ObjectiveTo investigate the regulatory effect of overexpressed protein tyrosine phosphatase non-receptor type 2 （Ptpn2） on the inflammatory response of mouse alveolar macrophages （MH-S） induced by SiO₂. MethodsCells with overexpressed Ptpn2 were constructed and induced by SiO₂. The experimental groups were divided into four groups： the negative control group with an empty vector （NC）， the overexpressed Ptpn2 group （P）， the negative control group with an empty vector + SiO₂ induction （NS）， and the overexpressed Ptpn2 + SiO₂ induction group （PS）. Isobaric tags for relative and absolute quantification （iTRAQ） combined with liquid chromatography-tandem mass spectrometry （LC-MS/MS） were used to screen differential proteins， followed by Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） database analyses. Immunofluorescence staining was used to detect the expressions of Tumor necrosis factor （TNF） α， Gasdermin D （GSDMD）， and Transforming growth factor （TGF）-β1. Western blot was used to detect the protein expression levels of PTPN2， Toll-like receptor 4 （TLR4）， tumor necrosis factor-α （TNF-α）， nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3）， and proteins related to the TGF-β1 signaling pathway in the cells of each group. ResultsiTRAQ results identified 144 differential proteins among the four groups. GO analysis showed that in biological processes （BP）， these differential proteins were mainly enriched in IκB kinase/nuclear factor-κB （NF-κB） signaling， cell activation and signal transduction involved in immune responses， and regulation of receptor signaling pathways by signal transducer and activator of transcription （STAT）， etc. KEGG analysis revealed that the differential proteins were mainly enriched in Toll-like receptor signaling pathway， NF-κB signaling pathway， NOD-like receptor signaling pathway， TGF-β signaling pathway， and TNF signaling pathway. The results of immunofluorescence staining showed that compared with the NC group， the expressions of TNF α， GSDMD， and TGF-β1 in the cells of the NS group increased （P < 0.05）； compared to the NS group， the expression of the aforementioned proteins in the PS group decreased in cellular proteins（P < 0.05）. The results of Western blot showed that compared with the NC group， the protein expression levels of PTPN2， p-NF-κB，MyD88，TLR4，NLRP3，GSDMD，Caspase-1，IL-1β， TGF-βR1， TGF-βR，p-Smad2/3 in the NS group were significantly upregulated （P < 0.05）； compared with the NS group， the expression levels of the aforementioned proteins in the PS group were significantly downregulated （P < 0.05）. ConclusionOverexpression of Ptpn2 can inhibit the protein expressions of TLR4-TNF-α signaling， NLRP3 signaling， and TGF-β1 signaling closely related to inflammatory response in SiO₂-mediated MH-S macrophages.

Objective To investigate the temporal changes in pathological damage and macrophage polarization in liver and spleen tissues of mice infected with Angiostrongylus cantonensis, and to preliminarily unravel the peripheral immune responses during the early stage of A. cantonensis infection. Methods Forty female BALB/c mice at ages of 6 to 8 weeks were randomly divided into four groups, including the control group and 7-, 14-, and 21-day infection groups, with 10 mice in each group. Each mouse in the infection groups was inoculated with 30 third-stage (L3) larvae of A. cantonensis by oral gavage, and five mice were randomly selected from each infection group on days 7, 14, and 21 post-infection, while mice in the control group were given the same volume of physiological saline and five mice were randomly selected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled. The histopathological changes of mouse liver and spleen tissues were observed using hematoxylin and eosin (HE) staining, and the percentage of positive staining area and the co-localization positive rates of the macrophage surface antigens F4/80, CD86, and CD206 were quantified in mouse liver and spleen tissues using immunohistochemical and immunofluorescence staining. In addition, five mice were collected from each infection group on days 7, 14, and 21 post-infection, and five mice were collected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled for detection of macrophage markers CD86 and CD206 and macrophage phenotyping using flow cytometry, and the expression of M1 macrophage markers, including inducible nitric oxide synthase (Nos2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and