Association between NTCP hepatic expression and inflammation/fibrosis as well as gender-specific differences in chronic HBV-infected patients.

To investigate the relationship between the expression of hepatitis B virus (HBV) functional receptor sodium taurocholate cotransporting polypeptide (NTCP) with disease progression and gender-specific differences in chronic HBV-infected patients. Liver samples were collected from chronic HBV-infected patients who underwent percutaneous liver biopsy or liver surgery. HBV DNA levels and the mRNA and protein expression levels of NTCP in liver tissues were determined. The relationship between NTCP expression and HBV DNA levels, inflammatory activity, fibrosis, and gender-specific differences were analyzed. A total of 94 chronic HBV-infected patients were included. Compared with patients with a METAVIR score of A0-1 or F0-1, patients with score of A2 or F2/F3 had a relatively higher level of NTCP expression. NTCP levels were positively correlated with HBV DNA levels. The inflammatory activity scores and fibrosis scores of women <50 years were significantly lower than those of women ≥50 years and age-matched males. In patients with score A0-2 or F0-3, women <50 years have lower NTCP expression level compared to women ≥50 years and age-matched males. NTCP can promote the disease progression by affecting the viral load of HBV. The NTCP expression difference may be why male and postmenopausal women are more prone to disease progression than reproductive women.

Spiritual Coping in Family Caregivers of Patients With Advanced Cancer: A Cross-Sectional Study.

CONTEXT: Family caregivers face significant challenges when providing care to individuals with advanced cancer. Spiritual coping strategies may support caregivers in addressing these challenges. OBJECTIVES: We evaluated spiritual coping levels among Chinese family caregivers of patients with advanced cancer and explored associated factors. METHODS: This cross-sectional study recruited 358 family caregivers of patients with advanced cancer. The Spiritual Coping Scale was used to evaluate spiritual coping levels, while various scales, including the Caregiver Reaction Assessment Scale, General Self-Efficacy Scale-Schwarzer, and Perceived Social Support Scale, were used to identify influencing factors. T-tests and analysis of variance were used for group comparisons. Pearson's correlation and multivariate linear regression were used to analyze the associated factors. RESULTS: Chinese family caregivers of patients with advanced cancer had moderate spiritual coping levels. Differences in spiritual coping levels were observed in sex, religion, and the presence or absence of anxiety and depression (p < 0.05). Women and caregivers who identified as religious had higher levels, while those with anxiety or depression had lower levels. Spiritual coping was positively correlated with self-efficacy and spiritual health (p < 0.01). Multiple linear regression analysis revealed that religion, anxiety, depression, self-efficacy, and spiritual health were statistically significant associated factors for spiritual coping scores, explaining 43.3% of the variance in scores (F = 53.769, p < 0.001). CONCLUSION: The spiritual coping of Chinese family caregivers should be considered by health care providers, who should focus on alleviating their anxiety and depression while improving self-efficacy and spiritual health, especially among nonreligious caregivers.

Competence and perceptions of spiritual care among clinical nurses: A multicentre cross-sectional study.

AIMS: To identify latent profiles of competence and perceptions of spiritual care among clinical nurses and explore the possible influencing factors. BACKGROUND: Understanding nurses' level of spiritual care competence and their perceptions and acceptance of such care is important, which could help devise nurse training programmes to address such competence in clinical nurses. However, research addressing interindividual variability in competence and perceptions among Chinese nurses is lacking. DESIGN: Multicentre cross-sectional study. METHODS: Nurses working in departments with critically ill patients from 12 community, 5 secondary and 10 tertiary hospitals in Shanghai completed a demographic information questionnaire and the Chinese versions of the Spiritual Care Competence Scale, Spiritual Care-Giving Scale and Spiritual Perspectives Scale. The data were analysed using IBM SPSS v26.0 and Mplus version 8.3. Latent profile analysis identified subgroups with different levels of spiritual care competence. RESULTS: In total, 1277 Chinese nurses were recruited. Four profiles of competence and perceptions of spiritual care were revealed: Low ability (23.8%), High ability (6.4%), High acceptance (34.9%) and Moderate (34.9%). The level of job position, spiritual care-related education, hospital grade and nurses' perceptions and perspectives of spiritual care predicted the probability of profile memberships in their competence. CONCLUSIONS: There was heterogeneity in the characteristics of spiritual care competence. Nursing managers can implement individualised interventions, including relevant training, according to the influencing factors of different competence profiles to improve the level of such competence among nurses. RELEVANCE TO CLINICAL PRACTICE: The results provide a new and expanded view of improving nurses' spiritual care competence. Interprofessional collaboration with clinicians, administrators, educators and spiritual leaders can contribute to the development of related education and training. REPORTING METHOD: EQUATOR guidelines, STROBE checklist: cross-sectional studies. PATIENT OR PUBLIC CONTRIBUTION: All participants were clinical nurses. Participants were informed they could withdraw from the study at any time.

