Clinical and morphological features of large-cell neuroendocrine carcinomas and small-cell lung carcinomas expressing the DLL3 and ASCL1 oncoproteins

Abstract Intratumoral similarities and differences between large-cell neuroendocrine carcinomas (LCNECs) and small-cell lung carcinomas (SCLCs) are determined partially by the Notch signaling pathway, which controls the switch from neuroendocrine to slight/non-neuroendocrine cell fate. LCNECs are divided into two subgroups according to genomic alterations: type I LCNECs exhibit a neuroendocrine profile characterized by achaete‐scute homolog 1 (ASCL1)high/delta-like protein 3 (DLL3)high/NOTCHlow and type II LCNECs show the pattern ASCL1low/DLL3low/NOTCHhigh. Here, we used immunohistochemistry, transmission electron microscopy, and digital analysis to examine the role of the Notch ligand DLL3 as an immunomarker of the neuroendocrine state and ASCL1 as a regulator of cell-cell interactions in SCLCs and LCNECs. High DLL3 and ASCL1 expression was associated with atypical submicroscopic characteristics involving nuclear size, chromatin arrangement, Golgi apparatus, and endoplasmic reticulum, and was characteristic of type I LCNECs with similarity to SCLCs, whereas low DLL3 and ASCL1 expression was found in both SCLCs and type II LCNECs. In patients diagnosed at an early stage who did not have metastasis and who underwent chemotherapy, DLL3high and ASCL1high SCLCs and type I LCNECs were associated with a better prognosis and a lower risk of death. The present findings suggested that DLL3/ASCL1 are potential therapeutic targets and prognostic indicators in patients with SCLCs or LCNECs.

Small cell lung cancer: an overview of the targets

Abstract Lung cancer is the leading cause of cancer deaths worldwide. Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancer cases. Despite a frequently good response to first-line treatment with chemotherapy and/or radiotherapy, early relapse occurs in the majority of patients and 5-year survival is only about 5%. This histological subtype of lung cancer is strongly associated with tobacco smoking. The behavior of SCLC is unique within solid tumors. Initially, it positively responds to chemotherapy or radiotherapy. However, at relapse, which occurs early in the majority of cases, the tumor is resistant to available therapy and eventually will cause the death of the patient. These results in an overall 5-year survival of approximately 5% for the entire population of patients diagnosed with SCLC. This dismal prognosis has not significantly changed in past years. There is an urgent need for discovery targets to select patients more prone to having a proper response to the treatment, avoiding to reduce their resistance and resulting the increase of overall and progression-free survivals.

Expression of DLL4 in colorectal cancer and its relationship with prognosis and obesity / 西安交通大学学报(医学版)

Objective: Delta-like ligand 4 (DLL4) is the main ligand of Notch signaling pathway in regulating tumor angiogenesis. Obesity is a major risk factor for colorectal cancer, and its mechanism of promoting tumorigenesis needs further investigation. In the present study, we aimed to investigate the relationship of DLL4 expression with tumor progression and prognosis, as well as obesity in colorectal cancer. Methods: For this study we collected 265 samples of colorectal cancer tissues and paracancerous tissues resected at The First Affiliated Hospital of Xi'an Jiaotong University between January 2012 and December 2013. Immunohistochemistry was used to detect the expression of DLL4. We analyzed the relationship of DLL4 expression with clinicopathological characteristics, prognosis and obesity. The survival data was analyzed by Kaplan-Meier and Cox proportional hazard regression model. Results: The positive expression rate of DLL4 in colorectal cancer tissues was significantly higher than that in adjacent tissues (77.4% vs. 17.7%, P<0.05). The patients with high expression of DLL4 had a lower degree of differentiation, but a greater depth of invasion, a higher lymph node metastasis rate and higher TNM stage (P<0.05). The disease-free survival and overall survival were shorter in DLL4 positive expression group than in the negative group (P<0.001). Cox multiple regression analysis showed that DLL4 expression was an independent prognostic factor for colorectal cancer. The positive expression rate of DLL4 in overweight and obese patients was significantly higher than that in normal weight patients. BMI was positively correlated with the expression level of DLL4 (rs=0.578, P<0.05). Conclusion: The expression of DLL4 is upregulated in colorectal cancer tissues. Increased expression of DLL4 is associated with poor prognosis of patients, suggesting that DLL4-Notch pathway may be involved in the carcinogenesis and progression of obesity-induced colorectal cancer.

