OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure （CHF）. METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group， Qiangxin decoction low-dose and high-dose groups （12.25， 24.50 g/kg， calculated by crude drug）， and chemical medicine group （Sacubitril valsartan sodium tablets， 10.42 mg/kg）， with 10 rats in each group； control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication， the contents of N-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum and phosphatidic acid （PA） and cardiolipin （CL） in myocardial tissue were all detected； the pathological damage and collagen fibrosis of rat myocardial tissue were observed； the apoptosis of myocardial cells was determined； the ultrastructure of myocardial tissue was observed； the protein expressions of mitofusin 1 （Mfn1）， Mfn2， optic atrophy protein 1 （OPA1） and dynamin-related protein 1 （Drp1） were all detected in myocardial tissue. RESULTS Compared with control group，the serum content of NT-proBNP， apoptotic rate of myocardial cells， and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly； serum content of ATP，contents of PA and CL， and relative expressions of Mfn1， Mfn2 and L-OPA1 proteins were all significantly reduced （P＜0.05）. There were abnormal membrane tissue structure in various layers of myocardial tissue， degeneration and necrosis of myocardial cells， and severe fibrosis； the mitochondria were swollen， with reduced or absent cristae， and uneven matrix density. After intervention with Qiangxin decoction， the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats （excluding CL content in the Qiangxin decoction low- dose group） were significantly reversed （P＜0.05）； the pathological damage of myocardial tissue had significantly improved， fibrosis had significantly reduced， mitochondrial morphology tended to be normal， cristae had increased， and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats， thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis， the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure （CHF）. METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group， Qiangxin decoction low-dose and high-dose groups （12.25， 24.50 g/kg， calculated by crude drug）， and chemical medicine group （Sacubitril valsartan sodium tablets， 10.42 mg/kg）， with 10 rats in each group； control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication， the contents of N-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum and phosphatidic acid （PA） and cardiolipin （CL） in myocardial tissue were all detected； the pathological damage and collagen fibrosis of rat myocardial tissue were observed； the apoptosis of myocardial cells was determined； the ultrastructure of myocardial tissue was observed； the protein expressions of mitofusin 1 （Mfn1）， Mfn2， optic atrophy protein 1 （OPA1） and dynamin-related protein 1 （Drp1） were all detected in myocardial tissue. RESULTS Compared with control group，the serum content of NT-proBNP， apoptotic rate of myocardial cells， and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly； serum content of ATP，contents of PA and CL， and relative expressions of Mfn1， Mfn2 and L-OPA1 proteins were all significantly reduced （P＜0.05）. There were abnormal membrane tissue structure in various layers of myocardial tissue， degeneration and necrosis of myocardial cells， and severe fibrosis； the mitochondria were swollen， with reduced or absent cristae， and uneven matrix density. After intervention with Qiangxin decoction， the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats （excluding CL content in the Qiangxin decoction low- dose group） were significantly reversed （P＜0.05）； the pathological damage of myocardial tissue had significantly improved， fibrosis had significantly reduced， mitochondrial morphology tended to be normal， cristae had increased， and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats， thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis， the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

OBJECTIVE To systematically evaluate the incidence of anti-tuberculosis drug-induced liver injury （ATB-DILI） and its risk factors. METHODS PubMed， Embase， the Cochrane Library， Web of Science， China Knowledge Network， VIP， Wanfang data and China Biomedical Literature Database were searched to collect cohort studies and case-control studies on the incidence and risk factors of ATB-DILI from the establishment of the database to 31 May 2024. After screening literature， extracting data and evaluating the quality of literature， meta-analysis was performed using Stata 17.0 and RevMan 5.3 software. RESULTS A total of 26 literature involving 38 971 patients were included， of which 4 106 patients suffered from ATB-DILI. Meta-analysis showed that the incidence of ATB-DILI was 12.94% [95%CI （10.82%，15.06%）， P＜0.001]； subgroup analysis showed that the incidence of ATB-DILI in cohort studies， Chinese studies and pediatric patients was higher （P＜0.001）. Age≥60 years， abnormal body mass index， alcoholism， smoking， history of liver disease， hepatitis B surface antigen positivity， extrapulmonary tuberculosis， malnutrition， hypoproteinemia， cardiovascular disease， diabetes mellitus， systemic lupus erythematosus， no prophylactic use of hepatoprotective drugs， and high baseline alanine transaminase levels were risk factors for developing ATB-DILI （P＜0.05）. Sensitivity analysis and publication bias analysis showed that the results obtained in this study were relatively robust. CONCLUSIONS The incidence of ATB-DILI in tuberculosis patients is 12.94%. Age≥60 years， abnormal body mass index， alcoholism， smoking， history of liver disease， hepatitis B surface antigen positivity， extrapulmonary tuberculosis， malnutrition， hypoproteinaemia， cardiovascular disease， diabetes mellitus， systemic lupus erythematosus， non-prophylactic use of hepatoprotective medications， and high baseline levels of alanine transaminase are the risk factors for developing ATB-DILI.

Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

Objective To explore the value of ultrafast pulse wave velocity(UFPWV)technique for evaluating changes of carotid artery elasticity in Hashimoto thyroiditis(HT)patients with euthyroidism.Methods Conventional ultrasound and UFPWV for carotid artery were prospectively performed in 91 HT patients with euthyroidism(HT group)and 81 healthy subjects(control group).Clinical data and ultrasonic parameters were compared between groups.Spearman correlation analysis was performed to observe the correlations of carotid pulse wave velocity in end of systole(PWV-ES)with clinical indexes and other ultrasonic parameters in HT group.Multiple stepwise linear regression analysis was used to screen the independent impact factors of increased carotid PWV-ES in HT group.Results Significant differences of thyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TgAb),total cholesterol(TC),low density lipoprotein and neutrophil-lymphocyte ratio(NLR)were found between groups(all P＜0.05).The carotid PWV-ES in HT group was significantly higher than that in control group(P＜0.05),while no significant difference of carotid artery intima-media thickness(CIMT)nor carotid pulse wave velocity in beginning of systole(PWV-BS)was found between groups(both P＞0.05).Carotid PWV-ES in HT group was positively correlated with patients'age,body mass index,TPOAb,TC,triglyceride,NLR and CIMT(r=0.217-0.707,all P＜0.05).Patients'age,TPOAb and NLR were all independent impact factors of increased carotid PWV-ES in HT patients with euthyroidism(all P＜0.05).Conclusion UFPWV technique could be used to evaluate changes of carotid artery elasticity in HT patients with euthyroidism,among which PWV-ES was relatively sensitive.

Objective:To investigate the clinical efficacy and safety of amlodipine besylate and benazepril hydrochloride tablets (II) in the treatment of primary hypertension.Methods:A total of 280 patients with primary hypertension who were treated at Shougang Shuigang Hospital between June 2022 and June 2023 were selected as study subjects. A clinical case-control study was conducted, and the RAND function method was utilized to randomly allocate the subjects into four groups, each receiving a different treatment: amlodipine besylate group (Group A, n = 70), benazepril hydrochloride group (Group B, n = 70), compound formulation amlodipine besylate and benazepril hydrochloride tablets group (Group C, n = 71), and amlodipine besylate plus benazepril hydrochloride group (Group D, n = 69). Relevant therapeutic indicators (blood pressure compliance rate, changes in blood pressure values) and safety indicators (adverse reactions, medication adherence) were observed. Results:The blood pressure compliance rates of Group C and Group D were 91.5% (65/71) and 89.9% (62/69), respectively. There was no statistically significant difference between the two groups ( χ2 = 1.24, P = 0.143), but both were higher than the rates of 77.1% (54/70) and 74.3% (52/70) in Group A and Group B, respectively ( χ2 = 5.68, 4.86, P = 0.004, 0.012). Before treatment, there was no statistically significant difference in systolic and diastolic blood pressure among the four groups of patients (all P > 0.05). After treatment, there was a statistically significant decrease in both systolic and diastolic blood pressure among the four groups compared with their pre-treatment levels (all P < 0.05). Specifically, Group C and Group D exhibited significant reductions in blood pressure following treatment ( t = 4.35, 5.12, 7.25, 5.86, all P < 0.05). Meanwhile, there was no statistically significant difference in systolic blood pressure between Group C and Group D after treatment ( P > 0.05), while diastolic blood pressure was lower in Group C than Group D after treatment ( t = 6.01, P < 0.05). There was a significant downward trend observed in total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels (all P < 0.05). Notably, Group B and Group D reported higher incidences of dry cough, with 15 and 10 cases, respectively, compared with Group A and Group C, which had 1 and 3 cases, respectively. These differences were statistically significant ( χ2 = 4.25, 5.04, both P < 0.05). Furthermore, the treatment compliance rates for Group A, Group B, and Group C were 72.9% (51/70), 71.4% (50/70), and 74.6% (53/71), respectively, all exceeding the 46.4% (32/69) compliance rate of Group D. These differences were also statistically significant ( χ2 = 4.68, 5.24, 4.98, all P < 0.05). Conclusion:The clinical efficacy and safety of the compound formulation amlodipine besylate and benazepril hydrochloride tablets (II) in the treatment of primary hypertension are superior to those of single tablets and combination therapy.

