Aspartate aminotransferase to platelet ratio at admission can predict the prognosis of patients with hemorrhagic fever with renal syndrome.

Early indicators are needed to predict the prognosis of patients with hemorrhagic fever with renal syndrome (HFRS). Aspartate aminotransferase to platelet ratio index (APRI) has been shown to be related to mortality risk of patients with various diseases. This study evaluated the prognostic value of APRI and other inflammatory scores in HFRS patients. Data of hospitalized HFRS patients from a tertiary hospital in northwest China were collected and the inflammatory scores such as APRI and neutrophil to lymphocyte count ratio (NLR) were calculated at the day of patient admission. Independent factors related to the survival of patients were determined by multivariate logistic regression. Receiver operating characteristic curve was used to analyze the predictive value, and area under the curve (AUC) and 95% confidence interval (CI) were calculated for quantification. Of the 317 HFRS patients included in study, 15 patients died. Age (OR: 1.10, 95% CI: 1.04-1.16, p = 0.001), NLR (OR: 1.11, 95% CI: 1.02-1.19, p = 0.01), and APRI (OR: 1.06, 95% CI: 1.03-1.10, p = 0.001) were quantitative objective factors independently associated with the survival of patients. APRI had an AUC of 0.95 (95% CI: 0.91-1.00, p < 0.001) for predicting the prognosis of patients, with a sensitivity of 93.3% and a specificity of 86.8%. The performance of APRI was better than that of age or NLR. Patients with an APRI ≥ 6.15 had significantly decreased survival compared with those with an APRI < 6.15. In conclusion, this simple index APRI calculated at admission can serve as a biomarker to identify HFRS patients at risk of poor prognosis.

Clinical and laboratory features and factors predicting disease severity in pediatric patients with hemorrhagic fever with renal syndrome caused by Hantaan virus.

The clinical features and factors associated with disease severity in children with hemorrhagic fever with renal syndrome (HFRS) have not been well characterized. This study analyzed the clinical and laboratory factors associated with disease severity in children with HFRS caused by Hantaan virus. Data in pediatric patients with HFRS were retrospectively collected from Xi'an Children's Hospital over a 9-year period. Independent factors associated with disease severity were identified. Nomogram predicting disease severity was constructed based on variables filtered by feature selection. In total, 206 children with HFRS were studied. Fever, digestive tract symptoms, headache, backache, bleeding, and renal injury signs were the common symptoms. Elevated white blood cell, reduced platelet, hematuria, proteinuria, coagulation abnormalities, increased blood urea nitrogen (BUN) and procalcitonin (PCT), decreased estimated glomerular filtration rate and low serum Na+ , Cl- , and Ca2+ were the common laboratory findings. In the 206 patients, 21 patients had critical type disease and 4 patients (1.9%) died. Hydrothorax, hypotension and cerebral edema/cerebral herniation at hospital admission were independent clinical characteristics, and neutrophil %, prothrombin activity, PCT, BUN, and Ca2+ at hospital admission were independent laboratory factors associated with critical disease. Feature selection identified BUN, PCT and prothrombin time as independent factors related to critical disease. A nomogram integrating BUN and PCT at admission was constructed and calibration showed high accuracy for the probability prediction of critical disease. In conclusion, this study characterized the clinical and laboratory features and constructed a nomogram predicting disease severity in pediatric HFRS, providing references for disease severity evaluation in managing children HFRS.

Scores based on neutrophil percentage and lactate dehydrogenase with or without oxygen saturation predict hospital mortality risk in severe COVID-19 patients.

BACKGROUND: Risk scores are needed to predict the risk of death in severe coronavirus disease 2019 (COVID-19) patients in the context of rapid disease progression. METHODS: Using data from China (training dataset, n = 96), prediction models were developed by logistic regression and then risk scores were established. Leave-one-out cross validation was used for internal validation and data from Iran (test dataset, n = 43) was used for external validation. RESULTS: A NSL model (area under the curve (AUC) 0.932) and a NL model (AUC 0.903) were developed based on neutrophil percentage and lactate dehydrogenase with and without oxygen saturation (SaO2) using the training dataset. AUCs of the NSL and NL models in the test dataset were 0.910 and 0.871, respectively. The risk scoring systems corresponding to these two models were established. The AUCs of the NSL and NL scores in the training dataset were 0.928 and 0.901, respectively. At the optimal cut-off value of NSL score, the sensitivity and specificity were 94% and 82%, respectively. The sensitivity and specificity of NL score were 94% and 75%, respectively. CONCLUSIONS: These scores may be used to predict the risk of death in severe COVID-19 patients and the NL score could be used in regions where patients' SaO2 cannot be tested.

