A real-world study of the efficacy and safety of sofosbuvir and velpatasvir in the treatment of HCV-infected patients in a county in northern China / 中华肝脏病杂志

Objective: To evaluate the real-world efficacy and safety of sofosbuvir and velpatasvir (SOF/VEL) tablets in the treatment of Chinese patients with chronic HCV infection. Methods: An open-label, single-center, prospective clinical study was conducted in a county in northern China. A total of 299 cases were enrolled. Of these, 161 cases with chronic hepatitis C and 73 cases with compensated cirrhosis received SOF/VEL for 12 weeks. 65 cases with decompensated cirrhosis received SOF/VEL combined with ribavirin for 12 weeks (22 cases) or SOF/VEL for 24 weeks (43 cases). Virological indicators, liver and renal function indexes, and liver stiffness measurement were detected at baseline, the fourth week of treatment, the end of treatment, and the 12-weeks of follow-up. Adverse reactions and laboratory abnormalities were observed during the course of treatment . The primary endpoint was undetectable rate of HCV RNA (SVR12) at 12 weeks of follow-up with the use of modified intention-to-treat (mITT) approach. Measurement data between two groups were compared using t-test. One Way ANOVA was used for comparison between multiple groups. Enumeration data were analyzed by chi-square test or Fisher's exact test. Results: 291 cases had completed treatment. HCV RNA was undetectable after 12 weeks of follow-up, and the SVR12 rate was 97.3% (95% confidence interval: 95.4%-99.3%). Among them, 97.4% of genotype 1b, 96.4% of genotype 2a, and 100% of those with undetected genotype achieved SVR12. The SVR12 rates in patients with chronic hepatitis C, compensated and decompensated liver cirrhosis were 98.1%, 98.6% and 93.8%, respectively. An improvement in alanine aminotransferase, aspartate aminotransferase and other liver biochemical indicators accompanied with virological clearance and reduced liver stiffness measurement was observed in patients with compensated cirrhosis, with statistically significant difference. There was no significant abnormality in renal function before and after treatment. The most common adverse reactions were fatigue, headache, epigastric discomfort and mild diarrhea. The overall adverse reactions were mild. One patient died of decompensated liver cirrhosis combined with massive upper gastrointestinal bleeding, which was unrelated to antiviral treatment. Four patients discontinued treatment prematurely due to adverse events. Relapse was occurred in four cases, and drug-resistance related mutations were detected in three cases. Conclusion: Sofosbuvir and velpatasvir tablets in Chinese HCV-infected patients with different genotypes, different clinical stages or previously treated with pegylated interferon combined with ribavirin resulted in higher SVR12, indicating that the treatment safety profile is good.

Effect of Bufei Yishen Prescription on Airway Mucus Hypersecretion and Notch3 and HES1 Expression in Lung Tissues of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

ObjectiveTo observe the effects of Bufei Yishen prescription on airway mucus hypersecretion and Notch signaling pathway related protein Notch3 and enhancer of split homologue 1 （HES1） in rats with chronic obstructive pulmonary disease （COPD） and to explore its action mechanism. MethodForty-eight SD rats were randomly divided into the control group， model group， Bufei Yishen prescription group， and aminophylline （APL） group，with 12 rats in each group. The stable COPD rat model was established via cigarette smoking exposure combined with Klebsiella bacterial infection for 12 weeks， and the corresponding drugs （3.7 g·kg-1·d-1 Bufei Yishen prescription and 54 mg·kg-1·d-1 APL） were administered by gavage during the next eight weeks. After the last administration at week 20， the lung tissue was sampled for observing the pathological changes and the rat lung function was detected. The tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and mucoprotein 5AC （MUC5AC） in bronchial alveolar lavage fluid and the mRNA and protein expression levels of Notch3， HES1， and MUC5AC in lung tissues were assayed. ResultCompared with the control group， the model group exhibited significantly weakened pulmonary function （P<0.05，P<0.01）， reduced average number of alveoli （P<0.01）， elevated mean linear intercept （P<0.01）， and up-regulated TNF-α， IL-6， and MUC5AC in bronchial alveolar lavage fluid and Notch3， HES1， and MUC5AC mRNA and protein expression in lung tissue （P<0.05，P<0.01）. Compared with the model group， Bufei Yishen prescription and APL remarkably enhanced pulmonary function， alleviated its pathological injury （P<0.05，P<0.01）， and down-regulated TNF-α， IL-6， and MUC5AC in bronchial alveolar lavage fluid and the mRNA and protein expression levels of Notch3， HES1， and MUC5AC in lung tissues （P<0.05，P<0.01）. ConclusionThe mechanism of Bufei Yishen prescription in inhibiting airway mucus hypersecretion of COPD rats was related to its regulation of Notch3 and HES1.

