ObjectiveTo investigate the mechanism by which Kangxian Yixin prescription regulates the circular RNA 0006719 （circ0006719）/microRNA 6852-5p （miR-6852-5p）/transforming growth factor-β₁ （TGF-β₁）/Smad axis to ameliorate myocardial fibrosis in rats with dilated cardiomyopathy （DCM） and angiotensin Ⅱ （Ang Ⅱ）-induced activation of cardiac fibroblasts （CFs）. MethodsA DCM rat model was established by administration of furazolidone. The rats were divided into normal group， model group， captopril （CAP， 10.1 mg·kg^-1·d^-1） group， and low-， medium-， and high-dose Kangxian Yixin prescription groups （0.9， 1.8， 3.6 g·kg^-1·d^-1）， with 15 rats in each group. After modeling， the treatment groups received corresponding drug solutions by gavage， whereas the normal and model groups received an equal volume of normal saline for 60 consecutive days. Echocardiography was used to measure left ventricular end-systolic diameter （LVESD）， left ventricular end-diastolic diameter （LVEDD）， left ventricular ejection fraction （LVEF）， and left ventricular fractional shortening （LVFS）. Transmission electron microscopy （TEM）， hematoxylin-eosin （HE） staining， and Masson staining were used to observe myocardial ultrastructure， pathological changes， and collagen deposition. Immunohistochemistry （IHC） was used to detect the protein expression of collagen type Ⅰ alpha 1 （Col1A1） and collagen type Ⅲ（Col Ⅲ） in myocardial tissue. Real-time quantitative polymerase chain reaction （Real-time PCR）， Western blot， and fluorescence in situ hybridization （FISH） were used to detect the expression and localization of circ0006719， miR-6852-5p， fibrosis-related molecules， and TGF-β₁/Smad pathway-related molecules in myocardial tissue and CFs. CFs from neonatal rats were isolated and cultured in vitro. Cell Counting Kit-8 （CCK-8） assay was used to determine the optimal concentration of Kangxian Yixin prescription for subsequent intervention. An Ang Ⅱ-induced CF activation model was established， and the cells were divided into normal group， Ang Ⅱ group， Ang Ⅱ+CAP group， Ang Ⅱ+Kangxian Yixin prescription group， and Ang Ⅱ+Kangxian Yixin prescription+miR-6852-5p inhibitor group. CF viability and fibrosis-related molecular expression were detected. RNA immunoprecipitation （RNA IP） and dual-luciferase reporter assays were used to verify the targeting relationship between circ0006719 and miR-6852-5p. ResultsCompared with the normal group， the model group showed significantly increased LVESD and LVEDD， significantly decreased LVEF and LVFS， aggravated myocardial ultrastructural and histopathological injury， and significantly increased collagen volume fraction （CVF） in myocardial tissue （P<0.01）. The expression of circ0006719， Col1A1 mRNA， Col ⅢmRNA， and Col1A1， Col Ⅲ， TGF-β₁， Smad3， and Smad4 proteins in myocardial tissue was significantly upregulated， whereas miR-6852-5p expression and Smad7 protein expression were significantly downregulated （P<0.01）. Compared with the model group， the CAP group and the high- and medium-dose Kangxian Yixin prescription groups showed varying degrees of improvement in cardiac function， myocardial fibrosis， circ0006719/miR-6852-5p expression， and TGF-β₁/Smad pathway-related indicators， with more pronounced improvements in the CAP group and the high-dose Kangxian Yixin prescription group （P<0.05， P<0.01）. In in vitro experiments， 2.0 g·L^-1 was determined as the optimal concentration of Kangxian Yixin prescription for subsequent intervention. Compared with the normal group， the Ang Ⅱ group showed significantly increased CF viability， significantly upregulated expression of circ0006719， Col1A1 mRNA， α-smooth muscle actin （α-SMA） mRNA， and Col1A1， α-SMA， TGF-β₁， Smad3， and Smad4 proteins in CFs， and significantly downregulated miR-6852-5p expression and Smad7 protein expression （P<0.01）. Compared with the Ang Ⅱ group， the Ang Ⅱ+CAP group and the Ang Ⅱ+Kangxian Yixin prescription group showed markedly decreased CF viability and fibrosis-related mRNA and protein expression， markedly increased miR-6852-5p expression， and markedly attenuated TGF-β₁/Smad pathway activation （P<0.05， P<0.01）. Compared with the Ang Ⅱ+Kangxian Yixin prescription group， the Ang Ⅱ+Kangxian Yixin prescription+miR-6852-5p inhibitor group showed significantly increased CF viability （P<0.01）， markedly increased expression of circ0006719， Col1A1 mRNA， and Col1A1， TGF-β₁， and Smad4 proteins in CFs， and markedly decreased miR-6852-5p expression （P<0.05， P<0.01）. RNA IP and dual-luciferase reporter assays showed a targeting binding relationship between circ0006719 and miR-6852-5p （P<0.01）. ConclusionKangxian Yixin prescription may alleviate myocardial collagen deposition and myocardial fibrosis， improve cardiac function in DCM rats， and inhibit Ang Ⅱ-induced abnormal activation of CFs. Its mechanism may be associated with downregulation of circ0006719， restoration of miR-6852-5p expression， and inhibition of the TGF-β₁/Smad pathway.

