Blended Nephelium lappaceum and Durio zibethinus wastes for activated carbon production via microwave-ZnCl2 activation: optimization for methylene blue dye removal.

Herein, this work targets to employ the blended fruit wastes including rambutan (Nephelium lappaceum) peel and durian (Durio zibethinus) seed as a promising precursor to produce activated carbon (RPDSAC). The generation of RPDSAC was accomplished through a rapid and practical procedure (microwave-ZnCl2 activation). To evaluate the adsorptive capabilities of RPDSAC, its efficacy in eliminating methylene blue (MB), a simulated cationic dye, was measured. The Box-Behnken design (BBD) was utilized to optimize the crucial adsorption parameters, namely A: RPDSAC dose (0.02-01 g/100 mL), B: pH (4-10), and C: time (2-6 min). The BBD design determined that the highest level of MB removal (79.4%) was achieved with the condition dosage of RPDSAC at 0.1 g/100 mL, contact time (6 min), and pH (10). The adsorption isotherm data is consistent with the Freundlich concept, and the pseudo-second-order versions adequately describe the kinetic data. The monolayer adsorption capacity (qmax) of RPDSAC reached 120.4 mg/g at 25 °C. Various adsorption mechanisms are involved in the adsorption of MB dye onto the surface of RPDSAC, including π-π stacking, H-bonding, pore filling, and electrostatic forces. This study exhibits the potential of the RPDSAC as an adsorbent for removal of toxic cationic dye (MB) from contaminated wastewater.

Chitosan-grafted salicylaldehyde/algae composite for methyl violet dye removal: adsorption modeling and optimization.

In this study, a hydrothermal approach was employed to graft chitosan (Chit)/algae (ALG) with salicylaldehyde (SA), resulting in the synthesis of a biocomposite named salicylaldehyde-based chitosan Schiff base/algae (Chit-SA/ALG). The main objective of this biocomposite was to effectively remove methyl violet (MV), an organic dye, from aqueous solutions. The adsorption performance of Chit-SA/ALG toward MV was investigated in detail, considering the effects of three factors: (A) Chit-SA/ALG dose (ranging from 0.02 to 0.1 g/100 mL), (B) pH (ranging from 4 to 10), and (C) time (ranging from 10 to 120 min). The Box-Behnken design (BBD) was utilized for experimental design and analysis. The experimental results exhibited a good fit with both the pseudo-second-order kinetic model and the Freundlich isotherm, suggesting their suitability for describing the MV adsorption process on Chit-SA/ALG. The maximum adsorption capacity of Chit-SA/ALG, as calculated by the Langmuir model, was found to be 115.6 mg/g. The remarkable adsorption of MV onto Chit-SA/ALG can be primarily attributed to the electrostatic forces between Chit-SA/ALG and MV as well as the involvement of various interactions such as n-π, π-π, and H-bond interactions. This research demonstrates that Chit-SA/ALG exhibits promising potential as a highly efficient adsorbent for the removal of organic dyes from water systems.

The novelty of this work comes from introducing a new bio-organic based composite adsorbent of chitosan (Chit) biopolymer and algae (ALG) biomass. Moreover, the functionality and chemical stability of Chit­ALG composite was further developed by grafting process with salicylaldehyde (SA) using hydrothermal process. The incorporation of ALG biomass into polymeric matrix of Chit and grafting process with SA makes Chit a unique hybrid adsorbent toward cationic dye (methyl violet dye).

Multifunctional transmission-type microwave metadevice based on spin-decoupled and linear-to-circular metasurfaces.

Metasurfaces have enabled precise electromagnetic (EM) wave manipulation with strong potential to obtain unprecedented functionalities and multifunctional behavior in flat optical devices. One promising aspect to achieve multifunction is polarization-dependent metadevices enabled by simultaneous phase control over orthogonally polarized waves. Among these, metasurfaces with geometric phase shows their natural and robust phase control ability over different circularly polarized waves. However, the phase responses under the circularly polarized incidence are locked to be opposite with each other, resulting in limited multifunctionality. In this study, we propose what we believe to be a novel transmission-type microwave metadevice constructed by linear-to-circular metasurface and spin-decoupled metasurface. By endowing independent phase adjustment capability to each unit structure in a spin-decoupled metasurface, the metadevice can reconfigure arbitrary phase wavefronts under orthogonal polarization state incidence, thereby achieving flexible multifunctionality. As a proof-of-concept, the feasibility and reliability of proposed metasurfaces were verified by simulating multifunctional directional deflection, off-axis focusing, and focused vortex beam generation. Finally, the multifunctional manipulation capability of the metadevice is successfully demonstrated by actually measuring the generation of orbital angular momentum modes. This work is expected to drive the application development of metasurface devices in wireless communication.