M2 markers, including arginase 1 (Arg1), mannose receptor C-type 1 (Mrc1) and chitinase-like protein 3 (Chil3) was quantified in mouse liver and spleen tissues using real-time quantitative PCR (RT-qPCR) assay. Results Proliferative lesions of the hepatocyte were observed in mouse liver tissues and the follicular structures of the mouse spleen white pulp were disrupted 21 days post-infection with A. cantonensis. Immunohistochemical staining showed that there were significant differences in the percentages of F4/80, CD86 and CD206 positive staining areas in the liver and spleen tissues among the four groups of mice (F = 242.40, 197.14, 183.19, 157.65, 242.35 and 146.24; all P values < 0.001), and the percentages of positive staining in the liver and spleen tissues of mice in the 14-day infection group [(4.45 ± 0.51)%, (3.74 ± 0.67)%, (8.32 ± 0.72)%, (16.56 ± 1.14)%, (11.62 ± 0.52)%, and (8.29 ± 0.72)%, respectively] and the 21-day infection group [(3.70 ± 0.11)%, (3.22 ± 0.43)%, (11.53 ± 1.03)%, (12.59 ± 1.05)%, (9.02 ± 0.83)%, and (11.67 ± 1.10)%, respectively] were higher than in the control group [(0.35 ± 0.16)%, (0.40 ± 0.02)%, (0.93 ± 0.05)%, (2.78 ± 0.26)%, (2.33 ± 0.20)%, and (1.85 ± 0.20)%, respectively] (all P values < 0.05). Immunofluorescence staining showed significant differences in the positive rates of F4/80 co-localization with CD86 and CD206 in mouse liver and spleen tissues among the four groups (F = 24.42, 25.28, 54.51 and 130.55; all P values < 0.001). Flow cytometry detected significant differences in the proportions of CD86⁺ and CD206⁺ macrophages in mouse liver and spleen tissues among the four groups (F = 67.98, 18.41, 29.77, 172.80; all P values < 0.001), and the proportions of CD206⁺ macrophages in the liver and spleen of the 21-day infection group were significantly higher than those in the control group [(9.25 ± 2.55)% vs (3.83 ± 0.72)%, and (4.22 ± 0.56)% vs (0.47 ± 0.18)%, respectively] (both P values < 0.05). In addition, RT-qPCR assay quantified significant differences in the relative mRNA expression of M1 macrophage markers (IL-1β, TNF-α and Nos2) and M2 macrophage markers (Arg1, Chil3 and Mrc1) in mouse liver and spleen tissues among the four groups (F = 41.30, 31.82, 199.33, 19.96, 62.01, 119.76, 23.67, 95.90, 72.27, 82.59, 123.41 and 29.75; all P values < 0.05). Conclusions A. cantonensis infection may cause progressive pathological damage in mouse liver and spleen tissues, accompanied by dynamic temporal changes in macrophage polarization. M1 macrophage polarization predominates at the early stage of A. cantonensis infection and shifts towards M2 polarization at the later stages, suggesting that M2 polarization may participate in immune regulation at late stages of A. cantonensis infection by suppressing excessive inflammatory responses and promoting tissue repair.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Ambient air pollution is increasingly being recognized as a risk factor for heart failure; however, its effects on cardiac biomarkers remain unclear. This scoping review assessed the existing evidence on the association between air pollution and cardiac biomarkers in heart failure, described the key concepts, synthesized data, and identified research gaps. Following the PRISMA-ScR guidelines, PubMed, Embase, Web of Science, and CNKI databases were searched for studies on air pollution, heart failure, and biomarkers. A total of 765 records were screened, and 81 full texts were assessed for eligibility, resulting in 15 studies. The results showed that the exposure to particulate matter was associated with elevated N-terminal pro-B-type natriuretic peptide and troponin levels. Several studies have linked particulate matter exposure to a higher cardiovascular risk and heart failure biomarkers. Inflammatory and oxidative stress markers were consistently elevated across studies, supporting the biological relevance of these associations. However, few studies have focused specifically on populations with heart failure or clinically relevant biomarkers, and the evidence for gaseous pollutants remains inconclusive. These findings highlight the need to integrate environmental risk assessment into heart failure care and inform policy efforts to reduce the pollution-related cardiovascular burden. Further research should address these gaps through improved exposure assessments and the integration of mechanistic evidence.
