Aim To investigate the effect of ketamine plus fluoxetine on depressed behavior and the expres-sion of neuronal nitric oxide synthase (nNOS)and CA-PON in prefrontal lobe of mentally depressed rats at different time points,so as to study the possible mecha-nism of ketamine plus fluoxetine inducing antidepres-sant behavior.Methods Healthy adult male Sprague-Dawley rats,aged 2.5 ~3 months,weighing 220 ~270 g,were induced as the rodent model of depression by chronic unpredictable mild stress (CUMS).After the models of depression were established,96 of CUMS modeling successfully depressed rats were selected. Then they were randomly divided into four groups (n =24 each):the depressed group (group D,untreated group),ketamine group (group K,treated with intrap-eritoneal injection of ketamine 1 0 mg·kg -1 once a day for 3 days or 7 days),fluoxetine group (group F,trea-ted with gavage of fluoxetine 1 .8 mg·kg -1 once a day for 3 days or 7 days),or ketamine plus fluoxetine group (group KF,treated with intraperitoneal injection of ketamine 1 0 mg·kg -1 plus gavage of fluoxetine 1 .8 mg·kg -1 once a day for 3 days or 7 days).Open field test and sucrose preference test were performed 1 day before depression model was established,and 1 day before and after treatment.The rats were sacrificed 1 day after the last test for determination of the expres-sion of nNOS and CAPON protein (using immuno-his-tochemisity)and mRNA (by RT-PCR)in the prefron-tal lobe.Results After the models of depression were established,the total distance,rearing number and the sucrose preference percentage (SPP)were decreased significantly compared with those before (P <0.05). There was no significant difference among all groups in the total distance,rearing number and the SPP before treatment (P >0.05 ).Compared with groups D and F,the total distance was prolonged,the number of rea-ring and SPP were significantly increased,the expres-sion of nNOS protein and mRNA was down-regulated and the expression of CAPON protein and mRNA was up-regulated in groups K and KF,with 3 days’treat-ment (P <0.05).Compared with group D,the total distance was prolonged,the number of rearing and SPP were significantly increased,the expression of nNOS protein and mRNA was down-regulated and the expres-sion of CAPON protein and mRNA was up-regulated in groups K,F and KF with 7 days’treatment (P <0.05).Compared with group F,the total distance was prolonged,the number of rearing and SPP were signifi-cantly increased,the expression of nNOS protein and mRNA was down-regulated and the expression of CA-PON protein and mRNA was up-regulated in group KF with 7 days’treatment (P <0.05).Conclusion Co-administration of antidepressant fluoxetine with ket-amine may induce a more pronounced antidepressant activity than treatment with each antidepressant alone and it can shorten the time to improve the depressive state through promoting the expression of CAPON and inhibiting nNOS activity in the prefrontal lobe of men-tally depressed rats.

To identify and analyze the virulence of a bacteria strain isolated from the blood of a patient with suspected Streptococcus suis (S.suis) infection in a hospital of Beijing,we inoculated the bacteria strain isolated from the blood of the patient to the Columbia with sheep blood agar plate,after Gram staining and microscopical examination,serum agglutination test,VITEK 2 Compact microbial identification system test and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) test,S,suis species specific gene 16SrRNA,S.suis species serotype 2 specific virulence gene capsule polysaccharide 2J (cps2J) and virulence gene muramidase-released protein (mrp),hemolysin (sly),extracellular factor protein (ef),glutamate dehydrogenase (gdh) genes,fibronectin-binding protein (fbps),glyceraldehyde-3-phosphate dehydrogenase (gapdh) genes and virulence correlated gene orf2 were further detected by PCR.Results showed that the suspicious bacteria strain of S.suis was identified as S.suis type 2 (S.suis 2) by conventional methods,MALDI-TOF-MS and PCR.PCR results showed that cps2J,sly,ef,gdh,fbps,gapdh and or f2 genes were positive,and mrp gene was negative.In conclusion,the bacteria strain isolated from the patient's blood is sly+/ef+/mrp-virulent S.suis 2.

The effect of realgar nanoparticles (NPs) on endogenous small molecules in rat kidney was analyzed by mass spectrometry-based metabolomics.The relationship between the changes of metabolites and the nephrotoxicity of realgar NPs was also discussed to provide a basis for the further toxicity study and the clinical application of realgar NPs.SD rats were randomly divided into seven groups,including control group,three doses (40,200,1 000 mg/kg) of relegar and realgar NPs groups,respectly.After 28 days of continuous intragastric administration,all rats were sacrificed and their serum and kidney samples were collected.The toxic effect of realgar NPs on kidney tissues were examined by biochemical analysis and histopathologic examination,which revealed a dosedependent nephrotoxicity induced by realgar NPs.The LC-MS and GC-MS analysis were performed for the subsequent metabolomics study.A series of 32 metabolites were found to be altered significandy in the kindey of realgar NPs treated rats,and might serve as potential nephrotoxicity biomarkers.The results of metabolic pathway analysis indicated that the nephrotoxicity of realgar NPs might be associated with the disorders of the amino acids and phosphatidic acid metabolism.

