OBJECTIVE：To i nvestigate the metabolism stabilities of novel hypoglycemic compound LSM- 13 in rat liver microsomes，and to analyze the possible metabolites. METHODS ：LSM-13 was dissolved in rat liver microsome incubation system initiated by reduced nicotinamide adenine dinucleotide phosphate ，and was incubated in water at 37 ℃. The reaction was terminated with acetonitrile at 0，5，10，15，30，45 and 60 min，respectively. Using indomethacin as internal standard ，the concentration of LSM-13 in incubation system was determined by HPLC. The residual percentage and enzyme kinetic parameters of LSM- 13 were calculated at different incubation time points with the concentration of LSM- 13 incubated for 0 min as reference. UPLC-Q-TOF/MS was used to analyze and speculate the metabolites of LSM- 13 in rat liver microsomes. RESULTS ：After 60 min incubation ，the remaining percentage of LSM- 13 was（56.07±0.95）％，the half-life was 42.78 min，and the intrinsic clearance was 0.032 4 mL/（min·mg）. Compared with total ion flow diagram of rat liver microsome blank samples ，three chromatographic peaks were added in the samples incubated for 60 min；the corresponding molecular ion peaks were m/z 505.133 8，417.102 4，293.111 7 [M+H]+；the possible metabolites may be dehydrogenation ，O-debentylation and hydrolysis products of LSM- 13. CONCLUSIONS ： The compound LSM- 13 has moderate stability in rat liver microsomes ，and may undergo dehydrogenation ，O-debentylation and hydrolysis.

OBJECTIVE：To investigate th e stabilities of antitumor candid ate Gedatolisib in plasma in vitro and simulated gastric/intestinal fluids ，and to analyze the possible catabolites in plasma. METHODS ：HPLC method was adopted. Using indometacin as internal standard ，the contents of Gedatolisib incubated in plasma of SD rats （male）for 0，0.5，1.0，1.5，2.0，3.0 h and blank simulated gastric fluid （pH 1.3，no enzyme ），blank simulated intestinal fluid （pH 6.8，no enzyme ），simulated gastric fluid（pH 1.3，containing pepsin ）and simulated intestinal fluid （pH 6.8，containing trypsin ）for 0，0.5，1.0，2.0，3.0，4.0，6.0 h were determined. The remaining percentage of Gedatolisib was calculated. UPLC-Q-TOF/MS was used to analyze the TIC of blank plasma and incubated samples. The differential peaks were compared， and catabolites were inferred by MS 1Z073）.gzwjkj2019-1- chromatograms. RESULTS ： The remaining percentage in plasma of rats for 2.0 h was about 63％，and there was nosignificant change after continued incubation. The remaining percentage of Gedatolisib incubated in blank simulated intestinal fluid for different time ranged （99.18 ± 2.15）％ -（103.20 ± 3.41）％ . The remaining percentage in simulated com intestinal fluids for 2.0 h ranged （88.76 ± 1.53）％ . The remaining percentage in blank simulated gastric fluids for 2.0 h was ranged （85.63±1.55）％，and there was no significant change after continued incubation. The remaining percentage in simulated gastric fluid was from （94.94±3.52）％（0 h）to（16.19±1.17）％ （6.0 h）. TIC of UPLC-Q-TOF/MS showed that the differential peaks of incubated samples and blank plasma was 6.42 min under positive mode scanning ，molecular ion peak of m/z 616.335 1，simulated 632.327 7，630.317 0，602.278 6 [M+H]+ could be found in scanning channel. It was speculated that Gedatolisib could generate 1-（4-（3-（4，6-dimorpholino-1，3，5-triazin-2-yl）phenyl）urea） benzoyl）-N，N-dimethylpiperidin-4-amine oxide ，1-（4-（4-（dimethylamino）piperidine-1-carbonyl）phenyl）-3-（4-（4-morpholino-6- （3-oxomorpholino）-1，3，5-triazin-2-yl）phenyl）urea and 1-（4-（3-（4-（4，6-dimorpholino-1，3，5-triazin-2-yl）phenyl）urea） benzoyl）-N-methylpiperidine. CONCLUSIONS ：Gedatolisib is not stable in rat plasma ，and it may undergo terminal N oxidation， morpholine ring oxidation and terminal N demethylation. Gedatolisib is stable in artificial intestinal fluid and blank artificial gastric/ intestinal fluid ，and degrades obviously in the presence of pepsin.