Clinical Study of Jiawei Xiaochaihutang Combined with Microwave Ablation in Treatment of Primary Hepatocellular Carcinoma / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Jiawei Xiaochaihutang combined with microwave ablation （MWA） in the treatment of primary hepatocellular carcinoma （HCC） and its influence on tumor microenvironment. MethodA total of 128 patients were randomly divided into control group （64 cases： 2 cases of dropout，2 cases of elimination，and 60 cases of completion） and observation group （64 cases： 3 cases of dropout，2 cases of elimination，and 59 cases of completion）. Both groups were given comprehensive treatment after MWA surgery. Patients in control group took Biejiajian Wan orally （3 g/time，3 times/d）， and those in observation group took Jiawei Xiaochaihutang （1 dose/d）. The treatment lasted for 3 consecutive months. The size of solid tumor before and after treatment was evaluated to record the progression-free survival （PFS）. The alpha-fetoprotein-L13 （AFP-L3），des-γ-carboxy prothrombin （DCP），Golgi protein 73 （GP73），tumor necrosis factor-α （TNF-α），transforming growth factor-β （TGF-β），vascular endothelial growth factor （VEGF） and matrix metalloproteinase-2 （MMP-2） levels，as well as performance status （PS），liver function and syndrome of liver depression and Qi stagnation scores were also detected before and after treatment. In addition， the incidence of side effects of grade Ⅲ and above was compared. ResultThe total effective rate of solid tumor in observation group was 91.53% （54/59），higher than that （76.67%， 46/60） in control group（χ2=4.895，P<0.05）. The PFS in observation group was （7.16±0.95） months， longer than that （6.24±0.89 months） in control group （P<0.01）. The effective rate of traditional Chinese medicine （TCM） syndrome in observation and control groups were 88.14% （52/59）and 70.00% （42/60）， respectively （χ2=5.897，P<0.05）. The observation group （57.63%，34/59） had higher marked effective rate of TCM syndrome than control group （31.67%，19/60） （χ2=8.116，P<0.01）. The AFP-13，DCP，GP73，TNF-α，TGF-β，VEGF and MMP-2 levels and the PS，liver function and syndrome of liver depression and Qi stagnation scores in observation group were lower than those in control group （both P<0.01）. The cumulative incidence of side effects of grade Ⅲ and above in observation and control groups was 16.95% and 33.33%， respectively（χ2=4.261，P<0.05）. ConclusionConsolidation treatment of HCC after MWA surgery with Jiawei Xiaochaihutang relieved symptoms and side effects，improved PS and liver function，regulated tumor microenvironment，inhibited tumor markers and prolonged survival time. The clinical effect was better than that of Biejia decoction pill， and thus it was worthy of clinical use.

Effect of Taiji Quan on Sleep Quality of Patients with Chronic Insomnia Disorder / 中国康复理论与实践

Objective:To explore the effect of Taiji Quan on the sleep quality of patients with chronic insomnia disorder (CID) and its mechanism. Methods:From January, 2015 to December, 2017, 31 patients with CID were enrolled in the sleep disorder clinic. Before and 24 weeks after Taiji Quan exercise, the Pittsburgh Sleep Quality Index (PSQI) was used to assess their sleep quality, the serum levels of tumor necrosis factor (TNF)-α, TNF-β, soluble tumor necrosis factor receptor (sTNF-R)1 and sTNF-R2 were detected with protein chip, and the correlation between the total score of PSQI and the serum levels of TNF-α, TNF-β, sTNF-R1 and sTNF-R2 were analyzed after exercise. Results:After Taiji Quan exercise, the scores of PSQI factors (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, daytime dysfunction) and the total score of PSQI decreased (t > 4.080, P < 0.05). The serum levels of TNF-α and TNF-β decreased (t > 13.580, P < 0.01), however, the serum levels of sTNF-R1 and sTNF-R2 significantly increased (t > 160.189, P < 0.001). The serum levels of TNF-α and TNF-β were positively correlated with the total score of PSQI (r > 0.638, P < 0.001), while the serum levels of sTNF-R1 and sTNF-R2 were negatively correlated with the total score of PSQI (r > 0.532, P<0.001). Conclusion:Taiji Quan exercise could help to improve the sleep quality of patients with CID. The mechanism may be related to the decrease of the serum levels of TNF-α and TNF-β, and the increase of the serum levels of sTNF-R1 and sTNF-R2.

