circSLCO1B7 suppresses the malignant progression of hepatocellular carcinoma via the miR-556-3p/DAB2IP axis.

Circular RNAs (circRNAs) are noncoding RNAs with a circular colsed structure that play an important role in the occurrence and development of cancers. The functional mechanism of circRNAs as ceRNAs in hepatocellular carcinoma (HCC) and its effect on the invasion and metastasis of HCC need to be further studied. Five pairs of HCC tissues were selected for high-throughput sequencing, and 19 circRNAs with differential expression were obtained. The expression of circSLCO1B7 was obviously downregulated in 50 pairs of tumor tissues and plasma of HCC patients, which was closely related to the TNM stage, lymph node metastasis and tumor size. Cell functional experiments showed that circSLCO1B7 could inhibit cell growth, migration, invasion and promote cell apoptosis. In the regulatory mechanism, circSLCO1B7 sponged miR-556-3p to regulate the expression of the downstream target gene DAB2IP and induced the Epithelial-mesenchymal transition (EMT) progression. Our results indicated that circSLCO1B7 significantly inhibits the metastasis of HCC via the miR-556-3p/DAB2IP axis. Thus, circSLCO1B7 is a good candidate as a therapeutic target.

[Optimization and evaluation of Xiaoer Pudilan Xiaoyan Syrup based on characterization of material properties].

According to the taste analysis of Pudilan Xiaoyan Oral Liquid, the unpleasant taste of the oral liquid is mainly caused by the inherent taste of Chinese medicine and the taste introduced in the preparation process, which leads to its unpopularity among children. Therefore, aiming at the special children patient group, Xiaoer Pudilan Xiaoyan Syrup was developed via technology optimization and dosage form improvement to improve the unpleasant taste and enhance the medication compliance among children. Based on the material properties of Pudilan Xiaoyan Oral Liquid and Xiaoer Pudilan Xiaoyan Syrup extracts, the authors compared the properties(pH, density, turbidity, viscosity, chromaticity, particle size), taste, content of five quality markers and in vivo pharmacokinetic characteristics of these two preparations, to evaluate the suitability of Xiaoer Pudilan Xiaoyan Syrup. The results showed that compared with those of Pudilan Xiaoyan Oral Liquid, the pH, density, turbidity, viscosity and chromaticity of Xiaoer Pudilan Xiaoyan Syrup were significantly changed, and the unpleasant taste was reduced by 26%; the transfer rate of the main active ingredients chicoric acid was increased, while the transfer rate of baicalin had small difference from that of the oral liquid. In addition, pharmacokinetics revealed that the total absorption amount of baicalin in vivo was higher, and the time to peak T_(max) of baicalin and oroxindin in the syrup and the mean residence time MRT_(last )of corynoline in vivo were significantly prolonged. The absorption degree of Xiaoer Pudilan Xiaoyan Syrup and Pudilan Xiaoyan Oral Liquid in the body was the same: baicalin>oroxindin>corynoline. The new dosage form process was simpler than that of the original dosage form, safe, environmentally friendly, reasonable and feasible, meeting the mass production demand. This provided a basis for the reasonable and scientific optimization of Xiaoer Pudilan Xiaoyan Syrup, and also laid a foundation for its further safe and rational use, so as to expand the clinical application in children.

[Effective delivery of quality markers in alcohol precipitation of Pudilan Xiaoyan Oral Liquid].

