Perfluorobutane (Sonazoid) Contrast-enhanced ultrasound to diagnose hepatocellular carcinoma: A systematic review and meta-analysis.

AIM: This meta-analysis aimed to assess the precision of Sonazoid contrast-enhanced ultrasound (CEUS) to distinguish hepatocellular carcinoma (HCC) from focal liver lesions (FLLs). MATERIAL AND METHODS: The Cochrane Library, Embase, PubMed, and Web of Science databases were systematically searched and checked for studies using Sonazoid CEUS to characterize HCC. A comprehensive meta-analysis was conducted, involving data pooling, subgroup analyses, meta-regression, and investigation of publication bias. RESULTS: The meta-analysis included fourteen studies. The overall diagnostic accuracy for characterizing HCC was as follows (all ranges show the 95% confidence interval): pooled sensitivity of 0.87 (0.80-0.92), pooled specificity of 0.95 (0.91-0.97), and a diagnostic odds ratio of 121 (61-241). The overall weighted area under the curve was 0.97 (0.95-0.98). The pooled sensitivity, specificity, and diagnostic odds ratio for Sonazoid and Sonovue were 0.75 (0.63- 0.84), 0.97 (0.86-0.99), 82 (15-445); and 0.64 (0.51-0.76), 0.98 (0.91-0.99), 72 (17-311), respectively. The sources of heterogeneity were identified as the study location, prevailing risk factor, reference diagnosis standard, criteria of Sonazoid CUES, and the proportion of cases of HCC. We observed no potential publication bias. CONCLUSION: Sonazoid CEUS is efficient to distinguish HCC from FLLs, with good sensitivity and specificity. It is comparable to Sonovue CEUS to diagnose HCC.

Novel protein C6ORF120 promotes liver fibrosis by activating hepatic stellate cells through the PI3K/Akt/mTOR pathway.

BACKGROUND AND AIM: The role of C6ORF120 in promoting CCL4-induced hepatic fibrosis and its possible mechanisms were explored in C6orf120 knockout rats (C6orf120-/-) and LX-2 cells (a type of human hepatic stellate cell line). METHODS: In vivo experiments, wild-type and C6orf120-/- rats were used to investigate the function of C6ORF120. In the in vitro experiments, C6ORF120 recombinant protein (rC6ORF120) at a concentration of 200 ng/mL was used to stimulate LX-2 cells. Sirius Red staining, Masson staining, western blotting, polymerase chain reaction, immunohistochemistry, and immunofluorescence were used to explore fibrosis-associated factors. RESULTS: C6orf120-/- rats showed mild fibrosis and liver injury in the CCL4-induced liver fibrosis model. Furthermore, RNA-seq revealed that C6orf120-/- rats had less extracellular matrix deposition and activated stellate cells. Consistent with the in vivo, the rC6ORF120 induced LX-2 cell activation. Moreover, mechanistic studies revealed that the p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR levels were significantly elevated and LY294002 (a PI3K/Akt/mTOR typical pathway inhibitor) reversed the function of C6ORF120 in activating LX-2 cells. CONCLUSION: C6ORF120 could activate hepatic stellate cells and promote hepatic fibrosis via the PI3K/Akt/mTOR signaling pathway.

A nomogram for analyzing risk factors of poor treatment response in patients with autoimmune hepatitis.

OBJECTIVE: The objective of this study was to identify biochemical and clinical predictors of poor response (including incomplete response and non-response) to standard treatment in autoimmune hepatitis (AIH) patients. METHODS: This study retrospectively collected clinical data from 297 patients who were first diagnosed with AIH in Beijing Ditan Hospital from 2010 to 2019. Finally, 149 patients were screened out. Risk factors were screened by univariate and multifactorial logistic regression. Then they were used to establish the nomogram. The ROC curve, calibration curve, decision curves analysis (DCA) and clinical impact curves (CIC) were used to evaluate the nomogram. RESULTS: 149 patients were divided into two groups: the response group (n = 120, 80%) and the poor response group (n = 29, 20%). Multivariate logistic regression analysis found that IgG > 26.5 g/L (OR: 22.016; 95% CI: 4.677-103.640) in AIH patients increased the risk. In contrast, treatment response status was better in women (OR: 0.085; 95% CI: 0.015-0.497) aged >60 years (OR: 0.159; 95% CI: 0.045-0.564) with AST > 4.49 × ULN (OR: 0.066; 95% CI: 0.009-0.494). The C index (0.853) and the calibration curve show that the nomogram is well differentiated and calibrated; the DCA and CIC indicate that the model has good clinical benefits and implications. CONCLUSION: The study found that male patients aged ≤ 60 years with IgG > 26.5 g/L and elevated AST ≤ 4.49 × ULN were more likely to have a non-response/incomplete response to standard treatment.

