Robust finite-time adaptive control for high performance voice coil motor-actuated fast steering mirror.

Fast steering mirror (FSM) is an efficient and reliable mechanical device in aerial optical image systems for controlling the beam direction with high precision. With the advantages of compact size, high speed, simple structure, and long linear stroke, voice coil motors are ideal actuators for FSM systems. However, model uncertainty can lead to poor performance or even system divergence, especially in environments with temperature variations, electromagnetic environment changes, etc. This paper proposes a novel finite-time adaptive control (FAC) algorithm for an FSM system to obtain high performance, i.e., positioning accuracy, dynamic performance, and robustness. In addition, the finite-time convergence of the controller is analyzed. In the experiments, the controller is implemented in a DSP-based microprocessor. The step response results show that the proposed algorithm has a shorter setting time, smaller overshoot, and smaller steady-state error compared to classical sliding mode control (SMC). The sinusoidal signal tracking accuracy of FAC + SMC has been improved by 19.8%. In addition, as the model uncertainty increases 10%, the root mean square errors (RMSEs) are 1.73″ and 1.18″ for SMC and FAC + SMC, respectively. With 20% model uncertainty, the RMSEs increase to 2.56″ and 1.85″, respectively. Extensive experiments demonstrate the general effectiveness of the proposed algorithm.

One hundred and ninety-two weeks treatment of entecavir maleate for Chinese chronic hepatitis B predominantly genotyped B or C.

BACKGROUND: Entecavir (ETV) is a potent and selective nucleotide analog with significant activity against hepatitis B virus (HBV). ETV maleate is a derivative compound of ETV and was reported to have an efficacy and safety profile that is comparable to ETV (Baraclude) when used in Chinese patients with chronic hepatitis B (CHB) in phase III clinical trials (Clinical Trials.gov number, NCT01926288) at weeks 48, 96, and 144. AIM: To investigate the antiviral potency and safety of ETV maleate at week 192 in Chinese CHB patients predominantly genotyped B or C. METHODS: In this double-blind study, we randomly assigned patients to receive 0.5 mg/d ETV (Group A) or ETV maleate (Group B) (ratio, 1:1), each with a placebo tablet for 48 wk. Then, all patients received open-label treatment with 0.5 mg/d ETV maleate starting at week 49. The primary efficacy endpoint was the reduction in HBV DNA levels from baseline. Secondary endpoints included the proportion of patients with undetectable HBV DNA (< 20 IU/mL), serologic response, serum alanine aminotransferase (ALT) normalization and development of resistance mutations. RESULTS: Two hundred eighteen patients who were hepatitis B e antigen (HBeAg) positive and 57 who were HBeAg negative were analyzed and predominantly presented with genotype B (49.82%) or C (48.73%). For the HBeAg-positive CHB patients, the mean HBV DNA level decrease (6.61 Log10 IU/mL vs 6.69 Log10 IU/mL, P > 0.05), viral suppression with HBV DNA < 20 IU/mL (83.33% vs 79.17%, P > 0.05) and HBeAg seroconversion (28.77% vs 20.00%, P > 0.05) occurred similarly between Groups A and B at week 192. However, there was a significant difference in the proportion of patients with normal ALT levels (91.14% vs 78.38%, P < 0.05). For the HBeAg-negative CHB patients, no significant difference was found between Groups A and B at week 192 in terms of reductions in HBV DNA levels from baseline (6.05 Log10 IU/mL vs 6.03 Log10 IU/mL, P > 0.05), percentages of patients who achieved undetectable HBV DNA (100% vs 100%, P > 0.05) and rates of ALT normalization (95.65% vs 100.00%, P > 0.05). Safety and adverse event profiles were similar between Groups A and B. Two HBeAg-positive patients in Group A and 5 in Group B developed genotypic resistance to ETV. CONCLUSION: Long-term ETV maleate treatment for up to 192 wk is effective and safe in Chinese CHB patients predominantly genotyped as B or C.

