BACKGROUND: Previous evidence showed that ambient air pollution and cardiovascular mortality are related. However, there is a lack of evidence towards the modification effect of long-term lifestyle on the association between short-term ambient air pollution and death from cardiovascular events. METHOD: A total of 14,609 death from major adverse cardiovascular events (MACE) were identified among the China Kadoorie Biobank participants from 2013 to 2018. Ambient air pollution exposure including particulate matter 2.5 (PM_2.5), SO₂, NO₂, CO, and O₃ from the same period were obtained from space-time model reconstructions based on remote sensing data. Case-crossover design and conditional logistic regression was applied to estimate the effect of short-term exposure to air pollutants on MACE mortality. RESULTS: We found MACE mortality was significantly associated with PM_2.5 (relative percent increase 2.91% per 10 µg/m³ increase, 95% CI 1.32-4.53), NO₂ (5.37% per 10 µg/m³ increase, 95% CI 1.56-9.33), SO₂ (6.82% per 10 µg/m³ increase, 95% CI 2.99-10.80), and CO (2.24% per 0.1 mg/m³ increase, 95% CI 1.02-3.48). Stratified analyses indicated that drinking was associated with elevated risk of MACE mortality with NO₂ and SO₂ exposure; physical inactivity was associated with higher risk of death from MACE when exposed to PM_2.5; and people who had balanced diet had lower risk of MACE mortality when exposed to CO and NO₂. CONCLUSIONS The study results showed that short-term exposure to ambient PM_2.5, NO₂, SO₂, and CO would aggravate the risk of cardiovascular mortality, yet healthy lifestyle conduct might mitigate such negative impact to some extent.
Humans ; Cardiovascular Diseases/epidemiology* ; China/epidemiology* ; Male ; Female ; Air Pollution/adverse effects* ; Middle Aged ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; Environmental Exposure/adverse effects* ; Life Style ; Aged ; Adult ; Risk Factors ; Cross-Over Studies ; East Asian People

Traditional open thyroid surgery often leaves a scar on the neck,which can affect cosmetic outcomes.Therefore,various endoscopic thyroidectomy approaches via extra-cervical approaches have been developed.However,due to the unique anatomical characteristics of the neck and limitations of endoscopic instruments,conventional endoscopic techniques have certain drawbacks.Robot-assisted endoscopic thyroid surgery can help overcome these limitations.At present,robotic surgical systems remain expensive and the associated surgical costs are high,limiting their widespread adoption.Most surgeons are still relatively unfamiliar with the technique.Nevertheless,with ongoing technological advancements and cost reductions,robot-assisted surgery holds great promise for broader application.Based on years of large-scale experience in endoscopic thyroid surgery at our center,and drawing upon both domestic and international experiences with robotic thyroidectomy,this paper summarizes and proposes a seven-step protocol for robot-assisted endoscopic thyroidectomy via the bilateral axillo-breast approach,aiming to provide a practical reference for the clinical adoption of this technique.

