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 observe the effects of four different modeling method on the hypothalamus-pituitary-adrenal(HPA)axis,blood rheology,platelet aggregation rate,and myocardial ischemia in rats,and to provide new ideas for the establishment of a rat model of"double heart"disease in line with clinical diagnosis and treatment characteristics.Methods Sixty-nine male Sprague-Dawley rats were divided randomly into a Control group(unstimulated),chronic unpredictable mild stimulation(CUMS)group,isoproterenol(ISO)group(intraperitoneal injection of ISO),high-fat diet(HFD)group(fed high-fat chow),and composite model(CUMS+ISO+HFD)group(n=12 rats in the Control and HFD groups;n=15 rats in the other three groups,respectively).Modeling procedures were carried out for a total of 8 weeks,with ISO injection started from week 6 of the experiment for a total of 3 weeks.At the end of modeling,rats in each group were subjected to absent-field and sugar-water preference behavioral tests.Electrocardiography(ECG)was performed to observe changes in ECG lead Ⅱ in each group.Serum levels of adrenocorticotropic hormone(ACTH),cortisol(Cor),corticosterone(CORT),endothelin-1(ET-1),and soluble intercellular adhesion molecule-1(sICAM-1)were detected by enzyme-linked immunosorbent assay.Myocardial histopathological changes were detected by hematoxylin/eosin(HE)staining.Serum total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were measured using an enzyme labeling instrument.Whole-blood high-cut viscosity(200 V/S),whole-blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen were assessed using an automatic blood rheology analyzer.The maximum platelet aggregation rate(MAR)and average platelet aggregation rate(AAR)induced by arachidonic acid and adenosine diphosphate were detected using a whole-blood platelet aggregometer.Results Compared with the Control group,all four model groups had significantly lower absenteeism distance and number of entries into the central region in the absent-field test,and a lower sugar-water preference ratio(P＜0.01).ECG revealed ST-segment elevation in the ISO and CUMS+ISO+HFD groups,tachycardia in the CUMS group,and mild ST-segment elevation in the HFD.Serum ACTH,Cor,CORT,ET-1,and sICAM-1 were all significantly elevated in the four model groups(P＜0.01).HE staining showed that myocardial tissue was severely damaged in rats in the ISO and CUMS+ISO+HFD groups,with pathological changes such as localized fibrosis and inflammatory infiltration of the myocardium,while mild cardiomyocyte disarrangement and fracture was seen in the CUMS and HFD groups.Rats in the HFD group had increased serum TC and LDL(P＜0.01)and decreased HDL contents(P＜0.01).Compared with the Control group,whole-blood high-cut viscosity(200 V/S),whole-blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen were all increased in the CUMS,HFD,and CUMS+ISO+HFD groups(P＜0.01,P＜0.05),while whole blood high-cut viscosity(200 V/S),whole blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen levels were decreased in rats in the ISO group(P＜0.01,P＜0.05).MAR and AAR were significantly higher in rats in the CUMS,HFD,and CUMS+ISO+HFD groups(P＜0.01),while the platelet aggregation rate was decreased in the ISO group compared with the Control group(P＜0.01,P＜0.05).Conclusions These result showed that the rat CUMS+ISO+HFD model better reflected the complexity of clinical double heart disease than the other three models.