Automatic and inverse design of broadband terahertz absorber based on optimization of genetic algorithm for dual metasurfaces.

In this study, we introduce a genetic algorithm (GA) into the catenary theory model to achieve automatic and inverse design for terahertz (THz) metasurface absorbers. The GA method was employed by seeking optimal dispersion distributions to achieve broadband impedance matching. A THz dual-metasurface absorber was designed using the proposed approach. The designed metasurface absorber exhibits an absorbance exceeding 88% at 0.21-5 THz. Compared to the traditional design method, the proposed method can reduce time consumption and find the optimal result to achieve high performance. The investigations provide important guidance and a promising approach for designing metasurface-based devices for practical applications.

Serum qAnti-HBc combined with ALT and HBsAg predicts significant hepatic inflammation in HBeAg-positive immune active patients.

BACKGROUND AND AIM: Quantitative hepatitis B core antibody (qAnti-HBc) level has been reported to predict significant liver inflammation in treatment-naïve chronic hepatitis B patients. However, little evidence has been revealed that qAnti-HBc alone or with other serum parameters in predicting moderate to severe hepatic inflammation in HBeAg-positive immune active patients treated with entecavir (ETV). METHODS: A total of 142 patients with HBeAg-positive immune active hepatitis were recruited in our study. Serum liver biochemistry, qAnti-HBc, hepatitis B virus markers, and liver inflammation were evaluated during 48-week ETV treatment. The association between liver inflammation grades and serum markers was systematically analyzed. RESULTS: The patients with moderate to severe inflammation (≥ G2) had a significantly higher level of qAnti-HBc compared with those with no to mild liver inflammation patients (< G2). The levels of qAnti-HBc and alanine transaminase (ALT) were positively correlated with hepatic inflammation grades, and qAnti-HBc had a better correlation than ALT, whereas HBsAg was negatively correlated with hepatic inflammation grades before treatment. After 48-week ETV treatment, no correlation was observed between hepatic inflammation grades and qAnti-HBc, ALT, or HBsAg. The combination of qAnti-HBc, ALT, and HBsAg had better performance in predicting significant liver inflammation (≥ G2) than qAnti-HBc alone or its combination with ALT. CONCLUSION: Serum qAnti-HBc levels were positively correlated with hepatic inflammation grades before treatment, but no positive correlation between them was observed after 48-week treatment. The level of qAnti-HBc combined with ALT and HBsAg may serve as a more reliable marker for identifying significant liver inflammation before treatment in HBeAg-positive immune active patients.

Serum HBV RNA correlated with intrahepatic cccDNA more strongly than other HBV markers during peg-interferon treatment.

BACKGROUND: Serum hepatitis B virus RNA (HBV RNA) has been reported to be a surrogate marker of intrahepatic cccDNA during nucleos(t)ide analogs therapy. However, in HBeAg-positive patients treated with peg-interferon (peg-IFN), whether HBV RNA is superior to other HBV markers in reflecting cccDNA profile is still unclear. METHODS: Serum HBV RNA, HBcrAg, HBV DNA, and HBsAg were longitudinally assessed among 30 HBeAg-positive patients during 48-week peg-IFN treatment. Besides, intrahepatic cccDNA was detected at baseline and week 48 respectively. Then, the individual correlations between HBV RNA, HBcrAg, HBV DNA, HBsAg, and cccDNA were statistically analyzed. RESULTS: HBV RNA levels decreased more rapidly in patients with HBeAg seroconversion than those without HBeAg seroconversion. Among all patients, cccDNA correlated better with HBV RNA than with HBcrAg, HBV DNA, and HBsAg at baseline. After 48 weeks peg-IFN treatment, cccDNA still correlated more strongly with HBV RNA than other HBV markers. Further analysis indicated that in patients with HBeAg seroconversion cccDNA strongly correlated with HBV RNA and HBcrAg, whereas not correlate with HBV DNA and HBsAg. While in patients without HBeAg seroconversion, cccDNA highly correlated with HBV RNA and HBV DNA, moderately correlated with HBcrAg, and not correlated with HBsAg. CONCLUSION: Compared to HBcrAg, HBV DNA, and HBsAg, serum HBV RNA correlated more strongly with intrahepatic cccDNA levels before and after 48-week peg-IFN treatment. The level of serum HBV RNA may be a superior surrogate marker in reflecting the intrahepatic cccDNA profile in HBeAg-positive patients during peg-IFN treatment. Trial registration ClinicalTrials, NCT03546530. Registered 1 January 2015. https://clinicaltrials.gov/ct2/results?cond=&term=NCT03546530 .