ObjectiveTo investigate the mechanism by which Kangxian Yixin prescription regulates the circular RNA 0006719 （circ0006719）/microRNA 6852-5p （miR-6852-5p）/transforming growth factor-β₁ （TGF-β₁）/Smad axis to ameliorate myocardial fibrosis in rats with dilated cardiomyopathy （DCM） and angiotensin Ⅱ （Ang Ⅱ）-induced activation of cardiac fibroblasts （CFs）. MethodsA DCM rat model was established by administration of furazolidone. The rats were divided into normal group， model group， captopril （CAP， 10.1 mg·kg^-1·d^-1） group， and low-， medium-， and high-dose Kangxian Yixin prescription groups （0.9， 1.8， 3.6 g·kg^-1·d^-1）， with 15 rats in each group. After modeling， the treatment groups received corresponding drug solutions by gavage， whereas the normal and model groups received an equal volume of normal saline for 60 consecutive days. Echocardiography was used to measure left ventricular end-systolic diameter （LVESD）， left ventricular end-diastolic diameter （LVEDD）， left ventricular ejection fraction （LVEF）， and left ventricular fractional shortening （LVFS）. Transmission electron microscopy （TEM）， hematoxylin-eosin （HE） staining， and Masson staining were used to observe myocardial ultrastructure， pathological changes， and collagen deposition. Immunohistochemistry （IHC） was used to detect the protein expression of collagen type Ⅰ alpha 1 （Col1A1） and collagen type Ⅲ（Col Ⅲ） in myocardial tissue. Real-time quantitative polymerase chain reaction （Real-time PCR）， Western blot， and fluorescence in situ hybridization （FISH） were used to detect the expression and localization of circ0006719， miR-6852-5p， fibrosis-related molecules， and TGF-β₁/Smad pathway-related molecules in myocardial tissue and CFs. CFs from neonatal rats were isolated and cultured in vitro. Cell Counting Kit-8 （CCK-8） assay was used to determine the optimal concentration of Kangxian Yixin prescription for subsequent intervention. An Ang Ⅱ-induced CF activation model was established， and the cells were divided into normal group， Ang Ⅱ group， Ang Ⅱ+CAP group， Ang Ⅱ+Kangxian Yixin prescription group， and Ang Ⅱ+Kangxian Yixin prescription+miR-6852-5p inhibitor group. CF viability and fibrosis-related molecular expression were detected. RNA immunoprecipitation （RNA IP） and dual-luciferase reporter assays were used to verify the targeting relationship between circ0006719 and miR-6852-5p. ResultsCompared with the normal group， the model group showed significantly increased LVESD and LVEDD， significantly decreased LVEF and LVFS， aggravated myocardial ultrastructural and histopathological injury， and significantly increased collagen volume fraction （CVF） in myocardial tissue （P<0.01）. The expression of circ0006719， Col1A1 mRNA， Col ⅢmRNA， and Col1A1， Col Ⅲ， TGF-β₁， Smad3， and Smad4 proteins in myocardial tissue was significantly upregulated， whereas miR-6852-5p expression and Smad7 protein expression were significantly downregulated （P<0.01）. Compared with the model group， the CAP group and the high- and medium-dose Kangxian Yixin prescription groups showed varying degrees of improvement in cardiac function， myocardial fibrosis， circ0006719/miR-6852-5p expression， and TGF-β₁/Smad pathway-related indicators， with more pronounced improvements in the CAP group and the high-dose Kangxian Yixin prescription group （P<0.05， P<0.01）. In in vitro experiments， 2.0 g·L^-1 was determined as the optimal concentration of Kangxian Yixin prescription for subsequent intervention. Compared with the normal group， the Ang Ⅱ group showed significantly increased CF viability， significantly upregulated expression of circ0006719， Col1A1 mRNA， α-smooth muscle actin （α-SMA） mRNA， and Col1A1， α-SMA， TGF-β₁， Smad3， and Smad4 proteins in CFs， and