Mechanism of dact2 gene inhibiting the occurrence and development of liver fibrosis.

There are few reports about the relationship between dact2 and liver fibrosis. The inhibitory mechanism of dact2 in liver fibrosis is not clear, we need to further explore it. In this study has been shown that the dact2 gene can inhibit liver fibrosis. In this experiment, we used lentivirus as a vector to construct a lentivirus vector carrying the dact2 gene and packaged dact2 recombinant lentivirus and its control vector. HSC-T6 infected cells were observed. The effect of dact2 gene expression was activated by Wnt3a HSC-T6 cells. Immunoblot was used to detect α - SMA expression, TGF - ß 1, Smad3, Smad7, ß - Catenin and CyclinD1. The expression of MMP-2 and TIMP-1 was detected by real-time PCR. At the same time, dact2 recombinant lentivirus was injected into the tail vein. Carbon tetrachloride was used to establish the liver fibrosis model. After 7 weeks of modeling, the staining was used to observe the pathological changes of liver tissue, hydroxyproline was used to analyze the changes of collagen content in liver tissue, the expression of the protein was observed by immunohistochemistry, and the expression of fibrosis-related genes was detected by real-time PCR. Results showed that the dact2 gene expression could inhibit the activation of HSC-T6 cells and reduce the expression of TGF - ß 1. The percentage of Smad3, ß - Catenin and cyclinD1 protein was 50.02%, 46.73%, 47.58% and 37.50% respectively (P < 0.05).

The Chinese Society of Hepatology position statement on the redefinition of fatty liver disease.

Fatty liver disease associated with metabolic dysfunction is of increasing concern in mainland China, the world's most populous country. The incidence of fatty liver disease is highest in China, surpassing the incidence in European countries and the USA. An international consensus panel recently published an influential report recommending a novel definition of fatty liver disease associated with metabolic dysfunction. This recommendation includes a switch in name from non-alcoholic fatty liver disease (NAFLD) to metabolic (dysfunction)-associated fatty liver disease (MAFLD) and adoption of a set of positive criteria for disease diagnosis that are independent of alcohol intake or other liver diseases. Given the unique importance of this proposal, the Chinese Society of Hepatology (CSH) invited leading hepatologists and gastroenterologists representing their respective provinces and cities to reach consensus on alternative definitions for fatty liver disease from a national perspective. The CSH endorses the proposed change from NAFLD to MAFLD (supported by 95.45% of participants). We expect that the new definition will result in substantial improvements in health care for patients and advance disease awareness, public health policy, and political, scientific and funding outcomes for MAFLD in China.

Survival improvement and prognosis for hepatocellular carcinoma: analysis of the SEER database.

BACKGROUND: Hepatocellular carcinoma (HCC) incidences have been increasing in the United States. This study aimed to examine temporal trend of HCC survival and determine prognostic factors influencing HCC survival within the U.S. METHODS: The Surveillance Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with primary HCC from 1988 to 2015. Overall survival (OS) and disease-specific survival (DSS) were calculated by the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for prognostic factors and comparing survival between patients diagnosed at different periods (per 5-year interval). Results A total of 80,347 patients were included. The proportions of both young patients (< 45 years) and old patients (≥75 years) decreased over time (P < 0.001) and the male-to-female ratio increased over time (P < 0.001). Significant decreasing temporal trends were observed for HCC severity at diagnosis, including SEER stage, tumor size, tumor extent, and lymph node involvement (P < 0.001 for all). OS and DSS of patients with HCC improved over time (P < 0.001). After adjusting for patient and tumor characteristics and treatment difference, period of diagnosis retained an independent factor for improved DSS and its prognostic significance was evident for localized and regional HCC (P < 0.001), but not for distant HCC. On multivariate analyses, young age, female gender, Hispanic ethnicity, and married status were predictors favoring DSS, whereas a worse DSS was observed for patients with tumor > 5 cm, with vascular invasion, and with lymph node involvement. Patients treated with liver-directed therapy (HR = 0.54, 95% CI: 0.35-0.56), hepatic resection (HR = 0.35, 95% CI: 0.33-0.37), and transplantation (HR = 0.14, 95% CI: 0.13-0.15) had significantly longer DSS compared with those who received no surgery. In stratified analyses, the beneficial effects of surgical approach, regardless therapy type, were significant across all stages. CONCLUSIONS: Our results indicate a significant improvement in survival for HCC patients from 1988 to 2015, which may be attributable to advances in early diagnosis and therapeutic approaches.

