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 analyze the mechanism of action of seaweed-kunbu in the treatment of breast cancer through network pharmacology. Methods The active ingredients and their targets of seaweed-kunbu were retrieved through the TCMSP database. Relevant targets for breast cancer were obtained through the GeneCards and OMIM databases, and "drug-disease target" network diagram was constructed using Cytoscape software. Protein-protein interaction (PPI) network analysis was performed using the String platform. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using R language. Molecular docking technology was used to verify the binding ability of key compounds to targets, and functional verification was carried out through in vitro experiments. Results A total of 11 effective compounds were obtained from seaweed-kunbu in this study, among which 10 were related to breast cancer. There were 150 highly relevant intersecting targets between seaweed-kunbu and breast cancer, and 10 core genes including Serine/threonine kinase 1 (AKT1), p53 tumor protein (TP53), tumor necrosis factor (TNF), interleukin6 (IL6), vascular endothelial growth factor A (VEGFA), JUN, caspase 3 (CASP3), interleukin1B (IL1B), MYC and human epidermal growth factor receptor (EGFR) were screened out. GO analysis indicated that these compounds may be involved in biological processes such as signal transduction, apoptosis, cell proliferation, and inflammatory response. KEGG pathway analysis showed that the main enriched signaling pathways were PI3K/Akt, MAPK and TNF. Molecular docking and in vitro experimental results demonstrated that fucosterol, the main chemical component of seaweed-kunbu, had an antiproliferative effect on triple-negative breast cancer BT-549 cells. Conclusion Seaweed-kunbu may treat breast cancer through multiple targets and pathways, and its main chemical component fucosterol can effectively inhibit the proliferation activity of BT-549 cells.

Forty trainees who underwent position-transition training for general practitioner in the Affiliated Huai′an First People′s Hospital of Nanjing Medical University from August 2021 to July 2022 were randomly divided into the control group and the trial group with 20 in each group. The traditional teaching methods were applied in control group and the problem-based learning/case-based learning (PBL/CBL) combined scenario simulation teaching method were applied in trial group. The effect of the two teaching methods was evaluated by the examination results and the teaching satisfaction was assessed by the questionnaire survey. The exam scores of general practice thinking, comprehensiveness of inquiry content, integrity of preliminary diagnosis, comprehensiveness of preliminary treatment, ability to deal with critical and severe cases, ability of chronic disease management and concept of holistic care in trial group were significantly higher than those in control group( t=-15.79,-15.74,-16.67,-13.66,-18.57,-18.55,-19.74,all P<0.05). The satisfaction of trainees in the trial group was also significantly higher than that in the control group in terms of teaching methods, stimulating learning interest; and improvement of independent learning ability, general practice clinical thinking, doctor-patient communication ability, teamwork ability and community problem-solving ability( χ2=12.10,10.03,12.22,10.03,8.18,10.03,8.18,all P<0.05). The study shows that PBL/CBL combined scenario simulation teaching method can improve the learning effect and satisfaction of the trainees in position-transition training for general practitioner.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*

Clostridia inhabiting in jiupei and pit mud plays key roles in the formation of flavour during the fermentation process of Luzhou-flavour baijiu. However, the differences of Clostridial communities between jiupei and pit mud remains unclear. Here, the species assembly, succession, and metabolic capacity of Clostridial communities between jiupei and pit mud were analysed by high-throughput sequencing and pure culture approaches. The ratio of Clostridial biomass to bacterial biomass in the pit mud was relatively stable (71.5%-91.2%) throughout the fermentation process. However, it varied widely in jiupei (0.9%-36.5%). The dominant Clostridial bacteria in jiupei were Clostridium (19.9%), Sedimentibacter (8.8%), and Hydrogenispora (7.2%), while Hydrogenispora (57.2%), Sedimentibacter (5.4%), and Caproiciproducens (4.9%) dominated in the Clostridial communities in pit mud. The structures of Clostridial community in pit mud and jiupei were significantly different (P=0.001) throughout fermentation. Isolated Clostridial strains showed different metabolic capacities of volatile fatty acids in pure culture. Spatial and temporal heterogeneity of Clostridial communities existed in the baijiu fermentation pit, which was closely related to the main flavour components of Luzhou-flavour baijiu.
Alcoholic Beverages ; microbiology ; Bacteria ; classification ; metabolism ; Clostridium ; physiology ; Fatty Acids, Volatile ; metabolism ; Fermentation ; Food Microbiology

