PegIFN alpha-2a reduces relapse in HBeAg-negative patients after nucleo(s)tide analogue cessation: A randomized-controlled trial.

BACKGROUND & AIMS: Nucleo(s)tide analogue (NUC) cessation can lead to HBsAg clearance but also a high rate of virological relapse. However, the effect of pegylated interferon alpha-2a (PegIFN-α-2a) on virological relapse after NUC cessation is unknown. Therefore, this study aimed to evaluate the effect of switching from NUC to PegIFN-α-2a treatment for 48 weeks on virological relapse until week 96. METHODS: In this multicentre randomized controlled clinical trial, 180 non-cirrhotic HBeAg-negative chronic hepatitis B patients on continuous NUC therapy for ≥ 2.5 years with HBV DNA levels < 60 IU/mL were randomized to discontinue NUC (n=90) or receive 48 weeks of PegIFN-α-2a treatment (n=90) and followed up till 96 weeks. The primary endpoint was the virological relapse rate until week 96. RESULTS: Intention-to-treat analysis revealed patients in the interferon monotherapy group had significantly lower cumulative virological relapse rates than the NUC cessation group until week 96 (20.8% vs. 53.6%, P < 0.0001). Consistently, a significantly lower proportion of patients in the interferon monotherapy group had virological relapse than those in the NUC cessation group at 48 weeks off treatment (17.8% vs. 36.7%, P = 0.007). The virological relapse rate positively correlated with HBsAg levels in the NUC cessation group. The interferon monotherapy group had a lower cumulative clinical relapse rate (7.8% vs. 20.9%, P = 0.008) and a higher HBsAg loss rate (21.5% vs. 9.0%, P = 0.03) than the NUC cessation group. CONCLUSIONS: Switching from NUC to PegIFN-α-2a treatment for 48 weeks significantly reduces virological relapse rates and achieves higher HBsAg loss rates than NUC treatment cessation alone in HBeAg-negative chronic hepatitis B patients. IMPACT AND IMPLICATIONS: Nucleo(s)tide analogue (NUC) cessation can lead to HBsAg clearance but also a high rate of virological relapse, but an optimised scheme to reduce the virological relapse rate after NUC withdrawal is yet to be reported. This randomized controlled trial investigated the effect of switching from NUC to PegIFN-α-2a treatment for 48 weeks on virological relapse until week 96 in HBeAg-negative chronic hepatitis B patients. The interferon monotherapy group had a significantly lower cumulative virological relapse rate (20.8% vs. 53.6%, P < 0.0001) and higher HBsAg loss rate (21.5% vs. 9.0%, P= 0.03) than the NUC cessation group until week 96. This provides an optimized strategy for NUC cessation in HBeAg-negative patients. TRIAL REGISTRATION NUMBER: NCT02594293.

Inhibition effect of copper-bearing metals on arterial neointimal hyperplasia via the AKT/Nrf2/ARE pathway in vitro and in vivo.

In-stent restenosis can be caused by the activation, proliferation and migration of vascular smooth muscle cells (VSMCs), which affects long-term efficacy of interventional therapy. Copper (Cu) has been proved to accelerate the endothelialization and reduce thrombosis formation, but little is known about its inhibition effect on the excessive proliferation of VSMCs. In this study, 316L-Cu stainless steel and L605-Cu cobalt-based alloy with varying Cu content were fabricated and their effects on surface property, blood compatibility and VSMCs were studied in vitro and in vivo. CCK-8 assay and EdU assay indicated that the Cu-bearing metals had obvious inhibitory effect on proliferation of VSMCs. Blood clotting and hemolysis tests showed that the Cu-bearing metals had good blood compatibility. The inhibition effect of the Cu-bearing metals on migration of cells was detected by Transwell assay. Further studies showed that Cu-bearing metals significantly decreased the mRNA expressions of bFGF, PDGF-B, HGF, Nrf2, GCLC, GCLM, NQO1 and HO1. The phosphorylation of AKT and Nrf2 protein expressions in VSMCs were significantly decreased by Cu-bearing metals. Furthermore, it was also found that SC79 and TBHQ treatments could recover the protein expressions of phospho-AKT and Nrf2, and their downstream proteins as well. Moreover, 316L-Cu stent proved its inhibitory action on the proliferation of VSMCs in vivo. In sum, the results demonstrated that the Cu-bearing metals possessed apparent inhibitory effect on proliferation and migration of VSMCs via regulating the AKT/Nrf2/ARE pathway, showing the Cu-bearing metals as promising stent materials for long-term efficacy of implantation.

