To establish a UFLC-MS/MS method for the determination of valproate acid in human plasma. Methods:The sample was precipitated by methanol. The analysis of valproate acid and diclofenac sodium ( internal standard) was carried out on a Shim-pack XR-ODS II C18 column (2. 0 × 75 mm,2. 2 μm). Gradient elution was adopted with acetonitrile and water (containing 5 mmol·L-1 ammonium acetate) at a flow rate of 0. 3 ml·min-1. The detection was performed with multiple reactions monitoring (MRM) using nega-tive electrospray ionization (ESI) at m/z 142. 8→142. 8 for valproate acid and m/z 294. 0→249. 8 for diclofenac sodium. Results: The calibration curve of valproate acid was linear over the range of 8.4-168.0 μg·ml-1(r=0.997 5). Inter- and intra-day RSDs were less than 15%, and the analysis was proven to be stable. Totally 30 samples determined by EMIT were assayed by the method. And the results of the two methods analyzed by independent t-test showed no statistical significance. Conclusion:The method is rapid,sensitive and spe-cific,which can be applied in the determination of valproate acid in human plasma.

Aim To investigate the effect of N-n-butyl haloperidol iodide(F2) on mitochondria-dependent apoptotic pathway of H9c2 cardiac myocytes during hypoxia/reoxygenation(H/R) injury.Methods The H/R models of H9c2 cardiac myocytes were established.The H9c2 cardiac myocytes were randomly divided into five groups: control group(C group), hypoxia/reoxygenation group(H/R group), F2 low concentration group(L), F2 medium concentration group(M), F2 high concentration group(H).Apoptotic rate was evaluated by flow cytometry(FCM).The levels of Cyto C, Bcl-2, Bax were observed by Western blot.Caspase-3 activity was measured with colorimetry.Results Compared with H/R group, F2 low, medium and high concentrations group could significantly decrease apoptosis rate and increase the ratio of Bcl-2 to Bax proteins and inhibit the release of Cyto C into the cytosolic fraction, and decrease caspase-3 activity.Conclusion F2 can protect H9c2 cardiac myocytes against H/R-induced injury through interfering in mitochondria-dependent pathway.

Aim To investigate the effects of classic calcium antagonists verapamil(Ver),nifedipine(Nif),diltiazem(Dil)and the novel calcium antagonist N-n-butyl haloperidol iodide(F2)which was synthesized by our lab by regulating Ca2+-independent phospholipase A2(iPLA2)on hypoxia/reoxygenation(H/R)injury of cardiac microvascular endothelial cells(CMECs)and the mechanisms.Methods The CMECs were isolated from SD neonatal rats.The H/R model was established,then cells were treated with different concentrations of calcium antagonists and F2.The content of LDH in the cell supernatant was measured by colorimetric method.The levels of IL-6 and AA in cell supernatant were measured by ELISA;and late-stage apoptosis was measured by TUNEL.The mRNA and protein expression levels of iPLA2 in CMECs were examined by real time-PCR and Western blot analysis.Results Calcium antagonists except Dil decreased the generation of LDH,IL-6 and AA in a dose-dependent manner(P<0.05),and reduced the apoptosis(P<0.05).F2 and Ver decreased the mRNA and protein expression of iPLA2 in a dose-dependent manner,while there were no such effects for Nif and Dil.Conclusions Calcium antagonists except Dil have protective effects against H/R injury.F2 and Ver protect CMECs against H/R injury partly through iPLA2.

Objective:To detect the expression of tumor necrosis factor alpha in (TNF alpha) breast cacner and its relationship with imaging features.Methods:Using immunofluorescence and flow cytometry to detect the expression of TNF-α in MDA-MB-231 and MCF-7.Collect 82 patients with mammary gland disease,which was confirmed by pathological tissue,its pathological data,imaging data,and by immunohistochemistry to detect the expression of TNF-α in breast tissues,and analyze and the relationship between its expression and the pathological features and imaging characteristics.Results:TNF-α high expression in MDA-MB-231,the expression of TNF-oα in malignant breast tumor tissue significantly higher than that in benign tumor,the expression quantity associated with lymph node metastasis,TNM stages,strengthen uniform in MRI,the boundary and the shape of the X-ray Mammography (P=0.01),and color flow signal strength in ultrasound (P＜0.05).Conclusions:TNF alpha in breast tumor tissue was unusually high expression,and is closely related to some of the imaging features of breast tumor.

