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.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

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.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

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.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
Humans ; Immunoconjugates/adverse effects* ; Neoplasms/immunology* ; Animals ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use*

Skeletal muscle wasting refers to a loss of skeletal muscle mass and function.Mitochondrial quality control(MQC)is the basis by which normal physiological mitochondrial function is maintained and mainly involves the regulation of mitochondrial biogenesis,mitochondrial dynamics(fission/fusion),and mitophagy.MQC maintains muscle homeostasis by regulating the relative stability of mitochondrial shape,quantity,and quality.As an economical and effective treatment for muscular atrophy,exercise interventions are widely used,but the relationship between exercise intervention and MQC is not clear.This paper discusses the role of mitochondrial biogenesis,mitochondrial dynamics,and mitophagy in skeletal muscle atrophy and related molecular targets.We thoroughly analyze the mechanisms by which MQC-mediated exercise can improve the skeletal muscle atrophy caused by aging,disuse,and cancer cachexia in order to provide theoretical guidance for intervention.

Objective:To construct the clinical management model of a new type of smoke-purifying temperature-controlled moxibustion device based on the whole life cycle theory,and to explore its management effect on the new type of smoke-purifying temperature-controlled moxibustion device.Methods:The clinical management model of a new type of smoke purification and temperature-controlled moxibustion device was constructed based on the whole life cycle theory with the architecture of the basic layer,access layer,service layer,data layer and application layer.Eighteen new type of smoke purification and temperature-controlled moxibustion devices in clinical use in the Shijiazhuang Pingan Hospital from 2021 to 2022 were selected,and the conventional new smoke-purifying temperature-controlled moxibustion device management scheme(referred to as the conventional management mode)and the new smoke purification and temperature-controlled whole life cycle management model(referred to as the whole life cycle management mode)were adopted respectively according to different management modes.The management effect of the new smoke-purifying temperature-controlled moxibustion therapy device and the satisfaction of the relevant management personnel were compared between the two management modes.Results:The average scores of the management quality,temperature control effect,smoke control effect and moxa smoke purification effect of the new smoke purification moxibustion device using the whole life cycle management mode were(89.37±3.48)points,(93.53±4.26)points,(0.13±0.04)points and(0.11±0.03)points,respectively,the average scores of management quality and temperature control effect were higher those of the conventional management mode,and the average scores of smoke control effect and moxa smoke purification effect were lower than those of the conventional management mode,the difference was statistically significant(t=11.744,14.850,11.266,24.593,P<0.05).The satisfaction scores of engineers,medical staff and patients in the use of the new smoke purification and temperature control moxibustion therapy device adopting the whole life cycle management model were(95.69±6.62)points,(96.82±5.87)points and(95.34±5.14)points,respectively,which were higher than those of conventional management mode,the difference was statistically significant(t=9.334,19.549,33.694,P<0.05).Conclusion:The application of the clinical management model of a new type of smoke-purifying temperature-controlled moxibustion device based on the whole life cycle theory to new type of smoke purification and temperature control moxibustion therapy device can effectively improve the quality of equipment management,improve the temperature control effect of the new smoke and temperature control moxibustion device,and improve the satisfaction of relevant users.

Objective To discuss the clinical value of echocardiographic indicators in assessing the short-term efficacy of transcatheter aortic valve replacement(TAVR)and surgical aortic valve replacement(SAVR)in treating patients with severe aortic valve stenosis(AS).Methods The clinical data of 70 patients with severe AS,who received treatment at the Daping Hospital of Army Military Medical University of China between June 2019 and September 2022 were retrospectively analyzed.The patients were divided into SAVR group(n=40)and TAVR group(n=30).The preoperative one-week and postoperative one-month echocardiographic indicators were compared between the two groups.Results In both groups,the postoperative one-month peak aortic valve velocity(Vmax),aortic valve mean transvalvular pressure gradient(mPG),relative thickness of chamber wall(RWT),and left ventricular mass index(LVMI)were decreased when compared with preoperative values(all P＜0.05);in TAVR group the left ventricular ejection fraction(LVEF),LVMI and incidence of perivalvular leakage were remarkably higher than those in SAVR group,while the Vmax and mPG were obviously lower than those in SAVR group(all P＜0.05).In TAVR group,the mitral regurgitation decreased from preoperative 12 patients(40％)to postoperative 2 patients(6.7％)and the over-moderate tricuspid regurgitation decreased from preoperative 7 patients(23.3％)to postoperative one patient(3.3％)(all P＜0.05).In SAVR group,the mitral regurgitation decreased from preoperative 15 patients(37.5％)to postoperative 2 patients(5.0％)and the over-moderate tricuspid regurgitation decreased from preoperative 9 patients(22.5％)to postoperative one patient(2.5％)(all P＜0.05).The pulmonary artery hypertension in TAVR group decreased from preoperative 17 patients(56.7％)to postoperative 4 patients(13.3％),which in SAVR group decreased from preoperative 22 patients(55.0％)to postoperative 5 patients(12.5％)(P＜0.05),but the differences in the above indexes between the two groups were not statistically significant(all P＞0.05).Conclusion TAVR and SAVR have similar efficacy in improving secondary valve regurgitation and pulmonary artery hypertension caused by severe AS.TAVR is superior to SAVR in improving postoperative ventricular reverse remodeling and hemodynamics,although the incidence of paravalvular leakage in TAVR is higher than that in SAVR.(J Intervent Radiol,2024,33:479-482)