Insights on epithelial cells at the single-cell level in hepatocellular carcinoma prognosis and response to chemotherapy.

Background: Hepatocellular carcinoma (HCC) originates from Epithelial cells, and epithelial lineage plasticity has become a promising research direction for advancing HCC treatment. This study aims to focus on Epithelial cells to provide target insights for detecting HCC prognosis and response to drug therapy. Methods: Single-cell RNA sequencing (scRNA-seq) data from GSE149614 were clustered using Seurat, and the differentiation and evolution of epithelial cells were analyzed by Monocle 2. Scissor+ and Scissor- Epithelial cells associated with the prognostic phenotypes of bulk RNA-seq of HCC were screened using the Scissor algorithm for differential analysis to screen candidate genes. Candidate genes were overlapped with prognostic related genes screened by univariate Cox regression, and the Least Absolute Shrinkage and Selection Operator (LASSO) sparse penalty was imposed on the intersection genes to construct a risk assessment system. Results: Eight major cell subpopulations of HCC were identified, among which the proportion of epithelial cells in non-tumor liver tissues and HCC tissues was significantly different, and its proportion increased with advanced clinical stage. During the progression of HCC, the whole direction of epithelial cells differentiation trajectory was towards enhanced cell proliferation. Differential analysis between Scissor+ and Scissor- epithelial cells screened 1,265 upregulated and 191 downregulated prognostic candidate genes. Wherein, the upregulated genes were enriched in Cell processes, Genetic information processing, Metabolism and Human disease with Infection. Nevertheless, immune system related pathways took the main proportions in downregulated genes enriched pathways. There were 17 common genes between upregulated candidate genes and prognostic risk genes, of which CDC20, G6PD and PLOD2 were selected as components for constructing the risk assessment system. Risk score showed a significant correlation with tumor stage, epithelial-mesenchymal transition (EMT) related pathways and 22 therapeutic drugs, and was an independent prognostic factor for HCC. Conclusion: This study revealed the cellular composition of HCC, the differentiation evolution and functional landscape of epithelial cells in the further deterioration of HCC, and established a 3-gene risk model, which was closely related to clinical features, EMT, and drug sensitivity prediction. These findings provided insights in patient prognosis and drug therapy detection for HCC.

Two genetic variants in the SRD5A2 gene are found to be associated with sex differences in the disease characteristics of patients with chronic hepatitis B virus infection.

BACKGROUND: To examine the expression characteristics of single nucleotide polymorphisms (SNPs) in the SRD5A2 gene and investigate their potential association with differences in the clinical characteristics between sexes in patients with chronic hepatitis B virus (HBV) infection. METHODS: A total of 30 loci in six genes primarily involved in the metabolism and signaling of sex hormones/sex hormone receptors, namely AKR1C2, AKR1C3, HSD17B6, SRD5A1, SRD5A2, and ESR1, were genotyped in 1007 patients from eight counties (cities) in Northeastern China with chronic HBV infection and 1040 healthy controls, and their association with viral replication characteristics and the differences in disease severity between sexes was assessed. Western blotting was conducted to determine the hepatic SRD5A2 protein level and its relationship with the inflammatory activity and fibrosis degree in male and female patients. RESULTS: Two SNP loci in the SRD5A2 gene (rs12470143 and rs7594951) exhibited significant differences in genotype and allele frequencies between sexes, with the proportion of T alleles significantly higher in males than in females. It was found that the incidence and severity of HBV-related liver fibrosis were significantly higher in patients with the T/T genotype in SRD5A2 rs12470143 and rs7594951 than those with the non-T/T genotype. Additionally, serum HBV DNA levels were significantly elevated in T/T patients compared to non-T/T patients. Female patients exhibited significantly lower serum DNA levels compared to male patients. Western blot analysis indicated that greater hepatic SRD5A2 protein levels were associated with higher METAVIR inflammation and fibrosis scores. Furthermore, multivariate analysis showed that the two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T), together with the male sex, age > 50 years old, HBeAg positive status, elevated serum HBsAg load, high serum HBV DNA load, and HBV genotype C, were independent risk factors for HBV-related liver fibrosis. CONCLUSIONS: This study demonstrated that two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T) are associated with sex differences in the clinical characteristics of patients with chronic HBV infection.