Safety and Immunogenicity of the Inactivated COVID-19 Vaccine Booster in People Living with HIV in China.

Current knowledge regarding the long-term humoral response of people infected with human immunodeficiency virus to the third dose of inactivated coronavirus disease (COVID-19) vaccine is incomplete. As a result, concerns remain about the safety and efficacy of the vaccination. To improve our understanding of the safety and immunogenicity of the COVID-19 inactivated vaccine booster in people living with HIV (PLWH), a prospective study was conducted on participants who had not yet received a third dose of the COVID-19 inactivated vaccine, had no history of SARS-CoV-2 infection, and had received a second dose of the vaccine more than six months prior. The primary safety outcomes included the incidence of adverse reactions, changes in CD4+ T-cell count, viral load, blood routine examination, liver and kidney function examination, blood sugar, and blood lipid examination. The pseudovirus-neutralizing antibody responses to the D614G variant, Delta variant, and Omicron variants BA.5 and BF.7 were evaluated before vaccination, 14 days, 28 days, 3 months, and 6 months after vaccination to evaluate the immune response of PLWH to the injection of inactivated vaccine booster and the safety of the vaccine. In conclusion, COVID-19 vaccine booster shots were effective in PLWH, resulting in an increase in the number of CD4+ T-cells, neutralizing antibodies that lasted up to six months, and higher levels of neutralizing antibodies lasting approximately 3 months. However, the vaccine protection against the two variants of BA.5 and BF.7 was significantly lower than that of D614G and Delta.

Clinical significance of serum antinuclear antibodies in patients with autoimmune hepatitis and comorbidity.

Autoimmune hepatitis (AIH) is often complicated with immune diseases, which greatly affected the course and clinical outcome of AIH. We aimed to systematically assess clinical characteristics, prognosis in autoimmune hepatitis accompanied by immune diseases. Clinical records of 358 patients with AIH from Beijing Ditan Hospital in China were retrospectively reviewed. The clinical features of AIH with immune diseases were compared retrospectively, including clinical characteristics, prognosis and outcome. Prevalence of immune diseases in patients with AIH was 26.5%. Connective tissue disease (CTD) was the commonest immune diseases associated with AIH (33/358, 9.2%), and the incidence of primary biliary cholangitis (PBC) and thyroid dysfunction (TD) was low (4.7% and 8.5%, respectively). At diagnosis, AIH-PBC patients had higher IgM and ALP, lower weight, Hgb, ALT and AFP (P < 0.05). Meanwhile, AIH-CTD patients had lower mean platelet volume, serum K and triglyceride (P < 0.05). AIH-TD patients had a lower proportion of ANA positive (P < 0.05). The overall survival time of AIH-TD was significantly shorter than AIH patients (P = 0.0011), but there were no differences in AIH-PBC and AIH-CTD. Furthermore, ANA negative (HR: 0.21, 95%CI 0.13-0.35, P < 0.001) can be a factor to predict the poor prognosis of AIH, and also in AIH-TD patients. About 26.5% of AIH patients had at least one immune disease, and TD coexisted with AIH impaired patients' survival. ANA negative can be used as an independent indicator to predict the poor prognosis of AIH and AIH-TD.

Role of triglycerides as a predictor of autoimmune hepatitis with cirrhosis.

