ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）/cAMP-response element binding protein （CREB） signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet， intraperitoneal injection of isoproterenol （ISO）， and chronic unpredictable mild stress （CUMS）. A total of 108 SD male rats were randomly divided into normal group， model group， high （23.4 g·kg^-1）， medium （11.7 g·kg^-1）， and low （5.85 g·kg^-1） dose groups of modified Chaihu Shugansan， CaMKⅡ inhibitor （KN93） group， and KN93 + high， medium， and low dose groups of modified Chaihu Shugansan， with 12 rats in each group. From the first day of modeling to the end of modeling， drugs were administered once a day. In the seventh and eighth weeks， the KN93 group and the KN93 + high， medium， and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week， behavioral tests including sucrose preference， open field， and elevated plus maze were conducted. Electrocardiogram （ECG） lead Ⅱ changes were observed in each group of rats， and hematoxylin-eosin （HE） staining was performed to observe changes in heart tissue. Serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， low-density lipoprotein （LDL）， and lactate dehydrogenase （LDH） were measured by using an enzyme-labeled instrument. Creatine kinase （CK） and creatine kinase-MB （CK-MB） were detected by ultraviolet spectrophotometry， while serum monocyte chemoattractant protein-1 （MCP-1） was measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue， and Western blot was performed to assess protein expression of CaMKⅡ， phosphorylated （p）-CaMKⅡ， CREB， and p-CREB. ResultsCompared to the normal group， the model group showed significant reductions in sucrose preference rate， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）. The ECG showed ST-segment elevation， and HE staining showed serious degeneration of myocardial fibers， disordered arrangement， and infiltration of a large number of inflammatory cells. In addition， serum TC and LDL levels increased （P<0.01）， and HDL level decreased （P<0.01）. CK， CK-MB， LDH， and MCP-1 levels significantly increased （P<0.05， P<0.01）. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue （P<0.05， P<0.01）， but those increased in the heart tissue （P<0.01）. Compared to the model group， the high， medium， and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）， as well as decreased serum CK， CK-MB， LDH， and MCP-1 levels （P<0.05， P<0.01）. KN93 also reduced ST-segment elevation， alleviated the degeneration degree of myocardial fibrosis， and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced （P<0.05， P<0.01）. The KN93 + high， medium， and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression， possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway， with the high-dose modified Chaihu Shugansan showing the best effects.

Objective To investigate the relationship between between the levels of serum malondialdehyde(MDA)and superoxide dismutase(SOD),the balance of oxidative/antioxidant stress,and the prognostic nu-tritional index(PNI)and the risk of early neurological deterioration in patients with acute ischemic stroke(AIS).Methods A total of 95 patients with suspected AIS admitted to the Second People's Hospital of Fos-han,Foshan from January to April 2023 were selected as the research subjects.Among them,71 patients who were finally diagnosed with AIS were included in the stroke group,and the remaining 24 non-AIS patients were included in the control group.According to the National Institutes of Health Stroke Rating Scale(NIH-SS)score,the stroke group was divided into the moderate-severe stroke group and the mild stroke group.Ac-cording to whether early neurological deterioration(END)occurred,it was divided into the END group and the non-END group.To analyze the correlations between the levels of serum SOD and MDA,SOD/MDA,and the PNI and the severity of stroke.The receiver operating characteristic(ROC)curve was applied to evaluate the predictive value of each index for the risk of END.By fitting the indicators with high diagnostic efficacy,a Fisher discriminant function model for evaluating the risk of END was established to verify the overall accura-cy rate.Results The levels of serum MDA and SOD,SOD/MDA and the PNI in the moderate to severe stroke group were statistically different from those in the mild stroke group(P＜0.05).There were statistically sig-nificant differences in the levels of serum MDA and SOD,SOD/MDA and the PNI among the END group,the non-END group and the control group(P＜0.05).The areas under the curve(AUC)of SOD,MDA,SOD/MDA and PNI for evaluating END were 0.692,0.727,0.777 and 0.819,respectively.The Fisher discriminant function model established by fitting the NIHSS score,the SOD/MDA and the PNI has an overall accuracy rate of 85.9％.Conclusion The END risk prediction model established by applying the Fisher discriminant function can provide early and objective reference basis for clinical prediction of END risk and has certain practical value.