Objective To construct glucose oxidase（GOx）–loaded nanogels （GONGs）, optimize their formulation, and evaluate their capacity to inhibit the Warburg effect in glioma cells. Methods A responsive polymer （HAM） was synthesized and used to self-assemble GONGs, which were then characterized. Encapsulation efficiency and drug loading were determined using fluorescence spectrophotometry. Biocompatibility was tested by measuring cytotoxicity and hemolytic activity. Western blotting was used to evaluate the effects of GONGs on the expression of proteins associated with the Warburg phenotype and oxidative damage in glioma cells. Results GONGs prepared at a drug–to–polymer ratio of 1∶10 exhibited a particle size of 140.3 nm and a zeta potential of −27.2 mV. Compared with free GOx, GONGs markedly reduced cytotoxicity, increased the IC₅₀ in hUVEC cells from 2.150 nmol/L to 74.86 nmol/L, and significantly decreased hemolysis. At a GOx concentration of 2 nmol/L, GONGs effectively downregulated glycolysis-related proteins, such as HK2 and LDHA, and inhibited glutamine metabolism in glioma cells. Conclusion GONGs exhibited high GOx loading capacity, significantly reduced GOx-induced cytotoxicity, inhibited the Warburg effect in glioma cells and induced oxidative damage.

Hepatic fibrosis is a reversible pathological process in various chronic liver diseases and is closely associated with the development and progression of severe liver diseases such as liver cirrhosis and hepatocellular carcinoma， and it has emerged as a significant global health challenge. In recent years， studies have shown that histone lactylation， a newly discovered epigenetic modification， actively participates in regulating the progression of hepatic fibrosis. This article systematically reviews the core regulatory effect of histone lactylation modification in the interaction between inflammatory microenvironment and hepatic fibrosis， in order to clarify the cascade regulatory mechanism of “inflammation-hepatic fibrosis” and provide new insights for early diagnosis， targeted intervention， and prevention of malignant transformation in hepatic fibrosis.

Liver fibrosis is a critical pathological process in the progression of chronic liver diseases and is mainly driven by the activation of hepatic stellate cells， and it is characterized by excessive deposition of extracellular matrix. Programmed cell death is widely observed in liver fibrosis and plays diverse roles in different types of cells. It is not only a mechanism for maintaining cellular homeostasis through metabolism， but it can also regulate the development and progression of diseases. Ferroptosis has recently emerged as a research focus due to its close association with lipid metabolism. This article systematically reviews the related concepts of lipid metabolism， ferroptosis， and liver fibrosis， analyzes the bridging role and dual regulatory function of ferroptosis in lipid metabolism and liver fibrosis， and further highlights the clinical application value of targeting ferroptosis in hepatic stellate cells for the treatment of liver fibrosis， in order to provide new perspectives for the mechanistic studies on liver fibrosis and the optimization of related clinical intervention strategies.

With the acceleration of societal aging, heart failure in the elderly—characterized by a complex metabolic imbalance—has emerged as a pivotal challenge in public health.This condition severely compromises the physical well-being and quality of life among senior populations, primarily due to a pronounced imbalance between cardiac energy supply and demand.Among the various interventions studied, photosynthesis in plants, the principal energy source for aerobic organisms, presents a novel avenue for exploration.By effectively converting solar energy into chemical energy, photosynthesis sustains plant life.Introducing its principles into heart failure treatment could potentially optimize metabolism for elderly patients while significantly reducing oxidative stress and inflammation.Further investigations suggest that the antioxidants and bioactive byproducts generated during photosynthesis may play critical roles in heart failure treatments, particularly in modulating inflammatory pathways.In summary, emulating the mechanisms of photosynthesis could represent a promising strategy for treating heart failure in the elderly.This review aims to delve deeply into the application of photosynthesis in heart failure treatments for older adults and its underlying mechanisms, with the hope of providing insights and guidance for future endeavors in geriatric medicine.