BACKGROUND: Metabolism-related indicators have been suggested as possible prognostic indicators of liver disease in recent relevant studies, but their value in predicting autoimmune hepatitis (AIH) cirrhosis is unclear. This study evaluated the role of lipid levels in determining the prognosis of AIH-related cirrhosis. METHODS: We retrospectively included 345 patients with AIH who were initially diagnosed at Beijing Ditan Hospital from 2010-2019, and ultimately screened 196 patients who met the criteria. A logistic regression analysis was performed to screen factors associated with cirrhosis. Kaplan-Meier (KM) curves were constructed to analyze the effects of different triglyceride (TG) levels on the survival of patients with cirrhosis. A restricted cubic spline fitted Cox regression model was used to analyze the nonlinear relationship between serum TG levels and patient prognosis. RESULTS: Patients with AIH cirrhosis have lower TG levels than those without cirrhosis. Lower serum TG levels correlated with the severity of cirrhosis. The survival analysis showed that TG levels were associated with the overall survival of patients with AIH, as a lower 5-year survival rate (log-rank P<0.05) was observed for patients in the TG≤0.95 mmol/L group (hazard ratio (HR)=3.79, 95% CI: 1.528-9.423). In addition, lower TG levels were associated with a higher incidence of death in patients with AIH cirrhosis. The risk of death gradually increased for the interval of TG levels of 0.5-0.8 mmol/L (P for nonlinearity<0.001), and the hazard ratio per standard deviation increase in the TG level was 0.97 (95% CI: 0.94-0.99). The plot showed a U-shaped relationship between TG levels and the survival of patients with decompensated cirrhosis. The risk ratio progressively decreased with lower TG levels (P for nonlinearity=0.002). Below 0.6 mmol/L, the probability of TG risk per standard deviation prediction was 1.49 (95% CI: 1.00-2.24). CONCLUSION: Serum TG levels are closely related to the disease severity and overall survival of patients with AIH cirrhosis and may be used as a new indicator of advanced liver disease and long-term prognosis.

A nomogram for predicting paradoxical immune reconstitution inflammatory syndrome associated with cryptococcal meningitis among HIV-infected individuals in China.

BACKGROUND: Cryptococcal meningitis (CM) associated immune reconstitution inflammatory syndrome (CM-IRIS) is the second most common complication in HIV-infected individuals with cryptococcal meningitis, with a reported mortality rate ranging from 8 to 30%. Given the devastating consequences of CM-IRIS related intracranial neuroinflammation and its challenging in diagnosis, we conducted a study to explore the risk factors and the occurrence of paradoxical CM-IRIS in HIV-infected patients, which is of great value for prevention and clinical management. METHODS: We conducted a retrospective cohort study to identify the indicators associated with paradoxical CM-IRIS among 86 HIV-infected patients with CM using univariate and multivariate cox analysis. A nomogram was constructed using selected variables to evaluate the occurrence of paradoxical CM-IRIS at 6 months and 12 months after ART initiation. The discrimination and calibration of the nomogram were assessed by concordance index (C-index) and calibration plots. Decision curves analysis (DCA) were used to evaluate clinical effectiveness of the nomogram. Subsequently, to help clinicians recognize patients at high risk faster, patients were divided into high-risk and low-risk groups according to the best cutoff point identified by X-tile. RESULTS: Of 86 AIDS patients with CM, 22.1% experienced paradoxical CM-IRIS at a median of 32 days after antiretroviral therapy (ART) initiation. The occurrence of paradoxical CM-IRIS was associated with age, ART initiation within 4 weeks of antifungal treatment, a four-fold increase in CD4 T cell counts, C-reactive protein levels, and hemoglobin levels independently. These five variables were further used to construct a predictive nomogram. The C-index (0.876) showed the favorable discriminative ability of the nomogram. The calibration plot revealed a high consistency between the predicted and actual observations. DCA showed that the nomogram was clinically useful. Risk stratification based on the total score of the nomogram showed well-differentiated in the high-risk and low-risk groups. Clinicians should pay attention to patients with total points high than 273. CONCLUSIONS: We identified the predictive factors of paradoxical CM-IRIS and constructed a nomogram to evaluate the occurrence of paradoxical CM-IRIS in 6 months and 12 months. The nomogram represents satisfactory performance and might be applied clinically to the screening and management of high-risk patients.

