Mendelian-randomization study revealed causal relationship between nonalcoholic fatty liver disease and osteoporosis/fractures.

BACKGROUND: Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have a higher risk of osteoporosis/fractures; however, the causal relationship remains unclear. METHODS: Publicly available genome-wide association studies (GWASs) were used for Mendelian randomization (MR) analysis. GWASs of NAFLD and fractures were obtained from the FinnGen Consortium. GWASs of bone mineral density (BMD) were derived from a meta-analysis. GWASs of obesity, diabetes, liver function, and serum lipid-related metrics were used to clarify whether the accompanying NAFLD symptoms contributed to fractures. Moreover, two additional GWASs of NAFLD were applied. RESULTS: A causal association was not observed between NAFLD and BMD using GWASs from the FinnGen Consortium. However, a causal relationship between NAFLD and femoral neck-BMD (FN-BMD), a suggestive relationship between fibrosis and FN-BMD, and between NAFLD and osteoporosis were identified in replication GWASs. Genetically proxied body mass index (BMI), high-density lipoprotein (HDL), and hip circumference increased the likelihood of lower limb fractures. The waist-to-hip ratio decreased, whereas glycated hemoglobin (HbA1C) and homeostasis model assessment of ß-cell function (HOMA-B) increased the risk of forearm fractures. Low-density lipoprotein (LDL) reduced, whereas HbA1C increased the incidence of femoral fractures. Alkaline phosphatase (ALP) raised the risk of foot fractures. However, after a multivariate MR analysis (adjusted for BMI), all the relationships became insignificant. CONCLUSIONS: NAFLD caused reduced BMD, and genetically predicted HDL, LDL, HbA1C, HOMA-B, ALP, hip circumference, and waist-to-hip ratio causally increased the risk of fractures. BMI may mediate causal relationships. Larger GWASs are required to verify this finding.

Circular RNAs in non-alcoholic fatty liver disease: Functions and clinical significance.

Nonalcoholic fatty liver disease (NAFLD), which affects approximately 25% of the global population, is an urgent health issue leading to various metabolic comorbidities. Circular RNAs (circRNAs), covalently closed RNA molecules, are characterized by ubiquity, diversity, stability, and conservatism. Indeed, they participate in various biological processes via distinct mechanisms that could modify the natural history of NAFLD. In this review, we briefly introduce the biogenesis, characteristics, and biological functions of circRNAs. Furthermore, we summarize circRNAs expression profiles in NAFLD by intersecting seven sequencing data sets and describe the cellular roles of circRNAs and their potential advantages as biomarkers of NAFLD. In addition, we emphatically discuss the exosomal non-coding RNA sorting mechanisms and possible functions in recipient cells. Finally, we extensively discuss the potential application of targeting disease-related circRNAs and competing endogenous RNA networks through gain-of-function and loss-of-function approaches in targeted therapy of NAFLD.

Liver cancer stem cell dissemination and metastasis: uncovering the role of NRCAM in hepatocellular carcinoma.

BACKGROUND: Liver cancer stem cells (LCSCs) play an important role in hepatocellular carcinoma (HCC), but the mechanisms that link LCSCs to HCC metastasis remain largely unknown. This study aims to reveal the contributions of NRCAM to LCSC function and HCC metastasis, and further explore its mechanism in detail. METHODS: 117 HCC and 29 non-HCC patients with focal liver lesions were collected and analyzed to assess the association between NRCAM and HCC metastasis. Single-cell RNA sequencing (scRNA-seq) was used to explore the biological characteristics of cells with high NRCAM expression in metastatic HCC. The role and mechanism of NRCAM in LCSC dissemination and metastasis was explored in vitro and in vivo using MYC-driven LCSC organoids from murine liver cells. RESULTS: Serum NRCAM is associated with HCC metastasis and poor prognosis. A scRNA-seq analysis identified that NRCAM was highly expressed in LCSCs with MYC activation in metastatic HCC. Moreover, NRCAM facilitated LCSC migration and invasion, which was confirmed in MYC-driven LCSC organoids. The in vivo tumor allografts demonstrated that NRCAM mediated intra-hepatic/lung HCC metastasis by enhancing the ability of LCSCs to escape from tumors into the bloodstream. Nrcam expression inhibition in LCSCs blocked HCC metastasis. Mechanistically, NRCAM activated epithelial-mesenchymal transition (EMT) and metastasis-related matrix metalloproteinases (MMPs) through the MACF1 mediated ß-catenin signaling pathway in LCSCs. CONCLUSIONS: LCSCs typified by high NRCAM expression have a strong ability to invade and migrate, which is an important factor leading to HCC metastasis.