Cyano-Isocyanide Iridium(III) Complexes with Pure Blue Phosphorescence.

In this paper, we report a series of six neutral, blue-phosphorescent cyclometalated iridium complexes of the type Ir(C^Y)2(CNAr)(CN). The cyclometalating ligands in these compounds (C^Y) are either aryl-substituted 1,2,4-triazole or NHC ligands, known to produce complexes with blue phosphorescence. These cyclometalating ligands are paired with π-acidic, strongly σ-donating cyano and aryl isocyanide (CNAr) ancillary ligands, the hypothesis being that these ancillary ligands would destabilize the higher-lying ligand-field (d-d) excited states, allowing efficient blue photoluminescence. The compounds are prepared by substituting the cyanide ancillary ligand onto a chloride precursor and are characterized by NMR, mass spectrometry, infrared spectroscopy, and, for five of the compounds, by X-ray crystallography. Cyclic voltammetry establishes that these compounds have large HOMO-LUMO gaps. The mixed cyano-isocyanide compounds are weakly luminescent in solution, but they phosphoresce with moderate to good efficiency when doped into poly(methyl methacrylate) films, with Commission Internationale de L'Eclairage coordinates that indicate deep blue emission for five of the six compounds. The photophysical studies show that the photoluminescence quantum yields are greatly enhanced in the cyano complexes relative to the chloride precursors, affirming the benefit of strong-field ancillary ligands in the design of blue-phosphorescent complexes. Density functional theory calculations confirm that this enhancement arises from a significant destabilization of the higher-energy ligand-field states in the cyanide complexes relative to the chloride precursors.

Hydrogen bonding interactions can decrease clar sextet character in acridone pigments.

Computed nucleus-independent chemical shifts (NICS), contour plots of isotropic magnetic shielding (IMS), and gauge-including magnetically induced current (GIMIC) plots suggest that polarization of the π-system of acridones may perturb the numbers and positions of Clar sextet rings. Decreasing numbers of Clar sextets are connected to experimental observations of a narrowing HOMO-LUMO gap and increased charge mobility in solid-state assemblies of quinacridone and epindolidione.

Inositol-Requiring Kinase 1 Regulates Apoptosis via Inducing Endoplasmic Reticulum Stress in Colitis Epithelial Cells.

BACKGROUND: Endoplasmic reticulum stress (ERS) has been studied as critical factor during occurrence and development of ulcerative colitis (UC). However, the role of ERS in inflamed UC remains unclear. AIMS: The purpose of this study was to analyze the role of inositol-requiring kinase 1 (IRE-1), a major regulator of ER, in regulating ERS and cell viability. METHODS: In UC mucosa tissue, IRE-1, BiP, XBP-1s, CHOP caspase-12 and GADD34 mRNA were assayed by qRT-PCR. Then, human normal colon epithelial cell line (NCM-460) and colon fibroblast cell line (CCD-33Co) were cultured, and downregulated or upregulated IRE-1 expression. ERS was induced with 100 ng/mL of Interleukin 6 (IL-6). CCK8 assay was performed to analyze cell proliferation. Flow cytometry analysis was conducted to detect the apoptosis. Western blot assay was used to examine ERS markers. RESULTS: IRE-1, BiP, XBP-1s, caspase-12 and CHOP mRNA were highly expressed in UC mucosa tissue, and the expression of GADD34 mRNA significantly decreased. These results show that ERS-induced unfolded protein response was enhanced in UC mucosa tissue. In cells, silencing the expression of IRE-1 could suppress cell proliferation and promote apoptosis through activating unfolded protein response, while the over-expression of IRE-1 had the opposite effect. IL-6 could induce ERS and cells apoptosis. Furthermore, we demonstrated that shRNA IRE-1 could enhance the inhibition of IL-6 on cells viability. CONCLUSIONS: Inhibition of IRE-1 enhanced unfolded protein response and cells apoptosis and IL-6-induced ERS and suggested that IRE-1 might be a potential target of UC.