Objective To investigate the causal relationship between gut microbiota and viral pneumonia,as well as the underlying mechanisms,using two-sample and two-step Mendelian randomization(MR)approaches,thereby providing novel insights for the prevention and treatment of viral pneumonia.Methods All data were obtained from publicly available genome-wide association studies(GWAS)pooled datasets,including gut microbiota data from the MiBioGen Consortium and the Netherlands Microbiome Project,viral pneumonia data from the FinnGen R10 database,and plasma metabolome data from the publicly available GWAS Catalog.Instrumental variables(IVs)were extracted according to the predefined threshold values.MR analyses were conducted using inverse variance weighting(IVW),MR-Egger,weighted median(WME),weighted mode(WM),and Bayesian-weighted Mendelian randomization(BWMR)methods.Reverse MR analysis was performed to determine whether there was a reverse association.Two-step MR analysis was used to explore the potential mediating role of plasma metabolites,and a series of sensitivity analyses were performed to test the stability of the results.Results Among 196 gut microbiota taxa from the MiBioGen consortium GWAS,11 taxa were associated with viral pneumonia.An increase in the abundance of 4 taxa increased the risk of viral pneumonia,while an increase in the abundance of 7 taxa had a protective effect against viral pneumonia.Among the 207 gut microbiota taxa from the Dutch Microbiome Project GWAS data,10 taxa were associated with viral pneumonia,with 6 risk-increasing and 4 protective taxa identified.Mediation analysis results showed that the causal effect of Defluviitaleaceae on viral pneumonia(OR=0.708,95%CI 0.540-0.929,P=0.013)was mediated to some extent by the N6-acetyllysine levels,with a mediation ratio of 18.4%.Sensitivity analyses did not reveal significant heterogeneity or horizontal pleiotropy.Conclusions Specific gut microbiota are causally associated with viral pneumonia and show potential differences across different populations;the protective effect of Defluviitaleaceae against viral pneumonia may be mediated by the N6-acetyllysine levels.Targeting metabolites may become a potential therapeutic approach for viral pneumonia.

PANoptosis is a newly defined type of programmed cell death (PCD), which is triggered by a variety of stimuli and covers three known forms of PCD: apoptosis, pyroptosis and necroptosis. In physiological state, cell death plays an important protective role against pathogen invasion, but its over-activation may aggravate inflammatory response and cause tissue damage. Studies have shown that the occurrence and progression of acute lung injury/acute respiratory distress syndrome (ALI/ARDS), asthma, chronic obstructive pulmonary disease (COPD) and other lung diseases are closely related to PANoptosis. The purpose of this review is to deeply explore the molecular mechanism of PANoptosis and its regulatory factors in lung diseases, in order to discover potential therapeutic targets and provide new targets and innovative ideas for clinical treatment for lung diseases.
Humans ; Lung Diseases ; Apoptosis ; Pyroptosis ; Pulmonary Disease, Chronic Obstructive ; Necroptosis ; Acute Lung Injury

Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase It mediates trimethylation of lysine 27 on histone H3,thereby facilitating the epigenetic silencing of downstream genes.In conjunc-tion with SUZ12,EED,and other components,it constitutes the polycomb repressive complex 2(PRC2)complex.While EZH2 is intricately involved in cellular proliferation and cardiac development,the chan-ges in its expression during cardiac terminal differentiation remain elusive.In this study,we employed differential gene expression analysis of embryonic and adult myocardial cells using the GEO database,and found that EZH2 is highly expressed in embryonic myocardium,but is present at very low levels in adult myocardium(P＜0.0001).Conversely,the expression changes of PRC2 members SUZ12 and EED are not as pronounced.Online analysis through the Tabula Muris database indicates that under physiological conditions,various cell subpopulations in the adult mouse heart exhibit negligible expression of EZH2.Immunohistochemical staining of mouse cardiac tissues shows that EZH2 is highly expressed in embryonic and neonatal myocardium but declines progressively from the first day after birth(P＜0.0001),becoming almost undetectable by the third day.Western blotting further confirms the rapid disappearance of EZH2 expression post-birth(P＜0.05),with EZH1 compensating for the downregulation of EZH2 to maintain H3K27me3 modification levels.Additionally,using the P19 teratocarcinoma stem cell model for cardio-myocyte differentiation,it is observed that EZH2 is significantly upregulated during the transition from cardiac progenitor cells to spontaneously beating cardiomyocytes,correlating with the expression of the cardiomyocyte transcription factor Gata4(P＜0.01).Targeted degradation of EZH2 using the small mole-cule drug MS1943 significantly inhibits the proliferation of induced cardiomyocytes,as evidenced by 5-e-thynyl-2'-deoxyuridine(EdU)incorporation assays(P＜0.01),and RT-qPCR reveals a marked in-crease in the expression of the proliferation inhibitor CDKN1A(P＜0.01).In summary,the high expres-sion of EZH2 in embryonic myocardial cells is associated with enhanced cell proliferation.The rapid loss of EZH2 expression postnatally correlates with the loss of proliferative capacity in cardiomyocytes,mark-ing it as a key indicator of cardiac terminal differentiation.

