OBJECTIVE To investigate the effects and mechanisms of Buyang huanwu decoction （BYHWD） and its active fractions in ameliorating non-alcoholic fatty liver disease. METHODS BYHWD and its effective fractions obtained through ethanol precipitation， as well as 30% ethanol， 50% ethanol， and 75% ethanol fractions （namely， the CC effective fraction， 30YC effective fraction， 50YC effective fraction， and 75YC effective fraction）， were prepared. These preparations were administered to rats via intragastric administration to prepare corresponding drug-containing serum （blank serum and simvastatin-containing serum were prepared using the same protocol）. Human L02 hepatocytes were divided into control group， model group， simvastatin-containing serum group， BYHWD-containing serum group， CC-containing serum group， 30YC-containing serum group， 50YC-containing serum group， and 75YC-containing serum group. Except for the control group， other groups were given 0.2 mol/L oleic acid for 24 h to induce a lipid accumulation model， and then intervened with 20% drug-containing serum/blank serum for 24 h. The lipid deposition in cells was observed， and the proportion of lipid droplet area was calculated； the levels of triglycerides （TG） and indicators of oxidative stress [malondialdehyde （MDA）， superoxide dismutase （SOD）] as well as liver function [alanine amino- transferase （ALT）， aspartate amino-transferase （AST）] in cells were detected； protein and mRNA expressions of AMP-activated protein kinase （AMPK）/sterol regulatory element-binding protein-1 （SREBP-1）/glycerol-3-phosphate acyltransferase （GPAT） signaling pathway were also measured. RESULTS Compared with the control group， cells in the model group exhibited severe cellular steatosis， with a significantly increased proportion of lipid droplet area， as well as the elevated levels of TG， ALT， AST， and MDA in cells， along with significantly up-regulated mRNA and protein expression levels of SREBP-1 and GPAT （P＜0.05）. The level of SOD， mRNA expression of AMPK， as well as the protein phosphorylation level of AMPK were decreased significantly （P＜0.05）. Compared with the model group， cellular steatosis was alleviated in all drug-containing serum groups， and the levels of most of the aforementioned quantitative indicators were significantly reversed （P＜0.05）. CONCLUSIONS BYHWD and its active fractions can exert a therapeutic effect on improving non-alcoholic fatty liver disease by regulating the AMPK/SREBP-1/GPAT signaling pathway， inhibiting oxidative stress responses， and reducing lipid deposition.

ObjectiveGastrodia elata has evolved ecological types with shortened rhizome internodes and diversified flower and fruit coloration in response to different altitudes. Studying the genetic mechanisms of different ecotype germplasm is significant for guiding variety breeding in different cultivation areas. MethodsThe bHLH gene family was identified based on the whole-genome datasets of G. elata f. elata and G. elata f. glauca. Subsequently， the gene family members were subject to analysis， including gene structure， chromosomal localization， cis-acting elements， gene synteny， and phylogeny. Combined with transcriptome data and quantitative Real-time PCR， the expression patterns of bHLH genes in the stems of the different G. elata ecotype germplasm were analyzed. Finally， correlation analysis was conducted between gene expression patterns and color to obtain the key bHLH genes regulating the color formation of stem. ResultsA total of 63 bHLH genes were identified in both G elata f. elata and G. elata f. glauca， unevenly distributed across 17 chromosomes and clustered into 16 subfamilies， with significant expansion in some family members. Obvious inversions of bHLH genes on the same chromosome and interchromosomal translocations were detected in the two ecotype germplasm. Among these genes， 12 bHLH genes （such as bHLH62-3 and bHLH74） were associated with the bright yellow color of G elata f. elata stem， while 9 bHLH genes （such as PIL13， UNE12， and bHLH130） were correlated with the red color of G. elata f. glauca stem. Compared to G. elata f. glauca， the bHLH48 expression level was significantly higher in flowers and scale leaves of G elata f. elata， and the bHLH62-3 expression level was significantly higher in all organs of G elata f. elata. ConclusionsFunctional pathway divergence of the bHLH family members has occurred across different chromosomes in G elata f. elata and G. elata f. glauca. Through synergism or antagonism with other genes， 21 bHLH genes participate in the coloration metabolic pathway regulation of stems， flowers， and fruits. Specifically， bHLH62-3 is involved in regulating stem color differentiation in the anthocyanin biosynthesis pathway of G. elata， thus relevant to the color formation of stem. Additionally， GebHLH48 positively regulates flowering-related pathways to promote the early-flowering phenotype of G. elata f. elata. These findings have laid the foundation for analyzing the genetic regulatory mechanisms underlying the color formation of the G. elata stem.