Inosine triphosphate pyrophosphatase polymorphisms are predictors of anemia in Chinese patients with chronic hepatitis C during therapy with ribavirin and interferon.

BACKGROUND AND AIM: Polymorphisms of inosine triphosphate pyrophosphatase (rs1127354 and rs6051702) and interferon lambda 4 (IFLN4) (rs12979860) are indicators of anemia and/or sustained virological response (SVR) in patients with chronic hepatitis C on ribavirin/interferon. The study aims to investigate the associations of rs1127354, rs6051702, and rs12979860 with hemoglobin levels and SVR in patients on ribavirin/interferon. METHODS: Polymorphisms were detected by pyrosequencing. Levels of hemoglobin and hepatitis C virus (HCV) RNA were measured at weeks 2, 4, 12, 24, 36, 48, and 72 of treatment. RESULTS: A total of 351 patients (median age, 50 years; male, 71.2%) were recruited and had HCV genotypes 1b (55.8%) or 2a (37.0%). Vedian baseline hemoglobin and HCV RNA were 155 g/dL and 6.07 log10 IU/mL. Major allele homozygosity was observed in 76.3% for rs1127354 (CC), 70.9% for rs6051702 (AA), and 89.7% for rs12979860 (CC). At 4 weeks of ribavirin/interferon treatment, a more significant reduction in hemoglobin was observed with rs112754 CC than with AC/AA (P < 0.05). A decline ≥3 g/dL was more common in patients with the rs112754 CC than with the other two polymorphisms. No significant change was observed regarding rs6051702 and rs12979860 variants. In the multivariable analysis, rs1127354 AA/AC (vs CC) were independently associated with lower odds of hemoglobin decline of > 3 g/dL at 4 weeks (odds ratio, 0.21; 95% CI, 0.09-0.46; P < 0.0001). In 258 patients with 72-week outcome data available, rs1127354, rs6051702, and rs12979860 were not associated with SVR (all P > 0.05). CONCLUSION: rs1127354 polymorphisms are associated with hemoglobin levels in Chinese patients with chronic hepatitis C treated with ribavirin/interferon.

IL-33 Inhibits Hepatitis B Virus through Its Receptor ST2 in Hydrodynamic HBV Mouse Model.

Interleukin-33 has been demonstrated to be associated with liver damage. However, its potential value in hepatitis B virus (HBV) infection remains unknown. This study was designed to investigate the role of IL-33 in hydrodynamic HBV mouse model. Different doses of IL-33 were used to treat HBV wild-type, ST2 knockout, CD8+ T depletion, NK depletion C57BL/6 mice and C.B-17 SCID and nod SCID mouse, respectively. The concentrations of HBV DNA, HBsAg, HBeAg, and molecules related to liver function were detected in the collected serum at different time points from model mice. Intrahepatic HBcAg was visualized by immunohistochemical staining of liver tissues. In vitro, hepG2 cells were transfected with pAAV-HBV 1.2, then treated with IL-33. The results showed that IL-33 significantly reduced HBV DNA and HBsAg in a dose-dependent manner in HBV wild-type mice. However, in the IL-33 specific receptor ST2 knockout mice, their antiviral effects could not be exerted. Through immunodeficient animal models and in vivo immune cell depletion mouse model, we found that IL-33 could not play antiviral effects without NK cells. Moreover, IL-33 could reduce the levels of HBsAg and HBeAg in the supernatant of HBV-transfected hepG2 cells in vitro. Our study revealed that IL-33 could inhibit HBV through ST2 receptor in the HBV mouse model, and this effect can be impaired without NK cell. Additionally, IL-33 had the direct anti-HBV effect in vitro, indicating that IL-33 could be a potent inducer of HBV clearance and a promising drug candidate.

Alcohol inhibits T-cell glucose metabolism and hepatitis in ALDH2-deficient mice and humans: roles of acetaldehyde and glucocorticoids.