Multi-species solid-state fermentation in a mud pit is one of the typical features of strong-flavor baijiu, in which archaea plays important roles, however, the archaeal community distribution and diversity during fermentation are still lack of research. The biomass, composition and succession of archaea communities in fermented grains and pit mud were analyzed by high throughput sequencing. The potential interaction between archaea and bacteria was analyzed by co-occurrence network. Results demonstrate that the average biomass of archaea in pit mud was about 200 times higher than that of fermented grains. There was no significant difference in archaeal community structure between fermented grains and pit mud (r=0.017, P=0.074), but succession patterns between them showed significant correlation (r=0.30, P=0.03). Methanobacterium was the most abundant archaea in fermented grains and pit mud, and other dominant groups included Methanosarcina, Methanocorpusculum, Methanoculleus, and Methanobrevibacter. The co-occurrence network analysis showed that Methanobacterium was positively correlated with most bacteria in fermented grains and pit mud, especially with Hydrogenispora and Caproiciproducens, the dominant bacteria in pit mud. Our results revealed the temporal and spatial distribution characteristics and potential functions of the archaeal community in the mud pit of strong-flavor baijiu.
Alcoholic Beverages/analysis* ; Archaea/genetics* ; Bacteria ; Fermentation ; Taste

Hepatorenal syndrome (HRS) is a common complication of decompensated cirrhosis and is traditionally defined as progressive oliguria or anuria, azotemia, dilutional hyponatremia, and hyponatremia, while renal insufficiency without marked organic lesions in the kidney is the typical manifestation of HRS. Recent studies have found that besides the abnormalities in hemodynamics, inflammatory response, oxidative stress, and direct renal tubular toxicity of bile salts are jointly involved in the development and progression of HRS. HRS is not the only renal complication in patients with liver cirrhosis, and it is only a functional form of acute kidney injury (AKI). HRS meeting the criteria for AKI is called HRS-AKI, which is formerly known as HRS-Ⅰ type. For cirrhotic patients with acute kidney disease or chronic kidney disease, if they meet the criteria for HRS, they can be diagnosed with HRS-NAKI, which is formerly known as HRS-Ⅱ type. The most common risk factors for HRS are infection, digestive bleeding, and large-volume paracentesis without transfusion of human serum albumin for volume expansion.

Objective To evaluate the association between preoperative serum thyroglobulin concentration and aggressive behavior of papillary thyroid cancer(PTC).Methods A total of 334 PTC patients diagnosed by surgical pathology treated in our hospital from Jan.2013 to Dec.2017 were retrospectively reviewed.Patients were divided into two groups according to Tg levels and clinicopathological characteristics between the two groups were compared.Binary logistic regression analysis was conducted to evaluate the factors influencing extrathyroidal extension and lymph node metastasis of PTC.Results High level of preoperative serum Tg was signifcantly associated with old age,multifocality,larger maximum tumor size,more frequent extrathyroidal extension,lymph node metastasis,and advanced T and TNM stage(P＜0.05).Maximum tumor diameter ＞2 cm(P=0.031) and preoperative serum Tg level ＞17.21 ng/ml(P=0.028) were independent risk factors for extrathyroidal extension.Maximum tumor diameter ＞2 cm(P=0.007) and preoperative serum Tg levels ＞25.40 ng/ml (P=0.016) were independent risk factors for lymph node metastasis,whereas female was a significant protective predictive factor(P＜0.001).Conclusion Preoperative serum Tg levels may serve as an independent risk marker for extrathyroidal extension and lymph node metastasis of PTC,and partly contributes to predict aggressive behavior of PTC.