ObjectiveGastrodia elata has evolved ecological types with shortened rhizome internodes and diversified flower and fruit coloration in response to different altitudes. Studying the genetic mechanisms of different ecotype germplasm is significant for guiding variety breeding in different cultivation areas. MethodsThe bHLH gene family was identified based on the whole-genome datasets of G. elata f. elata and G. elata f. glauca. Subsequently， the gene family members were subject to analysis， including gene structure， chromosomal localization， cis-acting elements， gene synteny， and phylogeny. Combined with transcriptome data and quantitative Real-time PCR， the expression patterns of bHLH genes in the stems of the different G. elata ecotype germplasm were analyzed. Finally， correlation analysis was conducted between gene expression patterns and color to obtain the key bHLH genes regulating the color formation of stem. ResultsA total of 63 bHLH genes were identified in both G elata f. elata and G. elata f. glauca， unevenly distributed across 17 chromosomes and clustered into 16 subfamilies， with significant expansion in some family members. Obvious inversions of bHLH genes on the same chromosome and interchromosomal translocations were detected in the two ecotype germplasm. Among these genes， 12 bHLH genes （such as bHLH62-3 and bHLH74） were associated with the bright yellow color of G elata f. elata stem， while 9 bHLH genes （such as PIL13， UNE12， and bHLH130） were correlated with the red color of G. elata f. glauca stem. Compared to G. elata f. glauca， the bHLH48 expression level was significantly higher in flowers and scale leaves of G elata f. elata， and the bHLH62-3 expression level was significantly higher in all organs of G elata f. elata. ConclusionsFunctional pathway divergence of the bHLH family members has occurred across different chromosomes in G elata f. elata and G. elata f. glauca. Through synergism or antagonism with other genes， 21 bHLH genes participate in the coloration metabolic pathway regulation of stems， flowers， and fruits. Specifically， bHLH62-3 is involved in regulating stem color differentiation in the anthocyanin biosynthesis pathway of G. elata， thus relevant to the color formation of stem. Additionally， GebHLH48 positively regulates flowering-related pathways to promote the early-flowering phenotype of G. elata f. elata. These findings have laid the foundation for analyzing the genetic regulatory mechanisms underlying the color formation of the G. elata stem.

Aim To investigate the effect of total gly-cosides of peony on Th17/Treg balance in autoimmune thyroiditis(AIT)by regulating miR-155 expression.Methods Sixty female SD rats were randomly divided into a blank control group,a model group,high-dose,medium,and low-dose groups of total glycosides of peony,and a Western medicine control group(seleni-um yeast group).After eight weeks of modeling,the pathological changes in thyroid tissue were observed by HE staining,the expression of miR-155 in the thyroid of rats was detected by RT-PCR,the targeting effect of miR-155 on SOCS1 was verified by dual luciferase method,and the levels of TGAb,TPOAb,IL-10,and IL-17 in peripheral serum were detected by ELISA,the expression of thyroid SOCS1 was detected by WB,and the proportion of Th17 and Treg in CD4+cells of the spleen was detected by flow cytometry.Results Com-pared with the blank group,the expression of miR-155 in the thyroid gland of the model group rats significant-ly increased,and the serum levels of TGAb,TPOAb,and IL-17 significantly increased,with an increase in the proportion of Th17;the IL-10 level significantly decreased,the proportion of Treg decreased,and the expression of SOCS1 protein decreased,with statistical significance(P＜0.01);compared with the model group,the high,medium,and low dose groups of total glycosides of peony and selenium yeast groups showed a decrease in miR-155 expression,a decrease in TGAb,TPOAb,IL-17 levels,a decrease in Th17 pro-portion,an increase in IL-10 level,an increase in Treg proportion,and an increase in SOCS1 expression,all with statistical significance(P＜0.01).Moreover,the improvement in the medium dose group of total glyco-sides of peony was more significant.Conclusion To-tal glycosides of peony downregulate miR-155 expres-sion,regulate Th17/Treg balance,alleviate inflamma-tory response,and exert immune regulatory effects.