Role of extracellular vesicles in nonalcoholic fatty liver disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that affects approximately one-quarter of the global population and is becoming increasingly prevalent worldwide. The lack of current noninvasive tools and efficient treatment is recognized as a significant barrier to the clinical management of these conditions. Extracellular vesicles (EVs) are nanoscale vesicles released by various cells and deliver bioactive molecules to target cells, thereby mediating various processes, including the development of NAFLD. Scope of review: There is still a long way to actualize the application of EVs in NAFLD diagnosis and treatment. Herein, we summarize the roles of EVs in NAFLD and highlight their prospects for clinical application as a novel noninvasive diagnostic tool as well as a promising therapy for NAFLD, owing to their unique physiochemical characteristics. We summarize the literatures on the mechanisms by which EVs act as mediators of intercellular communication by regulating metabolism, insulin resistance, inflammation, immune response, intestinal microecology, and fibrosis in NAFLD. We also discuss future challenges that must be resolved to improve the therapeutic potential of EVs. Major conclusions: The levels and contents of EVs change dynamically at different stages of diseases and this phenomenon may be exploited for establishing sensitive stage-specific markers. EVs also have high application potential as drug delivery systems with low immunogenicity and high biocompatibility and can be easily engineered. Research on the mechanisms and clinical applications of EVs in NAFLD is in its initial phase and the applicability of EVs in NAFLD diagnosis and treatment is expected to grow with technological progress.

LncRNA and circRNA in Patients with Non-Alcoholic Fatty Liver Disease: A Systematic Review.

Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide. Early identification and prompt treatment are critical to optimize patient management and improve long-term prognosis. Long non-coding RNA (lncRNA) and circular RNA (circRNA) are recently emerging non-coding RNAs, and are highly stable and easily detected in the circulation, representing a promising non-invasive approach for predicting NAFLD. A literature search of the Pubmed, Embase, Web of Science, and Cochrane Library databases was performed and 36 eligible studies were retrieved, including 18 on NAFLD, 13 on nonalcoholic steatohepatitis (NASH), and 11 on fibrosis and/or cirrhosis. Dynamic changes in lncRNA expression were associated with the occurrence and progression of NAFLD, among which lncRNA NEAT1, MEG3, and MALAT1 exhibited great potential as biomarkers for NAFLD. Moreover, mitochondria-located circRNA SCAR can drive metaflammation and its inhibition might be a promising therapeutic target for NASH. In this systematic review, we highlight the great potential of lncRNA/circRNA for early diagnosis and progression assessment of NAFLD. To further verify their clinical value, large-cohort studies incorporating lncRNA and circRNA expression both in liver tissue and blood should be conducted. Additionally, detailed studies on the functional mechanisms of NEAT1, MEG3, and MALAT1 will be essential for elucidating their roles in diagnosing and treating NAFLD, NASH, and fibrosis.

Crisis communication in the WHO COVID-19 press conferences: A retrospective analysis.