Biodegradable high-nitrogen iron alloy anastomotic staples: In vitro and in vivo studies.

For gastrointestinal anastomosis, metallic biodegradable staples have a broad application potential. However, both magnesium and zinc alloys have relatively low strength to withstand the repeated peristalsis of the gastrointestinal tract. In this study, we developed a novel kind of biodegradable high-nitrogen iron (HN-Fe) alloy wires (0.23 mm), which were fabricated into the staples. The tensile results showed that the ultimate tensile strength and elongation of HN-Fe wires were 1023.2 MPa and 51.0 %, respectively, which was much higher than those of other biodegradable wires. The degradation rate in vitro of HN-Fe wires was slightly higher than that of pure Fe wires. After 28 days of immersion, the tensile strength of HN-Fe wires remained not less than 240 MPa, meeting the clinical requirements. Furthermore, sixteen rabbits were enrolled to conduct a comparison experiment using HN-Fe and clinical Ti staples for gastroanastomosis. After 6 months of implantation, a homogeneous degradation product layer on HN-Fe staples was observed and no fracture occurred. The degradation rate of HN-Fe staples in vivo was significantly higher than that in vitro, and they were expected to be completely degraded in 2 years. Meanwhile, both benign cutting and closure performance of HN-Fe staples ensured that all the animals did not experience hemorrhage and anastomotic fistula during the observation. The anastomosis site healed without histopathological change, inflammatory reaction and abnormal blood routine and biochemistry, demonstrating good biocompatibility of HN-Fe staples. Thereby, the favorable performance makes the HN-Fe staples developed in this work a promising candidate for gastrointestinal anastomosis.

Synthesis and evaluation of L-quebrachitol derivatives against platelet aggregation.

Thrombosis plays an important role in the occurrence and development of cardiovascular and cerebrovascular diseases that contribute to high mortality and morbidity in patients. L-(-)-Quebrachitol (QCT), a natural product, was first isolated from quebracho bark. It can inhibit PAF receptor and decrease gastric damage induced by indomethacin, as a drug against platelet aggregation. Here, five QCT derivatives were synthesized and investigated for their inhibitory effects on platelet aggregation. Among them, compound 3a showed anticoagulant effects comparable to aspirin, while compound 4b showed dose-independent inhibitory activities in rats that were stronger than aspirin.

M6A-mediated upregulation of HOXC10 promotes human hepatocellular carcinoma development through PTEN/AKT/mTOR signaling pathway.

Human Hox genes (Homeobox) play a crucial role in embryonic development and cancer. The HOXC10 gene, a member of the HOX family, has been reported abnormally expressed in several cancers. However, the association between HOXC10 and hepatocellular carcinoma (HCC) remains to be elucidated. In the present study, tissue microarray cohort data showed that high levels of HOXC10 expression predicted a poor survival in HCC patients. Meanwhile, HOXC10 was significantly upregulated in the Huh7 cell line compared with the well differentiated cell line HepG2 and human normal liver cells. Functionally, silencing HOXC10 in Huh7 cells inhibited cell proliferation, increased apoptosis, and inhibited invasion and migration of HCC cells. HOXC10 overexpression in HepG2 cells increased cell proliferation, decreased apoptosis, and increased invasion and migration of HCC cells. In the HepG2 xenograft models, HOXC10 increased the tumor volume and weight compared with control. Mechanistically, the m6A modification of HOXC10 by METTL3 enhanced its expression by enhancing its mRNA stability. Both the in vitro and in vivo results showed that overexpressed HOXC10 activated the PTEN/AKT/mTOR pathway. In summary, the findings highlight the importance of HOXC10 in the regulation of HCC progression. HOXC10 is potentially a future therapeutic target for HCC treatment.

[Sulfonated magnetic graphite carbon nitride solid-phase extraction-ultra performance liquid chromatography-tandem mass spectrometry for screening malachite green and leucomalachite green in freshwater fish].