OBJECTIVE: Aldehyde dehydrogenase 2 (ALDH2), a key enzyme to detoxify acetaldehyde in the liver, exists in both active and inactive forms in humans. Individuals with inactive ALDH2 accumulate acetaldehyde after alcohol consumption. However, how acetaldehyde affects T-cell hepatitis remains unknown. DESIGN: Wild-type (WT) and Aldh2 knockout (Aldh2-/-) mice were subjected to chronic ethanol feeding and concanavalin A (ConA)-induced T-cell hepatitis. Effects of acetaldehyde on T-cell glucose metabolism were investigated in vitro. Human subjects were recruited for binge drinking and plasma cortisol and corticosterone measurement. RESULTS: Ethanol feeding exacerbated ConA-induced hepatitis in WT mice but surprisingly attenuated it in Aldh2-/- mice despite higher acetaldehyde levels in Aldh2-/- mice. Elevation of serum cytokines and their downstream signals in the liver post-ConA injection was attenuated in ethanol-fed Aldh2-/- mice compared to WT mice. In vitro exposure to acetaldehyde inhibited ConA-induced production of several cytokines without affecting their mRNAs in mouse splenocytes. Acetaldehyde also attenuated interferon-γ production in phytohaemagglutinin-stimulated human peripheral lymphocytes. Mechanistically, acetaldehyde interfered with glucose metabolism in T cells by inhibiting aerobic glycolysis-related signal pathways. Finally, compared to WT mice, ethanol-fed Aldh2-/- mice had higher levels of serum corticosterone, a well-known factor that inhibits aerobic glycolysis. Blockade of corticosterone partially restored ConA-mediated hepatitis in ethanol-fed Aldh2-/- mice. Acute alcohol drinking elevated plasma cortisol and corticosterone levels in human subjects with higher levels in those with inactive ALDH2 than those with active ALDH2. CONCLUSIONS: ALDH2 deficiency is associated with elevated acetaldehyde and glucocorticoids post-alcohol consumption, thereby inhibiting T-cell activation and hepatitis.

Identification of key genes and pathways associated with different immune statuses of hepatitis B virus infection.

We aimed to identify key genes and pathways associated with different immune statuses of hepatitis B virus (HBV) infection. The gene expression and DNA methylation profiles were analysed in different immune statuses of HBV infection. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified, followed by their functional and integrative analyses. The differential expression of IgG Fc receptors (FcγRs) in chronic HBV-infected patients and immune cells during different stages of HBV infection was investigated. Toll-like receptor (TLR) signalling pathway (including TLR6) and leucocyte transendothelial migration pathway (including integrin subunit beta 1) were enriched during acute infection. Key DEGs, such as FcγR Ib and FcγR Ia, and interferon-alpha inducible protein 27 showed correlation with alanine aminotransferase levels, and they were differentially expressed between acute and immune-tolerant phases and between immune-tolerant and immune-clearance phases. The integrative analysis of DNA methylation profile showed that lowly methylated and highly expressed genes, including cytotoxic T lymphocyte-associated protein 4 and mitogen-activated protein kinase 3 were enriched in T cell receptor signalling pathway during acute infection. Highly methylated and lowly expressed genes, such as Ras association domain family member 1 and cyclin-dependent kinase inhibitor 2A were identified in chronic infection. Furthermore, differentially expressed FcγR Ia, FcγR IIa and FcγR IIb, CD3- CD56+ CD16+ natural killer cells and CD14high CD16+ monocytes were identified between immune-tolerant and immune-clearance phases by experimental validation. The above genes and pathways may be used to distinguish different immune statuses of HBV infection.

ALDH2 deficiency promotes alcohol-associated liver cancer by activating oncogenic pathways via oxidized DNA-enriched extracellular vesicles.

