1.Current situation and progress in the comprehensive treatment of locally advanced gastroesophageal junction adenocarcinoma
Wei LIU ; Yudong WANG ; Long WANG
Chinese Journal of Clinical Oncology 2014;(3):149-152
Based on special biological characteristics and prognosis, the incidence of gastroesophageal junction adenocarcinoma (GEJA) has rapidly increased over recent years, and its diagnosis and treatment remain controversial. Compared with simple surgery, neo-adjuvant and adjuvant therapies can improve the survival of patients with locally advanced GEJA. Under neo-adjuvant therapy, neo-adjuvant chemoradiation is superior to neo-adjuvant chemotherapy alone for improving the resectability, maintaining loco-regional control, and improving the quality of life of the patient. The combination of this therapy with targeted drugs may further increase the ef-ficacy of GEJA. Most data on GEJA-treated patients were obtained from randomized clinical studies on esophageal cancer or gastric cancer. Thus, prospective randomized controlled studies with a large sample size should be performed to optimize the strategy of neo-adjuvant and adjuvant therapies, and further improve the treatment outcome. In this article, studies on the comprehensive treatment of GEJA were reviewed.
4.Clinical research progress in adenocarcinoma of the esophagogas-tric junction
Long WANG ; Xue ZHANG ; Wei LIU
Chinese Journal of Clinical Oncology 2015;(2):120-124
The adenocarcinoma of the esophagogastric junction (EGJA) is located in a unique anatomical position and at the junction of the squamous epithelium and the columnar epithelium. The biological characteristics of this disease are different from those of esophageal or gastric cancer. The diagnostic classification of EGJA has been subject to controversies, and no gold standard therapeu-tic regimens have been established, especially in the choice of treatment of locally advanced EGJA. Results from large-scale clinical tri-als and imaging technology development showed that the treatment of EGJA has been individualized. Furthermore, this problem high-lights the importance of multidisciplinary collaboration. This article focuses on current progress in studies on EGJA.
5.Screening for selective TGF-βⅠinhibitors and structure-activity relationship analysis
Long LONG ; Feifei LI ; Xingzhou LI ; Wei CHEN ; Wei LI ; Lili WANG
Journal of International Pharmaceutical Research 2017;44(6):544-550
Objective To screen for selective transforming growth factor β(TGF-β)inhibitors from the compound library, and analyze their structure-activity relationship. Methods The inhibiting activities of 170 compounds to TGF-βpathway were evaluat-ed by the SMAD3 luciferase reporter system;the positive hits were examined for their selectivity towards activin receptor like kinase (ALK)4、ALK5 or ALK7 by a molecule based screening system composed of SMAD3,ATP and the purified kinase domain for ALK4, ALK5 or ALK7;the EGFP-SMAD2 fusion protein redistribution assay was used to confirm the inhibiting effects of positive hits. The structure-activity relationship was analyzed by comparing the docking module of SB431542 with ALK5 kinase domain. Results Fif-teen compounds were found capable of inhibiting luciferase expression downstream of SMAD3 with≥25%inhibitory rate;several of them showed different selectivity towards ALK4,ALK5 and ALK7. Compound 63 selectively inhibited the activity of ALK4 and ALK7 with IC500.234 and 0.370μmol/L,respectively,while compound 64 showed inhibiting activity towards all three kinases with the IC50 values 10,6 and 85 nmol/L for ALK4、ALK5 and ALK7,respectively. In addition,compounds 63 and 64 further inhibited the TGF-β1 induced EGFP-SMAD2 nuclear translocation,with the IC50 values of 0.45 and 6.30μmol/L,respectively. The MTT anti-proliferative assay indicated that compounds 63 and 64 exerted these activities at non-toxic concentrations. The analysis of structure-activity rela-tionship indicated that the compounds sharing a core structure,the 1,2,4-triarylimizazole or 1,3,5-triarylpyrazoline,with the 3,4 methyoenedioxyphenyl,6-methylpyridine and 4-aminocarboxyl substitution groups tended to exhibit better activities. Conclusion The two potent TGF-βpathway inhibitors,63 and 64 are identified through this screening project,of which,63 selectively inhibited the ALK4 and ALK7 activity,while 64 showed inhibiting activity towards all three tested types of ALKs.