Malachite green (MG) and its metabolite, leucomalachite green (LMG), exert toxic effects on the human body. The use of these dyes is illegal, but they are still detected in aquatic products. Freshwater fish are aquatic products with the high non-qualified rates. Therefore, the sensitive screening of MG and LMG in freshwater fish is of great importance to ensure the safety of aquatic products. Owing to the low contents of MG and LMG in fish and the complex matrix of actual samples, sample preparation is required before detection to purify impurities and enrich the target compounds. Graphite carbon nitride (GCN), a polymer material composed of C, N, and H, has good chemical and thermal stability, a large specific surface area, and a large number of active sites. It has a wide range of application prospects in adsorption and can be used in food safety testing when compounded with Fe3O4 to form magnetic graphite carbon nitride (MGCN). In this study, sulfonated magnetic graphite carbon nitride (S-MGCN) was prepared by further functionalizing MGCN with sulfonic acid. After characterization by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and vibrating sample magnetometry (VSM), a magnetic solid-phase extraction (MSPE) method based on S-MGCN was established to extract MG and LMG from freshwater fish. The targets were screened using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Following sulfonic acid functionalization, S-MGCN showed increased electrostatic interactions based on the MGCN adsorption mechanism, which includes hydrogen bonds and π-π interactions; thus, its adsorption efficiency was significantly improved. The matrix effects were -42.21% and -33.77% before functionalization, -11.40% and -7.84% after functionalization, thus confirming that S-MGCN has significant matrix removal ability. Given that S-MGCN demonstrated excellent efficiency as an MSPE adsorbent, the adsorption conditions for S-MGCN were optimized. The optimal conditions were as follows: adsorbent dosage, 15 mg; adsorption time, 2 min; solution pH, 5; and ionic strength, not adjusted. Under these conditions, the adsorption efficiency of S-MGCN could reach 94.2%. Different organic solvents were used to elute adsorbed MG and LMG, and the desorption efficiency peaked when 1%(v/v) ammonia acetonitrile was used as the elution solvent. The elution volume was also optimized, and a maximum desorption efficiency of 93.2% was obtained when 1 mL of 1%(v/v) ammonia acetonitrile was added to S-MGCN. The limits of detection (LODs) and quantification (LOQs) of the two targets were determined at signal-to-noise ratios (S/N) of 3 and 10, respectively. The LODs and LOQs were 0.075 µg/kg and 0.25 µg/kg, respectively. The linear ranges of the two target compounds were 0.25-20.0 µg/kg with correlation coefficients (r) greater than 0.998. To assess accuracy and precision, we prepared spiked samples at three levels (low, medium, and high) with six parallel samples per level (n=6). The recoveries ranged from 88.8% to 105.9%. The intra- and inter-day relative standard deviations were 5.4%-13.7% (n=6) and 3.3%-11.1% (n=3), respectively. Compared with the national standard method, the proposed method features simpler sample pretreatment procedures, less use of organic reagents (5 mL), and a shorter extraction time (2 min); moreover, the method does not require complicated elution steps, and the eluent can be directly analyzed by UPLC-MS/MS. The test results of actual samples were consistent with those obtained via the national standard method, thus confirming the practical feasibility of the developed method. The proposed MSPE method based on S-MGCN is an efficient and environmentally friendly method that could provide a new methodological reference for the sensitive screening of MG and LMG in actual samples.

Effective oxygen metabolism-based prognostic signature for colorectal cancer.

Backgroud: Oxygen metabolism is an important factor affecting the development of tumors, but its roles and clinical value in Colorectal cancer are not clear. We developed an oxygen metabolism (OM) based prognostic risk model for colorectal cancer and explored the role of OM genes in cancer. Methods: Gene expression and clinical data obtained from The Cancer Genome Atlas, Clinical Proteomic Tumor Analysis Consortium databases were consider as discovery and validation cohort, respectively. The prognostic model based on differently expressed OM genes between tumor and GTEx normal colorectal tissues were constructed in discovery cohort and validated in validation cohort. The Cox proportional hazards analysis was used to test clinical independent. Upstream and downstream regulatory relationships and interaction molecules are used to clarify the roles of prognostic OM genes in colorectal cancer. Results: A total of 72 common differently expressed OM genes were detected in the discovery and validation set. A five-OM gene prognostic model including LRT2, ATP6V0E2, ODC1, SEL1L3 and VDR was established and validated. Risk score determined by the model was an independent prognostic according to routine clinical factors. Besides, the role of prognostic OM genes involves transcriptional regulation of MYC and STAT3, and downstream cell stress and inflammatory response pathways. Conclusions: We developed a five-OM gene prognostic model and study the unique roles of oxygen metabolism in of colorectal cancer.