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)pre-sents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2％dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2％ DSS-induced Rag1-/-mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage indepen-dently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned me-dium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

ObjectiveTo reveal the targets and molecular mechanisms of the action of Qiangxin Decoction （强心汤） for the treatment of chronic heart failure based on the combination of network pharmacology and molecular docking. MethodsThe active ingredients of Qiangxin Decoction were retrieved from TCMSP database， and the targets of chronic heart failure were screened by searching GeneCards， OMIM， TTD， PharmGkb， and DrugBank databases， and the intersections were taken to obtain the intersecting targets of Qiangxin Decoction for the treatment of chronic heart failure. STRING platform was used to construct the protein-protein interaction network （PPI）， Cytoscape 3.8.0 software was used to calculate the network topology to screen the core targets， and R 4.2.3 was used to construct the “active ingredient-target” network by analyzing the GO enrichment analysis and KEGG pathway enrichment analysis. AutoDock 1.5.7 was used for molecular docking to predict the binding performance of active ingredients and core targets. ResultsSeventy-five intersecting targets were identified for the treatment of chronic heart failure with Qiangxin Decoction， among which the core targets were estrogen receptor 1 （ESR1， degree value=7）， nuclear receptor coactivator 1 （NCOA1， degree value=8）， glucocorticoid receptor （NR3C1， degree value=7）， and nuclear receptor coactivator 2 （NCOA2， degree value=7）. GO enrichment analysis showed that the top 3 items with the smallest P value in molecular function were G protein-coupled amine receptor activity， postsynaptic neurotransmitter receptor activity， and neurotransmitter receptor activity （P＜0.01）； the top 3 items with the smallest P value in biological process were adenylyl cyclase-activated adrenergic receptor signaling pathway， adrenergic receptor signaling pathway， and adenylyl cyclase-regulated G protein-coupled receptor signaling pathway （P＜0.01）； the top 3 items with the smallest P values in cellular composition were components of the postsynaptic membrane， synaptic membrane， and presynaptic membrane （P＜0.01）. KEGG enrichment analysis showed that the top 5 key signaling pathways were neuroactive ligand-receptor interactions， calcium signaling pathway， dopaminergic synapses， cocaine addiction， and cyclic guanosine monophosphate-protein kinase G （cGMP-PKG） signaling pathway. The molecular docking results showed that lignans and isoflavones had lower binding energies and more structural stability with the four core targets （ESR1， NCOA1， NR3C1， NCOA2）. ConclusionThe treatment of chronic heart failure by Qiangxin Decoction was associated with neuroactive ligand-receptor interactions， calcium signaling pathway， dopaminergic synapses， chemoattractant-receptor activation， cGMP-PKG signaling pathway， lipids and atherosclerosis， and cAMP signaling pathway， and lignans and isoflavones may be the core active compounds in its treatment of chronic heart failure.

Humans ; Asthma/drug therapy* ; Biological Therapy

【Objective】 To establish and evaluate a nephelometric assay for the determination of immunoglobulin A (IgA) residues in human intravenous immunoglobulin(IVIG). 【Methods】 BN ProSpec^© automatic protein analyzer and its supporting immunoglobulin A determination kit (nephelometry) produced by German Siemens and the national standard of human IgA were used to establish the nephelometric assay to determine IgA residue in test products and verify the methodology. The test products include IVIG (pH4) prepared by low-temperature ethanol protein separation process and a novel IVIG prepared by chromatography. 【Results】 The average deviation of three calibration curves for IgA residues determination by the nephelometric assay were 1.08%, 0.95% and 1.54%,, and the three deviations of the quality control were 4.00%, -2.30% and -0.20%, respectively, which indicated good calibration and quality control. In the specificity test, the average recovery rates of IgA for reference substance 1 containing 100g/L maltose and reference substance 2 containing 20g/L glycine were 102.7% and 105.8%, respectively. The relative standard deviation (RSD) values of the repeatability tests of the two test products were 3.9% and 1.9%, and the RSD values of the intermediate precision test were 3.6% and 2.3%, respectively.The difference values at each time point in the durability test of test products′ storage time were all less than 10%, and the RSD values of the two test products in the durability test of kits of different batches were 2.8% and 2.2%, respectively. In the accuracy test, the average recovery rates of IVIG (pH4) added to the standard were 94.2%, 101.7% and 96.2%, respectively, and the average recovery rates of the novel IVIG added to the standard were 102.8%, 106.3% and 99.7%, respectively. The average recovery rate of the limit quantification test was 101.0%, and the RSD was 4.0%. 【Conclusion】 Nephelometric assay has the advantages of strong specificity, high precision and accuracy, good repeatability, simple and rapid operation, and automation, and can be used for the determination of IgA residue in IVIG (pH4) and novel IVIG products.