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Background & Aims: Functional cure is achieved by a limited number of patients with chronic hepatitis B (CHB) after nucleotide analogue(s) and interferon treatment. It is urgent to develop therapies that can help a larger proportion of patients achieve functional cure. The present study was designed to explore the anti–hepatitis B virus (HBV) potency of interleukin-6 family cytokines and to characterize the underlying mechanisms of the cytokine displaying the highest anti-HBV potency. Methods: HBV-infected cells were used to screened the anti-HBV potency of interleukin-6 family cytokines. The concentration of oncostatin M (OSM) in patients with chronic HBV infection was examined by enzyme-linked immunosorbent assay. The underlying mechanism of OSM anti-HBV was explored through RNA-seq. C57BL/6 mice injected with rAAV8-1.3HBV were used to explore the suppression effect of OSM on HBV in vivo. Results: OSM is the most effective of the interleukin-6 family cytokines for suppression of HBV replication (percentage of average inhibition: hepatitis B surface antigen, 34.44%; hepatitis B e antigen, 32.52%; HBV DNA, 61.57%). Hepatitis B e antigen–positive CHB patients with high OSM levels had lower hepatitis B surface antigen and hepatitis B e antigen than those with low levels. OSM activated JAK-STAT signaling pathway promoting the formation of STAT1-IRF9 transcription factor complex. Following this, OSM increased the expression of various genes with known functions in innate and adaptive immunity, which was higher expression in patients with CHB in immune clearance phase than in immune tolerance phase (data from GEO: GSE65359). Interferon-induced transmembrane protein 1, one of the most differentially expressed genes, was identified as an HBV restriction factor involved in OSM-mediated anti-HBV effect. In vivo, we also found OSM significantly inhibited HBV replication and induced expression of antiviral effector interferon-induced transmembrane protein 1. Conclusions: Our study shows that OSM remodels the immune response against HBV and exerts potent anti-HBV activity, supporting its further development as a potential therapy for treating CHB.

ABSTRACTDeoxycholic acid (DCA) serves essential functions in both physiological and pathological liver processes; nevertheless, the relationship among DCA, gut microbiota, and metabolism in chronic liver injury remain insufficiently understood. The primary objective of this study is to elucidate the potential of DCA in ameliorating chronic liver injury and evaluate its regulatory effect on gut microbiota and metabolism via a comprehensive multi-omics approach. Our study found that DCA supplementation caused significant changes in the composition of gut microbiota, which were essential for its antagonistic effect against CCl4-induced chronic liver injury. When gut microbiota was depleted with antibiotics, the observed protective efficacy of DCA against chronic liver injury became noticeably attenuated. Mechanistically, we discovered that DCA regulates the metabolism of bile acids (BAs), including 3-epi DCA, Apo-CA, and its isomers 12-KLCA and 7-KLCA, IHDCA, and DCA, by promoting the growth of A.muciniphila in gut microbiota. This might lead to the inhibition of the IL-17 and TNF inflammatory signaling pathway, thereby effectively countering CCl4-induced chronic liver injury. This study illustrates that the enrichment of A. muciniphila in the gut microbiota, mediated by DCA, enhances the production of secondary bile acids, thereby mitigating chronic liver injury induced by CCl4. The underlying mechanism may involve the inhibition of hepatic IL-17 and TNF signaling pathways. These findings propose a promising approach to alleviate chronic liver injury by modulating both the gut microbiota and bile acids metabolism.

ObjectivesTo comprehensively analyze the epidemiological features of human papillomavirus (HPV) and HPV-related cervical diseases in females aged 35–64 years.MethodsA total of 149,559 samples of exfoliated cervical cells screened for HPV and related cervical lesions from January 2018 to December 2023 were enrolled. The prevalence of 15 high-risk and 6 low-risk HPV genotypes were detected, and the cervical cytology were analyzed. The impact of single and multiple HPV infections was characterized, and the effect of age was studied.ResultsThe cervix cytology was normal in 86.60% of the females, while 7.13% of the females were diagnosed with cervix inflammation, 0.60% with ASC-US, 0.22% with ASC-H, 0.72% with LSIL, 0.49% with HSIL, 0.03% with ICC. The highest median age was observed in ASC-H group with 54 years old. Females with primary school education or lower have the highest positive rates. The overall HPV prevalence was 8.60%. The relatively prevalent HPV types were HPV52, 58, 16, 39, 51. HPV16, HPV18, HPV58, HPV33 and HPV52 were the top5 predominant types in ICC patients. 17.41% females suffered from multiple HPV infection with the most frequently co-infection subtypes being HPV52, HPV58 and HPV16. The prevalence of all HPV subtypes increased with age. Multiple HPV infections accounted for a larger proportion in those aged above 55 years. The peak HPV16 prevalence was observed in ICC group in cases aged 45–49 and 55–59. The peak HPV33 prevalence was observed in younger individuals aged 40–44 who developed ICC.ConclusionMore action should be taken against HPV33 infection.