Kinetics changes in total cholesterol predict HBeAg seroconversion in chronic hepatitis B patients treated with pegylated interferon-alfa.

There is no satisfactory standard for predicting HBeAg seroconversion during Pegylated interferon alpha (PegIFNα) treatment. Studies have shown that IFNα therapy in chronic hepatitis C patients could alter serum lipid profiles. However, there have been no studies on lipid changes that predict the outcome of PegIFNα monotherapy in treated-naive chronic hepatitis B (CHB) patients. This retrospective study included 130 treated-naive HBeAg-positive CHB patients receiving PegIFNα monotherapy. The relationship between serum lipid changes and HBeAg seroconversion was analysed. The TC-ALT-HBsAg-HBeAg-Genotype-Age (CASEGA) model was established to predict HBeAg seroconversion after PegIFN-α monotherapy. Among 130 patients, 33 achieved HBeAg seroconversion (SR) and 97 did not achieve HBeAg seroconversion (NR). The decrease in serum total cholesterol (TC) in the NR group was significantly higher than in the SR group at Week 24 (-9.59% vs. -0.31%, p < 0.001). Multivariate logistic regression analysis showed that the change in TC at Week 24 (odds ratio = 1.065, p = 0.009) was an independent predictor of HBeAg seroconversion. The area under the receiver operating characteristic curve for the CASEGA model was 0.883. The model score at the maximum Youden index was 90, and the specificity, sensitivity, positive predictive value and negative predictive value were 0.727, 0.794, 0.546 and 0.895, respectively. The HBeAg seroconversion rate at Week 72 in patients with scores >90 was significantly higher than that in patients with scores <90 (54.55% vs. 10.47%, p < 0.001). This study indicated that the change in the TC level at 24 weeks in CHB patients treated with PegIFNα was associated with HBeAg seroconversion. The CASEGA prediction model based on the TC change rate of 24 weeks has good predictive efficiency for HBeAg seroconversion.

Effect of nucleos(t)ide analogues on blood lipid profiles in patients with chronic hepatitis B: A cross-sectional survey.

This study aimed to explore the effects of the 3 nucleos(t)ide analogues (NAs) on lipid levels. We retrospectively included patients treated with NAs at 2 centers and collected their clinical data at their visiting points. Differences in blood lipid levels were analyzed by statistical methods, and factors related to hyperlipidemia were discussed. In these 2 centers, the prevalence rates of hypercholesterolemia were 12/181 (6.6%) for tenofovir alafenamide fumarate (TAF)-, 0/158 (0%) for tenofovir disoproxil fumarate (TDF)-, and 13/182 (7.1%) for entecavir (ETV)-treated individuals (P = .003). The prevalence rates of hypertriglyceridemia were 30/181 (16.6%) for TAF-, 11/158 (7.0%) for TDF-, and 26/182 (14.3%) for ETV-treated individuals (P = .025). In TAF (n = 181, 10 [6, 15] months), TDF (n = 158, 18 [7.5, 45] months), and ETV (n = 182, 24 [10, 60] months) groups, total cholesterol (TC) levels were 4.63 ±â€…0.91 mmol/L, 3.86 ±â€…0.61 mmol/L, and 4.53 ±â€…0.87 mmol/L, respectively; triglyceride (TG) levels were 1.27 ±â€…0.76 mmol/L, 0.87 ±â€…0.51 mmol/L, and 1.14 ±â€…0.67 mmol/L, respectively (P < .001). In multivariate regression analysis, factors associated with hypercholesterolemia were age (adjusted hazard risk [HR] = 1.055 [1.018-1.094]; P = .003) and body mass index (BMI) (adjusted HR = 0.817 [0.669-0.998]; P = .048). Factors associated with hypertriglyceridemia were TAF group (vs. TDF group) (adjusted HR = 0.405 [0.167-0.980]; P = .045), age (adjusted HR = 1.028 [1.002-1.055]; P = .038), and sex (adjusted HR = 0.190 [0.079-0.456]; P < .001). Among the patients treated with TAF (10 [6, 15] months), TDF (18 [7.5, 45] months), and ETV (24 [10, 60] months), the blood lipid levels in the TDF group were lower than those in the TAF group and ETV group, and the occurrence of hyperlipidemia was associated with age, sex, BMI, and different treatment.

