Objective To investigate dynamic changes of vascular endothelial growth factor(VEGF)and endostatin(ES)in guinea.Pig of asthma and its effect on airway remodeling.Methods 40 guinea-pigs were randomly divided into normal control group(C),NS group(N),3d asthma group(A1),7d asthma group(A2)and 21d asthma group(A3),8 pigs ofeach group·Nothing was done on C Group guinea.Pigs.N group were intraperitoneal injected 2ml NS on the Ist day and the 8th day.NS inhalation started on the 15th day,1 time every day,3-5rain for each times,lasted for 3 day.Al,A2 and A3 Group were injected with 10rag ovalbumin(OVA),which made of aluminum hydroxide 20mg suspension in place of2ml NS,in place ofNS inhalation for3d,7d and 21d.At the end of24h-shot line after anesthesia BAL.Enzynle-linked immunosorbent(ELISA)was used to determine the concentration of VEGF and ES in bronchoalveolar lavnge fluid collection(BALF).Image analysis was used to determine airway circumference(Pi),outer circumference(Pe),and calculate the wall area(WA),airway smooth muscle area(SMC-A),airway smooth muscle cells(N).WA,SMC-A and N were standardized by Pi.Results With the extension of the duration of asthmatic guinea.Pigs,WA/Pi,SMC-A/Pi,N/Pi and concentration of VEGF in the airway were increased.Compared with group C and N,SMC-A/Pi,N/Pi and concentration of VEGF in asthma group were siguitlcanfly different.WA/Pi were siguificanfly different in A2 group and A3 group.The relation of the concentration of VEGF in Asthma guinea-pigs airway and WA/Pi was positive correlation.VEGF/ES and WA/Pi was highly positive correlated.Conclusions VEGF/ES inlbalance may play all important role in the airway remodeling of asthmatic guinea-pigs.

Objective To investigate the antithrombosis effects of Buyang Huanwu Decoction(BHD) and its active fractions on cultured vascular endothelial cells(VEC) following the stimulation of thrombin and their mechanism.Methods The human umbilicus vein endothelial cells(ECV 304) were cultured in media containing 10 U/mL thrombin and different dosese of drugs.The levels of tPA and PAI-1 were detected by ELISA,the expression of TF,TFPI,and TM mRNA was measured by RT-PCR,and the expression of PKC? was examined by immunohistochemical staining 24 h later.Results Compared to the control without any treatment,the release of tPA was increased evidently(P0.05).Compared to the data after the mere stimulus of thrombin,each dose of BHD increased the release of tPA(P0.05);And glycoside(1.25 mg/mL) increased the release of tPA(P

Objective To investigate the level change of interleukin-4(IL-4) and IL-12, and their effect on airway inflammation in rat asthma. Methods Rat model of asthma was set up by ovalbumin sensitization. Total cell count and eosinophil count in branchoalveolar lavage fluid(BALF) were performed, and levels of IL-4 and IL-12 in BALF were measured by ELISA. Results After ovalbumin sensitization, airway occurred obvious inflammation. Eosinophil count began increasing at 1 hour after sensitization, obviously increased at 8 hours, reached a maximum at 24 hours, started declining at 96 hours, and decreased to near normal range at 7 to 14 days. The changes of total cell count had the same tendency as eosinophil count changes. The level of IL-4 in BALF elevated at 1h after sensitization, reached a maximun at 8 to 96 hours, and reduced to near normal level at 7 to 14 days. The changes of IL-12 in BALF had the same tendency as IL-4 level changes. Eosinophil count was positively related with IL-4 level(r=0.74,P0.05). There was a close correlation between IL-4/IL-12 ratio and eosinophil count (r=0.85,P