Induction and Diverse Assessment Indicators of Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is a typical autoimmune disease of the central nervous system (CNS) characterized by inflammatory infiltration, demyelination, and axonal damage. Currently, there are no measures to cure MS completely, but multiple disease-modifying therapies (DMT) are available to control and mitigate disease progression. There are significant similarities between the CNS pathological features of experimental autoimmune encephalomyelitis (EAE) and MS patients. EAE has been widely used as a representative model to determine MS drugs' efficacy and explore the development of new therapies for MS disease. Active induction of EAE in mice has a stable and reproducible effect and is particularly suitable for studying the effects of drugs or genes on autoimmune neuroinflammation. The method of immunizing C57BL/6J mice with myelin oligodendrocyte glycoprotein (MOG35-55) and the daily assessment of disease symptoms using a clinical scoring system is mainly shared. Given the complex etiology of MS with diverse clinical manifestations, the existing clinical scoring system can't satisfy the assessment of disease treatment. To avoid the shortcomings of a single intervention, new indicators to assess EAE based on clinical manifestations of anxiety-like moods and osteoporosis in MS patients are created to provide a more comprehensive assessment of MS treatment.

Methyl butyrate attenuates concanavalin A-induced autoimmune hepatitis by inhibiting Th1-cell activation and homing to the liver.

Con A-induced hepatitis is the most commonly used animal model for simulating autoimmune hepatitis (AIH). In this study, we investigated whether methyl butyrate (MB) alleviates Con A-induced hepatitis and how it affects Con A-stimulated lymphocytes. MB improves liver function in AIH mice, reducing the expression of several inflammatory cytokines and Th1 cell-associated chemokines in the liver, while significantly inhibiting toll-like receptor signaling pathway. Also in the liver, we verified that infiltrating Th1 cells were fewer after MB treatment. In vitro, we found that the activation of both human and mouse Th1 cells by Con A were inhibited by MB and the human-derived cells were even more sensitive. And MB caused a reduction in IFN-γ secretion together with TNF-α and IL-6. The above findings suggest that MB inhibits the activation and homing of Th1 cells to the liver, thereby attenuating Con A-induced liver injury, and may be a potential therapeutic agent for AIH.

240-week entecavir maleate treatment in Chinese chronic hepatitis B predominantly genotype B or C.

This study aimed to evaluate the efficacy and safety of entecavir(ETV) versus ETV maleate in Chinese patients with chronic hepatitis B(CHB). This was a randomized, double-blind, double-dummy, controlled, multicentre study. Patients were randomly assigned to receive 48 weeks of treatment with 0.5 mg/day ETV (group A) or 0.5 mg/day ETV maleate (group B), then, all patients received treatment with 0.5 mg/day ETV maleate from week 49 onwards. Patients were regularly followed up. Serum hepatitis B virus (HBV) markers were detected. Adverse events (AE) were recorded. The primary endpoint was the decline in HBV DNA in each group at the end of treatment. Secondary endpoints included the rate of HBV DNA below the lower limit of detection (LLOD) (20 I U/ml) at the end of treatment, the rate of hepatitis B e antigen (HBeAg) loss, the rate of HBeAg seroconversion and serum alanine aminotransferase (ALT) normalization. One hundred and thirty-seven (71 in group A) patients with HBeAg-positive CHB and 46 (21 in group A) patients with HBeAg-negative CHB completed the 240-week treatment and follow-up. Baseline characteristics were well balanced between the two groups. For the HBeAg-positive CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.67 log10 IU/ml vs. B: by 6.74 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA (<20 IU/ml) at Week 240 were similar between groups (A:91.55% vs. B:87.88%; p > .05). Both groups achieved similar HBeAg seroconversion rates at week 240 (A:26.98% vs. B:20.97%; p > .05). Both groups achieved similar normalization of ALT (A:87.32% vs. B:83.61%; p > .05) at Week 240 (p > .05). For the HBeAg-negative CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.05 log10 IU/ml vs. B: by 6.10 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA at Week 240 were similar between groups (A:100% vs. B:100%). Both groups achieved similar normalization rates (A:90.91% vs. B: 95.45%; p > .05) of ALT at Week 240 (p > .05). In conclusion, long-term ETV maleate treatment was safe and efficient in Chinese CHB predominantly of genotype B or C.

