Background: This study aimed to estimate temporal trends in metabolically unhealthy obesity (MUO) among United States (US) adults by age, sex, race/ethnicity, and income from 1999 to 2018. Methods: We included 17,230 non-pregnant adults from a nationally representative cross-sectional study, the National Health and Nutrition Examination Survey (NHANES). MUO was defined as body mass index ≥30 kg/m2 with any metabolic disorders in blood pressure, blood glucose, and blood lipids. The age-adjusted percentage of MUO was calculated, and linear regression models estimated trends in MUO. Results: The weighted mean age of adults was 47.28 years; 51.02% were male, 74.64% were non-Hispanic White. The age-adjusted percentage of MUO continuously increased in adults across all subgroups during 1999–2018, although with different magnitudes (all P<0.05 for linear trend). Adults aged 45 to 64 years consistently had higher percentages of MUO from 1999–2000 (34.25%; 95% confidence interval [CI], 25.85% to 42.66%) to 2017–2018 (42.03%; 95% CI, 35.09% to 48.97%) than the other two age subgroups (P<0.05 for group differences). The age-adjusted percentage of MUO was the highest among non-Hispanic Blacks while the lowest among non-Hispanic Whites in most cycles. Adults with high-income levels generally had lower MUO percentages from 1999–2000 (22.63%; 95% CI, 17.00% to 28.26%) to 2017–2018 (32.36%; 95% CI, 23.87% to 40.85%) compared with the other two subgroups. Conclusion This study detected a continuous linear increasing trend in MUO among US adults from 1999 to 2018. The persistence of disparities by age, race/ethnicity, and income is a cause for concern. This calls for implementing evidence-based, structural, and effective MUO prevention programs.

Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

Background: This study aimed to estimate temporal trends in metabolically unhealthy obesity (MUO) among United States (US) adults by age, sex, race/ethnicity, and income from 1999 to 2018. Methods: We included 17,230 non-pregnant adults from a nationally representative cross-sectional study, the National Health and Nutrition Examination Survey (NHANES). MUO was defined as body mass index ≥30 kg/m2 with any metabolic disorders in blood pressure, blood glucose, and blood lipids. The age-adjusted percentage of MUO was calculated, and linear regression models estimated trends in MUO. Results: The weighted mean age of adults was 47.28 years; 51.02% were male, 74.64% were non-Hispanic White. The age-adjusted percentage of MUO continuously increased in adults across all subgroups during 1999–2018, although with different magnitudes (all P<0.05 for linear trend). Adults aged 45 to 64 years consistently had higher percentages of MUO from 1999–2000 (34.25%; 95% confidence interval [CI], 25.85% to 42.66%) to 2017–2018 (42.03%; 95% CI, 35.09% to 48.97%) than the other two age subgroups (P<0.05 for group differences). The age-adjusted percentage of MUO was the highest among non-Hispanic Blacks while the lowest among non-Hispanic Whites in most cycles. Adults with high-income levels generally had lower MUO percentages from 1999–2000 (22.63%; 95% CI, 17.00% to 28.26%) to 2017–2018 (32.36%; 95% CI, 23.87% to 40.85%) compared with the other two subgroups. Conclusion This study detected a continuous linear increasing trend in MUO among US adults from 1999 to 2018. The persistence of disparities by age, race/ethnicity, and income is a cause for concern. This calls for implementing evidence-based, structural, and effective MUO prevention programs.

Background: This study aimed to estimate temporal trends in metabolically unhealthy obesity (MUO) among United States (US) adults by age, sex, race/ethnicity, and income from 1999 to 2018. Methods: We included 17,230 non-pregnant adults from a nationally representative cross-sectional study, the National Health and Nutrition Examination Survey (NHANES). MUO was defined as body mass index ≥30 kg/m2 with any metabolic disorders in blood pressure, blood glucose, and blood lipids. The age-adjusted percentage of MUO was calculated, and linear regression models estimated trends in MUO. Results: The weighted mean age of adults was 47.28 years; 51.02% were male, 74.64% were non-Hispanic White. The age-adjusted percentage of MUO continuously increased in adults across all subgroups during 1999–2018, although with different magnitudes (all P<0.05 for linear trend). Adults aged 45 to 64 years consistently had higher percentages of MUO from 1999–2000 (34.25%; 95% confidence interval [CI], 25.85% to 42.66%) to 2017–2018 (42.03%; 95% CI, 35.09% to 48.97%) than the other two age subgroups (P<0.05 for group differences). The age-adjusted percentage of MUO was the highest among non-Hispanic Blacks while the lowest among non-Hispanic Whites in most cycles. Adults with high-income levels generally had lower MUO percentages from 1999–2000 (22.63%; 95% CI, 17.00% to 28.26%) to 2017–2018 (32.36%; 95% CI, 23.87% to 40.85%) compared with the other two subgroups. Conclusion This study detected a continuous linear increasing trend in MUO among US adults from 1999 to 2018. The persistence of disparities by age, race/ethnicity, and income is a cause for concern. This calls for implementing evidence-based, structural, and effective MUO prevention programs.

