Research collaboration and interdisciplinary integration is anecessary trend of the development of science and technology,and is especially true in biomedical field.This paper describes the interdisciplinary practice of the projects at Peking University Health Science Center in recent years.Problems and the efficiency of the management is also analysed.

Objective To construct DNA vaccine expressing Mycobacterium tuberculosis(Mtb) immunodominant antigen Ag85A and analyze its anti-tuberculosis T cell responses in BCG primed-mice after DNA vaccination boosting.Methods The coding gene of Ag85A mature fragment was amplified by PCR with H37Rv genomic DNA as template,and then cloned into the eukaryotic expression vector pVAX1 to construct Ag85A DNA vaccine.After purification,Ag85A DNA vaccine was injected intramuscularly twice in BCG primed-mice with BCG vaccination and DNA vaccination alone as control.Eight weeks post-vaccination,spleen lymphocytes were separated and were then used to analyze Mtb antigen specific effector T cell response and polyfuntional IFN-γ/TNF-α/IL-2 secreting CD4+ T cell frequencies and intensities,and CD8+T cell responses by IFN-γ ELISPOT assay and intracellular staining,respectively.Results Compared to BCG vaccinated-and DNA vaccinated-mice,Ag85A DNA boosting not only enhanced significantly BCG primed-mice IFN-γ+TNF-α+IL-2+,IFN-γ+ IL-2+,TNF-α+IL-2+ and IL-2+ CD4+ T cell frequencies and IL-2 secretion,but also improved significantly IFN-γ-secreting and IL-2-secreting CD8+ T cell frequencies.Condusion Ag85A DNA vaccine was constructed successfully and was demonstrated to enhance significantly BCG primed-mice Mtb antigen specific CD4+ and CD8+ T cell responses when boosting,which is beneficial to improve BCG immunogenicity and its waning immune protection against Mtb.

Objective To discuss the clinical manifestations,imaging features and prognosis of children with mild encephalitis/encephalopathy with a reversible splenial lesion(MERS).Methods Twenty-five patients with MERS admitted to Beijing Children′s Hospital,Capital Medical University,between November 2013 and March 2016 were enrolled and their clinical and imaging data were retrospectively analyzed.Ages of onset of these 25 cases were from 6 months to 13 years old.Because of different clinical manifestations in different onset ages,these 25 cases were divided into 2 groups:≤6 years old group (20 cases),with the onset age of 6 months to 3 years and 9 months old(average 2 years and 2 months);>6 years old group(5 cases),with the onset age of 9 years 3 months to 13 years old (average 10 years and 10 months).Results Nineteen cases among the 25 patients had infection history before onset,including 10 cases of digestive tract infection(all were ≤6 years old children),9 cases of respiratory tract infection(6 children ≤6 years old and 3 children >6 years old).The main clinical manifestations included convulsion (18/25 cases,72.0%),fever (17/25 cases,68.0%),vomiting (11/25 cases,44.0%),and disturbance of consciousness (11/25 cases,44.0%).The main clinical manifestation of ≤6 years old group was convulsion (18/20 cases,90.0%),while the main clinical manifestations of the>6 years old group were fever(3/5 cases,60.0%),headache and dizziness(2/5 cases,40.0%),and none of the patients in >6 years old group had convulsion.Eight cases had liver function injury,myocardial enzymes increased in 10 cases,and hyponatremia occurred in 9 cases.Magnetic resonance imaging (MRI) showed 21 cases were type Ⅰ MERS(only involving corpus callosum),and 4 cases of type Ⅱ MERS which involved corpus callosum as well as deep brain white matter,subcortical white matter (centrum semiovale).MRI lesions disappeared after 8-56 days (average 16.5 days) of anti-infection and reducing intracranial pressure treatment.Conclusion MERS is more common in ≤6 years old children,and digestive tract infection is common in ≤6 years old children,while respiratory tract infection is common in >6 years old children.The symptoms in children are mainly manifested as fever,convulsion,vomiting,conscious disturbance,and so on.Infection and hyponatremia are the main causes of MERS in children.MRI is the first choice of imaging examination methods.