Thiosquaramide-Based Supramolecular Polymers: Aromaticity Gain in a Switched Mode of Self-Assembly.

Despite a growing understanding of factors that drive monomer self-assembly to form supramolecular polymers, the effects of aromaticity gain have been largely ignored. Herein, we document the aromaticity gain in two different self-assembly modes of squaramide-based bolaamphiphiles. Importantly, O → S substitution in squaramide synthons resulted in supramolecular polymers with increased fiber flexibility and lower degrees of polymerization. Computations and spectroscopic experiments suggest that the oxo- and thiosquaramide bolaamphiphiles self-assemble into "head-to-tail" versus "stacked" arrangements, respectively. Computed energetic and magnetic criteria of aromaticity reveal that both modes of self-assembly increase the aromatic character of the squaramide synthons, giving rise to stronger intermolecular interactions in the resultant supramolecular polymer structures. These examples suggest that both hydrogen-bonding and stacking interactions can result in increased aromaticity upon self-assembly, highlighting its relevance in monomer design.

Efficient Deep Blue Platinum Acetylide Phosphors with Acyclic Diaminocarbene Ligands.

Here we report five blue-phosphorescent platinum bis-phenylacetylide complexes with an investigation of their photophysical and electrochemical attributes. Three of the complexes (1-3) are of the general formula cis-Pt(CNR)2 (C≡CPh)2 , in which CNR is a variably substituted isocyanide and C≡CPh is phenylacetylide. These isocyanide complexes serve as precursors for complexes of the general formula cis-Pt(CNR)(ADC)(C≡CPh)2 (4 and 5), in which ADC is an acyclic diaminocarbene installed by amine nucleophilic addition to one of the isocyanides. All of the complexes exhibit deep blue phosphorescence with λmax ∼430 nm in poly(methyl methacrylate) (PMMA) thin films. Whereas isocyanide complexes 1-3 exhibit modest photoluminescence quantum yields (ΦPL ), incorporation of one acyclic diaminocarbene ligand results in a three-fold to 16-fold increase in ΦPL while still maintaining an identical deep blue color profile.

LncRNA ANCR promotes hepatocellular carcinoma metastasis through upregulating HNRNPA1 expression.

LncRNA ANCR plays important roles in the modulation of epithelial mesenchymal transition (EMT) and tumour metastasis in many tumours. However, the role of ANCR in regulating hepatocellular carcinoma (HCC) metastasis is still not known. The current study aims to investigate the underlying mechanism for tumour oncogenesis of ANCR in HCC metastasis. HCC cell proliferation and migration/invasion were measured by MTT and Transwell assays. Xenograft model was established to determine the effect of ANCR on HCC growth and metastasis. ChIP assay was used to detect the H3 and H4 histone acetylation levels at the ANCR promoter region. RNA pull-down and RIP assay was performed to analyse the relationship between ANCR and heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1). Dual-luciferase reporter gene assay was conducted to determine the interaction between ANCR and miR-140-3p. The results indicated that ANCR was highly expressed in HCC tissues and cells, which promoted the proliferation and migration/invasion of HCC cells. In vivo experiments showed interfering ANCR suppressed the growth and metastasis of HCC. H3/H4 histone acetylation levels at the ANCR promoter region were elevated in HCC tissues and cells, and interfering histone deacetylases 3 (HDAC3) significantly up-regulated ANCR expression. ANCR could bind to HNRNPA1, and promoted the expression of HNRNPA1 through regulating its degradation. In addition, ANCR upregulated the expression of HNRNPA1 through sponging miR-140-3p. Finally, we found that ANCR promoted the EMT and invasion/migration of HCC cells through regulating HNRNPA1. In conclusion, ANCR promoted HCC metastasis by upregulating HNRNPA1, inhibiting HNRNPA1 degradation and sponging miR-140-3p.

Homoleptic Platinum Azo-iminate Complexes via Hydrogenative Cleavage of Formazans.