6.Effects and Mechanisms of Xuebijing on Early Sepsis Induced Acute Lung Injury in Rats
Wei WANG ; Yuxiang ZHANG ; Hongshan LI ; Long YANG ; Zheng WANG
Progress in Modern Biomedicine 2017;17(25):4820-4823
Objective:To investigate the effects and mechanisms of Xuebijing injection on early sepsis induced acute lung injury and explore a new therapy.Methods:Thirty healthy male Sprague-Dawley rats were randomly divided into 3 groups:Sham group(n=10),NS group (NS 4mL/kg n=10),Xuebijing Group(Xuebijing 4mL/kg n=10).Cecal ligation and puncture (CLP) was used to duplicate severe sepsis model.At 6h after CLP,the rats were sacrificed,the lungs were resected and histopathological characteristic was observed by transmission electron microscopy technique.The change of the lung wet/dry (W/D) weight ratio were studied.Meanwhile,the lungs were resected for detection of ET-1,iNOS,MMP-9,TIMP-1 mRNA with reverse transcription-polymerase chain raction (RT-PCR).Results:The changes of pulmonary alveoli and the interstitial edema as well as lung tissue in Xuebijing group were better than those of NS group.The change of lung wet/dry (W/D) weight ratio in septic rats showed was significantly increased at 6 h after CLP (vs Sham group:5.37± 0.12 vs 4.33± 0.06,P<0.01).The lung W/D was significantly decreased in XBJ group (vs NS group:4.67± 0.09 vs 5.37± 0.12,P<0.05).The expressions in XBJ group lung tissue of ET-1 (0.511 ± 0.111 vs 0.705± 0.122,P<0.01),iNOS(0.45610.075 vs 0.548± 0.098,P<0.05)、MMP-9 (0.617± 0.079 vs 0.732± 0.131,P<0.05),TIMP-1 (0.438± 0.043 vs 0.515± 0.049,P <0.01) mRNA were significantly decreased than those in NS group.And the expressions of ET-1 (0.705± 0.122vs 0.400± 0.033,P<0.01),iNOS (0.548± 0.098 vs 0.334± 0.027,P<0.01),MMP-9(0.732± 0.131 vs 0.352± 0.061,P<0.01),TIMP-1(0.515± 0.049 vs 0.365± 0.068,P<0.01) mRNA in NS group were significantly increased compared with those in the sham group.Conclusions:Xuebijing could protect against sepsis induced acute lung injury,which might be related with the decrease ofET-1,iNOS,MMP-9 and TIMP-1 mRNA expressions.
7.The Development Status and Countermeasures of Medical Sci-tech Novelty Assessment Work
Xinling WANG ; Liyan LONG ; Wei HE ; Bin CHEN
Journal of Medical Informatics 2015;(6):84-87
〔Abstract〕 Medical and health sci-tech novelty assessment plays a key role in information supporting in the hospital scientific research and management work of health sector.Combining with the current status of medical and health sci-tech novelty assessment work station in the Military Hospital of Beijing PLA, the paper puts forward countermeasures acoording to the existing problems, namely, weak management and personnel and so on, in order to promote comprehensive development of medical and health sci-tech novelty assessment work.
8.Clinicopathologic features and prognostic analysis of intrahepatic mucinous cholangiocarcinoma and intrahepatic cholangiocarcinoma
Long HUANG ; Maolin YAN ; Shaoming WEI ; Yaodong WANG
Chinese Journal of Digestive Surgery 2016;15(4):335-338
Objective To investigate the clinicopathologic features and prognostic analysis of intrahepatic mucinous cholangiocarcinoma (IMCC) and intrahepatic cholangiocarcinoma (ICC).Methods The retrospective cohort study was adopted.The clinicopathological data of 20 patients with IMCC and 51 patients with ICC who were admitted to the Fujian Provincial Hospital from March 2003 to March 2014 were collected.The observation indicators included (1) clinicopathologic features:gender,age,clinical symptoms (fever,jaundice,abdominal pain and peritoneal effusion),preoperative laboratory examination [alanine transaminase (ALT),aspartate transaminase (AST),direct bilirubin (DBil),carcinoembryonic antigen (CEA),CA19-9 and alphafetoprotein (AFP)],operation methods (radical resection,palliative resection) and pathological features (tumor location,lymph node metastasis,vascular invasion and pathological stage).(2) The follow-up of outpatient examination and telephone interview was performed to detect the survival of patients up to March 2015.Measurement data with normal distribution were represented as x-± s and comparison between groups was analyzed using t test.Count data were analyzed using the chi-square test.The survival curve was drawn by Kaplan-Meier method,and the survival rate was analyzed using the Log-rank test.Result The numbers of patients with fever,jaundice,elevated level of AST and DBil,lymph node metastasis,vascular invasion and numbers of patients with stage 0,Ⅰ,Ⅱ,Ⅲ,Ⅳ were 13,11,10,11,3,1 and4,6,2,6,2 with IMCC,12,10,9,2,22,36 and 0,14,5,3,29 with ICC,respectively,showing statistically significant differences in the above indicators (x2=10.830,8.639,7.672,25.059,8.036,24.765,26.601,P < 0.05).All the patients were followed up for a median time of 14 months (range,1-118 months).The survival time and 1-,3-,5-year survival rates were (55 ± 8)months,94.4%,44.0%,16.7% in 20 patients with IMCC and (30 ±6) months,36.5%,12.5%,4.0% in 51 patients with ICC,respectively,showing a statistically significant difference (x2 =8.126,P < 0.05).Conclusion The patients with MICC are more easily complicated with fever,jaundice and liver dysfunction,while they have less lymph node metastasis and vascular invasion,earlier pathological stage and better prognosis compared with patients with ICC.
