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OBJECTIVES Hepatitis E virus (HEV) infection causes high mortality in pregnant women of developing regions during large outbreaks. The aim of this study was to investigate the clinical features of HEV-infected pregnant women in Shanghai, China where the epidemiology of HEV has shifted from large outbreaks to the sporadic form. METHODS Clinical data of 516 pregnant and nonpregnant child-bearing age women diagnosed with HEV infection during 2009-2020 was collected at the Shanghai Public Health Clinical center. Patients' data were analysed for clinical features and laboratory parameters accordingly. RESULTS Most of the hospitalized HEV-infected pregnant women (85.23%, 127/149) showed no obvious clinical symptoms and the disease outcome was generally benign with no liver failure or maternal mortality observed in the patients. By comparison, fewer (37.21%, 32/86) of the HEV-infected nonpregnant women were asymptomatic, and five cases (5.81%, 5/86) of liver failure were observed among them. The levels of serum alanine aminotransferase, aspartate aminotransferase, total bilirubin (TBiL), direct bilirubin (DBiL) and total bile acids (TBA) were significantly higher (P < 0.05) in nonpregnant women than those of the pregnant women. We found 42.99% (46/107) births had adverse foetal/neonatal outcome. Mothers who presented with adverse foetal/neonatal outcome showed higher (P < 0.05) serum TBiL, DBiL and TBA levels than those without. CONCLUSION We found that the clinical features of sporadic HEV infection in pregnant women in Shanghai, China are generally mild and no maternal mortality occurred. However foetal/neonatal adverse outcomes including preterm births and stillbirths were observed in HEV-infected pregnant women. more...

BACKGROUND AND AIM Antiviral therapy is effective in decreasing disease progression in HBV cirrhosis. However, the long-term effect of antiviral therapy on health-related quality of life (HRQoL) in patients with compensated HBV cirrhosis is unknown. METHODS The patients with compensated HBV cirrhosis enrolled in a randomized controlled trial of entecavir-based therapy were recruited in the present study, if they had HRQoL score at 5-year follow-up or who developed liver-related events (LRE) during follow-up were included. HRQoL was measured with 36-Item Short-Form Health Survey (SF-36) and EuroQol-5D (EQ-5D) at baseline and yearly during follow-up. LRE was defined as the development of decompensation, HCC, or death. RESULTS A total of 161 patients were included in the present study, with a median age of 48.0 (41.0, 53.0) years, 77.6% being male and 37.2% being HBeAg-positive. During 5 years, 45 patients developed LRE. All eight dimensions of SF-36 were significantly improved after 5 years of antiviral therapy (all p more...

Many models have been developed to predict liver-related events (LRE) in chronic hepatitis B, few focused on compensated HBV-induced cirrhosis. We aimed to describe the incidence of LRE and to determine independent risk predictors of LRE in compensated HBV-induced cirrhosis patients receiving antiviral therapy using routinely available parameters. Prospective cohorts of treatment-naive adults with compensated HBV-induced cirrhosis were enrolled. Patients were treated with entecavir (ETV) or ETV + thymosin-alpha1 (Thy-α1) or lamivudine (LAM) + adefovir (ADV). Data were collected at baseline and every 6 months. LRE was defined as development of decompensation, HCC or death. Totally 937 patients were included, 608 patients treated with ETV, 252 with ETV + Thy-α1, and 77 with LAM + ADV. After a median follow-up of 4.5 years, 88 patients developed LRE including 48 with HCC. The cumulative incidence of LRE at year 1, 3, and 5 was 2.1%, 7.0%, and 12.7%, respectively, and was similar for three treatment groups. All models using variables at month 6 or 12 had better fit than models using baseline values. The best model for prediction of LRE used PLT, GGT, and AFP at month 6 [AUC: 0.762 (0.678–0.814)], for hepatic decompensation—PLT, LSM and GGT at month 12 (AUC: 0.834 (0.675–0.919)), and for HCC—AFP and GGT at month 6 [AUC 0.763 (0.691–0.828)]. All models had negative predictive values of 94.0–98.8%. Models using on-treatment variables are more accurate than models using baseline variables in predicting LRE in patient with compensated HBV-induced cirrhosis receiving antiviral therapy. ClincialTrials.gov number NCT01943617, NCT01720238, NCT03366571, NCT02849132. more...