BACKGROUND & AIMS: Excessive alcohol consumption is one of the major causes of hepatocellular carcinoma (HCC). Approximately 30-40% of the Asian population are deficient for aldehyde dehydrogenase 2 (ALDH2), a key enzyme that detoxifies the ethanol metabolite acetaldehyde. However, how ALDH2 deficiency affects alcohol-related HCC remains unclear. METHODS: ALDH2 polymorphisms were studied in 646 patients with viral hepatitis B (HBV) infection, who did or did not drink alcohol. A new model of HCC induced by chronic carbon tetrachloride (CCl4) and alcohol administration was developed and studied in 3 lines of Aldh2-deficient mice: including Aldh2 global knockout (KO) mice, Aldh2*1/*2 knock-in mutant mice, and liver-specific Aldh2 KO mice. RESULTS: We demonstrated that ALDH2 deficiency was not associated with liver disease progression but was associated with an increased risk of HCC development in cirrhotic patients with HBV who consumed excessive alcohol. The mechanisms underlying HCC development associated with cirrhosis and alcohol consumption were studied in Aldh2-deficient mice. We found that all 3 lines of Aldh2-deficient mice were more susceptible to CCl4 plus alcohol-associated liver fibrosis and HCC development. Furthermore, our results from in vivo and in vitro mechanistic studies revealed that after CCl4 plus ethanol exposure, Aldh2-deficient hepatocytes produced a large amount of harmful oxidized mitochondrial DNA via extracellular vesicles, which were then transferred into neighboring HCC cells and together with acetaldehyde activated multiple oncogenic pathways (JNK, STAT3, BCL-2, and TAZ), thereby promoting HCC. CONCLUSIONS: ALDH2 deficiency is associated with an increased risk of alcohol-related HCC development from fibrosis in patients and in mice. Mechanistic studies reveal a novel mechanism that Aldh2-deficient hepatocytes promote alcohol-associated HCC by transferring harmful oxidized mitochondrial DNA-enriched extracellular vesicles into HCC and subsequently activating multiple oncogenic pathways in HCC. LAY SUMMARY: Alcoholics with an ALDH2 polymorphism have an increased risk of digestive tract cancer development, however, the link between ALDH2 deficiency and hepatocellular carcinoma (HCC) development has not been well established. In this study, we show that ALDH2 deficiency exacerbates alcohol-associated HCC development both in patients and mouse models. Mechanistic studies revealed that after chronic alcohol exposure, Aldh2-deficient hepatocytes produce a large amount of harmful oxidized mitochondrial DNA via extracellular vesicles, which can be delivered into neighboring HCC cells and subsequently activate multiple oncogenic pathways, promoting HCC.

Aberrant DNA methylation profile of hepatitis B virus infection.

We aimed to study the aberrant DNA methylation profile associated with hepatitis B virus (HBV) infection and, to identify key genes and pathways associated with the HBV infection stage. A total of 54 antiviral treatment-naïve HBV-infected patients and six healthy controls were included. Genome-wide methylated DNA immunoprecipitation analysis was performed, as previously described, after which the chip data were preprocessed. Subsequently, Cytoscape software was used for the construction of a protein-protein interaction network, and a database for annotation, visualization, and integrated discovery software was used to conduct functional enrichment analysis. A total of 711 794 CpGs were obtained after data quality control, among which 152 780, 113 814, 90 747, and 175 868 CpGs showed differential methylation in acute hepatitis B (AHB) vs control, total-C vs control, CH1 vs CA1, and AHB vs total-C, respectively. Furthermore, RIPK3, PRDM10, JUN, and SNAI1 were at the center of the four associated networks, respectively. Differential methylated genes differentially methylated in these four comparisons were significantly enriched with olfactory transduction; positive regulation of transport; negative regulation of protein amino acid phosphorylation (eg, JUN), phosphorylation, phosphorus metabolic process, and phosphate metabolic process; and programmed cell death, respectively. RIPK3, PRDM10, JUN, and SNAI1 as well as olfactory transduction, positive regulation of transport, negative regulation of phosphorylation, and programmed cell death are important for the transformation associated with HBV infection stage. Moreover, JUN may be involved in HBV infection, mainly via the negative regulation of amino acid phosphorylation.

The association of hepatitis c virus infection status with serum glucose levels.