Objective To observe the effects of four different modeling method on the hypothalamus-pituitary-adrenal(HPA)axis,blood rheology,platelet aggregation rate,and myocardial ischemia in rats,and to provide new ideas for the establishment of a rat model of"double heart"disease in line with clinical diagnosis and treatment characteristics.Methods Sixty-nine male Sprague-Dawley rats were divided randomly into a Control group(unstimulated),chronic unpredictable mild stimulation(CUMS)group,isoproterenol(ISO)group(intraperitoneal injection of ISO),high-fat diet(HFD)group(fed high-fat chow),and composite model(CUMS+ISO+HFD)group(n=12 rats in the Control and HFD groups;n=15 rats in the other three groups,respectively).Modeling procedures were carried out for a total of 8 weeks,with ISO injection started from week 6 of the experiment for a total of 3 weeks.At the end of modeling,rats in each group were subjected to absent-field and sugar-water preference behavioral tests.Electrocardiography(ECG)was performed to observe changes in ECG lead Ⅱ in each group.Serum levels of adrenocorticotropic hormone(ACTH),cortisol(Cor),corticosterone(CORT),endothelin-1(ET-1),and soluble intercellular adhesion molecule-1(sICAM-1)were detected by enzyme-linked immunosorbent assay.Myocardial histopathological changes were detected by hematoxylin/eosin(HE)staining.Serum total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were measured using an enzyme labeling instrument.Whole-blood high-cut viscosity(200 V/S),whole-blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen were assessed using an automatic blood rheology analyzer.The maximum platelet aggregation rate(MAR)and average platelet aggregation rate(AAR)induced by arachidonic acid and adenosine diphosphate were detected using a whole-blood platelet aggregometer.Results Compared with the Control group,all four model groups had significantly lower absenteeism distance and number of entries into the central region in the absent-field test,and a lower sugar-water preference ratio(P＜0.01).ECG revealed ST-segment elevation in the ISO and CUMS+ISO+HFD groups,tachycardia in the CUMS group,and mild ST-segment elevation in the HFD.Serum ACTH,Cor,CORT,ET-1,and sICAM-1 were all significantly elevated in the four model groups(P＜0.01).HE staining showed that myocardial tissue was severely damaged in rats in the ISO and CUMS+ISO+HFD groups,with pathological changes such as localized fibrosis and inflammatory infiltration of the myocardium,while mild cardiomyocyte disarrangement and fracture was seen in the CUMS and HFD groups.Rats in the HFD group had increased serum TC and LDL(P＜0.01)and decreased HDL contents(P＜0.01).Compared with the Control group,whole-blood high-cut viscosity(200 V/S),whole-blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen were all increased in the CUMS,HFD,and CUMS+ISO+HFD groups(P＜0.01,P＜0.05),while whole blood high-cut viscosity(200 V/S),whole blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen levels were decreased in rats in the ISO group(P＜0.01,P＜0.05).MAR and AAR were significantly higher in rats in the CUMS,HFD,and CUMS+ISO+HFD groups(P＜0.01),while the platelet aggregation rate was decreased in the ISO group compared with the Control group(P＜0.01,P＜0.05).Conclusions These result showed that the rat CUMS+ISO+HFD model better reflected the complexity of clinical double heart disease than the other three models.

Objective To evaluate the differences in chemical composition and pharmacological effects between Angelica-Astragalus medicine pair decoction(DGD)and traditional decotion,and to provide a reference for the rational clinical application of Danggui Buxue decoction.Methods With the two comparison methods of unified and non-uniform raw material source batches,we set up different sample groups,established characteristic maps by HPLC,and evaluated the chemical components based on the similarity of characteristic maps,component types,index component content,common peak area,and other factors.The efficacy of the drug was evaluated in the hemorrhagic blood deficiency model mice.Results ①The similarity of the feature map between the DGD and TD was high(similarity was greater than 0.87).②The number of chromatographic peaks was inconsistent.Traditional decoction from self-purchased decoction pieces,or traditional decoction-Factory A decoction pieces had a total of 12 chromatographic peaks each.The DGD of Factory A had a total of 15 chromatographic peaks.There were 10 chromatographic peaks in the DGD of Factory B.③The contents of ferulic acid and calycosin 7-O-glucoside(CG)in DGD of Factory A were higher than those in traditional decoction(P<0.05,n=3).There was no significant difference between DGD and TD ferulic acid content in Factory B,but the content of CG was lower than that in traditional decoction(P<0.05).④The total area of common peaks in DGD was different from that in TD.The relative total ratios of the contents of the components in the self-purchased traditional decoction pieces,the traditional decoction pieces of Factory A,the formula granules of Factory A,and the formula granules of Factory B were 1.00,0.96,2.14,0.60,respectively.⑤Both DGD and traditional decoction could significantly promote the recovery of hemoglobin and red blood cells in hemorrhagic anemia model mice(P<0.01);Compared with the model control group,there was a significantly difference(P<0.05)except for the DGD group of Plant B.There was no significant difference between DGD and TD of Plant A,but there was a very significant difference between DGD and TD of Plant B(P<0.01).Conclusion Whether the raw material source batch is consistent or not,DGD and TD have certain differences in chemical composition.In terms of pharmacological effect,DGD,prepared from a unified batch of decoction pieces,has similar efficacy to traditional decoction in alleviating hemorrhagic anemia.There are certain differences in the pharmacological effects between DGD prepared from different batches of decoction pieces and traditional decoctions.The differences caused by the different preparation processes of the same source batch of prepared slices were compared,and the quality differences of the formula granules from different manufacturers were caused by the different source batches of prepared slices and different preparation processes,indicating the necessity and urgency of the country to formulate a unified quality standard for formula granules and related process specifications.