Homoleptic platinum azo-iminate complexes are formed when triarylformazans are treated with Pt(DMSO)2Cl2 under reducing conditions. The transformation represents a three-proton, three-electron reduction of each formazan and offers a new route for accessing this class of redox-active ligands. The reaction is general for triarylformazans with both electron-donating and electron-withdrawing substituents, and four complexes in total are described. X-ray crystal structures of all four complexes are presented and are consistent with an electronic structure consisting of a formal Pt(II) center, where each azo-iminate is in a monoanionic radical form and contributes five π electrons. The complexes are all diamagnetic, indicating delocalization of the π system over both ligands. The complexes are further characterized by cyclic voltammetry, which shows multiple ligand-centered redox events, including proton-coupled oxidation waves. UV-vis spectroelectrochemistry provides further insight into the nature of the redox events. UV-vis absorption spectroscopy shows strong visible absorption bands attributed to HOMO → LUMO transitions, which is corroborated by time-dependent DFT computations on representative examples.

Silencing of Xeroderma Pigmentosum Group D Gene Promotes Hepatoma Cell Growth by Reducing P53 Expression.

BACKGROUND This study investigated the effect of xeroderma pigmentosum group D (XPD) silencing on the growth of hepatoma cells and assessed the mechanisms. MATERIAL AND METHODS XPD gene was silenced by siRNA in hepatoma cells. The experiments were randomly divided into a control group, a liposome control group, a negative control (NC) group, an XPD siRNA group, and an XPD siRNA + P53 inhibitor group. 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) was used to detect cell viability 24 h after gene silencing and treatments. Terminal deoxynucleotidyl transferases (TdT)-mediated dUTP nick-end labeling (TUNEL) and flow cytometry were used to detect apoptosis. Invasive ability was detected by Transwell assay. Additionally, the expression of mouse double-minute 2 homolog (Mdm2), mouse double-minute 4 homolog (Mdm4), CyclinD1, P21, Bax, P53, C-sis, and Bcl-2 was detected by real-time polymerase chain reaction and Western blotting. RESULTS Compared with the NC group, XPD siRNA significantly reduced XPD expression at both mRNA and protein levels. XPD siRNA significantly promoted cell proliferation, reduced apoptosis, and promoted cell invasive ability. Expression of CyclinD1, Bcl-2, and C-sis increased significantly after XPD silencing, while the expression of P21, Mdm2, Mdm4, Bax, and P53 significantly decreased (vs. NC, P<0.05). Importantly, P53 inhibitor (1 µM bpV) further enhanced the effect of XPD silencing (vs. XPD silencing, P<0.05). CONCLUSIONS Our data revealed that XPD silencing promoted growth of hepatoma cells by reducing P53 expression.

CXCR4 attenuates cardiomyocytes mitochondrial dysfunction to resist ischaemia-reperfusion injury.

The chemokine (C-X-C motif) receptor 4 (CXCR4) is expressed on native cardiomyocytes and can modulate isolated cardiomyocyte contractility. This study examines the role of CXCR4 in cardiomyocyte response to ischaemia-reperfusion (I/R) injury. Isolated adult rat ventricular cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) to simulate I/R injury. In response to H/R injury, the decrease in CXCR4 expression was associated with dysfunctional energy metabolism indicated by an increased adenosine diphosphate/adenosine triphosphate (ADP/ATP) ratio. CXCR4-overexpressing cardiomyocytes were used to determine whether such overexpression (OE) can prevent bio-energetic disruption-associated cell death. CXCR4 OE was performed with adenoviral infection with CXCR4 encoding-gene or non-translated nucleotide sequence (Control). The increased CXCR4 expression was observed in cardiomyocytes post CXCR4-adenovirus transduction and this OE significantly reduced the cardiomyocyte contractility under basal conditions. Although the same extent of H/R-provoked cytosolic calcium overload was measured, the hydrogen peroxide-induced decay of mitochondrial membrane potential was suppressed in CXCR4 OE group compared with control group, and the mitochondrial swelling was significantly attenuated in CXCR4 group, implicating that CXCR4 OE prevents permeability transition pore opening exposure to overload calcium. Interestingly, this CXCR4-induced mitochondrial protective effect is associated with the enhanced signal transducer and activator of transcription 3 (expression in mitochondria. Consequently, in the presence of H/R, mitochondrial dysfunction was mitigated and cardiomyocyte death was decreased to 65% in the CXCR4 OE group as compared with the control group. I/R injury leads to the reduction in CXCR4 in cardiomyocytes associated with the dysfunctional energy metabolism, and CXCR4 OE can alleviate mitochondrial dysfunction to improve cardiomyocyte survival.