Background: To analysis of quasispecies (QS) changes and high-frequency mutations in the BCP/PreC/C region of patients at different phases of hepatitis B virus (HBV) infection and provides novel biomarkers for the diagnosis of chronic hepatitis B (CHB) patients. Methods: With the application of next-generation sequencing technology, we were able to sequence the HBV BCP/PreC/C regions in 40 patients, each at different phases of the HBV infection. The heterogeneity of QS and the frequency of mutations were calculated using MEGA 7 software. Results: Our results show that the complexity and diversity of the BCP/PreC/C QS in HBeAg-positive CHB patients are significantly higher than those in HBeAg-positive chronic infection patients, while HBeAg-negative chronic infection patients had significantly higher QS complexity and diversity than HBeAg-negative CHB patients. In addition, HBeAg-negative patients showed reduced complexity but increased diversity compared with HBeAg-positive patients. Receiver operating characteristic curves showed that G1764A, C2102T, dN and complexity of QS could be used as potential biomarkers for diagnosing HBeAg-positive CHB, while the A2189C, dS and complexity of QS could be used as potential biomarkers for diagnosing HBeAg-negative chronic hepatitis. Finally, our study also found that G1896A and A2159G may be hotspot mutations affecting HBeAg seroconversion. Conclusion: Our research elucidates the evolution of HBV by analyzing QS heterogeneity and mutation patterns, offering novel serum biomarkers for enhancing clinical diagnosis and disease prognosis. This comprehensive approach sheds light on the intricate dynamics of HBV progression and paves the way for more precise medical interventions.

Hepatitis B virus (HBV) exists as quasispecies (QS). However, the evolutionary characteristics of haplotypes of HBV X gene in the hepatocellular carcinoma (HCC) microenvironment remain unclear. Mutations across X gene are essential for the tumorigenicity of HBV X protein (HBx). However, the functional phenotypes of many mutant HBx remain unknown. This study aims to compare the characteristics of X gene evolution between tumour and non-tumour tissues in HCC patients and investigate the tumorigenic phenotype of HBx harbouring mutation T81P/S101P/L123S. This study included 24 HCC patients. Molecular cloning of X gene was performed to analyse characteristics of haplotypes in liver tissues. HCC cell lines stably expressing wild-type or mutant HBx and subcutaneous tumour xenograft mouse model were used to assess HBx-T81P/S101P/L123S tumorigenicity. The mean heterogeneity of HBV QS across X gene in tumour tissues was lower than that in non-tumour tissues. A location bias was observed in X gene clones with genotype C or D in tumour tissues compared to those with genotype B. Mutations in genotype-C or – D clones were mainly clustered in the dimerization region and aa110-aa140 within the transactivation region. A novel mutation combination at residues 81, 101 and 123 was identified in tumour tissues. Further, HBx-T81P/S101P/L123S promotes cell proliferation and increases genomic instability, which was mediated by MYC. This study elucidates the compartmentalized evolution patterns of HBV X gene between intra tumour and non-tumour tissues in HCC patients and provides a new mechanism underlying HBV-driven hepatocarcinogenesis, suggesting a potential viral marker for monitoring HCC.

ABSTRACT Increasing evidence indicates that interferon alpha (IFN-α) therapy is an effective treatment option for a subgroup of patients with chronic hepatitis B virus (HBV) infection. It has been confirmed that interferon-induced protein with tetratricopeptide repeats 3 (IFIT3), a member of the interferon-stimulated genes (ISGs), could inhibit the replication of various viruses. However, its effect on HBV replication is unclear. The present study sought to explore the role and mechanism of IFIT3 in IFN-α antiviral activities against HBV. IFIT3 mRNA levels in the peripheral blood of 108 treatment-naive patients and 70 healthy controls were analyzed first. The effect of IFIT3 on the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway under the dual intervention of IFN-α and HBV was also explored in vitro. Treatment-naive individuals exhibited elevated levels of IFIT3 mRNA compared to the controls (P