Objective:To evaluate the left ventricular myocardial strain in patients with light chain cardiac amyloidosis (AL-CA) with normal left ventricular ejection fraction (LVEF) by three-dimensional speckle tracking imaging(3D-STI), and to explore the clinical value of 3D-STI in predicting the prognosis of AL-CA patients with normal LVEF.Methods:A total of 80 patients with AL-CA and LVEF≥50% were retrospectively analyzed in the Xijing Hospital of Air Force Military Medical University from October 2014 to May 2020.According to whether the patients had endpoint events, they were divided into endpoint event group and non-endpoint event group. The clinical data, conventional echocardiographic parameters, 3D-STI related parameters and follow-up results were collected. Cox regression proportional hazards model was used to analyze the survival status of AL-CA patients with univariate and multivariate regression analyses, in order to find the relevant indicators of conventional echocardiography and 3D-STI to predict adverse events.Results:All patients were followed up for 20(7.3, 40.8) months. At the end of follow-up, 25 patients had all-cause deaths. Compared with the non-endpoint group, the endpoint event group had significantly increased left ventricular end diastolic maximum wall thickness (MLVWT), peak early diastolic flow velocity/peak early diastolic velocity at mitral annulus(E/e′) (all P<0.05), and decreased LVEF, left ventricular global longitudinal strain (GLS) and basal segment longitudinal strain (LS) (all P<0.05). Multivariate cox regression analysis after adjusting for age and gender showed that basal segment LS ( HR=0.812, 95% CI=0.675-0.976, P=0.026) was an independent predictor of end-point events in patients with AL-CA. Kaplan-Meier survival curve showed that AL-CA patients with basal segment LS≤13.07% were more likely to have endpoint events. Conclusions:Basal segment LS can be used as a predictor of endpoint events in patients with AL-CA.

BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.

Objective To explore the mechanism of 3-methyladenine(3-MA)for alleviating early diabetic renal injury.Methods Mouse models of streptozotocin(STZ)-induced diabetes mellitus were randomized into model group and 3-MA treatment group for daily treatments with normal saline and 10 mg/kg 3-MA by gavage for 6 weeks,respectively.Body weight and fasting blood glucose of the mice were recorded every week.After the treatments,the kidneys of the mice were collected for measurement kidney/body weight ratio,examination of glomerular size with PAS staining,and detection of α-SMA and PCNA expressions using Western blotting and immunohistochemistry.SV40 MES 13 cells cultured in normal glucose(5.6 mmol/L)and high glucose(30 mmol/L)were treated with 24.4 mmol/L mannitol and 5 mmol/L 3-MA for 24 h,respectively,and the changes in cell viability and PCNA expression were examined using CCK8 assay and Western blotting.Bioinformatics analysis of the intersecting gene targets of diabetic kidney disease(DKD)and 3-MA was performed,and the results were verified by Western blotting both in vivo and in vitro.Results In the diabetic mice,treatment with 3-MA produced a short-term hypoglycemic effect,reduced the kidney/body weight ratio and glomerular hypertrophy,and decreased the expressions of α-SMA and PCNA in the renal cortex.In the in vitro study,3-MA significantly lowered the viability and reduced PCNA expression in SV40 MES 13 cells exposed to high glucose.The results of bioinformatic analysis identified AKT1 as the key gene in the therapeutic mechanism of 3-MA for DKD.Western blotting confirmed that 3-MA inhibited the phosphorylation of AKT and S6 in both the renal cortex of diabetic mice and high glucose-treated SV40 MES 13 cells.Conclusion 3-MA suppresses mesangial cell proliferation and alleviates early diabetic renal injury in mice possibly by inhibiting AKT signaling.

Objective To explore the mechanism of 3-methyladenine(3-MA)for alleviating early diabetic renal injury.Methods Mouse models of streptozotocin(STZ)-induced diabetes mellitus were randomized into model group and 3-MA treatment group for daily treatments with normal saline and 10 mg/kg 3-MA by gavage for 6 weeks,respectively.Body weight and fasting blood glucose of the mice were recorded every week.After the treatments,the kidneys of the mice were collected for measurement kidney/body weight ratio,examination of glomerular size with PAS staining,and detection of α-SMA and PCNA expressions using Western blotting and immunohistochemistry.SV40 MES 13 cells cultured in normal glucose(5.6 mmol/L)and high glucose(30 mmol/L)were treated with 24.4 mmol/L mannitol and 5 mmol/L 3-MA for 24 h,respectively,and the changes in cell viability and PCNA expression were examined using CCK8 assay and Western blotting.Bioinformatics analysis of the intersecting gene targets of diabetic kidney disease(DKD)and 3-MA was performed,and the results were verified by Western blotting both in vivo and in vitro.Results In the diabetic mice,treatment with 3-MA produced a short-term hypoglycemic effect,reduced the kidney/body weight ratio and glomerular hypertrophy,and decreased the expressions of α-SMA and PCNA in the renal cortex.In the in vitro study,3-MA significantly lowered the viability and reduced PCNA expression in SV40 MES 13 cells exposed to high glucose.The results of bioinformatic analysis identified AKT1 as the key gene in the therapeutic mechanism of 3-MA for DKD.Western blotting confirmed that 3-MA inhibited the phosphorylation of AKT and S6 in both the renal cortex of diabetic mice and high glucose-treated SV40 MES 13 cells.Conclusion 3-MA suppresses mesangial cell proliferation and alleviates early diabetic renal injury in mice possibly by inhibiting AKT signaling.