Optical effect and pre-forming temperature field of in situ laser-assisted micro-stamping by a diamond indenter.

During in situ laser-assisted micro-stamping (In-LAS) using a diamond indenter, the temperature of the machined area cannot be accurately predicted because of the coupling of the beam with the diamond indenter. This study uses geometrical optics and wave optics to determine the effect of the taper angle on laser direction, the light intensity distribution at the diamond indenter tip, and the temperature field of the machined area. This research provides data support and a theoretical basis for the selection of related process parameters of In-LAS and delivers a feasible theoretical method for a similar in situ laser-assisted machining.

Methyl Butyrate Alleviates Experimental Autoimmune Encephalomyelitis and Regulates the Balance of Effector T Cells and Regulatory T Cells.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by demyelinating neuropathy. The etiology of MS is not yet clear and its treatment remains a major medical challenge. While we search for drugs that can effectively treat experimental autoimmune encephalomyelitis (EAE), the animal model of MS, we also hope to further explore its possible pathogenesis. In the present study, we investigated whether methyl butyrate (MB) could alleviate EAE and its potential mechanisms. In EAE mice, we found that administration of MB was effective in alleviating their clinical signs and improving histopathological manifestations of the CNS. In the CNS and intestinal lamina propria, we observed fewer effector T cells, including Th1 and Th17, in the MB-treated group. MB also increased the proportion of regulatory T cells and the secretion of IL-10 in peripheral immune organs. In vitro, MB led to suppression of Th1 cells and promotion of regulatory T cells in their differentiation. Given that MB had no direct effect on Th17 cell differentiation in vitro, we hypothesized that MB suppressed Th17 cells indirectly by inhibiting the secretion of IL-6, which was later confirmed both in vitro and in vivo. In addition, we found that MB treatment upregulated Maf gene expression in mice, which explained its promotion of IL-10 secretion. The above findings suggest that MB may provide new ideas for the study of the mechanism of MS and have positive implications for new drug development.

DZNep, an inhibitor of the histone methyltransferase EZH2, suppresses hepatic fibrosis through regulating miR-199a-5p/SOCS7 pathway.

BACKGROUND: Hepatic fibrosis is a common response to chronic liver injury. Recently, the role of DZNep (a histone methyltransferase EZH2 inhibitor) in repressing pulmonary and renal fibrosis was verified. However, the potential effect of DZNep on hepatic fibrosis has not been elucidated. METHODS: The hepatic fibrosis model was established in rats treated with CCl4 and in hepatic stellate cells (HSCs) treated with TGF-ß1. The liver tissues were stained with H&E and Masson's trichrome. The expression of EZH2, SOCS7, collagen I, αSMA mRNA and miR-199-5p was assessed using qPCR, immunohistochemical or western blot analysis. A dual-luciferase reporter assay was carried out to validate the regulatory relationship of miR-199a-5p with SOCS7. RESULTS: The EZH2 level was increased in CCl4-treated rats and in TGF-ß1-treated HSCs, whereas DZNep treatment significantly inhibited EZH2 expression. DZNep repressed hepatic fibrosis in vivo and in vitro, as evidenced by the decrease of hepatic fibrosis markers (α-SMA and Collagen I). Moreover, miR-199a-5p expression was repressed by DZNep in TGF-ß1-activated HSCs. Notably, downregulation of miR-199a-5p decreased TGF-ß1-induced expression of fibrosis markers. SOCS7 was identified as a direct target of miR-199a-5p. The expression of SOCS7 was decreased in TGF-ß1-activated HSCs, but DZNep treatment restore d SOCS7 expression. More importantly, SOCS7 knockdown decreased the effect of DZNep on collagen I and α SMA expression in TGF-ß1-activated HSCs. CONCLUSIONS: DZNep suppresses hepatic fibrosis through regulating miR-199a-5p/SOCS7 axis, suggesting that DZNep may represent a novel treatment for fibrosis.