The need to be diagnosed with liver biopsy makes the clinical progression of chronic HBV infection diagnosis a challenge. Existing HBV serum biochemical assays are used throughout clinical but have limited effects. Studies have shown that mitochondrial function is tightly coupled to HBV infection. Here, we verified the diagnostic value of serum Adenosine Triphosphate (ATP) as a potential marker for differential HBV infection progress by detecting the level of ATP in the serum from a wide spectrum of HBV-infected populations, and confirmed the role of ATP in the deterioration of HBV infection-related diseases through HBV-infected cells and mouse models. The results showed that there were significantly lower serum ATP levels in HBeAg-positive CHB patients compared with healthy controls. And during the progression of CHB to liver cirrhosis and hepatocellular carcinoma, the ATP level was increased but not higher than healthy controls. The area under the curve (AUC) of serum ATP was 0.9063 to distinguish HBeAg-positive CHB from healthy, and another AUC was 0.8328 in the CHB against the HCC group. Preliminary exploration of the mechanism indicated that the decline of serum ATP was due to impaired mitochondria in CHB patients. Our data provide evidence that serum ATP distinguishes the various progress of HBV infection-related diseases and expands diagnostic biomarkers for HBeAg-positive CHB patients with healthy controls.

ABSTRACTBackground and Aims: The drug resistance of hepatitis B virus (HBV) originates from mutations within HBV reverse transcriptase (RT) region during the prolonged antiviral therapy. So far, the characteristics of how these mutations distribute and evolve in the process of therapy have not been clarified yet. Thus we aimed to investigate these characteristics and discuss their contributing factors.Methods: HBV RT region was direct-sequenced in 285 treatment-naive and 214 post-treatment patients. Mutational frequency and Shannon entropy were calculated to identify the specific mutations differing between genotypes or treatment status. A typical putative resistance mutation rtL229V was further studied using in-vitro susceptibility assays and molecular modeling.Results: The classical resistance mutations were rarely detected among treatment-naive individuals, while the putative resistance mutations were observed at 8 AA sites. rtV191I and rtA181T/V were the only resistance mutations identified as genotype-specific mutation. Selective pressure of drug usage not only contributed to the classical resistance mutations, but also induced the changes at a putative resistance mutation site rt229. rtL229V was the major substitution at the site of rt229. It contributed to the most potent suppression of viral replication and reduced the in-vitro drug susceptibility to entecavir (ETV) when coexisting with rtM204V, consistent with the hypothesis based on the molecular modeling and clinical data analysis.Conclusions: The analysis of mutations in RT region under the different circumstances of genotypes and therapy status might pave the way for a better understanding of resistance evolution, thus providing the basis for a rational administration of antiviral therapy.

The length of Alloxiphidiopsis emarginata complete mitogenome was 16,207 bp and contained the typical gene arrangement, base composition, codon usage found in other related species. The overall base composition exhibited obvious anti-G (10.6%) and AT bias (71.6%). The initiation codons of all PCGs were typical ATN (ATA/ATG/ATT), and the termination codons were TAA, TAG, or incomplete stop codon T. All tRNAs could be folded into typical cloverleaf secondary structures, except tRNASer (AGN). Phylogenetic analyses showed that A. emarginata was closer with Xizicus howardi.

Objective To observe the white matter and gray matter impairment of Duchenne muscular dstrophy (DMD) patients with diffusion tensor imaging (DTI). Methods Forteen male patients with DMD (6-11 years old) and 10 age-matched healthy boys participated into this study. All patients' diagnosis was based on typical signs and symptoms, serum creatine kinase (CK), electromyography, multiplex ligation-dependent probe amplification (MLPA) for DMD gene test and muscle biopsy results. All participants were scanned by DTI. The fractional anisotropy (FA) values of regions of interest (ROIs), including bilateral parietal lobe white matter, bilateral frontal lobe white matter, genu of corpus callosum, splenium of corpus callosum, bilateral caput nuclei caudati, bilateral anterior cingulate gyrus, bilateral cingulate gyrus, bilateral posterior cingulate gyrus, bilateral lenticular nucleus, bilateral anterior limb of internal capsule, bilateral posterior limb of internal capsule, bilateral thalamus, bilateral occipital lobe whitematter, bilateral temporal lobe white matter, bilateral hippocampus, bilateral superior cerebellar peduncle and bilateral middle cerebellar peduncle, were measured. The data was analyzed and compared between control group and DMD group. Results Compared with control group, the FA value of splenium of corpuscallosum in DMD group was significantly reduced (t = -2.187, P = 0.045). No significant difference was found in FA values of other ROIs between 2 groups (P > 0.05, for all). Conclusions It is found in China for the first time that DMD patients had microstructural changes in splenium of corpus callosum. However, the correlation between this change and cognitive changes of DMD patients remains to be further studied. DOI: 10.3969/j.issn.1672-6731.2015.05.006

Xiphidiopsis (Xiphidiopsis) gurneyi belongs to Meconematinae. The complete mitochondrial genome of X. (X.) gurneyi was sequenced by the next-generation sequencing (NGS) technology. The total length of the mitogenome was 16,225 bp and contains the typical gene arrangement, base composition, codon usage found in Meconematinae species. Phylogenetic tree was constructed based on concatenated datasets of PCGs and rRNAs of X. (X.) gurneyi and 19 Tettigoniidae species to assess their phylogenic relationship. Phylogenetic analysis showed that X. (X.) gurneyi was more closely related to the genus of Xizicus.