Background & aims Some patients with SARS-CoV-2 infection have abnormal liver function. We aimed to clarify the features of COVID-19-related liver damage to provide references for clinical treatment. Methods We performed a retrospective, single-center study of 148 consecutive patients with confirmed COVID-19 (73 female, 75 male; mean age, 50 years) at the Shanghai Public Health Clinical Center from January 20 through January 31, 2020. Patient outcomes were followed until February 19, 2020. Patients were analyzed for clinical features, laboratory parameters (including liver function tests), medications, and length of hospital stay. Abnormal liver function was defined as increased levels of alanine and aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, and total bilirubin. Results Fifty-five patients (37.2%) had abnormal liver function at hospital admission; 14.5% of these patients had high fever (14.5%), compared with 4.3% of patients with normal liver function (P = .027). Patients with abnormal liver function were more likely to be male, and had higher levels of procalcitonin and C-reactive protein. There was no statistical difference between groups in medications taken before hospitalization; a significantly higher proportion of patients with abnormal liver function (57.8%) had received lopinavir/ritonavir after admission compared to patients with normal liver function (31.3%). Patients with abnormal liver function had longer mean hospital stays (15.09 ± 4.79 days) than patients with normal liver function (12.76 ± 4.14 days) (P = .021). Conclusions More than one third of patients admitted to the hospital with SARS-CoV-2 infection have abnormal liver function, and this is associated with longer hospital stay. A significantly higher proportion of patients with abnormal liver function had received lopinavir/ritonavir after admission; these drugs should be given with caution. more...

The prevalence of high-risk varices (HRV) is low among compensated cirrhotic patients undergoing esophagogastroduodenoscopy (EGD). Our study aimed to identify a novel machine learning-based model, named ML EGD, for ruling out HRV and avoiding unnecessary EGDs in patients with compensated cirrhosis.An international cohort from 17 institutions from China, Singapore, and India were enrolled (CHESS2001, NCT04307264). The variables with the top three importance scores (liver stiffness, platelet count, and total bilirubin) were selected by shapley additive explanation and inputted into light gradient boosting machine algorithm to develop ML EGD for identification of HRV. Furthermore, we built a web-based calculator of ML EGD and it was free with open access at http://www.pan-chess.cn/calculator/MLEGD_score. Spared EGDs and the rates of missed HRV were used to assess the efficacy and safety for varices screening.A total of 2,794 patients were enrolled. Of them, 1,283 patients in a real-world cohort from one university hospital in China were to develop and internally validate the performance of ML EGD for varices screening. They were randomly assigned into the training (n = 1154) and validation (n = 129) cohorts with a ratio of 9:1. In the training cohort, ML EGD spared 607 (52.6%) unnecessary EGDs with a missed HRV rate of 3.6%. In the validation cohort, ML EGD spared 75 (58.1%) EGDs with a missed HRV rate of 1.4%. To externally test the performance of ML EGD, 966 patients from 14 university hospitals in China (test cohort 1) and 545 from two hospitals in Singapore and India (test cohort 2) comprised two test cohorts. In the test cohort 1, ML EGD spared 506 (52.4%) EGDs with a missed HRV rate of 2.8%. In the test cohort 2, ML EGD spared 224 (41.1%) EGDs with a missed HRV rate of 3.1%. Comparing with Baveno VI criteria, ML EGD spared more screening EGDs in all cohorts (training cohort, 52.6% vs 29.4%; validation cohort, 58.1% vs 44.2%; test cohort 1, 52.4% vs 26.5%; test cohort 2, 41.1% vs 21.1%) (p0.001).We identified a novel model based on liver stiffness, platelet count, and total bilirubin, named ML EGD, as a free web-based calculator. ML EGD could efficiently help rule out HRV and avoid unnecessary EGDs in patients with compensated cirrhosis. more...

Background and Aims: Chronic hepatitis B virus (HBV) infection remains a major public health problem globally. Here, we describe the baseline characteristics and treatment profiles of HBV-infected patients recruited to the China Registry of Hepatitis B. Methods: Inclusion criteria were patients with different stages of chronic HBV infection and complete key data. Exclusion criteria were patients with hepatocellular carcinoma. The baseline clinical, laboratory and treatment profiles were analyzed. Results: Finally, 40,431 patients were included. The median age was 43 years, with 65.2% being men and 51.3% being positive for hepatitis B e antigen (HBeAg). The most common initial diagnosis was chronic hepatitis B (81.0%), followed by cirrhosis (9.3%), inactive carrier of hepatitis B surface antigen (HBsAg) (6.7%), and immune tolerant phase of hepatitis B infection (3.0%). Among the 21,228 patients who were on treatment, 88.0%, 10.0% and 2.0% received nucleos(t)ide analogues (NAs), interferon or combination of NAs and interferon, respectively. The proportion of patients who received preferred NAs (entecavir or tenofovir disoproxil fumarate) had increased from 13.5% in 2003 to 79.7% in 2016. Conclusions: We concluded that middle-aged men accounted for most of the patients with chronic hepatitis B in this cross-sectional study. About half of the patients were HBeAg-positive. NAs were the most commonly used therapy, and use of the preferred NAs had steadily increased in the past decade. more...