OBJECTIVES: The objective of this study is to investigate, from a longitudinal perspective, how WHO communicated COVID-19 related information to the public through its press conferences during the first two years of the pandemic. METHODS: The transcripts of 195 WHO COVID-19 press conferences held between January 22, 2020 and February 23, 2022 were collected. All transcripts were syntactically parsed to extract highly frequent noun chunks that were potential topics of the press conferences. First-order autoregression models were fit to identify "hot" and "cold" topics. In addition, sentiments and emotions expressed in the transcripts were analyzed using lexicon-based sentiment/emotion analyses. Mann-Kendall tests were performed to capture the possible trends of sentiments and emotions over time. RESULTS: First, eleven "hot" topics were identified. These topics were pertinent to anti-pandemic measures, disease surveillance and development, and vaccine-related issues. Second, no significant trend was captured in sentiments. Last, significant downward trends were found in anticipation, surprise, anger, disgust, and fear. However, no significant trends were found in joy, trust, and sadness. CONCLUSIONS: This retrospective study provided new empirical evidence on how WHO communicated issues pertaining to COVID-19 to the general public through its press conferences. With the help of the study, members of the general public, health organizations, and other stake-holders will be able to better understand the way in which WHO has responded to various critical events during the first two years of the pandemic.

CircRNA-PI4KB Induces Hepatic Lipid Deposition in Non-Alcoholic Fatty Liver Disease by Transporting miRNA-122 to Extra-Hepatocytes.

Ectopic fat deposition in the liver, known as non-alcoholic fatty liver disease (NAFLD), affects up to 30% of the worldwide population. miRNA-122, the most abundant liver-specific miRNA, protects hepatic steatosis and inhibits cholesterol and fatty acid synthesis in NAFLD. Previously, we have shown that compared with its expression in healthy controls, miRNA-122 decreased in the liver tissue but gradually increased in the serum of patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, suggesting that miRNA-122 could have been transported to the serum. Here, we aimed to confirm and unravel the mechanism of transportation of miRNA-122 to extra-hepatocytes. Our findings showed a decrease in the intra-hepatocyte miRNA-122 and an increase in the extra-hepatocyte (medium level) miRNA-122, suggesting the miRNA-122 "escaped" from the intra-hepatocyte due to an increased extra-hepatocyte excretion. Using bioinformatics tools, we showed that miRNA-122 binds to circPI4KB, which was further validated by an RNA pull-down and luciferase reporter assay. The levels of circPI4KB in intra- and extra-hepatocytes corresponded to that of miRNA-122, and the overexpression of circPI4KB increased the miRNA-122 in extra-hepatocytes, consequently accomplishing a decreased protective role of miRNA-122 in inhibiting the lipid deposition. The present study provides a new explanation for the pathogenesis of the hepatic lipid deposition in NAFLD.

Clinical features, natural history and outcomes of pseudolymphoma of liver: A case-series and systematic review.

BACKGROUND: Pseudolymphoma is a rare, benign, nonspecific condition that forms a mass-like lesion characterized by the proliferation of non-neoplastic lymphocytes. Lacking of specific clinical symptoms, serological markers, and imaging features, the diagnosis is difficult. We reporte five cases of hepatic pseudolymphoma and provide a systematic review of existing literatures to improve our understanding of this rare liver disease. METHODS: We followed-up five cases of hepatic pseudolymphoma in West China Hospital from January 2002 to January 2022. We also summarized the cases of hepatic pseudolymphoma from January 1981 to December 2021 through the PubMed database and comprehensively analyzed the characteristics of the cases. RESULTS: The pathologic features of the five cases were characterized by benign lymphoid tissue hyperplasia, lymphoid follicle formation, and a polarized germinal center. Immunohistochemistry, in situ hybridization, and gene rearrangement revealed non-malignant lymphoma. Besides, a total of 116 cases have been reported in the PubMed database from 1981 to 2021. The incidence of hepatic pseudolymphoma is higher in middle-aged and elderly women and has been reported more frequently in Asia. All cases were pathologically diagnosed, among which 85.95% of the patients were treated by surgery. CONCLUSIONS: Hepatic pseudolymphoma is an extremely rare benign disease, mainly in middle-aged and elderly women. Without distinctive clinical and imaging characteristics, pathological diagnosis is the highly reliable method at present. Thus, in the absence of risk factors for a primary liver tumor or metastatic tumor in middle-aged and elderly women, the possibility of pseudolymphoma should be considered to avoid extensive treatments.

Concomitant Diseases and Co-contribution on Progression of Liver Stiffness in Patients with Hepatitis B Virus Infection.