A three-gene signature might predict prognosis in patients with acute myeloid leukemia.

The identification of effective signatures is crucial to predict the prognosis of acute myeloid leukemia (AML). The investigation aimed to identify a new signature for AML prognostic prediction by using the three-gene expression (octamer-binding transcription factor 4 (OCT4), POU domain type 5 transcription factor 1B (POU5F1B) and B-cell-specific Moloney murine leukemia virus integration site-1 pseudogene 1 (BMI1P1). The expressions of genes were obtained from our previous study. Only the specimens in which three genes were all expressed were included in this research. A three-gene signature was constructed by the multivariate Cox regression analyses to divide patients into high-risk and low-risk groups. Receiver operating characteristic (ROC) analysis of the three-gene signature (area under ROC curve (AUC) = 0.901, 95% CI: 0.821-0.981, P<0.001) indicated that it was a more valuable signature for distinguishing between patients and controls than any of the three genes. Moreover, white blood cells (WBCs, P=0.004), platelets (PLTs, P=0.017), percentage of blasts in bone marrow (BM) (P=0.011) and complete remission (CR, P=0.027) had significant differences between two groups. Furthermore, high-risk group had shorter leukemia-free survival (LFS) and overall survival (OS) than low-risk group (P=0.026; P=0.006), and the three-gene signature was a prognostic factor. Our three-gene signature for prognosis prediction in AML may serve as a prognostic biomarker.

Low Expression of Pseudogene POU5F1B Affects Diagnosis and Prognosis in Acute Myeloid Leukemia (AML).

BACKGROUND The transcription factor Oct-4 is necessary for maintaining pluripotency and self-renewal of embryonic stem cells, and POU5F1B is a processed pseudogene of Oct-4 with coding capacity. The purpose of this study is to evaluate the expression and clinical implication of POU5F1B in AML. MATERIAL AND METHODS The expression of the POU5F1B transcript was evaluated in 175 newly diagnosed AML patients and 39 healthy controls by use of real-time quantitative PCR (RQ-PCR). RESULTS POU5F1B was underexpressed in AML compared with controls (P<0.001). The receiver operating characteristic (ROC) curve revealed that the POU5F1B transcript level was able to differentiate AML patients from healthy individuals (AUC=0.682). In non-APL AML patients, the POU5F1Blow group had significantly higher WBC than the POU5F1Bhigh group (20.2×109 vs. 4.6×109 L⁻¹, P=0.021). Among whole-cohort AML, non-APL AML, and intermediate-risk AML, POU5F1Bhigh patients had obviously higher complete remission (CR) rates than POU5F1Blow patients (P=0.012, P=0.012 and P=0.027). In addition, Kaplan-Meier analysis demonstrated better overall survival (OS, P=0.019, P=0.007 and P=0.046, respectively) in POU5F1Bhigh patients compared with POU5F1Blow patients. Furthermore, in multivariate survival analysis, POU5F1B was independently associated with OS in non-APL AML patients and intermediate-risk AML as a favorable prognostic factor. CONCLUSIONS POU5F1B was frequently underexpressed in AML, and might contribute to the diagnosis and prognosis of AML.

MiR-378 promoted cell proliferation and inhibited apoptosis by enhanced stem cell properties in chronic myeloid leukemia K562 cells.

Dysregulation of miR-378 has been found in diverse types of tumors as well as in leukemia. The role of miR-378 in chronic myeloid leukemia (CML) remains unclear. The aim of the study was to reveal the potential effects of miR-378 in the pathological process and progress in CML. Our results showed general level of miR-378 was significant higher in CML patients compared to controls. Overexpression of miR-378 dramatically promoted cell proliferation and drug-resistance. Additionally, apoptosis was inhibited in cells transfected with miR-378. More and bigger stem cell sphere formation was observed in miR-378 transfected cells. Furthermore, enhanced expression of miR-378 was associated with upregulation of stem-cell makers OCT4 and c-Myc. Further study validated that miR-378 inhibited the expression of FUS1. Our research demonstrated the oncogenic nature of miR-378 in CML, and might contribute to the progress of CML.