Effects of clonidine on learning and memory and protein levels of ERK signal pathway-related proteins in rats with chronic cerebral ischemia / 中国病理生理杂志

AIM:To investigate the regulatory effects and underlying molecule-mechanism of clonidine on learning and memory in rats with chronic cerebral ischemia.METHODS: Sprague-Dawley rats(n=45)were randomly divided into sham-operation group,cerebral ischemia model group and clonidine group,15 rats in each group.The chronic cerebral ischemia rat model was established by right middle cerebral artery occlusion for 2 h and reperfusion for 30 d. Clonidine was administrated by i.g.for 7 days in clonidine group.The ability of spatial reference memory of the rats with cerebral ischemia was tested by Morris water maze.The protein levels of extracellular signal-regulated kinase 1/2(ERK1/2),phosphorylated ERK1/2(p-ERK1/2), cAMP-response element binding protein(CREB)and phosphorylated CREB (p-CREB)were determined by immunohistochemistry and Western blot.RESULTS:The results of Morris water maze test showed that compared with the sham-operation group,the ability of spatial reference memory was obviously impaired in the cerebral ischemia model group.Compared with the cerebral ischemia model group,the ability of spatial reference memory in the clonidine group were improved.Compared with the sham-operation group, the protein levels of p-ERK1/2 and p-CREB in hippocampus were increased in model group(P<0.01).Compared with the cerebral ischemia model group,the protein levels of p-ERK1/2 and p-CREB in hippocampus were decreased in the clonidine group(P<0.01).CONCLU-SION:Clonidine improves the learning and memory abilities of the rats with cerebral ischemia, and ERK1/2 and CREB are involved in this process.

Inhibitory effect of Panax notoginseng saponins on alveolar epithelial to mesenchymal transition / 中国中药杂志

In the study, the effects of Panax notoginseng saponins (PNS) on alveolar epithelial to mesenchymal transition (EMT) and extracellular matrix degradation were observed in a type of human alveolar epithelial cell, A549 cells, stimulated by TGF-beta1. Firstly, MTT method was applied to evaluation of cellular proliferation and found that PNS from 12.5 mg x L(-1) to 200 mg x L(-1) dosage could not inhibit significantly cellular proliferation. Then, cells were divided into five groups, normal group, TGF-beta1 group, TGF-beta1 + 50 mg x L(-1) PNS group, TGF-beta1 + 100 mg x L(-1) PNS group and TGF-beta1 + 200 mg x L(-1) PNS group. Normal cells were not stimulatec by TGF-beta1; TGF-beta1 cells were only stimulated by TGF-beta1 and the other cells were stimulated by TGF-beta1 with different doses of PNS, respectively. After stimulation, cells and supernatants were collected for assays. Cellular roundness was applied to quantitative evaluation of morphological change. Immunocytochemistry was applied to examine E-cadherion, a-SMA and FN proteins expression in the cells. Enzyme linked-immunosorbent assay was applied to MMP-9 and TIMP-1 levels. The results showed that EMT of A549 cells was induced by TGF-beta1, showing significant change of roundness, E-cadherion, alpha-SMA and FN (P < 0.05, P < 0.01). Compared to TGF-beta1, PNS significantly inhibited the changes of roundness (P < 0.05), FN and alpha-SMA (P < 0.05, P < 0.01) and not significantly inhibited the change of E-cadherion. Furthermore, MMP-9 levels were significantly increased by TGFbeta1 stimulation (P < 0.05), without significant change of TIMP-1. Compared with TGF-beta1, PNS could significantly increase MMP-9 level (P < 0.05) and decrease TIMP-1 levels (P < 0.05, P < 0.01). In conclusion, PNS could inhibit alveolar epithelial cell EMT induced by TGF-beta1, with increase of extracellular matrix degradation ability, which showed anti-fibrosis of lung ability.

Changes in lymphocyte surface expression of CD8 and CD38 molecules in peripheral blood of inactive HBsAg carriers following pegylated interferon a-2a therapy / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effects of pegylated interferon a-2a (Peg-INFa-2a) treatment on expression of CD8 and CD38 surface molecules on lymphocytes from peripheral blood of inactive hepatitis B surface antigen (HBsAg) carriers.</p><p><b>METHODS</b>Forty-four patients with hepatitis B virus (HBV) chronic infection (CHB) received a 48-week course of Peg-INFa-2a treatment, with 30 administered 135 mug/week and 14 administered 180 mug/week. Every 12 weeks of treatment, the subjects were assessed for HBsAg titer, presence of anti-hepatitis B e (HBe) antibody, serum alanine amino transaminase (ALT) levels, and lymphocyte surface expression of CD8 and CD38 molecules. Patients were classified as responders and non-responders according to standard parameters. Dynamic differences between the two groups over time were assessed by multivariate repeated measures ANOVA with Greenhouse-Geisser correction and differences at single time points were assessed by univariate ANOVA. Linear regression analysis was performed to evaluate the relationship of two variables.</p><p><b>RESULTS</b>The responders showed a significantly higher increase in ALT at week 12 (60.75+/-24.95 U/L vs. non-responders: 37.03+/-18.45 U/L; t = 2.905, P less than 0.01) and significantly higher proportion of CD8+CD38+ cells at week 24 (71.20+/-11.70% vs. non-responders: 56.79+/-7.72%; F = 23.941, P less than 0.01). The decline in level of HBsAg at week 24 was positively correlated with the increase in ALT level at week 12 (r = 0.386, P less than 0.01) and with expression levels of CD8 and CD38 molecules on lymphocytes at week 24 (r = 0.397, P less than 0.01).</p><p><b>CONCLUSION</b>Lower baseline levels of HBsAg correlated to better Peg-INFa-2a-related HBsAg clearance. Increased expression of CD8 and CD38 on lymphocytes is suggestive of intensive cellular immunity in CHB patients and may be related to HBV-induced hepatocyte damage and may promote the HBsAg clearance.</p>

The clinical significance of PreS1Ag and anti-PreS1 in patients with chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the positive ratio and clinical significance of PreS1Ag and anti-PreS1 in patients with chronic hepatitis B.</p><p><b>METHODS</b>428 patients with chronic HBV infection were collected, these patients were divided into e antigen-positive CHB group, e antigen-negative CHB group, inactive HBsAg carrier group and HBsAg serum conversion group. The difference of positive ratio of PreS1Ag and anti-PreS1 among all groups or between every two groups were analyzed; The relationship of PreS1Ag and anti-PreS1 with HBV M and HBV DNA were also analyzed. SPSS13.0 software was used for statistical treatment. Fourfold table chi-square test or matched-pairs chi-square test was used for enumeration data, and independent sampler t test or rank-sum test was used for measurement data.</p><p><b>RESULTS</b>The differences of PreS1Ag among four groups were statistically significant (X2=141.7, P<0.05). The positive ratio of PreS1Ag in e antigen-positive CHB group was 95.7%, followed by 82.8% in e antigen-negative CHB group, 13.2% in inactive HBsAg carrier group and 2.2% in HBsAg serum conversion group. The difference of positive ratio of anti-PreS1 between HBsAg seroconversion group and HBsAg positive group was statistically significant (X2=6.919, P<0.05), which indicated that anti-PreS1 had good correlation with HBsAg seroconversion. The average absorbance ratio of PreS1Ag in high viral replication group (179.30) was higher than that in low viral replication group (133.87), statistical significance appeared (Z=-3.86, P<0.05). Though the difference of absorbance ratio of anti-PreS1 between two groups had no statistical significance (P>0.05), descent trend was apparent with virus replication level ascending. We analyzed the concordance of anti-HBs and anti-PreS1 by matched-pairs chi-square test, result showed no statistical significance of detection rate between them, X2=0.262, P>0.05. Serum PreS1Ag, HBeAg or HBcAg in liver tissue in reflecting hepatitis B replication had correlation with HBV DNA (X2=33.840, 24.159, 4.854 in order, P<0.05). Correlation coefficient between PreS1Ag and HBV DNA was higher (r=0.628) than that between HBeAg and HBV DNA (r=0.563).</p><p><b>CONCLUSION</b>PreS1Ag was more sensitive than HBeAg in diagnosing viral replication in patients with chronic hepatitis B. Anti-PreS1 as protective antibody may be involved in clearance of hepatitis B, positive result indicated recovery of chronic hepatitis B.</p>

Effects of Xinjining extract on inward rectifier potassium current in ventricular myocytes of guinea pig / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effect of Xinjining extract (, XJN) on inward rectifier potassium current (I(K1)) in ventricular myocyte (VMC) of guinea pigs and its anti-arrhythmic mechanism on ion channel level.</p><p><b>METHODS</b>Single VMC was enzymatically isolated by zymolisis, and whole-cell patch clamp recording technique was used to record the I(k1) in VMC irrigated with XJN of different concentrations (1.25, 2.50, 5.00 g/L; six samples for each). The stable current and conductance of the inward component of I(K1) as well as the outward component of peak I(K1) and conductance of it accordingly was recorded when the test voltage was set on -110 mV.</p><p><b>RESULTS</b>The suppressive rate of XJN on the inward component of I(K1) was 9.54% + or - 5.81%, 34.82% + or - 15.03%, and 59.52% + or - 25.58% with a concentration of 1.25, 2.50, and 5.00 g/L, respectively, and that for the outward component of peak I(K1) was 23.94% + or - 7.45%, 52.98% + or - 19.62%, and 71.42% + or - 23.01%, respectively (all P<0.05). Moreover, different concentrations of XJN also showed effects for reducing I(K1) conductance.</p><p><b>CONCLUSION</b>XJN has inhibitory effect on I(K1) in guinea pig's VMC, and that of the same concentration shows stronger inhibition on outward component than on inward component, which may be one of the mechanisms of its anti-arrhythmic effect.</p>