BACKGROUND: The association between hepatitis B and concomitant diseases, such as fatty liver, T2DM, MetS, and Hp infection, remains unclear. AIM: The present study was to illustrate the association and explore the co-contribution on abnormal transaminase and progression of liver stiffness. METHODS: A total of 95,998 participants underwent HBsAg screening in West China Hospital from 2014 to 2017. Multivariable logistic regression was used to determine the adjusted odds ratios. RESULTS: The prevalence of HBsAg-positive rate was 8.30% of our included study population. HBsAg positive was associated with negative risk of fatty liver (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.65-0.78, p < 0.001) and MetS (OR 0.74, 95% CI 0.67-0.84, p < 0.001), and with positive risk of Hp infection (OR 1.09, 95% CI 1.02-1.17, p = 0.012) and T2DM (OR 1.18, 95% CI 1.01-1.40, p = 0.043). Besides, HBsAg-positive patients with T2DM had higher risk of elevated ALT (OR 2.09, 95% CI 1.69-2.83, p < 0.001 vs OR 1.59, 95% CI 1.51-1.68, p < 0.001), AST (OR 2.69, 95% CI 1.98-3.65, p < 0.001 vs OR 1.89, 95% CI 1.76-2.02, p < 0.001) than HBV alone. In addition to HBV, T2DM also can increase the risk of liver fibrosis (OR 3.23, 95% CI 1.35-7.71, p = 0.008) and cirrhosis (OR 4.31, 95% CI 1.41-13.20, p = 0.010). CONCLUSION: Hepatitis B patients have a lower risk of fatty liver and MetS, and a higher risk of T2DM and Hp infection. Besides, T2DM might be possibly associated with abnormal liver transaminase and fibrosis progression in HBsAg-positive patients.

Black liver in a patient with Wilson's disease.

Wilson's disease is an autosomal recessive inherited disease with congenital copper metabolism disorder, characterized by decreased ceruloplasmin and increased urine copper, which can involve multiple organs. This case was complicated by iron overload, which is of great value in differentiating hereditary hemochromatism.

Association of serum pepsinogens and gastrin-17 with Helicobacter pylori infection assessed by urea breath test.

Background: Association of gastric atrophy or cancer with levels of serum pepsinogens, gastrin-17 and anti-Helicobacter pylori IgG antibody have been extensively studied. However, the association of serum pepsinogen and gastrin-17 with H. pylori infection has not been studied in a large population. Aim: To investigate the impact of H. pylori infection on serum levels of pepsinogens and gastrin-17. Methods: A total of 354, 972 subjects who underwent health check-ups were included. Serum levels of pepsinogens and gastrin-17 were measured using the enzyme-linked immunosorbent assay. H. pylori infection was detected using 14C-urea breath test (UBT). Multivariable logistic regression analysis was used to investigate the association of serum pepsinogen and gastrin-17 with H. pylori infection. Results: H. pylori prevalence was 33.18% in this study. The mean levels of pepsinogens and gastrin-17 were higher, while the mean pepsinogen-I/II ratio were lower among H. pylori-positive than -negative subjects. In H. pylori-positive subjects, pepsinogen and gastrin-17 levels correlated positively, whereas the pepsinogen-I/II ratio correlated negatively with UBT values (e.g., the mean serum level of pepsinogen-I in subjects with UBT values in the range of 100-499dpm, 500-1499dpm, and ≥1500dpm was 94.77 ± 38.99, 102.77 ± 43.59, and 111.53 ± 47.47 ng/mL, respectively). Compared with H. pylori-negative subjects, the adjusted odds ratio (aOR) of having pepsinogen-I ≤ 70 ng/mL in the three H. pylori-positive but with different UBT value groups was 0.31 (p<0.001), 0.16 (p<0.001), and 0.08 (p<0.001), respectively; while the aOR of having G-17>5.70 pmol/L was 4.56 (p<0.001), 7.43 (p<0.001), and 7.12 (p<0.001). This suggested that H. pylori-positive subjects with higher UBT values were less likely to have pepsinogen-I ≤70 ng/mL (a serum marker for gastric atrophy), but more likely to have gastrin-17 >5.70 pmol/L (a marker for peptic ulcer). Conclusions: H. pylori-positive subjects with higher UBT values are unlikely to have gastric atrophy, but may have greater risk of severe gastritis or peptic ulcers. Our study suggests that H. pylori-positive patients with high UBT values may benefit the most from H. pylori eradication.

