Predictive models for functional cure in patients with CHB receiving PEG-IFN therapy based on HBsAg quantification through meta-analysis.

BACKGROUND AND AIMS: The efficacy of achieving HBsAg clearance through pegylated interferon (PEG-IFNα) therapy in patients with chronic hepatitis B (CHB) remains uncertain, especially regarding the probability of achieving functional cure among patients with varying baseline HBsAg levels. We aimed to investigate the predictive value of HBsAg quantification for HBsAg seroclearance in CHB patients undergoing PEG-IFNα treatment. METHODS: A systematic search was conducted in PubMed, Embase, and the Cochrane Library up to January 11, 2022. Subgroup analyses were performed for HBeAg-positive and HBeAg-negative patients, PEG-IFNα monotherapy and PEG-IFNα combination therapy, treatment-naive and treatment-experienced patients, and patients with or without liver cirrhosis. RESULTS: This predictive model incorporated 102 studies. The overall HBsAg clearance rates at the end of treatment (EOT) and the end of follow-up (EOF) were 10.6% (95% CI 7.8-13.7%) and 11.1% (95% CI 8.4-14.1%), respectively. Baseline HBsAg quantification was the most significant factor. According to the model, it is projected that when baseline HBsAg levels are 100, 500, 1500, and 10,000 IU/ml, the HBsAg clearance rates at EOF could reach 53.9% (95% CI 40.4-66.8%), 32.1% (95% CI 24.8-38.7%), 14.2% (95% CI 9.8-18.8%), and 7.9% (95% CI 4.2-11.8%), respectively. Additionally, treatment-experienced patients with HBeAg-negative status, and without liver cirrhosis exhibited higher HBsAg clearance rates after PEG-IFNα treatment. CONCLUSION: A successful predictive model has been established to predict the achievement of functional cure in CHB patients receiving PEG-IFNα therapy.

Prediction model for hepatitis B e antigen seroconversion in chronic hepatitis B with peginterferon-alfa treated based on a response-guided therapy strategy.

BACKGROUND: Models for predicting hepatitis B e antigen (HBeAg) seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) after nucleos(t)ide analog treatment are rare. AIM: To establish a simple scoring model based on a response-guided therapy (RGT) strategy for predicting HBeAg seroconversion and hepatitis B surface antigen (HBsAg) clearance. METHODS: In this study, 75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa (PEG-IFNα) treatment and a 24-wk follow-up. Logistic regression analysis was used to assess parameters at baseline, week 12, and week 24 to predict HBeAg seroconversion at 24 wk post-treatment. The two best predictors at each time point were used to establish a prediction model for PEG-IFNα therapy efficacy. Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0. RESULTS: The two most meaningful predictors were HBsAg ≤ 1000 IU/mL and HBeAg ≤ 3 S/CO at baseline, HBsAg ≤ 600 IU/mL and HBeAg ≤ 3 S/CO at week 12, and HBsAg ≤ 300 IU/mL and HBeAg ≤ 2 S/CO at week 24. With a total score of 0 vs 2 at baseline, week 12, and week 24, the response rates were 23.8%, 15.2%, and 11.1% vs 81.8%, 80.0%, and 82.4%, respectively, and the HBsAg clearance rates were 2.4%, 3.0%, and 0.0%, vs 54.5%, 40.0%, and 41.2%, respectively. CONCLUSION: We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNα therapy.

Quaternary stratigraphy and paleoenvironmental evolution of the Ningbo Coastal Plain revealed by core Z02.

The Quaternary sediment in the Ningbo Coastal Plain was the deposit due to sea-land interaction, which recorded information of past climate changes. The region is therefore an ideal area to study paleoclimate changes and sedimentary characteristics. We determined the stratigraphic division and paleoenvironmental evolution based on 14C and paleomagnetic dating, along with detailed analyses of lithology, pollen assemblage, foraminifera and ostracodes assemblage, and grain size of sediment in core Z02 located in the southeastern Ningbo Coastal Plain. The results showed that the boundary between the Holocene and Upper Pleistocene in the core Z02 record was at 30.5 m, the boundary between the Upper and Middle Pleistocene was at 82.65 m, and the boundary between the Quaternary and Lower Cretaceous was at 90 m. The Middle Pleistocene section of the core contained few sediments, while the Lower Pleistocene section was completely missed. During the late Pleistocene, the hydrodynamic conditions experienced energy levels of medium to medium low to medium, and sedimentary facies changed from alluvial lake to overbank to river to lake to alluvial lake to lake to overbank. During the Holocene, the hydrodynamic changes experienced energy levels of medium low to low to medium, and the sedimentary facies changed from shoreland to shallow sea to shoreland lake. The Ningbo Coastal Plain had experienced tectonic uplift, weathering and erosion stage in the Early and Middle Pleistocene, from warm and humid to dry in the Late Pleistocene, and from warm and humid to dry and cool in the Holocene, as revealed by the core Z02 record. This study provided useful information in investigating past environmental changes in the subtropical coastal region of eastern China.