The complete chloroplast genome of Fargesia qinlingensis (Poaceae) has been reconstructed from the whole-genome Illumina sequencing data. The complete chloroplast genome sequence of F. qinlingensis obtained in this study was 139,640 bp in length, with a large single copy (LSC) region of 83,220 bp, a small single copy (SSC) region of 12,826 bp, separated by two inverted repeat (IR) regions of 21,797 bp each. The GC content was 38.9%, and in the LSC, SSC, and IR regions were 37.0%, 33.2%, and 44.2%, respectively. A total of 130 genes were annotated, including 83 protein-coding genes (PCGs), 39 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. The result of the phylogenetic analysis showed that F. qinlingensis was more closely related to the species of F. denudata.

The complete chloroplast genome sequence of Echinocodon lobophyllus was determined by Illumina pair-end sequencing. The results showed that the complete plastid genome was 169,419 bp in length, containing a large single copy (LSC) of 85,599 bp and a small single copy (SSC) of 8054 bp, which were separated by a pair of 37,883 bp inverted repeats (IRs). A total of 109 unique genes were annotated, including 75 protein coding genes, 30 tRNA genes, and 4 rRNA genes. Among these genes, 16 genes contained one or two introns. The overall GC contents of the plastid genome were 38.4%. A maximum likelihood phylogenetic analysis showed that E. lobophyllus and Codonopsis minima formed one clade at the base of the phylogenetic tree of Campanulaceae with a high support value.

Based on the structural scaffolds of natural products, two series of flavonoid derivatives, for a total of twelve compounds, were designed and synthesized as potential human telomerase inhibitors. Using a modified TRAP-PCR assay, compound 5c exhibited the most potent inhibitory activity against human telomerase with an IC50 value of less than 50 μM. In vitro, the results demonstrated that compound 5c had potent anticancer activity against five classes of tumor cell lines. The molecular docking and molecular dynamics analyses binding to the human telomerase holoenzyme were performed to elucidate the binding mode of active compound 5c. This finding helps the rational design of more potent telomerase inhibitors based on the structural scaffolds of natural products.

Background: Empyema is a serious infection in pleural space. Finding out seasonal variations of empyema and its pathogens can help in providing preventive measures, and implicating future researches. Methods: This study is a 10-year observational study in a single center. Patients with empyema thoracis receiving thoracoscopic decortication between January 2012 and December 2021 were included in the study. Results: There were 1082 empyema patients enrolled in this study. No seasonal variation was noted (spring = 25.7 %, summer =25.5 %, autumn = 24.8 %, winter = 24.0 %). However, we observed seasonal variations in pathogens. Streptococcus species had slightly higher prevalence in winter and spring than summer and autumn (54.3 % vs. 45.7 %) without significant difference (p = 0.251). On the contrary, Staphylococcus species occurred more often in summer and autumn than winter and spring (61.5 % vs. 38.5 %) (p = 0.035). Klebsiella species were more likely found in autumn (34.9 %) (p = 0.050), and Pseudomonas species showed no peak prevalence in any season (p = 0.423). The incidence of Streptococcus species increased over the years. Conclusions: Although no seasonal variation was found in severe empyema patients requiring surgery, there were seasonal variations for the pathogens in Taiwan. The medical community should focus on Streptococcus species in winter and spring and Staphylococcus species in summer and autumn.

Lung cancer stands as the primary cause of cancer-related death across the globe. The standard therapeutic approach for lung cancer involves concurrent chemoradiotherapy, with consideration of prophylactic cranial irradiation for younger or well-performing patients. In this study, we aimed to investigate prognostic factors and the impacts of different treatment methods on overall survival for stage IIIA small cell lung cancer in Taiwan. We obtained data from the Taiwan Cancer Registry, which included clinical and pathology data of 579 stage IIIA small cell lung cancer patients from January 2010 to December 2018, for this retrospective study. The enrolled patients had data on age, sex, Charlson Comorbidity Index score, histologic grading, clinical T, clinical N, clinical stage, treatment modality, and overall survival time. We compared overall survival among different subgroups to assess the impacts of these prognostic factors. The five-year survival rate for all patients was 20.57%, with a median survival time of 15.79 months. The data suggest that Charlson Comorbidity Index score, histologic grade, and clinical stage subgroups did not reach statistically significant differences. During the multivariate analysis, age over 70 years, sex, and treatment method were determined to be statistically significant independent prognostic factors. Patients who underwent surgical intervention exhibited significantly better outcomes compared to those who did not undergo operation.. In conclusion, stage IIIA small cell lung cancer is a highly heterogeneous disease. Operation should be considered as one of the alternative treatments in stage IIIA Small cell lung cancer patients.