9.2D-FIESTA Sequence of MRI in the Evaluation of the Biliary Tract for the Infants and Young Children
Xiaoying WANG ; Liuming HUANG ; Long LI ; Wei SUN ; Xuexiang JIANG
Journal of Practical Radiology 2001;0(01):-
Objective To evaluate the diagnostic value of 2D-FIESTA sequence of MRI in the detection of the biliary tract lesions in infant and young children patients(less than 3 years).Methods 8 infant and young children patients were examined by MRI to evaluatetheir biliary tract.Images were obtained with a 1.5T whole body MRI system(GE Medical System,Milwakee,Wis,USA),using theCARDIAC coil.The patients were sedated by chloral hydrate orally or by pentobarbital sodium intravenously.No contrast agents wererequired.All of the axial,coronal and sagittal images were reviewed on an independent workstation and maximum intensity projection(MIP) and multiplanar reformations(MPR) techniques were applied.Results The 2D-FIESTA pulse sequence results in images in which the hepatic vascular structures and the biliary tract were highlighted.In this way,a clear visualization of the hepatic vessels and biliarytract could be obtained in all 8 cases.MRI could demonstrate the anatomy and pathology of post-transplantation changes in 3 patients,choledochal cysts in 2 patients,anomalous connection between the bile and pancreatic ducts in 1 patient.All the abnormalities were proved by operation.2 examinees were diagnosed normal by MRI and were confirmed by follow-up.Conclusion 2D-FIESTA is a fast sequence that allows the high quality images to be generated without breath-hold and without administration of contrast material.It has a potential wide application in the evaluation of biliary tract in the infant patients.
10.Exogenous hydrogen sulfide reduces focal cerebral ischemia/reperfusion injury in rats via nuclear factor-κB-mediated inflammatory response pathway
Xia WEI ; Long CHENG ; Qingqing WANG ; Bing ZHANG
International Journal of Cerebrovascular Diseases 2016;24(10):918-923
Objective To investigate the effect of hydrogen sulfide (H2S) on brain injury and inflammatory response after cerebral ischemia/reperfusion in rats.Methods Forty-eight malc SD rats were randomly divided into four groups:sham operation group,ischemia/reperfusion (I/R) group,H2S-30 ppm group,and H2S-60 ppm group (n=12 in each group;1 ppm=1 mg/L).The middle cerebral artery occlusion method was used to induce a model of focal cerebral ischemia for 2 h and reperfusion for 24 h.After reperfusion for 24 h,the tape remove experiment was used to perform the nerve function evaluation.2,3,5-triphenyl-tetrazolium chloride staining method was used to measure the percentage of cerebral infarction volume.Enzyme-linked immunosorbent assay was used to measure the levels of interleukin (IL)-1 β and IL-6.Western blotting was used to detect the expression levels of inducible nitric oxide synthase (iNOS) and intercellular cell adhesion molecule-1 (ICAM-1),as well as the transposition activation of nuclear factor-κB (NF-κB).Results Inhalation of H2S could shorten the time required to remove the tape in a dose-dependent manner compared with the I/R group (I/R group vs.H2S 30 ppm group and H2S 60 ppm group:180 s vs.130 [113-157]s vs.110 [87-138] s;P< 0.05),reduced the cerebral infarct volume (48.8% ± 9.1% vs.23.3 % ± 5.1% vs.17.3 % ± 3.5 %;P < 0.05),downregulated the expression levels of IL-1β (39.53± 6.02 pg/mg protein vs.30.17± 3.46 pg/mg protein vs.22.69± 6.09 pg/mg protein;P <0.05) and IL-6 (54.65 ± 10.68 pg/mg protein vs.37.89 ±4.54 pg/mg protein vs.27.00 ±3.08 pg/mg protein;P < 0.05) in ischemic brain tissue,significantly decreased NF-κB nucleus/ cytoplasm ratio (4.40 ± 1.05 vs.3.07 ± 0.82 vs.2.30 ± 0.60;P < 0.05),inhibited expressions of iNOS (4.22 ±0.67 vs.3.14 ±0.90 vs.2.08 ±0.35;P <0.05),and ICAM-1 (5.45 ± 1.08 vs.3.45 ±0.67 vs.2.21 ±0.39;P <0.05).Conclusions Inhalation of exogenous H2S can reduce cerebral infarct volume after cerebral ischemia/reperfusion in a dose-dependent manner and improve neurological function.Its mechanism may be associated with the inhibition of NF-κB activation,down-regulation of its downstream iNOS and ICAM-1 expression levels,and decrease of IL-1β and IL-6 levels.