Objective:To investigate the molecular markers involved in death related to acute myocardial infarction (AMI) and provide new targets for early intervention.Methods:Consecutive patients who hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from January 2017 to December 2021 and diagnosed with AMI were enrolled. The clinical factors and markers associated with in-hospital death after AMI were analyzed. In addition, patients diagnosed with AMI hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from September 2022 to April 2023 were enrolled. We prospectively analyzed the plasma protein of death related to AMI via Olink Precision Proteomics based on proximity extension assay (PEA) technology.Results:In the retrospective study, 2 325 patients with AMI were analyzed, including 75 patients in the in-hospital death group and 2 250 subjects in the survival group. The overall mortality rate during hospitalization was 3.23% (75/2325). The patients in the death group were older: 72 (64, 80) years vs. 63 (55, 71) years. And Interleukin-6 (IL-6), hypersensitive C-reactive protein (Hs-CRP), leukocyte counts and neutrophil counts were markedly higher in the death group than those in the survival group: 69.0 (26.7, 136.6) ng/L vs. 18.2 (9.4, 36.5) ng/L, 45.7 (28.7, 50.5) mg/L vs. 5.5 (2.0, 17.2) mg/L, 12.0 (9.8, 14.1) ×10 9/L vs. 8.9 (7.2, 11.2) × 10 9/L, 9.8 (7.8, 12.1) ×10 9/L vs. 6.5(4.7, 8.8) ×10 9/L ( P<0.01). In this prospective study, 86 patients with AMI were analyzed. 61 proteins including Insulin-like growth factor-binding protein 1, 2 (IGFBP-1, IGFBP-2), Chitotriosidase-1 (CHIT1), Complement component C1q receptor (CD93) were independently associated with in-hospital death related to AMI ( P<0.05). The differential proteins were mainly enriched in inflammatory response, cell adhesion, cytokine signaling pathway and apoptosis. Moreover, 22 proteins including Urokinase plasminogen activator surface receptor (U-PAR), Trefoil factor 3 (TFF3), Perlecan (PLC), Growth differentiation factor 15 (GDF-15), Junctional adhesion molecule A (JAM-A) were plotted according to a logistic regression model, and the area under the curve (AUC) was more than 0.9, showing the high accuracy in predicting in-hospital death after AMI. Conclusions:Molecular markers of the inflammatory response, cell adhesion, cell growth and apoptosis might be involved in death related to AMI, which provides new targets for early intervention.

Objective To investigate the therapeutic efficacy of combination of dapagliflozin and sacubitril valsartan on patients with heart failure(HF)complicated with type 2 diabetes mellitus(T2DM).Methods A retrospective study was conducted on 160 patients with HF and T2DM admitted to our hospital from November 2020 to November 2022.According to drug treatment,they were classified into sacubitril valsartan group(80 cases)and combined group(dapagliflozin combined with sacubitril valsartan,80 cases).After 3 months of treatment,the differences were compared between the two groups in following aspects:blood glucose fluctuations,left ventricular diastolic function,and vascular endothelial function,and the incidence of adverse events after 1 year of follow-up.Results After 3 months of treatment,serum FPG,2 h-PG and HbAlc levels,and MAGE,LAGE,MODD and SDBG values were significantly lower in the combined group than the sacubitril valsartan group(P＜0.05,P＜0.01).The combined group had obviously higher e'and LVEF values while lower LVMI and BNP levels than the other group(P＜0.05,P＜0.01).After 3 months of treatment,NO and FMD were notably higher[96.18±6.70 ng/L vs 92.34±6.85 ng/L,P=0.000;(8.25±1.16)％vs(7.72±1.28)％,P=0.007],while ET-1(59.72±4.95 ng/L vs 63.90±4.63 ng/L,P=0.000)was remarkably lower in the combined group than the sacubitril valsartan group.There was no statistical significance in the total incidence of adverse events between both groups after 1 year of follow-up(P＞0.05).Conclusion The combination of dapagliflozin and sacubitril valsartan has a significant improvement effect on blood glucose,left ventricular diastolic function and vascular endothelial function in T2DM patients with HF,with good drug safety.

Objective To systematically evaluate the level of proteus mirabilis(PM)infection in patients with rheumatoid arthritis(RA)and to investigate its potential association with the development of RA.Methods Based on Meta-analysis of observational studies in epidemiology and preferred reporting items for systematic review and Meta-analysis guide,a comprehensive search of PubMed,Web of Science and Embase databases was conducted to screen relevant literature published up to December 2024 for studies comparing the levels of anti-PM antibodies between RA patients and healthy populations,and the quality of the included studies was assessed by using the Newcastle-Ottawa scale.Heterogeneity among studies was assessed by Q-test and I2-test,and accordingly,fixed-effects or random-effects models were selected,and the robustness of the results was assessed by sensitivity analyses,Begg's test,and clipping and patching method.Results Finally,18 eligible articles were included,involving 753 RA patients and 716 healthy controls.The total antibody levels[weighted mean difference(WMD)=0.86,95％CI:0.38-1.34,I2=98.3％,P=0.000]and IgA antibody levels(WMD=0.17,95％CI:0.06-0.28,I2=96.7％,P=0.000)of RA patients were higher than those of healthy controls,and subgroup analyses revealed significant heterogeneity among geographic regions and testing methods.Conclusion Prevention and treatment of PM infections may be a complementary strategy for RA management and provide evidence-based support for the"PM antigen-genitourinary tract mucosa-autoimmunity"pathology hypothesis.