Reduction of Hepatitis B Surface Antigen May Be More Significant in PEGylated Interferon-Alpha Therapy Combined with Nucleotide Analogues than Combined with Nucleoside Analogues in Chronic Hepatitis B Patients: A Propensity Score Matching Study.

Background: Nucleotide analogues (NTs) monotherapy may have a more significant effect on reducing hepatitis B surface antigen (HBsAg) than nucleoside analogues (NSs) due to their immunomodulatory function. However, this superiority remains unknown when combined with PEGylated interferon α (PegIFNα). Therefore, this study aimed to explore whether NTs have more significant antiviral effects than NSs in combination therapy with PegIFNα. Methods: Chronic hepatitis B (CHB) patients treated with PegIFNα plus nucleos(t)ide analogues (NAs) were retrospectively recruited. Efficacy and the predictors of hepatitis B surface antigen (HBsAg) reduction >1 log10 IU/mL after 48 weeks were analyzed. Results: A total of 95 patients were included and divided into the PegIFNα + NTs group and the PegIFNα + NSs group. Propensity score matching (PSM) was performed. The PegIFNα + NTs group had a greater reduction of HBsAg (-3.52 vs. -2.33 log10 IU/mL, P=0.032) and a higher proportion of patients with HBsAg reduction >1 log10 IU/mL (100.0% vs. 72.2%, P=0.003) even after PSM. However, HBsAg and hepatitis B e-antigen (HBeAg) loss rates, HBeAg seroconversion rates, degree of HBeAg and hepatitis B virus (HBV) DNA decline, HBV DNA undetectable rates, and alanine aminotransferase (ALT) normalization rates showed no significant differences. Subgroup analyses showed the difference in the reduction of HBsAg was particularly evident in HBeAg-positive and the "add-on" subgroups. PegIFNα plus NTs (OR = 36.667, 95% CI = 3.837-350.384) was an independent predictor for HBsAg reduction >1 log10 IU/mL after 48 weeks. Conclusion: This study suggests that PegIFNα plus NTs may lead to more HBsAg reduction, especially in HBeAg-positive and "add-on" patients.

The efficacy and safety of adding on or switching to peginterferon α-2b in HBeAg-positive chronic hepatitis B patients with long-term entecavir treatment: a multicentre randomised controlled trial.

BACKGROUND & AIMS: The strategies of adding on or switching to peginterferon (PEG-IFN) improved the serological response rates in patients with chronic hepatitis B (CHB) who had previously experienced treatment with nucleos(t)ide analogues. However, robust data on which combination strategy is more effective remain lacking. METHODS: In this multicentre, parallel, open-label, randomised, controlled trial, patients with HBeAg-positive CHB who were treated with entecavir ≥2 years, and had hepatitis B surface antigen (HBsAg) <3000 IU/ml, HBeAg <200S/CO and HBV DNA <50 IU/ml were randomly assigned in a 1:1:1 ratio to add on PEG-IFN, switch to PEG-IFN or continue entecavir monotherapy for 48 weeks. The primary endpoint was HBeAg seroconversion at week 48. RESULTS: A total of 153 patients were randomised into three treatment arms (50 in add-on, 52 in switch-to and 51 in monotherapy). Compared with continuous entecavir monotherapy, both add-on and switch-to strategies achieved higher rates of HBeAg seroconversion (18.0% vs. 2.0%, p = 0.007; 19.2% vs. 2.0%, p = 0.005, respectively), HBeAg loss (24.0% vs. 5.9%, p = 0.010; 23.1% vs. 5.9%, p = 0.013, respectively), HBsAg < 100 IU/ml (30.0% vs. 0%, p < 0.001; 34.6% vs. 0%, p < 0.001, respectively), and higher HBsAg reduction (-0.90 vs. -0.06 log10 IU/ml, p < 0.001; -0.92 vs. -0.06 log10 IU/ml, p < 0.001, respectively) at week 48. The efficacy was comparable between add-on and switch-to arms (p > 0.05). Adverse events were mainly related to PEG-IFN but generally tolerable. CONCLUSION: In patients with CHB who achieved virological response with long-term entecavir, both adding on and switching to PEG-IFN are alternative strategies resulting in higher rates of HBeAg seroconversion and HBsAg reduction than continuous entecavir. CLINICAL TRIALS REGISTRATION: Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR-IPR-17012055).

