Objective By using cardiac ischemia reperfusion model, the muscarinic receptor path way of cardiac signal conduction in both young and aged myocardium was studied. The aim was to study the pathogenesis of ischemia reperfusion injury in aged myocardium. Methods 20 dogs (15～20 kg) were randomly divided into two groups: group A (young, 3～4 years old, n=10), group B (old, 7～8 years old, n=10). All dogs underwent 60 minutes of global ischemia and 30 minutes of reperfusion under cardiopulmonary bypass (CPB). A tunnel was inserted through the left ventricular apex, to measure the LVEDP、+dp/dt、-dp/dt and ECG. . Myocardial specimens were collected at the beginning of reperfusion, 30 min after reperfusion and 60 min after reperfusion. Myocardium was prepared or studied of density of muscarinic receptor, G protein level, cGMP, guanylate cyclase activity, value of NO, protein level of eNOS, mRNA level of iNOS and eNOS. Results (1) Group B had higher LVEDP but lower +dp/dt max and -dp/dt max than group A in each stage. After CPB, the LVEDP showed no difference between pre and post surgery in two groups, while +dp/dt max and -dp/dt max were decreased in both groups, more significantly in group B. (2) At 30 min and 60 min after reperfusion, the density of M receptor was significantly increased in group B than that in group A. (3) There was no significant difference in Gs pre and post surgery in group A. Compared with group B, the level of Gi decreased significantly after the reperfusion in group A. There were decreasing in Gs and Gi after reperfusion in group B, more greater in the former. The ratio of Gi/Gs in group B was much higher than that in group A. (4) Compared with group A, the mRNA level of eNOS and protein level of eNOS decreased more significantly in group B during each stage of reperfusion. After ischemia reperfusion, the mRNA level of iNOS, NO, cGMP and guanylate cyclase activity were obviously increased in group B than that in group A.Conclusion (1) After the cardiac surgery in elder model, the M receptor path way increased significantly, which is negatively correlated with cardiac function, hence promote the ischemia reperfusion injury in elder myocardium. (2) In the ischemia reperfusion injury in elder myocardium, higher vagotonic does more harm to the old myocardium through NO and NO cGMP pathway.

Objective To investigate the regulatory effects and possible mechanisms of autophagy induction and bactericidal activity in muring bone marrow derived macrophages ( BMDMs) . Methods Murine BMDMs were isolated and cultured in vitro. Then standard strain of E. coli was used to infect BMDMs and cellular autophagy levels and AMPK activation were detected. We next modulated functions of AMPK by pretreating cells with the specific agonist or antagonist of AMPK. Then cellular AMPK activation, autophagy levels and bactericidal activity were observed after E. coli infection. Results In E. coli infected BMDMs,autophagy related molecules like LC3B and Beclin1 were upregu-lated,accompanied with elevated LC3Ⅱ/Ⅰratio. Phosphorylation of AMPK was also upregulated by E. coli treatment. Enhanced AMPK activi-ty by its agonist leads to increased cellular autophagy and bactericidal activity,whereas inhibition of AMPK by its suppressor downregulated autophagy and dampened bactericidal activity. Conclusion AMPK and its related signaling pathway is required for anti-bacterial response in macrophage,which is dependent on its function in upregulating autophagy related molecules and inducing autophagy.

Objective To investegate the value of dual-source CT (DsCT) in the diagnosis of tetralogy of Fallot (TOF).Methods The measurement results of the main pulmonary artery( PA),left pulmonary artery (LPA),right pulmonary artery( RPA ),right entricular outflow tract(ROVT) of 42 cases with TOF by DsCT,echocardiography aud surgery were ret rospectively analyzed.Results Of the 42 cases,a total of 232 cardiac nomalies were found by surgery ( 145 intra cardiac anomalies,53 ventricular-aterial connection anomalies,34 external cardiac anomalies),DsCT and echocardiography found 204 cardiac nomalies (130 intra cardiac anomalies,12 ventricular-aterial connection anomalies,53 external cardiac anomalies),224 cardiac nomalies ( 145 intra cardiac anomalies,31 ventricular-aterial connection anomalies,48 external cardiac anomalies)respectively;and the diagnostic accuracy of DsCT and echocardiography was 88％ (204/232),97％ (224/232) respectively.There was not significant difference between DsCT and surgery ( P ＞ 0.05 ).There was significant difference between echocardiography and surgery in PA,LPA and RPA (P＜0.05),but not in ROVT and over-riding of the aorta (P＞0.05).There was not significant difference between DsCT and echocardiography ( P ＞ 0.05 ).Conclusion Echocardiography was superior to DsCT in intra cardiac anomalies,especially in the cardiac septal defects and heart valve diseases.DsCT had the advantages in external cardiac anomalies,particularly in assessing pulmonary artery.

Objective:The hemolytic prediction model of the axial flow impeller blood pump is carried out by using a computational fluid dynamics(CFD) multiphase flow model.Methods:The hydrodynamic performance of the pump and the flow field in the pump, and the shear stress distribution are analyzed. A hemolytic prediction model based on the shear stress is built based on the calculation results. Hemolysis tests in vitro were performed 6 times with fresh bovine blood. At each time, the flow of the ventricular assist device(VAD) is 5 L/min and the outflow tract pressure is 100 mmHg(13.3kPa). According to the tests, the plasma free hemoglobin(FHB) content and the hematocrit(HCT) are measured every half hour. At the end of each experiment Normal Index of Hemolysis(NIH) is calculated.Results:The average of NIH is 0.0055 g/100L, almost identical with that obtained from the hemolytic prediction model.Conclusion:Multiphase flow model can be used for quantitative predictions of the hemolytic behavior of a VAD. This method can be applied in the selection stage of a blood pump.