Taking Pudilan Xiaoyan Oral Liquid as a demonstration, the effective delivery of quality markers in alcohol precipitation of Chinese medicine oral liquid preparations was studied. With the transfer rates of adenosine, corynoline, cichoric acid, baicalin, and wogonin as evaluation indexes, the effect of the density of concentrate before alcoholic precipitation, volume fraction of ethanol, stirring speed, temperature of concentrated solution, stirring time, alcohol concentration, alcohol precipitation time, alcoholic precipitation temperature, alcohol addition rate, and the pH of concentrate on the alcohol precipitation process was investigated by Plackett-Burman trial design, thus obtaining the key factors that influenced the alcohol precipitation process. The key factors were further optimized by Box-Behnken design to determine the optimal alcohol precipitation conditions. When the density of concentrate before alcoholic precipitation was 1.12 g·mL~(-1), the pH of concentrate was 6.86, and the alcohol concentration was 50.00%, the transfer rates of baicalin and wogonin were 91.86% and 87.78%, respectively. When the density of concentrate before alcoholic precipitation was 1.13 g·mL~(-1), the concentration of alcohol was 74.50%, and the alcoholic precipitation temperature was 17.0 ℃, the transfer rates of adenosine, corynoline, and cichoric acid were 85.95%, 71.62% and 83.19%, respectively. The method of optimizing alcohol precipitation techniques and determining the parameters of Pudilan Xiaoyan Oral Liquid by response surface methodology is reasonable and feasible, which provides guidance and experience for the effective delivery of quality markers in Chinese medicine oral liquid preparations.

Circular RNA hsa_circ_0051040 Promotes Hepatocellular Carcinoma Progression by Sponging miR-569 and Regulating ITGAV Expression.

Accumulating evidence has demonstrated the roles of circular RNAs (circRNAs) in hepatocellular carcinoma (HCC); however, their roles in HCC need to be further studied. Through high-throughput human circRNA microarray analysis of HCC and adjacent normal tissues, we identified hsa_circ_0051040 as a novel candidate circRNA for the diagnosis and treatment of HCC. In this study, we found that hsa_circ_0051040 was overexpressed in HCC tissues and cell lines and that its expression was correlated with poor prognosis. Knockdown of hsa_circ_0051040 inhibited the migration, invasion, and proliferation of HCC cells in vitro and in vivo, whereas overexpression of hsa_circ_0051040 had the opposite effects. Moreover, our data demonstrated that hsa_circ_0051040 acted as a sponge for miR-569 to regulate ITGAV expression and induce EMT progression. Our findings indicated that hsa_circ_0051040 promotes HCC development and progression by sponging miR-569 to increase ITGAV expression. Thus, hsa_circ_0051040 is a good candidate as a therapeutic target.

Risk factors of severe fever with thrombocytopenia syndrome combined with central neurological complications: A five-year retrospective case-control study.

Objective: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality rate, especially SFTS combined with central neurological complications. The purpose of this study was to explore risk factors of central neurological complications in SFTS patients. Methods: In this retrospective study, SFTS patients admitted to the First Affiliated Hospital of Nanjing Medical University between January 2017 and December 2021 were enrolled. Based on the presence or absence of central neurological complications, SFTS patients were divided into case group and control group. The patients' laboratory parameters and clinical data were collected for statistical analysis. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction accuracy of independent risk factors in identifying SFTS patients with central neurological complications. Results: In total, 198 hospitalized SFTS patients with complete medical records, clear etiological diagnosis and clinical outcomes were enrolled in this study. Of these, 74 (37.4%) cases were diagnosed with SFTS with central neurological complications, 29 (39.2%) cases died, and no death occurred in the control group. Multivariate logistic regression analysis revealed pulmonary rales, atrial fibrillation, and high serum SFTSV RNA, lactate dehydrogenase level during the fever stage as independent risk factors for the development of central neurological complications in SFTS patients. ROC curve analysis showed that the area under the ROC curve (AUC) of serum SFTSV RNA and lactate dehydrogenase levels were 0.748 (95%CI: 0.673-0.823, p < 0.001) and 0.864 (95%CI: 0.815-0.914, p < 0.001), respectively, in central neurological complications predicted in SFTS patients. Conclusion: Severe fever with thrombocytopenia syndrome (SFTS) combined with central neurological complications has high morbidity and mortality and diverse clinical manifestations. Early monitoring of lung signs, electrocardiogram, blood SFTSV RNA, and lactate dehydrogenase levels in SFTS patients may be useful in predicting the occurrence of central neurological complications.

Interleukin-34 deficiency aggravates development of colitis and colitis-associated cancer in mice.