Circular RNA of vimentin expression as a valuable predictor for acute myeloid leukemia development and prognosis.

The focus of this study was to investigate the expression status of Circ-vimentin (VIM) and further analyze its pathogenesis and clinical significance in acute myeloid leukemia (AML) patients. Real-time quantitative polymerase chain reaction was carried on Circ-VIM in 113 AML patients and 42 healthy controls. Circ-VIM was significantly upregulated in AML compared with control and was positively correlated with white blood cells (WBC) count. Receiver operating characteristic curve analysis indicated that the performance of Circ-VIM expression could serve as a promising biomarker for differentiating AML patients from controls. Significant correlations of Circ-VIM expression were found with WBC and French-American-British classifications. Survival analyses further showed that over-expressed Circ-VIM were associated with markedly shorter overall survival (OS) and leukemia-free survival (LFS) in whole-cohort AML, nonacute promyelocytic leukemia AML and cytogenetically normal-AML patients. Multivariate analysis also disclosed that Circ-VIM over-expression was an independent poor prognostic factor for OS and LFS in AML patients. Remarkably, Pearson correlation analysis evidenced that the expression of Circ-VIM was positively correlated with VIM expression in all AML patients. These results indicated that overexpression Circ-VIM could serve as a significant biomarker.

Low Expression of FUS1 Is Negatively Correlated with miR-378 and May Predict Adverse Prognoses in Acute Myeloid Leukemia.

FUS1 is a tumor suppressor gene that has been found to be frequently lost in a variety of solid tumors. In this study, we aimed to investigate the expression status of the FUS1 gene in acute myeloid leukemia (AML), as well as its clinical significance. We further explored the correlation between the expression of FUS1 and miR-378 in AML. We detected expression of the FUS1 transcript in bone marrow mononuclear cells from 23 controls and 158 newly diagnosed AML patients by real-time quantitative polymerase chain reaction. Downregulated FUS1 expression was found in 139 out of 158 (87.97%) AML cases; this rate was significantly lower than that in all 23 controls (p = 0.012). Receiver operating characteristic curve analysis revealed that the FUS1 transcript level could discriminate AML patients from controls effectively (area under the ROC curve = 0.663). Kaplan-Meier analysis demonstrated that non-M3-AML patients with a low FUS1 expression had a shorter overall survival (p = 0.049) and leukemia-free survival (p = 0.051) than those with a high FUS1 expression. Furthermore, we studied the correlation between the expression of FUS1 and miR-378 in 53 newly diagnosed AML patients. We found that the correlation coefficient was -0.346, which showed that FUS1 and miR-378 were negatively correlated in AML patients (p = 0.011). These results indicate that the low expression of FUS1 is a common molecular event in AML.

Reduced expression of chemerin is associated with poor clinical outcome in acute myeloid leukemia.

Chemerin is dysregulation in numerous solid cancers. However, only little is known about the role of chemerin in acute myeloid leukemia (AML). In this study, we aimed to investigate the expression and clinical significance of recently described chemerin in acute myeloid leukemia (AML). The expression of chemerin in 149 patients with de novo AML and 35 normal controls was quantified by Real-time quantitative PCR (RQ-PCR). Chemerin was down-expressed in AML compared with controls (P=0.042). A receiver operating characteristic (ROC) curve revealed that chemerin expression could differentiate patients with AML from control subjects (AUC=0.611, 95% CI: 0.490-0.732; P=0.042) respectively. The cohort of AML patients was divided into two groups according to the cut-off value of 0.0826 (79% sensitivity and 54% specificity, respectively). In addition, the AML patients with low chemerin expression had significantly shorter overall survival (OS) than those with high chemerin expression (P=0.049). Moreover, multivariate survival analysis confirmed that chemerin was an independent prognostic factor for AML patients. In conclusion, downregulation of chemerin might be a useful diagnostic and prognostic factor for AML patients.