Genetic association of polymorphisms at the intergenic region between PRDM1 and ATG5 with hepatitis B virus infection in Han Chinese patients.

Chronic hepatitis B virus (HBV) infection is related to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), and the interplay between the virus and host immune response leads to different outcomes of the infection. PR domain zinc finger protein 1 (PRDM1) and autophagy-related protein 5 (ATG5) are involved in immune response and HBV infection. An intergenic region between PRDM1 and ATG5 (PRDM1-ATG5 region) has been identified, and single-nucleotide polymorphisms (SNPs) in this region were shown to be involved in immune regulation. This study investigated the functionally relevant rs548234, rs6937876, and rs6568431 polymorphisms at the PRDM1-ATG5 region in a Han Chinese population (403 patients with chronic HBV infection [171 chronic hepatitis, 119 cirrhosis, and 113 HCC], 70 infection resolvers, and 196 healthy controls). The frequencies of the rs6568431 allele A in HBV patients (P = .005) and genotype CA in infection resolvers (P = .005) were significantly higher than in healthy controls. In the dominant model, HCC patients had significantly higher frequencies of rs548234 genotypes CC + TC than cirrhosis patients (P = .009). Rs548234 was an independent factor for HCC in comparison with either cirrhosis (P = .005) or all chronic HBV infection without HCC (P = .018). Functional annotation showed evidence of the role of the SNPs in gene regulation. In conclusion, through this study it is revealed for the first time that rs6568431 may be associated with susceptibility to HBV infection and that rs548234 may be associated with HCC risk in chronic HBV infection, supporting the presence of HBV-related disease-causing regulatory polymorphisms in the PRDM1-ATG5 intergenic region.

Association of LIN28B polymorphisms with chronic hepatitis B virus infection.

BACKGROUND: LIN28B is involved in multiple cellular developmental processes, tissue inflammatory response and tumourigenesis. The association of LIN28B polymorphisms with hepatitis B virus (HBV) infection remains unknown. METHODS: This study investigated the association of LIN28B rs314277, rs314280, rs369065 and rs7759938 polymorphisms in patients with chronic HBV infection, a major cause of liver disease including hepatocellular carcinoma (HCC). A total of 781 individuals including 515 cases of chronic HBV infection (91 asymptomatic carrier status, 128 chronic hepatitis, 127 cirrhosis and 169 HCC), 97 HBV infection resolvers and 169 healthy controls were investigated. RESULTS: LIN28 rs314280 genotypes GA + AA were higher in resolver and controls than patients (P = 0.011). Patients had significantly lower rs314280 allele A than resolvers (P = 0.031, OR 0.689, 95%CI 0.491-0.969) or controls (P = 0.034, OR 0.741, 95%CI 0.561-0.978). In dominant model, patients had significantly lower rs314280 genotypes AA+GA than controls (P = 0.008, OR 0.623, 95%CI 0.439-0.884). LIN28 rs7759938 genotypes TC + CC were higher in resolvers and controls than patients (P = 0.015). Patients had significantly lower rs7759938 allele C than resolvers (P = 0.048, OR 0.708, 95%CI 0.503-0.999). In dominant model, patients had significantly lower rs7759938 genotypes TC + CC than controls (P = 0.010, OR 0.632, 95%CI 0.445-0.897). Chronic hepatitis patients had lower frequency of rs369065 genotype TC than asymptomatic carriers, cirrhosis and HCC (P = 0.019). CONCLUSIONS: These results suggest that LIN28 rs314280 and rs7759938 may be related to the susceptibility of chronic HBV infection. Further studies are warranted to examine the association of LIN28B polymorphisms with HBV-related diseases, especially HCC.

High sustained virologic response rates of sofosbuvir-based regimens in Chinese patients with HCV genotype 3a infection in a real-world setting.