This study genotyped 30 genetic loci in six genes primarily involved in the metabolism and signaling pathways of sex hormones/sex hormone receptors, including AKR1C2, AKR1C3, HSD17B6, SRD5A1, SRD5A2, and ESR1, in 1007 patients with chronic hepatitis B virus (HBV) infection and 1040 healthy controls. It was found that two single nucleotide polymorphism (SNP) loci in the SRD5A2 gene (rs12470143 and rs7594951) showed significant differences in genotype and allele frequencies between male and female patients. Further, the proportion of the T alleles was significantly higher in males than in females. The study also found that patients with the T/T genotype had a higher incidence and severity of HBV-related liver fibrosis compared to those with other genotypes. Additionally, serum HBV DNA levels were significantly higher in T/T patients compared to non-T/T patients. Female patients had lower serum DNA levels compared to male patients. Further analysis showed that higher levels of the SRD5A2 protein were associated with increased inflammation and fibrosis scores in the liver. Multivariate analysis revealed that the two genetic variants in the SRD5A2 gene, together with male sex, age over 50, HBeAg positive status, elevated serum HBsAg load, high serum HBV DNA load, and HBV genotype C, were independent risk factors for HBV-related liver fibrosis. In summary, this study demonstrated that genetic variations in the SRD5A2 gene are associated with differences in the clinical characteristics of male and female patients with chronic HBV infection.

Metabolic disorders induced by PNPLA3 and TM6SF2 gene variants affect chronic kidney disease in patients infected with non-genotype 3 hepatitis C virus.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) infections differ in their risk for metabolic disorders and chronic kidney disease (CKD). The aim of this study was to investigate the effect of metabolic disorders induced by genetic factors on CKD in HCV-infected patients. METHODS: Patients with chronic non-genotype 3 HCV infection with or without CKD were examined. PNPLA3 and TM6SF2 variants were determined using high-throughput sequencing. The relationships of variants and different combinations with metabolic disorders were analyzed in CKD patients. Univariate and multivariate analyses were used to identify factors associated with CKD. RESULTS: There were 1022 patients with chronic HCV infection, 226 with CKD and 796 without CKD. The CKD group had more severe metabolic disorders, and also had higher prevalences of liver steatosis, the PNPLA3 rs738409 non-CC genotype, and the TM6SF2 rs58542926 CC genotype (all P < 0.05). Relative to patients with the PNPLA3 rs738409 CC genotype, patients with the non-CC genotype had a significantly decreased eGFR and a greater prevalence of advanced CKD (CKD G4-5). Patients with the TM6SF2 rs58542926 CC genotype had a lower eGFR and a higher prevalence of CKD G4-5 than those with the non-CC genotype. Multivariable analysis indicated that multiple metabolic abnormalities, including liver steatosis and the PNPLA3 rs738409 C > G variant, increased the risk of CKD, but the TM6SF2 rs58542926 C > T variant decreased the risk of CKD. CONCLUSION: Specific PNPLA3 rs738409 and TM6SF2 rs58542926 variants are independent risk factors for CKD in patients with chronic HCV infections and are associated with the severity of renal injury.

Regional Citrate Anticoagulation or Heparin Anticoagulation for Renal Replacement Therapy in Patients With Liver Failure: A Systematic Review and Meta-Analysis.