Fabrication of nano/microstructures for SERS substrates using an electrochemical method.

Based on an electrochemical method, three-dimensional arrayed nanopore structures are machined onto a Mg surface. The structured Mg surface is coated with a thin gold (Au) film, which is used as a surface-enhanced Raman scattering (SERS) substrate. A rhodamine 6G (R6G) probe molecule is used as the detection agent for the SERS measurement. Different sizes of arrayed micro/nanostructures are fabricated by different treatment time using the electrochemical process. The topographies of these micro/nanostructures and the thickness of the Au film have an influence on the Raman intensity of the Mg substrate. Furthermore, when the thickness of Au film coating is held constant, the Raman intensity on the structured Mg substrates is about five times higher after a treatment time of 1 min when compared with other treatment times. The SERS enhancement factor ranges from 106 to 1.75 × 107 under these experimental conditions. Additionally, a 10-6 mol·L-1 solution of lysozyme was successfully detected using the Mg-Au nanopore substrates. Our low-cost method is reproducible, homogeneous, and suitable for the fabrication of SERS substrates.

Effect of Preoperative Nutritional Risk Screening on Postoperative Recovery in Patients with Laparoscopic-Assisted Radical Resection for Colorectal Cancer.

RESULTS: There were statistically significant differences in BMI, albumin, total cholesterol, and lymphocyte count between patients from the two groups (all P < 0.05). There was no difference in the incidence rate of postoperative complications between the two groups, but there was a statistically significant difference in the total number of complications (P < 0.05). There were no significant differences between the two groups regarding abdominal drainage volume, exhaust (flatus) time, hospitalization cost, morbidity, or 60 d readmission rate (all P > 0.05). However, patients with nutritional risk had higher postoperative blood transfusion volumes, albumin infusions, weight difference before and after surgery, and postoperative hospital stays than the nonnutritional risk group (all P < 0.05). Smoking, diabetes, and preoperative nutritional risk were the risk factors by the univariate and multivariate logistic regression analyses. CONCLUSIONS: The postoperative complication rate was increased, and the short-term efficacy was decreased in the preoperative nutritional risk group compared with those without nutritional risk.

Association Between Negative Results From Tests for HBV DNA and RNA and Durability of Response After Discontinuation of Nucles(t)ide Analogue Therapy.

BACKGROUND & AIMS: There is no satisfactory way to identify patients who will maintain a response after discontinuation of nuleos(t)ide analogue therapy for chronic hepatitis B virus (HBV) infection. We investigated whether patients with negative results from tests for HBV DNA and HBV RNA (double negative) at the end of treatment maintain a long-term response to treatment. METHODS: We performed a post-hoc analysis of data from a 2-year multi-center randomized controlled trial, and its long-term extension trials, on 130 patients with chronic HBV infection who were positive for the HB e antigen (HBeAg-positive; mean age, 30.8 ± 6.9 years; 72.3% male) and received telbivudine with or without adefovir and stopped therapy after they had HBeAg seroconversion and levels of HBV DNA <300 copies/mL for at least 48 weeks (evaluation cohort). Clinical and laboratory assessments were made every 12 or 16 weeks until clinical relapse (defined as HBV DNA > 2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal) or until 4 years off treatment. We validated our findings in a cohort of 40 HBeAg-positive patients (36.5 ± 9.4 years old; 72.5% male) treated with entecavir or tenofovir, and followed after discontinuation for up to 5.5 years. Patients were considered to be negative for HBV DNA if it was not detected in the COBAS Taqman assay. Patients were considered to be negative for HBV RNA if it was not detected by quantitative real-time PCR with 2 different pairs of primers. RESULTS: After 4 years off treatment, in the evaluation cohort, 30.8% of patients had a clinical relapse, 54.7% had virologic relapse (HBV DNA >2000 IU/mL in 2 tests), and 16.8% had reappearance of HBeAg in 2 tests (reversion). A significantly lower proportion of double negative patients had a clinical relapse 4 years later (2/35; 8.0%) than of patients who tested positive for either HBV DNA or RNA (32/102; 31.4%; P = .018). In the validation cohort, after 5.5 years of follow up, a lower proportion of double negative patients had clinical relapse (2/13; 15.4%) than of patients who tested positive for either HBV DNA or RNA at the end of treatment (9/27; 33.3%; P = .286) CONCLUSIONS: In an analysis of data from 2 independent cohorts, we associated negative results from tests for HBV DNA and RNA (double negative) at the end of treatment with continued response 4 or more years after discontinuation of therapy in HBeAg-positive patients. These results might be used to identify the best candidates for discontinuation of nuleos(t)ide analogue therapy.