Objective:To construct the rpoN gene knockout strain (Δ rpoN) and the complemented strain (CΔ rpoN) of Vibrio vulnificus ( V. vulnificus), and investigate the role of the rpoN gene in regulating bacterial motility and biofilm formation. Methods:The Δ rpoN strain of V. vulnificus was constructed using homologous recombination. Bacterial motility was assessed via swimming assays, and flagellar morphology was observed by transmission electron microscopy. Biofilm formation capacity was evaluated using crystal violet and Congo red staining assays, as well as colony morphology analysis. Real-time quantitative RT-PCR (qRT-PCR) was used to detect mRNA levels of target genes associated with flagellar synthesis and biofilm formation in Δ rpoN and the wild-type strains. Results:The V. vulnificus genome harbored a single rpoN gene, encoding a protein with high amino acid sequence similarity to RpoN homologs in other bacterial species. The Δ rpoN strain was successfully constructed. Compared with the wild-type strain, the Δ rpoN strain exhibited complete loss of motility on soft agar plates, absence of flagellar, and downregulated mRNA levels of flagellar synthesis-related genes. Conclusions:In V. vulnificus, RpoN regulates flagellar assembly by modulating the expression of flagellar synthesis genes, thereby controlling bacterial motility and biofilm formation.

Background:Liver cirrhosis is characterized by chronic inflammation,progressive fibrosis,and eventual liver dysfunction,and poses a major global health challenge.Aims:To assess the global burden of liver cirrhosis and its risk factors from 1990 to 2021.Methods:Using data extracted from the Global Burden of Diseases,Injuries,and Risk Factors Study(GBD)2021,the incidence,mortality,disability-adjusted life years(DALYs),and their age-standardized rates of liver cirrhosis were analyzed.Furthermore,a stratified analysis was conducted by sex,age,region,and etiology,with projections of the trends in the next 15 years.Results:Compared to 1990,the global incidence number of liver cirrhosis in 2021 was increased by 58.2%,the death number and DALYs rose by 39.5%and 27.9%,respectively.While the global age-standardized incidence rate(ASIR)showed a slight increase,the age-standardized death rate(ASDR)and DALY rate continued to decline.Both ASIR and ASDR exhibited negative correlations with the sociodemographic index(SDI).All age-standardized rates were higher in males than in females.Since 1990,the incidence rate increased in younger populations,while the mortality and DALY rates declined in most age groups.Non-alcoholic fatty liver disease(NAFLD)emerged as the leading cause of incidence,whereas chronic hepatitis B and C remained the primary contributors to deaths and DALYs.The incidence of NAFLD was prominent in high and high-middle SDI regions,while chronic hepatitis B was concentrated in low SDI regions.Projections to 2036 indicated a continuing rise in ASIR,and declines in ASDR and DALY rate.The incidence of chronic hepatitis B was projected to decrease markedly,whereas that of NAFLD was expected to continue increasing.Conclusions:Between 1990 and 2021,the global incidence of liver cirrhosis showed a modest increase;in contrast,both mortality and DALY rates demonstrated a steady decline.Burden of liver cirrhosis poses notable regional disparities.NAFLD dominates incidence in high-income regions,while viral hepatitis remains predominant in low-income areas,highlighting the need for region-specific prevention strategies.