Background: This study aimed to estimate temporal trends in metabolically unhealthy obesity (MUO) among United States (US) adults by age, sex, race/ethnicity, and income from 1999 to 2018. Methods: We included 17,230 non-pregnant adults from a nationally representative cross-sectional study, the National Health and Nutrition Examination Survey (NHANES). MUO was defined as body mass index ≥30 kg/m2 with any metabolic disorders in blood pressure, blood glucose, and blood lipids. The age-adjusted percentage of MUO was calculated, and linear regression models estimated trends in MUO. Results: The weighted mean age of adults was 47.28 years; 51.02% were male, 74.64% were non-Hispanic White. The age-adjusted percentage of MUO continuously increased in adults across all subgroups during 1999–2018, although with different magnitudes (all P<0.05 for linear trend). Adults aged 45 to 64 years consistently had higher percentages of MUO from 1999–2000 (34.25%; 95% confidence interval [CI], 25.85% to 42.66%) to 2017–2018 (42.03%; 95% CI, 35.09% to 48.97%) than the other two age subgroups (P<0.05 for group differences). The age-adjusted percentage of MUO was the highest among non-Hispanic Blacks while the lowest among non-Hispanic Whites in most cycles. Adults with high-income levels generally had lower MUO percentages from 1999–2000 (22.63%; 95% CI, 17.00% to 28.26%) to 2017–2018 (32.36%; 95% CI, 23.87% to 40.85%) compared with the other two subgroups. Conclusion This study detected a continuous linear increasing trend in MUO among US adults from 1999 to 2018. The persistence of disparities by age, race/ethnicity, and income is a cause for concern. This calls for implementing evidence-based, structural, and effective MUO prevention programs.

OBJECTIVES: To investigate the effect of avitinib for suppressing NLRP3 inflammasome activation and alleviating septic shock and explore the underlying mechanism. METHODS: Mouse bone marrow-derived macrophages (BMDM), human monocytic leukemia cell line THP-1, and peripheral blood mononuclear cells (PBMC) isolated from healthy volunteers were pre-treated with avitinib, followed by activation of the canonical NLRP3 inflammasome using agonists including nigericin, monosodium urate (MSU) crystals, or adenosine triphosphate (ATP). Non-canonical NLRP3 inflammasome activation was induced via intracellular transfection of lipopolysaccharide (LPS). Western blotting was used to detect the secretory protein markers of NLRP3 inflammasome activation and assess pyroptosis, and the levels of inflammatory cytokines in cell culture supernatant were determined with ELISA. In a mouse model of LPS-induced septic shock, the effect of avitinib treatment on the levels of inflammatory cytokines in serum and peritoneal lavage fluid were examined with ELISA, and survival curves of the mice were plotted using the Kaplan-Meier method. RESULTS: Avitinib significantly inhibited NLRP3 inflammasome activation in multiple cell types, and dose-dependently reduced IL-1β secretion and caspase-1 cleavage while suppressing GSDMD-mediated pyroptosis without obviously affecting IL-6 or TNF-α levels. In the mouse models of LPS-induced septic shock, avitinib significantly lowered IL-1β levels in serum and peritoneal fluid and extended survival time of the mice. CONCLUSIONS Avitinib suppresses NLRP3 inflammasome activation and alleviates septic shock in mice.
Animals ; Shock, Septic/metabolism* ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein ; Inflammasomes/drug effects* ; Humans ; Macrophages/metabolism* ; Interleukin-1beta/metabolism* ; Lipopolysaccharides

Objective To investigate the clinical prognosis of untreated residual coronary artery dissection treated with drug coated balloon(DCB).Methods A retrospective analysis was conducted on the clinical and imaging data of patients with primary coronary artery lesions(2.5-4.0 mm)treated with DCB under angiography guidance at Xuzhou Cancer Hospital,Xuzhou New Health Geriatric Hospital,and Peixian Guotai Hospital from September 2017 to April 2023.According to the observation of coronary artery dissection through angiography,the patients were divided into a dissection group and a non dissection group.The main endpoint of this study was the major adverse cardiovascular event(MACE)during a 12-month follow-up.Results A total of 381 patients were enrolled in the three research centers,with 30 cases(30 lesions)in the dissection group and 351 cases(367 lesions)in the non dissection group.There was no significant difference between the two groups in terms of age,gender,hypertension,hyperlipidemia,diabetes,smoking,previous myocardial infarction,previous percutaneous coronary intervention,coronary artery bypass grafting and other baseline clinical characteristics(all P＞0.05).Except for the reference vessel diameter(P=0.049)and DCB pressure(P=0.032),there was no statistically significant difference in the characteristics of coronary angiography lesions between the two groups of patients(both P＞0.05).During a 12-month follow-up,there was no statistically significant difference(P＞0.05)in the incidence of MACE between the dissection group and the non dissection group after DCB treatment for primary coronary artery lesions in situ.Conclusions Untreated residual dissection after DCB treatment of de novo coronary lesions does not lead to an increase in clinical MACE.