Objective To explore the relationship between the polymorphism of excision repair cross-complementation group 1 (ERCC1) C8092A locus and the efficacy and prognosis of platinum-based chemotherapy for lung cancer (LC), and to provide a theoretical basis for precision treatment of LC. Methods From January 2014 to October 2017, 120 patients from two tertiary hospitals in Haikou City, and with pathologically confirmed lung cancer treated with platinum-based chemotherapy were selected as the research objects. After informed consent was obtained, peripheral blood samples were collected for DNA extraction, and the genotype of ERCC1 C8092A locus was detected by mass spectrometry. WHO's Response Evaluation Criteria in Solid Tumours (RECIST) was used to judge patients' chemotherapy efficacy and patients' survival status was obtained by telephone follow-up and other means. Results Among the 120 LC patients, the genotype frequencies of ERCC1 C8092A locus were 67 cases of CC wildtype (55.8%), 45 cases of CA heterozygous type (37.5%), and 8 cases of AA rare mutation type (6.7%), which conformed to Hardy-Weinberg equilibrium (χ2=0.140, P>0.05). The total effective rate of chemotherapy was 32.5%, with the highest effective rate in patients with the CA genotype (42.2%) at the ERCC1 C8092A locus and the lowest in patients with the CC genotype (25.4%). The overall one-year survival rate was 68.3% and the three-year survival rate was 35.8%. The patients with ERCC1 C8092A AA genotype had the lowest survival rate, with a one-year survival rate of 50.0% and three-year survival rate of only 25.0%. However, there were no statistical differences in the overall survival rate among the three genotypes of carriers of ERCC1 C8092A (χ2=0.328, P=0.849). Conclusions The polymorphism of ERCC1 C8092A locus is associated with the efficacy of platinum-based chemotherapy for LC, and patients with CA genotype have the highest efficacy. The one-year and three-year survival rates of patients with CC genotype are significantly higher than those of CA and AA genotypes.

Objective To evaluate the effects of exendin-4 on glial brillary acidic protein (GFAP ) and interleukin-1β(IL-1β) expression in hippocampi of aged rats .Methods Forty-eight healthy male Sprague-Dawley rats ,aged 22-24 weeks ,weighing 500-700 g ,were randomly divided into 4 groups (n=12 each) using a random number table:control group (group C ) ,exendin-4 group (group E ) ,operation group (group O ) and exendin-4 plus operation group (group OE) .The rats were anesthetized with intraperitoneal fentanyl and droperidol .Groups C and E did not receive anesthesia or splenectomy .In O and OE groups ,splenectomy was carried out .In E and OE groups , exendin-4 5 μg/kg was injected intraperitoneally at 30 min before skin incision and 12 h after operation .C and O groups received the equal volume of normal saline instead of exendin-4 .Learning and memory function was assessed using Morris water maze test (escape latency (EL) and total swimming distance (TSD) at 1 day before operation (T0 ) .The fasting blood glucose was measured after anesthesia (T1 ) ,at the end of operation (T2 ) and on postoperative day 1 (T3 ) .The rats were sacrificed after assessment of the cognitive function at T 3 and the hippocampi were removed for determination of the expression of GFAP (by immuno-histochemistry ) and IL-1β(by Western blot ) .Results There was no significant difference in the EL and TSD at T0 between the four groups ( P>0.05) .Compared with group C ,the EL and TSD were significantly prolonged at T3 and fasting blood glucose was increased at T2 ,3 ,and the expression of IL-1βand GFAP was up-regulated at T3 in O and OE groups ( P<0.05) .Compared with group O ,the EL and TSD were significantly prolonged at T3 and fasting blood glucose was decreased at T2 ,3 ,and the expression of IL-1βand GFAP was down-regulated at T3 in group OE ( P<0.05) . Conclusion Exendin-4 can improve the postoperative cognitive function of aged rats by inhibiting inflammatory responses in hippocampi and maintaining stable perioperative blood glucose .