Objective To investigate the clinical pathological characteristics and prognosis of primitive neuroectodermal tumor (PNET) of breast.Methods Patients with breast PNET were retrieved from CNKI,Pubmed,Europe PMC and other databases from Jan.1980 to Dec.2016.The clinical data of one patient with breast PNET in our hospital were analyzed retrospectively.Results 18 cases had painless,rapid growth mass as the main clinical features.The pathological morphology showed small round cell tumors,PAS staining positive.Immunohistochemistry CD99 and Fli-1 characteristic expression were the main indexes for the diagnosis of breast PNET.The positive expression of Vimentin,NSE,Syn and negative expression of CK,EMA,Desmin,CgA,LCA,S-100 also played an important role in the diagnosis of breast PNET.The positive expression of genetic marker EWSRI was the golden standard for diagnosis of breast PNET.The size of the tumor,surgical treatment,lymph node metastasis,distant metastasis and chemotherapy were the important factors that affect the prognosis of the PNET.The survival rates of 1 and 3 years were 71.4％ and 33.3％ respectively.Conclusions Breast PNET is a rare tumor with poor prognosis,and its diagnosis is highly dependent on pathology.Surgery can significantly improve the prognosis of the patients.Surgery should be the main treatment,combined with radiotherapy and chemotherapy.The current study does not show evidence of effectiveness in terms of endocrine or targeted drug therapy for breast PNET patients.

OBJECTIVE:To investigate the effects ofAlisma orientalis polysaccharides on the insulin resistance and lipid metabolism disorder in type 2 diabetes mellitus (T2DM) rats and its possible mechanism.METHODS:T2DM rat model was induced by high fat diet combined with intraperitoneal injection of streptozotocin (30 mg/kg).50 model rats were randomly divided into model group (normal saline),glibenclamide group (positive control,25 mg/kg) and A.orientalis polysaccharide high-dose,medium-dose and low-dose groups (400,200,100 mg/kg),with 10 rats in each group.Other 10 normal rats were included in normal control group (normal saline).All groups were given drugs ig,once a day,for consecutive 6 weeks.After 5 weeks of administration,the glucose tolerance test was conducted.Fasting blood glucose (FBG) levels were measured in rats 0,30,60,90,120 min after intraperitoneal injection of 2 g/kg Glucose solution,respectively.After 6 weeks of administration,serum levels of FINS and FBG were measured,and HOMA-IR and insulin sensitivity index (ISI) were calculated;serum levels of FFA,LDL-C,HDL-C,TG and TC were detected,and the levels of SOD,GSH-Px and MDA in liver tissue were detected.RESULTS:Compared with normal control group,FBG levels of rats in model group at 0-120 min were increased significantly in glucose tolerance test.After 6 weeks of administration,the serum levels of FINS,LDL-C and ISI,and the levels of SOD and GSH-Px in the liver tissue of the model group were decreased,and the differences were statistically significant (P＜0.05).Compared with model group,each index of other administration group were improved significantly (P＜0.05),except that HOMA-IR,the serum levels of LDL-C and HDL-C were not significantly improved in A.orientalis polysaccharide low-dose group (P＞0.05).CONCLUSIONS:A.orientalis polysaccharide can improve insulin resistance and lipid metabolism disorder in T2DM rats through antioxidant effect.

Objective To learn the acceptance of rural community health workers (CHWs ) following the reform of rural health workers′team building in Pudong New Area.Methods 3 295 CHWs were surveyed with questionnaire for their acceptance of the incentive policies,and chisquare test analysis was used to analyze the differences among CHWs in individual areas.Results Over 80.0% of the CHWs reported that they were motivated by the incentive policies to improve their professional competence, medical service and organizational commitment;40.9% of them reported that the policies improved their social status;and 47.3% of them believed the policies could promote the rural areas to attract and retain talents.When a comparison was made of CHWs′feedbacks on different aspects,significant differences indicated that the proportion of CHWs′positive attitudes was the highest at remote rural communities. Conclusions The rural health workers′team building reform could promote incentive on the CHWs,yet with obvious regional differences.

