OBJECTIVE To analyze the chemical constituents and absorbed prototype components in blood of Zhenyang jiuxin decoction， and explore its potential active substances in the treatment of chronic heart failure （CHF）. METHODS SD rats were divided into a blank group （distilled water） and administration groups with blood collection at 0， 15， 30 and 60 min after dosing （14.96 g/kg calculated by crude drug）， with 2 rats in each group. Intragastric administration was conducted once every 12 hours for 3 consecutive days. After the last administration， rat blood was collected to prepare drug-containing serum. UPLC-Q-Exactive Orbitrap HRMS combined with the Global Natural Products Social Molecular Networking technology was adopted to identify the chemical constituents of Zhenyang jiuxin decoction and the absorbed prototype components in blood in drug-containing serum. Moreover， network pharmacology， molecular docking and molecular dynamics simulation were used to predict the potential active components and action targets for CHF treatment. RESULTS A total of 116 chemical constituents were identified from Zhenyang jiuxin decoction， including flavonoids （29 species）， terpenoids （26 species）， saponins （22 species） and other compounds. Twenty absorbed prototype components in blood were detected in drug-containing serum， including icariin， ginsenoside Rg 1 and atractylenolide Ⅰ. Six key active components （icariin， ginsenoside Rg 1 ， atractylenolide Ⅰ， hexadecanamide， etc.） and six core k ey targets such as glycogen synthase kinase-3β （GSK-3β）， amyloid precursor protein （APP） and epidermal growth factor receptor （EGFR） were screened out via network pharmacology. Molecular docking results showed that all key active components had favorable binding activity with core targets； among them， icariin had the strongest binding capacity to APP. Molecular dynamics simulation verified that the complex formed by icariin and APP possessed excellent stability. CONCLUSIONS The potential active substances of Zhenyang jiuxin decoction against CHF are icariin， ginsenoside Rg₁， atractylenolide Ⅰ and other ingredients， which act on APP， EGFR， GSK-3β and other targets. APP may serve as one of the important action targets of icariin.

OBJECTIVE To analyze the chemical constituents and absorbed prototype components in blood of Zhenyang jiuxin decoction， and explore its potential active substances in the treatment of chronic heart failure （CHF）. METHODS SD rats were divided into a blank group （distilled water） and administration groups with blood collection at 0， 15， 30 and 60 min after dosing （14.96 g/kg calculated by crude drug）， with 2 rats in each group. Intragastric administration was conducted once every 12 hours for 3 consecutive days. After the last administration， rat blood was collected to prepare drug-containing serum. UPLC-Q-Exactive Orbitrap HRMS combined with the Global Natural Products Social Molecular Networking technology was adopted to identify the chemical constituents of Zhenyang jiuxin decoction and the absorbed prototype components in blood in drug-containing serum. Moreover， network pharmacology， molecular docking and molecular dynamics simulation were used to predict the potential active components and action targets for CHF treatment. RESULTS A total of 116 chemical constituents were identified from Zhenyang jiuxin decoction， including flavonoids （29 species）， terpenoids （26 species）， saponins （22 species） and other compounds. Twenty absorbed prototype components in blood were detected in drug-containing serum， including icariin， ginsenoside Rg 1 and atractylenolide Ⅰ. Six key active components （icariin， ginsenoside Rg 1 ， atractylenolide Ⅰ， hexadecanamide， etc.） and six core k ey targets such as glycogen synthase kinase-3β （GSK-3β）， amyloid precursor protein （APP） and epidermal growth factor receptor （EGFR） were screened out via network pharmacology. Molecular docking results showed that all key active components had favorable binding activity with core targets； among them， icariin had the strongest binding capacity to APP. Molecular dynamics simulation verified that the complex formed by icariin and APP possessed excellent stability. CONCLUSIONS The potential active substances of Zhenyang jiuxin decoction against CHF are icariin， ginsenoside Rg₁， atractylenolide Ⅰ and other ingredients， which act on APP， EGFR， GSK-3β and other targets. APP may serve as one of the important action targets of icariin.