Objective:To evaluate the safety,efficacy,and prognosis of interventional treatment for pregnan-cy-related uterine arteriovenous malformations(UAVM).Methods:A retrospective analysis was conducted of the clinical data from 8 patients with pregnancy-associated UAVM who underwent interventional therapy after initial di-agnosis by ultrasound at Peking Union Medical College Hospital between February 1,2016,and January 4,2024.Results:All 8 patients underwent ultrasound examination,and color Doppler imaging revealed abundant blood flow signals within the lesions,presenting a high-velocity and low-resistance blood flow spectrum.The median age of patients was 29 years,with termination of pregnancy occurring at 7-38 weeks of gestation.Clinical manifesta-tions included persistent irregular vaginal bleeding in 2 cases(25.0％),"on-off"hemorrhage in 2 cases(25.0％),acute massive vaginal bleeding(≥400 ml per episode)in 5 cases(62.5％),abdominal pain in 3 ca-ses(37.5％),secondary anemia in 4 cases(50.0％),and persistent elevation of serum β-hCG in 2 cases(25.0％).All 8 patients underwent uterine artery angiography.Postoperatively,5 cases were diagnosed with preg-nancy-related UAVM,with 1 case also complicated by a right ovarian arteriovenous fistula.The remaining 3 cases revealed only abnormal vascular clusters without early venous opacification.Bilateral uterine artery embolization(UAE)was performed in 4 cases,unilateral UAE(all right-sided)in 2 cases,and no UAE was performed in 2 ca-ses.Hysteroscopic lesion resection or curettage was performed in 3 cases,with 2 cases receiving adjuvant gona-dotropin-releasing hormone agonist(GnRH-a)therapy postoperatively.All 5 patients ultimately diagnosed with UAVM achieved hemostasis within 24 hours after UAE,with mild post-embolization syndrome observed in 1 case.During follow-up,only the patient with the concomitant ovarian arteriovenous fistula experienced recurrent sudden vaginal bleeding and subsequently underwent laparoscopic uterine lesion resection following GnRH-a therapy.Conclusions:UAE is the treatment of choice for pregnancy-related UAVM patients with complex or severe bleed-ing initially diagnosed by ultrasound.However,management should be tailored based on imaging and clinical fea-tures to balance therapeutic efficacy with fertility preservation.

Objective:To explore the treatment methods and prognosis of pregnancy-related uterine arteriovenous malformation (UAVM).Methods:A retrospective analysis was conducted on clinical data from 81 patients with UAVM treated at Peking Union Medical College Hospital between March 2019 and March 2024. Clinical manifestations, diagnostic approaches, treatment strategies and prognosis were evaluated.Results:(1) General Information: the age of patients with UAVM was (32.7±4.6) years, with median gravidity and parity of 1 (quartile range: 1, 2) and 0 (0, 1), respectively. Pregnancy termination methods included surgical abortion or curettage in 46 cases (57%, 46/81), medical induction in 17 cases (21%, 17/81), spontaneous abortion in 16 cases (20%, 16/81), vaginal delivery in 1 case (1%, 1/81), and laparoscopic pregnancy tissue removal in 1 case (1%, 1/81). (2) Clinical manifestations: clinical presentations comprised vaginal bleeding in 59 cases [73%, 59/81; median blood loss: 740 ml (440, 1 360 ml)], massive hemorrhage in 9 cases (11%, 9/81, and bleeding combined with lower abdominal pain in 8 cases (10%, 8/81). Ultrasonography revealed intrauterine masses in 65 cases [80%, 65/81; median size: 2.5 cm (1.8, 4.2 cm)]. Elevated serum human chorionic gonadotrophin-β subunit (β-hCG) levels were observed in in 55 cases [85%, 55/65; median: 62.6 U/L (14.9, 300.1 U/L)]. The median time to UAVM diagnosis via ultrasound was 30.0 days (16.0, 52.0 days) after pregnancy termination, with median peak systolic velocity (PSV) and resistance index of 59.8 cm/s (45.0, 79.6 cm/s) and 0.39 (0.36, 0.43), respectively. (3) Treatment and prognosis: treatment modalities included expectant management in 49 cases (36%, 29/81), medication in 13 cases (16%, 13/81), lesion resection in 31 cases (38%, 31/81), and uterine artery angiography in 8 cases (10%, 8/81; 5 confirmed as arteriovenous fistula). The median time of PSV returning to normal after treatment was 53.8 days (36.0, 93.4 days). The average time for β-hCG returning to normal was (60.4±20.4) days. The median return time of menses was 59.0 days (43.0, 75.4 days).Conclusions:Pregnancy-related UAVM carries a high risk of life-threatening hemorrhage, necessitating management in centers equipped for emergency uterine artery embolization. Informed consent must emphasize disease progression risks and prognosis. Treatment stratification should integrate clinical parameters and imaging features.

