Intrauterine growth retardation (IUGR) is one of the most commonly encountered developmental toxicity, which could lead to perinatal morbidity and mortality, be also extended from the fetus to adulthood, and seriously affect the quality of the population. Caffeine widely exists in a variety of daily beverages and some drugs. Its consumption is increasing year by year. Caffeine intake during pregnancy is one of the risk factors for IUGR. However, its mechanism of adverse outcome based on embryonic research is still unclear. In this paper, the possible mechanisms of caffeine-induced IUGR focusing on 3 important factors-the mother, placenta and fetus were explored. Caffeine's impact on the mother is the chronic activation of renin-angiotensin system; on the placenta, caffeine induces cell damage or the failure of the cell proliferation/apoptosis balance, leading to blockage of blood supply to the placenta; caffeine is also capable of directly affecting fetal development through interfering its neuroendocrine.

Objective To investigate the inhibitory effect of icariin(ICA) on the xenograft tumors growth of esophageal car‐cinoma and to preliminarily investigate its mechanism .Methods The MTT assay and Giemsa staining were applied to detect and observe the in vitro inhibitory effect of ICA on esophagus cancer cell lines Eca‐109 and TE‐13 .The xenograft tumor model of nude mouse esophagus cancer cell was constructed and divided into 3 groups ,6 cases in each group .Each mouse in the experimental group was intraperitoneally injected by ICA 50 mg/kg ;while the control group was injected by the same volume of normal saline and the positive control group was injected by cis‐platinum 2 mg/kg ,once every 2 days ,a total of 14 days .The tumor volume was measured once per 3 d .After experiment ,the tumor weight was measured;the TUNEL staining was used to observe the morphological chan‐ges and cell apoptosis of tumor tissue in each group .The changes of Fas and FasL protein expression in tumor tissues were analyzed by immunohistochemistry .The FasL and IFN‐γlevels in peripheral blood were tested by the ELISA assay .Results ICA exerted no obvious inhibitory effect on the proliferation of Eca‐109 and TE‐13 cell in vitro .The average volume and weight of xenografts tumor had statistical difference between the experimental group and the positive control group (P<0 .05) .The TUNEL staining results showed that the tumor tissues had obvious apoptosis ,the number of apoptosis cells was significantly increased compared with the control group(P<0 .05) .The immunohistochemistry experimental results showed that the expression of Fas and FasL was signifi‐cantly increased(P<0 .05) .The ELISA experimental results demonstrated that the FasL and IFN‐γlevels of peripheral blood in the experimental group were significantly increased(P<0 .05) .Conclusion ICA had no obvious inhibitory effect on esophageal cancer cell proliferation in vitro ,but could induce in vivo apoptosis through the Fas expression and secretion of FasL and IFN‐γ,thus plays the role of anti‐esophageal cancer .

Objective To investigate the characteristics of chronic Keshan disease (CKD) and ischemic cardiomyopathy ( ICM ) and provide a basis for differential diagnosis . Methods Forty-two cases of CKD were randomly sampled from 6 Keshan disease districts in Sishui, Zoucheng, Juxian, Wulian, Yishui and Qingzhou Counties of Shandong Province, as CKD group. Thirty-one cases of ICM were selected from Qianfushan Hospital as ICM group. Echocardiography was used to analyze the cardiac morphology , hemodynamic and function. Results Left atrial internal diameter(LA), left ventricular(LV), end-diastolic internal diameter(LVd), right ventricular diameter(RV) and right atrial transverse diameter(RAtd) of the CKD group[(45.14 ± 6.93),(68.48 ± 6.24),(28.90 ± 3.14),(52.79 ± 6.62)mm] were higher than those of ICM group[(40.68 ± 5.12),(60.55 ± 4.07),(24.35 ± 2.12), (47.68 ± 8.53)mm , t = 3.03, 6.55, 7.38, 2.88, all P < 0.01]. In CKD group, several atrioventricular carities were enlarged, and the ventricular wall tended to become thin. In ICM group, left atrioventricular cavities were enlarged, and the apex of LV was thin spherical. The LV ejection fraction(LVEF) and fractional shortening of LV (LVFS) of the CKD group [(40.50 ± 10.68)%, (22.81 ± 6.24)%] were lower than those of the ICM group [(54.61 ± 6.58)%, (30.71 ± 4.29)%, t = - 6.957, - 5.976, all P < 0.01]. Diffuse hypokinetic motion of LV reduced in 85.7%(36/42) of CKD patients, and 83.9%(26/31) of ICM patients had segmental LV dyskinesia. Slight regurgitation of single valve was common in ICM group , but several regurgitation of multiple valves were more common in CKD group. Conclusion Echocardiography is a valuable noninvasive technology for differentiating CKD and ICM.

A series of novel quinolinone acid-containing compounds were designed and synthesized. Their structures were confirmed with 1H NMR and MS. The target compounds were tested for anti-HIV-1 integrase activities in vitro with enzyme linked immunosorbent assay (ELISA). The result showed that D-2, D-4 and D-7 have anti-integrase activity with IC50 < 100 micromol L(-1).