BACKGROUND: Patients with hepatitis C virus (HCV) genotype 3 infection remain a difficult-to-cure population. This study evaluated the efficacy and safety of sofosbuvir-based regimen in genotype 3 patients in a real-world setting. METHODS: HCV genotype 3a-infected adults with compensated liver disease were treated with sofosbuvir (SOF)/velpatasvir (VEL) or SOF/daclatasvir (DCV) with or without ribavirin (RBV) for 12 or 24 weeks, respectively. Efficacy was measured by sustained virologic response at post-treatment week 12 (SVR12). Adverse events were evaluated throughout the treatment and follow-up course. RESULTS: A total of 41 genotype 3a-infected patients were included. Of them, 10 patients (24%) had cirrhosis, 3 (7%) had renal impairment, and 2 (5%) failed previous treatment. Nine patients (22%) were treated with SOF/VEL and 32 (78%) with SOF/DCV with or without RBV. SVR 12 was achieved in 100% (9/9) of patients treated with SOF/VEL for 12 weeks and in 97% (31/32) of those treated with SOF/DCV for 12 or 24 weeks. RBV addition and extension of treatment duration did not improve the SVR of SOF/DCV (RR: 1.04; P = 0.99 and RR: 1.09; P = 0.375, respectively). Ten patients with cirrhosis, 1 on hemodialysis and 2 with treatment-experience achieved SVR12. One treatment-naïve non-cirrhotic patient on hemodialysis treated with SOF/DCV for 24 weeks relapsed at week 8 post-treatment. No serious adverse events and relevant laboratory abnormalities were observed. CONCLUSION: SOF/VEL and SOF/DCV are highly efficacious and well tolerated in genotype 3a-infected patients with or without cirrhosis. RBV coadministration and extension of SOF/DCV treatment appear to add no improvement for efficacy.

Use of oral contraceptives and risk of ulcerative colitis - A systematic review and meta-analysis.

Numerous studies have investigated the link between oral contraceptives and risk of ulcerative colitis (UC), but the results have been controversial. We systematically reviewed all relevant published studies and evaluated the association between the use of oral contraceptives and the development of UC by meta-analysis. Databases including PubMed, EMbase, CNKI and WanFang data were thoroughly searched from inception to September 2018 to collect the studies on the correlation between oral contraceptives and the risk of UC. The studies were screened according to the inclusion and exclusion criteria by two researchers independently, and the data were extracted and the quality was evaluated. Meta-analysis was performed using Stata 13.0 software. There were 12 studies involving 303,340 participants that reported on the association between oral contraceptives and UC. The pooled odds ratio (OR) of UC in oral contraceptive users was 1.25 [95% confidence interval (CI) 1.04-1.51, p = 0.02]. The risk was significant in the current oral contraceptive users (OR 1.49, 95% CI 1.12-1.96, p = 0.005) whereas the past oral contraceptive use was not significantly associated with UC (OR 1.17, 95% CI 0.95-1.43, p = 0.141). This study provides evidence of an association between the use of oral contraceptives and the onset risk of UC. The study also shows that the risk for patients who stop using the oral contraceptives was decreased. These findings may be used as important reference for the use of oral contraceptives and the management of UC patients.

Autophagy-Related 5 Gene rs510432 Polymorphism Is Associated with Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Virus Infection.