Heat shock improves Sca-1+ stem cell survival and directs ischemic cardiomyocytes toward a prosurvival phenotype via exosomal transfer: a critical role for HSF1/miR-34a/HSP70 pathway.

Stem cell-based therapy is a promising intervention for ischemic heart diseases. However, the functional integrity of stem cells is impaired in an ischemic environment. Here, we report a novel finding that heat shock significantly improves Sca-1(+) stem cell survival in an ischemic environment by the regulation of the triangle: heat shock factor 1 (HSF1), HSF1/miR-34a, and heat shock protein 70 (HSP70). Initially we prove that HSP70 is the key chaperone-mediating cytoprotective effect of heat shock in Sca-1(+) cells and then we establish miR-34a as a direct repressor of HSP70. We found that miR-34a was downregulated in heat shocked Sca-11 stem cells (HSSca-11 cells) [corrected]. Intriguingly, we demonstrate that the downregulation of miR-34a is attributed to HSF1-mediated epigenetic repression through histone H3 Lys27 trimethylation (H3K27me3) on miR-34a promoter. Moreover, we show that heat shock induces exosomal transfer of HSF1 from Sca-1(+) cells, which directs ischemic cardiomyocytes toward a prosurvival phenotype by epigenetic repression of miR-34a. In addition, our in vivo study demonstrates that transplantation of (HS) Sca-1(+) cells significantly reduces apoptosis, attenuates fibrosis, and improves global heart functions in ischemic myocardium. Hence, our study provides not only novel insights into the effects of heat shock on stem cell survival and paracrine behavior but also may have therapeutic values for stem cell therapy in ischemic heart diseases.

Identification roles of NFE2L3 in digestive system cancers.

BACKGROUND: Morbidity and mortality rates of Digestive System Cancers (DSC) continue to pose human lives and health. Nuclear factor erythroid 2-like protein 3 (NFE2L3) is aberrantly expressed in DSC. This study aimed to explore the clinical value and underlying mechanisms of NFE2L3 as a novel biomarker in DSC. METHODS: We utilized data from databases and clinical gastric cancer specimens to validate the aberrant expression level of NFE2L3 and further assessed the clinical value of NFE2L3. To investigate the potential molecular mechanism of NFE2L3, we analyzed the correlation of NFE2L3 with immune molecular mechanisms, constructed PPI network, performed GO analysis and KEGG analysis, and finally explored the biological function of NFE2L3 in gastric cancer cells. RESULTS: NFE2L3 expression is up-regulated in DSC and has both prognostic and diagnostic value. NFE2L3 correlates with various immune mechanisms, PPI network suggests proteins interacting with NFE2L3, GSEA analysis suggests potential molecular mechanisms for NFE2L3 to play a role in cancer promotion, and in vitro cellular experiments also confirmed the effect of NFE2L3 on the biological function of gastric cancer cells. CONCLUSION: Our study confirms the aberrant expression and molecular mechanisms of NFE2L3 in DSC, indicating that NFE2L3 could serve as a novel biomarker for diagnosis and prognosis of DSC.

Prolonged elevated heart rate and 90-Day mortality in acute pancreatitis.

Prolonged elevated heart rate (peHR) is recognized as a risk factor for poor prognosis among critically ill patients. However, there is currently a lack of studies investigating the association between peHR and patients with acute pancreatitis. Multiparameter Intelligent Monitoring in Intensive Care IV (MIMIC-IV) database was used to identify patients with acute pancreatitis. PeHR was defined as a heart rate exceeding 100 beats per minute for at least 11 out of 12 consecutive hours. Cox regression analysis was used to assess the association between peHR and the 90-Day mortality. A total of 364 patients (48.9%) experienced a peHR episode. The 90-day mortality was 25%. PeHR is an independent risk factor for 90-day mortality (HR, 1.98; 95% CI 1.53-2.56; P < 0.001). KM survival curves exhibited a significant decrease in the survival rate at 90 days among patients who experienced a peHR episode (P < 0.001, 84.5% vs. 65.1%). We revealed a significant association of peHR with decreased survival in a large cohort of ICU patients with acute pancreatitis.