Objective This study sought to establish a non-alcoholic fatty liver disease(NAFLD)model in Wistar-SD hypercholesterolemia(WSHc)rats induced by a high-fat diet and to reveal the pathogenesis of NAFLD in these rats through the Srebp-1 gene.Methods After 2 weeks of dietary treatment,thirty 6-week-old WSHc rats were divided into High-fat control group,HFD+AAV no load group,and HFD+AAV group,with 10 rats in each group.The HFD+AAV no load group and HFD+AAV group were intravenously injected with a vector virus and an shRNA-containing virus,respectively.WSHc rats were fed with a normal fat diet as a normal control group.Serum levels of ALT,AST,TBIL,ALP,TBA,GLU,CHOL,and TG were measured every 2 weeks.After a further 8 weeks of feeding,the rats were euthanized and livers were excised for HE staining,Oil Red O staining,Masson staining,and Sirius red staining to observe the morphology,lipid deposition,and fibrosis of the liver tissues.RT-qPCR was performed to detect the expression of lipid metabolism-related genes namely Srebp-1,Aacs,FASN and LDLR in the livers.Furthermore,hepatocytes were isolated,cultured,and divided into a normal control group and a high-fat control group.Next,expression of the Srebp-1 gene was detected by RT-qPCR.Srebp-1 knockout(KO)hepatocytes were constructed,then TG content was detected and the lipid accumulation was observed by Oil Red O staining.Results After 10 weeks of high-fat diet treatment,serum ALT(P＜0.001),ALP(P＜0.001),TBA(P＜0.05),GLU(P＜0.001),and CHOL(P＜0.001)significantly increased in WSHc rats.Abnormal lipid deposition with formation of large vacuolar lipid droplets and fibrotic lesions in livers were observed.The mRNA expression of Srebp-1 noticeably increased in WSHc rats(P＜0.001).Moreover,compared with the high-fat control group,the ALT(P＜0.05)and GLU(P＜0.01)in the HFD+AAV group decreased,and liver lipid deposition and the formation of large vacuolar lipid droplets were alleviated.Expressions of genes such as FASN(P＜0.05)and LDLR(P＜0.01)were significantly upregulated.Additionally,there was a significant increase in the expression of Srebp-1 in hepatocytes of the high-fat control group(P＜0.001),while after Srebp-1 gene knockout,cellular TG levels decreased and the degree of lipid droplet aggregation was reduced.Conclusions The Srebp-1 gene plays a regulatory role in hepatic lipid metabolism and deposition,modulating the expression of lipid metabolism-related genes in WSHc rats with NAFLD.In vitro experiments demonstrated that downregulation of Srebp-1 alleviates lipotoxic injury in hepatocytes,suggesting that the development of NAFLD in WSHc rats is closely associated with abnormally high expressions of the Srebp-1 gene.

Traditional open thyroid surgery often leaves a scar on the neck,which can affect cosmetic outcomes.Therefore,various endoscopic thyroidectomy approaches via extra-cervical approaches have been developed.However,due to the unique anatomical characteristics of the neck and limitations of endoscopic instruments,conventional endoscopic techniques have certain drawbacks.Robot-assisted endoscopic thyroid surgery can help overcome these limitations.At present,robotic surgical systems remain expensive and the associated surgical costs are high,limiting their widespread adoption.Most surgeons are still relatively unfamiliar with the technique.Nevertheless,with ongoing technological advancements and cost reductions,robot-assisted surgery holds great promise for broader application.Based on years of large-scale experience in endoscopic thyroid surgery at our center,and drawing upon both domestic and international experiences with robotic thyroidectomy,this paper summarizes and proposes a seven-step protocol for robot-assisted endoscopic thyroidectomy via the bilateral axillo-breast approach,aiming to provide a practical reference for the clinical adoption of this technique.

Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase It mediates trimethylation of lysine 27 on histone H3,thereby facilitating the epigenetic silencing of downstream genes.In conjunc-tion with SUZ12,EED,and other components,it constitutes the polycomb repressive complex 2(PRC2)complex.While EZH2 is intricately involved in cellular proliferation and cardiac development,the chan-ges in its expression during cardiac terminal differentiation remain elusive.In this study,we employed differential gene expression analysis of embryonic and adult myocardial cells using the GEO database,and found that EZH2 is highly expressed in embryonic myocardium,but is present at very low levels in adult myocardium(P＜0.0001).Conversely,the expression changes of PRC2 members SUZ12 and EED are not as pronounced.Online analysis through the Tabula Muris database indicates that under physiological conditions,various cell subpopulations in the adult mouse heart exhibit negligible expression of EZH2.Immunohistochemical staining of mouse cardiac tissues shows that EZH2 is highly expressed in embryonic and neonatal myocardium but declines progressively from the first day after birth(P＜0.0001),becoming almost undetectable by the third day.Western blotting further confirms the rapid disappearance of EZH2 expression post-birth(P＜0.05),with EZH1 compensating for the downregulation of EZH2 to maintain H3K27me3 modification levels.Additionally,using the P19 teratocarcinoma stem cell model for cardio-myocyte differentiation,it is observed that EZH2 is significantly upregulated during the transition from cardiac progenitor cells to spontaneously beating cardiomyocytes,correlating with the expression of the cardiomyocyte transcription factor Gata4(P＜0.01).Targeted degradation of EZH2 using the small mole-cule drug MS1943 significantly inhibits the proliferation of induced cardiomyocytes,as evidenced by 5-e-thynyl-2'-deoxyuridine(EdU)incorporation assays(P＜0.01),and RT-qPCR reveals a marked in-crease in the expression of the proliferation inhibitor CDKN1A(P＜0.01).In summary,the high expres-sion of EZH2 in embryonic myocardial cells is associated with enhanced cell proliferation.The rapid loss of EZH2 expression postnatally correlates with the loss of proliferative capacity in cardiomyocytes,mark-ing it as a key indicator of cardiac terminal differentiation.

Objective This study sought to establish a non-alcoholic fatty liver disease(NAFLD)model in Wistar-SD hypercholesterolemia(WSHc)rats induced by a high-fat diet and to reveal the pathogenesis of NAFLD in these rats through the Srebp-1 gene.Methods After 2 weeks of dietary treatment,thirty 6-week-old WSHc rats were divided into High-fat control group,HFD+AAV no load group,and HFD+AAV group,with 10 rats in each group.The HFD+AAV no load group and HFD+AAV group were intravenously injected with a vector virus and an shRNA-containing virus,respectively.WSHc rats were fed with a normal fat diet as a normal control group.Serum levels of ALT,AST,TBIL,ALP,TBA,GLU,CHOL,and TG were measured every 2 weeks.After a further 8 weeks of feeding,the rats were euthanized and livers were excised for HE staining,Oil Red O staining,Masson staining,and Sirius red staining to observe the morphology,lipid deposition,and fibrosis of the liver tissues.RT-qPCR was performed to detect the expression of lipid metabolism-related genes namely Srebp-1,Aacs,FASN and LDLR in the livers.Furthermore,hepatocytes were isolated,cultured,and divided into a normal control group and a high-fat control group.Next,expression of the Srebp-1 gene was detected by RT-qPCR.Srebp-1 knockout(KO)hepatocytes were constructed,then TG content was detected and the lipid accumulation was observed by Oil Red O staining.Results After 10 weeks of high-fat diet treatment,serum ALT(P＜0.001),ALP(P＜0.001),TBA(P＜0.05),GLU(P＜0.001),and CHOL(P＜0.001)significantly increased in WSHc rats.Abnormal lipid deposition with formation of large vacuolar lipid droplets and fibrotic lesions in livers were observed.The mRNA expression of Srebp-1 noticeably increased in WSHc rats(P＜0.001).Moreover,compared with the high-fat control group,the ALT(P＜0.05)and GLU(P＜0.01)in the HFD+AAV group decreased,and liver lipid deposition and the formation of large vacuolar lipid droplets were alleviated.Expressions of genes such as FASN(P＜0.05)and LDLR(P＜0.01)were significantly upregulated.Additionally,there was a significant increase in the expression of Srebp-1 in hepatocytes of the high-fat control group(P＜0.001),while after Srebp-1 gene knockout,cellular TG levels decreased and the degree of lipid droplet aggregation was reduced.Conclusions The Srebp-1 gene plays a regulatory role in hepatic lipid metabolism and deposition,modulating the expression of lipid metabolism-related genes in WSHc rats with NAFLD.In vitro experiments demonstrated that downregulation of Srebp-1 alleviates lipotoxic injury in hepatocytes,suggesting that the development of NAFLD in WSHc rats is closely associated with abnormally high expressions of the Srebp-1 gene.