significantly downregulated miR-6852-5p expression and Smad7 protein expression （P<0.01）. Compared with the Ang Ⅱ group， the Ang Ⅱ+CAP group and the Ang Ⅱ+Kangxian Yixin prescription group showed markedly decreased CF viability and fibrosis-related mRNA and protein expression， markedly increased miR-6852-5p expression， and markedly attenuated TGF-β₁/Smad pathway activation （P<0.05， P<0.01）. Compared with the Ang Ⅱ+Kangxian Yixin prescription group， the Ang Ⅱ+Kangxian Yixin prescription+miR-6852-5p inhibitor group showed significantly increased CF viability （P<0.01）， markedly increased expression of circ0006719， Col1A1 mRNA， and Col1A1， TGF-β₁， and Smad4 proteins in CFs， and markedly decreased miR-6852-5p expression （P<0.05， P<0.01）. RNA IP and dual-luciferase reporter assays showed a targeting binding relationship between circ0006719 and miR-6852-5p （P<0.01）. ConclusionKangxian Yixin prescription may alleviate myocardial collagen deposition and myocardial fibrosis， improve cardiac function in DCM rats， and inhibit Ang Ⅱ-induced abnormal activation of CFs. Its mechanism may be associated with downregulation of circ0006719， restoration of miR-6852-5p expression， and inhibition of the TGF-β₁/Smad pathway.

Objective To investigate the effect of Astragalus polysaccharides(APS)on ventricular remodeling in mice with dilated cardiomyopathy(DCM)based on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)/stimu-lator of interferon gene(STING)pathway.Methods The cTnTR141w transgenic DCM mice were randomly assigned into DCM group,APS low-dose group,APS high-dose group,Captopril group,and APS high-dose+cG AS STING pathway activator(Roc A)group,each with 12 mice.A total of 12 C57BL/6J mice were designated as control group.Each group was administered the corresponding drugs,once a day for 8 weeks.The left ventricular end diastolic diameter(LVEDD),left ventricular ejection frac-tion(LVEF),and left ventricular end systolic diameter(LVESD)of mice were measured.ELISA was used to detect serum crea-tine kinase(CK)and troponin T(cTn-T).The mouse heart mass index and left ventricular mass index were measured.Masson staining was used to detect myocardial tissue fibrosis.ELISA was used to test interleukin(IL)-10,tumor necrosis factor-a(TNF-α),and IL-6 in myocardial tissue.Western blot was used to test cGAS and STING proteins in myocardial tissue.Results The a-mount of blue stained myocardial fibers generated in the myocardium was increased,the LVEDD,LVESD,serum CK and cTn-T levels,cardiac mass index,left ventricular mass index,myocardial tissue TNF-α and IL-6 levels,and cGAS and STING proteins were elevated,while the LVEF and myocardial tissue IL-10 were decreased in the DCM group as compared with those in the control group(all P＜0.05).Compared with the DCM group,the generation of blue stained myocardial fibers in the myocardium of mice decreased,the LVEDD,LVESD,serum CK and cTn-T levels,cardiac mass index,left ventricular mass index,myocardial tissue TNF-α and IL-6 levels,and cGAS and STING proteins were reduced,while the LVEF and myocardial tissue IL-10 were increased in the APS low-and high-dose groups,and Captopril group(all P＜0.05).Compared with the high-dose APS group,the generation of blue stained myocardial fibers in the myocardium of mice increased,the LVEDD,LVESD,serum CK and cTn-T levels,cardiac mass index,left ventricular mass index,myocardial tissue TNF-α and IL-6 levels,and cGAS and STING pro-teins were elevated,while the LVEF and myocardial tissue IL-10 were reduced in the high-dose APS+Roc A group(all P＜0.05).Conclusion The mechanism by which APS inhibits inflammation and improves ventricular remodeling in DCM mice may be related to the inhibition of cGAS/STING pathway.