BACKGROUND & AIMS Non-invasive assessment criteria to rule out high-risk varices (HRV) in compensated hepatitis B virus (HBV) cirrhosis on antiviral therapy remains unclear. METHODS HBV-related compensated cirrhotic patients who underwent screening endoscopy during antiviral therapy were enrolled and randomly divided into the derivation and validation sets. HRV were defined as medium to large varices or small varices with red signs. Univariate and multivariate logistic analysis were used to determine the parameters associated with HRV. RESULTS A total of 436 HBV-related compensated cirrhotic patients screened for varices were enrolled, the median duration of antiviral therapy was 4 years (IQR: 2.5-5.5 years). In the derivation set (N = 290, 17.2% with HRV), only platelet (PLT) count (OR = 0.972, 95% CI 0.961-0.984, P more...

The aim of this study is to investigate the role of microRNA-499 (miR-499) in hepatocellular carcinoma tumor growth and the underlying molecular mechanisms. The expression of miR-499 was significantly decreased in hepatocellular carcinoma tissues compared with that in adjacent normal tissues. Furthermore, miR-499 overexpression in HEPG2 cell was related to the tumor growth in nude mice xenograft models. Likewise, miR-499 mimic or inhibitor decreased or accelerated cell proliferation, respectively. Mechanistically, miR-499 directly targeted the 3′- untranslated region of astrocyte elevated gene-1 and downregulate astrocyte elevated gene-1 expression. Restoration of astrocyte elevated gene-1 expression in hepatocellular carcinoma cells reversed the inhibitory effect of miR-499 on cell growth. In addition, astrocyte elevated gene-1 and miR-499 expression were inversely correlated in human and mice hepatocellular carcinoma tissues. Our study identified miR-499 as a tumor-suppressive miR in hepatocellular carcinoma, thus providing a candidate therapeutic target for the future diagnosis or treatment of hepatocellular carcinoma. more...

COVID‐19 has become a global pandemic and garnered international attention. Although the clinical features of COVID‐19 related liver injury have been investigated, there have been no reports and studies on the clinical characteristics of COVID‐19 patients co‐infected with Hepatitis B Virus (HBV). This study aimed to evaluate whether SARS‐CoV‐2/HBV co‐infection could influence liver function and the disease outcome. All 326 confirmed COVID‐19 cases in Shanghai Public Health Clinical Center (The COVID‐19 designated hospital in Shanghai, China) from January 20, 2020 to February 24, 2020 were enrolled and followed up until February 29 in this study. The clinical, laboratory data and the length of stay were collected and analyzed retrospectively. 20 patients with HBV co‐infection (6.1%) and 306 patients (93.9%) without HBV infection showed no differences in the level of liver function parameters. However, compared with HBsAg‐ patients [145.4 mg/L (103.9‐179.2)], HBsAg+ patients had a lower level of prealbumin [(102.3 mg/L (76.22‐160.2), P=.0367]. There were also no significant differences for the discharge rate and the length of stay between two groups. Taken together, we found no evidence that SARS‐CoV‐2/HBV co‐infection could aggravate liver injury or extend duration of hospitalization. more...

Crop water productivity models are valuable tools for investigate the crop responses to the water-management strategies and ameliorate the efficiency of water use in agriculture. The objective of this study was to evaluate the performance of AquaCrop model for maize crop (Zea mays L.) under full, excessive and deficit applications of drip irrigation in semi-humid region of China. The evaluation results emphasized the model accuracy in simulations CC, SWC, B*, Y and WUE with satisfactory performance in full irrigation, and moderate water stressed treatment T2 of 75% of full irrigation. This accuracy declines in circumstances of excessive irrigation T1 of 125% of full irrigation, and high water stressed T3 of 50% of full irrigation. The RMSEs and NRMSEs in simulated CC, and SWC for full irrigation, T1, T2 and T3 treatments were 7.3–8.6, 6.3–7.2, 5.4–6.3 and 4.9–5.6% CC, respectively, and 9.4–4.8, 16.1–8.1, 16.4–9.3 and 20.9–13.4% SWC, respectively. Whereas, the D-index and R2 of CC varied between 0.72 to 0.89 and 0.99 to 1.0, while in the SWC varied between 0.54 to 0.83 and 0.48 to 0.96 for the four irrigation treatments. The differences (S.D) in final biomass and grain yield were within the range of 0.23 to 4.45% and 0.30 to 1.46% between the measurement and simulation. Simulated WUEs of biomass and yield under different irrigation treatments ranged between 6.07 to 6.52 kg/m3 and 3.07 to 3.16 kg/m3, AquaCrop’s performance trends to underestimate the WUEs of biomass and yield, and emphasizes that the yield WUE increased linearly with water stress condition increased. more...