Prognosis factors of predicting survival in spontaneously ruptured hepatocellular carcinoma.

AIM: To investigate predictors affecting survival in patients with spontaneously ruptured hepatocellular carcinoma (srHCC). METHODS: One-hundred-and-twenty-seven patients experiencing srHCC between January 2010 and December 2020 were enrolled. The clinical features, treatments, and outcomes were reviewed. Statistics included univariate analysis, Kaplan-Meier analysis, multivariate analysis using Cox proportional hazards model and logistic regression model, and receiver operating characteristic (ROC) curve analysis. RESULTS: Of the 127 srHCC patients, 24, 42, and 61 patients received conservative treatment, surgical treatment, and transarterial chemoembolization/embolization (TACE/TAE) treatment at HCC rupture, respectively. The largest tumor size [hazard ratio (HR) 1.127; p < 0.001], Barcelona-Clinic Liver Cancer (BCLC) stage (HR 2.184, p = 0.023), international normalized ratio (INR; HR 3.895; p = 0.012), total bilirubin level (TBil; HR 1.014; p = 0.014), TACE after rupture (compared with conservative treatment) (HR 0.549; p = 0.029), TACE/TAE and surgery at rupture, and albumin level (HR 0.949; p = 0.017) were independent predictors affecting overall survival. A survival predictive model for HCC rupture (SPHR) using these predictors was created. ROC analysis showed that the area under the curve (AUC) of the SPHR model for 30 day survival was 0.925, and the AUCs of the model for end-stage liver disease (MELD) score and Child-Pugh score for 30 day survival were 0.767 and 0.757, respectively. CONCLUSION: The largest tumor size, advanced BCLC stage, higher INR and TBil, lower albumin, and conservative treatment were negative independent predictors for overall survival. The SPHR model may be more suitable than the MELD score and Child-Pugh score for predicting 30 day survival in srHCC.

Development and Validation of a Non-invasive Model to Predict Liver Histological Lesions in Chronic Hepatitis B Patients With Persistently Normal Alanine Aminotransferase and Detectable Viremia.

Background: A critical and controversial issue is whether antiviral therapy should be recommended in chronic hepatitis B virus (HBV) infection patients with persistently normal alanine aminotransferase (PNALT) and detectable HBV DNA. The study aimed to develop a non-invasive model for predicting significant liver histological changes (SLHC), which is the histological indication for antiviral therapy in chronic hepatitis B (CHB) patients with PNALT and detectable HBV DNA. Methods: 398 chronic HBV infection patients with PNALT and detectable HBV DNA who underwent liver biopsy were divided into the estimation set (n = 256) and validation set (n = 142). A multivariate logistic regression model was developed to predict SLHC in the estimation set, and the diagnostic performance was further validated in the validation set. Results: 132 patients (33.2%) with PNALT and detectable HBV DNA had SLHC. Aspartate aminotransferase (AST), cholinesterase (ChE), and liver stiffness measurement (LSM) were identified as the independent predictors of SLHC. The AUROC of the SLHC index, which combined AST, ChE, and LSM, was 0.824 and 0.816 in the estimation and validation set, respectively, for the prediction of SLHC. Applying the SLHC index ≤ 0.15, the presence of SLHC could be excluded with high negative predictive value in the estimation set (93.2%) and in the validation set (90.2%). Applying the SLHC index ≥ 0.55, the presence of SLHC could be considered with high positive predictive value in the estimation set (79.2%) and in the validation set (76.5%). Conclusion: The SLHC index provides a high accuracy in predicting liver histological indication for antiviral therapy in CHB patients with PNALT and detectable HBV DNA.

STAT4 genetic polymorphism significantly affected HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients receiving Peginterferon-α therapy: A prospective cohort study in China.