BACKGROUND: Hepatitis C virus (HCV) infection is commonly associated with a disturbance of glucose metabolism. However, there have been conflicting reports on whether the clearance of the HCV may be followed by changes of serum blood glucose and insulin resistance. The aim of the present study was to evaluate the impact of HCV and antiviral treatment on serum glucose levels and other glucose metabolism parameters. METHODS: A retrospective analysis of 306 HCV-infected patients was performed. Fasting serum blood glucose (FBG) levels in these patients were compared with that of 325 healthy individuals. Serum parameters of glucose metabolism were measured in 183 patients with chronic hepatitis C at baseline, at the end of interferon α-2b plus ribavirin treatment, and at 24 weeks post-treatment. RESULTS: Patients with HCV infection had significantly higher FBG level than healthy controls (5.57 ± 0.74 vs. 5.11 ± 0.83 mmol/l, P < 0.001). After antiviral treatment, we found a significant reduction in FBG levels regardless of the outcome of treatment. However, after stopping treatment the serum FBG levels were significantly elevated in the sustained virological response (SVR) and non-responder groups, and maintained high level until week 24 post-treatment. In both groups, the levels of serum FBG after 24 weeks post-treatment were still lower than pre-treatment levels. In sustained responders, fasting insulin (P = 0.007), C-peptide (P < 0.001) and HOMA-IR (P < 0.001) significantly decreased, and the insulin sensitivity index (ISI) increased (P < 0.001) at the end of the treatment comparing with pre-treatment levels, while no significant difference was observed in non-responder group. HOMA-ß values were increased in both groups at the end of treatment (both P < 0.001). CONCLUSION: The total serum FBG level in HCV infected patients was higher than that in healthy controls. Clearance of HCV was associated with reduced glucose and improved insulin resistance.

Epidemiological study of hepatitis B and hepatitis C infections in Northeastern China and the beneficial effect of the vaccination strategy for hepatitis B: a cross-sectional study.

BACKGROUND: Viral hepatitis, mainly hepatitis B and C, is a serious public health problem worldwide. In China, the prevalence of hepatitis B virus (HBV) infection remains high, while that of hepatitis C virus (HCV) infection is controversial. This study investigated the epidemiology of HBV and HCV infections and assessed the beneficial effect of the vaccination strategy for hepatitis B in Northeastern China. METHODS: From June 2016 to August 2016, 6541 residents of Changchun in Northeastern China were recruited for this cross-sectional study. Demographic characteristics as well as HBV and HCV serological test results were reviewed and analyzed. RESULTS: Among all study participants, 3.8% and 0.36% tested positive for hepatitis B surface antigen (HBsAg) and anti-HCV, respectively. The HBsAg- and anti-HCV-positive rates were significantly higher in male participants (4.58% and 0.43%) than in female individuals (3.0% and 0.33%). Notably, among all age groups, the lowest rate of HBsAg positivity (0.2%) was found in children born after the implementation of the vaccination strategy for hepatitis B. Conversely, participants aged 40-49 years had significantly greater positive rates of HBsAg (5.9%) compared with those of other age groups. Furthermore, the highest rates of anti-HCV positivity (1.1%) were observed in participants aged 50-59 years. CONCLUSIONS: The rate of HBsAg-positivity declined significantly following successful implementation of the policy on hepatitis B vaccination, indicating a beneficial impact on the control of HBV infection. However, only a slight decrease was observed in the anti-HCV-positivity rate, identifying an area in need of improvement within viral hepatitis prevention and control programs in China.

Accuracy of M2BPGi, compared with Fibro Scan®, in analysis of liver fibrosis in patients with hepatitis C.

BACKGROUND: Mac-2 Binding Protein Glycosylation isomer (M2BPGi) is a novel serological glyco-biomarker for staging liver fibrosis. Here, we aimed to evaluate the efficiency of serum M2BPGi in identifying liver fibrosis stages in Chinese patients with chronic hepatitis C infection. METHODS: Serum M2BPGi levels were evaluated in 680 patients with chronic hepatitis C and 164 healthy controls who underwent the Fibro Scan® test of liver fibrosis. The diagnostic accuracy of serum M2BPGi values was compared to that of other fibrosis markers, including Fibro Scan®, the aspartate transaminase to platelet ratio index (APRI), the fibrosis index based on four factors (FIB4), and the gamma-glutamyltranspeptidase to platelet ratio (GPR). RESULTS: Among the chronic hepatitis C patients, the median serum M2BPGi level increased with increasing fibrosis score as follows: 0.88 (≤F2), 1.70 (F2/F3), and 5.68 (cirrhosis). M2BPGi concentrations could also distinguish between healthy controls (0.38 ± 0.24) and hepatitis C patients (1.57 ± 2.28). After adjusting for potential confounders, M2BPGi was the most significant factor associated with the liver stiffness measurement (effect size = 0.275, P < 0.001). The optimum cutoff values of serum M2BPGi for patients with F2 and F4 were 0.945 and 1.355, respectively. The area under the curve of serum M2BPGi for prediction of significant fibrosis (F ≥ 4) using was comparable to that of APRI (0.892 vs. 0.873), while it was superior to that of other alternative markers, including FIB4 (0.818) and GPR (0.851). Compared with other non-invasive markers, M2BPGi had the greatest specificity for diagnosing cirrhosis and cirrhosis in hepatitis C patients. CONCLUSIONS: Our results suggest that the level of serum M2BPGi would be a simple and reliable diagnostic tool for identifying liver fibrosis stage in Chinese patients with chronic hepatitis.