Introduction and objective A recent outbreak of coronavirus disease 2019 (COVID-19) occurs in the worldwide. Angiotensin-converting enzyme 2 (ACE2) can mediate coronavirus entry into host cells. Therefore, renin–angiotensin system inhibitors (RASI) were suspected of contributing to the increase of coronavirus infection. We aimed to analyze the effects of RASI in COVID-19 patients with hypertension. Patients and method In this retrospective, single-center study, 27 COVID-19 patients with hypertension, who were admitted to the Shanghai Public Health Clinical Center from January 25, 2020 to January 31, 2020, were analyzed for clinical features, laboratory parameters, medications and the length of stay. All the patients were given antiviral and antihypertension treatment, of which 14 patients were treated with RASI and 13 patients without RASI. Results Comparing the two groups, we did not found statistically significant differences in clinical symptoms and laboratory tests. Furthermore, cough was not aggravated. Conclusions Through the analysis of this small sample, RASI could be deemed safe and effective to control high blood pressure of COVID-19 patients. Further analysis with a larger sampling size is required to explore the underlying mechanisms. more...

A three-stage plug flow moving bed biofilm reactor (PF - MBBR, consisting of three identical chambers of N1, N2 and N3) was proposed for nitrifier enrichment using synthetic wastewater. During the stable operation, the average NH more...

Background: Thymosin alpha-1 (Ta-1) suppresses HBV viral replication, while the evidence of combination effect with nucleoide is still limited. We aimed to investigate the efficacy and safety of combination therapy of Ta-1 with entecavir (ETV) in patients with compensated liver cirrhosis.A total of 690 patients were randomized to receive Ta-1 plus ETV (n = 351) or ETV monotherapy (n = 339) for 52 weeks after 26 weeks of ETV treatment, followed by continued entecavir therapy. The primary endpoint was defined as liver decompensation, hepatocellular carcinoma (HCC) or death.The median followed up was 38.2 months. The cumulative incidence of liver decompensation, HCC, or death were similar between two groups. During the Ta-1 combination treatment, the HCC incidence was 1.7% in combination group and 2.1% in ETV group, without new HCC cases developed during week 39 to week 77 in combination group. The virologic response, serologic response, biochemical response was similar between two groups at week 104. Both therapies were well-tolerated.There was no significant difference between two groups in endpoint events, while combination therapy with Ta-1 has a tendency to inhibit the development of HCC. more...

Accelerated urbanization places extraordinary demands on sewer networks; thus optimization research to improve the design of these systems has practical significance. In this article, a subsystem nonlinear programming model is developed to optimize pumping station layout and sewage pipe network design. The subsystem model is expanded into a large-scale complex nonlinear programming system model to find the minimum total annual cost of the pumping station and network of all pipe segments. A comparative analysis is conducted using the sewage network in Taizhou City, China, as an example. The proposed method demonstrated that significant cost savings could have been realized if the studied system had been optimized using the techniques described in this article. Therefore, the method has practical value for optimizing urban sewage projects and provides a reference for theoretical research on optimization of urban drainage pumping station layouts. more...

BACKGROUNDA recent outbreak of SARS-CoV-2 infection occurs mainly in China, with rapidly increasing the number of cases (namely COVID-19). Abnormal liver functions are frequently present in these patients, here we aimed to clarify the clinical features of COVID-19-related liver damage to provide some references for the clinical treatment.METHODSIn this retrospective, single-center study, we included all confirmed COVID-19 cases in Shanghai Public Health Clinical Center from January 20 to January 31, 2020. The outcomes were followed up until February 19, 2020. A total of 148 cases were analyzed for clinical features, laboratory parameters (including liver function tests), medications and the length of stay.FINDINGSOf 148 confirmed SARS-CoV-2-infected patients, 49.3% were females and 50.7% were males. The median age was 50.5 years (interquartile range, 36-64). Patients had clinical manifestations of fever (70.1%), cough (45.3%), expectoration (26.7%) at admission. 75 patients (50.7%) showed abnormal liver functions at admission. Patients (n = 75) who had elevated liver function index were more likely to have a moderate-high degree fever (44% vs 27.4%; p = 0.035) and significantly present in male patients (62.67% vs 38.36%; p = 0.005). The numbers of CD4+ and CD8+ T cells were significantly lower in abnormal liver function group than those in normal liver function group. There was no statistical difference in prehospital medications between normal and abnormal liver function groups, while the utilization rate of lopinavir/ritonavir after admission was significantly higher in patients with emerging liver injury than that in patients with normal liver functions. Importantly, the emerging abnormal liver functions after admission caused a prolonged length of stayINTERPRETATIONSARS-CoV-2 may cause the liver function damage and the Lopinavir/ritonavir should be applied carefully for the treatment of COVID-19.FUNDINGShanghai Science and Technology Commission Fund Project and National Science and Technology Major Project more...