Based on the analyses of the status of humanistic medicine education both at home and abroad, the article emphasized the need for the implement of medical humanities education with the whole process and multidisciplinary integration. In combination with practice, from the three modules of the ex-plicit curriculum, implicit curriculum and integrated curriculum, the author discussed the specific conno-tation of the whole course of medical humanities education. The article also summarized the main points of the course system in teaching practice from the aspects of training objectives, teaching staff construction, teaching methods improvement and innovation, and humanistic quality evaluation of medical students.

Objective:To explore the effect of irinotecan combined with apatinib on the prognosis of patients with advanced gastric cancer.Methods:Sixty-two patients with advanced gastric cancer who were admitted to Shanghai Minhang District Cancer Hospital from January 2016 to October 2018 were selected. Among them, 30 patients were treated with apatinib (control group), and 32 cases were treated with irinotecan combined with apatinib(observation group). Before administration, the two groups were given routine symptomatic intervention, including prevention of vomiting, improvement of leukocyte, nutrition supplement, etc. During the treatment, routine blood examination, liver and kidney function examination were carried out regularly, and the drug dosage was adjusted according to the situation. The chemotherapy regimen was given once every 3 weeks, and both groups received 4 cycles of treatment. After 3 months of treatment, the short-term efficacy was evaluated, and the therapeutic effects of the two groups were compared. The incidence of side effects was analyzed. After 12 months of follow-up, the survival curves were drawn by Kaplan-Meier method, and the progression-free survival (PFS) and overall survival (OS) of the two groups were analyzed.Results:The recent overall remission rates of the observation group and the control group were 9.38% (3/32) and 3.33% (1/30), and the difference was not statistically significant ( χ2 = 0.203, P = 0.652). The disease progression rate of the observation group was lower than that of the control group, and the difference was statistically significant [28.13% (9/32) vs. 53.33% (16/30), χ2 = 4.089, P = 0.043]. There was no statistical difference in the incidence of platelet decline, hemoglobin decline, white blood cell decline, diarrhea, nausea and vomiting, liver damage, and bone marrow suppression between the two groups (both P > 0.05). The median PFS and OS time in the observation group were 5.8 months (5.0-6.3 months) and 8.1 months (7.2-9.3 months), respectively, which were longer than those in the control group [4.9 months (4.7-5.1 months) and 6.0 months (5.2-6.9 months), and the differences were statistically significant (both P < 0.01). Conclusion:The combination of irinotecan and apatinib can reduce the disease progression rate, prolong the survival time, and does not increase the adverse reactions.

Objective To study the impacts of pre-pregnancy maternal BMI and gestational weight gain(GWG)on pregnancy outcomes. Methods We adopted a prospective cohort study with cluster sampling in single pregnant women,who were not with hypertension,diabetes,hyperlipidemia or other diseases in the previous history,neither did they have diseases of heart,liver,kidney,thyroid etc. related to current pregnancy. Those pregnant women who visited the prenatal nutrition clinic under‘informed consent’were surveyed with questionnaire to track their peri-natal complications,delivery mode and neonate birth outcomes etc. Pearson and partial correlations,chi-square test and binary logistic regression were used to study the association between pre-pregnancy maternal BMI,GWG and pregnancy outcomes. Results A total of 623 pregnant women were recruited in the cohort,with 592(95%)of them eligible for analysis. Results from the Multivariate Logistic Regression analysis indicated that,after controlling the potential confounding factors,when compared to women with pre-pregnancy BMI between 18.5 and 24.0,the odds ratios(ORs)for low birth ponderal index(PI) were 2.34[95%confidence interval(CI),1.24-4.42)]among those with BMI<18.5,respectively,while 2.73(1.12-6.68)for high birth PI among those with BMI>24.0. Similarly,when compared to pregnant women with normal GWG(defined as weight gain range from P15 to P85 by stratification of pre-pregnancy BMI),low GWG(P85)appeared the risk factor for high birth weight,high birth PI,and gestational diabetes mellitus,with ORs as 3.83(1.74-8.44),2.39(1.14-5.01) and 2.21(1.07-4.55),respectively. Conclusion Low or high pre-pregnancy maternal BMI and GWG were associated with adverse pregnancy outcomes.