Objective:To culturally adapt the eHealth Literacy Questionnaire (eHLQ) into Chinese and validate its reliability and validity in stroke patients, so as to provide a basis for comprehensive evaluation of electronic health literacy in stroke patients.Methods:From May to September 2024, the Brislin translation model was adopted for translation, and the expert consultation was used for cultural adaptation. Followed by preliminary testing to finalize the Chinese version of eHLQ. A convenience sample of the stroke patients was recruited from Beijing Tiantan Hospital, Capital Medical University and Tianjin Huanhu Hospital between October 2024 to February 2025 to conduct a cross-sectional study and evaluate the scale's reliability and validity.Results:Finally, 415 stroke patients were included, with 284 males and 131 females, aged (61.26 ± 9.75) years. The Chinese eHLQ comprised 7 dimensions and 35 items. The item-level content validity index ranged from 0.875 to 1.000, and the scale-level content validity index of universal agreement was 0.857. Exploratory factor analysis revealed KMO value of 0.922, with a cumulative variance contribution rate of 68.90% and factor loading ranging from 0.515 to 0.803. Confirmatory factor analysis demonstrated satisfactory model fit indices: χ2/ df was 1.639, incremental fit index was 0.913, Tucker-Lewis index was 0.902, comparative fit index was 0.912, goodness-of-fit index was 0.812, and root mean square error of approximation was 0.056. The overall Cronbach α coefficient was 0.941, with subscale Cronbach α ranging from 0.825 to 0.894. The test-retest reliability was 0.954. Conclusions:The Chinese version of the eHLQ exhibits excellent reliability and validity, serving as an effective tool for assessing eHealth literacy among stroke patients in China.

Objective To investigate the therapeutic efficacy of combination of dapagliflozin and sacubitril valsartan on patients with heart failure(HF)complicated with type 2 diabetes mellitus(T2DM).Methods A retrospective study was conducted on 160 patients with HF and T2DM admitted to our hospital from November 2020 to November 2022.According to drug treatment,they were classified into sacubitril valsartan group(80 cases)and combined group(dapagliflozin combined with sacubitril valsartan,80 cases).After 3 months of treatment,the differences were compared between the two groups in following aspects:blood glucose fluctuations,left ventricular diastolic function,and vascular endothelial function,and the incidence of adverse events after 1 year of follow-up.Results After 3 months of treatment,serum FPG,2 h-PG and HbAlc levels,and MAGE,LAGE,MODD and SDBG values were significantly lower in the combined group than the sacubitril valsartan group(P＜0.05,P＜0.01).The combined group had obviously higher e'and LVEF values while lower LVMI and BNP levels than the other group(P＜0.05,P＜0.01).After 3 months of treatment,NO and FMD were notably higher[96.18±6.70 ng/L vs 92.34±6.85 ng/L,P=0.000;(8.25±1.16)％vs(7.72±1.28)％,P=0.007],while ET-1(59.72±4.95 ng/L vs 63.90±4.63 ng/L,P=0.000)was remarkably lower in the combined group than the sacubitril valsartan group.There was no statistical significance in the total incidence of adverse events between both groups after 1 year of follow-up(P＞0.05).Conclusion The combination of dapagliflozin and sacubitril valsartan has a significant improvement effect on blood glucose,left ventricular diastolic function and vascular endothelial function in T2DM patients with HF,with good drug safety.

Objective To systematically evaluate the level of proteus mirabilis(PM)infection in patients with rheumatoid arthritis(RA)and to investigate its potential association with the development of RA.Methods Based on Meta-analysis of observational studies in epidemiology and preferred reporting items for systematic review and Meta-analysis guide,a comprehensive search of PubMed,Web of Science and Embase databases was conducted to screen relevant literature published up to December 2024 for studies comparing the levels of anti-PM antibodies between RA patients and healthy populations,and the quality of the included studies was assessed by using the Newcastle-Ottawa scale.Heterogeneity among studies was assessed by Q-test and I2-test,and accordingly,fixed-effects or random-effects models were selected,and the robustness of the results was assessed by sensitivity analyses,Begg's test,and clipping and patching method.Results Finally,18 eligible articles were included,involving 753 RA patients and 716 healthy controls.The total antibody levels[weighted mean difference(WMD)=0.86,95％CI:0.38-1.34,I2=98.3％,P=0.000]and IgA antibody levels(WMD=0.17,95％CI:0.06-0.28,I2=96.7％,P=0.000)of RA patients were higher than those of healthy controls,and subgroup analyses revealed significant heterogeneity among geographic regions and testing methods.Conclusion Prevention and treatment of PM infections may be a complementary strategy for RA management and provide evidence-based support for the"PM antigen-genitourinary tract mucosa-autoimmunity"pathology hypothesis.