Objective To explore the association between non-high density lipoprotein cholesterol(non-HDL-C)and total MRI burden in cerebral small vessel disease(CSVD)patients.Methods A total of 303 inpatients(≥60 years old)admitted in our department from January 2021 to July 2024 were recruited,and divided into 0-burden score group(108 cases),1-burden score group(61 cases),2-burden score group(66 cases),3-burden score group(35 cases),and≥4-burden score group(33 cases)according to the total CSVD burden.The association between non-HDL-C and to-tal MRI burden was analyzed by binary logistic regression analysis.Results The levels of TC and non-HDL-C were gradually increased with increment of 0-MRI burden score in the 0-,1-,2-,3-and ≥4-burden score groups in turn(P＜0.01).The non-HDL-C level was significantly higher in the 3-than the 0-burden score group(P=0.001),and in the 2-,3-and ≥4-than the 1-burden score group(P＜0.05).The total CSVD MRI burden was positively correlated with the non-HDL-C level(P=0.001).After adjustment of confounding factors such as age,gender,hypertension,dia-betes and hyperlipidemia,non-HDL-C was still an independent risk factor for CSVD(OR=2.869,95％CI:1.012-8.136,P=0.047).Conclusion Higher non-HDL-C is strongly associated with in-creased total CSVD MRI burden in the elderly,and it can serve as an early intervention indicator for CSVD.

Objective To investigate the inhibitory effect of Scutellaria baicalensis combined with 5-Fu on Lewis tumor bearing mouse lung cancer based on the JAK2/STAT3 signaling pathway.Methods To detect the changes in body mass,food intake and tumor volume of Lewis tumor-bearing mice after intervention of Scutellaria baicalensis(20 mg/kg)combined with 5-Fu.Pathological changes in tumor tissue were observed by HE staining,expression levels of proliferation related protein Ki67 were observed by immunohistochemical staining,changes in cell apoptosis levels in tumor tissue were observed by TUNEL staining,and changes in expression levels of JAK2,p-JAK2,STAT3,and p-STAT3 proteins in tumor tissue were observed by immunohistochemical staining.Results Compared with the model group,the tumor volume of mice after combined intervention significantly decreased(P＜0.01)and body mass increased(P＜0.05),but there was no significant change food intake.The expression of proliferation related protein Ki67 in tumor tissue was significantly reduced,and the number of apoptotic cells labeled with TUNEL was significantly increased;The expression of p-JAK2 and p-STAT3 proteins is elevated.Conclusions Scutellaria baicalensis decoction can inhibit the JAK2/STAT3 signaling pathway and increase the inhibitory effect of 5-Fu on mouse lung cancer.

Objective: To assess the association between Life eight ( LE8) scores and diabetes mellitus ( DM) ， and to examine the mediating effect of Methylmalonic acid (MMA). Methods: Based on cross-sectional data from the 2011—2014 National Health and Nutrition Examination Survey (NHANES) ，weighted multivariable logistic regression analyses were conducted to assess the association between the LE8 score and DM．A mediation model was further constructed to evaluate the mediating effect of MMA． Results: The weighted multivariable logistic regression analysis showed a significant negative correlation between LE8 score and the risk of DM．After adjusting for poten- tial confounders，a 1-point increase in LE8 was associated with a 7% reduction in DM risk ( OR = 0. 93，95% CI: 0. 92－0. 93，P = 0. 000 1) ．In contrast，the level of circulating MMA did not show a statistically significant rela- tionship with DM risk ( OR = 0. 99，95% CI: 0. 89 －1. 10，P = 0. 886 8) ．Further subgroup analysis by age re- vealed that in participants under 60 years of age，circulating MMA levels were positively associated with DM risk ( OR = 1. 39，95% CI: 1. 19 －1. 62 ，P ＜0. 000 1 ) ． Mediation analysis indicated that circulating MMA levels played a partial mediating role in the relationship between LE8 and DM，with a mediation ratio of 1. 5% (P < 0. 000 1) ． Conclusion High LE8 scores significantly reduce the risk of DM ，and circulating MMA levels may play a role in this，particularly among individuals younger than 60 years (individuals＜60 years of age

