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The invasive nature of liver biopsy makes the histopathological diagnosis of non-alcoholic fatty liver disease (NAFLD) difficult and its diagnostic performance unsatisfactory. The present study aimed to identify a serum microRNA (miRNA) expression profile that could serve as a novel diagnostic biomarker for NAFLD. Serum miRNA expression was investigated using three cohorts comprising 465 participants (healthy controls and NAFLD patients) recruited between August 2010 and June 2013. miRNA expression was initially screened by Illumina sequencing using serum samples pooled from 20 patients and 20 controls. Quantitative reverse transcriptase polymerase chain reaction assay was then used to evaluate the expression of selected miRNAs. A logistic regression model was constructed using a training cohort (n = 242) and validated using another cohort (n = 183). The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. We identified an miRNA panel (hsa-miR-122-5p, hsa-miR-1290, hsa-miR-27b-3p, and hsa-miR-192-5p) with a high diagnostic accuracy for NAFLD. The satisfactory diagnostic performance of the miRNA panel remained regardless of the NAFLD activity score (NAS) status. There was significant difference between the AUC values of the miRNA panel and those of ALT (AUC = 0.786, 95% CI = 0.717-0.855; P = 0.142) and FIB-4 (AUC = 0.795, 95% CI = 0.730-0.860; sensitivity = 69.9%, specificity = 83.7%. We identified a serum microRNA panel with considerable clinical value in NAFLD diagnosis. The results indicate that the miRNA panel is a more sensitive and specific biomarker for NAFLD than ALT and FIB-4.

The identification of new high-sensitivity and high-specificity markers for HCC are essential. We aimed to identify serum microRNAs (miRNAs) as biomarkers to be used in diagnosing hepatitis B virus (HBV) -related hepatocellular carcinoma (HCC). We investigated serum miRNA expression in (261 HCC patients, 233 cirrhosis patients, and 173 healthy controls), recruited between August 2010 and June 2013. An initial screening of miRNA expression by Illumina sequencing was performed using serum samples pooled from HCC patients and controls. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was used to evaluate the expression of selected miRNAs. A logistic regression model was constructed using a training cohort (n = 357) and then validated using an independent cohort (n = 241). The area under the receiver operating characteristic curve (AUC) was used to evaluate the accuracy of the use of the biomarkers for disease diagnosis. We identified 8 miRNAs (hsa-miR-206, hsa-miR-141-3p, hsa-miR-433-3p, hsa-miR-1228-5p, hsa-miR-199a-5p, hsa-miR-122-5p, hsa-miR-192-5p, and hsa-miR-26a-5p) and constructed an miRNA set that provided high diagnostic accuracy for HCC (AUC = 0.887 and 0.879 for training and validation sets, respectively). The miRNAs could also be used to differentiate HCC patients from healthy (AUC = 0.893) and cirrhosis (AUC = 0.892) patients. We identified a serum of miRNA panel that has considerable clinical value in HCC diagnosis.

Objective To investigate the association between inflammatory cytokines and liver function indices in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients and chimeric antigen receptor (CAR) T therapy recipients, with the aim of identifying prognostic biomarkers and elucidating the pathophysiological roles of inflammatory cytokines in HBV-ACLF. Methods This retrospective cohort study analyzed clinical data from three groups: 68 patients with confirmed HBV-ACLF, 30 patients with pre-HBV-ACLF, and 372 hematologic malignancy patients receiving CAR-T therapy with preserved liver function at the First Affiliated Hospital of Soochow University. Results Serum interleukin (IL)-10 levels demonstrated a progressive increase across the groups [healthy controls: 0.15 (0.10;2.18) pg/mL; pre-HBV-ACLF: 3.80 (2.38;11.83) pg/mL; HBV-ACLF: 5.95 (3.90;14.75) pg/mL; p  < 0.001]. Patients with clinical improvement exhibited significantly lower IL-10 concentrations and higher IL-6/IL-10 ratios compared to those with disease progression ( p  < 0.05). Notably, IL-6 levels remained stable across clinical stages, with HBV-ACLF patients without secondary infection showing lower IL-6 levels than pre-HBV-ACLF patients ( p  < 0.05). Following CAR-T therapy, hematologic patients displayed significantly elevated IL-6 levels, accompanied by increases in AST and INR prolongation, whereas TBIL and ALT remained stable ( p  > 0.05). Consistent with HBV-ACLF observations, improved CAR-T recipients demonstrated significantly lower IL-6/IL-10 ratios than progression patients ( p  < 0.05). Conclusions IL-10 exhibits stage-dependent dynamics in HBV-ACLF pathogenesis and progression, closely mirroring hepatic functional deterioration. The IL-6/IL-10 ratio serves as a prognostic biomarker for both HBV-ACLF and CAR-T therapy-related liver injury, with lower ratios indicating better clinical outcomes. Clinical trial number Not applicable.