BACKGROUND: Although expression of interleukin (IL)-34 is upregulated in active ulcerative colitis (UC), the molecular function and underlying mechanism are largely unclear. AIM: To investigate the function of IL-34 in acute colitis, in a wound healing model and in colitis-associated cancer in IL-34-deficient mice. METHODS: Colitis was induced by administration of dextran sodium sulfate (DSS), and carcinogenesis was induced by azoxymethane (AOM). Whether the impact of IL-34 on colitis was dependent on macrophages was validated by depletion of macrophages in a murine model. The association between IL-34 expression and epithelial proliferation was studied in patients with active UC. RESULTS: IL-34 deficiency aggravated murine colitis in acute colitis and in wound healing phase. The effect of IL-34 on experimental colitis was not dependent on macrophage differentiation and polarization. IL-34-deficient mice developed more tumors than wild-type mice following administration of AOM and DSS. No significant difference was shown in degree of cellular differentiation in tumors between wild-type and IL-34-deficient mice. IL-34 was dramatically increased in the active UC patients as previously reported. More importantly, expression of IL-34 was positively correlated with epithelial cell proliferation in patients with UC. CONCLUSION: IL-34 deficiency exacerbates colonic inflammation and accelerates colitis-associated carcinogenesis in mice. It might be served as a potential therapeutic target in UC.

Expression of plasma IFN signaling-related miRNAs during acute SARS-CoV-2 infection and its association with RBD-IgG antibody response.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a huge challenge worldwide. Although previous studies have suggested that type I interferon (IFN-I) could inhibit the virus replication, the expression characteristics of IFN-I signaling-related miRNAs (ISR-miRNAs) during acute severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and its relationship with receptor-binding domain (RBD) IgG antibody response at the recovery phase remain unclear. METHODS: Expression profiles of 12 plasma ISR-miRNAs in COVID-19 patients and healthy controls were analyzed using RT-qPCR. The level of RBD-IgG antibody was determined using the competitive ELISA. Spearman correlation was done to measure the associations of plasma ISR-miRNAs with clinical characteristics during acute SARS-CoV-2 infection and RBD-IgG antibody response at the recovery phase. RESULTS: Compared with the healthy controls, COVID-19 patients exhibited higher levels of miR-29b-3p (Z = 3.15, P = 0.002) and miR-1246 (Z = 4.98, P < 0.001). However, the expression of miR-186-5p and miR-15a-5p were significantly decreased. As the results shown, miR-30b-5p was negatively correlated with CD4 + T cell counts (r = - 0.41, P = 0.027) and marginally positively correlated with fasting plasma glucose in COVID-19 patients (r = 0.37, P = 0.052). The competitive ELISA analysis showed the plasma level of miR-497-5p at the acute phase was positively correlated with RBD-IgG antibody response (r = 0.48, P = 0.038). CONCLUSIONS: Our present results suggested that the expression level of ISR-miRNAs was not only associated with acute SARS-CoV-2 infection but also with RBD-IgG antibody response at the recovery phase of COVID-19. Future studies should be performed to explore the biological significance of ISR-miRNAs in SARS-CoV-2 infection.

Cyr61 Alleviates Cholangitis by Inhibiting Cytotoxic Effects of CD8+ T Cells on Biliary Epithelial Cells.

OBJECTIVE: Primary biliary cholangitis (PBC) is a chronic progressive cholestatic liver disease. In recent years, researchers have found that cysteine-rich angiogenic inducer 61 (Cyr61, also known as CCN1) has a potential role in reducing portal inflammation in patients with PBC. This study aimed to explore the relationship between Cyr61 and PBC to provide new ideas and an experimental basis for the clinical treatment of PBC. METHODS: After induction of the overexpression of Cyr61 in a mouse model of PBC using recombinant adenovirus, hematoxylin and eosin staining and pathological scores were used to indicate intrahepatic inflammation and bile duct damage. Real-time PCR was used to detect changes in inflammation-related cytokines in the liver. To further study the mechanism, we assessed whether Cyr61 protects bile duct epithelial cells from cytotoxic effects. RESULTS: Serum and hepatic Cyr61 levels were increased in the murine model of PBC. Overexpression of Cyr61 alleviated hepatic inflammation and bile duct injury in vivo. Cyr61 inhibited the cytotoxic effects of CD8+ T cells by acting on biliary epithelial cells (BECs) in vitro. CONCLUSION: Our results provide novel insight into the pathogenesis of PBC and suggest that Cyr61 plays a dominant role in the cytotoxic effects on BECs in PBC. Consequently, therapeutic strategies targeting Cyr61 could be a potent therapy for PBC.