COVID-19 has become a global pandemic and garnered international attention. Although the clinical features of COVID-19 related liver injury have been investigated, there have been no reports and studies on the clinical characteristics of COVID-19 patients co-infected with Hepatitis B Virus (HBV). This study was aimed to evaluate whether SARS-CoV-2/HBV co-infection could influence liver function and the disease outcome. All 326 confirmed COVID-19 cases in Shanghai Public Health Clinical Center (The COVID-19 designated hospital in Shanghai, China) from January 20, 2020 to February 24, 2020 were enrolled and followed up until February 29 in this study. The clinical, laboratory data and the length of stay were collected and analyzed retrospectively. 20 patients with HBV co-infection (6.1%) and 306 patients (93.9%) without HBV infection showed no differences in the level of liver function parameters. However, compared with HBsAg- patients [145.4 mg/L (103.9-179.2)], HBsAg+ patients had a lower level of prealbumin [(102.3 mg/L (76.22-160.2), P=.0367]. There were also no significant differences for the discharge rate and the length of stay between two groups. Our study is the first to elaborate on the clinical characteristics of SARS-CoV-2/HBV co-infection patients and no evidence shows SARS-CoV-2/HBV co-infection could aggravate liver injury or extend hospitalization time. Funding Statement: This study was funded by the first-class discipline construction project of Fudan university (ISF162005),Shanghai Science and Technology Development Fund (No.17411969500), National Science and Technology Major Project (2017ZX10203202-003-007) and Shanghai Public Health Clinical Center Fund (2020YJKY01, XKJS-2019HBV-06, KY-GW-2019-32) joined in hepatitis prevention and control procedures. Declaration of Interests: All authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the Ethics Committee of the Shanghai Public Health Clinical Center (2019-S047-02, Review date: Jan 13, 2020) and was exempted from the need for informed consent from patients. more...

Background and Aim The efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding Peg-interferon to ongoing ETV treatment leads to a better curative effect or not. Methods Eligible HBV patients (n=144) were randomly divided (1:1) to receive either ETV monotherapy (n=70) or peg-interferon add-on therapy from weeks 26 to 52 (n=74). Patients were followed-up for 2 years. We evaluated hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response (SVR), transient elastography value, and histological scores. Results At week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase (ALT)and aspartate aminotransferase (AST) levels and transient elastography values decreased significantly compared with baseline. Both group showed a favorable decrease in alpha fetoprotein(AFP) (monotherapy:23.4±77.3 vs 2.4±0.91, P=0.149; combination therapy: 33.3±96.9 vs 4.3±5.5,P=0.085) and an improved result of liver biopsy examination scores. The combination group showed a better improvement in histology compared with the monotherapy group(mean transient elastography value 7.5±3.4 kPa [SD 1.9] vs. 12.8±13.9 kPa [SD 1.9], P=0.037). But this research didn’t show significant difference in HBsAg conversion rate (1.79% (1/56) vs 4.11% (3/73), P=0.632) as well as HBV-DNA sustained virologic response(93.2% vs 98.5%,P=0.15) between two groups. Conclusions Both therapies supported liver function recovery and histology improvement. Combination therapy did not show better antiviral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy. However, combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy. more...

