OBJECTIVES: To analyze the differentially expressed exosomal miRNAs in patients with chronic heart failure (CHF) complicated by hyperuricemia (HUA) and explore their potential as novel diagnostic molecular markers and their target genes. METHODS: This study was conducted among 30 CHF patients with HUA (observation group) and 30 healthy volunteers (control group) enrolled between September, 2020 and September, 2023. Peripheral blood samples were collected from 6 CHF patients with HUA for analyzing exosomal miRNAs by high-throughput sequencing, and the results were validated in the remaining 24 patients using qRT-PCR. GO and KEGG enrichment analyses were performed to predict the the target genes of the identified differential miRNAs. We also validated the differentially expressed miRNAs by animal experiment. RESULTS: A total of 42 differentially expressed exosomal miRNAs were detected in observation group by high-throughput sequencing; among them, miR-27a-5p was significantly upregulated (P=0.000179), and miR-139-3p was significantly downregulated (P=0.000058). In the 24 patients with both CHF and PUA, qRT-PCR validated significant upregulation of miR-27a-5p (P=0.004) and downregulation of miR-139-3p (P=0.005) in serum exosomes. When combined, miR-27a-5p and miR-139-3p had a maximum area under the curve (AUC) of 0.899 (95% CI: 0812-0.987) for predicting CHF complicated by HUA. GO and KEGG enrichment analyses suggested that the differential expressions of miR-27a-5p and miR-139-3p was associated with the activation of the AMPK-mTOR signaling pathway to activate the autophagic response. We obtained the same conclusion from animal experiment. CONCLUSIONS Upregulated exosomal miR-27a-5p combined with downregulated exosomal miR-139-3p expression can serve as a novel molecular marker for diagnosis of CHF complicated by HUA, and their differential expression may promote autophagy in cardiomyocytes by activating the AMPK-mTOR signaling pathway.
Humans ; Hyperuricemia/diagnosis* ; Heart Failure/genetics* ; MicroRNAs/metabolism* ; Exosomes/metabolism* ; Chronic Disease ; Male ; Female ; Middle Aged ; Animals

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 evaluate whether 6-gingerol(6G)can inhibit fibrosis and improve the cardiac and renal function and in rats with cardiorenal syndrome.Methods In the in vitro experiments of this study,the incorporation of isotope-labeled amino acids was used to detect the intervention of 6-gingerol on normal rat kidney-49F(NRK-49F)and normal rat kidney-52E(NRK-52E)cells.68 male SD rats weighing 200～250 g were used to establish a rat model of cardiorenal syndrome by ligating the left anterior descending coronary artery and performing 5/6 nephrectomy.The rats were randomly divided into a control group,a model group,a low dose 6-gingerol group(6 mg/kg),a high dose 6-gingerol group(30 mg/kg),and a losartan potassium group(20 mg/kg).The 6-gingerol group received intraperitoneal injection of 6-gingerol,while the control group and model group received intraperito-neal injection of an equal amount of physiological saline.The losartan group received oral administration of losartan potassium for a total of 6 weeks.After successful modeling,blood samples were taken for biochemical and cardiac ultrasound examinations.After the experiment,blood,heart,and kidney samples were taken for Masson,immuno-histochemistry,and Western blot.Results 6-gingerol 20 μmol/L can reduce NRK-49F collagen synthesis and inhibit NRK-52E protein synthesis.Biochemical results showed that the serum creatinine,urea nitrogen,and brain natriuretic peptide(BNP)levels of rats in the low and high dose 6-gingerol groups and the losartan group were all reduced,with high dose 6-gingerol groups and losartan group showing the most significant decrease(P<0.05).Echocardiographic parameters showed that the 6-gingerol group and losartan potassium group improved cardiac contractile function and ventricular remodeling in rats(P<0.05).Masson staining and Western Blot showed renal collagen deposition,with reduced expression of collagen I and α-SMA(P<0.05).Immunofluorescence showed a decrease in the expression of renal collagen deposition I,α-SMA,and TGF-β1(P<0.05).Conclusion 6-Gin-gerol may improve the cardiac and renal function and renal fibrosis in rats with cardiorenal syndrome.

Objective To evaluate whether 6-gingerol(6G)can inhibit fibrosis and improve the cardiac and renal function and in rats with cardiorenal syndrome.Methods In the in vitro experiments of this study,the incorporation of isotope-labeled amino acids was used to detect the intervention of 6-gingerol on normal rat kidney-49F(NRK-49F)and normal rat kidney-52E(NRK-52E)cells.68 male SD rats weighing 200～250 g were used to establish a rat model of cardiorenal syndrome by ligating the left anterior descending coronary artery and performing 5/6 nephrectomy.The rats were randomly divided into a control group,a model group,a low dose 6-gingerol group(6 mg/kg),a high dose 6-gingerol group(30 mg/kg),and a losartan potassium group(20 mg/kg).The 6-gingerol group received intraperitoneal injection of 6-gingerol,while the control group and model group received intraperito-neal injection of an equal amount of physiological saline.The losartan group received oral administration of losartan potassium for a total of 6 weeks.After successful modeling,blood samples were taken for biochemical and cardiac ultrasound examinations.After the experiment,blood,heart,and kidney samples were taken for Masson,immuno-histochemistry,and Western blot.Results 6-gingerol 20 μmol/L can reduce NRK-49F collagen synthesis and inhibit NRK-52E protein synthesis.Biochemical results showed that the serum creatinine,urea nitrogen,and brain natriuretic peptide(BNP)levels of rats in the low and high dose 6-gingerol groups and the losartan group were all reduced,with high dose 6-gingerol groups and losartan group showing the most significant decrease(P<0.05).Echocardiographic parameters showed that the 6-gingerol group and losartan potassium group improved cardiac contractile function and ventricular remodeling in rats(P<0.05).Masson staining and Western Blot showed renal collagen deposition,with reduced expression of collagen I and α-SMA(P<0.05).Immunofluorescence showed a decrease in the expression of renal collagen deposition I,α-SMA,and TGF-β1(P<0.05).Conclusion 6-Gin-gerol may improve the cardiac and renal function and renal fibrosis in rats with cardiorenal syndrome.