Plasma circRNAs as Biomarkers in Cancer.

The incidence and mortality of cancer are increasing each year. At present, the sensitivity and specificity of the blood biomarkers that were used in clinical practice are low, which make the detection rate of cancer decrease. With advances in bioinformatics and technology, some non-coding RNA as biomarkers can be easily detected through some traditional and new technologies. Circular RNAs (circRNAs) are non-coding RNAs, that is, they do not encode proteins, and have important regulatory functions. CircRNAs can remain stable in bodily fluids, such as in saliva, blood, urine, and especially plasma. The difference in the expression of plasma circRNAs between cancer patients and normal people may suggest that plasma circRNAs may play an important role in the occurrence and development of cancer. In this review, we summarized the clinical effect of plasma circRNAs in several high-incidence cancers. CircRNAs may be effective biomarkers for tumour diagnosis, treatment selection and prognosis evaluation.

Genetic Variants in KIR/HLA-C Genes Are Associated With the Susceptibility to HCV Infection in a High-Risk Chinese Population.

Background: KIR/HLA-C signaling pathway influences the innate immune response which is the first defense to hepatitis C virus (HCV) infection. The aim of this study was to determine the association between the genetic polymorphisms of KIR/HLA-C genes and the outcomes of HCV infection in a high-risk Chinese population. Methods: In this case-control study, four single nucleotide polymorphisms (SNPs) of KIR/HLA-C genes (KIR2DS4/KIR2DS1/KIR2DL1 rs35440472, HLA-C rs2308557, HLA-C rs1130838, and HLA-C rs2524094) were genotyped by TaqMan assay among drug users and hemodialysis (HD) patients including 1,378 uninfected control cases, 307 subjects with spontaneous viral clearance, and 217 patients with persistent HCV infection. Bioinformatics analysis was used to functionally annotate the SNPs. Results: After logistic regression analysis, the rs35440472-A and rs1130838-A alleles were found to be associated with a significantly elevated risk of HCV infection (OR = 1.562, 95% CI: 1.229-1.987, P < 0.001; OR = 2.134, 95% CI: 1.180-3.858, P = 0.012, respectively), which remained significant after Bonferroni correction (0.05/4). The combined effect of their risk alleles and risk genotypes (rs35440472-AA and rs1130838-AA) were linked to the increased risk of HCV infection in a locus-dosage manner (all Ptrend < 0.001). Based on the SNPinfo web server, rs35440472 was predicted to be a transcription factor binding site (TFBS) while rs1130838 was predicted to have a splicing (ESE or ESS) function. Conclusion: KIR2DS4/KIR2DS1/KIR2DL1 rs35440472-A and HLA-C rs1130838-A variants are associated with increased susceptibility to HCV infection in a high-risk Chinese population.

Upregulation of TRIP13 promotes the malignant progression of lung cancer via the EMT pathway.

Lung cancer is the most common malignant tumor type and it is associated with poor prognosis. The identification of potential biomarkers is of great significance for the early diagnosis and treatment of lung cancer. Non­small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The present study aimed to investigate the mechanism via which thyroid hormone receptor­interacting protein 13 (TRIP13) participates in the malignant progression of NSCLC. Immunohistochemistry, reverse transcription­quantitative PCR and western blotting were used to assess the expression level of TRIP13. According to The Cancer Genome Atlas database, TRIP13 was upregulated in NSCLC tissues compared with adjacent normal tissues. Moreover, TRIP13 knockdown increased apoptosis, induced cell cycle arrest in the S phase and inhibited the proliferation, invasion and migration of H1299 cells in vitro. Furthermore, TRIP13 upregulation was closely associated with tumor metastasis via epithelial­mesenchymal transformation. In conclusion, TRIP13 could promote the malignant progression of lung cancer, and TRIP13 may be a potential biomarker for the early diagnosis and treatment of NSCLC.