Analysis of critical negative rake angle and friction characteristics in orthogonal cutting of AL1060 and T2.

The stagnant region often appears in front of the tool cutting edge, which is caused by mechanical inlay and excessive pressing in plastic metal cutting with large negative rake angle tools at a low speed. It results in the change of the effective negative rake angle which can affect the flow characteristics of material, the quality of machined surface and the abrasion loss of cutting tools. However, the critical negative rake angle model based on the existence of the stagnant region has not been reported yet. Therefore, in order to investigate the critical negative rake angle value considering the stagnant region, a critical negative rake angle model based on the principle of minimum required energy is established, and the correctness of the theoretical model is verified by orthogonal cutting experiments. At the same time, the influence of the critical value of the large negative rake angle tool on the machined surface quality is studied through different cutting experiments. These experimental results show that the deviations of both experimental and theoretical critical negative rake angle are less than 5% during the orthogonally cutting of the aluminium (AL1060) and copper (T2) materials by the negative rake angle tool. Meanwhile, the critical negative rake angle is related to the adhesive friction coefficient of tool-workpiece contact surface. The analysis of friction characteristics shows that the deviation values of both theoretical and experimental critical negative rake angle are proportional to the coefficient of adhesive friction and the thickness of the stagnant region. Critical negative rake angle has a significant effect on roughness and residual stress of the machined surface.

Comparison of non-invasive models for predicting liver damage in chronic hepatitis B patients.

INTRODUCTION: Inexpensive blood tests have been well established as alternatives to liver biopsies to evaluate liver fibrosis in CHB patients. Here, we aim to compare their diagnostic accuracy in assessing liver fibrosis and necroinflammation. PATIENTS AND METHODS: A retrospective study was performed to evaluate the predictive value of non-invasive models in chronic hepatitis B patients with liver fibrosis by the area under receiver operating characteristic curve (AUROC). The clinical data of 160 patients were collected from medical records. RESULTS: Of the 160 consecutive treatment-naïve CHB patients, 29 (16%) had significant fibrosis and 34 (21%) had severe necroinflammation. The AUROC of the gamma-glutamyl transpeptidase to platelet ratio (GPR) (0.761, 95% CI 0.671-0.850) for predicting significant fibrosis was significantly higher than that of the aspartate transaminase-to-platelet ratio index (APRI) (0.680, 95% CI 0.585-0.774, p=0.034), but comparable with the fibrosis index based on four factors (Fib-4) (0.746, 95% CI 0.656-0.836, p=0.703), while for predicting severe necroinflammation, the performance of the GPR (AUROC=0.869, 95% CI 0.800-0.937) was better than the APRI (AUROC=0.816, 95% CI 0.740-0.892, p=0.085) and Fib-4 (0.792, 95% CI 0.711-0.873, p=0.023). DISCUSSION: GPR is a satisfactory model to stage liver fibrosis and to grade necroinflammation activity, representing a convenient non-invasive alternative to liver biopsy in China.

Early steep decline of liver stiffness predicts histological reversal of fibrosis in chronic hepatitis B patients treated with entecavir.

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.

Label-free highly sensitive probe detection with novel hierarchical SERS substrates fabricated by nanoindentation and chemical reaction methods.