Effects of Buyang Huanwu Decoction on Endothelial-mesenchymal Transformation of Lung Tissue in Idiopathic Pulmonary Fibrosis Model Rats and Mechanism Study / 中国药房

OBJECTIVE： To investigate the effects of Buyang huanwu decoction on endothelial-mesenchymal transformation （EndMT） of lung tissue in idiopathic pulmonary fibrosis （IPF） model rats， and to explore its potential mechanism. METHODS： Male SD rats were randomly divided into normal group， model gorup， dexamethasone group [0.405 mg/（kg·d）]， Buyang huanwu decoction low-dose， medium-dose and high-dose groups [6.435， 12.87， 25.74 g/（kg·d）， by raw material]， with 8 rats in each group. Except for normal group， other groups were given endotracheal injection of bleomycin to induce IPF model. On the second day after modeling， normal group and model group were given water intrgastrically [10 mL/（kg·d）]； administration groups were given relevant medicine intragastrically， once a day， for consecutive 28 days. 24 h after last medication， the expression of endothelial cell markers [platelet endothelial cell adhesion molecule 1， vascular endothelial cell cadherin] and interstitial cell markers [α-smooth muscle actin， fibroblast specific protein 1] were detected by immunohistochemistry method. The expression of Notch4 and DLL4 in lung tissue of rats were detected by Western blotting assay. RESULTS： Compared with normal group， the expression of endothelial cell markers were decreased significantly in lung tissue of model group， while the expressipon of interstitial cell markers， Notch4 and DLL4 were increased significantly （P＜0.01）. Compared with model group， the expression of endothelial cell markers in lung tissue of rats were increased significantly in administration groups， while Buyang huanwu decoction low-dose group was significantly lower than dexamethasone group； the expression of interstitial cell markers， Notch4 and DLL4 were decreased significantly， while Buyang huanwu decoction low-dose group was significantly higher than dexamethasone group （P＜0.05 or P＜0.01）. CONCLUSIONS： Buyang huanwu decoction can relieve IPF of model rats by intervening in EndMT， the mechanism of which may be associated with inhibiting DLL4/Notch4 singaling pathway.

NBP promotes angiogenesis of HUVECs by activating VEGF/VEGFR2-Notch1/Dll4 signal pathway / 中国病理生理杂志

AIM:To investigate the effects of DL-3-n-butylphthalidle (NBP) on angiogenesis of human um-bilical vein endothelial cells ( HUVECs) and the role of vascular endothelial growth factor ( VEGF)/VEGF receptor 2 (VEGFR2)-Notch1/Delta-like ligand 4 (Dll4) signaling pathway in this process. METHODS:The serum-free medium and anoxic tank were used to simulate the conditions of hypoxia and ischemia ( H/I). HUVECs were divided into control group, H/I group, H/I+NBPhigh group and H/I+NBPlow group. The HUVECs in control group were conventionally cul-tured, and those in H/I group were cultured under H/I intervention. The HUVECs in H/I+NBPhigh group were treated with NBP at 20 μmol/L under H/I intervention. The HUVECs in H/I+NBPlow group were treated with NBP at 5 μmol/L under H/I intervention. The cell viability of each group was measured by CCK-8 assay. The migration ability of the HUVECs in each group was detected by cell scratch test. The vessel formation ability of the HUVECs was examined by in vitro angiogenesis assay. The expression of VEGFR2, Notch1 and Dll4 at mRNA and protein levels was determined by qPCR and Western blot, and the expression of VEGF was determined by qPCR and ELISA. RESULTS:NBP increased the viability of HUVECs, and promoted the migration ability and the formation of blood vessels in vitro under H/I interven-tion. These effects of NBP at high dose were more significant than those at low dose. NBP increased the expression of VEGF, VEGFR2, Notch1 and Dll4 at mRNA and protein levels (P<0.05). CONCLUSION:NBP promotes HUVECs to form blood vessels under H/I intervention. The mechanism may be related to the activation of VEGF/VEGFR2-Notch1/Dll4 signaling pathway.