Objective To compare the iodine contrast agent dosage,radiation dose and image quality in CT pulmonary angiogra-phy (CTPA)with low tube voltage and high tube current in 64-slice spiral CT.Methods 60 patients with suspected pulmonary em-bolism in our hospital were randomly chosen and divided into three groups:Group Ⅰ:20 patients,using 120 kV,180 mA,contrast dose of 70 mL.Group Ⅱ:20 patients,using 100 kV,280 mA,contrast dose of 50 mL.Group Ⅲ:20 patients,using 80 kV,automat-ic tube current modulation techniques (300-500 mA),comparative dose of 30 mL.CT values and image noise of three pulmonary central areas and a segment branch were measured in each group.Objective indicators,subjective image quality assessment,CT dose index volume (CTDIvol),dose-length product (DLP)and effective absorbed dose (ED)were compared in three groups to evaluate the value of low kV,high mA with low-contrast dose in CTPA.Analysis of variance and t-test was used for data analysis.Results Compared with those of the standard method of CTPA,all pulmonary dry in two groups of low dose were well displayed.There was no statistical significance between each two groups in image quality score (P > 0.05),but was statistical significance in CT values, noise,SNR and CNR (P < 0.01).The CT radiation dose,CTDIvol and DLP of Group Ⅱ and Group Ⅲ were significantly lower than those of Group Ⅰ (P < 0.01).Conclusion Compared with traditional methods,low dose contrast agent injections under 80 kV could reduce the dose of contrast agent and the effect of hardening artifacts due to contrast agent in superior vena cava on right pul-monary artery.It is helpful to reduce the risk of contrast induced nephropathy and reduce patients’exposure to X-ray radiation.

Aim To determine the effective compo-nents of Semen Ziziphi Spinosae for sedative-hypnotic and its mechanism. Methods The extraction of Se-men Ziziphi Spinosae and the rat brain homogenates were prepared. High concentrations of Diazepam com-petitively replaced the ligand compounds of Semen Ziz-iphi Spinosae combining BDZ receptor in brain tissue, and all the compounds with sedative and hypnotic effects were collected and identified by HPLC and LC-MS technique, as the compounds extracted from the brain tissue were administered with Semen Ziziphi Spi-nosae. The brain tissue was administered with Diaze-pam, and with Semen Ziziphi Spinosae and Diazepam. Results The HPLC chromatograms show that the peak time of BDZ receptor ligand compounds was 2. 71 min and 46. 87min, when compared with Diazepam. And the LC-MS chromatograms display the relative molecu-lar weight of the ligand compounds was 274. 28 m/z, 453. 34 m/z,496. 34 m/z and 608. 38 m/z respective-ly. According to the fingerprint of Semen Ziziphi Spi-nosae, these compounds may be fatty acid substances and lupine pill triterpene compounds. Conclusions On the basis of the principle of receptor ligand bind-ing, we established a way to quickly analyze and iden-tify the role of natural products in the same drug target compounds. The method not only can clearly define the effective components of natural products, but also clar-ify the mechanism of action of the compounds. The ac-tive ingredient of calm hypnosis in Semen Ziziphi Spi-nosae may be fatty acid substances Palmitic acid ( C16 H32 O2 ) and lupine pill triterpene compounds Alphitolic acid( C30 H48 O4 ) and Spinosin( C28 H32 O15 ) . They exert their sedative and hypnotic effects by combining with BDZ receptor, and the research has laid a theoretical foundation for the further study about mechanism of Se-men Ziziphi Spinosae.

On the basis of analysis of the current status and future tendency of development of the health services industry in Shanghai,the authors identified key problems and bottlenecks.Thus they made clear the target positioning and principles of the industry,and proposed the basic ideas and pattern of the industry in the 13 th five-year plan period,focusing on such fields as private and high-end healthcare services,traditional Chinese medicine services,public health services,commercial health insurance,and other related industries.In the end,corresponding supporting polices were proposed.

OBJECTIVETo analyze and evaluate the clinical efficacy of heat-sensitive moxibustion for symptoms of large intestine cancer.

METHODSSixty patients with large intestine cancer were randomly divided into an observation group and a control group, 30 cases in each one. FOLFOX chemotherapy regimen was used in the two groups,and heat-sensitive moxibustion was added in the observation group. The acupoints were Zusanli(ST 36), Sanyinjiao (SP 6) Xuehai (SP 10) and Geshu (BL 17), etc. The treatment was applied once a day,five-day treatment as one course. Four courses were required. The reaction rates of uncomfortable symptoms by the Chinese version of the M. D. Anderson symptom inventory (MDASI-C) scale and clinical effects were analyzed and evaluated in the two groups.

RESULTSAfter treatment, the MDASI-C reaction rate of uncomfortable symptoms in the observation group was 50.4% which was lower than 53.3% in the control group (P < 0.05). The total effective rate of symptom improvement in the observation group was 83.3% (25/30), which was higher than 60.0% (18/30) in the control group (P < 0.05).

CONCLUSIONHeat-sensitive moxibustion can improve symptoms of chemotherapy for large intestine cancer.

Aged ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; Drug-Related Side Effects and Adverse Reactions ; etiology ; therapy ; Female ; Fluorouracil ; adverse effects ; therapeutic use ; Humans ; Intestine, Large ; drug effects ; Leucovorin ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Moxibustion ; instrumentation ; Organoplatinum Compounds ; adverse effects ; therapeutic use ; Treatment Outcome