ObjectiveTo investigate the mechanism of Si Junzitang in treating liver injury in rats with spleen Qi deficiency syndrome based on transcriptomics and to experimentally verify its effects. MethodsSixty male SD rats were randomly divided into blank group， model group， low-dose Si Junzitang （6 g·kg^-1·d^-1）， medium-dose Si Junzitang group （12 g·kg^-1·d^-1）， high-dose Si Junzitang group （24 g·kg^-1·d^-1）， and natural recovery group， with 10 rats in each group. A composite multifactorial modeling method （forced swimming + intragastric administration of Xiao Chengqitang + irregular diet） was used to establish a spleen Qi deficiency model. After 30 days of continuous intervention， body weight and 3-hour food intake were measured， and macroscopic symptom scores for spleen Qi deficiency syndrome were evaluated. Serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） in each group were detected， and hematoxylin and eosin （HE） staining was used to observe histopathological changes in liver tissue. Transcriptome sequencing （RNA-Seq） was used to identify differentially expressed genes （DEGs） among the blank， model， and high-dose Si Junzitang groups. Gene ontology（GO） and Kyoto encyclopedia of genes and genome（KEGG） enrichment analyses were performed on the DEGs. Immunofluorescence （IF） and Western blot were used to detect NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein （ASC）， Caspase-1， and the N-terminal domain of gasdermin D （GSDMD-N）. Immunohistochemistry （IHC） was used to detect the expression of downstream inflammatory cytokines interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and interleukin-18 （IL-18）. ResultsCompared with the blank group， the model group showed significantly reduced body weight and 3-hour food intake， significantly increased macroscopic symptom scores， and elevated serum AST and ALT levels （P<0.01）， with mild inflammatory liver injury observed histologically. Compared with the model group， Si Junzitang at all doses significantly improved these parameters and alleviated liver injury in a dose-dependent manner （P<0.05，P<0.01）. RNA-Seq analysis revealed 1 254 DEGs between the blank and model groups， and 842 DEGs between the model and high-dose Si Junzitang groups. GO and KEGG enrichment analyses indicated that the NOD-like receptor signaling pathway was activated in liver injury associated with spleen Qi deficiency， suggesting that the NLRP3 inflammasome may be a key target. Results from IF， IHC， and Westernblot showed that compared with the blank group， the expression of NLRP3， ASC， Caspase-1， GSDMD-N， and the downstream inflammatory cytokines IL-1β， IL-6， and IL-18 were significantly increased in the model group （P<0.01）， while these levels were markedly decreased in the high-dose Si Junzitang group （P<0.01）. ConclusionSi Junzitang effectively improves mild inflammatory liver injury in rats with spleen Qi deficiency syndrome in a dose-dependent manner. Its mechanism may be associated with inhibition of the NLRP3/ASC/Caspase-1 signaling pathway， downregulation of the pyroptosis executioner protein GSDMD-N， and reduction of pyroptosis-related inflammatory cytokine release.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Objective:To analyze the cerebral hemodynamic characteristics of uremic patients complicated with depressive symptoms by transcranial color-coded Doppler(TCCD),and explore the correlation between cerebral hemodynamic indicators and uremia complicated with depressive symptoms.Methods:A total of 70 uremic patients received hemodialysis in our hospital from Dec 2022 to Dec 2023 were enrolled,in which 37 patients complicated with depressive symptoms were selected as the research group,and 40 patients without depressive symptoms were selected as the control group.Peak systolic velocity(PSV),end diastolic velocity(EDV),mean velocity(MV),and pulsatility index(PI)of bilateral middle cerebral artery(MCA)were compared.Binary logistic regression was used to analyze risk factors for uremia complicated with depressive symptoms,and receiver operating characteristic(ROC)curves were generated for key parameters.Results:There was no significant difference in PSV between the two groups(P＞0.05),while EDV and MV of bilateral MCA in the research group were lower but PI was higher than those in the control group(P＜0.05).Age was positively correlated with the depressive symptoms in uremic patients,while EDV,MV of bilateral MCA and left PSV were negatively correlated with depressive symptoms of uremic patients(P＜0.05).The elevated level of HCO3-in blood increased the risk of uremia complicated with depressive symptoms(OR=1.245,95%CI:1.024-1.513).When the left EDV was 41.25 cm/s,the predicted occurrence rate of depressive symptoms in uremic patients was 74.6%,with a specificity of 62%and a sensitivity of 85%.Conclusions:EDV and MV of bilateral MCA in patients with uremia complicated with depressive symptoms were lower than those in patients with uremia without depressive symptoms.Age,EDV and MV of bilateral MCA and PSV of left MCA were associated with depressive symptoms.Left EDV＜41.25 cm/s may serve as a hemodynamic marker for early clinical detection of depressive symptoms in uremia.TCCD can provide a reference for early clinical detection of uremic patients complicated with depressive symptoms.