Polycystic ovary syndrome (PCOS) is a common disease that lead to endocrine disorders and infertility in women of child-bearing age.A large number of studies have shown that the pathogenesis of PCOS is related to insulin resistance (IR),hyperandrogenism and high body mass index.At present,remarkable progress has been made in the study of conception methods and the reduction of multiple pregnancies in PCOS patients.However,there is relatively little research on the adverse pregnancy outcomes after conception.Therefore,this study will use evidence-based medicine to make a review of complications in maternal.For instance,pregnancy-induced hypertension syndrome (PIH),gestational diabetes mellitus (G DM),miscarriage,premature delivery and so on.This study provides an overall basis for early prevention and intervention in clinical work through discussing the pathophysiology of PCOS,the risk factors of its occurrence and development,and the management strategies of pre-pregnancy and gestation period.

Objective: To investigate the effects of donor-specific HLA antibodies(DSA) for graft failure in un-manipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT) and the feasible treatment for DSA. Methods: HLA antibodies were examined using the Luminex-based single Ag assay for 92 patients who were going on haplo-SCT and the correlations of graft failure and DSA among the patients who had finished SCT were analyzed. Results: Of the total 92 patients who were going on haplo-HSCT, sixteen (17.4%) patients were HLA Ab-positive, including six (6.5%) patients with antibodies corresponding to donor HLA Ags (DSA-positive). Among the patients who had finished the haplo-HSCT with conventional myeloablative conditioning regimen, the engraftment rate was significantly higher in DSA (-) patients than that in DSA (+) patients [92.3% (24/26) vs 25.0%(1/4), χ²=8.433, P=0.004] and DSA was the only factor relevant with graft failure in multiple-factor analysis [OR=12.0(95% CI 1.39-103.5), P=0.024]. Strategies to decrease antibody levels were taken for 4 patients, two were their first transplantations, and the other two patients were their second haplo-HSCT. Three of the four patients were HLA-I-DSA positive and had gained donor engraftment by means of donor platelet transfusions to decreased the level of DSA, the fourth patient with both HLA-I and HLA-II DSA also gained engraftment with the treatments of TBI, rituximab and donor platelet transfusion. Conclusion DSA is one of the key factors of graft failure in haplo-HSCT. Donors should be selected on the basis of an evaluation of HLA antibodies before transplantation. If haplo-HSCT from donors with DSA must be performed, then recipients should be treated for DSA to improve the chances of successful engraftment.

Objective: To evaluate the outcomes of myelodysplastic syndromes (MDS) patients who received HLA-matched sibling donor allogeneic peripheral blood stem cell transplantation (MSD-PBSCT) . Methods: The clinical data of 138 MDS patients received MSD-PBSCT from Sep. 2005 to Dec. 2017 were retrospectively analyzed, and the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (RR) , non-relapse mortality (NRM) rate and the related risk factors were explored. Results: ①After a median follow-up of 1 050 (range 4 to 4 988) days, the 3-year OS and DFS rates were (66.6±4.1) % and (63.3±4.1) %, respectively. The 3-year cumulative incidence of RR and NRM rates were (13.9±0.1) % and (22.2±0.1) %, respectively. ②Univariate analysis showed that patients with grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD) or hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2 points or patients in very high-risk group of the Revised International Prognostic Scoring System (IPSS-R) had significantly decreased OS[ (42.9±13.2) %vs (72.9±4.2) %, χ²=8.620, P=0.003; (53.3±7.6) %vs (72.6±4.7) %, χ²=6.681, P=0.010; (53.8±6.8) %vs (76.6±6.2) %vs (73.3±7.7) %, χ²=6.337, P=0.042]. For MDS patients with excess blasts-2 (MDS-EB2) and acute myeloid leukemia patients derived from MDS (MDS-AML) , pre-transplant chemotherapy or hypomethylating agents (HMA) therapy could not improve the OS rate[ (60.4±7.8) %vs (59.2±9.6) %, χ²=0.042, P=0.838]. ③Multivariate analysis indicated that the HCT-CI was an independent risk factor for OS and DFS (P=0.012, HR=2.108, 95%CI 1.174-3.785; P=0.008, HR=2.128, 95%CI 1.219-3.712) . Conclusions HCT-CI was better than the IPSS-R in predicting the outcomes after transplantation. The occurrence of grade Ⅲ-Ⅳ aGVHD is a poor prognostic factor for OS. For patients of MDS-EB2 and MDS-AML, immediate transplantation was recommended instead of receiving pre-transplant chemotherapy or HMA therapy.