Identification of m6A-associated autophagy genes in non-alcoholic fatty liver.

Background: Studies had shown that autophagy was closely related to nonalcoholic fat liver disease (NAFLD), while N6-methyladenosine (m6A) was involved in the regulation of autophagy. However, the mechanism of m6A related autophagy in NAFLD was unclear. Methods: The NAFLD related datasets were gained via the Gene Expression Omnibus (GEO) database, and we also extracted 232 autophagy-related genes (ARGs) and 37 m6A. First, differentially expressed ARGs (DE-ARGs) and differentially expressed m6A (DE-m6A) were screened out by differential expression analysis. DE-ARGs associated with m6A were sifted out by Pearson correlation analysis, and the m6A-ARGs relationship pairs were acquired. Then, autophagic genes in m6A-ARGs pairs were analyzed for machine learning algorithms to obtain feature genes. Further, we validated the relationship between feature genes and NAFLD through quantitative real-time polymerase chain reaction (qRT-PCR), Western blot (WB). Finally, the immuno-infiltration analysis was implement, and we also constructed the TF-mRNA and drug-gene networks. Results: There were 19 DE-ARGs and four DE-m6A between NAFLD and normal samples. The three m6A genes and five AGRs formed the m6A-ARGs relationship pairs. Afterwards, genes obtained from machine learning algorithms were intersected to yield three feature genes (TBK1, RAB1A, and GOPC), which showed significant positive correlation with astrocytes, macrophages, smooth muscle, and showed significant negative correlation with epithelial cells, and endothelial cells. Besides, qRT-PCR and WB indicate that TBK1, RAB1A and GOPC significantly upregulated in NAFLD. Ultimately, we found that the TF-mRNA network included FOXP1-GOPC, ATF1-RAB1A and other relationship pairs, and eight therapeutic agents such as R-406 and adavosertib were predicted based on the TBK1. Conclusion: The study investigated the potential molecular mechanisms of m6A related autophagy feature genes (TBK1, RAB1A, and GOPC) in NAFLD through bioinformatic analyses and animal model validation. However, it is critical to note that these findings, although consequential, demonstrate correlations rather than cause-and-effect relationships. As such, more research is required to fully elucidate the underlying mechanisms and validate the clinical relevance of these feature genes.

Single-Cell RNA Sequencing Identifies Crucial Genes Influencing the Polarization of Tumor-Associated Macrophages in Liver Cancer.

Background: In the context of hepatocellular carcinoma (HCC), tumor-associated macrophages (TAMs) are pivotal for the immunosuppressive nature of the tumor microenvironment (TME). This investigation delves into the functional transformations of TAMs within the TME by leveraging single-cell transcriptomics to pinpoint critical genes influencing TAM subset polarization. Methods: We procured single-cell and bulk transcriptomic data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), implementing quality assurance, dimensional reduction, clustering, and annotation on the single-cell sequencing data. To examine cellular interactions, CellChat was utilized, while single-cell regulatory network inference and clustering (SCENIC) was applied to deduce transcription factors (TFs) and their associated targets. Through gene enrichment, survival, and immune infiltration correlation analyses, we sought to pinpoint and validate influential genes. A TAM model under HCC conditions was then established to confirm the expression levels of these key genes. Results: Our analysis encompassed 74,742 cells and 23,110 genes. Through postdimensional reduction and clustering, we identified seven distinct cell types and nine TAM subtypes. Analysis via CellChat highlighted a predominance of M2-phenotype-inclined TAM subsets within the tumor's core. SCENIC pinpointed the transcription factor PRDM1 and its target genes as pivotal in this region. Further analysis indicated these genes' involvement in macrophage polarization. Employing trajectory analysis, survival analysis, and immune infiltration correlation, we scrutinized and validated genes likely directing M2 polarization. Experimental validation confirmed PRDM1's heightened expression in TAMs conditioned by HCC. Conclusions: Our findings suggest the PRDM1 gene is a key regulator of M2 macrophage polarization, contributing to the immunosuppressive TME in HCC.