Objective:To evaluate the clinical efficacy of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) in the treatment of obstructive hypertrophic cardiomyopathy (HOCM) with mild septal hypertrophy.Methods:Forty-five HOCM patients with mild septal hypertrophy (the maximal left ventricular wall thickness is 15-19 mm) who were treated with PIMSRA between November 2016 to February 2021 in the Hypertrophic Cardiomyopathy Center of Xijing Hospital of Air Force Military Medical University were enrolled, and their clinical datas were collected and analyzed. The clinical symptoms and NYHA functional class before operation, 6 months and 1 year after operation were collected. Interventricular septum thickness, left ventricular outflow tract pressure gradient, left ventricular outflow tract diameter, mitral regurgitation, left ventricular systolic and diastolic function were evaluated by transthoracic echocardiography before operation, 6 months and 1 year after operation, intraoperative complications were monitored and recorded. Postoperative arrhythmias were monitored by routine 12 lead ECG and 24-hour ambulatory ECG.Results:All patients successfully completed PIMSRA procedure.No clinical adverse events such as death, bleeding and stroke occurred during and around the operation.No left bundle branch block, complete atrioventricular block and malignant arrhythmia occurred after the operation. All patients did not need permanent pacemaker implantation.NYHA functional class and clinical symptoms of patients were significantly improved after 6 months compared with values before operation (all P<0.001, respectively), it remained stable for 1 year after operation; Anterior interventricular septum, posterior interventricular septum, maximal left ventricular wall thickness all significantly decreased (all P<0.001, respectively), left ventricular outflow tract diameter widened ( P<0.001), continuous improvement 1 year after operation; left ventricular outflow tract gradient and provoked left ventricular outflow tract gradient all significantly decreased, mitral regurgitation decreased and SAM classification reduced after 6 months compared with values before operation (all P<0.001, respectively); left ventricular end-diastolic diameter widened and left atrial diameter decreased (all P<0.001, respectively), it remained stable for 1 year after operation. Left atrial volume index decreased ( P<0.001), with continuous improvement 1 year after operation; The ratio of early diastolic mitral valve velocity to early diastolic mitral annulus velocity (E/e′) decreased ( P=0.001), it remained stable for 1 year after operation. There were no significant differences in left ventricular end diastolic volume, left ventricular end systolic volume and left ventricular ejection fraction among the three groups (all P>0.05). Conclusions:PIMSRA is effective in the treatment of obstructive hypertrophic cardiomyopathy with mild ventricular septal hypertrophy.

Objective:To investigate the effect of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) guided by echocardiography on the Lown classification of ventricular arrhythmias in patients with hypertrophic obstructive cardiomyopathy (HOCM).Methods:A total of 85 patients with HOCM who received PIMSRA treatment at Xijing Hospital of Air Force Military Medical University from May 2017 to October 2019 were retrospectively selected. All patients underwent 24-hour Holter examinations before and 1 year after PIMSRA to obtain parameters related to Lown classification. The changes in Lown grades after PIMSRA were analyzed. The patients were divided into improved group and unimproved group according to whether there was significant improvement in Lowen′s grades, and the difference of the parameters related were compared. The influencing factors of the changes in Lown classification were analyzed.Results:Compared with before PIMSRA, there was a significant improvement in the Lown classification after PIMSRA ( P=0.001). The patients with Lown grade Ⅰ increased significantly ( P=0.001), and the patients with grade Ⅲ decreased significantly ( P=0.005). There were no significant changes in patients with Lown grades 0, Ⅱ, and Ⅳ (all P>0.05). The proportion of patients with family history of hypertrophic cardiomyopathy (HCM), the baseline Lown classes, the reduction rate of the maximum left ventricular wall thickness and the reduction rate of the provocative left ventricular outflow tract gradient (LVOTG) were higher in the improved group than the unimproved group (all P<0.05). Multivariate Logistic regression results showed that HCM family history ( OR=3.95, 95% CI=1.34-11.64, P=0.013), baseline Lown classes ( OR=2.01, 95% CI=1.25-3.22, P=0.004) and the reduction rate of the provocative LVOTG gradient ( OR=1.02, 95% CI=1.00-1.04, P=0.041) were independent factors of postoperative Lown classification improvement. Conclusions:The Lown classes of HOCM patients after PIMSRA is significantly improved.HCM family history, the baseline Lown classes, and the reduction rate of postoperative provocative LVOTG are independent influencing factors for the improvement of Lown grade.