Genetic Variants in TNFSF4 and TNFSF8 Are Associated With the Risk of HCV Infection Among Chinese High-Risk Population.

BACKGROUND: The tumor necrosis factor superfamily (TNFSF) and TNF receptor superfamily (TNFRSF) play important roles in the immune responses to infections. The aim of this study was to determine the impact of single nucleotide polymorphisms (SNPs) of several TNFSF/TNFRSF genes on the risk of hepatitis C virus (HCV) infection in the Chinese high-risk population. METHODS: The TNFSF4-rs1234313, TNFSF4-rs7514229, TNFSF8-rs3181366, TNFSF8-rs2295800, TNFRSF8-rs2298209, and TNFRSF8-rs2230625 SNPs were genotyped in 2309 uninfected controls, 597 subjects with spontaneous HCV clearance and 784 patients with persistent HCV infection using the TaqMan-MGB assay. The putative functions of the positive SNPs were determined using online bioinformatics tools. RESULTS: After adjusting for gender, age, high-risk population, alanine transaminase (ALT), aspartate aminotransferase (AST), IL28B-rs12979860 and rs8099917 genotypes, the non-conditional logistic regression showed that rs7514229-T, rs3181366-T, and rs2295800-C were associated with an increased risk of HCV infection (all P FDR < 0.05). Combined analysis of rs7514229-T and rs3181366-T risk alleles showed that the subjects carrying 2-4 risk alleles were more susceptible to HCV infection compared with those lacking any risk allele (all P < 0.001). Furthermore, the risk of HCV infection increased with the number of risk alleles (P trend < 0.001). In silico analysis showed that rs7514229, rs3181366, and rs2295800 polymorphisms may affect the transcription of mRNA by regulating miRNA binding, TF binding, and promoter activation, respectively, which may have biological consequences. CONCLUSION: TNFSF4-rs7514229, TNFSF8-rs3181366, and TNFSF8-rs2295800 are associated with increased risk of HCV infection in the Chinese high-risk population.

Mucosal-associated invariant T cells in hepatitis B virus-related liver failure.

BACKGROUND: Liver failure has high mortality and poor prognosis, and establishing new reliable markers for predicting its prognosis is necessary. Mucosal-associated invariant T (MAIT) cells are a novel population of innate-like lymphocytes involved in inflammatory liver disease, and their potential role in liver failure remains unclear. AIM: To investigate alteration of circulating MAIT cells and assess its prognostic value in patients with hepatitis B virus (HBV)-related liver failure. METHODS: We recruited 55 patients with HBV-related liver failure, 48 patients with chronic hepatitis B and 40 healthy controls (HCs) from Nantong Third People's Hospital Affiliated to Nantong University. Peripheral blood mononuclear cells were isolated, and the percentage and number of circulating MAIT cells were detected by flow cytometry. Plasma levels of interleukin (IL)-7, IL-12p70, IL-18 and interferon-α were measured by Luminex assay. RESULTS: Circulating MAIT cells were significantly decreased in HBV-related liver failure patients (percentage: 2.00 ± 1.22 vs 5.19 ± 1.27%, P < 0.0001; number: 5.47 ± 4.93 vs 84.43 ± 19.59, P < 0.0001) compared with HCs. More importantly, there was a significant reduction of MAIT cells in patients with middle/late-stage compared with early-stage liver failure. Circulating MAIT cells partially recovered after disease improvement, both in percentage (4.01 ± 1.21 vs 2.04 ± 0.95%, P < 0.0001) and in cell count (17.24 ± 8.56 vs 7.41 ± 4.99, P < 0.0001). The proportion (2.29 ± 1.01 vs 1.58 ± 1.38%, P < 0.05) and number (7.30 ± 5.70 vs 2.94 ± 1.47, P < 0.001) of circulating MAIT cells were significantly higher in the survival group than in the dead/liver transplantation group, and the Kaplan-Meier curve showed that lower expression of circulating MAIT cells (both percentage and cell count) predicted poor overall survival (P < 0.01). Also, the levels of IL-12 (20.26 ± 5.42 pg/mL vs 17.76 ± 2.79 pg/mL, P = 0.01) and IL-18 (1470.05 ± 1525.38 pg/mL vs 362.99 ± 109.64 pg/mL, P < 0.0001) were dramatically increased in HBV-related liver failure patients compared with HCs. CONCLUSION: Circulating MAIT cells may play an important role in the process of HBV-related liver failure and can be an important prognostic marker.