Nanostructures have been widely employed in surface-enhanced Raman scattering (SERS) substrates. Recently, in order to obtain a higher enhancement factor at a lower detection limit, hierarchical structures, including nanostructures and nanoparticles, appear to be viable SERS substrate candidates. Here we describe a novel method integrating the nanoindentation process and chemical redox reaction to machine a hierarchical SERS substrate. The micro/nanostructures are first formed on a Cu(110) plane and then Ag nanoparticles are generated on the structured copper surface. The effect of the indentation process parameters and the corrosion time in the AgNO3 solution on the Raman intensities of the SERS substrate with hierarchical structures are experimentally studied. The intensity and distribution of the electric field of single and multiple Ag nanoparticles on the surface of a plane and with multiple micro/nanostructures are studied with COMSOL software. The feasibility of the hierarchical SERS substrate is verified using R6G molecules. Finally, the enhancement factor using malachite green molecules was found to reach 5.089 × 109, which demonstrates that the production method is a simple, reproducible and low-cost method for machining a highly sensitive, hierarchical SERS substrate.

Analysis of the influence of installation tilt error on the tool setting accuracy by laser diffraction.

In the ultra-precision machining process, it is important to detect the tool-workpiece distance by the laser diffraction effect. However, there is no absolute ideal situation for the tool setting of laser diffraction. It is necessary to consider the influence of installation tilt error on the tool setting accuracy and its compensation. In this paper, referring to the ideal optical axis, the influences of the incident laser tilt, CCD tilt, and rectangular orifice tilt on the peak position of the diffraction fringes in the CCD phase are modeled and analyzed to determine the relative effects on the tool setting accuracy for tool-workpiece distance detection. The tilt angle of the incident laser is measured by extracting the CCD pixel position, where the central peak point is located. The CCD tilt angle is detected by extracting the CCD pixel positions, where the first-degree peak points are located. The inclination direction and the inclination angle of the rectangular orifice are detected by extracting the bending direction and the bending degree of the fringes in the horizontal direction, and the error compensation is performed according to the inclination angle. This study establishes a compensation method for installing tilt error, and the optimized installation process parameters can be acquired under certain experimental conditions according to the experimental data to ensure the results' accuracy.

Involvement of epithelial-mesenchymal transition in liver fibrosis.

Fibrosis of the liver is an inherent wound healing response to chronic liver injury. Regeneration of liver epithelium and restoration of normal liver structure were generally involved in this process. Although the liver has a striking capacity to adapt to damage through tissue repair, excessive accumulation of extracellular matrix during this process often leads to scar tissue formation and subsequent fibrosis. Epithelial to mesenchymal transition (EMT) enables a polarized epithelial cell to undergo multiple changes biochemically and to bear a mesenchymal cell phenotype. EMT plays a critical role in tissue and organ development and embryogenesis. In the liver, it is proposed that epithelial cells can acquire fibroblastic phonotype via EMT and contribute to fibrogenesis. This made EMT a potential target for antifibrotic strategies. Following an original passion, many investigators devote themselves to exploring this mechanism in liver fibrosis. However, as research continues, this hypothesis became highly controversial. The exact contribution of EMT to fibrogenesis was challenged due to the contradictory results from related studies. In this review, we summarized the recent advances regarding EMT in hepatic fibrosis and discussed the potentially involved liver cell types and pathways in order to reach rational and helpful conclusions.

Association of baseline vitamin D level with genetic determinants and virologic response in patients with chronic hepatitis B.