Objective To establish and evaluate a gas chromatography-tandem mass spectrometry(GC-MS/MS)method for the detection of six common drugs(methamphetamine,meperidine,caffeine,codeine,cocaine and ketamine)in blood,and to improve the determination basis of results.Methods The above six drugs were added into the blank blood,and GC-MS/MS was used for detection after ether extraction.The collection,quantification and confirmation were carried out under the mode of multi-reaction monitoring(MRM).The qualitative results of the above six drugs were evaluated based on the maximum allowable deviation of the retention time and relative ion abundance ratio in the qualitative results of GC-MS/MS.Results There was a good linear relationship between the six common drugs,among which ketamine and caffeine had the lowest detection limit(0.01 μg/mL),methamphetamine had the highest detection limit(0.5 μg/mL).The retention time(RT)and relative retention time(RRT)of the target substance were stable under the six supplemental levels,and the absolute deviation(ΔRTabsolute)of RT was within±0.025 min.The absolute deviation of RRT(ΔRRTabsolute)was within±0.004.The relative ion abundance ratio absolute deviation(ΔIabsolute)is±20%,and the relative ion abundance ratio relative deviation(ΔIrelative)is±50%.Conclusion This study clarified the reference range for qualitative determination of six common drugs in blood matrix detected by GC-MS/MS,and effectively supplemented the qualitative determination indicators of existing instrumental analysis methods.

ObjectiveTo investigate the current status of psychosocial services in various institutions as well as the mental health status of residents in Northeast Sichuan， so as to provide references for the further construction and implementation of psychosocial services in this area. MethodsA total of 148 institutions in Tongjiang county of Bazhong city， Lizhou district of Guangyuan city and Dazhu county of Dazhou city were surveyed through self-compiled questionnaires covering the construction status of psychosocial service system and the implementation of mental health service in each institution. Meantime， the mental health status and psychological service needs of 21 505 residents in pilot areas of three cities were investigated using the Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）， Generalized Anxiety Disorder Scale-7 item （GAD-7） and the self-designed mental health service needs questionnaire. ResultsAmong the 148 institutions in the pilot areas， 81 （54.7%） of which had dedicated mental health service， and 58 （39.2%） were equipped with full-time or part-time mental health service personnel. In 2019， 95 （64.2%） institutions conducted mental health services for employees， and 104 （70.3%） conducted mental health propaganda activities. Of the 75 educational institutions， 67 （89.3%） conducted mental health education for students， and 47 （62.7%） achieved full coverage of the mental health education curriculum among students. The detection rates of depression and anxiety among the residents were 36.8% and 30.8%， respectively， and 83.7% of the residents had the mental health service needs， mainly in the aspects of personal growth， marriage and family， children's education and stress management. ConclusionThe psychosocial services in the pilot areas of the three cities in northeast Sichuan are well conducted， while the guarantee of workplace， funds and personnel remains to further strengthen. Furthermore， residents have prominent emotional problems such as depression and anxiety， and have a high demand for mental health services.

ObjectiveTo investigate the effect and mechanism of Polygonatum neutral polysaccharides from sibiricum （PSP-NP） on colon injury in mice with chronic obstructive pulmonary disease （COPD）. MethodsMale C57BL/6J mice were randomly divided into a control group， a COPD model group， and a PSP-NP group. The COPD model was established using smoke exposure combined with intranasal LPS administration. The PSP-NP group was simultaneously treated daily with 200 mg/kg of PSP-NP via intragastric gavage， while the other groups received an equal volume of saline. HE staining was used to observe the pathological changes in the colon. ELISA was employed to detect the levels of LPS in serum and the expressions of ZO-1， Occludin， IL-6， and TNF-α in colon tissue. UPLC-MS was used to detect the types and contents of bile acids in colonic content， and to screen for differential bile acids. Differential microbial flora were identified using 16S rRNA gene sequencing， and correlation analysis was conducted with differential bile acids. PSP-NP was combined with the differential bile acids cholic acid （CA）， and deoxycholic acid （DCA） in vitro to analyze the binding capacity of PSP-NP for CA and DCA. PSP-NP was applied to NCM460 normal colonic epithelial cells cultured in CA and DCA. Cell migration ability was assessed using the scratch assay， and the mRNA expression levels of inflammatory cytokines TNF-α， IL-6， and NF-κB were measured by RT-qPCR. ResultsPSP-NP effectively improved colonic damage in COPD model mice， enhanced mechanical barrier function， alleviated inflammatory response， and regulated abnormal changes in colonic flora and bile acid metabolism. Correlation analysis further revealed that PSP-NP regulated colonic bile acid metabolism and reduced the redundancy of secondary bile acids by increasing the relative abundance of Bacteroidota， Verrucomicrobiota， Bacteroides， and Akkermansia， while decreasing the relative abundance of Lactobacillus and Bifidobacterium. Notably， in vitro binding assays demonstrated that PSP-NP bound to differential bile acids DCA and CA， with the strongest binding capacity for DCA at 58.2%. In cellular functional studies， DCA inhibited the migration ability of colonic epithelial cells NCM460 and significantly increased the relative mRNA expression levels of inflammatory factors TNF-α， IL-6， and NF-κB. Importantly， co-treatment with PSP-NP significantly ameliorated the impact of DCA on NCM460 cells. ConclusionsPSP-NP may significantly improve colonic damage in COPD model mice. The mechanism may involve the regulation of colonic bile acid metabolism and bile acid profiles through both microbial modulation and direct binding， thereby reducing the damage caused by secondary bile acids such as DCA to colonic epithelial cells.

Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug-drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice.