Daclatasvir plus asunaprevir in treatment-na?ve patients with hepatitis C virus genotype 1b infection

AIM To assess daclatasvir plus asunaprevir(d UAL) in treatment-na?ve patients from China's Mainland, Russia and South Korea with hepatitis C virus(HCV) genotype 1 b infection. METHODS Patients were randomly assigned(3:1) to receive 24 wk of treatment with d UAL(daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period(immediate treatment arm) or following 12 wk of matching placebo(placebodeferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12(SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin(70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in d UAL-treated patients compared with placebo patients during the first 12 wk(doubleblind phase), and during 24 wk of d UAL in both arms combined.RESULTS In total, 207 patients were randomly assigned to immediate(n = 155) or placebo-deferred(n = 52) treatment. Most patients were Asian(86%), female(59%) and aged < 65 years(90%). Among them, 13% had cirrhosis, 32% had IL28 B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/m L. Among patients in the immediate treatment arm, SVR12 was achieved by 92%(95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate(70%). SVR12 was largely unaffected by cirrhosis(89%), age ≥ 65 years(92%), male sex(90%), baseline HCV RNA ≥ 6 million(89%) or IL28 B non-CC genotypes(96%), although SVR12 was higher among patients without(96%) than among those with(53%) baseline NS5 A resistanceassociated polymorphisms(at L31 or Y93 H). during the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving d UAL. during 24 wk of d UAL therapy(combined arms), the most common adverse events(≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were infrequently observed, and all grade 3-4 aminotransferase abnormalities(alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within 8-11 d. Two patients discontinued d UAL treatment; one due to aminotransferase elevations, nausea, and jaundice and the other due to a fatal adverse event unrelated to treatment. There were no treatment-related deaths.CONCLUSION d UAL was well-tolerated during this phase 3 study, and SVR12 with d UAL treatment(92%) exceeded thehistorical SVR rate for peg-interferon plus ribavirin of 70%.

Phase Ⅱb trial of in vivo electroporation mediated dualplasmid hepatitis B virus DNA vaccine in chronic hepatitis B patients under lamivudine therapy

AIM To assess the efficacy and safety of in vivo electroporation(EP)-mediated dual-plasmid hepatitis B virus(HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine(LAM) in patients with chronic hepatitis B. METHODS Two hundred and twenty-five patients were randomized to receive either LAM + vaccine(vaccine group, n = 109) or LAM + placebo(control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12(start of treatment with vaccine or placebo, SOT), 16, 24, and 36(end of treatment with vaccine or placebo, EOT). RESULTS In the modified intent-to-treat population, morepatients had a decrease in HBV DNA > 2 log10 IU/m L in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir(ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeA g seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations. CONCLUSION The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy.

Effects of soil moisture regimes on growth and photosynthesis of the riparian plant Bolboschoenus planiculmis

Plants distributed in riparian regions experience frequent episodes of flooding and drought between years, and hence, riparian plants need to be flood- and drought-tolerant. Riparian plants possess various traits to survive flooding, while their sensitivity to drought has received less attention. To investigate the growth and photosynthetic responses of a riparian species （Bolboschoenus planiculmis） to flooding and drought, plants of this species were subjected to 60-d flooding or drought stress under greenhouse conditions. Growth and photosynthetic traits were measured at the end of the treatments. As well, we determined the efficiency of photosynthetic apparatus in mature leaves. Plants of B. planiculmis adequately adjusted their growth and photosynthetic traits under both flooding and drought conditions. Flooding did not affect the above-ground growth of B. planiculmis. Increased growth of roots and rhizomes and the generation of new tubers suggested a high ability of below-ground lateral growth by capturing resources under flooding conditions. Enhanced photosynthetic capacity, retained leaf pigment concentrations and chlorophyll a fluorescence capacity indicated photosynthetic adaptation to flooding. In contrast, drought significantly decreased the above-ground growth of B. planiculmis, especially the leaves, thereby minimizing water loss due to transpiration. Its increased root to shoot ratio and ＂phalanx＂ asexual propagation pattern might enhance soil water uptake ability. Although the functional leaves of B. planiculmis could retain their leaf pigment concentrations, as well as photosynthesis and chlorophyll a fluorescence, the total biomass of plants decreased, which may be a consequence of the reduced leaf area, suggesting adverse effects by drought. Therefore, both growth and photosynthetic responses of B. planiculmis are likely to contribute to the ability of this species to thrive in riparian regions, but remain susceptive to drought.

Development of a rat model of D-galactosamine/lipopolysaccharide induced hepatorenal syndrome

AIM:To develop a practical and reproducible rat model of hepatorenal syndrome for further study of the pathophysiology of human hepatorenal syndrome. METHODS:Sprague-Dawley rats were intravenously injected with D-galactosamine and lipopolysaccharide(LPS) via the tail vein to induce fulminant hepatic failure to develop a model of hepatorenal syndrome. Liver and kidney function tests and plasma cytokine levels were measured after D-galactosamine/LPS administration,and hepatic and renal pathology was studied. Glomerular filtration rate was detected in conscious rats using micro-osmotic pump technology with fluorescein isothiocyanate-labelled inulin as a surrogate marker.RESULTS:Serum levels of biochemical indicators including liver and kidney function indexes and cytokines all significantly changed,especially at 12 h after D-galactosamine/LPS administration [alanine aminotransferase,3389.5 ± 499.5 IU/L; blood urea nitrogen,13.9 ± 1.3 mmol/L; Cr,78.1 ± 2.9 μmol/L; K+,6.1 ± 0.5 mmol/L; Na+,130.9 ± 1.9 mmol/L; Cl-,90.2 ± 1.9 mmol/L; tumor necrosis factor-α,1699.6 ± 599.1 pg/m L; endothelin-1,95.9 ± 25.9 pg/m L; P < 0.05 compared with normal saline control group]. Hepatocyte necrosis was aggravated gradually,which was most significant at 12 h after treatment with D-galactosamine/LPS,and was characterized by massive hepatocyte necrosis,while the structures of glomeruli,proximal and distal tubules were normal. Glomerular filtration rate was significantly decreased to 30%-35% of the control group at 12 h after D-galactosamine/LPS administration [Glomerular filtration rate(GFR)1,0.79 ± 0.11 m L/min; GFR2,3.58 ± 0.49 m L/min·kg BW-1; GFR3,0.39 ± 0.99 m L/min·g KW-1]. The decreasing timing of GFR was consistent with that of the presence of hepatocyte necrosis and liver and kidney dysfunction.CONCLUSION:The joint use of D-galactosamine and LPS can induce liver and kidney dysfunction and decline of glomerular filtration rate in rats which is a successful rat model of hepatorenal syndrome.

High expression of type I inositol 1,4,5-trisphosphate receptor in the kidney of rats with hepatorenal syndrome

AIM To detect the expression of typeⅠ inositol 1,4,5-trisphosphate receptor(IP3 RI) in the kidney of rats with hepatorenal syndrome(HRS).METHODS One hundred and twenty-five Sprague-Dawley rats were randomly divided into four groups to receive an intravenous injection of D-galactosamine(D-Gal N) plus lipopolysaccharide(LPS; group G/L, n = 50), D-Gal N alone(group G, n = 25), LPS alone(group L, n = 25), and normal saline(group NS, n = 25), respectively.At 3, 6, 9, 12, and 24 h after injection, blood, liver, and kidney samples were collected. Hematoxylineosin staining of liver tissue was performed to assess hepatocyte necrosis. Electron microscopy was used to observe ultrastructural changes in the kidney. Western blot analysis and real-time PCR were performed to detect the expression of IP3 RI protein and m RNA in the kidney, respectively.RESULTS Hepatocyte necrosis was aggravated gradually, which was most significant at 12 h after treatment with D-galactosamine/lipopolysaccharide, and was characterized by massive hepatocyte necrosis. At the same time, serum levels of biochemical indicators including liver and kidney function indexes were all significantly changed. The structure of the renal glomerulus and tubules was normal at all time points. Western blot analysis indicated that IP3 RI protein expression began to rise at 3 h(P < 0.05) and peaked at 12 h(P < 0.01). Real-time PCR demonstrated that IP3 RI m RNA expression began to rise at 3 h(P < 0.05) and peaked at 9 h(P < 0.01).CONCLUSION IP3 RI protein expression is increased in the kidney of HRS rats, and may be regulated at the transcriptional level.

An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir

Background and Aims:Chronic hepatitis B(CHB)can cause liver fibrosis and lead to cirrhosis and cancer.As the effectiveness of antiviral therapy to reverse liver fibrosis is limited,We aimed to evaluate the effect of An-Luo-Hua-Xian pill(ALHX)on fibrosis regression in CHB patients treated with entecavir(ETV).Methods:Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX(ETV+ALHX)between October 1,2013 and December 31,2020.Demographic,laboratory,and liver histology data before and after 78 weeks of treatment were collected.The Ishak fibrosis score(F)was used and fibrosis regression required a decrease in F of≥1 after treatment.Results:A total of 780 patients were enrolled,and 394 with a second liver biopsy after treatment were included in the per-protocol population,132 in ETV group and 262 in ETV+ALHX group.After 78 weeks of treatment,the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients:124/211(58.8%)vs.45/98(45.9%),p=0.035.The percentage of patients with a decreased liver stiffness measurement(LSM)was higher in the ETV+ALHX group:156/211(73.9%)vs.62/98(63.%),p=0.056.Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression[odds ratio(OR)=1.94,p=0.018],and a family history of hepatocellular carcinoma was on the contrary.(OR=0.41,p=0.031).Conclusions:ETV combined with ALHX increased liver fibrosis regression in CHB patients.

黄河三角洲溶解有机质的光谱特征及其驱动因素

河口三角洲是生物地球化学循环的热点地区。了解该区域溶解有机质(DOM)的来源及其驱动因素对于评估其在调节全球碳通量中的作用具有重要意义。本研究分析了黄河三角洲淡水和潮汐区域中土壤DOM的光谱特征。通过平行因子分析(PAFARAC),以及与在线数据库(http://www.openfluor.org)的对比最终确定了5种荧光组分(包括2种类腐殖酸、2种类蛋白质和1种可能的污染物)。淡水和潮汐区域中土壤DOM及各荧光组分的浓度、光谱性质和来源均不同。潮汐区DOM的浓度较低,而相对分子质量较高。在淡水地区,土壤DOM主要来源于浮游植物和微生物;而在潮汐地区,土壤DOM主要来源于微生物和人类活动。这两个地区土壤DOM的差异主要由环境因素驱动,尤其是土壤碳(C)、氮(N)及其化学计量比C/N,能够解释DOM和CDOM变化的80.7%和69.6%。此外,浮游植物也对该地区土壤中的DOM、CDOM和荧光组分(C1–C4)有重要的影响,结果发现它们之间存在显著的正相关关系。研究结果表明,黄河三角洲土壤DOM的浓度和组成受土壤性质和浮游植物密度的强烈驱动。

Soil heterogeneity affects ramet placement of Hydrocotyle vulgaris

Aims Soil heterogeneity is common in natural habitats.It may trigger for-aging responses(placing more ramets and/or roots in nutrient-rich patches than in nutrient-poor patches)and further affect the growth of plants.However,the impact of soil heterogeneity on competitive interactions has been little tested.Methods We conducted a greenhouse experiment to investigate the effects of soil heterogeneity on intraspecific competition with a stolonif-erous herb Hydrocotyle vulgaris.We grew one(without com-petition)or nine ramets(with competition)of H.vulgaris under a homogeneous environment and two heterogeneous environ-ments differing in patch size(large or small patches).In the het-erogeneous treatment,the soil consisted of the same number of nutrient-rich and nutrient-poor patches arranged in a chessboard manner,and in the homogeneous treatment,the soil was an even mixture of the same amount of the nutrient-rich and the nutrient-poor soil.Important Findings Irrespective of intraspecific competition,H.vulgaris showed for-aging responses to soil heterogeneity in the large patch treatment,e.g.it produced significantly more biomass,ramets,aboveground mass and root mass in the nutrient-rich patches than in the nutrient-poor patches.In the small patch treatment,foraging responses were observed when intraspecific competition was present,but responses were not observed when there was no competition.However,we find a significant effect of soil heterogeneity on neither overall growth nor competitive intensity of H.vulgaris.Our results suggest that foraging responses to soil heterogeneity may not necessarily be adaptive and intraspecific competition may not be influenced by soil heterogeneity.