Nucleos(t)ide analogues (NAs) can indirectly restore host immunity against hepatitis B virus (HBV) by inhibiting virus replication. We aimed to investigate whether telbivudine could prevent HBV-related fibrosis progression by their influence on CD4(+) T-cell response.Thirty-six HBeAg-positive patients with chronic hepatitis B (CHB) were enrolled for 52-week telbivudine monotherapy and were followed at treatment week (TW)-0, 4, 12, 24 and 52. By TW-52, the patients were classified into a complete-response group (CR, n = 10) with both negative HBV-DNA and HBeAg, or a part-response group (PR, n = 11) only with negative DNA, or a non-response group (NR, n = 15) still with positive DNA. The peripheral blood mononuclear cells (PBMCs) were prepared for further flow cytometric and real-time PCR analyses, and also for the in vitro experiments with primary hepatic stellate cells (HSCs).Peripherally, all chronic HBV-infected subjects showed the involvement of CD4(+) T-cell responses, among whom the inactive carriers (IC) had Th1 (CD4(+) IFNγ(+) ) dominated, CHB had Th17 (CD4(+) IL-17(+) ) dominated, while the immune tolerant (IT) subjects had Treg (CD4(+) CD25(high) Foxp3(+) ) dominated. Besides, we found the therapeutic responses to telbivudine were especially associated with up-regulation of Th1 and Th17, and down-regulation of Treg. Furthermore, compared to CD4(+) cells from CR, those from NR could in vitro significantly exacerbate cell activation, proliferation and cytokine production of HSCs, which were partly mediated by IL-4 and TGF-β1.Telbivudine might slow down HBV-related liver fibrosis progression by restoring CD4(+) T-cell responses against HBV.
To analyze the clinical features, risk factors and drug uses of senior hospitalized patients with chronic constipation.A total of 162 hospitalized patients aged 85 years and over at our hospital during the period of January-March 2012 conducted a questionnaire survey. There were 137 males and 25 females. And 112 cases of chronic constipation were diagnosed in accordance with the Rome III criteria. The survey included general condition, risk factors of constipation, spectrum of symptoms, associated symptoms, previous medication and medication for constipation after admission. The results were statistically analyzed by Logistic regression.Their average age was (90 ± 4) years old. And the total prevalence of chronic constipation was 69.1% (112/162). Logistic regression analysis showed that less activity (OR = 10.873) and diet (OR = 4.752) were the important risk factors. Defecation effort was the most common symptom (n = 85, 75.9%). A total of 88 cases (78.6%) took lactulose alone or lactulose plus other laxatives. The reasons of using lactulose were as follows: dietary restrictions (n = 31, 35.2%), aspiration prevention (n = 21, 23.9%) and poor efficacy of other laxatives (n = 36, 40.9%).Prevalence of constipation is high among senior hospitalized patients. Less activity and diet are the main risk factors. And lactulose should be a first-line therapy.
Abstract The conductance increment method (INC) can be quickly and accurately stabilized at the maximum power point (MPP) but easily falls into the local extreme point (LMPP) in the shadow environment. Considering the particle swarm optimization (PSO) can quickly achieve global optimal search but the number of iterations is too large when local convergence, leading to fluctuation and energy loss. Therefore, a global maximum power point tracking (GMPPT) is proposed, which combined the PSO and INC and improved them. In this paper, the research object is the single-phase two-stage PV grid-connected system. The GMPPT needs a stable DC voltage (U dc ) to track accurately and the grid-connected inverter needs a stable U dc in order to ensure the quality of grid power. Therefore, the goal of the inverter control is to achieve the combination of GMPPT and grid-connected control. Based on the characteristics of PV power generation, a PV grid-connected droop control strategy based on GMPPT is proposed, which realizes the stability of Udc and the output of MPP and meets grid-connected requirements. Finally, the simulation model of PV grid-connected system based on Matlab/Simulink software is used to verify the effectiveness of the proposed control strategy.
The paper first introduced the background and causes of arrears of project arrears, and got the following four reasons: unimplemented Project funds; imbalance supply and demand of the construction market; layers of subcontracting; imperfect credit system of the market.This paper talked about the implication of Game Theory in this problem, which introduced the project guarantee to start the complete information repetaed game theory between the owner and the general contractor.By introducing the principle and characteristics of game theory in detail and analyzing the advantages and disadvantages of static game and repeated game, summed up the use of the repeated game to discuss the project problem is more applicable.The paper deals with the game process and obtains the sub-game refined Nash equilibrium, obtaining the following points to solve the project arrears:reducing the total contractor's performance guarantee amount,increasing the amount of the owner's project guarantee, reducing the owner's delayed payment benefit, reducing the total contractor's delay in paying the cost of savings.
The endocannabinoids system (ECs) mediated mainly by CB1 and CB2 receptors plays an important role in non-alcoholic fatty liver disease by regulating lipid metabolism. This study is to further investigate the expression of CB1 and CB2 in the fat accumulation liver cells and to identify possible underlying mechanism by detecting the key lipogenesis factors.Sodium oleate and sodium palmitate were added into the HepG2 cell line for forming fat accumulation liver cell. MTT assay was used to test the cell's cytotoxicity. The accumulation rate of fat in HepG2 cell was analyzed by the fluorescent staining. The mRNA and protein expression levels of CB1, CB2, SREBP-1c, ChREBP, L-PK, ACC1, FAS, LXRs and RXR were detected by RT-PCR and Western blot before and after the use of the antagonist.The receptors of CB1 were expressed in HepG2 cells with low levels while in HepG2 fatty liver cells with higher levels (p < 0.05). However, after the application of antagonist, the expressions were significantly decreased (p < 0.05). The expressions of SREBP-1c, ChREBP and LXRs were detectable in HepG2 cells and the expressions were increased in HepG2 fatty liver cells (p < 0.05). After using the antagonists, the expressions of SREBP-1c, ChREBP, LXRs, ACC1 and FAS were significantly decreased (p < 0.05). But L-PK and RXR changed little in two groups (p > 0.05).Results of the present study demonstrated that CB1 receptors had important pathophysiological effects on the formation of fatty liver. CB1 receptors could be regulated by SREBP-1c, ChREBP and LXRs. Therefore, targeting CB1 receptors for the treatment of NAFLD might have a potential application value.
ObjectivesThe aim of this study was to identify the predictors of relapse after the withdrawal of nucleos(t)ide analog (NA) therapy in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB).MethodsThe PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched through January 2019. A random-effects model meta-analysis was performed, with hazard ratios (HR) and 95% confidence intervals (CI) used as summary statistics.ResultsSeventeen studies were included in the meta-analysis. Age (HR = 1.022 per year), baseline hepatitis B surface antigen (HBsAg) (HR = 1.509 per log IU/l), end of treatment (EOT) HBsAg level (HR = 1.896 per log IU/l), EOT HBsAg level ≥1000 IU/ml (HR = 1.749), and HBsAg decline from baseline to EOT (HR = 0.748 per log IU/l) were associated with virological relapse. The predictors of clinical relapse were baseline HBsAg level (HR = 1.312 per log IU/l), EOT HBsAg level (HR = 1.458 per log IU/l), EOT HBsAg level ≥100 IU/ml (HR = 3.199) or ≥1000 IU/ml (HR = 1.810), and duration of consolidation therapy (HR = 0.991 per month).ConclusionsThis meta-analysis indicates that age, the duration of consolidation therapy, and levels of baseline and EOT HBsAg were factors predictive of relapse in HBeAg-negative CHB patients who discontinued NA treatment.
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