Objective To investigate the effects of glycosaminoglycans (HGAG) on the immune function of peripheral blood cells from patients with pulmonary tuberculosis.Methods Peripheral blood monouclear cells (PBMC) were isolated from peripheral blood of 40 healthy people (healthy group) and 30 tuberculosis patients (tuberculosis group) and cocultured with HGAG in vitro for 24 hours.Flow cytometry was used to detect the expression of CD45RA and CD45RO,as well as the expression of CD1a and CD83.Results The results showed that the expression of CD45RA and CD45RO in the tuberculosis group was the most significant (P ＜ 0.05) at the concentration of 50 μg/m coculturing with HGAG.The expression of CD45RA and CD45RO were most obvious in the healthy group at the concentration of 10 μg/ml and 50 μg/ml respectively (P ＜0.001).The difference of CD45RA between the two groups was no significant (P ＞0.05),while the difference of CD45RO was statistically significant (P ＜ 0.01) before co-culturing.The expression of CD45RA and CD45RO at 10 μg/ml and 50 μg/ml after co-culturing with HGAG were statistically significant (P ＜ 0.05).There was no statistical difference in CD1a and CD83 in healthy group before and after co-culturing (P ＞ 0.05),while there was statistically difference (P ＜ 0.05) before and after culturing in tuberculosis group.Before co-culturing,there was no significant difference in the expression of CD1a between the healthy group and the tuberculosis group (P ＞ 0.05),but CD83 expression was statistically different (P ＜ 0.001).After co-culturing,there were no significant differences in CD1a and CD83 expression between healthy and healthy groups (P ＞ 0.05).Conclusions HGAG can down-regulate the expression of CD45RA and up-regulate the expression of CD45RO in a certain concentration range,and promote the maturation of dendritic cells (DC) in tuberculosis patients and regulate the cellular immunity of patients with pulmonary tuberculosis in vitro.

Objective:To evaluate the effects of different rates of compliance with the enhanced recovery after surgery (ERAS) protocol on postoperative recovery in patients undergoing hysterectomy.Methods:A total of 312 patients, aged 18-60 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, scheduled for hysterectomy, were enrolled in the study.ERAS protocol was implemented.The patients were divided into 3 groups based on compliance rates: compliance rate<70% group (group A), 70%≤compliance rate<85% group (group B) and compliance rate≥85% group (group C). The development of postoperative complications, hospitalization time, patients′ satisfaction score and hospitalization cost were recorded. Results:Compared with group A ( n=88) and group B ( n=118), the total incidence of complications was significantly decreased in group C ( n=96) ( P<0.05). The patients′ satisfaction scores were gradually increased in A, B, and C groups on the day of discharge and at 30 days after discharge ( P<0.05). Conclusions:Higher compliance with the ERAS protocol is helpful for postoperative recovery in patients undergoing hysterectomy.

Objective To evaluate the value of perioperative multimodal stratified analgesia guided by PPRS-CYMZ 2.0. Methods One hundred and sixteen patients of both sexes, aged 16-85 yr, of A-merican Society of Anesthesiologists physical statusⅠ-Ⅲ, scheduled for elective surgery in our hospital in August 2016, were included in this study and assigned into empirical analgesia group(group E, n=79) and stratified analgesia group(group S, n=73). The risk of postoperative pain was estimated by an expe-rienced associate chief anesthesiologist based on his clinical experience, and the perioperative analgesic protocol was determined in group E. The risk of postoperative pain was assessed using the perioperative pain risk scale PPRS-CYMZ 2.0 by another experienced associate chief anesthesiologist, the risk was stratified according to the scores, and the corresponding stratified analgesic protocol was determined in group S. Vis-ual analog scale scores and parents′satisfaction with analgesia were recorded on postoperative day 30. The requirement for preventive analgesia, total pressing times of patient-controlled analgesia(PCA)pump in 0-6 h, 6-24 h and 24-72 h periods, PCA background infusion dose and consumption of rescue analgesics were recorded. The development of adverse events during postoperative hospital stay and postoperative re-covery were also recorded. Analgesia-related parameters of medical economics were calculated. Results There was no significant difference in postoperative pain risk stratification between group E and group S(P>0.05), and the majority of patients were at moderate risk. Compared with group E, no significant change was found in visual analog scale scores on postoperative day 30, PCA background infusion dose or incidence of postoperative adverse effects(P>0.05), the requirement for preventive analgesia and satisfaction scores were significantly increased in high risk patients, the consumption of rescue analgesics was decreased in moderate risk patients(P<0.05), no significant change was found in the total pressing times of PCA pump in each time period in low risk patients(P>0.05), the total pressing times of PCA pump was significantly decreased, and the direct analgesic cost per patient and total analgesic cost were decreased in moderate and high risk patients, and the first ambulation time and length of postoperative hospital stay were shortened in high risk patients in group S(P<0.05). Conclusion PPRS-CYMZ 2.0 can achieve perioperative multi-modal stratified analgesia and individualized treatment.