In patients with liver failure complicated by acute kidney injury, renal replacement therapy (RRT) is often required to improve the internal environment. The use of anticoagulants for RRT in patients with liver failure remains controversial. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for studies. The methodological quality of the included studies was assessed using the Methodological Index for Nonrandomized Studies. A meta-analysis was performed using R software (version 3.5.1) and Review Manager (version 5.3.5). During RRT, 348 patients from 9 studies received regional citrate anticoagulation (RCA), and 127 patients from 5 studies received heparin anticoagulation (including heparin and LMWH). Among patients who received RCA, the incidence of citrate accumulation, metabolic acidosis, and metabolic alkalosis were 5.3% (95% confidence interval [CI]: 0%-25.3%), 26.4% (95% CI: 0-76.9), and 1.8% (95% CI: 0-6.8), respectively. The potassium, phosphorus, total bilirubin (TBIL), and creatinine levels were lower, whereas the serum pH, bicarbonate, base excess levels, and total calcium/ionized calcium ratio were higher after treatment than before treatment. Among patients who received heparin anticoagulation, the TBIL levels were lower, whereas the activated partial thromboplastin clotting time and D-dimer levels were higher after treatment than before treatment. The mortality rates in the RCA and heparin anticoagulation groups were 58.9% (95% CI: 39.2-77.3) and 47.4% (95% CI: 31.1-63.7), respectively. No statistical difference in mortality was observed between the 2 groups. For patients with liver failure, the administration of RCA or heparin for anticoagulation during RRT under strict monitoring may be safe and effective.

METTL3 (Methyltransferase Like 3)-Dependent N6-Methyladenosine Modification on Braf mRNA Promotes Macrophage Inflammatory Response and Atherosclerosis in Mice.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease, in which macrophages determine the progression of atherosclerotic plaques. However, no studies have investigated how METTL3 (methyltransferase like 3) in macrophages affects atherosclerotic plaque formation in vivo. Additionally, whether Braf mRNA is modified by METTL3-dependent N6-methyladenosine (m6A) methylation remains unknown. METHODS: We analyzed single-cell sequencing data of atherosclerotic plaques in mice fed with a high fat diet for different periods. Mettl3fl/fl Lyz2cre Apoe-/- mice and littermate control Mettl3fl/fl Apoe-/- mice were generated and fed high fat diet for 14 weeks. In vitro, we stimulated peritoneal macrophages with ox-LDL (oxidized low-density lipoprotein) and tested the mRNA and protein expression levels of inflammatory factors and molecules regulating ERK (extracellular signal-regulated kinase) phosphorylation. To find METTL3 targets in macrophages, we performed m6A-methylated RNA immunoprecipitation sequencing and m6A-methylated RNA immunoprecipitation-qPCR. Further, point mutation experiments were used to explore m6A-methylated adenine. Using RNA immunoprecipitation assay, we explored m6A methylation-writing protein bound to Braf mRNA. RESULTS: In vivo, METTL3 expression in macrophages increased with the progression of atherosclerosis. Myeloid cell-specific METTL3 deletion negatively regulated atherosclerosis progression and the inflammatory response. In vitro, METTL3 knockdown or knockout in macrophages attenuated ox-LDL-mediated ERK phosphorylation rather than JNK (c-Jun N-terminal kinase) and p38 phosphorylation and reduced the level of inflammatory factors by affecting BRAF protein expression. The negative regulation of inflammation response caused by METTL3 knockout was rescued by overexpression of BRAF. In mechanism, METTL3 targeted adenine (39725126 in chromosome 6) on the Braf mRNA. Then, YTHDF1 could bind to m6A-methylated Braf mRNA and promoted its translation. CONCLUSIONS: Myeloid cell-specific Mettl3 deficiency suppressed hyperlipidemia-induced atherosclerotic plaque formation and attenuated atherosclerotic inflammation. We identified Braf mRNA as a novel target of METTL3 in the activation of the ox-LDL-induced ERK pathway and inflammatory response in macrophages. METTL3 may represent a potential target for the treatment of atherosclerosis.

Effect of Anticoagulant Versus Non-Anticoagulant Therapy on Mortality of Sepsis-Induced Disseminated Intravascular Coagulation: A Systematic Review and Meta-Analysis.