BACKGROUND: Despite the identification of autophagy-related protein 5 (ATG5) as a molecule involved in the activated autophagy machinery during hepatitis B virus (HBV) infection and hepatocarcinogenesis, the consequences of ATG5 mutation carriage for patients with chronic HBV infection remain unclear. This study examined the association of ATG5 polymorphisms with HBV-related diseases including hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Two functionally relevant polymorphisms ATG5 rs573775 and rs510432 were genotyped by ligase detection reaction-polymerase chain reaction in 403 patients with chronic HBV infection (171 chronic hepatitis, 119 cirrhosis and 113 HCC) and 196 healthy controls. Univariate and multivariate logistic regression was performed to evaluate factors associated with HCC. RESULTS: The rs573775 genotype and allele frequencies had no significant differences between patients with different clinical diseases. However, HCC patients had significantly higher frequency of rs510432 genotype AA (odds ratio [OR] 2.185, 95% confidence interval [CI] 1.042-4.581, P = 0.037, P value by Bonferroni correction [Pc] = 0.074) and allele A (OR 1.435, 95% CI 1.023-2.013, Pc = 0.036) than chronic hepatitis patients. In multivariate analyses, rs510432 allele A-containing genotypes (AA+GA) were independently associated with cirrhosis in comparison to chronic hepatitis (OR 1.927, 95%CI 1.011-3.017, P = 0.032). The rs510432 genotypes AA+GA were also independently associated with HCC in comparison to chronic hepatitis (OR 2.583, 95% CI 1.025-3.911, P = 0.006) or chronic HBV infection without HCC (OR 2.632, 95% CI 1.067-3.482, P = 0.032). CONCLUSION: These results indicate that rs510432 genotypes AA+GA are associated with disease progression and HCC risk in chronic HBV infection, providing novel evidence for a role of ATG5 in the pathogenesis of HBV-related HCC. ABBREVIATIONS: HBV: hepatitis B virus; HCC hepatocellular carcinoma; TNFSF10: tumor necrosis factor superfamily member 10; ATG5: autophagy-related protein 5; DNA: deoxyribonucleic acid; LDR-PCR: ligase detection reactions-polymerase chain reaction; PCR: polymerase chain reaction; SLE: systemic lupus erythematosus; BD: Behçet's disease; IL-10: interlukin-10; LPS: lipopolysaccharide; PBMC: peripheral blood mononuclear cells; CWP: coal workers' pneumoconiosis; TNF-α: tumor necrosis factor-α.

Bioinformatics Analysis based on Multiple Databases Identifies Hub Genes Associated with Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common liver cancer and the mechanisms of hepatocarcinogenesis remain elusive. OBJECTIVE: This study aims to mine hub genes associated with HCC using multiple databases. METHODS: Data sets GSE45267, GSE60502, GSE74656 were downloaded from GEO database. Differentially expressed genes (DEGs) between HCC and control in each set were identified by limma software. The GO term and KEGG pathway enrichment of the DEGs aggregated in the datasets (aggregated DEGs) were analyzed using DAVID and KOBAS 3.0 databases. Protein-protein interaction (PPI) network of the aggregated DEGs was constructed using STRING database. GSEA software was used to verify the biological process. Association between hub genes and HCC prognosis was analyzed using patients' information from TCGA database by survminer R package. RESULTS: From GSE45267, GSE60502 and GSE74656, 7583, 2349, and 553 DEGs were identified respectively. A total of 221 aggregated DEGs, which were mainly enriched in 109 GO terms and 29 KEGG pathways, were identified. Cell cycle phase, mitotic cell cycle, cell division, nuclear division and mitosis were the most significant GO terms. Metabolic pathways, cell cycle, chemical carcinogenesis, retinol metabolism and fatty acid degradation were the main KEGG pathways. Nine hub genes (TOP2A, NDC80, CDK1, CCNB1, KIF11, BUB1, CCNB2, CCNA2 and TTK) were selected by PPI network and all of them were associated with prognosis of HCC patients. CONCLUSION: TOP2A, NDC80, CDK1, CCNB1, KIF11, BUB1, CCNB2, CCNA2 and TTK were hub genes in HCC, which may be potential biomarkers of HCC and targets of HCC therapy.

Association of polymorphism rs1053005 in STAT3 with chronic hepatitis B virus infection in Han Chinese population.

BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is involved in hepatitis B virus (HBV) infection and HBV-related hepatocellular carcinoma (HCC). The association between polymorphism rs1053005 and haplotypes formed by rs1053004 and rs1053005 in the 3'UTR of STAT3 and chronic HBV infection has yet to be investigated. METHODS: This study included 567 patients with chronic HBV infection (239 chronic hepatitis, 141 liver cirrhosis and 187 HCC), 98 HBV infection resolvers, and 169 healthy controls. STAT3 rs1053004 and rs1053005 polymorphisms were genotyped by TaqMan SNP Genotyping Assays. RESULTS: The rs1053004 genotype CC [P value by Bonferroni correction (P c ) = 0.002] and allele C (P c = 0.019) were more frequent in patients with chronic HBV infection than in healthy controls. The rs1053005 genotype GG was also more frequent in patients with chronic HBV infection than in healthy controls (P c = 0.046). The rs1053004-rs1053005 haplotype T-G was less frequent in patients with chronic HBV infection than in healthy controls (Pc < 0.001). Haplotype C-A was more frequent in patients with liver cirrhosis than in patients with HCC (P c = 0.042). The rs1053004 genotype TC, rs1053005 genotype AG and rs1053004-rs1053005 haplotype T-A were associated with higher HBV DNA levels. CONCLUSIONS: STAT3 rs1053004 and rs1053005 polymorphisms and haplotypes formed by rs1053004 and rs1053005 are associated with chronic HBV infection and the haplotypes appear to be also associated with the development of liver disease. Studies in large sample sizes of patients and control populations are required to verify and extend these findings.