One-Step Chemical Vapor Deposition Synthesis of 3D N-doped Carbon Nanotube/N-doped Graphene Hybrid Material on Nickel Foam.

3D hybrid nanostructures connecting 1D carbon nanotubes (CNTs) with 2D graphene have attracted more and more attentions due to their excellent chemical, physical and electrical properties. In this study, we firstly report a novel and facile one-step process using template-directed chemical vapor deposition (CVD) to fabricate highly nitrogen doped three-dimensional (3D) N-doped carbon nanotubes/N-doped graphene architecture (N-CNTs/N-graphene). We used nickel foam as substrate, melamine as a single source for both carbon and nitrogen, respectively. The morphology and microstructure were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, isothermal analyses, X-ray photoelectron microscopy and Raman spectra. The obtained 3D N-CNTs/N-graphene exhibits high graphitization, a regular 3D structure and excellent nitrogen doping and good mesoporosity.

Interferon-α-induced CD100 on naïve CD8+ T cells enhances antiviral responses to hepatitis C infection through CD72 signal transduction.

Objectives We investigated the effects of CD100 on naïve CD8+ T cells during hepatitis C virus (HCV) infection after interferon-α (IFN-α) therapy to clarify the mechanism underlying the effect of IFN-α in enhancing the antiviral response. Methods The CD100 molecules on subsets of CD8+ T cells were analysed with flow cytometry. The effects of CD100-overexpressing naïve CD8+ T cells were determined with ELISAs and an MTT cytotoxicity assay. The role of CD100-CD72 signal transduction was analysed with a neutralization and transwell assays. Results HCV infection reduced CD100 expression on CD8+ T cells, whereas IFN-α treatment significantly increased CD100 expression on naïve CD8+ T cells. The increased CD100 interacted with the CD72 receptor and enhanced PBMC cytokine secretion (IFN-γ and tumour necrosis factor-α) and cytotoxicity. Conclusions IFN-α-induced CD100 on naïve CD8+ T cells promotes PBMC cytokine secretion and cytotoxicity through CD100-CD72 signalling during HCV infection.

DNA-binding and photoactivated enantiospecific cleavage of chiral polypyridyl ruthenium(II) complexes.

A series of enantiomeric polypyridyl ruthenium(II) complexes Delta- and Lambda-[Ru(bpy)2CNOIP](PF6)2 (Delta-1 and Lambda-1; BPY=2,2'-bipyridine, CNOIP=2-(2-chloro-5-nitrophenyl)imidazo[4,5-f][1,10]phenanthroline), Delta- and Lambda-[Ru(bpy)2HPIP](PF6)2 (Delta-2 and Lambda-2; HPIP=2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline), Delta- and Lambda-[Ru(bpy)2DPPZ](PF6)2 (Delta-3 and Lambda-3; DPPZ=dipyrido[3,2:a-2',3':c]-phenazine), Delta- and Lambda-[Ru(bpy)2TAPTP](PF6)2 (Delta-4 and Lambda-4; TAPTP=4,5,9,18-tetraazaphenanthreno[9,10-b] triphenylene) have been synthesized. Binding of these chiral complexes to calf thymus DNA has been studied by spectroscopic methods, viscosity, and equilibrium dialysis. The experimental results indicated that all the enantiomers of these complexes bound to DNA through an intercalative mode, but the binding affinity of each chiral complex to DNA was different due to the different shape and planarity of the intercalative ligand. After binding to DNA, the luminescence property of complex 1 was distinctly different from complexes 2 to 4. Upon irradiation at 302 nm, complexes 2-4 were found to promote the cleavage of plasmid pBR 322 DNA from supercoiled form I to nicked form II, and obvious enantioselectively was observed on DNA cleavage for the enantiomers of complexes 2 and 4. The mechanisms for DNA cleavage by these enantiomeric complexes were also proposed.