AIM: The role of vitamin D in individuals with chronic hepatitis B (CHB) is unclear. We aimed to explore the association of baseline vitamin D level with genetic determinants and week-104 treatment outcome in CHB patients. METHODS: Baseline serum 25-hydroxycholecalciferol (25(OH)D) levels and genetic polymorphism within GC, DHCR7, and CYP2R1 were determined in stored serum of 560 patients who were enrolled into a multicenter, randomized, controlled study and completed 104 weeks of telbivudine monotherapy or telbivudine-based optimized therapy. Virologic response was defined as hepatitis B virus DNA <300 copies/mL (52 IU/mL) at week 104. RESULTS: The mean 25(OH)D value was 29.64 ng/mL. The percentage of patients with vitamin D insufficiency (<30 ng/mL) and vitamin D deficiency (<20 ng/mL) were 55.0% and 20.9%, respectively. Gender, season, latitude, and GC rs2282679 polymorphism were independent factors of vitamin D status. Patients with sufficient vitamin D (≥30 ng/mL) achieved a higher virologic response rate than those with vitamin D insufficiency (81.7% vs. 67.2%, P < 0.001). The area under the curve of 25(OH)D to predict virologic response was 0.65 (P < 0.001; 95% confidence interval, 0.62-0.67). On multivariate analysis, 25(OH)D level was an independent predictor of virologic response, but not associated with hepatitis B envelope antigen (HBeAg) seroconversion or alanine aminotransferase (ALT) normalization. CONCLUSIONS: Vitamin D insufficiency was highly prevalent in treatment-naïve CHB patients in mainland China. Latitude and genetic determinants affect vitamin D status. Baseline vitamin D level can predict week-104 virologic response, but not HBeAg seroconversion or ALT normalization.

miR-96-5p prevents hepatic stellate cell activation by inhibiting autophagy via ATG7.

Activation of hepatic stellate cell (HSC), which is the main source of extracellular matrix, plays a pivotal role in liver fibrogenesis. Autophagy of hepatic stellate cell has been recently implicated in liver fibrosis, but the regulation of hepatic stellate cell autophagy during this process remains poorly understood. Here, we first identified miR-96-5p as an aberrantly expressed miRNA in fibrotic liver tissues. Next, we transfected miR-96-5p mimic into human hepatic stellate cell line LX-2 and observed decreased protein and mRNA levels of α-SMA and Col1A1. In addition, transfection of miR-96-5p mimic significantly reduced autophagy activity of LX-2 cells, while transfection of miR-96-5p inhibitor promoted LX-2 cell autophagy. Moreover, autophagy-related protein 7 (ATG7) was predicted as a potential target of miR-96-5p and luciferase assay confirmed its direct interaction with miR-96-5p. Finally, reintroduction of ATG7 into LX-2 cells reversed miR-96-5p-mediated inhibition of autophagy as well as α-SMA and Col1A1 expression. In conclusion, we demonstrated that miR-96-5p can inhibit hepatic stellate cell activation by blocking autophagy via ATG7. These findings provide new insight into the development of miRNA-based anti-fibrotic strategies. KEY MESSAGES: • Altered miRNA expression profile is observed in fibrotic liver tissues. • miR-96-5p can inhibit HSC activation. • Autophagy of HSC is repressed by miR-96-5p during activation. • ATG7 is a direct target of miR-96-5p. • ATG7 can rescue miR-96-5p-mediated inhibition of autophagy and HSC activation.

The role of T helper 17 cells in the pathogenesis of hepatitis B virus-related liver cirrhosis (Review).

In chronic hepatitis B virus (HBV)-infected patients, T helper 17 (Th17) cells are significantly elevated. Th17 cells initiate immune­mediated pathogenesis and have a critical role in the process of HBV­related liver cirrhosis (HBV­LC). The mechanisms underlying this process are attributed to Th17­secreted cytokines, which include interleukin (IL)­17, IL­21 and IL­22; however, a systemic analysis regarding these mechanisms has yet to be conducted. Therefore, the present study aimed to investigate the role of Th17 cells in the pathogenesis of HBV­LC. All randomized clinical trials, case series, case reports and meta­analyses that contained the aforementioned keywords were included in the review process. In addition, unpublished information from the Food and Drug Administration was included. The findings indicated that Th17­secreted cytokines, including IL­17, IL­21 and IL­22, function by activating or silencing hepatic stellate cells, modulating proinflammatory and pro­ or antifibrogenic effectors, regulating extracellular matrix formation, upregulating chemokine expression, and inducing hepatocellular damage or hepatoprotection during the HBV­LC process. In addition, Th17 cells and Th17­secreted cytokines may be considered a potential tool in the diagnosis or treatment of HBV­LC. The present review summarized the role of Th17 cells in the pathogenesis of HBV­LC in order to deepen the clinical understanding of the role of Th17 cells and also to support the development of effective therapies for patients with HBV­LC.