Objective To investigate the effect of Astragalus polysaccharides(APS)on ventricular remodeling in mice with dilated cardiomyopathy(DCM)based on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)/stimu-lator of interferon gene(STING)pathway.Methods The cTnTR141w transgenic DCM mice were randomly assigned into DCM group,APS low-dose group,APS high-dose group,Captopril group,and APS high-dose+cG AS STING pathway activator(Roc A)group,each with 12 mice.A total of 12 C57BL/6J mice were designated as control group.Each group was administered the corresponding drugs,once a day for 8 weeks.The left ventricular end diastolic diameter(LVEDD),left ventricular ejection frac-tion(LVEF),and left ventricular end systolic diameter(LVESD)of mice were measured.ELISA was used to detect serum crea-tine kinase(CK)and troponin T(cTn-T).The mouse heart mass index and left ventricular mass index were measured.Masson staining was used to detect myocardial tissue fibrosis.ELISA was used to test interleukin(IL)-10,tumor necrosis factor-a(TNF-α),and IL-6 in myocardial tissue.Western blot was used to test cGAS and STING proteins in myocardial tissue.Results The a-mount of blue stained myocardial fibers generated in the myocardium was increased,the LVEDD,LVESD,serum CK and cTn-T levels,cardiac mass index,left ventricular mass index,myocardial tissue TNF-α and IL-6 levels,and cGAS and STING proteins were elevated,while the LVEF and myocardial tissue IL-10 were decreased in the DCM group as compared with those in the control group(all P＜0.05).Compared with the DCM group,the generation of blue stained myocardial fibers in the myocardium of mice decreased,the LVEDD,LVESD,serum CK and cTn-T levels,cardiac mass index,left ventricular mass index,myocardial tissue TNF-α and IL-6 levels,and cGAS and STING proteins were reduced,while the LVEF and myocardial tissue IL-10 were increased in the APS low-and high-dose groups,and Captopril group(all P＜0.05).Compared with the high-dose APS group,the generation of blue stained myocardial fibers in the myocardium of mice increased,the LVEDD,LVESD,serum CK and cTn-T levels,cardiac mass index,left ventricular mass index,myocardial tissue TNF-α and IL-6 levels,and cGAS and STING pro-teins were elevated,while the LVEF and myocardial tissue IL-10 were reduced in the high-dose APS+Roc A group(all P＜0.05).Conclusion The mechanism by which APS inhibits inflammation and improves ventricular remodeling in DCM mice may be related to the inhibition of cGAS/STING pathway.

Objective To explore the feasibility of prototype of flexible ultrasound array transducer for measuring intravascular diameter and blood flow velocity.Methods A prototype of flexible ultrasonic array transducer composed of a surface mount flexible ultrasonic array transducer(referred to as the transducer)and acquisition system was designed and fabricated.Doppler body model and vascular simulation control system was used to simulate human blood.Mindray M7 color multi-functional ultrasound diagnostic instrument(abbreviated as M7)and the prototype were adopted to detect pulse wave excitation mode,spectral morphology,echo signal time interval,blood flow velocity,etc.Taken the results of M7 as standards,the effectiveness of the prototype was evaluated.Then the inner diameter and flow velocity of left common carotid artery,left brachial artery and left radial artery of 20 healthy controls(HC)were measured respectively using M7 and the prototype,and the consistency of measurement results were analyzed to evaluate the accuracy of the prototype.The safety of the prototype was evaluated according to subjectively scoring the comfort level of HC applying the transducer and whether there was skin discomfort,injury,etc.after removing the transducer.Results The collected blood flow spectrum of the above vascular simulation control system acquire with the prototype were clear,and the spectral morphology,flow velocity,as well as echo signal time interval were basically consistent with those of M7.The consistency of the inner diameter of left common carotid artery,left brachial artery and left radial artery measured by the prototype and M7 in 20 HC were all very strong(ICC=0.919-0.992),while of flow velocities were moderate or very strong(ICC=0.524-0.831).The subjective score of comfort level of application of transducer was 3(2,3),and no skin discomfort occurred.Conclusion Flexible ultrasound array transducer technology could be used to measure intravascular diameter and blood flow velocity.

Objective To explore the feasibility of prototype of flexible ultrasound array transducer for measuring intravascular diameter and blood flow velocity.Methods A prototype of flexible ultrasonic array transducer composed of a surface mount flexible ultrasonic array transducer(referred to as the transducer)and acquisition system was designed and fabricated.Doppler body model and vascular simulation control system was used to simulate human blood.Mindray M7 color multi-functional ultrasound diagnostic instrument(abbreviated as M7)and the prototype were adopted to detect pulse wave excitation mode,spectral morphology,echo signal time interval,blood flow velocity,etc.Taken the results of M7 as standards,the effectiveness of the prototype was evaluated.Then the inner diameter and flow velocity of left common carotid artery,left brachial artery and left radial artery of 20 healthy controls(HC)were measured respectively using M7 and the prototype,and the consistency of measurement results were analyzed to evaluate the accuracy of the prototype.The safety of the prototype was evaluated according to subjectively scoring the comfort level of HC applying the transducer and whether there was skin discomfort,injury,etc.after removing the transducer.Results The collected blood flow spectrum of the above vascular simulation control system acquire with the prototype were clear,and the spectral morphology,flow velocity,as well as echo signal time interval were basically consistent with those of M7.The consistency of the inner diameter of left common carotid artery,left brachial artery and left radial artery measured by the prototype and M7 in 20 HC were all very strong(ICC=0.919-0.992),while of flow velocities were moderate or very strong(ICC=0.524-0.831).The subjective score of comfort level of application of transducer was 3(2,3),and no skin discomfort occurred.Conclusion Flexible ultrasound array transducer technology could be used to measure intravascular diameter and blood flow velocity.

BACKGROUND:Mesenchymal stem cells are susceptible to senescence during in vitro expansion,which greatly hinders their application in vivo and in vitro.How to improve the replicative senescence of mesenchymal stem cells is an urgent problem to be solved in tissue engineering. OBJECTIVE:To determine whether vascular endothelial growth factor combined with basic fibroblast growth factor can improve the aging of bone marrow mesenchymal stem cells caused by replicative passage. METHODS:Rat bone marrow mesenchymal stem cells were extracted by whole bone marrow adhesion method.Passage 2 cells were selected as normal control group.Passage 7 and later algebraic cells were selected as aging model group.Vascular endothelial growth factor(50 μg/L),basic fibroblast growth factor(10 μg/L),and their combination were administered.Cell proliferation was detected by CCK-8 assay.Cell senescence was observed by β-galactosidase activity staining.Cytoskeleton size and colony formation ability were observed by phalloidine staining and Giemsa staining,respectively,and the levels of senescence-related genes P16,P21,and P53 were detected by qRT-PCR.Gene expression levels of P16,P21,and P53 were tested by qRT-PCR. RESULTS AND CONCLUSION:(1)Vascular endothelial growth factor combined with basic fibroblast growth factor could promote the proliferation of aged bone marrow mesenchymal stem cells,which began to enter the plateau stage on day 9,and the absorbance value of the combined intervention group was significantly higher than that of the model group on day 9(P<0.05).(2)The phenotypic markers of the cells in the combined intervention group did not change,and the cell morphology changed from broad to slender.(3)Compared with the model group,the positive rate of β-galactosidase was significantly decreased(P<0.01);the number of nuclei increased(P<0.001);the total area of cytoskeleton increased(P<0.01);colony formation ability was enhanced(P<0.05);expression level of P16 was decreased(P<0.01)in the combined intervention group.These results indicate that vascular endothelial growth factor combined with basic fibroblast growth factor can improve the senescence of bone marrow mesenchymal stem cells caused by replicative passage without changing the cell phenotype.

Dilated cardiomyopathy(DCM)has a concealed onset with left or even whole heart enlargement as the main imaging manifestation.It is a common primary disease of heart failure and arrhythmia.With the continuous deepening of research in recent years,the intrinsic molecular mechanism of regulatory cell death(RCD)has gradually become clear.Researchers have found that the RCD mode plays a very important role in the occurrence and development of DCM.At present,the RCD modes involved in DCM mainly include apoptosis,necrotic apoptosis,pyroptosis,iron death,autophagy,and cuproptosis,and a certain correlation exists among them,which interact and regulate each other.This article provides an overview of the current research status on the mechanisms of the six RCD modes involved in DCM to provide a reference for future basic research and clinical applications.

Objective:To evaluate the efficacy of ultrasound-guided semispinalis capitis plane (SCP) block for treatment of occipital neuralgia (ON).Methods:This was a prospective study. Ninety patients of both sexes, aged 29-66 yr, suffering ON for 3 months-6 yr in Zibo Municipal Hospital from January 2022 to December 2023, were divided into 3 groups ( n=30 each) using a random number table method: combination of greater occipital nerve (GON) block and the third occipital nerve (TON) block group (group GT), SCP block via the medial head of semispinalis capitis muscle (SCM) group (group Sm), and SCP block via the space between obliquus capitis inferior and C 2, 3 facet joint (OCI-C 2, 3) group (group OC). In GT group, the analgesic and anti-inflammatory compound solution 2.5 ml was injected around GON in the SCM-OCI space at the C 2 level of the cervical vertebra and at the lateral surface of C 2, 3 facet joint. In Sm group, the analgesic and anti-inflammatory compound solution 5 ml was injected into the medial head of SCM at the level of C 1. In OC group, the analgesic and anti-inflammatory compound solution 5 ml was injected into the OCI-C 2, 3 space in the deep part of SCM. The Visual Analogue Scale (VAS) score and Pittsburgh Sleep Quality Index (PSQI) score were recorded before treatment (T 1) and at 1, 3, 7, 10 and 14 days after treatment (T 2-6), and then the rates of pain relief and improvement in sleep quality were calculated. The time spent in blocking, onset time of blocking, completion time of blocking, duration of block, and occurrence of adverse reactions within 24 h after block were recorded. Results:There were no significant differences in VAS scores and PSQI scores at T 1-3 and T 5-6 among the three groups ( P>0.05), and VAS and PSQI scores were significantly higher at T 4 in Sm group than in OC and GT groups ( P<0.05). Compared with GT group, the time spent in blocking was significantly shortened, the onset time and completion time of block was prolonged, and the duration of block was shortened in Sm group, and the time spent in blocking was significantly shortened, the onset time and completion time of block was shortened ( P<0.05), and no significant change was found in the duration of block in OC group ( P>0.05). No severe complications were observed in the three groups. Conclusions:Compared with the combination of GON and TON blocks, ultrasound-guided SCP block for treating ON is simple and highly safe, SCP block via the OCI-C 2, 3 space has rapid onset and long duration, leading to significant improvements in pain and sleep quality, and it can be used as the first-choice block method for treating ON.

Objective To explore the effect of Kangxian Yixin decoction on PKA/CaMKⅡ Signal Pathway and Mitochondrial membrane potential of cardiomyocyte hypertrophy in dilated cardiomyopathy rats.Methods Drinking furazolidone to duplicate the DCM rats model for 10 weeks,then the rats were checked by ultrasound,the successfully established model rats were randomly divided into model group,low dose Kangxian Yixin decoction group,middle dose Kangxian Yixin decoction group,high dose Kangxian Yixin decoction group and captopril group.Normal group was separated.After 4 weeks of drug intervention,This experiment was over,ATP,Ca2+-Mg2+-ATP enzymatic activity,CaMKⅡ,PKA and UCP2 mRNA were tested.H9c2 cardiomyocyte hypertrophy model was set up by norepinephrine,after 24 h of drug intervention,mitochondrial membrane potential was tested.Results Compared with the normal group,cardiomyocyte mitochondria were damaged in each model group,ATP,Ca2+-Mg2+-ATP enzymatic activity and PKA mRNA were lower,UCP2 mRNA and CaMKⅡ mRNA were higer,mitochondrial membrane potential obviously decreased(P<0.05 or P<0.01).The mitochondria were protected in every drug group,the tested indexes get well in different degree,especially in hige dose Kangxian Yixin decoction group(P<0.05 or P<0.01).Conclusion Kangxian Yixin decoction can reduce myocardial cell mitochondrial damage in model rats with DCM,improve myocardial cell energy metabolism and cardiac systolic and diastolic functions,one of the mechanisms may be optimizing PKA/CaMKⅡ signal pathway and improving mitochondrial membrane potential.