Luteolin is an important member of the flavonoid family. It has been reported that luteolin can inhibit the proliferation of serials of tumor cells including solid tumor, ascites cancer and human myeloid leukemia. Luteolin can also sensitize a number of apoptosis-inducing factors by unique mechanisms.
Angiogenesis Inhibitors ; pharmacology ; Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Humans ; Luteolin ; pharmacology ; Neoplasms ; blood supply ; pathology ; Tumor Cells, Cultured

Objective To compare the clinical effect of neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemotherapy (nCT) in the treatment of locally advanced esophageal squamous cell carcinoma.Methods The retrospective cohort study was conducted.The clinicopathological data of 156 patients with local advanced esophageal squamous cell carcinoma who were admitted to the Zhongshan Hospital of Fudan University from January 1,2010 to December 31,2015 were collected.Among 156 patients,59 undergoing nCRT were allocated into the nCRT group and 97 undergoing nCT were allocated into the nCT group.Patients in the nCRT group and nCT group respectively received 2 cycles chemotherapy by the TP regimen+40 Gy radiotherapy (2 Gy/d) and 2 cycles chemotherapy by the TP regimen.Patients were evaluated by imaging examinations after 6 weeks neoadjuvant therapy completion,and then underwent abdominal and right chest-left cervico three-incision thoracoscopic surgery.Observation indicators:(1) treatment situations;(2) postoperative pathological examination;(3) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed once every 3 months within 2 years and once every 6 months after 3 years up to January 2017.Follow-up included levels of tumor markers [carcinoembryonic antigen (CEA) and SCC-Ag],thoracic or abdominal computed tomography (CT),neck and abdominal ultrasonography and gastroscopy or PET/CT examination if necessary.Measurement data with normal distribution were represented as (x)±s and comparison between groups was analyzed using the t test.Measurement data with skewed distribution were described as M (range) and comparison between groups was analyzed using the nonparametric test.Count data were analyzed using the chi-square test or Fisher exact probability.Comparison of ordinal data was done by the nonparametric test.The survival rate was calculated using the life table method and survival was analyzed by the Log-rank test.Results (1) Treatment situations:all the patients in the 2 groups were able to burden neoadjuvant therapy and thoracic esophagectomy.Six patients in the nCRT group and 15 in the nCT group had conversion to open surgery.Operation time,volume of intraoperative blood loss,cases with postoperative readmission of ICU,cases with complications,cases with perioperative death and duration of hospital stay were (201 ± 25) minutes,(137± 66)mL,5,24 (10 with pulmonary complications,8 with anastomotic leakage,3 with hoarseness,2 with cardiovascular complications and 1 with chylopleura),0,12 days (range,9-93 days) in the nCRT group and (195±20) minutes,(133±58) mL,8,30 (11 with anastomotic leakage,10 with pulmonmy complications,4 with hoarseness,2 with cardiovascular complications,1 with postoperative hemorrhage,1 with delayed gastric emptying and 1 with chylopleura),1,11 days (range,9-78 days) in the nCT group,respectively,with no statistically significant difference between the 2 groups (x2 =0.883,t =0.102,0.692,x2 =0.048,1.541,Z =0.225,P＞ 0.05).(2) Postoperative pathological examination:R0 resection rate was 96.6％ in the nCRT group and 93.8％ in the nCT group,with no statistically significant difference between the 2 groups (x2 =0.589,P＞0.05).Results of postoperative pathological examination showed that G0,G1,G2 and G3 of tumor regression grade were respectively detected in 18,16,7,18 patients in the nCRT group and 4,5,4,84 patients in the nCT group,with a statistically significant difference between the 2 groups (Z=-7.151,P＜0.05).Stage 0,Ⅰ,Ⅱ,ⅢA,Ⅲ B and ⅣA of postoperative ypTNM stage were respectively detected in 16,9,23,4,6,1 patients in the nCRT group and 4,9,37,6,34,7 in the nCT group,with a statistically significant difference between the 2 groups (Z=-4.890,P＜0.05).The down-staging was detected in 48 patients of the nCRT group and 50 patients of the nCT group,with a statistically significant difference between the 2 groups (x2=13.957,P＜0.05).(3) Follow-up and survival situations:of 156 patients,153 were followed up for 12-82 months,with a median time of 36 months.The 1-,3-,5-year overall survival rates were 88.1％,61.4％,34.9％ in the nCRT group and 81.4％,43.8％,23.1％ in the nCT group,with a statistically significant difference between the 2 groups (x2=4.336,P＜0.05).Conclusion The nCRT in the treatment of locally advanced esophageal squamous cell carcinoma can enhance postoperative pathological response rate,down-staging rate and overall survival rate compared with nCT,without increasing incidence of perioperative complications.