The design scheme of open intake will often increase the shaft length and the height of wet-pit pump house when the range of intake water level varies relatively large. And if the pump house is far away from the discharge bay, a longer discharge pipe may be inevitable, and the arrangement of full passage model pumping system may exceed the allowed size of a specific test bench. Aiming at a long-shaft vertical pumping system with open intake design, larger water level variation and longer discharge pipe, a methodology of performance prediction for the pump and pumping system was proposed by combining numerical simulation and non-full passage model test because of less experiment funds, shorter research periods and restricted test bench. Through numerical simulation, the hydraulic losses and drag coefficients of sump and discharge pipe were calculated and followed by the experiment design and model test of non-full passage pumping system. Based on the calibration accuracy of measurement instruments and test results, the experimental uncertainties were analyzed. Through combination of numerical simulation and non-full passage model test, the prediction of model pump and pumping system performance was realized. The performance of prototype pump and pumping system was obtained by applying the similarity law of pump. When operated under the designed head of 13.59 m, the flow rate and efficiency of the prototype pumping system reached 11.86 m3/s and 86.56%, respectively, exceeding the requirements stipulated in the bidding documents and showing that it possessed greater pumping capacity and higher efficiency. The methodology proposed in this paper can be referenced and applied to the engineering design of similar pump stations. more...

// Xiqiang Liu 1,* , Gaojian Luo 2,* , Jingbo Jiang 3 , Tonghui Ma 1 , Xiaozhu Lin 4 , Liping Jiang 1 , Jilin Cheng 5 and Ran Tao 1 1 Department of Hepatobiliary-Pancreatic Surgery, Zhejiang Provincial People’s Hospital (ZJPPH), Hangzhou, Zhejiang, PR China 2 Department of General Surgery, Affiliated Yiwu Hospital, Wenzhou Medical University, Yiwu, Zhejiang, PR China 3 Department of Surgery, Qilu Hospital, Shandong University School of Medicine, Jinan, Shandong, PR China 4 Department of Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China 5 Department of Gastroenterology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, PR China * These authors have contributed equally to this work Correspondence to: Ran Tao, email: // Keywords : apoptosis, hepatocyte, hypoxia, inflammation, vasopressin receptor, Pathology Section Received : August 05, 2016 Accepted : September 29, 2016 Published : October 04, 2016 Abstract Terlipressin has been used extensively in the management of certain complications associated with end-stage liver diseases (ESLDs). In our pilot study, terlipressin treatment showed beneficial effects on liver function in patients with decompensated cirrhosis, however whether it plays a role in liver ischemia-reperfusion injury (IRI) remains unknown. Using a mouse nonlethal hepatic IR model, we found terlipressin administration significantly ameliorated IR-induced liver apoptosis, necrosis and inflammation. Furthermore, despite its known effect on visceral vasoconstriction, hemodynamic evaluation of murine hepatic tissue after IR revealed no change of overall hepatic blood flow after terlipressin treatment. Further studies identified the upregulation of vasopressin receptor 1 (V1R) expression on hepatocytes upon IR. In isolated hepatocyte hypoxia/reoxygenation model, the active component of terlipressin, lysine vasopressin, conferred hepatocytes resistant to oxidative stress-induced apoptosis. Mechanistic studies revealed the V1R engagement activated the Wnt/β-catenin/FoxO3a/AKT pathway, which subsequently circumvented the proapoptotic events, thus ameliorated hepatocyte apoptosis. Furthermore, genetic knockdown of V1R expression in hepatocyte cell lines or blockade of this signaling pathway abrogated such protective effect. Conclusion: These data highlight the functional importance of the hepatocyte V1R/Wnt/β-catenin/FoxO3a/AKT pathway in protecting liver from oxidative stress-induced injury. more...

Ni-P coated diamond (NPCD) with different phosphorus content was prepared by electroless plating through adjusting NaH 2 PO 2 concentration in plating bath. Effect of phosphorus content on the properties of NPCD as surface microstructure, phase structure and heat resistance was studied and compared with that of diamond with no Ni-P coatings. The surface microstructure and the chemical composition were determined by environmental scanning electron microscope (ESEM). The phase structure was observed by X-ray diffraction (XRD). The results demonstrated that a lower phosphorus content of NPCD corresponds to better surface properties with lower roughness and higher heat resistance. A higher phosphorus content, on the contrary, leads to worse overall performance of Ni-P coating. more...

An experimental study was conducted to determine the optimum water amounts, irrigation water use efficiencies (IWUE) and irrigation water saving for waxy maize and cucumber, and the optimum nitrogen (N) quantity and nitrogen use efficiency (NUE) for maize under fertigation. The different irrigation treatments were estimated using the CROPWAT model based on the Penman–Monteith method, and the different N fertigation rates were determined based on the locally recommended dose. The results showed that the vegetative growth, yield and quality traits of maize and cucumber were significantly affected by different irrigation water amounts and N fertigation rates. The water application depths of 50% and 100% of the crop evapotranspiration inside the greenhouse (ETc,in) for maize and cucumber were found to be the optimum amounts that resulted in the highest yield of 26.8 t ha−1 for maize and 37.8 t ha−1 for cucumber. The 50% and 100% ETc,in for maize and cucumber resulted in water saving of 102.9 mm and 29.0 mm, respectively. The fertigation quantity of 125% N dose was the optimum N level that obtained highest maize yield of 26.2 t ha−1, and the NUE was 7.198 t ha−1 kg−1. The vegetative growth and fruit quality reached the best at irrigation depth of 50% ETc,in and N dose of 125% for maize, and irrigation depth of 100% ETc,in for cucumber. The IWUE varied from 0.102 to 0.209 t ha−1 mm−1 for maize and 0.152–0.340 t ha−1 mm−1 for cucumber. Furthermore, the IWUE and NUE increased with the decreasing irrigation water amount and the N application dose. Findings from this research may provide technical guidance for reducing irrigation water use in agriculture in order to solve the water scarcity problem. There is water saving potential observed in this study. more...