Design of HL7 communication module for ECG system based on dynamic link library / 医疗卫生装备

Objective To realize the standardization of medical information under the same principle of retaining the existing ECG system framework. Methods The localization of HL7 medical information standard was studied, and the plug-in technique was used to reconstruct HL7 standard ECG system. Results After adding the HL7 communication module, the original ECG system could send and receive HL7 messages in real time to complete higher level medical data exchange and reduce the project implementation cost. Conclusion This study has important practical reference values for the standardization of HL7 in the existing medical information system,which is helpful to promote the standardization of medical information system.

Role of Notch-Dll4 signaling pathway in autoimmune damage of Hashimoto thyroiditis / 中华内分泌代谢杂志

Forty patients with Hashimoto thyroiditis ( HT) and 20 healthy subjects with matched age-and sex-features ( NC) were selected. The patients with HT were further divided into normal thyroid function ( HT-A) and hypothyroidism ( HT-B) groups. Real-time PCR was performed to evaluate the expressions of Notch1, Dll4, and retinoid-related orphan receptor ( ROR )-γt mRNA. Flow-cytometry was used to detect the percentage of Th17 cells. Thyroid function, thyroid peroxidase antibody ( TPOAb) , and thyroglobulin antibody ( TgAb) were detected by electrochemiluminescence immunoassaies. The results showed that the Notch1, Dll4, ROR-γt mRNA levels and Th17 cell percentage were significantly increased in HT group compared with NC group (all P<0.01), especially in HT-B group. In HT patients, Notch1 and Dll4 mRNA expression levels were positively correlated with Th17 cell percentage and its transcription factor ROR-γt ( all P<0.01) . Besides, there were significantly positive correlations of Notch1 and Dll4 mRNA expressions with TPOAb and TgAb titers (P<0.05 or P<0.01). These results suggest that Notch1-Dll4 signaling pathway might be involved in the pathogenesis of thyroid-specific autoimmune damage by regulating Th17 cells in HT patients.

Expression of Notch signaling pathway in cultured human osteoarthritic articular chondrocytes / 局解手术学杂志

Objective To explore the role of Notch signaling pathway in the matrix synthesis of osteoarthritis cartilage cell and its possi -ble mechanism.Methods Selected the femoral condylar cartilage of 8 patients who were admitted into our hospital and treated with knee joint replacement as the observation group,while the normal femoral condyle cartilage of one patient with above-knee amputation was selected as the control group.The specimens were given histological examination or cell isolation culture and detection.The cultured cells were divided into 4 groups,namely the normal cartilage cells,OA cartilage cells,OA cartilage cells with γ-secretase inhibitor DAPT,OA cartilage cells with recombinant human proteins Delta4.Then immunohistochemistry and Western blot were used for detecting the expression of Notch -1,Notch-3, Jagged-1,Jagged-2 and HES5 in chondrocytes in vitro.Results The expression of Notch signaling pathway and the phenotype of cartilage cells changed in the osteoarthritis.The expression of Notch-1,Jagged-1,Jagged-2 and HES5 were activated.γ-secretase inhibitor DAPT (20 μmol/L)could inhibit the expression of Notch-1,HES5,Jagged-1,and Notch-3,while it had no obvious effect on the expreesion of Jag-ged-2.Recombinant human proteins Delta 4(100 ng/μL)could promote the expression of Notch-1,Jagged-2,and HES5,and it had no obvi-ous effect on the expreesion of Jagged-1 and Notch-3.Conclusion The expression of Notch signaling pathway of cartilage cells changed in the osteoarthritis.DLL4 can activate the Notch signaling pathway and DAPT can inhibit the Notch signaling pathway.

Expression and significance of Notch3, DLL1 and CD133 in colorectal adenocarcinoma / 重庆医学