Association of the tandem polymorphisms (rs148314165, rs200820567) in TNFAIP3 with chronic hepatitis B virus infection in Chinese Han population.

BACKGROUND: Chronic hepatitis B virus (HBV) infection remains an important public health issue. A20, a ubiquitin-editing protein encoded by tumor necrosis factor alpha-inducible protein 3 (TNFAIP3) gene, is complicated in HBV infection and liver injury. The tandem polymorphisms (rs148314165, rs200820567), deletion T followed by a T to A transversion and collectively referred to as TT > A in TNFAIP3, may attenuate A20 expression. METHODS: The rs148314165 and rs200820567 polymorphisms were examined using PCR amplification followed by direct sequencing in 419 patients with chronic HBV infection, 77 HBV infection resolvers and 175 healthy controls of Chinese Han ethnicity. RESULTS: The genotypes and alleles of rs148314165 and rs200820567 polymorphisms determined and the haplotypes constructed were consistently identical, confirming the reliable determination of the TT > A variant. The genotypes of rs148314165 and rs200820567 in HBV patients, HBV infection resolvers and healthy controls are in Hardy-Weinberg equilibrium (P > 0. 05). The patients with chronic HBV infection had higher frequency of TT > A variant than healthy controls (6.6% vs. 3.4%; OR, 1.979; 95% CI, 1.046-3.742; P = 0.033). The frequency of TT > A variant between patients with chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma had no significant differences. CONCLUSIONS: The TT > A variant of TNFAIP3 may be associated with the susceptibility of chronic HBV infection but not the clinical diseases. Studies in large sample size of HBV patient and control populations are required to further clarify the role of this important variant in chronic HBV infection and the disease progression related to the infection.

Differential association of STAT3 and HK-II expression in hepatitis B virus- and hepatitis C virus-related hepatocellular carcinoma.

STAT3 and hexokinase II (HK-II) are involved in viral infection and carcinogenesis of various cancers including hepatocellular carcinoma (HCC). The roles of STAT3 and HK-II in hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related HCC remain largely unclear. This study examined STAT3 and HK-II expression in HBV- and HCV-related HCC, HBV-related liver fibrosis, and normal control liver by using tissue microarray and immunohistochemical method. Results showed that STAT3 expression in HBV-related HCC, HCV-related HCC, and HBV-related liver fibrosis was significantly higher than in control liver (P < 0.001, P = 0.016, and P = 0.005, respectively) and had no significant differences between these three diseased liver tissues. The HK-II expression in HBV-related HCC was significantly higher than that in HCV-related HCC, HBV-related liver fibrosis, and control liver (P = 0.007, P = 0.029, and P = 0.008, respectively) but had no significant elevation in and no significant differences between HCV-related HCC, HBV-related liver fibrosis, and control liver. The HK-II expression was significantly correlated to STAT3 expression in HBV-related HCC (P = 0.022), but no correlation was observed in HCV-related HCC, HBV-related liver fibrosis, and control liver. In conclusion, STAT3 expression is upregulated in both HBV- and HCV-related HCC, while HK-II is predominantly upregulated and correlated to STAT3 in HBV-related HCC. These differential expression and association may suggest the distinct roles of STAT3 and HK-II in hepatocarcinogenesis of HBV and HCV infection. Studies are needed to confirm the relationship of STAT3 and HK-II and to examine the underlying mechanisms. J. Med. Virol. 88:1552-1559, 2016. © 2016 Wiley Periodicals, Inc.