Urine Proteome in Distinguishing Hepatic Steatosis in Patients with Metabolic-Associated Fatty Liver Disease.

Background: In patients with metabolic-associated fatty liver disease (MAFLD), hepatic steatosis is the first step of diagnosis, and it is a risk predictor that independently predicts insulin resistance, cardiovascular risk, and mortality. Urine biomarkers have the advantage of being less complex, with a lower dynamic range and fewer technical challenges, in comparison to blood biomarkers. Methods: Hepatic steatosis was measured by magnetic resonance imaging (MRI), which measured the proton density fat fraction (MRI-PDFF). Mild hepatic steatosis was defined as MRI-PDFF 5−10% and severe hepatic steatosis was defined as MRI-PDFF > 10%. Results: MAFLD patients with any kidney diseases were excluded. There were 53 proteins identified by mass spectrometry with significantly different expressions among the healthy control, mild steatosis, and severe steatosis patients. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of these significantly changed urinary molecular features correlated with the liver, resulting in the dysregulation of carbohydrate derivative/catabolic/glycosaminoglycan/metabolic processes, insulin-like growth factor receptor levels, inflammatory responses, the PI3K−Akt signaling pathway, and cholesterol metabolism. Urine alpha-1-acid glycoprotein 1 (ORM1) and ceruloplasmin showed the most significant correlation with the clinical parameters of MAFLD status, including liver fat content, fibrosis, ALT, triglycerides, glucose, HOMA-IR, and C-reactive protein. According to ELISA and western blot (30 urine samples, normalized to urine creatinine), ceruloplasmin (ROC 0.78, p = 0.034) and ORM1 (ROC 0.87, p = 0.005) showed moderate diagnostic accuracy in distinguishing mild steatosis from healthy controls. Ceruloplasmin (ROC 0.79, p = 0.028) and ORM1 (ROC 0.81, p = 0.019) also showed moderate diagnostic accuracy in distinguishing severe steatosis from mild steatosis. Conclusions: Ceruloplasmin and ORM1 are potential biomarkers in distinguishing mild and severe steatosis in MAFLD patients.

Predicting progression to severe COVID-19 using the PAINT score.

OBJECTIVES: One of the major challenges in treating patients with coronavirus disease 2019 (COVID-19) is predicting the severity of disease. We aimed to develop a new score for predicting progression from mild/moderate to severe COVID-19. METHODS: A total of 239 hospitalized patients with COVID-19 from two medical centers in China between February 6 and April 6, 2020 were retrospectively included. The prognostic abilities of variables, including clinical data and laboratory findings from the electronic medical records of each hospital, were analysed using the Cox proportional hazards model and Kaplan-Meier methods. A prognostic score was developed to predict progression from mild/moderate to severe COVID-19. RESULTS: Among the 239 patients, 216 (90.38%) patients had mild/moderate disease, and 23 (9.62%) progressed to severe disease. After adjusting for multiple confounding factors, pulmonary disease, age > 75, IgM, CD16+/CD56+ NK cells and aspartate aminotransferase were independent predictors of progression to severe COVID-19. Based on these five factors, a new predictive score (the 'PAINT score') was established and showed a high predictive value (C-index = 0.91, 0.902 ± 0.021, p < 0.001). The PAINT score was validated using a nomogram, bootstrap analysis, calibration curves, decision curves and clinical impact curves, all of which confirmed its high predictive value. CONCLUSIONS: The PAINT score for progression from mild/moderate to severe COVID-19 may be helpful in identifying patients at high risk of progression.