Objective To investigate the expression of Notch3,DLL1 and CD133 in human colorectal adenocarcinoma and its clinical pathology meaning.Methods Immunohistochemical staining was used to detect the expression of Notch3,DLL1 and CD133 in 12 cases of normal colorectal mucosa tissue,30 cases of colorectal adenoma tissue and 50 cases of colorectal adenocarcinoma tissue,and the relationship between them and clinicopathological data wereanalyzed.Results The positive rates of Notch3,DLL1 and CD133 were 64.0 ％ (32/50),68.0 ％ (34/50) and 54.0 ％ (27/50) in colorectal carcinoma tissues,respectively,which were remarkably higher than those in colorectal adenoma tissue(26.7 ％,33.3％％,36.7 ％)and those in normal colorectal mucosa tissue (8.3％,16.7％,8.3％) (P＜0.05).There was no significant difference between the adenoma group and the normal group(P＞0.05).The expression levels of Notch3,DLL1 and CD133 were not correlated to age,gender,tumor location,degree of differentiation and the tumor size,except lymph node metastasis,in addition,the expression of Notch3 and DLL1 were also associated with Dukes staging,and The expression of DLL1 were also associated with tumor infiltration depth (P＜0.05).The expression of Notch3 protein was positively related to that of DLL1 protein(r=0.478,P=0.000).Conclusion The positive expression rates of Notch3,DLL1 and CD133 in colorectal adenocarcinoma tissue are remarkably higher than those in the normal colorectal mucosa and colorectal adenoma tissue,which prompts that the high expression of Notch3,DLL1 and CD133 may all participate in the process and metastasis of colorectal adenocarcinoma.Moreover Notch3 signalling pathway may act through the cancer stem cells and eventually regulate the initiation and development of colorectal adenocarcinoma.

Expression of Notch pathway receptors and ligands in cutaneous malignant melanoma / 中华皮肤科杂志

Objective To determine the expression of Notch pathway receptors (Notch1 and Notch4) and ligands (Jagged1 and Dll4) in cutaneous malignant melanoma (CMM) tissues,and to preliminarily explore the role of the Notch signaling pathway in the pathogenesis of CMM.Methods Immunohistochemical study was performed to determine the expression pattern and intensity of Notch1,Notch4,Jagged1 and Dll4 in 40 paraffin-embedded CMM specimens and 15 paraffin-embedded pigmented nevus specimens.Statistical analysis was carried out by chi-square test and Spearman rank correlation analysis with the SPSS 21.0 software.Results Notchl was detected in 31 (77.5％) of 40 CMM specimens,as well as in 3 of 15 pigmented nevus specimens,and the positive rates significantly differed between the two groups (x2 =15.281,P ＜ 0.001).However,no significant difference in the expression intensity of Notch1 was observed between 18 in situ melanoma tissues and 22 invasive melanoma tissues (x2 =0.631,P =0.427).In addition,the positive rates of Notch4,Jagged1 and Dll4 were also significantly higher in the CMM group than those in the pigmented nevus group (all P ＜ 0.05),and the expression intensity of Notch4,Jagged1 and Dll4 significantly differed between in situ and invasive melanoma tissues (all P ＜ 0.05).In CMM tissues,the expression of Notch1 was positively correlated with that of Jagged1 (rs =0.350,P =0.027) and Dll4 (rs =0.562,P ＜ 0.001),while the expression of Jaggedl was negatively correlated with that of Dl14 (rs =-0.734,P ＜ 0.001).Conclusion Abnormality of the Notch signaling pathway may be involved in the pathogenesis of melanoma,but further researches are still needed to elucidate the detailed mechanism.

Inhibitory effect of recombinant human endostatin on angiogenesis in atherosclerotic plaque of rats by regulating Dll4/Notch pathway / 中国病理生理杂志

AIM: To observe the inhibitory effect of recombinant human endostatin (rhES) on plaque angio-genesis, and to explore the regulatory mechanism of Dll4 /Notch pathway in the anti-angiogenic effect of rhES.METH-ODS: Male Wistar rats were randomized into 3 groups: normal control group (N group), atherosclerotic model group (AS group), and rhES treated group (AS +rhES group).The rats in N group were fed a normal diet, while the remaining 2 groups were established to atherosclerotic rat model via high-cholesterol diet, intraperitoneal injection of vitamin D3 and aor-tic balloon injury.The rats in AS +rhES group received intraperitoneal injection of rhES.The blood total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), interleukin-1 (IL-1) and troponin I (TnI) were measured.The atherosclerotic abdominal aortas were taken for pathological observation.Immu-nohistochemical staining was used to measure the density of neovessels in the plaques, which were marked by CD31.The protein levels of Dll4 and Notch1 in the aortas were analyzed by Western blot.RESULTS: The levels of blood TC, TG, LDL-C, CRP and IL-1 in AS group and AS +rhES group were much higher than those in N group (P <0.05), and no sta-tistical difference between AS group and AS +rhES group was observed.The expression of CD31 in AS group was the high-est among all groups.Compared with AS group, the density of neovessels in the plaques of AS +rhES group decreased sig-nificantly (P <0.05).The protein expression of Dll4 and Notch1 in AS group was lower than that in N group (P <0.05). Compared with AS group, the protein expression of Dll4 and Notch1 increased significantly (P <0.05).CONCLUSION:rhES has the ability to inhibit plaque angiogenesis in rats.The activation of Dll4 /Notch pathway may be the mechanism of rhES in inhibiting plaque angiogenesis.