Elevated serum soluble CD14 levels in chronic HBV infection are significantly associated with HBV-related hepatocellular carcinoma.

Hepatitis B virus (HBV) infection is a major cause of chronic liver diseases including hepatocellular carcinoma (HCC). CD14 and its soluble form sCD14 play important roles in immunity and are involved in the translocation of bacteria and their products which is related to the pathogenesis in chronic HBV infection. This study investigated serum sCD14 levels in HBV chronically infected patients with various clinical diseases. Serum sCD14 levels in HBV patients were significantly elevated compared with those of healthy controls. HCC patients had significantly highest levels of serum sCD14 across all the HBV-related diseases. Serum sCD14 levels significantly discriminated HCC from other HBV-related non-HCC diseases. The area under the receiver operating characteristic curve (AUC) of sCD14 levels for HCC was significantly higher in comparison with other HBV-related non-HCC diseases. The AUC of sCD14 for HCC (0.868, 95 % CI 0.791-0.946, P < 0.001) was higher than that of alpha-fetoprotein (0.660, 95 % CI 0.508-0.811, P = 0.039). Serum level of sCD14 was associated with the overall survival (OS) of HCC patients, with sCD14 levels >20 ng/mL being significantly related to poorer OS (P = 0.017). Multivariate regression showed that serum sCD14 level was an independent factor associated with the OS rates of HBV-related HCC patients (HR 2.544, 95 % CI 1.169-5.538, P = 0.019). HCC resection resulted in a significant decrease of sCD14 levels (P < 0.001). These findings suggest the potential role of sCD14 in the pathogenesis of chronic HBV infection, especially the development of HCC, and the potential usefulness of sCD14 as a biomarker for discriminating clinical diseases and predicting survival of HCC patients in chronic HBV infection.

Association between TNFAIP3 nonsynonymous single-nucleotide polymorphism rs2230926 and chronic hepatitis B virus infection in a Chinese Han population.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in tumor necrosis factor alpha-inducible protein 3 (TNFAIP3) gene have been linked to inflammatory, immunological and malignant diseases. Hepatitis B virus (HBV) infection is characterized by immunopathogenesis. This study investigated the association of rs2230926, a nonsynonymous SNP in TNFAIP3 gene, with chronic HBV infection. METHODS: Four hundred and fifty-five patients with chronic HBV infection with clinical diseases of chronic hepatitis (n = 183), liver cirrhosis (n = 167) and hepatocellular carcinoma (n = 105), 92 HBV infection resolvers and 171 healthy controls were included. All subjects were of Chinese Han ethnicity. Genotyping of rs2230926 was carried out by polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The gender and age between HBV patients, HBV infection resolvers and healthy controls had no statistical difference. The genotypes of rs2230926 in HBV patients, HBV infection resolvers and healthy controls are in Hardy-Weinberg equilibrium. The genotype and allele frequencies of TNFAIP3 rs2230926 polymorphism between HBV patients, HBV infection resolvers and healthy controls had no significant difference. The genotype and allele frequencies of TNFAIP3 rs2230926 polymorphism between HBV patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma also showed no significant difference. CONCLUSIONS: The TNFAIP3 rs2230926 polymorphism is not suggested to be associated with the susceptibility of chronic HBV infection or the progression of HBV-related diseases in this study. Replicative studies and studies in large control and HBV patient populations of different ethnicity by genotyping more polymorphisms in TNFAIP3 gene are needed.

IL17A gene polymorphisms, serum IL-17A and IgE levels, and hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection.

