotechnology, the electrophysiology of repairing heart tissues of myocardial infarction or myocardial hypertrophy by using bone marrow mesenchymal stem cell has become a hot spot. OBJECTIVE: To overview the research progress of cardiac electrophysiological characteristics after transplantation of induced differentiation of bone marrow mesenchymal stem cells into cardiomyocytes. METHODS: The databases of PubMed, Springer Link, Science Direct and CNKI were retrieved for papers published from January 2000 to October 2010 with the key words of bone marrow mesenchymal stem cells, cardiac/heart, electrophysiology/electrophysiological characteristics. The relevant articles concerning cardiac electrophysiological characteristics of induce differentiation and transplantation of bone marrow stem cells were collected. RESULTS AND CONCLUSION: Totally 208 papers have been searched. Preliminary screening by reading abstracts to exclude 162 papers that study purpose do not coincident with this review either contents duplicated, and internalized 46 papers at last. Bone marrow mesenchymal stem cells after induced differentiation and transplantation could improve heart function of animal experimental model and myocardial infarction or myocardial hypertrophy patients. Although the cardiomyocyte-like cells from bone marrow mesenchymal stem cells could help to improve heart function, the cardiac electrophysiological characteristics may be influenced by them.
5.Effects of Chinese herbal medicine Jinmaitong-medicated serum on inducible nitric oxide synthase and NADPH oxidase p22-phox subunit of rat Schwann cells cultured in high-glucose medium.
Li ZHAO ; Xiaochun LIANG ; Hong ZHANG ; Puyan WANG ; Qing SUN ; Wenzhi HUANG ; Bowu LI
Journal of Integrative Medicine 2011;9(3):299-305
To investigate the effects of medicated serum prepared by administration of Jinmaitong (JMT), a compound Chinese herbal medicine, on nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22-phox subunit and inducible nitric oxide synthase (iNOS) of rat Schwann cells cultured in high-glucose medium.

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