Association of hypertension with the severity and fatality of SARS-CoV-2 infection: A meta-analysis.

Hypertension is a common comorbidity in COVID-19 patients. However, the association of hypertension with the severity and fatality of COVID-19 remain unclear. In the present meta-analysis, relevant studies reported the impacts of hypertension on SARS-CoV-2 infection were identified by searching PubMed, Elsevier Science Direct, Web of Science, Wiley Online Library, Embase and CNKI up to 20 March 2020. As the results shown, 12 publications with 2389 COVID-19 patients (674 severe cases) were included for the analysis of disease severity. The severity rate of COVID-19 in hypertensive patients was much higher than in non-hypertensive cases (37.58% vs 19.73%, pooled OR: 2.27, 95% CI: 1.80-2.86). Moreover, the pooled ORs of COVID-19 severity for hypertension vs. non-hypertension was 2.21 (95% CI: 1.58-3.10) and 2.32 (95% CI: 1.70-3.17) in age <50 years and ⩾50 years patients, respectively. Additionally, six studies with 151 deaths of 2116 COVID-19 cases were included for the analysis of disease fatality. The results showed that hypertensive patients carried a nearly 3.48-fold higher risk of dying from COVID-19 (95% CI: 1.72-7.08). Meanwhile, the pooled ORs of COVID-19 fatality for hypertension vs. non-hypertension was 6.43 (95% CI: 3.40-12.17) and 2.66 (95% CI: 1.27-5.57) in age <50 years and ⩾50 years patients, respectively. Neither considerable heterogeneity nor publication bias was observed in the present analysis. Therefore, our present results provided further evidence that hypertension could significantly increase the risks of severity and fatality of SARS-CoV-2 infection.

CCN1 promotes hepatic steatosis and inflammation in non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) is characterized by increased uptake and accumulation of lipids in hepatocytes. Simple steatosis may progress to non-alcoholic steatohepatitis (NASH) with inflammation, hepatocellular injury and fibrosis. CCN1 is an important matrix protein that regulates cell death and promotes immune cell adhesion and may potentially control this process. The role of CCN1 in NASH remains unclear. We investigated the role of CCN1 in the pathogenesis of steatohepatitis. CCN1 upregulation was found to be closely related with steatosis in patients with NASH, obese mice and a FFA-treated hepatocyte model. Controlling the expression of CCN1 in murine NASH models demonstrated that CCN1 increased the severity of steatosis and inflammation. From the sequence results, we found that fatty acid metabolism genes were primarily involved in the MCD mice overexpressing CCN1 compared to the control. Then, the expression of fatty acid metabolism genes was determined using a custom-designed pathway-focused qPCR-based gene expression array. Expression analysis showed that CCN1 overexpression significantly upregulated the expression of fatty acid metabolism-associated genes. In vitro analysis revealed that CCN1 increased the intracellular TG content, the pro-inflammatory cytokines and the expression level of apoptosis-associated proteins in a steatosis model using murine primary hepatocytes. We identified CCN1 as an important positive regulator in NASH.

Transmembrane protein 106C promotes the development of hepatocellular carcinoma.