Interleukin (IL)-17A plays important roles in hepatitis B virus (HBV)-induced liver diseases. This study aims to investigate IL17A single nucleotide polymorphisms (SNPs) and the predispositions to chronic HBV infection and hepatocellular carcinoma (HCC) risk and the correlations to IL-17A and IgE levels. Three hundred ninety-five chronic HBV patients, 75 HBV infection resolvers, and 174 healthy controls were included. IL17A SNPs rs8193036 (C/T) and rs2275913 (A/G) and serum IL-17A and IgE levels were determined. HBV infection resolvers had higher rs8193036 allele T and allele T-containing genotypes than HBV patients or controls. Compared with chronic hepatitis, HCC patients had more frequent rs2275913 genotype GG (odds ratios [OR] 3.317, 95% confidence interval [CI] 1.663-6.617, P = 0.001) and allele G (OR 1.844, 95% CI 1.311-2.595, P < 0.001), and more frequent haplotypes CG (OR 1.868, 95% CI 1.256-2.778, P = 0.002) and TG (OR 1.788, 95% CI 1.031-3.101, P = 0.037) of rs8193036 and rs2275913. Comparison of HCC patients with cirrhosis yielded similar findings. Apart from male gender and older ages, IL-17A level (OR 1.020, 95% CI 1.003-1.036, P = 0.019) and rs2275913 genotypes AG and GG (OR 1.704, 95% CI 1.214-2.390, P = 0.006) were factors significantly associated with HCC risk in multivariate analysis in comparison with HBV patients without HCC. These factors remained significant in multivariate analysis in relation to cirrhosis. IL17A rs2275913 genotype GG was associated with significantly increased IL-17A and IgE levels. IL17A polymorphisms may influence HCC risk in chronic HBV infection via regulating IL-17A production.

Inhibition of hepatitis C virus replication in vitro by xanthohumol, a natural product present in hops.

Hepatitis C virus is a major cause of chronic liver disease worldwide. Xanthohumol, a prenylated flavonoid from hops, has various biological activities including an antiviral effect. It was previously characterized as a compound that inhibits bovine viral diarrhea virus, a surrogate model of hepatitis C virus. In the present work, xanthohumol was examined for its ability to inhibit hepatitis C virus replication in a cell culture system carrying replicating hepatitis C virus RNA replicon. 0.2 % DMSO and 500 units/mL interferon-alpha treatments were set as a negative and positive control, respectively. The inhibitory effect by xanthohumol was determined by the luciferase activity of the infected Huh7.5 cell lysates and the hepatitis C virus RNA levels in the culture. Xanthohumol at 3.53 µM significantly decreased the luciferase activity compared to the negative control (p < 0.01). Xanthohumol at 7.05 µM further decreased the luciferase activity compared to xanthohumol at 3.53 µM (p = 0.015). Xanthohumol at 7.05 µM or 14.11 µM achieved an inhibitory effect similar to that of interferon-alpha 2b (p > 0.05). Xanthohumol at 3.53 µM significantly reduced the hepatitis C virus RNA level compared to the negative control (p = 0.001). Although the results of xanthohumol at 7.05 µM had a higher variation, xanthohumol at the 7.05 µM and 14.11 µM decreased the hepatitis C virus RNA level to that achieved by interferon-alpha (p > 0.05). In conclusion, xanthohumol displays anti-hepatitis C virus activity in a cell culture system and may be potentially used as an alternative or complementary treatment against the hepatitis C virus.

A Case Report of Cutaneous Anthrax Diagnosed by Using a Metagenomic Next-Generation Sequencing (mNGS) Approach.

Anthrax is caused by Bacillus anthracis. Humans are mainly infected through contact with the fur and meat of livestock. The cutaneous form is the most common form. The skin lesions of typical cutaneous anthrax are characterized by shallow ulcers with black crusts, surrounded by small blisters and nonpitting edema of nearby tissues. Metagenomic next-generation sequencing (mNGS) is a new pathogenic detection method which is rapid and unbiased. We reported the first case of cutaneous anthrax diagnosed by mNGS. Ultimately, the man received prompt antibiotic therapy and had a good prognosis. In conclusion, mNGS is proved to be a good method for etiological diagnosis, especially for rare infectious diseases.

Effect of antiviral therapy on the survival and incidence of major complications in HBV-associated cirrhotic patients after splenectomy for hypersplenism and portal hypertension.