Sustained viral response and treatment-induced cytopenia correlate with SLCs and KLF12 genotypes in interferon/ribavirin-treated Chinese chronic hepatitis C patients.

BACKGROUND AND AIM: Genetic variations in solute carrier (SLC) genes are associated with liver diseases, and Kruppel-like factor 12 (KLF12) affects the b chain of hemoglobin. We investigated possible correlations of SLC and KLF12 polymorphisms with viral clearance (spontaneous and treatment-induced) and adverse effects in Chinese chronic hepatitis C (CHC) patients. METHODS: We genotyped the single nucleotide polymorphisms in 525 CHC patients, 137 patients with spontaneous clearance, and 207 healthy controls. Three hundred fifty-seven CHC patients received recombinant interferon-alpha2b/ribavirin (IFN-α2b/RBV) treatment, and 175 patients were chosen for analysis of drug-induced cytopenia. All raw P-values were corrected by the Bonferroni method. RESULTS: A higher rate of sustained viral response was detected in patients with SLC4A11 rs3810560 CC variant versus TT/TC variant (76.9% vs 59.2%; OR, 2.42; 95% CI, 1.06-5.56, P = 0.037 after adjustment), but there was no significant difference among different hepatitis C virus genotypes. RBV-induced anemia was independently correlated with SLC29A1 rs760370 AA genotype (OR, 2.90; 95% CI, 1.29-6.54, P = 0.010), and the severity of IFN-induced thrombocytopenia was related to GG genotype (OR, 4.98; 95% CI, 1.27-19.61; P = 0.021); the detected effects held true for HCV-2a patients but weakened in HCV-1b patients. A reactive increase in platelet count was closely associated with KLF12 rs9543524 TT variant. CONCLUSION: SLC4A11 rs3810560 polymorphism independently affected the sustained viral response rates in CHC patients, whereas SLC29A1 rs760370 and KLF12 rs9543524 single nucleotide polymorphisms correlated with treatment-induced adverse events. Clearly, the predictive power varied with HCV genotypes and the reason for genotype-dependent discrepancy was not fully understood.

CD24 Ala57Val polymorphism is associated with spontaneous viral clearance in the HCV-infected Chinese population.

BACKGROUND & AIMS: Host immune response to hepatitis C virus (HCV) is a vital factor involved in both viral clearance and liver disease pathogenesis. CD24 plays an important role in inflammation and immune response and CD24 polymorphisms are associated with risk and progression of chronic hepatitis B virus infection. Our study evaluated whether CD24 polymorphisms affect HCV clearance. METHODS: We genotyped 544 chronic hepatitis C (CHC) patients, 78 spontaneous hepatitis C clearance (SHC) patients and 215 healthy controls for CD24 gene variants at positions -P534, P170, P1527 and IFNL3 rs12979860 by pyrosequencing. In CHC patients, 362 individuals were treated with a recombinant IFN-α2b/ribavirin combination for 48 weeks and were followed up for an additional 24 weeks. Lymphocyte CD24 expression was analysed by flow cytometry. RESULTS: We show that P170 CT and CT/TT genotypes were over-represented in the SHC group compared to CHC patients (62.8% vs. 47.2% and 75.6% vs. 60.3%, for respective polymorphisms). In multivariate logistic analysis, P170 (CD24 Ala57Val) polymorphism was an independent predictor of SHC (adjusted OR = 2.11, 95%CI = 1.19-3.73, P = 0.010 for CT genotype; OR = 2.01, 95%CI = 1.15-3.49, P = 0.014 for CT/TT genotype). No significant associations were found between the CD24 polymorphisms and treatment-induced viral clearance in log-rank analysis and Cox regression analysis. Patients with the CT/TT genotype had greater T-cell CD24 expression than patients with the CC genotype. CONCLUSIONS: Our findings suggest that CD24 Ala57Val polymorphism and associated variations in CD24 expression may be an important predictor for SHC, but have no effect on antiviral drug treatment response in Chinese CHC patients.