Objective:To clarify the transitional components in the blood of compound Banlangen Granules; To explore the mechanism of drugs in the treatment of epidemic encephalitis B, hepatitis and parotitis.Methods:The transitional components in blood of compound Banlangen Granules were analyzed by ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS). The regulatory targets and pathways of compound Banlangen Granules in the treatment of epidemic encephalitis B, hepatitis and parotitis were analyzed based on UPLC-MS/MS and network pharmacology.Results:A total of 9 blood components were identified, of which 8 were prototype components, including sucrose, o-aminobenzoic acid, uridine, adenosine, guanosine, indole-3-acetonitrile-2 murine-S-β-D-glucopyranoside and salicylic acid. Through network pharmacological analysis, it was concluded that compound Banlangen Granules may treat epidemic encephalitis B, hepatitis and parotitis by regulating lipid and atherosclerosis, insulin resistance, IL-17 and other signal pathways.Conclusion:The 9 blood components of compound Banlangen Granules may treat epidemic encephalitis B, hepatitis and parotitis by regulating lipid and atherosclerosis, insulin resistance, IL-17 and other signal pathways.

Nucleos(t)ide analogues (NAs), which are widely used as the first-line anti-hepatitis B virus (HBV) drugs in clinical practice, can effectively inhibit the replication of HBV DNA, significantly slow down disease progression in chronic hepatitis B (CHB) patients, and reduce the development of end-stage liver diseases such as liver failure and liver cancer. However, for some CHB patients receiving first-line NAs for 48 weeks or longer, serum HBV DNA is still persistently or intermittently higher than the lower detection of limit of sensitive nucleic acid detection reagents. After discussion by the authors, low-level viremia (LLV) is defined as follows: persistent LLV refers to the condition in which CHB patients, who receive entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate for ≥48 weeks, test positive for HBV DNA by two consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml; intermittent LLV refers to the condition in which patients test positive for HBV DNA intermittently by at least three consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml. For the diagnosis of LLV, the issues of poor compliance and drug-resistant mutations should be excluded. LLV might be associated with the increased risk of progression to liver fibrosis or hepatocellular carcinoma in patients with liver cirrhosis under NA treatment, but there are still controversies over whether the original treatment regimen with NAs should be changed after the onset of LLV. This article summarizes the incidence rate of LLV under NA treatment and the influence of LLV on prognosis and analyzes the possible mechanisms of the osnet of LLV, so as to provide a reference for the management of LLV in patients treated with NAs.

Objective:To Investigate the correlation of eosinophil count and stroke-associated pneumonia (SAP) in patients with acute ischemic stroke.Methods:Patients with acute ischemic stroke within 24 h after onset admitted to the Department of Encephalopathy, Suzhou Integrated Traditional Chinese and Western Medicine Hospital from August 2016 to September 2018 were enrolled prospectively. Their general clinical data and eosinophil counts were collected. National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of stroke. Multivariate logistic regression analysis was used to determine the independent risk factors for SAP. Results:A total of 521 patients were enrolled, including 106 (20.35%) SAP. Univariate logistic analysis showed that SAP was associated with the classification of eosinophil count (odds ratio [ OR] 0.37, 95% confidence interval [ CI] 0.20-0.68; P=0.001), and tended to be associated with eosinophil count ( OR 0.08, 95% CI 0.01-1.01; P=0.051). Multivariate logistic regression analysis showed that both eosinophil count and eosinophil count classification were not the independent risk factors for SAP, and advanced age ( OR 1.077, 95% CI 1.045-1.109; P< 0.001), chronic obstructive pulmonary disease ( OR 6.931, 95% CI 1.295-37.106; P=0.024) and high baseline NIHSS score ( OR 1.148, 95% CI 1.003-1.314; P=0.045) were significantly independently associated with SAP. Conclusions:Eosinophil count was not an independent predictor of SAP in patients with acute ischemic stroke.

Objective To study the diagnostic value of endoscopic ultrasonography (EUS) in patients with cholangiopancreatic duct dilatation (CPDD).Methods Forty-five patients with CPDD and without any visual or detected obstructive lesions after traditional uhrasonography (US) were re-examined by EUS,CT and MRI.The diagnostic rates of EUS and the other imaging technologies were compared.Results All the 45 patients underwent successful EUS examination.Among them,there were 18 patients with periampullary tumor,10 patients with lower common bile duct stones,1 patient with pancreatic duct stones,3 patients with chronic pancreatitis,1 patient with an intrapancreatic choledochal cyst,4 patients with inflammatory strictures of papilla of duodenum and 2 patients with terminal bile duct inflammatory stenosis.However,1 patient with a lower common bile duct tumor,1 patient with a small pancreatic head carcinoma and 1 patient with sphincter of Oddi dysfunction (SOD) were not diagnosed.The diagnostic rates of obstructive lesions by US,EUS,CT and MRI were 7.1％,92.9％,33.3％,31.0％,respectively.The diagnostic rates of tumor were 10.0％,90.0％,35.0％,25.0％,respectively.As compared with the other examination methods,EUS was best in detecting small carcinoma.Conclusion EUS plays an important role in the diagnosis of lesions causing cholangiopancreatic duct dilatation.