BACKGROUND: Splenectomy remains a common approach for the management of hypersplenism and portal hypertension in hepatitis B virus (HBV)-associated cirrhotic patients in China and some other Asian countries. The effects of antiviral therapy on the survival and occurrence of complications in asplenic HBV-associated cirrhotic patients are unknown. This study analyzed the effect of antiviral therapy on survival and occurrence of major complications in HBV-associated cirrhotic patients after splenectomy for hypersplenism and portal hypertension. RESULTS: Of the 57 eligible patients for analysis, 28 patients received nucleos(t)ide analogs (treatment group) for antiviral treatment after splenectomy, while 29 patients received no antiviral treatment (control group). After a median of 3 years and 9 months, the overall survival and complication-free survival in the treatment group were higher though not statistically significant than those in the control group. Multivariate analysis showed that antiviral treatment was associated with increased but not statistically significant overall survival (hazard ratio (HR): 2.272, 95% confidence interval (CI): 0.952-5.424, P=0.064) and the antiviral treatment was significantly associated with increased complication-free survival of the patients (HR: 7.229, 95% CI: 1.271-41.117, P=0.026). The complication-free survival in patients aged ≤ 40 years was higher than that in patients aged>40 years in the antiviral treatment patients (P=0.020). CONCLUSIONS: Antiviral therapy initiating after splenectomy may reduce the incidence of complications and tend to improve the survival in asplenic HBV-associated cirrhotic patients, especially in younger patients, supporting the use of antiviral therapy in these patients after splenectomy.

Alterations in circadian rhythms aggravate Acetaminophen-induced liver injury in mice by influencing Acetaminophen metabolization and increasing intestinal permeability.

Acetaminophen (APAP) is the most common antipyretic and analgesic drug causing drug-induced liver injury (DILI). Alterations in circadian rhythms can adversely affect liver health, especially metabolic and detoxification functions. However, the effect of circadian rhythm alterations induced by environmental factors on APAP-induced liver injury and the underlying mechanisms are not well known. In this study, a mouse model of circadian rhythm alterations was established by light/dark cycle shift and then treated with excessive APAP. The liver injury indexes, APAP-related metabolic enzymes, and intestinal permeability in mice were evaluated by biochemical analysis, quantitative real-time PCR, enzyme-linked immunosorbent assays, and histopathology. Results showed that circadian rhythm alterations resulted in increased reactive oxygen species (ROS) and malondialdehyde (MDA) and decreased liver superoxide dismutase (SOD), glutathione, and CYP1A2 and CYP3A11 mRNA expression, and increased serum diamine oxidase, lipopolysaccharide, and D-lactate in the mice. Compared with control mice, APAP induced higher serum alanine aminotransferase and aspartate aminotransferase, liver interleukin-1ß and tumor necrosis factor-α mRNA, ROS and MDA, lower SOD, glutathione, and UDP-glucuronosyltransferases /sulfotransferases mRNA and more severe liver necrosis and intestinal damage in mice with alterations in circadian rhythms. In conclusion, circadian rhythm alterations by light/dark cycle shift resulted in increased oxidative stress and intestinal permeability in the mice and exacerbated APAP-induced liver injury by influencing APAP metabolization and increasing intestinal permeability.

Case report: Brucellosis with rare multiple pulmonary nodules in a depressed patient.

Background: Brucellosis is a zoonotic disease that threatens public health and creates an economic burden. Unfortunately, it is often overlooked in developing countries, with misdiagnosis causing negative impacts on those with low income. Although the symptoms of brucellosis are commonly reported as fever and fatigue, rare pulmonary, and psychiatric involvements should also be considered. We present the first brucellosis patient in China with multiple pulmonary nodules and depression. Furthermore, this report highlights the importance of collecting patient history in epidemic areas of brucellosis. Case presentation: We report the case of a 40-year-old woman with intermittent fever for 2 months and gradually accompanied by chills, dry cough, arthralgia, and fatigue. The patient was also diagnosed with depression after fever. She received symptomatic treatment at a regional hospital; however, there was no significant symptom relief. She suddenly developed hemoptysis 1 day prior to arrival at our hospital, where we discovered that her liver, spleen, neck, and axillary lymph nodes were enlarged, and there were multiple nodules in both lungs. The patient was eventually diagnosed with brucellosis after the serum agglutination test and received antibiotic therapy, which provided symptom relief. Conclusion: This report describes a case of brucellosis with uncommon multipulmonary nodules and depression in China. This study has widened the evidence of respiratory involvement due to brucellosis. Second, it demonstrates the importance of collecting a comprehensive medical history, especially in epidemic areas. In conclusion, for febrile patients with pulmonary nodules and depression, especially in endemic areas, brucellosis should be considered.