Objective To determine the mutant status of BRAF gene in Chinese colorectal cancer (CRC) patients and analyze the association with clinicopathological parameters.Methods 676 CRC samples were collected in Cancer Institute/ Hospital,Chinese Academy of Medical Science from December 2009 to December 2011.The direct sequencing was conducted to detect mutations in the BRAF (exon 15 and exon 11).The correlation between mutant status with clinicopathological parameters were analyzed.Results Beside 10 colorectal cancer samples,among the 666 colorectal cancer patients 4.35％ (29/666) of the tumors harbored a BRAF mutation,of which 1.94％ (13/669) in exon 15 (V600E),2.39％ (16/670) in exon 11.Statistical analysis revealed that BRAF15 mutations appeared to occur more frequently in poor-differentiation tumors than high or moderate-differentiation tumors (5.81％ vs 1.46％,r =0.105,P=0.040).But BRAF15 mutations were not correlated with age,gender,smoking and drinking history,tumor site,tumor type,tumor(T/N) staging,histological type,or distant metastasis [r equals to 0.007,-0.018,-0.049,-0.023,-0.098,-0.038,0.040(0.034/0.059),0.065,0.042,respectively,P ＞ 0.05] ; BRAF11 mutations appeared to occur more frequently in patients with drinking history (6.02％vs 1.81％,r =0.093,P =0.035).However,age,gender,smoking history,tumor site,tumor type,tumor differentiation,tumor(N) staging,histological type,or distant metastasis showed no significant correlation with this mutation [r equals to-0.004,0.047,0.020,0.042,0.029,0.040,0.006 (-0.008),0.008,0.030,respectively,P ＞ 0.05].Conclusion A higher proportion of BRAF15 (V600E) mutations occurred in poor-differentiation tumors among the Chinese patients with CRC; BRAF11 mutations appeared more frequently in patients with drinking history.

Objective　To investigate the effect of positive pressure ventilation on radiosensitivity of the patients suffering from primary lung cancer. Methods　Thirty cases of lung cancer were randomly divided into two groups: ① combining therapy group: patients treated with posi tive pressure ventilation using BiPAP respirator and radiotherapy;② simple radi otherapy group. The changes of PaO2, SaO2, blood white cells and the cellula r immunological function were observed before and after treatment. Resul ts　Nasal or naso-facial positive pressure ventilation with BiPAP respi rator increased PaO2 significantly with the maximum of 7.5 kPa, SaO2 was ma inteined at above 95%. No significant change for the cellular immunological func tion was found in the combining therapy group （P>0.05）and only one patient with leukopenia（6.7%）. But in the radiotherapy group, the lymphocyte transfor mation efficiency and the ratio of CD4/CD8 were obviously decreased（P<0 .01), and leukopenia was found in 5 cases（33.3%）. Conclusion　 Nasal or naso-facial positive pressure ventilation with BiPAP respirator could improve the effect of radiotherapy for lung cancers. It could also increase PaO 2 significantly and has protective rote to the marrow and cellular immunologic al function of the patients.

Objective To establish the reference ranges of the spatial angles among cardiac chambers and great vessels in second and third trimester fetuses measured by spatiotemporal image correlation (STIC).Methods Volume images of 352 normal fetuses from 20 to 38 weeks of gestation were recruited in the study.An off-line analysis of acquired volume datasets was carried out with multiplanar mode.Parameters measured included angles between:(1) the 4-chamber view and the left ventricular long axis view; (2) the left ventricular long axis view and main pulmonary artery; and (3) the ductal arch and aortic arch.The relationships between above-mentioned angles and gestational age were assessed by correlation and regression analysis.Results The angle between the 4-chamber view and the left ventricular long axis view (range:55.7° - 35.7°,mean:45.7° ± 5.12°) was uncorrelated with gestational age (r = 0.03,P = 0.51).In contrast,the angle between the left ventricular long axis view and main pulmonary artery,and the angle between the ductal arch and aortic arch were correlated with gestational age (P ＜ 0.001),and the correlation coefficient was - 0.53 and 0.57 respectively.The best-fit exponential curve regression equations of the angle between the left ventricular long axis view and main pulmonary artery was:Y = 154- 4.24X +0.05X2 ,and the angle between the ductal arch and aortic arch was:Y = - 20.8 + 2.65X - 0.37X2.Conclusions The angles among cardiac chambers and great arteries of fetuses from 20 to 38 weeks of gestation can be quantitatively measured by STIC.The reference ranges provide a reliable quantitative standard to estimate the spatial relationships of the cardiac large arteries of fetuses,which may be clinically useful in prenatal screening congenital heart disease.