ObjectiveTo explore the amelioration of cognitive dysfunction in diabetes mellitus （DM） by Jianpi Qinghua prescription （JPQH） based on type 2 diabetes （T2DM） model rats. MethodFifty healthy male Wistar rats of SPF grade were randomly divided into control group （n=10） and experimental group （n=40）. The rats in the control group were fed conventionally， while those in the experimental group were fed on a high-sugar， high-fat diet for six weeks and administered with streptozotocin （STZ） for the induction of the DM model. The model rats were randomly divided into model group， sitagliptin group （1.2 g·L^-1）， pioglitazone group （0.8 g·L^-1）， and JPQH group （1.3 g·mL^-1）， with 10 rats in each group. After six weeks of drug intervention， the changes in body weight， blood glucose， and other related indexes of each group were recorded. Enzyme-linked immunosorbent assay （ELISA） was performed to detect the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the peripheral blood and brain. The Morris water maze test was used to evaluate the cognitive function in rats. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology of the hippocampal CA region. The amyloid β-protein 40 （Aβ₄₀） level was detected by immunohistochemistry. The protein expression of t-tau and p-tau in hippocampal neurons of rats was detected by Western blot. ResultCompared with blank group， the body weight of model group was significantly decreased （P<0.05）， blood glucose level was significantly increased （P<0.01）， inflammatory cytokines TNF-α and IL-1β were increased （P<0.05）， learning and spatial ability were significantly decreased （P<0.01）， the arrangement of hippocampal cells was loose and disordered， and the intercellular space was significantly increased. The number of cells decreased significantly， and the expression of Aβ₄₀ increased significantly. and increased t-tau and p-tau protein content in the hippocampus （P<0.01）. Compared with model group， the JPQH group showed reduced blood glucose （P<0.01）， decreased TNF-α and IL-1β levels in the peripheral blood and cerebrospinal fluid （P<0.05）， a downward trend of IL-6 without a statistical difference， improved learning and spatial memory ability （P<0.01）， densely arranged cells in the hippocampal CA1 area， increased cell number， reduced Aβ₄₀ expression， and decreased p-tau protein expression （P<0.05）. ConclusionJPQH can prevent cognitive dysfunction in DM by reducing inflammatory factor levels， decreasing neurotoxicity caused by Aβ₄₀ deposition， and inhibiting hyperphosphorylation of tau protein in DM rats.

Objective:To compare the efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co., Ltd. (the generic drug) and ticagrelor tablets produced by AstraZeneca Pharmaceutical Co., Ltd. (the original drug) in antiplatelet therapy.Methods:The study design was a retrospective cohort study. The subjects were patients who underwent percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and postoperative antiplatelet therapy with ticagrelor tablets at First Affiliated Hospital of Dalian Medical University during January 2020 to July 2021. Through the hospital electronic medical record system, relevant clinical data of patients (age, gender, comorbidities, blood lipid level on admission, PCI indications, antiplatelet treatment regimen, efficacy and safety assessment endpoint events within 12 months of treatment, etc.) were collected. The patients were divided into the generic drug group and the original drug group. To exclude confounders, propensity score matching (PSM) method was used. The efficacy evaluation index was the incidence of the primary endpoint events (cardiogenic death, stroke, target revascularization, recurrent infarction) and secondary endpoint events (all-cause mortality, peripheral artery occlusion, stent thrombosis, angina attacks) within 12 months of treatment. The safety evaluation index was the incidence of bleeding event within 12 months of treatment.Results:A total of 1 486 patients were included in this study, including 734 in the generic drug group and 752 in the original drug group. The proportion of women and unstable angina, and the level of high-density lipoprotein cholesterol were higher than those in the original drug group (all P<0.05). The proportion of patients with hyperlipidemia and ST-segment elevation myocardial infarction were lower than those in the original drug group (both P<0.05). After PSM, 690 patients were enrolled in the generic drug group and 690 patients in the original drug group (all P>0.05). No differences in the comparison of clinical features between the 2 groups was significant (all P>0.05). No differences in the incidences of primary endpoints, secondary endpoints, and bleeding events between the 2 groups was significant before and after PSM [before PSM: 12.1%(89/734) vs. 10.9%(82/752), 10.8%(79/734) vs. 8.4%(63/752), 0.3%(2/734) vs. 0.5%(4/752); after PSM: 12.6%(87/690) vs. 12.3%(85/690), 11.0%(76/690) vs. 8.3%(57/690), 0.3%(2/690) vs. 0.4%(3/690); all P>0.05]. No death occurred in patients of both groups. Bleeding is predominantly characterized by epistaxis and subcutaneous petechiae, which did not lead to interruption of antiplatelet therapy. Conclusion:The efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co., Ltd. for antiplatelet therapy in ACS patients after PCI surgery were basically the same as those of the original drug.

