Liver failure is a common severe syndrome of liver diseases with high mortality. The function and structural integrity of the intestinal barrier as an entity are closely associated with the development and progression of liver failure. The cGAS-STING signaling pathway can participate in innate immune response by recognizing DNA produced by pathogen invasion and host cell damage and inducing the production of type I interferon. Numerous studies have shown that activation of the cGAS-STING pathway can significantly impact the cellular structure， mucosal components， and commensal bacteria of the intestinal barrier. This article reviews the interplay between the cGAS-STING signaling pathway and intestinal barrier disruption in liver failure， in order to provide novel insights for the clinical management of liver failure.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Objective To investigate the association between lifestyle and risk of heart disease and diabetes in the elderly population in Xi'an City. Methods From January 2021 to January 2024, a staged cluster sampling method was used to investigate the lifestyle and the occurrence of heart disease and diabetes in elderly population aged 60 years and above in the communities of Xi'an. Multivariate logistic regression was used to analyze the relationship between lifestyle and the risk of heart disease and diabetes. Results A total of 413 elderly people were investigated, of which 31.96% had heart disease, 27.12% had diabetes, and 10.90% had diabetes with heart disease. Multivariate logistic regression analysis revealed that age, BMI, family history, sweet food preference, smoking, and sitting and lying for a long time were risk factors for diabetes in the elderly population (P<0.05). Age, BMI, family history, history of diabetes, preference for salted products, smoking, drinking, and sitting and lying for a long time were risk factors for heart disease in the elderly population (P<0.05). Conclusion The incidence rates of heart disease and diabetes are high in the elderly population in Xi'an City. The risk of diabetes is related to unhealthy lifestyles such as sweet food preference, smoking, and sitting and lying for a long time, while heart disease is related to unhealthy lifestyles such as preference for salted products, smoking, drinking, and sitting and lying for a long time.

OBJECTIVE: To explore the application of targeted mRNA sequencing in fusion gene diagnosis of hematologic diseases. METHODS: Bone marrow or peripheral blood samples of 105 patients with abnormally elevated eosinophil proportions and 291 acute leukemia patients from January 2015 to June 2023 in the First Affiliated Hospital of Soochow University were analyzed and gene structural variants were detected by targeted mRNA sequencing. RESULTS: Among 105 patients with abnormally elevated eosinophil proportions, 6 cases were detected with gene structural variants, among which fusion gene testing results in 5 cases could serve as diagnostic indicators for myeloid neoplasms with eosinophilia. In addition, a IL3∷ETV6 fusion gene was detected in one patient with chronic eosinophilic leukemia, not otherwise specified. Among 119 patients with acute myeloid leukemia (AML), 38 cases were detected structural variants by targeted mRNA sequencing, accounting for 31.9%, which was significantly higher than 20.2% (24/119) detected by multiple quantitative PCR (P < 0.05). We also found one patient with AML had both NUP98∷PRRX2 and KCTD5∷JAK2 fusion genes. A total of 104 patients were detected structural variants by targeted mRNA sequencing in 172 cases with acute B-lymphoblastic leukemia who were tested negative by multiple quantitative PCR, with a detection rate of 60.5% (102/172). CONCLUSION Targeted mRNA sequencing can effectively detect fusion gene and has potential clinical application value in diagnosis and classificatation in hematologic diseases.
Humans ; Hematologic Diseases/diagnosis* ; RNA, Messenger/genetics* ; Oncogene Proteins, Fusion/genetics* ; Sequence Analysis, RNA ; Leukemia, Myeloid, Acute/diagnosis*