BACKGROUND: Sepsis is a syndrome of severe systemic inflammatory response. When combined with disseminated intravascular coagulation, mortality is increased. The need for anticoagulant therapy is still the focus of debate. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched. Adult patients with sepsis-induced disseminated intravascular coagulation were included in this study. All-cause mortality as efficacy and serious bleeding complications as adverse effect were measured as primary outcomes. Methodological quality of included studies were assessed using the Methodological Index for Non-randomized Studies (MINORS). Meta-analysis was performed using R software (version 3.5.1) and Review Manager (version 5.3.5). RESULTS: There were nine eligible studies with 17,968 patients included. There were no significant reductions in mortality between the anticoagulant group and the non-anticoagulant group (RR, 0.89; 95% CI, 0.72-1.10; P = 0.27). The DIC resolution rate in the anticoagulation group has a statistically significant increase compared with the control group [OR: 2.62, 95% CI (1.54-4.45), P < 0.05]. And there was no significant difference in bleeding complications between the two groups (RR, 1.27; 95% CI, 0.77-2.09; P = 0.69). SOFA score reduction did not change significantly between the two groups (P = 0.13). CONCLUSIONS: Our study observed no significant benefit of anticoagulant therapy on mortality of sepsis-induced DIC. Anticoagulation therapy can promote DIC resolution in sepsis-induced DIC. In addition, anticoagulant therapy does not increase the risk of bleeding in these patients.

E3 ligase RNF99 negatively regulates TLR-mediated inflammatory immune response via K48-linked ubiquitination of TAB2.

Innate immunity is the first line to defend against pathogenic microorganisms, and Toll-like receptor (TLR)-mediated inflammatory responses are an essential component of innate immunity. However, the regulatory mechanisms of TLRs in innate immunity remain unperfected. We found that the expression of E3 ligase Ring finger protein 99 (RNF99) decreased significantly in peripheral blood monocytes from patients infected with Gram negative bacteria (G-) and macrophages stimulated by TLRs ligands, indicating the role of RNF99. We also demonstrated for the first time, the protective role of RNF99 against LPS-induced septic shock and dextran sodium sulfate (DSS)-induced colitis using RNF99 knockout mice (RNF99-/-) and bone marrow-transplanted mice. In vitro experiments revealed that RNF99 deficiency significantly promoted TLR-mediated inflammatory cytokine expression and activated the NF-κB and MAPK pathways in macrophages. Mechanistically, in both macrophages and HEK293 cell line with TLR4 stably transfection, RNF99 interacted with and degraded TAK1-binding protein (TAB) 2, a regulatory protein of the kinase TAK1, via the lysine (K)48-linked ubiquitin-proteasomal pathway on lysine 611 of TAB2, which further regulated the TLR-mediated inflammatory response. Overall, these findings indicated the physiological significance of RNF99 in macrophages in regulating TLR-mediated inflammatory reactions. It provided new insight into TLRs signal transduction, and offered a novel approach for preventing bacterial infections, endotoxin shock, and other inflammatory ills.

Identification and Validation of Immune Molecular Subtypes and Immune Landscape Based on Colon Cancer Cohort.

Background: The incidence and mortality rates of colon adenocarcinoma (COAD), which is the fourth most diagnosed cancer worldwide, are high. A subset of patients with COAD has shown promising responses to immunotherapy. However, the percentage of patients with COAD benefiting from immunotherapy is unclear. Therefore, gaining a better understanding of the immune milieu of colon cancer could aid in the development of immunotherapy and suitable combination strategies. Methods: In this study, gene expression profiles and clinical follow-up data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and molecular subtypes were identified using the ConsensusClusterPlus package in R. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic value of immune subtypes. The graph structure learning method was used to reduce the dimension to reveal the internal structure of the immune system. Weighted correlation network analysis (WGCNA) was performed to identify immune-related gene modules. Finally, western blotting was performed to verify the gene expression patterns in COAD samples. Results: The results showed that 424 COAD samples could be divided into three subtypes based on 1921 immune cell-related genes, with significant differences in prognosis between subtypes. Furthermore, immune-related genes could be divided into five functional modules, each with a different distribution pattern of immune subtypes. Immune subtypes and gene modules were highly reproducible across many data sets. There were significant differences in the distribution of immune checkpoints, molecular markers, and immune characteristics among immune subtypes. Four core genes, namely, CD2, FGL2, LAT2, and SLAMF1, with prognostic significance were identified by WGCNA and univariate Cox analysis. Conclusion: Overall, this study provides a conceptual framework for understanding the tumor immune microenvironment of colon cancer.

Signal transducer and activator of transcription 3 cooperates with androgen receptor/cell cycle-related kinase signalling pathway in the progression of hepatitis B virus infection and gender differences.