Comprehensive bioinformatics analysis of a RBM family-based prognostic signature with experiment validation in hepatocellular carcinoma.

BACKGROUND: Although some RBM proteins family members play important roles in hepatocellular carcinoma (HCC) development, their value of prognosis and tumor treatment is not clear. To reveal the expression patterns and clinical significance of RBM family members in HCC, we constructed a RBM family-based prognosis signature. METHOD: We collected the data of HCC patients from TCGA and ICGC database. The prognostic signature was constructed in TCGA and verified using ICGC cohort. Based on this model, risk score was calculated and patients were divided into high- and low-risk group. Comparison of immune cell infiltration, the response to immunotherapy, and IC50 of chemotherapeutic drugs were employed between different risk subgroups. Besides, CCK-8 and EdU assays were performed to investigate the role of RBM45 in HCC. RESULT: Among 19 differential expression RBM protein family genes, 7 prognostic genes were picked out. Through LASSO Cox regression, a 4-gene prognostic model was successfully constructed, which included RBM8A, RBM19, RBM28 and RBM45. Results of validation and estimation suggested this model could be applied for prognostic prediction in HCC patients with a well predictive value. Risk score was shown to be an independent predictor and high-risk patients had poor prognosis. High-risk patients had an immunosuppressive tumor microenvironment while patients with low risk could benefit more from ICI therapy and sorafenib treatment. In addition, knockdown of RBM45 inhibited the proliferation of HCC. CONCLUSION: This prognostic signature based on RBM family had a great value for predicting OS of HCC patients. Low-risk patients were more suitable for receiving immunotherapy and sorafenib treatment. The RBM family members made of the prognostic model might promote the progression of HCC.

Evaluation of the efficacy of Biejia decoction pill combined with entecavir in the treatment of hepatitis B liver fibrosis/cirrhosis by VCTE.

The vibration controlled transient elastography (VCTE) technique was used to assess the effectiveness of a Biejia Decoction pill in combination with Entecavir in the treatment of hepatitis B liver fibrosis/cirrhosis. We randomly selected 120 patients to receive entecavir and 119 patients to receive both entecavir and Biejia Decoction Pill, which both with hepatitis B liver fibrosis/cirrhosis visited the Second Affiliated Hospital of Nanchang University between January 2019 and February 2022. The observation group got ETV (entecavir) and Biejia Decoction pills, whereas the control group received only standard ETV antiviral medication. Based on the grading of the VCTE detection value (LSM) initially diagnosed for patients with hepatitis B liver fibrosis/cirrhosis, we divided the patients into two subgroups of liver fibrosis and cirrhosis. In addition, patients with liver fibrosis were divided into mild and moderate subgroups according to their VCTE values. Patients were measured for liver hardness after three, six, nine, and twelve months of treatment with VCTE. Biejia Decoction Pill combined with ETV on HBV liver fibrosis/cirrhosis was evaluated by comparing patients' changes in liver hardness and HBV-DNA negative conversion rates before and after treatment in each group at the same baseline. The LSM (liver elasticity value) of the observation group and the control group after treatment was lower than that before treatment, and the difference was statistically significant (P < 0.0001); The LSM of the observation group after treatment was significantly lower than that of the control group, and the difference was also statistically significant (P = 0.0005 < 0.05). In the subgroup of liver fibrosis, the number of patients with moderate and severe liver fibrosis who completely reversed liver fibrosis after treatment in the treatment group was far more than that in the control group, and the difference between the two groups was statistically significant (χ2 = 4.82 P = 0.028 < 0.05) 。 When the treatment course was more than 9 months, the negative conversion rate of patients in the observation group reached 87.4%, which was higher than that in the control group (70.8%), and the difference was statistically significant (P = 0.002 < 0.05); After 12 months of treatment, the negative conversion rate of patients in the observation group was as high as 95%, which was significantly higher than 76.67% in the control group (P < 0.001). The degree of liver fibrosis was significantly improved when Biejia Decoction Pill was combined with ETV in patients with liver fibrosis/cirrhosis due to hepatitis B. The virological response rate to HBV-DNA increased with the prolongation of treatment, and the Biejia Decoction Pill assists with entecavir in antiviral therapy.