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.

BACKGROUND: Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China. METHODS: We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model. RESULTS: From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%). CONCLUSIONS CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.
Humans ; Heart Defects, Congenital/mortality* ; Male ; Female ; China/epidemiology* ; Infant ; Child, Preschool ; Adult ; Child ; Adolescent ; Infant, Newborn ; Middle Aged ; Young Adult ; Aged ; Rural Population

Objective:To investigate the effects of botulinum toxin type A (BTX-A) and magnesium sulfate on the survival rate of random-pattern skin flaps (RSF) with different length-to-width ratios.Methods:Using a random number table method, 45 SD rats were divided into three groups: the saline group (Group A), the BTX-A group (Group B), and the magnesium sulfate group (Group C), with 15 rats in each group. Each group was further subdivided into three subgroups based on different length-to-width ratios of RSF (1∶1, 2∶1, 3∶1), with 5 rats in each subgroup. The preparation of the RSF involved using the midline of the rat’s back as the axis and the level 1 cm below the iliac crest line as the base, extending towards the head. The skin tissue was incised to the dorsal fascia layer, separating the subcutaneous tissue at the superficial layer of the deep fascia, while severing the blood vessels and their branches on both sides and at the base. After hemostasis, the flap was sutured in place. Immediately after surgery, 0.2 ml of saline, BTX-A (25 U/ml), or magnesium sulfate solution (50 mg/ml) was injected into the proximal, middle, and distal ends of the flap. On the seventh day post-surgery, the gross appearance of the flap was assessed, and the survival rate was calculated. The surviving flap tissue underwent hematoxylin and eosin (HE) staining to evaluate microvascular density (MVD) and the degree of vasodilation (including vessel outer diameter, inner diameter, and wall thickness). Immunohistochemistry was used to detect the expression level of vascular endothelial growth factor (VEGF). Statistical analysis was performed using GraphPad Prism 9.0.1 software, with data expressed as Mean ± SD. One-way ANOVA was used for multiple group comparisons, and Tukey’s test was used for pairwise comparisons.Results:On the seventh day post-surgery, flaps with a length-to-width ratio of 1∶1 healed well in all subgroups. In the case of flaps with a 2∶1 ratio, Group A exhibited partial necrosis at the distal end, characterized by blackened, non-elastic scabs and exudate. Groups B and C generally healed well. For flaps with a 3∶1 ratio, Group A exhibited extensive necrosis at both the middle and distal ends, with similar blackened, non-elastic scabs, non-bleeding cut sections, and exudate. Groups B and C showed only partial blackening at the distal end, with most areas healing effectively. The survival rates of flaps with a 1∶1 ratio did not show significant differences among the three groups ( P>0.05). Compared to Group A, Groups B and C had significantly higher survival rates for flaps with 2∶1 and 3∶1 ratios ( P<0.01), with no significant difference between Groups B and C ( P>0.05). HE staining indicated that as the length-to-width ratios increased, tissue edema and inflammatory cell infiltration also increased in all groups. Groups B and C had significantly reduced inflammatory changes compared to Group A, with a greater number of newly formed microvessels observed. Quantitative analysis revealed that MVD in Groups B and C was significantly higher than in Group A, regardless of the flap ratio ( P<0.05), with no significant difference between Groups B and C ( P>0.05). Vasodilation analysis showed that the outer diameter and wall thickness of vessels in Groups B and C were significantly greater than those in Group A ( P<0.05), with no significant difference between Groups B and C ( P>0.05). Immunohistochemical staining revealed that VEGF expression levels in Groups B and C were higher than in Group A, regardless of the flap ratio ( P<0.01). In flaps with a 1∶1 ratio, VEGF expression was higher in Group C than in Group B ( P<0.05), with no significant difference between the two groups for other flap ratios ( P>0.05). Conclusion:In RSF with length-to-width ratios of 2∶1 and 3∶1, subcutaneous injections of BTX-A or magnesium sulfate after replantation can promote the expansion and formation of blood vessels in the flap, increase the expression of VEGF, and improve the survival rate of the RSF.

Objective:To investigate the effects of botulinum toxin type A (BTX-A) and magnesium sulfate on the survival rate of random-pattern skin flaps (RSF) with different length-to-width ratios.Methods:Using a random number table method, 45 SD rats were divided into three groups: the saline group (Group A), the BTX-A group (Group B), and the magnesium sulfate group (Group C), with 15 rats in each group. Each group was further subdivided into three subgroups based on different length-to-width ratios of RSF (1∶1, 2∶1, 3∶1), with 5 rats in each subgroup. The preparation of the RSF involved using the midline of the rat’s back as the axis and the level 1 cm below the iliac crest line as the base, extending towards the head. The skin tissue was incised to the dorsal fascia layer, separating the subcutaneous tissue at the superficial layer of the deep fascia, while severing the blood vessels and their branches on both sides and at the base. After hemostasis, the flap was sutured in place. Immediately after surgery, 0.2 ml of saline, BTX-A (25 U/ml), or magnesium sulfate solution (50 mg/ml) was injected into the proximal, middle, and distal ends of the flap. On the seventh day post-surgery, the gross appearance of the flap was assessed, and the survival rate was calculated. The surviving flap tissue underwent hematoxylin and eosin (HE) staining to evaluate microvascular density (MVD) and the degree of vasodilation (including vessel outer diameter, inner diameter, and wall thickness). Immunohistochemistry was used to detect the expression level of vascular endothelial growth factor (VEGF). Statistical analysis was performed using GraphPad Prism 9.0.1 software, with data expressed as Mean ± SD. One-way ANOVA was used for multiple group comparisons, and Tukey’s test was used for pairwise comparisons.Results:On the seventh day post-surgery, flaps with a length-to-width ratio of 1∶1 healed well in all subgroups. In the case of flaps with a 2∶1 ratio, Group A exhibited partial necrosis at the distal end, characterized by blackened, non-elastic scabs and exudate. Groups B and C generally healed well. For flaps with a 3∶1 ratio, Group A exhibited extensive necrosis at both the middle and distal ends, with similar blackened, non-elastic scabs, non-bleeding cut sections, and exudate. Groups B and C showed only partial blackening at the distal end, with most areas healing effectively. The survival rates of flaps with a 1∶1 ratio did not show significant differences among the three groups ( P>0.05). Compared to Group A, Groups B and C had significantly higher survival rates for flaps with 2∶1 and 3∶1 ratios ( P<0.01), with no significant difference between Groups B and C ( P>0.05). HE staining indicated that as the length-to-width ratios increased, tissue edema and inflammatory cell infiltration also increased in all groups. Groups B and C had significantly reduced inflammatory changes compared to Group A, with a greater number of newly formed microvessels observed. Quantitative analysis revealed that MVD in Groups B and C was significantly higher than in Group A, regardless of the flap ratio ( P<0.05), with no significant difference between Groups B and C ( P>0.05). Vasodilation analysis showed that the outer diameter and wall thickness of vessels in Groups B and C were significantly greater than those in Group A ( P<0.05), with no significant difference between Groups B and C ( P>0.05). Immunohistochemical staining revealed that VEGF expression levels in Groups B and C were higher than in Group A, regardless of the flap ratio ( P<0.01). In flaps with a 1∶1 ratio, VEGF expression was higher in Group C than in Group B ( P<0.05), with no significant difference between the two groups for other flap ratios ( P>0.05). Conclusion:In RSF with length-to-width ratios of 2∶1 and 3∶1, subcutaneous injections of BTX-A or magnesium sulfate after replantation can promote the expansion and formation of blood vessels in the flap, increase the expression of VEGF, and improve the survival rate of the RSF.

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)