Relationships between Notch1, DLL4, HES-1 expression and angiogenesis, lymphangiogenesis of gastric carcinoma and their significances / 国际肿瘤学杂志

Objective To investigate the expression of Notch1,Delta-like ligand 4 (DLL4),hairy and enhancer of split-1 (HES-1),microvessel density (MVD),lymphatic vessel density (MLD) in gastric carcinoma,so as to discuss their roles in the development of gastric carcinoma.Methods Gastric carcinoma,paracancer tissues which was apart from the edge of cancer tissue ＞ 60 mm obtained during operation and normal gastric mucosa obtained during gastroscopy were used as controls.All specimens were made tissue microarray.The expressions of Notchl,DLL4,HES-1 were detected by immunohistochemistry.Immunohistochenical double taining was used to detect MVD and MLD.The relationships between Notch1,DLL4,HES-1 expression and angiogenesis,lymphangiogenesis and their significances were analyzed.Results The positive rate of Notch1 in gastric carcinoma was 48.30％,significantly higher than that of paracancerous (25.00％,x2 =6.38,P ＜ 0.05) and control group (16.67％,x2 =10.18,P ＜0.05).The differences of the positive rate of DLL4 in gastric carcinoma (55.94％),paracancerous (45.70％) and control group (56.67％) were not significant (x2 =1.18,P ＞0.05 ; x2 =0.005,P ＞ 0.05).The differences of the positive rate of HES-1 in gastric carcinoma (36.64％),paracancerous (34.40％) and control group (33.33％) were not significant (x2 =0.05,P ＞ 0.05 ;,x2 =0.11,P ＞ 0.05).The mean of MVD in gastric carcinoma group was 28.84 ± 14.17,which was significantly higher than that in paracancerous group (17.02 ±8.54,t =4.03,P＜0.05) and control group (16.69 ±7.21,t =5.01,P＜0.05).The mean of MLD in gastric carcinoma group was 8.55 ±4.98,which was significantly higher than that in paracancerous group (4.05 ± 2.48,t =9.30,P ＜ 0.05) and control group (3.99 ± 1.56,t =10.32,P ＜ 0.05).The expression of DLL4 was correlated with MVD (t =2.77,P ＜ 0.05),but wasn't correlated with MLD (t =1.89,P ＞0.05).There were no correlations between the expression of Notch1,HES-1 and tissues MVD,MLD (P ＞0.05).Conclusion Notch1 plays important roles in the development of gastric carcinoma.There are many angiogenesis and lymphangiogenesis in gastric carcinoma.The expression of DLL4 in gastric carcinoma has certain effect in the formation of microvessel.

Expression of DLL4 in NSCLC and and its clinical significance / 临床与实验病理学杂志

Purpose To assess the expression of DLL4 in non-small cell lung cancer ( NSCLC) patients and to determine its associa-tion with clinicopathological parameters and prognosis. Methods DLL4 expression was evaluated in NSCLC tissues and adjacent non-cancerous normal lung tissues from 89 patients undergoing surgical treatment by immunohistochemistry. Results DLL4 had high ex-pression in 52 of 89 cases of NSCLC (58. 4%), which was significantly higher than that in adjacent non-cancerous lung tissues (P<0. 05). Moreover, DLL4 overexpression was significantly correlated with TNM stage (P=0. 010 78). Kaplan-Meier survival analysis showed that the overall survival times in patients expressing DLL4 in NSCLC were shorter. Conclusion High level of DLL4 expression is significantly correlated with NSCLC progression and unfavorable prognosis. Thus, DLL4 expression may be used as a clinical param-eter for predictive prognostication of NSCLC patients.