In China, traditional Chinese medicines （TCMs） have been used in clinical applications for thousands of years. The successful hyphenation of high-performance liquid chromatography （HPLC） and mass spectrometry （MS） has been applied widely in TCMs and biological samples analysis. Undoubtedly, HPLC/MS technique has facilitated the understanding of the treatment mechanism of TCMs. We reviewed more than 350 published papers within the last 5 years on HPLC/MS in the analysis of TCMs. The present review focused on the applications of HPLC/MS in the component analysis, metabolites analysis, and pharmacokinetics of TCMs etc. 50% of the literature is related to the component analysis of TCMs, which show that this field is the most popular type of research. In the metabolites analysis, HPLC coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry has been demonstrated to be the powerful tool for the characterization of structural features and fragmentation behavior patterns. This paper presented a brief overview of the applications of HPLC/MS in the analysis of TCMs. HPLC/MS in the fingerprint analysis is reviewed elsewhere.

Objective To investigate the sedative and hypnotic interaction between remifentanil and propofol by target-controlled infusion (TCI) during induction of anesthesia.Methods Third-two ASA Ⅰ or Ⅱpatients,aged 22-63 yr,body mass index 18-25 kg/m2,scheduled for elective surgery under general anesthesia,were randomly divided into 4 groups(n=8 each).Group Ⅰ only received TCI pmpofol.GroupⅡ,Ⅲ,and Ⅳreceived a target concentration of 2,4 or 6 ng/ml remifentanil respectively.While the blood-effect site concentrations of remifentanil were equilibrated,patients received TCI of propefol,with an initial target concentration of 0.5μg/ml.After the blood-effect site concentrations of propofol were equilibrated then with 0.5μg/ml increments until the loss consciousness was achieved.The eyelash reflex and state of consciousness were assessed and radial arterial blood sample 6 ml was taken every 3 min to determine the remifentanil and propofol concentrations in blood.Propofol and remifentanil concentrations in blood were measured by reversed-phase high-performance liquid chromatography and high-performance liquid chromatography with ultraviolet detection respectively.The sedative and hypnotic interaction between propofol and remifentanil was determined with a pharmacodynamie interaction model by regression analysis and determined using the isobolographic method.Results Propofol concentrations in blood were lower in group Ⅱ,Ⅲ and Ⅳ than group Ⅰ(P<0.05).The propofol concentratopms in blood were significantly decreased in trun with the increase in the remifentanil concentrations in blood in group Ⅱ-Ⅳ(P<0.05).At loss of eyelash reflex and loss of consciousness of patients,the pharmacodynamic interaction model by curve fitting was superior to linear regression (P<0.05).At loss of eyelash reflex of patients,the curve fitting result showed EC50,prop=2.77μg/ml and EC50,rem=26.67 ng/ml,and the isobolographic method equation is ECprop/2.77+ECrem/26.67=0.69.At loss of consciousness of patients,the curve fitting result showed EC50,prop==3.76μg/ml and EC50,rem=31.56ng/ml,and the isobolographic method equation is Ecprop/3.76+Ecrem/31.56=0.65.Conclusion Remifentanil (Cp 2-6 ng/ml) and propofol by TCI shows a synergistic type of pharmacodynamic interaction on the sedative and hypnotic during induction of anesthesia.

Objective:To construct GST-tagged human NRP-1 fusion protein expression vector and induce its expression in Escherichia coli ( E.coli) ,then carry on inclusion body refolding and purification so as to obtain GST-NRP-1 fusion protein.Methods:NRP-1 gene was amplified by RT-PCR and inserted into pCR-blunt vector.Then the reconstructed plasmid was inserted into prokaryotic expression vector pGEX-4T-1.The constructed pGEX-4T-1-NRP-1 expression vector was transformed into BL21 cells and induced by i-sopropyl-β-D-thiogalactoside ( IPTG).Bacterial bodies were disrupted by sonication.Then the soluble fraction of fusion proteins were verified by Western blot and purified by Glutathione Sepharose 4B after inclusion body refolding.Results: The NRP-1 gene fragment was amplified by RT-PCR and inserted into pCR-blunt vector.Fusion protein expression vector pGEX-4T-1-NRP-1 was constructed suc-cessfully.After transformation, GST-NRP-1 expression vector was detected in BL21 cells and obtained purifying protein after refolding.Conclusion:The plasmid GST-NRP-1 was constructed successfully and laid basis for subsequent studies.