Several protein-coding genes have been identified to play essential roles in cancer biology, and they are dysregulated in many tumors. Transmembrane protein 106C (TMEM106C) is differentially expressed in several human and porcine diseases; however, the expression and biological functions of TMEM106C in hepatocellular carcinoma (HCC) are not clear. In our study, we obtained paired tissue samples from patients undergoing resection for HCC and public databases, which were analyzed for TMEM106C expression using quantitative real-time polymerase chain reaction (qRT-PCR). We further conducted in vitro and in vivo experiments in HCC cell lines and nude mice, respectively, in which TMEM106C was overexpressed or knocked down. Cell-Counting Kit-8 and colony formation experiments were used to determine the influence of TMEM106C on cell proliferation, flow cytometric assays were used to detect the influence on cell cycle distribution and apoptosis, and transwell assays were used for detecting changes in cell migration and invasion. TMEM106C levels were significantly elevated in HCC tissues and cell lines from public databases and our collected specimens from patients. Moreover, higher TMEM106C expression levels predicted a poor prognosis in HCC patients in survival analysis. Overexpression of TMEM106C in HCC cells accelerated cell growth, migration, and invasion, but it inhibited cell apoptosis by targeting forkhead box O-1 (FOXO1) and FOXO3. Conversely, TMEM106C knockdown impeded cell proliferation and metastasis, whereas it enhanced the rate of apoptosis. More important, knockdown of the expression of TMEM106C in HCC cells inhibited the growth of xenograft tumors in vivo. Collectively, these results suggest that TMEM106C acts as an oncogene and can serve as a potential therapeutic target for HCC in the future.

Efficacy and Safety of Glecaprevir/Pibrentasvir in HCV Patients With Previous Direct-Acting Antiviral Therapy Failures: A Meta-Analysis.

Background: Since a greater number of hepatitis C virus (HCV) patients have access to direct-acting antiviral (DAA) based therapies, the number of patients not properly responding to prior DAA regimens is increasing. The objective of this comprehensive analysis was to assess the efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) in HCV patients who experienced previous DAA therapy failures. Methods: Bibliographic databases were systematically searched for relevant articles published by November 2020. The main endpoints were sustained viral response after 12 weeks (SVR12), adverse events (AEs; any grade) and severe adverse events (SAEs). Publication bias assessment was performed using funnel plots and the Egger's test. Results: Fourteen studies consisting of a total of 1,294 subjects were included in this study and the pooled estimate of SVR12, AEs and SAEs rates were 96.8% (95%CI: 95.1-98.2), 47.1% (95%CI: 26.0-69.3), and 1.8% (95%CI: 0.7-3.4), respectively. Subgroup analysis showed that pooled SVR12 rates were 97.9% (95%CI: 96.7-98.9) for Japan and 91.1% (95%CI: 87.3-94.3) for the United States; 95.8% (95%CI: 93.9-97.4) for genotype (GT)1 and 100.0% (95%CI: 99.6-100.0) for GT2; 95.3% (95%CI: 92.4-97.2) for cirrhosis and 96.3% (95%CI: 94.2-97.7) for non-cirrhosis cases. There was no publication bias included this study. Conclusion: This comprehensive analysis revealed that GLE/PIB is an effective and secure retreatment option for patients who did not optimally respond to DAA treatment, especially the Asian population with GT1-2.

Different Hepatitis C Virus Infection Statuses Show a Significant Risk of Developing Type 2 Diabetes Mellitus: A Network Meta-Analysis.