Objective:To evaluate the safety,efficacy,and prognosis of interventional treatment for pregnan-cy-related uterine arteriovenous malformations(UAVM).Methods:A retrospective analysis was conducted of the clinical data from 8 patients with pregnancy-associated UAVM who underwent interventional therapy after initial di-agnosis by ultrasound at Peking Union Medical College Hospital between February 1,2016,and January 4,2024.Results:All 8 patients underwent ultrasound examination,and color Doppler imaging revealed abundant blood flow signals within the lesions,presenting a high-velocity and low-resistance blood flow spectrum.The median age of patients was 29 years,with termination of pregnancy occurring at 7-38 weeks of gestation.Clinical manifesta-tions included persistent irregular vaginal bleeding in 2 cases(25.0％),"on-off"hemorrhage in 2 cases(25.0％),acute massive vaginal bleeding(≥400 ml per episode)in 5 cases(62.5％),abdominal pain in 3 ca-ses(37.5％),secondary anemia in 4 cases(50.0％),and persistent elevation of serum β-hCG in 2 cases(25.0％).All 8 patients underwent uterine artery angiography.Postoperatively,5 cases were diagnosed with preg-nancy-related UAVM,with 1 case also complicated by a right ovarian arteriovenous fistula.The remaining 3 cases revealed only abnormal vascular clusters without early venous opacification.Bilateral uterine artery embolization(UAE)was performed in 4 cases,unilateral UAE(all right-sided)in 2 cases,and no UAE was performed in 2 ca-ses.Hysteroscopic lesion resection or curettage was performed in 3 cases,with 2 cases receiving adjuvant gona-dotropin-releasing hormone agonist(GnRH-a)therapy postoperatively.All 5 patients ultimately diagnosed with UAVM achieved hemostasis within 24 hours after UAE,with mild post-embolization syndrome observed in 1 case.During follow-up,only the patient with the concomitant ovarian arteriovenous fistula experienced recurrent sudden vaginal bleeding and subsequently underwent laparoscopic uterine lesion resection following GnRH-a therapy.Conclusions:UAE is the treatment of choice for pregnancy-related UAVM patients with complex or severe bleed-ing initially diagnosed by ultrasound.However,management should be tailored based on imaging and clinical fea-tures to balance therapeutic efficacy with fertility preservation.

Background:Liver cirrhosis is characterized by chronic inflammation,progressive fibrosis,and eventual liver dysfunction,and poses a major global health challenge.Aims:To assess the global burden of liver cirrhosis and its risk factors from 1990 to 2021.Methods:Using data extracted from the Global Burden of Diseases,Injuries,and Risk Factors Study(GBD)2021,the incidence,mortality,disability-adjusted life years(DALYs),and their age-standardized rates of liver cirrhosis were analyzed.Furthermore,a stratified analysis was conducted by sex,age,region,and etiology,with projections of the trends in the next 15 years.Results:Compared to 1990,the global incidence number of liver cirrhosis in 2021 was increased by 58.2%,the death number and DALYs rose by 39.5%and 27.9%,respectively.While the global age-standardized incidence rate(ASIR)showed a slight increase,the age-standardized death rate(ASDR)and DALY rate continued to decline.Both ASIR and ASDR exhibited negative correlations with the sociodemographic index(SDI).All age-standardized rates were higher in males than in females.Since 1990,the incidence rate increased in younger populations,while the mortality and DALY rates declined in most age groups.Non-alcoholic fatty liver disease(NAFLD)emerged as the leading cause of incidence,whereas chronic hepatitis B and C remained the primary contributors to deaths and DALYs.The incidence of NAFLD was prominent in high and high-middle SDI regions,while chronic hepatitis B was concentrated in low SDI regions.Projections to 2036 indicated a continuing rise in ASIR,and declines in ASDR and DALY rate.The incidence of chronic hepatitis B was projected to decrease markedly,whereas that of NAFLD was expected to continue increasing.Conclusions:Between 1990 and 2021,the global incidence of liver cirrhosis showed a modest increase;in contrast,both mortality and DALY rates demonstrated a steady decline.Burden of liver cirrhosis poses notable regional disparities.NAFLD dominates incidence in high-income regions,while viral hepatitis remains predominant in low-income areas,highlighting the need for region-specific prevention strategies.