Objective To investigate the safety and feasibility of the reversed π-shaped esophagojejunal anastomosis in laparoscope-assisted total gastrectomy (LATG) for gastric cancer (GC).Methods The retrospective corss-sectional study was conducted.The clinicopathological data of 18 GC patients who were admitted to the Subei People's Hospital of Jiangsu Province between January 2015 and October 2016 were collected.All the 18 GC patients underwent LATG,surgical procedures included free stomach and lymph node dissection firstly,side-to-side jejunal anastomosis secondly and laparoscopic gastrointestinal reconstruction using reversed π-shaped anastomosis finally.Observation indicators:(1) surgical situations:side-to-side jejunal anastomosis method,conversion to open surgery,operation time,reversed π-shaped anastomosis time,volume of intraoperative blood loss and number of lymph node dissected;(2) postoperative situations:time for initial out-of-bed activity,time to initial anal exsufflation,time for postoperative water intake,time of drainage tube removal,postoperative complications and duration of hospital stay;(3) postoperative pathological examination;(4) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect diet intake,anastomosis patency,gastrointestinal obstruction and patients' survival up to March 2017.Measurement data with normal distribution were represented as (x)±s.Results (1) Surgical situations:18 patients underwent successful LATG and reversed π-shaped esophagojejunal anastomosis,without conversion to open surgery and perioperative death.Five patients used in vitro hand-sewn side-to-side esophagojejunal anastomosis through small incision of specimens sampling,and 13 completed all surgery under laparoscopy.Operation time,reversed π-shaped anastomosis time,volume of intraoperative blood loss and number of lymph node dissected of 18 patients were (187±12)minutes,(37±5) minutes,(735±18)mL and 29±2,respectively.(2) Postoperative situations:time for initial out-of-bed activity,time to initial anal exsufflation,time for postoperative water intake and time of drainage tube removal in 18 patients were (1.6±0.5) days,(2.3±0.4) days,(2.5±0.5) days and (7.5± 1.5) days,respectively.One patient complicated with esophagojejunal anastomosis fistula at postoperative day 3 was cured by drainage and symptomatic treatment and then discharged from hospital.Eighteen patients received regularly angiography using oral water-soluble contrast medium after recovering fluid diet intake,showing anastomosis patency and no contrast medium leakage,and then discharged from hospital.Duration of hospital stay of 18 patients was (12± 11) days.(3) Postoperative pathological examination:of 18 patients,15 were diagnosed with adenocarcinoma and 3 with signet-ring cell carcinoma.T2,T3 and T4 of T staging were respectively detected in 3,3 and 12 patients.N0,N1,N2 and N3 of N staging were respectively detected in 8,3,2 and 5 patients.Stage Ⅰ,Ⅱ and Ⅲ of TNM stage were detected in 3,5 and 10 patients,respectively.(4) Follow-up and survival situations:17 of 18 patients were followed up for 6-25 months,with a median time of 12 months.During the follow-up,2 patients were complicated with sour regurgitation and vomiting after eating at month 6 and 12 postoperatively and received gastrointestinal contrast examination,showing anastomotic stenosis,and then were cured by endoscopic dilation and discharged form hospital.Other patients had good diet and survival,without anastomotic complications.Conclusion The reversed π-shaped esophagojejunal anastomosis in LATG for GC is safe and feasible,with good short-term outcomes.

Objective To explore the feasibility and safety of the posterior approach of robotassisted laparoscopic radical prostatectomy and to the approach.Methods From November 2001 to April 2017,32 patients underwent posterior approach of robot-assisted laparoscopic radical prostatectomy.Patients aged 53 to 81 years,with mean of 66.9 years old.Their prostate volumes were 12.0-73.7 ml with an average of 32.9 ml.All patients were diagnosed by prostate biopsy before surgery.The operation time,blood loss and length of hospital stay were recorded.Results All the operations were completed by robotic assisted laparoscopy with no transition to open surgery.The surgery time was 129-210 minutes with an average of 163.6 minutes.The estimated blood loss was 20-200 ml with an average of 59.3 ml.The hospital stay was 8-21 days with an average of 12.8 days.The postoperative hospital stay was 3-13 days with an average of 6.9 days.The time of postoperative catheter removal was 4-14 days with an average of 7.5 days.Postoperative follow-up was 1-6 months.Twenty-four (75％) patients had early recovery of continence,and all (100％) patients regained continence 3-month postoperatively.Conclusion The posterior approach of robotic assisted laparoscopic radical prostatectomy was a safe and effective surgical technique,which was beneficial in early continence recovery.

Objective To investigate the neuroimaging features in mitochondrial encephalomyopatbies with lactic acidosis and stroke-like episodes(MELAS).Methods Twenty-two clinically diagnosed patients who came from department of neurology,Huashan hospital in October 2003 to July 2006 were analyzed for CT,MRI,MRI contrast,MRA and MRS.Results In all 22 patients,the neuroimaging results of 21 were positive.There were 9 patients lying in hemisphere,12 in both cerebral hemispheres,including occipital,parietal,temporal and frontal lobe.The abnormal areas showed low signal intensity on T_1-weighted MRI,high signal intensity on T_2-weighted MRI and fluid attenuated inversion recovery(FLAIR)images.The lesions of 12/16 patients on MR contrasted images were enhanced.The lesions of one patient showed malacoma-like changes,one showed Fahr syndrome' s change and another showed high signal intensity on MR contrasted images.Conclusion Although the neuroimaging features of MELAS are complicated,the specific ones could help to make the diagnosis.