Diagnostic accuracy of circulating microRNA in hepatitis B virus-related hepatocellular carcinoma: a meta-analysis based on Asian data

Background and aim: hepatitis B virus (HBV) is the main risk factor for hepatocellular carcinoma (HCC). We performed a meta-analysis based on Asian data to evaluate the diagnostic accuracy of circulating microRNA as a non-invasive biomarker in the diagnosis of HBV-related HCC.Methods: a comprehensive literature search (updated to May 12, 2021) in PubMed, Embase, Web of Science, Wanfang Database, and China National Knowledge Infrastructure (CNKI) was performed to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) for diagnosing HBV-related HCC were pooled in this meta-analysis. A subgroup analysis was performed to explore heterogeneity, and Deeks' funnel plot was used to assess publication bias.Results: a total of 19 articles including 32 studies were included in the current meta-analysis. The overall sensitivity, specificity, PLR, NLR, DOR and AUC were 0.83 (95 % CI: 0.79 to 0.87), 0.78 (95 % CI: 0.73 to 0.83), 3.9 (95 % CI: 3.0 to 4.9), 0.21 (95 % CI: 0.16 to 0.27), 18 (95 % CI: 12 to 27) and 0.88 (95 % CI: 0.85 to 0.91), respectively. Subgroup analysis shows that miRNA clusters with a large sample size showed better diagnostic accuracy. Although there is no publication bias, the research still has some limitations.Conclusions: circulating miRNAs could serve as a potential non-invasive biomarker in diagnosing HBV-related HCC in Asian populations. (AU)

Determinants of suboptimal immune recovery among a Chinese Yi ethnicity population with sustained HIV suppression.

OBJECTIVES: Despite sustained viral suppression with effective antiretroviral therapy (ART), HIV-infected patients with suboptimal immune recovery are still at high risk of both non-AIDS-related and AIDS-related events. The aim of this study was to investigate determinants potentially associated with suboptimal CD4 + T cell count recovery during free ART with sustained viral suppression among an HIV-infected Yi ethnicity population in Liangshan Prefecture, an area in China with high HIV prevalence. METHODS: This retrospective study included HIV-infected Yi adults (≥ 18 years and baseline CD4 + T cell count less than 500 cells/µL) for whom ART supported by National Free Antiretroviral Treatment Program was initiated between January 2015 and December 2018 in Zhaojue County, Liangshan Prefecture. Virological suppression (viral load < 50 copies/mL) was achieved within 12 months after ART initiation, and sustained virological suppression was maintained. Multivariate log-binomial regression analysis was used to assess determinants of suboptimal immune recovery. RESULTS: There were 140 female and 137 male patients in this study, with a mean age of 36.57 ± 7.63 years. Most of the Yi patients were infected through IDU (48.7%) or heterosexual contact (49.8%), and the anti-HCV antibody prevalence was high (43.7%, 121/277). Of the 277 patients with a mean ART duration of 3.77 ± 1.21 years, complete immune recovery occurred in only 32.9%. The baseline CD4 + T cell count in patients with suboptimal and intermediate immune recovery was 248.64 ± 108.10 and 288.59 ± 108.86 cells/µL, respectively, which was much lower than the baseline 320.02 ± 123.65 cells/µL in patients who achieved complete immune recovery (p < 0.001). Multivariable analysis demonstrated that low pre-ART CD4 + cell count and coinfection with HCV were associated with immune recovery of the HIV patients. CONCLUSIONS: Our study suggests that for HIV-infected Yi patients in Liangshan Prefecture, prompt ART initiation after diagnosis of HIV infection should be applied, and curative HCV treatment should be given to patients with HCV/HIV coinfection to improve the immunological effectiveness of ART. Trial registration None.

Two-year immune effect differences between the 0-1-2-month and 0-1-6-month HBV vaccination schedule in adults.