The study aimed to investigate the role of androgen receptor (AR)/cell cycle-related kinase (CCRK) signalling pathway in chronic hepatitis B virus (HBV) infection and gender differences, and the contribution of AR regulatory factor signal transducer and activator of transcription 3 (STAT3) in it. AR, CCRK, and phosphorylated STAT3 expressions in liver tissues of chronic HBV-infected patients and non-HBV controls were determined by western blot and compared between genders. The relationships of expression levels with serum HBV DNA levels, liver inflammation activity, and fibrosis score were analysed in chronic HBV-infected patients. The relationships between expression levels of three proteins were also analysed. HBV-infected patients had significantly higher expression levels of AR, CCRK, and p-STAT3Tyr705 compared with controls (p < .01). The expression levels of AR, CCRK, and p-STAT3Tyr705 in chronic HBV-infected patients with severe inflammation were significantly higher than those with mild inflammation (p < .05). Expression levels in patients with heavier fibrosis (stage F4) were higher than in those with less fibrosis (stages F0-3) (p < .01). No gender differences were observed in AR, CCRK, and p-STAT3Tyr705 levels in non-HBV controls; higher levels were observed in HBV-infected males than in HBV-infected females (p < .05). AR, CCRK, and p-STAT3Tyr705 levels in liver tissues positively correlated with each other (p < .0001) and with serum HBV DNA levels (p < .0001). In conclusion, in this study, we first found concordant over-expression of AR, CCRK, and STAT3 in liver tissues of chronic HBV-infected patients who have not yet developed HCC, significantly correlated with the severity of the disease and showed gender differences. STAT3 may be a potential therapeutic co-target for chronic HBV infection.

Development and clinical validation of a 3-miRNA signature to predict prognosis of gastric cancer.

AIMS: Identification of miRNA signature to predict the prognosis of gastric cancer (GC) patients by integrating bioinformatics and experimental validation. METHODS: The miRNA expression profile and clinical data of GC were collected. The univariable and LASSO-Cox regression were used to construct the risk signature. The receiver operating characteristic (ROC) curve analysis confirmed the good performance of the prognostic model. RESULTS: A 3-miRNA prognostic signature was constructed, which included hsa-miR-126-3p, hsa-miR-143-5p, and hsa-miR-1275. A nomogram, including the prognostic signature to predict the overall survival, was established, and internal validation in the The Cancer Genome Atlas (TCGA) cohort was performed. We found that compared with the traditional pathological stage, the nomogram was the best at predicting the prognosis. CONCLUSIONS: The predictive model and the nomogram will enable patients with GC to be more accurately managed in clinical practice.

Long-term clinical benefit of Peg-IFNα and NAs sequential anti-viral therapy on HBV related HCC.

Analysis of the value of long-term antiviral therapy using sequential Peg-IFN therapy and nucleos(t)ide analogues (NAs) improves the prognosis of HBV-related HCC. HBV-related HCC patients were classified into sequential therapy with Peg-IFNα-2a and NAs, and NAs therapy alone. All patients were followed up for 5 years. The survival rate, HCC recurrence rate, Child-Pugh score, and side effects of drugs were evaluated. Firstly, the early and late cumulative survival rate was higher in patients receiving antiviral therapy compared with the control patients (p<0.05). Patients receiving sequential therapy with Peg-IFNα-2a and NAs showed a higher late cumulative survival rate and significantly reduced early and late recurrence rate, compared to those in the NA-alone group (p<0.05). Single NAs therapy only reduced the late recurrence rate in HCC-patients. Secondly, NAs therapy significantly increased the Child-Pugh score after five years of therapy (five-year therapy 7.03±1.50 vs. initial score 6.63±0.85; p<0.05), whereas the sequential therapy with Peg-IFNα-2a and NAs did not greatly alter the Child-Pugh score (6.88±1.26; p>0.05). Compared to the control patients, patients receiving antiviral therapy (NAs alone or sequential therapy with Peg-IFNα-2a and NAs) exhibited a significantly decreased Child-Pugh score (p<0.05). Compared to NAs alone, sequential therapy with Peg-IFNα-2a and NAs provided a more efficient strategy for improving both the five-year survival rate and the two-year or five-year recurrence rate in patients.

Gene's co-expression network and experimental validation of molecular markers associated with the drug resistance of gastric cancer.