Objective:To evaluate the effect of hydrogen on lipopolysaccharide (LPS) and nigericin-induced pyroptosis in macrophages and the role of long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1).Methods:Human monocyte-derived macrophages THP-1 cells were cultured in vitro and divided into 4 groups ( n=25 each) using a random number table method: control group (group C), LPS and nigericin group (group LN), hydrogen-rich medium+ LPS and nigericin group (group H+ LN), and lentiviral transfection+ hydrogen-rich medium+ LPS-nigericin group (group LV+ H+ LN). THP-1 cells were cultured in the common culture medium for 24 h in group C. LPS at a final concentration of 100 ng/ml and nigericin 10 μmol/L were added to the culture medium, and the cells were incubated for 24 h in group LN. In group H+ LN, the culture medium was replaced with 0.6 mmol/L hydrogen-rich medium, then LPS at a final concentration of 100 ng/ml and nigericin 10 μmol/L were immediately added, and the cells were incubated for 24 h. In group LV+ H+ LN, THP-1 cells over-expressing NEAT1 stably after being transfected with lentivirus were used, then LPS at a final concentration of 100 ng/ml and nigericin 10 μmol/L were immediately added, and the cells were incubated for 24 h. Cell viability was detected by CCK-8 assay. Lactic dehydrogenase (LDH) release was assessed by colorimetric method. The amount of LDH released was measured by colorimetry. The concentrations of interleukin-1beta (IL-1β) and IL-18 in culture medium were measured by enzyme-linked immunosorbent assay. The pyroptotic rate was detected by flow cytometry. The expression of nucleotide-binding oligomerization domain-like receptor-containing pyrin domain 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1 and gasdermin D (GSDMD) was detected by Western blot. The expression of NEAT1 gene was determined by quantitative real-time polymerase chain reaction. Results:Compared with group C, the cell viability was significantly decreased, the amount of LDH released, concentrations of IL-1β and IL-18, and pyroptotic rate were increased, and the expression of NEAT1 gene, NLRP3, ASC, caspase-1 and GSDMD was up-regulated in group LN ( P<0.05). Compared with group LN, the cell viability was significantly increased, the amount of LDH released, concentrations of IL-1β and IL-18, and pyroptotic rate were decreased, and the expression of NEAT1 gene, NLRP3, ASC, caspase-1 and GSDMD was down-regulated in group H+ LN ( P<0.05). Compared with group H+ LN, the cell viability was significantly decreased, the amount of LDH released, concentrations of IL-1β and IL-18, and pyroptotic rate were increased, and the expression of NEAT1 gene, NLRP3, ASC, caspase-1 and GSDMD was up-regulated in group LV+ H+ LN ( P<0.05). Conclusions:Hydrogen can ameliorate LPS and nigericin-induced pyroptosis in macrophages, and the mechanism may be associated with down-regulating the expression of lncRNA NEAT1.