Objective:To explore the feasibility, accuracy and reproducibility of a novel, fully automated three-dimensional echocardiography right ventricular(RV) quantification software(3D Anto RV) to evaluate the RV volume and RV ejection fraction (RVEF) using artificial intelligence in patients after heart transplantation (HT) comparing with the gold reference-cardiac magnetic resonance (CMR).Methods:Forty-six patients after HT who were scheduled for echocardiogram at their routine follow-up examinations and also agreed to undergo CMR examination within the following 24 hours in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from October 2018 to June 2019 were prospectively included. The right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV), right ventricular stroke volume (RVSV) and RVEF of HT patients were measured by CMR 3D Auto RV and conventional semi-automated three-dimensional echocardiography RV quantification software (Tomtec 4D RV function 2.0). The results of the 3D Auto RV and conventional semi-automated Tomtec were respectively compared with CMR using paired two-tailed student′s t-tests, Pearson correlation coefficients and Bland-Altman analyses. Results:The feasibility of the 3D Auto RV was 87%.The fully automated analysis realized in 27 (59%) patients by 3D Auto RV and the analysis time required only (12±1)s. The results of the remaining 19 (41%) patients needed manual adjustment and the mean analysis time in manual adjustment was also <2 min that was shorter than the conventional semi-automated three-dimensional echocardiography RV quantification software[(108±15)s vs (160±34)s, P<0.001]. For the results of RV volumes: There were good correlations between the 3D Auto RV and CMR, conventional semi-automated Tomtec and CMR for the measurements of RVEDV, RVESV and RVSV ( r=0.77-0.84, all P<0.001). In addition, compared with CMR, although there were significantly underestimated RV volumes by the 3D Auto RV and conventional semi-automated Tomtec, the negative bias was smaller in the 3D Auto RV than the conventional semi-automated Tomtec. For the results of RVEF: the corresponding RVEF derived from 3D Auto RV and CMR showed an excellent correlation and consistency ( r=0.84, P<0.001; bias=-1.1%, Limit of agreement=-8.1%-6.0%). In addition, the correlations between the manual adjustment by 3D Auto RV and the CMR ( r=0.63-0.72, all P<0.001) was lower than the correlations between the 3D Auto RV and the CMR ( r=0.76-0.82, all P<0.001) for RV volumes and RVEF.Finally, 3D Auto RV had a good reproducibility. Conclusions:The new fully 3D Auto RV quantification software underestimate RV volumes that less than the conventional semi-automated Tomtec. And the 3D Auto RV quantification software can accurately evaluate the RVEF in patients after HT with rapid analysis and higher reproducibility, which may also support the routine adoption of this method during follow-ups of HT patients in the daily clinical workflow.

Objective: To investigate the effects and mechanism of Holothurian Glycosaminoglycan (hGAG) alone in combination with cisplatin (DDP) on apoptosis of pulmonary adenocarcinoma cell A549. Methods: A549 cells were separately treated with blank, hGAG, DDP and hGAG combined with DDP (hGAG + DDP). The cell morphology in 4 groups was observed using light microscope. CCK8 assay was used to determine the cell viability. Flow cytometry by Hoechst 33258 and AnnexinV-FITC/PI staining was applied to detect cell apoptosis. Western blot was then used to detect the protein expression of Bax, Bcl-2, survivin and caspase-3. Results: After treatment for 24 h, the inhibitory rates of A549 cells in control, hGAG, DDP and hGAG + DDP groups were 0, (19.74±5.39)%, (42.01±2.57)% and (53.89±4.58)%, respectively. Moreover, after treatment for 48 h and 72 h, the inhibitory rates in each group were 0, (23.17±4.78)% and (29.17±4.21 )%, (54.00±7.64)% and (59.35±7.31)%, as well as (77.58±4.26)% and (79.94±4.58)%, respectively. The cell viability was significantly lower in drug treatment groups compared with those in control group at the same time point (P<0.05). Hochest 33258 staining showed that no obvious apoptotic cells were detected in the control group, while apoptotic cells were visible in hGAG, cisplatin and combination groups. Flow cytometry showed that cell apoptotic rates were (2.38±0.59)%, (12.59±4.22)%, (16.36±3.63)% and (44.60±5.45)% in the control, hGAG, DDP and hGAG + DDP groups, respectively. The cell apoptosis was significantly lower in drug treatment groups compared with those in control group at the same time point (P<0.05). Furthermore, western blot results showed that the expression of Bax and caspase-3 protein was increased (P<0.05), whereas Bcl-2 and survivin was decreased (P<0.05) in the hGAG+ DDP group compared with cisplatin alone (P<0.05). Conclusions HGAG can inhibit the proliferation and promote the apoptosis of human lung adenocarcinoma A549 cells. Meanwhile, it can strengthen the chemosensitivity of A549 cells to DDP via up-regulation of Bax, caspase-3 and down-regulation of Bcl-2 and survivin.