It is unknown whether dynamic changes of liver stiffness measurement (LSM) can predict the reversibility of fibrosis. Therefore, we evaluated the utility of LSM changes in predicting histological changes of fibrosis in patients with chronic hepatitis B (CHB) on antiviral therapy. In a prospective cohort of CHB patients treated with entecavir, virological measurement and biochemical measurement along with LSM were measured at baseline and every 6 months. Liver biopsies were conducted at baseline and month 18 of treatment. Fibrosis regression was defined by the following two criteria: (a) Ishak score decrease ≥1 stage, (b) Ishak score decrease ≥1 stage or predominantly regressive by post-treatment PIR classification. The dynamic changes of LSM and its predictive value for histological reversibility were evaluated with piecewise linear mixed-effects model and ROC analysis. We found that at month 18 of antiviral therapy, liver fibrosis was reserved in 86 of 212 (40.6%) CHB patients by Ishak reversal criterion. Overall, a decline in LSM was associated with attenuation of Ishak score. The rate of LSM decline in the first 6 months was significantly faster in patients with fibrosis reversal (ΔLSM%Ishak = -2.19%/month, P = 0.0025; ΔLSM%Ishak/PIR = -2.56%/month, P = 0.0004). The predictive model based on baseline FIB-4 and Ishak score as well as baseline LSM, PLT, albumin and their changes during the first 6 months could predict histological reversal (AUROCIshak = 0.74, 95% CI: 0.67-0.80; AUROCIshak/PIR = 0.81, 95% CI: 0.74-0.87). We conclude that in CHB patients, changes in LSM during the first 6 months of entecavir therapy can predict histological reversibility of liver fibrosis at month 18 of antiviral therapy. more...

Aiming at the minimum power consumption for water pumping in a cascade pumping station system, we established a complex nonlinear mathematical model by taking optimized lift head and blade ...

Axial-flow pumps are widely used in every sector of China. After many years of operation, the aging of mechanical and electrical facilities poses threats to their steady and safe operation. Taking the technical innovation of an axial-flow pump station as an example, the study is focused on the pump selection and performance prediction. The pump similarity law and specific speed were applied to guide the pump selection based on the designed head and discharge. The performances of pump models were compared and it is suggested for the technical innovation that when the selected model pump is adopted, the impeller diameter is kept at 3100 mm and the rotational speed is reduced from 150r/min to 136.4r/min to improve its cavitation performance. A three-dimensional pumping system model was established by using software Pro/E and CFD analyses were conducted to predict the hydraulic performance of the pumping system for the evaluation of technical innovation. It is shown through the comparison of computed results with model test results that the designed flow rate corresponding to the designed head can be fully satisfied with the selected pump and stronger pumping capacity can be prospected at the designed and mean lifting head. The pumping system model tests, in comparison between the original and the selected model pump, indicate that when the innovated pump station operates under characteristic heads, the pumping system efficiency can be raised by more than 3 percentages, and the cavitation allowance can be decreased by 0.90m; thus, better engineering and economic benefits can be prospected through the technical innovation. more...

2–2 type Ba2Ti9O20–BaFe12O19 composite ceramics were prepared by a tape casting method. Interface, dielectric and magnetic properties of prepared composite ceramics have been reported. Obvious interface diffusion between the dielectric and the ferrite has been observed by scanning electron microscopy and energy dispersive spectrometer. It was observed that the thickness of interface increased with increasing of sintering temperature. Compared with pure Ba2Ti9O20 ceramic, relatively high dielectric constant and loss of the prepared composite have been obtained. Meanwhile, lower saturation and remnant magnetizations, and higher coercive field than that of pure BaFe12O19 ferrite has also been obtained. The dielectric constant of the prepared composites increased and then decreased, with increasing of sintering temperature accompanied with an opposite variation for the dielectric loss. At the same time, the saturation magnetization, the remnant magnetization and the coercive field decreased. more...