BACKGROUND: The role of hepatitis C virus (HCV) infection statuses in the development of type 2 diabetes mellitus (T2DM) has not been completely understood. AIM: To evaluate the prevalence of T2DM in patients with different HCV infection statuses. METHODS: We conducted a systematic study on T2DM risk in five types of individuals with different HCV infection statuses: non-HCV controls, HCV-cleared patients, chronic HCV patients without cirrhosis, patients with HCV cirrhosis and patients with decompensated HCV cirrhosis. Studies published from 2010 to 2019 were selected. Both pairwise and network meta-analyses were employed to compare the T2DM risk among patients with different HCV infection statuses. RESULTS: The pairwise meta-analysis showed that non-HCV (OR = 0.60, 95% CI [0.47-0.78]) had a lower risk of T2DM compared with CHC, while cirrhosis had a significant higher risk (OR = 1.90, 95% CI [1.60-2.26]). Network meta-analysis further demonstrated patients with HCV infection were at a significantly higher risk of T2DM than those without HCV infection or with HCV clearance, while decompensated cirrhosis had a significant higher T2DM risk than non-HCV (OR = 3.84, 95% CI [2.01-7.34]), patients with HCV clearance (OR = 3.17, 95% CI [1.49-6.73]), and CHC patients (OR = 2.21, 95% CI [1.24-3.94]). CONCLUSIONS: HCV infection is a significant risk factor for developing T2DM. CHC, cirrhosis, and decompensated cirrhosis contribute to an increasingly greater risk of T2DM, but HCV clearance spontaneously or through clinical treatment may immediately reduce the risk of the onset and development of T2DM.

[Qualitative evaluation of Forsythia suspensa by HPLC-PDA fingerprint combined with UFLC-Q-TOF-MS qualitative identification].

The analysis of Forsythia suspensa was performed on Waters Symmetry C18 column( 4. 6 mm×250 mm,5 µm) and mobile phase was methanol( A)-0. 1% formic acid aqueous solution( B) with the elution gradient. Column temperature was maintained at 30℃,and the flow rate was 1. 0 m L·min-1 with detection wavelength 265 nm. The HPLC-PDA fingerprint of F. suspensa was optimized.Chemical constituents in F. suspensa were analyzed by UFLC-Q-TOF-MS in positive and negative ion mode. The quality of 48 batches of F. suspensa from different habitats,processing methods and specifications was evaluated by similarity evaluation and cluster analysis.The 18 common peaks were confirmed. The similarity of F. suspensa from different habitats was more than 0. 98,and 56 chemical constituents were identified. Different processing methods had great influence on the quality of F. suspensa. Compared with boiled and direct drying,the quality of F. suspensa processed by sun-drying was obviously decreased. The similarity was about 0. 58. Different specifications of F. suspensa also had obvious distinction,and the similarity was about 0. 78. The effective components of grown F. suspensa,such as forsythoside A and phillyrin,were significantly reduced. The results of cluster analysis were basically consistent with the results of similarity evaluation. The establishment of fingerprint and the recognition of chemical pattern of F. suspensa can provide a more comprehensive reference for the quality control of herbs.

Is It Necessary to Perform the Pharmacological Interventions for Intrahepatic Cholestasis of Pregnancy? A Bayesian Network Meta-Analysis.

BACKGROUND AND OBJECTIVE: Although many meta-analyses have evaluated the pharmacotherapy of intrahepatic cholestasis of pregnancy (ICP) and recommended ursodeoxycholic acid (UDCA) as an effective treatment, the defect of the pair-wise analyses and the mixture of the control group made the outcome uncertain and unclear. We aimed to employ Bayesian network meta-analysis (NMA) to compare the maternal and fetal outcomes after UDCA, S-adenosylmethionine (SAMe) mono-therapy or the combination treatment of these two drugs for ICP patients. METHODS: Multiple electronic database searches were conducted for articles published up to 1 September 2018. The relevant information was extracted from the published reports with a predefined data extraction sheet, and the risk of bias was assessed with the Cochrane risk-of-bias tool. Poisson Bayesian network meta-analysis was employed to identify the synthesized evidence from the relevant trials, with reporting hazard risks (HRs) and 95% credible intervals (CrIs). RESULTS: The pooled outcomes of the 13 randomized controlled trials (RCTs) with 625 participants indicated that none of the three regimens can significantly improve maternal and fetal outcomes. CONCLUSION: This NMA of the RCTs clarified that the current intervention has no favorable effect on pruritus and other symptoms in ICP patients.