Objeetive To investigate the clinical significance of combined detection of lipoprotein associated serum phospholipase A2 (Lp-PLa2),homocysteine (Hcy) and cystatin C (CysC) in the diagnosis of hypertensive disorders complicating pregnancy (HDCP).Methods From January 2013 to May 2016 in Changan Hospital,selected 113 cases of pregnancy induced hypertension patients as the observation group,and were divided into three group A,B and C (group A:55 cases of HDCP patients,group B:32 cases of mild preeclampsia and group C for patients with severe preeclampsia 26 cases).At the same period,selected 50 cases of normal college pregnancy as control group,serum Lp-PLa2 (enzyme-linked immunosorbent assay),Hcy (cyclophorase method) and CysC (particle enhanced turbidimetric method),the test results were analyzed and compared.Results Serum Lp-PLa2,Hcy and CysC test results in the control group,the observation group A,observation group B and observation group C increased significantly,in the observation group C increased most obviously.Compared with the control group,the serum levels of Lp-PLa2,Hcy and CysC in the observation group were significantly higher,the difference was statistically significant (F=8.102,7.231 and 6.926,all P＜0.05).Pearson correlation analysis showed that there was a positive correlation between serum Lp-PLa2,Hcy and CysC and blood pressure (r=0.71,0.69,0.63,all P＜0.05).The abnormal rate of serum Lp-PLa2,Hcy and CysC for three joint detection was higher than that of single detection,and the difference was statistically significant (x2 =6.725,P＜0.001).The abnormal rate of serum Lp-PLa2,Hcy and Cys single test results increased with the exacerbation of HDCP,and the difference was statistically significant (x2=9.351,P＜0.000).Conclusion Serum Lp-PLa2,Hey,CysC and pregnancy would be closely related to the occurrence and development of hypertension syndrome,so combined detection of HDCP can improve the detection rate of abnormal results,and it has important clinical significance for early diagnosis and prognosis of HDCP.

OBJECTIVETo investigates the mechanism of hypooglycemic effect of conduritol A of stems of Gymnema sylvestre.

METHODFourteen days later after administration, observation is taken on the change of these mice and rats weight, the FBG, TG, CHO, SOD, MDA, INS, TNF in serum were also detected with enzymology method and Radioimmuoassay method. Take the liver to determine the disposal of glucose. Take the pancreas to do the HE and immunohistochemistrial staining, and show pancreas islet beta-cell. Calulate thymus, pancreas, splenica index.

RESULTCompared with diabetic model mice, high and middosage of conduritol A could remarkably reduce fasted blood sugar in diabetic rats induced by alloxan (P < 0.01). Significantly increase the level of serum insulin (P < 0.05). Activity of SOD was obviously increased, and amount of MDA was obviously decreased (P < 0.05). The amount of conduritol A disposal of glucose was obviously increased (P < 0.05). Significantly increase thymus, pancreas, splencia index (P < 0.01 or 0.05); inhibited the atrophy of thymus, pancreas, splencias of the diabetic rats induced by alloxan. Compared with diabetic model group, cell structure and form of conduritol A had been some way improved. The immunohistochemistry results showed that beta-cells numbers of pancreas in each conduritol A group were more than those in the model group.

CONCLUSIONConduritol A could have an effect on regulating the metabolism of blood lipid, free-radical scavenging, enhancing the antioxidant ability, potentiating immune function. Promoting synthesis of hepatic to decrease fasted blood suger.

Animals ; Blood Glucose ; drug effects ; Diabetes Mellitus ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gymnema sylvestre ; chemistry ; Humans ; Hypoglycemic Agents ; pharmacology ; Male ; Models, Animal ; Random Allocation ; Rats ; Rats, Wistar