Objective To investigate the inhibitory effect of Scutellaria baicalensis combined with 5-Fu on Lewis tumor bearing mouse lung cancer based on the JAK2/STAT3 signaling pathway.Methods To detect the changes in body mass,food intake and tumor volume of Lewis tumor-bearing mice after intervention of Scutellaria baicalensis(20 mg/kg)combined with 5-Fu.Pathological changes in tumor tissue were observed by HE staining,expression levels of proliferation related protein Ki67 were observed by immunohistochemical staining,changes in cell apoptosis levels in tumor tissue were observed by TUNEL staining,and changes in expression levels of JAK2,p-JAK2,STAT3,and p-STAT3 proteins in tumor tissue were observed by immunohistochemical staining.Results Compared with the model group,the tumor volume of mice after combined intervention significantly decreased(P＜0.01)and body mass increased(P＜0.05),but there was no significant change food intake.The expression of proliferation related protein Ki67 in tumor tissue was significantly reduced,and the number of apoptotic cells labeled with TUNEL was significantly increased;The expression of p-JAK2 and p-STAT3 proteins is elevated.Conclusions Scutellaria baicalensis decoction can inhibit the JAK2/STAT3 signaling pathway and increase the inhibitory effect of 5-Fu on mouse lung cancer.

Objective To explore the association between non-high density lipoprotein cholesterol(non-HDL-C)and total MRI burden in cerebral small vessel disease(CSVD)patients.Methods A total of 303 inpatients(≥60 years old)admitted in our department from January 2021 to July 2024 were recruited,and divided into 0-burden score group(108 cases),1-burden score group(61 cases),2-burden score group(66 cases),3-burden score group(35 cases),and≥4-burden score group(33 cases)according to the total CSVD burden.The association between non-HDL-C and to-tal MRI burden was analyzed by binary logistic regression analysis.Results The levels of TC and non-HDL-C were gradually increased with increment of 0-MRI burden score in the 0-,1-,2-,3-and ≥4-burden score groups in turn(P＜0.01).The non-HDL-C level was significantly higher in the 3-than the 0-burden score group(P=0.001),and in the 2-,3-and ≥4-than the 1-burden score group(P＜0.05).The total CSVD MRI burden was positively correlated with the non-HDL-C level(P=0.001).After adjustment of confounding factors such as age,gender,hypertension,dia-betes and hyperlipidemia,non-HDL-C was still an independent risk factor for CSVD(OR=2.869,95％CI:1.012-8.136,P=0.047).Conclusion Higher non-HDL-C is strongly associated with in-creased total CSVD MRI burden in the elderly,and it can serve as an early intervention indicator for CSVD.