Objective:To explore the effect of ginsenoside Rg1 on spermatogenic dysfunction in mice caused by diabetes and its mechanism of action.Methods:Eighteen male C57BL mice were randomly divided into control group, the model group and the ginsenoside Rg1 group by completely random method, with 6 mice in each group. Type 2 diabetes models were established in the model group and the ginsenoside Rg1 group by a high-fat diet combined with intraperitoneal injection of streptozotocin, while control group was injected with the same amount of normal saline. After successful modeling, control group was given a regular diet for 8 weeks, while the model group and ginsenoside Rg1 group were given a high-fat diet for 8 weeks. The ginsenoside Rg1 group was also treated with ginsenoside Rg1 medication. Reproductive hormone levels were detected by enzyme-linked immunosorbent assay test kits, and Western blotting was used to detect the expressions of apoptosis-related proteins (Bcl2 protein, Caspase-3 protein, Bax protein), autophagy-related proteins (P62, LC3Ⅰ, LC3Ⅱ, Beclin1), β-Catenin protein, mTOR protein, LAMP1 protein and transcription factor EB. The body weight, blood glucose levels, testicular index of mice in each group were compared, as well as the testicular injury status.Results:The body weight [(18.77±1.14) g], testosterone level [(141.07±8.47) ng/L], follicle-stimulating hormone level [(9.19±0.74) U/L], and luteinizing hormone level [(1 497.91±99.57) pg/L] of mice in the model group were significantly lower than those in the control [(31.57±2.35) g, P<0.001; (171.50±11.76) ng/L, P<0.001; (12.46±1.54) U/L, P<0.001; (1 807.29±92.76) pg/L, P<0.001]; fasting blood glucose level [(20.82±1.11) mmol/L], glycosylated hemoglobin (12.67%±1.03%), the testis index (0.65%±0.03%) were significantly higher than those in the control [(6.40±1.34) mmol/L, P<0.001; 5.17%±1.17%, P<0.001; 0.48%±0.04%, P<0.001]. Compared with the model group, the body weight [(22.62±0.92) g, P=0.023], testosterone level [(172.63±9.20) ng/L, P<0.001], follicle-stimulating hormone level [(12.37±1.15) U/L, P<0.001], and luteinizing hormone level [(1 847.80±108.80) pg/L, P<0.001] of mice in the ginsenoside Rg1 group increased significantly, fasting blood glucose level [(18.63±1.14) mmol/L, P=0.017], glycosylated hemoglobin (8.50%±1.05%, P<0.001) and testicular index (0.54%±0.02%, P<0.001) decreased significantly. Compared with the control, the expressions of P62 ( P=0.039), LC3Ⅱ/LC3Ⅰ( P<0.001), Beclin1 ( P=0.002) and mTOR ( P=0.036) in the testicular tissue of mice in the model group all increased, the expression of β-Catenin ( P<0.001), LAMP1 ( P=0.005), transcription factor EB ( P<0.001) all decreased. Compared with the model group, the expressions of autophagy-related proteins P62 ( P=0.048), LC3Ⅱ/LC3Ⅰ( P<0.001) , Beclin1 ( P=0.023) and mTOR ( P=0.005) in the ginsenoside Rg1 group all decreased, while the expression of β-Catenin ( P=0.001), LAMP1 ( P=0.011) and transcription factor EB ( P=0.022) all increased. Transmission electron microscopy detected a decrease in the number of autophagosomes in the testicles of mice in the model group, and it improved after drug intervention. The HE staining showed that the testes of mice in the model group exhibited phenotypes such as the shedding and disorganization of spermatogenic cells, while ginsenoside Rg1 was able to improve these phenotypes. Conclusion:Ginsenoside Rg1 can improve testicular injury caused by diabetes in mice by regulating autophagy.

Phosphodiesterase type 5(PDE5)participates in the physiological functions of multiple organs by regulating the nitric oxide(NO)-cyclic guanosine monophosphate(cGMP)pathway.As a long-acting PDE5 inhibitor,tadalafil has been used clinically for over 20 years and is approved for the treatment of male erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia.Furthermore,tadalafil maintains cGMP levels by inhibiting PDE5,thereby activa-ting the downstream NO-cGMP signaling pathway to exert multiple effects,including relaxing smooth muscle,exerting antioxidant actions,regulating apoptosis,and modulating metabolism.Clinical evidence indicates that tadalafil shows promising therapeutic potential in multi-organ system diseases such as pulmonary arterial hypertension,heart failure,type 2 diabetes,cognitive impair-ment,female infertility,and fetal growth restriction.This article systematically reviews the action mechanisms and research pro-gress of tadalafil in treating diseases beyond erectile dysfunction,aiming to summarize its potential for cross-disease system clini-cal applications and provide references for optimizing treatment strategies for patients with chronic diseases.