OBJECTIVE: To explore the impact factors and the clinical significance of the urination intermittences in benign prostatic hyperplasia (BPH) patients. METHODS: A retrospective study was performed in BPH patients who underwent urodynamic studies in Beijing Jishuitan Hospital form January 2016 to June 2021. The patients were aged 45 to 84 years with a median age of 63 years, and all the patients had no previous history of neurological disease and had no positive findings in neurological examinations. All the patients had free uroflometry followed by urethral catheterization and urodynamic tests. The voiding work of bladder was calculated using the detrusor power curve method, and the voiding power of bladder and the voiding energy consumption were also calculated. The frequency of urination intermittences generated in uroflometry was also recorded and the patients were divided into different groups according to it. The detrusor pressure at maximal flow rate (P_detQ_max), the maximal flow rate (Q_max), the bladder contractile index (BCI), the bladder outlet obstruction index (BOOI), the voiding work, the voiding power, and the voiding energy consumption were compared among the different groups. Multiva-riate analyses associated with presence of urination intermittences were performed using step-wise Logistic regressions. RESULTS: There were 272 patients included in this study, of whom, 179 had no urination intermittence (group A), 46 had urination intermittence for only one time (group B), 22 had urination intermittence for two times (group C), and 25 had urination intermittence for three times and more (group D). The BCI were 113.4±28.2, 101.0±30.2, 83.3±30.2, 81.0±30.5 in groups A, B, C, and D, respectively; The voiding power were (29.2±14.8) mW, (16.4±9.6) mW, (14.5±7.1) mW, (8.5±5.0) mW in groups A, B, C, and D, respectively, and the differences were significant (P < 0.05). The BOOI were 41.6±29.3, 46.4±31.0, 41.4±29.0, 42.7±22.8 in groups A, B, C, and D, respectively; The voiding energy consumption were (5.41±2.21) J/L, (4.83±2.31) J/L, (5.02±2.54) J/L, (4.39±2.03) J/L in groups A, B, C, and D, respectively, and the differences were insignificant (P>0.05). Among the patients, 179 cases were negative in presence of urination intermittences and 93 cases were positive. Step-wise Logistic regression analysis showed that bladder power (OR=0.814, 95%CI: 0.765-0.866, P < 0.001), BCI (OR=1.023, 95%CI: 1.008-1.038, P=0.003), and bladder work (OR=2.232, 95%CI: 1.191-4.184, P=0.012) were independent risk factors for urination intermittences in the BPH patients. CONCLUSION The presence of urination intermittences in the BPH patients was mainly influenced by bladder contractile functions, and was irrelevant to the degree of bladder outlet obstruction. The increase of frequency of urination intermittences seemed to be a sign of the decrease of the bladder contractile functions in the BPH patients.
Prostatic Hyperplasia/physiopathology* ; Humans ; Male ; Urodynamics ; Urination ; Retrospective Studies ; Middle Aged ; Aged ; Aged, 80 and over ; Urinary Bladder/physiopathology* ; Urination Disorders/etiology*

OBJECTIVE: To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern, substrate utilization, and mechanistic modulation. METHODS: In vivo, echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation. In vitro, a hypoxia-induced H9C2 model was established, mitochondrial damage was evaluated by flow cytometry, and nuclear translocation of hypoxia-inducible factor-1 α (HIF-1 α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions. RESULTS: QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1 α pathway, and improved cardiac function in HF rats. Specifically, QSG promoted HIF-1 α expression and entry into the nucleus at high levels of hypoxia (P<0.05), thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1 α at relatively low levels of hypoxia (P<0.05), promoting the increased lipid metabolism. CONCLUSIONS QSG regulates the protein stability of HIF-1 α, thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.
Animals ; Myocardial Infarction/physiopathology* ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Rats, Sprague-Dawley ; Glucose/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Energy Metabolism/drug effects* ; Rats ; Fatty Acids/metabolism* ; Myocardium/pathology*