To facilitate the delivery of nucleotide-based therapeutics to cells and tissues, a variety of pronucleotide approaches have been developed. Our laboratory and others have demonstrated that nucleoside phosphoramidates can be activated intracellularly to the corresponding 5‘-monophosphate nucleotide and that histidine triad nucleotide binding proteins (Hints) are potentially responsible for their bioactivation. Hints are conserved and ubiquitous enzymes that hydrolyze phosphoramidate bonds between nucleoside 5‘-monophosphate and an amine leaving group. On the basis of the ability of nucleosides to quench the fluorescence of covalently linked amines containing indole, a sensitive, continuous fluorescence-based assay was developed. A series of substrates linking the naturally fluorogenic indole derivatives to nucleoside 5‘-monophosphates were synthesized, and their steady state kinetic parameters of hydrolysis by human Hint1 and Escherichia coli hinT were evaluated. To characterize the elemental and stereochemical effect on the reaction, two P-diastereoisomers of adenosine or guanosine phosphoramidothioates were synthesized and studied to reveal a 15−200-fold decrease in the specificity constant (k_(cat)/K_m) when the phosphoryl oxygen is replaced with sulfur. While a stereochemical preference was not observed for E. coli hinT, hHint1 exhibited a 300-fold preference for d-tryptophan phosphoramidates over l-isomers. The most efficient substrates evaluated to date are those that contain the less sterically hindering amine leaving group, tryptamine, with k_(cat) and K_m values comparable to those found for adenosine kinase. The apparent second-order rate constants (k_(cat)/K_m) for adenosine tryptamine phosphoramidate monoester were found to be 10⁷ M⁻¹ s⁻¹ for hHint1 and 10⁶ M⁻¹ s⁻¹ for E. coli hinT. Both the human and E. coli enzymes preferred purine over pyrimidine analogues. Consistent with observed hydrogen bonding between the 2‘-OH group of adenosine monophosphate and the active site residue, Asp43, the second-order rate constant (k_(cat)/K_m) for thymidine tryptamine phosphoramidate was found to be 3−4 orders of magnitude smaller than that for uridine tryptamine phosphoramidate for hHint1 and 2 orders of magnitude smaller than that for E. coli hinT. Ara-A tryptamine phosphoramidate was, however, shown to be a good substrate with a specificity constant (k_(cat)/K_m) only 10-fold lower than the value for adenosine tryptamine phosphoramidate. Consequently, nucleoside phosphoramidates containing unhindered primary amines and either an α or β 2‘-OH group should be easily bioactivated by Hints with efficiencies rivaling those for the 5‘-monophosphorylation of nucleosides by nucleoside kinases. The differential substrate specificity observed for human and E. coli enzymes represents a potential therapeutic rationale for the development of selective antibiotic phosphoramidate pronucleotides. more...

The attribute recognition model (ARM) has been widely used to make comprehensive assessment in many engineering fields, such as environment, ecology, and economy. However, large numbers of experiments indicate that the value of weight vector has no relativity to its initial value but depends on the data of Quality Standard and actual samples. In the present study, the ARM is enhanced with the technique of data driving, which means some more groups of data from the Quality Standard are selected with the uniform random method to make the calculation of weight values more rational and more scientific. This improved attribute recognition model (IARM) is applied to a real case of assessment on seawater quality. The given example shows that the IARM has the merits of being simple in principle, easy to operate, and capable of producing objective results, and is therefore of use in evaluation problems in marine environment science. more...

Chronic hepatitis B virus (CHB) infection can cause persistent hepatic inflammation and cirrhosis, which may lead to hepatocellular carcinoma (HCC). CHB is considered the dominant cause of HCC in Asia because of the endemic status of hepatitis B virus (HBV) infection. A persistently high viral load, long duration of infection, and cirrhosis are the major risk factors for developing HCC in CHB patients. Antiviral therapies using interferon (IFN) and nucleos(t)ide analogues (NAs) could suppress viral replication, reduce liver injury, and preserve liver function, thereby lowering the risk of developing HCC. Recurrence of HCC after therapy is closely related to high levels of HBV DNA at the initial stage. Western studies have found that persistent antiviral treatments on CHB patients could not only reduce their risk of developing HCC, but also prevent or delay HCC recurrence after liver transplantation, hepatic resection, or radiation therapies. This review will focus on Asian clinical studies, where there is a higher prevalence of CHB and HCC. The outcomes of antiviral therapies on HCC in these Asian studies were compared to those in the Western studies. more...