A variant in signal transducer and activator of transcription 4 (STAT4) was reported to correlate with the response of interferon-α (IFN-α) in a retrospective study in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (CHB) patients. Here, we conducted a prospective study to analyze the effect of STAT4 genetic polymorphism on the response of pegylated interferon-α-2a (PegIFN-α-2a) in HBeAg-positive patients. A prospective, multicenter, open-label, parallel cohort study was performed. One hundred and fifty treatment-naïve and 156 nucleos(t)ide analog (NA)-experienced HBeAg-positive CHB patients were enrolled, respectively. All patients received PegIFN-α-2a treatment for 48 weeks and 24-week follow-up post PegIFN-α-2a treatment. Before treatment, STAT4 genetic polymorphism was determined by PCR and DNA sequencing. Serological markers, serum HBV DNA levels, and adverse events were collected at each visit. We observed a larger reduction of HBV DNA load and a significantly higher HBeAg seroconversion rate in the GT/TT group than in the GG group at week 72 (p = 0.002 and p = 0.023) in treatment-naïve patients. In NA-experienced patients, the HBeAg seroconversion rate in the GT/TT group was higher than that in the GG group at week 72 (p = 0.005). STAT4 rs7574865 gene polymorphism was the strongest independent predictor of HBeAg seroconversion in both paralleled cohorts. Also, patients in the GT/TT group had a higher hepatitis B surface antigen loss rate than in the GG group in the study. There was no significant difference in adverse events between GG and GT/TT groups. This prospective cohort study confirmed that STAT4 rs7574865 gene polymorphism is associated with HBeAg seroconversion and HBsAg loss irrespective of naïve and NA-experienced HBeAg-positive CHB patients treated with PegIFN-α-2a.

Isolated sixth nerve palsy: a rare first presentation in multiple sclerosis.

True isolated sixth nerve palsy as the initial presentation of multiple sclerosis (MS) is rare. MS is a chronic inflammatory, immune-mediated disease of the central nervous system. This is the most common cause of neurological disability in young adults. Common symptoms include acute episodes of muscle weakness, altered sensation, balance and gait disturbances, visual loss and bladder dysfunction.Diagnosis of MS is supported with the incidence of symptomatic clinical episodes with subsequent cross-sectional imaging to confirm radiological lesions that are disseminated in space and time.In the following report, we discuss the case of a woman in her 30s who presented to ophthalmology with a sixth nerve palsy in the absence of ocular or systemic disease. This is the first presentation of MS, a rare clinical event.

Development and Validation of a New Integrative Score Based on Various Systemic Inflammatory and Nutritional Indicators in Predicting Prognosis in Patients With Resectable Esophageal Squamous Cell Carcinoma: A Retrospective Cohort Study.

BACKGROUND: Recent studies revealed that various inflammatory and nutritional indexes were associated with prognosis in esophageal cancer (EC). However, these studies only evaluated one or two indexes, and the prognostic value of these indexes individually or in combination is unclear. This study aimed to construct an integrative score based on various inflammatory and nutritional indexes for prognosis in resectable esophageal squamous cell carcinoma (ESCC). METHODS: A total of 421 consecutive patients were randomly divided into either a training or validation cohort at a ratio of 7:3 for retrospective analysis. Using logic regression analyses, independent risk factors from peripheral blood indexes were screened to construct an integrative score. The associations regarding the integrative score, clinical characteristics, cancer-specific survival (CSS), and overall survival (OS) were analyzed. RESULTS: Out of 20 indexes, hemoglobin (HB), C-reactive protein to albumin ratio (CAR), and platelet to lymphocyte ratio (PLR) were independent risk factors based on logical regression analyses. Then, an integrative score with the optimal cut-off value of .67 was established according to the Combination Of HB, CAR, and PLR (COHCP). The area under the curve (AUC) indicated higher predictive ability of COHCP on prognosis than other indicators. Multivariate analyses revealed that COHCP serves as an independent prognostic score. Patients with COHCP low group (≤.67) had better 5-year CSS (57.3% vs 13.5%, P < .001) and OS (51.1% vs 12.3%, P < .001) than those with high group, respectively. Finally, the nomogram based on COHCP was established and validated regarding CSS and OS, which can accurately and effectively predict individual survival in resected ESCC. CONCLUSION: The COHCP was a novel, simple, and useful predictor in resectable ESCC. The COHCP-based nomogram may accurately and effectively predict survival.

Thyroid dysfunction incidence and risk factors in Chinese chronic hepatitis B patients treated with pegylated interferon alpha: A long-term follow-up study.