Aim: Chemotherapy can significantly improve the overall survival rate of patients with gastric cancer; however, so far little is known about the molecular mechanism of resistance to chemotherapy. Therefore, this study was proposed to elucidate molecular markers of resistance to chemotherapeutic agent in gastric cancer. Materials & methods: Weighted gene co-expression network analyses were performed in gastric cancer cohort. The most relevant genes modules for gastric cancer resistance were selected. Gene oncology function enrichment of genes was conducted. The biological function of resistant genes were identified in vitro. Results & conclusion: Two resistant hub genes, SPTBN1 and LAMP1, were selected. Experiments showed that downregulation of SPTBN1and LAMP1 proteins significantly enhanced the sensitivity of human gastric cancer cells SGC7901 to 5-FU and cisplatin. Thus, our results provide a baseline about the potential factors of drug resistance in gastric cancer.

CXCL8 is a potential biomarker for predicting disease progression in gastric carcinoma.

BACKGROUND: To find potential biomarkers for predicting disease progression in gastric cancer (GC). METHODS: An extensive bioinformatics study of the Cancer Genome Atlas (TCGA) and Oncomine datasets was conducted to define potential mRNA biomarkers for GC. The mRNA expression profiles of 375 GC and 32 neighboring noncancerous adrenal tissues were analyzed. The Oncomine database was used to validate the hub genes. The correlation between candidate hub gene expression and survival of GC patients was analyzed using the Kaplan-Meier method. RESULTS: Ten differentially expressed genes were identified as hub genes, and CXCL8 was the only gene validated as being up-regulated in GC tissues compared to control tissues using both the TCGA and Oncomine databases. Immunofluorescence staining showed that CXCL8 was expressed in GC tissues, and its higher expression predicted worse relapse-free survival in GC patients. CONCLUSIONS: CXCL8 is a potential biomarker for predicting disease progression in GC.

Peg-interferon and nucleos(t)ide analogue combination at inception of antiviral therapy improves both anti-HBV efficacy and long-term survival among HBV DNA-positive hepatocellular carcinoma patients after hepatectomy/ablation.

Antiviral therapy has been shown to improve the prognosis of hepatitis B virus (HBV) DNA-positive hepatocellular carcinoma (HCC) after radical treatment, but antiviral treatments require further optimization. This study aimed to evaluate the efficacies of different antiviral strategies with HCC patients after hepatectomy/ablation. This prospective, randomized, controlled and multi-centre trial enrolled HBV DNA-positive primary HCC patients after hepatectomy/ablation between January 2007 and January 2009. Patients were divided into four groups: early combination (entecavir plus Peg-interferon [IFN]α-2a co-administration during year 1); late combination (addition of Peg-IFNα-2a for 48 weeks after 1 year of entecavir); nucleos(t)ide analogue[NA] monotherapy; and non-antiviral treatment. Primary endpoints included recurrence-free survival and overall survival. A total of 447 patients were enrolled. The 2-year and 8-year recurrence-free survival and 8-year overall survival rates were significantly higher in the early combination group than in the other two antiviral groups (P < .05). After 48-week treatment, more patients achieved an HBsAg reduction >1500 IU/mL and the mean HBsAg level was significantly lower in the early combination group compared with the late combination and NA monotherapy groups (P < .05). Multivariate analysis showed that early combination therapy and a reduction in HBsAg by >1500 IU/mL after 48 weeks of therapy correlated with reduced mortality and disease recurrence. Early introduction of combination antiviral treatment may represent a more effective therapeutic strategy for patients with HBV DNA-positive HCC after hepatectomy/ablation. A reduction in HBsAg by >1500 IU/mL after 48-week treatment is associated with reduced mortality and disease recurrence of HBV DNA-positive HCC patients after hepatectomy/ablation.

RETRACTED: lncRNA PEG10 promotes cell survival, invasion and migration by sponging miR-134 in human bladder cancer.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief as unusual similarity between the background of various Western Blots have been detected post-publication. Also, quadrants within various FACS plots appear similar to each other in Figure 2E. Panels from Figures 2C,D, 4C,D and 6D,E appear similar to panels from Figures 1B,C, 2D,E, 3D,E and 5C,D of the article that Zhiliang Guo, Lanlan Li, Yu Gao, Xiaoyun Zhang and Min Cheng have published in the Artificial Cells, Nanomedicine, and Biotechnology 47 (2019) 2624-2633 https://doi.org/10.1080/21691401.2019.1629953. Although this article was published earlier than the other article, the Editor decided to retract this article given concerns about the reliability of the data.