Objective:To compare the efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co., Ltd. (the generic drug) and ticagrelor tablets produced by AstraZeneca Pharmaceutical Co., Ltd. (the original drug) in antiplatelet therapy.Methods:The study design was a retrospective cohort study. The subjects were patients who underwent percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and postoperative antiplatelet therapy with ticagrelor tablets at First Affiliated Hospital of Dalian Medical University during January 2020 to July 2021. Through the hospital electronic medical record system, relevant clinical data of patients (age, gender, comorbidities, blood lipid level on admission, PCI indications, antiplatelet treatment regimen, efficacy and safety assessment endpoint events within 12 months of treatment, etc.) were collected. The patients were divided into the generic drug group and the original drug group. To exclude confounders, propensity score matching (PSM) method was used. The efficacy evaluation index was the incidence of the primary endpoint events (cardiogenic death, stroke, target revascularization, recurrent infarction) and secondary endpoint events (all-cause mortality, peripheral artery occlusion, stent thrombosis, angina attacks) within 12 months of treatment. The safety evaluation index was the incidence of bleeding event within 12 months of treatment.Results:A total of 1 486 patients were included in this study, including 734 in the generic drug group and 752 in the original drug group. The proportion of women and unstable angina, and the level of high-density lipoprotein cholesterol were higher than those in the original drug group (all P<0.05). The proportion of patients with hyperlipidemia and ST-segment elevation myocardial infarction were lower than those in the original drug group (both P<0.05). After PSM, 690 patients were enrolled in the generic drug group and 690 patients in the original drug group (all P>0.05). No differences in the comparison of clinical features between the 2 groups was significant (all P>0.05). No differences in the incidences of primary endpoints, secondary endpoints, and bleeding events between the 2 groups was significant before and after PSM [before PSM: 12.1%(89/734) vs. 10.9%(82/752), 10.8%(79/734) vs. 8.4%(63/752), 0.3%(2/734) vs. 0.5%(4/752); after PSM: 12.6%(87/690) vs. 12.3%(85/690), 11.0%(76/690) vs. 8.3%(57/690), 0.3%(2/690) vs. 0.4%(3/690); all P>0.05]. No death occurred in patients of both groups. Bleeding is predominantly characterized by epistaxis and subcutaneous petechiae, which did not lead to interruption of antiplatelet therapy. Conclusion:The efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co., Ltd. for antiplatelet therapy in ACS patients after PCI surgery were basically the same as those of the original drug.

Objective:To construct a standardized training program for full-time nursing postgraduate students, and to provide a basis for the training the high-quality nursing talents in hospitals.Methods:Through literature review and demi structured interview, preliminarily develop the training program was established from January to March 2021. Through two rounds of expert consultations of 16 experts, the standardized training program for nursing postgraduates was formulated.Results:The recovery rate of the two rounds were both 16/16. The expert authority coefficients of the two rounds of consultation were 0.819, respectively. The Kendall′s coordination coefficients of the two rounds of consultation were 0.329 and 0.334, respectively, and the difference was statistically significant ( P< 0.01). Finally, a standardized training program for entry-level nursing postgraduates was formed, which included five parts: training objects and quality requirements, training methods, training objectives, training contents and evaluation, with a total of 225 items. Conclusions:The standardized training program for nursing postgraduates formed is reliable, scientific and practical, which provides guidance and reference for the training and use of highly educated clinical nursing talents in hospitals.

Since the discovery of circulating hepatitis B virus (HBV) RNA in the peripheral blood of patients with chronic hepatitis B in 1996, a growing number of studies have focused on clarifying the biological characteristics and clinical application value of serum HBV RNA. This consensus mainly summarizes the research progress of serum HBV RNA existing profiles, quantitative detection methods, and current clinical applications. In order to better apply this indicator for the clinical management of patients with chronic HBV infection, recommendations on quantitative detection target regions, detection results, and clinical applications are put forward.

Purpose: Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic autosomal recessive disease caused by mutations in ATP8B1, ABCB11 or ABCB4. Mutational analysis of these genes is a reliable approach to identify the disorder. Methods: We collected and analyzed relevant data related to clinical diagnosis, biological investigation, and molecular determination in nine children carrying these gene mutations, who were from unrelated families in South China. Results: Of the nine patients (five males, four females) with PFIC, one case of PFIC1, four cases of PFIC2, and four cases of PFIC3 were diagnosed. Except in patient no. 8, jaundice and severe pruritus were the major clinical signs in all forms. γ-glutamyl transpeptidase was low in patients with PFIC1/PFIC2, and remained mildly elevated in patients with PFIC3. We identified 15 different mutations, including nine novel mutations (p.R470HfsX8, p.Q794X and p.I1170T of ABCB11 gene mutations, p.G319R, p.A1047P, p.G1074R, p.T830NfsX11, p.A1047PfsX8 and p.N1048TfsX of ABCB4 gene mutations) and six known mutations (p.G446R and p.F529del of ATP8B1 gene mutations, p.A588V, p.G1004D and p.R1057X of ABCB11 gene mutations, p.P479L of ABCB4 gene mutations). The results showed that compared with other regions, these three types of PFIC genes had different mutational spectrum in China. Conclusion The study expands the genotypic spectrum of PFIC. We identified nine novel mutations of PFIC and our findings could help in the diagnosis and treatment of this disease.