BACKGROUND: The short-term 0-1-2-month hepatitis B virus (HBV) vaccination schedule was previously implemented in the adult population; however, its long-term immune effect remains unclear. The present study aimed to investigate (1) the 2-month and 2-year immune effects of HBV vaccination and (2) the compliance rate between the 0-1-2-month and 0-1-6-month vaccination schedules in adults. METHOD: A total of 1281 subjects tested for hepatitis B surface antigen HBsAg(-) and hepatitis B surface antibody (anti-HBs)(-) were recruited. Participants from two distant counties were inoculated with the hepatitis B yeast vaccine at 10 µg per dose, with vaccination schedules of 0, 1, and 2 months (n = 606) and 0, 1, and 6 months (n = 675); sequential follow-up was performed at 2 months and 2 years after the 3rd injection. RESULTS: There were no significant differences in the anti-HBs seroconversion rates between the those in the 0-1-2-month and 0-1-6-month vaccination schedule groups at 2 months (91.96% vs. 89.42%, p = 0.229) and 2 years (81.06% vs. 77.14%, p = 0.217). The quantitative anti-HBs level in those in the 0-1-2-month vaccination schedule group was not different from that in those in the 0-1-6-month vaccination schedule group at 2 months (anti-HBs1) (342.12 ± 378.42 mIU/ml vs. 392.38 ± 391.96 mIU/ml, p = 0.062), but it was higher at 2 years (anti-HBs2) (198.37 ± 286.44 mIU/ml vs. 155.65 ± 271.73 mIU/ml, p = 0.048). According to the subgroup analysis, the 0-1-2-month vaccination schedule induced better maintenance (p = 0.041) and longer reinforcement (p = 0.019) than the 0-1-6 vaccination schedule. The 0-1-2-month vaccination schedule group also had a higher 3rd injection completion rate (89.49% vs. 84.49%, p = 0.010). CONCLUSION: The 0-1-2-month vaccination schedule was associated with a similar short-term immune effect and might induce better long-term immune memory and a higher completion rate in the adult population. Trial registration None.

Distribution characteristics of soil microbial communities and their responses to environmental factors in the sea buckthorn forest in the water-wind erosion crisscross region.

Soil microorganisms are an important part of forest ecosystems, and their community structure and ecological adaptations are important for explaining soil material cycles in the fragile ecological areas. We used high-throughput sequencing technology to examine the species composition and diversity of soil bacterial and fungal communities in sea buckthorn forests at five sites in the water-wind erosion crisscross in northern Shaanxi (about 400 km long). The results are described as follows: (1) The soil bacterial community of the sea buckthorn forest in the study region was mainly dominated by Actinobacteria, Proteobacteria, and Acidobacteria, and the fungi community was mainly dominated by Ascomycota. (2) The coefficient of variation of alpha diversity of microbial communities was higher in the 0-10 cm soil layer than in the 10-20 cm soil layer. (3) Soil electrical conductivity (36.1%), available phosphorous (AP) (21.0%), available potassium (16.2%), total nitrogen (12.7%), and the meteorological factors average annual maximum temperature (33.3%) and average annual temperature (27.1%) were identified as the main drivers of structural changes in the bacterial community. Available potassium (39.4%), soil organic carbon (21.4%), available nitrogen (AN) (13.8%), and the meteorological factors average annual maximum wind speed (38.0%) and average annual temperature (26.8%) were identified as the main drivers of structural changes in the fungal community. The explanation rate of soil factors on changes in bacterial and fungal communities was 26.6 and 12.0%, respectively, whereas that of meteorological factors on changes in bacterial and fungal communities was 1.22 and 1.17%, respectively. The combined explanation rate of environmental factors (soil and meteorological factors) on bacterial and fungal communities was 72.2 and 86.6%, respectively. The results of the study offer valuable insights into the diversity of soil microbial communities in the water-wind erosion crisscross region and the mechanisms underlying their interaction with environmental factors.

Diagnostic accuracy of circulating microRNA in hepatitis B virus-related hepatocellular carcinoma: a meta-analysis based on Asian data.