Heart Failure/epidemiology* ; Biomarkers/metabolism* ; Humans ; Air Pollution/adverse effects* ; Air Pollutants/adverse effects* ; Particulate Matter/adverse effects* ; Environmental Exposure ; Natriuretic Peptide, Brain/blood* ; Oxidative Stress ; Troponin/blood*

Background Pneumoconiosis is the most serious occupational disease in China, among which silicosis accounts for more than 50%. microRNA (miRNA) plays an important role in the occurrence process of silicosis fibrosis, but the mechanism of it has not been fully clarified yet. Objective To explore the molecular mechanism by which miR-411-3p modulates the ubiquitination degradation of SMAD specific E3 ubiquitin protein ligase (SMURF) 2/Smad7, thereby suppressing epithelial-mesenchymal transition (EMT) in mouse alveolar type II epithelial cells and counteracting silica-induced pulmonary fibrosis. Methods Twenty-four 8-week-old SPF male C57BL/6J mice were randomly divided into four groups: Control group, silica group, silica +miR-411-3p agomir-NC group, and silica +miR-411-3p agomir group, with 6 mice in each group. Silicosis model was prepared by a one-time bronchial infusion of silicon dioxide (SiO₂) (200 mg·mL^-1, 50 μL). In vitro MLE-12 cells were divided into (1) control group and SiO₂ group, (2) SiO₂+negative control siRNA (siRNA-NC) group and SiO₂+Smurf2 gene silencing (si-Smurf2) group, (3) SiO₂+solvent (DMSO) group and SiO₂+protease inhibitor (MG132) group, (4) mutant sequence plasmid (Mut)+miR-411-3p mimic control (miR-NC) group, Mut+miR-411-3p mimic group, wild sequence plasmid (Wt)+miR-NC group, and Wt+miR-411-3p mimic group, (5) SiO₂+miR-NC group and SiO₂+miR-411-3p mimic group. The pathological morphology and collagen deposition of lung tissue were observed after staining. Detection of miR-411-3p and proteins was conducted by real-time fluorescent quantitative PCR and Western blot. The binding of SMURF2 to Smad7 protein and Smad7 to ubiquitin (Ub) were detected by co-immunoprecipitation (Co-IP) method. Dual-luciferase reporter gene assay was adopted to verify the regulatory effect of miR-411-3p on Smurf2. Results In the SiO₂-induced MLE-12 cells, compared to the control group, the SiO₂-treated group showed significantly upregulated expressions of N-cadherin (N-Cad), collagen I (CoL I), SMURF2, transforming growth factor-β1 (TGF-β1), and phosphorylated Smad2/3 (p-Smad2/3). In contrast, the expressions of E-cadherin (E-Cad), Smad7, and miR-411-3p were significantly downregulated (P<0.05). The dual-luciferase reporter gene assay revealed a regulatory effect of miR-411-3p on Smurf2 (P<0.05). Meanwhile, in the MLE-12 cells induced by SiO₂, the miR-411-3p mimic down-regulated the protein expressions of SMURF2, N-Cad, CoL I, TGF-β1, and p-Smad2/3, while up-regulated the protein expressions of E-Cad and Smad7 (P<0.05). The silenced Smurf2 gene inhibited the expressions of N-Cad, CoL I, and p-Smad2/3 proteins, while promoted the expressions of E-Cad and Smad7 proteins in the MLE-12 cells (P<0.05). The Co-IP results showed that the binding of SMURF2 to Smad7 was enhanced, and the ubiquitin binding ability of Smad7 was enhanced in the SiO₂ group. In the lung tissue of mice, the results of pathological observation with hematoxylin-eosin (HE) and sirius red (VG) staining showed that compared with the agomir-NC, the lesion was relieved in the lung tissue of the miR-411-3p agomir group. Meanwhile, the expressions of SMURF2, N-Cad, CoL I, TGF-β1, and p-Smad2/3 were significantly down-regulated, while the expressions of E-Cad and Smad7 were significantly up-regulated (P<0.05). Conclusion MiR-411-3p alleviates the EMT of alveolar type II epithelial cells and antagonizes silicosis fibrosis progression in mice by inhibiting SMURF2-mediated ubiquitination and degradation of Smad7.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.