OBJECTIVES: To explore the correlation of serum tryptophan level with 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: This retrospective study was conducted among 108 patients with HBV-ACLF, whose survival outcomes within 90 days after diagnosis were recorded. The correlation of baseline serum tryptophan levels measured by high-performance liquid chromatography with 90-day mortality of the patients was analyzed, and the predictive value of serum tryptophan for 90-day mortality was explored. RESULTS: Within 90 days after diagnosis, 53 (29.4%) of the patients died and 127 (70.6%) survived. The deceased patients had significantly lower baseline serum tryptophan levels than the survivors (7.31±3.73 pg/mL vs 13.32±7.15 pg/mL, P<0.001). Multivariate analysis suggested that serum tryptophan level was an independent factor correlated with mortality of HBV-ACLF after adjustment for confounding variables. The patients with serum tryptophan levels below the median level (10.14 pg/mL) at admission had significantly higher 90-day mortality risks than those with higher tryptophan levels (43.3% vs 15.6%, HR: 3.157, 95% CI: 1.713-5.817), and the complication by kidney dysfunction further increased the risk to 73.3% as compared with patients with higher serum tryptophan levels with normal kidney function (15.0%; HR: 7.558, 95% CI: 3.369-16.960). Serum tryptophan levels had an area under the receiver operating characteristic curve of 0.771 (95% CI: 0.699-0.844) for predicting 90-day mortality. CONCLUSIONS Serum tryptophan level is closely correlated with the survival outcomes of patients with HBV-ACLF, and a decreased tryptophan level indicates a high 90-day mortality risk, which can be further increased by the complication by kidney dysfunction.
Humans ; Tryptophan/blood* ; Retrospective Studies ; Acute-On-Chronic Liver Failure/virology* ; Male ; Female ; Middle Aged ; Adult ; Prognosis ; Hepatitis B/complications* ; Hepatitis B virus

OBJECTIVES: To investigate the impact of hepatitis B virus (HBV) infection on oral microbiota and metabolites in patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and the underlying mechanisms. METHODS: This prospective study was conducted in 47 MAFLD patients complicated with chronic hepatitis B (CHB) and 48 MAFLD patients without CHB enrolled from November, 2023 to January, 2024. Fasting tongue coating samples were collected from the patients for analyzing microbial community structures and metabolites using high-throughput 16S rDNA sequencing and non-targeted metabolomics techniques, and their associations with clinical indicators and biological pathways were explored using correlation analysis and functional annotation. RESULTS: The levels of fasting blood glucose, total cholesterol (TC), gamma-glutamyl transferase (GGT), and severity of fatty liver were all significantly lower in MAFLD+CHB group than in MAFLD group. Microbiota analysis showed that the abundances of Patescibacteria (at the phylum level), Hydrogenophaga, and Absconditabacteriales (at the genus level) were significantly increased, while the abundance of Megasphaera was decreased in MAFLD+CHB group. The differential microbiota were significantly correlated with TC, GGT and low-density lipoprotein (r=-0.68‒0.75). Metabolomics analysis revealed that 469 metabolites (including lipids and amino acids) were upregulated and 2306 (including organic oxygen-containing compounds and phenylpropanoids) were downregulated in MAFLD+CHB group, for which KEGG enrichment analysis suggested abnormal activation of the linoleic acid metabolism and glycerophospholipid metabolism pathways. Correlation analysis between microbiota and metabolites indicated that Patescibacteria and Megasphaera, which were positively correlated with lipid metabolites and negatively with fatty acid metabolites, respectively, jointly affected glycolipid metabolism and oxidative stress pathways. CONCLUSIONS Compared to patients with MAFLD alone, MAFLD patients with concurrent chronic HBV infection showed lower levels in some lipid metabolism indicators and the degree of hepatic steatosis, accompanied by alterations in oral microbiota structure and metabolic profiles. The precise mechanisms involved require further investigation to be fully elucidated.
Humans ; Lipid Metabolism ; Prospective Studies ; Microbiota ; Hepatitis B, Chronic/microbiology* ; Male ; Female ; Adult ; Fatty Liver/microbiology* ; Middle Aged ; Mouth/microbiology* ; Metabolomics