Background Most of the biological functions of circular RNAs (circRNAs) and the potential underlying mechanisms in hepatocellular carcinoma (HCC) have not yet been discovered. Methods In this study, using circRNA expression data from HCC tumor tissues and adjacent tissues from the Gene Expression Omnibus database, we identified out differentially expressed circRNAs and verified them by qRT-PCT. Functional experiments were performed to evaluate the effects of circFAM13B in HCC in vitro and in vivo. Results We found that circFAM13B was the most significantly differentially expressed circRNA in HCC tissue. Subsequently, in vitro and in vivo studies also demonstrated that circFAM13B promoted the proliferation of HCC. Further studies revealed that circFAM13B, a sponge of miR-212, is involved in the regulation of E2F5 gene expression by competitively binding to miR-212, inhibits the activation of the P53 signalling pathway, and promotes the proliferation of HCC cells. Conclusions Our findings revealed the mechanism underlying the regulatory role played by circFAM13B, miR-212 and E2F5 in HCC. This study provides a new theoretical basis and novel target for the clinical prevention and treatment of HCC.

Mesenchymal stromal cells (MSCs) function as a formidable regulator of inflammation and tissue homeostasis and expanded MSCs are shown to be effective in treating various inflammatory diseases. Their therapeutic effects require the existence of certain inflammatory cytokines. However, in the absence of sufficient proinflammatory stimuli or in the presence of anti‐inflammatory medications, MSCs are animated to promote immune responses and unable to alleviate inflammatory disorders. In this study, it is demonstrated that steroid co‐administration interferes the efficacy of MSCs in treating acute graft‐versus‐host disease (aGvHD). Molecular analysis reveals that vascular endothelial growth factor C (VEGF‐C) is highly induced in MSCs by steroids and TNFα and VEGF‐C in turn promotes CD8+ T cell response. This immune promoting effect is abolished by blockade or specific genetic ablation of VEGFR3 in CD8+ T cells. Additionally, administration of VEGF‐C alone exacerbates aGvHD progression through eliciting more vigorous CD8+ T cell activation and proliferation. Further studies demonstrate that VEGF‐C augments the PI3K/AKT signaling process and the expression of downstream genes, such as Cyclin D1. Thus, the data demonstrate that steroids can reverse the immunosuppressive effect of MSCs via promoting VEGF‐C‐augmented CD8+ T cell response and provide novel information for designing efficacious MSC‐based therapies. Steroids are first‐line drugs for treating acute graft‐versus‐host disease (aGvHD). Recently, mesenchymal stromal cells (MSCs) have emerged as a superb choice. However, concomitant use of both worsens the disease course. This manuscript reveals that steroids, together with TNFα, synergistically induce MSCs to produce abundant vascular endothelial growth factor C, which enhances CD8+ T cell response and exacerbates aGvHD progression. ​

Background The risk factors for recurrence and death after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) remain poorly known. This study was aimed to study the 10-year overall survival (OS) of HCC treated by ultrasound (US)-guided RFA and the risk factors for recurrence and death. Methods Between June 2005 and June 2016, 1000 patients with HCC treated by US-guided RFA at 4 hospitals in China; among them, 525 patients met the criteria for radical ablation and 410 had high AFP levels before RFA treatment. Clinical and biochemical factors were tested for association with recurrence and survival. Patients were divided into the recurrence ( n  = 348) and no recurrence groups ( n  = 62). Results The 5- and 10-year survival rates were 66 and 35%, respectively. Tumor size (HR = 1.36, 95% CI 1.12–1.65), albumin levels (HR = 0.76, 95% CI 0.65–0.91), prothrombin time (HR = 2.18, 95% CI 1.54–3.10), and α-fetoprotein levels (HR = 1.13, 95% CI 1.00–1.26) were independently associated with mortality after RFA for HCC. Tumor size (HR = 1.27, 95% CI: 1.15–1.40), HBV-DNA (HR = 7.70, 95% CI 3.57–16.63), AFP levels before treatment (HR = 2.172, 95% CI 1.256–3.756, P  = 0.006), and AFP response (HR = 4.722, 95% CI 1.053–21.184, P  = 0.0427) were independently associated with the risk of recurrence of HCC after RFA. The median survival of the patients with and without recurrence after RFA was 54 (95% CI 45–58) and 62 (95% CI 48–80) months, respectively (log-rank, P  = 0.04). Conclusions Tumor size, albumin, prothrombin time, and α-fetoprotein levels were independently associated with mortality after US-guided RFA for HCC, while tumor size and HBV-DNA were independently associated with recurrence. Patients with recurrence had a poorer survival compared with those without.

Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a severe hyperinflammatory illness that affects adults and is caused by an EBV infection. Without allogeneic hematopoietic stem cell transplantation (allo-HSCT), the overall survival of adult patients with EBV-HLH is unsatisfactory, necessitating the development of innovative therapeutic approaches. The clinical records of twelve EBV-HLH patients who received sintilimab therapy combined with ruxolitinib on a compassionate basis at the First Affiliated Hospital of Soochow University were retrospectively examined in this investigation. All the patients responded without fever, but three patients relapsed within a week. Among the nine patients achieving complete response (CR), 55.6% (5/9) maintained CR for >4.5 months, and 33.3% (3/9) relapsed following CR. Neither patients with no response (NR) nor relapsed patients were fit for allo-HSCT, and all died soon after discharge. Six patients had clinical CR with a median follow-up of 5 (4.4–14.7) months. There were no documented severe negative effects. Additional information on this innovative treatment for adult EBV-HLH is provided in our report.

ObjectiveThe definition of acute-on-chronic liver failure (ACLF) based on cirrhosis, irrespective of aetiology, remains controversial. This study aimed to clarify the clinicopathological characteristics of patients with hepatitis B virus-related ACLF (HBV-ACLF) in a prospective study and develop new diagnostic criteria and a prognostic score for such patients.DesignThe clinical data from 1322 hospitalised patients with acute decompensation of cirrhosis or severe liver injury due to chronic hepatitis B (CHB) at 13 liver centres in China were used to develop new diagnostic and prognostic criteria.ResultsOf the patients assessed using the Chronic Liver Failure Consortium criteria with the exception of cirrhosis, 391 patients with ACLF were identified: 92 with non-cirrhotic HBV-ACLF, 271 with cirrhotic HBV-ACLF and 28 with ACLF with cirrhosis caused by non-HBV aetiologies (non-HBV-ACLF). The short-term (28/90 days) mortality of the patients with HBV-ACLF were significantly higher than those of the patients with non-HBV-ACLF. Total bilirubin (TB) ≥12 mg/dL and an international normalised ratio (INR) ≥1.5 was proposed as an additional diagnostic indicator of HBV-ACLF, and 19.3% of patients with an HBV aetiology were additionally diagnosed with ACLF. The new prognostic score (0.741×INR+0.523×HBV-SOFA+0.026×age+0.003×TB) for short-term mortality was superior to five other scores based on both discovery and external validation studies.ConclusionsRegardless of the presence of cirrhosis, patients with CHB, TB ≥12 mg/dL and INR ≥1.5 should be diagnosed with ACLF. The new criteria diagnosed nearly 20% more patients with an HBV aetiology with ACLF, thus increasing their opportunity to receive timely intensive management.

Cuproptosis has been recently used to indicate unique biological processes triggered by Cu action as a new term. This study aimed to explore the relationship between cuproptosis-related lncRNA and hepatocellular carcinoma (HCC) with regard to immunity and prognosis. RNA sequencing and the clinical data were downloaded from the TCGA database. The cuproptosis-related genes were sorted out through literature study. The cuproptosis-related IncRNA signature was identified by Cox regression analysis and the least absolute shrinkage and selection operator analysis. The K-M survival analysis, receiver operating characteristic analysis, and C-index analysis were adopted to evaluate the prognostic prediction performance of the signature. The functional enrichment, immune infiltration and tumor mutation analysis were further analyzed. Subsequently, we predicted the differences in chemosensitivity from tumor gene expression levels for some chemotherapy drugs. The prognostic signature consisting of 5 overall survival-related CUPlncRNAs. It showed an extraordinary ability to predict the prognoses of patients with HCC. The signature can predict the abundance of immune cell infiltration, immune functions, expression of immune checkpoint inhibitors, m6A genes, which was supported by the GO biological process and KEGG analysis. And it may also have a guiding effect in the sensitivity of different chemotherapeutic drugs and tumor mutation burden. We constructed a new cuproptosis-related lncRNA signature for HCC patients. The model can be used for prognostic prediction and immune evaluation, providing a reference for immunotherapies and targeted therapies.