Use of parenteral caffeinum natrio-benzoicum: an underestimated risk factor for HCV transmission in China.

BACKGROUND: Fuyu city in China has a high prevalence of hepatitis C virus (HCV) infection resulting in a high morbidity and mortality from chronic liver disease and hepatocellular carcinoma. This study was conducted to identify the risk factors for HCV infection in Fuyu city. METHODS: Recruitment of study subjects involved a cross-sectional survey using non-random, convenience sampling. Information on demographic variables, risk factors for HCV infection, clinical manifestations, behavioral practices and family history was collected by administering a questionnaire. Anti-HCV antibody was detected using Abbott ARCHITECT i2000SR. HCV infection was confirmed by HCV-RNA testing by the Roche Taqman HCV test. Univariate and multivariate analyses were performed to identify the factors associated with HCV infection. RESULTS: Out of 3,228 persons that participated in the survey, 3,219 were enrolled in the study. The prevalence of HCV infection was 42.1 % (1355/3219). Among 734 patients with chronic HCV infection whose HCV-RNA genotyping was performed, genotype 1b was the most common (58.0 %), followed by genotype 2a (40.2 %), while co-infection with genotypes 1b and 2a was detected in 1.8 % of the subjects. On univariate analysis, male gender, older age, parenteral caffeinum natrio-benzoicum and share syringes (PCNBSS), and nine other factors were significantly associated with HCV infection. After adjusting for potential confounders, male gender, old age, cigarette smoking, lower education level, history of blood transfusion, blood donation, prior dental surgery, and PCNBSS were found to be independently associated with HCV infection. CONCLUSIONS: The prevalence of HCV infection is likely to be high among residents in Fuyu and we observed that genotypes 1b and 2a dominated in the city. Our findings support the hypothesis that PCNBSS which became endemic in Fuyu city during 1970s-1980s is strongly associated with HCV positivity.

Exploring Female Relatives of Patients with Hemophilia' Awareness, Attitudes, and Understanding Towards Genetic Testing.

Purpose: A better understanding of the factors that influence engagement is needed to provide a reference for conducting genetic testing in female relatives of patients with hemophilia (PWH). We therefore determined the perceptions and understanding of genetic testing among female relatives of PWH in China. Methods: We carried out a qualitative study using in-depth, semi-structured interviews with 11 female relatives of PWH in Shanxi Province, China. The resulting data were analyzed using thematic analyses. Results: This study extracted four topics: uncertainty about carrier genetic status; limited understanding of genetic testing; coexistence of positive and negative coping; and multi-aspect demands. Conclusion: Healthcare professionals should provide personalized and multidimensional health education and comprehensive decision-making support to female relatives of PWH, to enhance their motivation and willingness to undergo genetic testing. It is also important to actively improve relevant policies, strengthen the genetic testing service system, and promote the popularization of genetic testing in female relatives of PWH.

Bisphenol-A-diglycidyl ether modified chitosan/nano-SiO2 via hydrothermal process: A statistical modeling and adsorption mechanism for reactive orange 16 dye removal.

In this study, chitosan/nano SiO2 (CTS/NS) was chemically modified with bisphenol A diglycidyl ether (BADGE) cross-linker-assisted hydrothermal process to create an effective adsorbent, CTS-BADGE/NS, for the removal of reactive orange 16 (RO16) dye from aquatic systems. Box-Behnken design (BBD) was used to optimize the adsorption process by varying the adsorbent dose (0.02-0.1 g/100 mL), pH (4-10), and time (20-360 min). The adsorption isotherm results indicated that the Langmuir model fits the experimental data well, suggesting that the adsorption process involves a monolayer formation of RO16 on the surface of CTS-BADGE/NS. The kinetic modeling of RO16 adsorption by CTS-BADGE/NS demonstrated that the pseudo-first-order model fits the adsorption data. CTS-BADGE/NS achieved an adsorption capacity of 97.8 mg/g for RO16 dye at optimum desirability functions of dosage 0.099 g/100 mL, solution pH of 4.44, and temperature of 25 °C. Overall, the π-π electron donor-acceptor system significantly improved the adsorption performance of the CTS-BADGE/NS. The results of the regeneration investigation demonstrate that the CTS-BADGE/NS exhibits effective adsorption of RO16, even after undergoing five consecutive cycles. The results of this study suggest that the developed CTS-BADGE/NS composite can be a promising adsorbent for water purification applications.