BACKGROUND AND AIM: hepatitis B virus (HBV) is the main risk factor for hepatocellular carcinoma (HCC). We performed a meta-analysis based on Asian data to evaluate the diagnostic accuracy of circulating microRNA as a non-invasive biomarker in the diagnosis of HBV-related HCC. METHODS: a comprehensive literature search (updated to May 12, 2021) in PubMed, Embase, Web of Science, Wanfang Database, and China National Knowledge Infrastructure (CNKI) was performed to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) for diagnosing HBV-related HCC were pooled in this meta-analysis. A subgroup analysis was performed to explore heterogeneity, and Deeks' funnel plot was used to assess publication bias. RESULTS: a total of 19 articles including 32 studies were included in the current meta-analysis. The overall sensitivity, specificity, PLR, NLR, DOR and AUC were 0.83 (95 % CI: 0.79 to 0.87), 0.78 (95 % CI: 0.73 to 0.83), 3.9 (95 % CI: 3.0 to 4.9), 0.21 (95 % CI: 0.16 to 0.27), 18 (95 % CI: 12 to 27) and 0.88 (95 % CI: 0.85 to 0.91), respectively. Subgroup analysis shows that miRNA clusters with a large sample size showed better diagnostic accuracy. Although there is no publication bias, the research still has some limitations. CONCLUSIONS: circulating miRNAs could serve as a potential non-invasive biomarker in diagnosing HBV-related HCC in Asian populations.

Abnormal transaminase and lipid profiles in coexisting diseases in patients with fatty liver: a population study in Sichuan.

Among chronic liver diseases, fatty liver has the highest incidence worldwide. Coexistence of fatty liver and other chronic diseases, such as diabetes, hepatitis B virus (HBV) and Helicobacter pylori (Hp) infection, is common in clinical practice. The present study was conducted to analyze the prevalence and association of coexisting diseases in patients with fatty liver and to investigate how coexisting diseases contribute to abnormal transaminase and lipid profiles. We enrolled participants who were diagnosed with fatty liver via ultrasound in the physical examination center of West China Hospital. Multivariable logistic regression was used to determine the adjusted odds ratios (ORs). We found that 23.6% of patients who underwent physical examinations were diagnosed with fatty liver. These patients had higher risks of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and hypertension and a lower risk of HBV infection. The risks of Hp infection and hyperthyroidism did not statistically differ. When fatty liver coexisted with T2DM, MetS and thyroid dysfunction, it conferred a higher risk of elevated transaminase. Fatty liver was positively correlated with triglycerides, cholesterol and low-density lipoprotein cholesterol (LDL-C) and negatively correlated with HBV; thus, HBV had a neutralizing effect on lipid metabolism when coexisting with fatty liver. In conclusion, patients with fatty liver that coexists with T2DM, MetS and thyroid dysfunction are more prone to elevated transaminase levels. Patients with both fatty liver and HBV may experience a neutralizing effect on their lipid metabolism. Thus, lipid alterations should be monitored in these patients during antiviral treatment for HBV.

Effectiveness of granulocyte colony-stimulating factor for patients with acute-on-chronic liver failure: a meta-analysis.

BACKGROUND: The safety and efficacy of granulocyte colony-stimulating factor (G-CSF) for the treatment of acute-on-chronic liver failure (ACLF) remain uncertain. Therefore, we conducted a meta-analysis to draw a firmer conclusion. METHODS: We searched the Cochrane library, PubMed, Embase, and China Biology Medicine disc to identify relevant RCTs performed before January 2020. Risk ratios (RRs) and their 95% confidence intervals (95% CIs) were calculated using a random effects model. MAIN OUTCOME MEASURES: RRs (95% CI) for 1-, 2-, and 3-month survival rates. SAMPLE SIZE: Six RCTs, including three open-label studies. RESULTS: The six studies included 246 subjects (121 in a G-CSF group and 125 in a control group). G-CSF administration significantly improved the 1-, 2-, and 3-month survival rates in patients with ACLF. The pooled RRs (95% CI, P) were 0.43 (0.27-0.69, P=.0004), 0.44 (0.32-0.62, P<.00001), and 0.39 (0.22-0.68, P=.0009), respectively. CONCLUSION: G-CSF may be beneficial and effective in the treatment of ACLF, but further studies are needed to verify this conclusion. LIMITATIONS: The sample size was small, and studies were restricted to countries in Asia. PROSPERO REGISTRATION NUMBER: CRD42021225681 CONFLICT OF INTEREST: None.