Lung cancer stands as the primary cause of cancer-related death across the globe. The standard therapeutic approach for lung cancer involves concurrent chemoradiotherapy, with consideration of prophylactic cranial irradiation for younger or well-performing patients. In this study, we aimed to investigate prognostic factors and the impacts of different treatment methods on overall survival for stage IIIA small cell lung cancer in Taiwan. We obtained data from the Taiwan Cancer Registry, which included clinical and pathology data of 579 stage IIIA small cell lung cancer patients from January 2010 to December 2018, for this retrospective study. The enrolled patients had data on age, sex, Charlson Comorbidity Index score, histologic grading, clinical T, clinical N, clinical stage, treatment modality, and overall survival time. We compared overall survival among different subgroups to assess the impacts of these prognostic factors. The five-year survival rate for all patients was 20.57%, with a median survival time of 15.79 months. The data suggest that Charlson Comorbidity Index score, histologic grade, and clinical stage subgroups did not reach statistically significant differences. During the multivariate analysis, age over 70 years, sex, and treatment method were determined to be statistically significant independent prognostic factors. Patients who underwent surgical intervention exhibited significantly better outcomes compared to those who did not undergo operation.. In conclusion, stage IIIA small cell lung cancer is a highly heterogeneous disease. Operation should be considered as one of the alternative treatments in stage IIIA Small cell lung cancer patients. [ABSTRACT FROM AUTHOR]

The title compound, C12H10N2O3, was obtained by the de­acetyl­ation reaction of 1-(6-amino-5-nitro­naphthalen-2-yl)ethanone in a concentrated sulfuric acid methanol solution. The mol­ecule comprises a naphthalene ring system bearing an acetyl group (C-3), an amino group (C-7), and a nitro group (C-8). In the crystal, the mol­ecules are assembled into a two-dimensional network by N⋯H/H⋯N and O⋯H/H⋯O hydrogen-bonding inter­actions. n–π and π–π stacking inter­actions are the dominant inter­actions in the three-dimensional crystal packing. Hirshfeld surface analysis indicates that the most important contributions are from O⋯H/H⋯O (34.9%), H⋯H (33.7%), and C⋯H/H⋯C (11.0%) contacts. The energies of the frontier mol­ecular orbitals were computed using density functional theory (DFT) calculations at the B3LYP-D3BJ/def2-TZVP level of theory and the LUMO–HOMO energy gap of the mol­ecule is 3.765 eV. [ABSTRACT FROM AUTHOR]

Background: The application of positron emission tomography/computed tomography (PET/CT) helps provide accurate clinical staging for lung cancer patients. However, the effects and trends in early-stage lung cancer remain unclear. The aim of this study was to compare differences between clinical stage I lung cancer patients who received PET/CT for staging and those who did not. Methods: Data were obtained from the Taiwan Society of Cancer Registry. There were 6587 clinical stage I lung cancer patients between 2009 and 2014 analyzed in this study. We compared the characteristics of the PET/CT and no PET/CT groups. After propensity score matching, it resulted in both groups having 2649 patients. We measured the overall survival rates of all clinical stage I lung cancer patients and the overall survival rates of patients with PET/CT and without PET/CT. Results: The 1-, 3-, and 5-year survival rates of all clinical stage I lung cancer patients were 97.2%, 88.2%, and 79.0%, respectively. Patients with a larger tumor size tended to receive PET/CT for staging (stage Ib: 38.25% vs. 27.82%, p < 0.0001) and a larger resection (lobectomy: 74.62% vs. 66.61%, p < 0.0001). The 5-year survival rates were 79.8% in the PET/CT group and 78.2% in the no PET/CT group after propensity score matching (p = 0.6528). Conclusions: For clinical stage I lung cancer in Taiwan, patients with larger tumor sizes tend to have PET/CT for staging. Although PET/CT provided more precise clinical staging, these patients still received larger resections and had more pathological migration. However, there was no overall survival rate benefit after PET/CT. [ABSTRACT FROM AUTHOR]