The long-term impact, incidence and risk factors of thyroid dysfunction in chronic hepatitis B (CHB) patients receiving pegylated interferon (IFN) alpha (PegIFN-alpha) therapy remain unclear. We aim to investigate the long-term safety of thyroid dysfunction in CHB patients receiving PegIFN-alpha. A retrospective observational study of 425 CHB patients with normal baseline thyroid function was carried out. Patients were followed up over 10 years to assess thyroid function after receiving IFN. At the end of the IFN therapy, 67 patients (15.8%) had developed thyroid dysfunction, 31 patients (46.3%) had hyperthyroidism and 64.4% presented with subclinical thyroid dysfunction. In follow-up of thyroid dysfunction patients, 37 patients (74.0%) spontaneously regained normal thyroid function. Pretreatment thyroid-stimulating hormone (TSH) level, thyroid peroxidase antibody (TPOAb) positivity and free thyroxine (FT4) were independent risk factors associated with thyroid dysfunction incidence. High TSH level (OR = 9.866, 95%CI, 3.245-29.998) was associated with a greater likelihood of hypothyroidism. High FT4 levels (OR = 0.464, 95%CI, 0.248-0.868) indicate a low likelihood of thyroid dysfunction. Thyroid dysfunction is a common but acceptable side effect of IFN therapy for CHB. Most thyroid dysfunction is reversible. Pretreatment TSH level and TPOAb positivity are risk factors for thyroid dysfunction development during IFN therapy. A high TSH level predicts an increased incidence of hypothyroidism. Moreover, FT4 may be a protective factor for thyroid dysfunction.

Antibacterial and anti-inflammatory activities of chitosan/copper complex coating on medical catheters: In vitro and in vivo.

Copper ions (Cu) grafted chitosan coating was prepared using the pneumatic spraying method on the silicone rubber surface. Coating's surface properties, morphology, composition, Cu releasing behavior, antibacterial, and anti-inflammatory activities are investigated and discussed. Surface properties, composition, and morphology were investigated by scanning electron microscopy (SEM) and contact angle measurements. The antibacterial activity has been tested with Escherichia coli and Staphylococcus aureus suspensions in vitro. Besides, the morphology of the biofilm was inspected with a field emission SEM. To evaluate the anti-inflammatory activity and biosafety of the coating in vivo, the optimized coating samples and control groups were implanted subcutaneously into the back of mice. The bacterial environment model was established by injection of the bacterial suspension. The morphology and bacterial adhered on the surface of catheters and the surrounding tissues were analyzed after 5 days of implantation. As in vitro results, the number of adhered bacterial on the surface of the silicon rubber surface was decreased, and the anti-inflammatory rate was increased by the intensify of the Cu content in chitosan coating. As for in vivo results, after 5 days of implantation, there was no evident inflammation in the surrounding tissues of all catheters in all without the S. aureus injected group. In the injected chitosan/Cu coated group; the inflammation, the number of the adhered bacteria were observed less than other injected samples without Cu; no inflammation were noticeable. Results indicate that the Cu-modified chitosan coating can confer excellent antibacterial and anti-inflammatory activity as applied on medical catheters.

DIC Score Combined With CLIF-C OF Score Is More Effective in Predicting Prognosis in Patients With Hepatitis B Virus Acute-on-Chronic Liver Failure.

Coagulation and fibrinolysis disorders are major prognostic factors in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients. Here, we aimed to clarify the role of disseminated intravascular coagulation (DIC) scores in predicting HBV-ACLF patient prognosis. We assessed the DIC score from HBV-ACLF patients at Huashan Hospital in Shanghai, China from June 2013 to May 2021 and evaluated it in relation to short-term mortality, clinical course, and infection. A novel prognostic scoring model was proposed based on DIC scores. A total of 163 transplant-free HBV-ACLF patients were enrolled. DIC scores were higher in non-survivors than survivors (6 vs. 4, P = 0.000) and were independently associated with short-term mortality [hazard ratio (HR): 1.397, 95% confidence interval (95% CI): 1.040-1.875, P = 0.026]. DIC scores were associated with ACLF grade, clinical course, and infection. Moreover, they were correlated with model for end-stage liver disease (MELD) scores (r = 0.521, P < 0.001). The area under the receiver operating curve (auROC) of CLIF-C OF-DICs [a novel prognostic score based on age, DIC score, and Chronic liver failure-consortium organ function score (CLIF-C OFs)] for 90-day mortality was 0.936, which was higher than six other generic prognostic scoring models. These results were confirmed in a validation cohort (n = 82). In conclusion, elevated DIC score is associated with poor prognosis in HBV-ACLF patients, and can be used jointly with CLIF-C OFs to improve the accuracy of prognosis prediction.