Expression and significance of DLL4 protein in endometriosis / 中国生化药物杂志

Objective To investigate the expression and significance of DLL4 in endometriosis.Methods 83 cases due to ovarian cyst surgery from December 2010 to September 2013,were selected in the Second Affiliated Hospital of Zhengzhou University,and were randomly divided into two groups in accordance with the random number table.Group A:48 cases were induded after staining from 83 patients who were tahen a part of cyst wall;Group B:of laparoscopic ovarian cyst surgery in 83 patients,37 cases of simultaneously hysteroscopy due to fertility requirements,exclude endometrial lesions,were taken reign uterine endometrium.The American fertility association revised standard (r-AFS)in 1985 was used to divide the clinical stage:Group A:21 cases of Ⅰ ~Ⅱ stage,27 cases of Ⅲ ~Ⅳ;Group B:16 cases of Ⅰ ~Ⅱ stage,21 cases of Ⅲ ~Ⅳ stage;Group C:30 cases hysteroscopic uterine septum resection with electricity due to lower mediastinal uterus were selected at the same period.The expression levels of DLL4 protein in Group A,B were detected by S-P method,and compared with the control group (Group C),then analyze its relationship with EMs stage. Results In Group A,B and C,the expression of DLL4 protein were (144.99 ±10.12 ),(1 15.42 ±10.39 ),(90.08 ±7.29 ),and there were significantly diffiences among three groups (F=314.220,P<0.05);The expression of DLL4 protein atⅠ~Ⅱstage were significantly lower than that inⅢ~Ⅳ stage (P<0.05).Conclusion DLL4 protein may play an important role in the pathogenisis of endometriosis.

The mechanism underlying the differentiation of human umbilical cord-derived mesenchymal stem cells into myocardial cells induced by 5-azacytidine.

Objective: To investigate the molecular mechanism underlying the differentiation of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) into myocardial cells induced by 5-azacytidine (5-aza), and to explore the expression and significance of DLL4-Notch signaling in this process. Materials and Methods: hUCMSCs were isolated and purified from the umbilical cords of normal or cesarean term deliveries under sterile conditions. After treatment with 5-aza for 24 h, hUCMSCs was continued to culture, the expression of GATA4 and NKx2.5 at 4 weeks after induction, DLL4 and Notch1 mRNA at 1d, 3d, 5d, 7d after induction were detected. The expression of cardiac troponin I (cTnI) after 4 weeks was determined by immunocytochemistry. Results: hUCMSCs treated with 5-aza were stained positively for cTnI 4 weeks after induction. The expression of Notch1 and DLL4 mRNA in the 5-aza-induced group was stable and significantly higher than that in the control group (mean Ct value for the Notch1 gene: 0.51 ± 0.21 in the 5-aza-induced group vs. 7.85 ± 0.35 in the control group; mean Ct value for the DLL4 gene: 1.60 ± 0.49 in the 5-aza-induced group vs. 12.42 ± 0.73 in the control group). Similar results were observed for Nkx2.5 and GATA4 genes. The expressions of Nkx2.5 and GATA4 mRNA in the 5-aza group were 4.72 ± 0.58 and 3.76 ± 0.06 times higher than that in the control group, respectively, with statistical significance. Conclusions: hUCMSCs can be differentiated into myocardial cells by 5-aza induction in vitro. 5-Aza may affect this process by regulating the expression of GATA4 and Nkx2.5 genes. The DLL4-Notch signal pathway may be involved in this process.

Design of a Brain-computer Interface System Based on Labview and VC / 中国医学物理学杂志

Objective:Labview and VC were used to design software based on the Active One biopotential measurement system to realize the visual evoked potential based brain-computer interface.Methods:The data acquisition software was designed by Labview,the human-interface,real time signal processing and dynamic link library software were designed by VC.Data transmission between Labview and VC was realized through the dynamic link library using shared memory technology.The multimedia timer,DirectDraw technology and parallel port data output were used to design the visual stimulation interface.The 5 points averaging filter combining with averaging method were used to detect the visual evoked potential and the correlation coefficient was computed for signal recognization.Results:The experiments showed that the visual stimulator can produce effective visual stimulation.The data transmission method using the dynamic link library can satisfy the requirement of the system.Conclusions:The real-time signal processing method can improve signal-noise ratio and realize detection and recognization of visual evoked potential.The system can determine which module the subject was fixating and the result was feedback to the subject in real time.

Effect of anti-HER-2 engineered antibody chA21 on angiogenesis in nude mice xenografts of human ovarian cancer SKOV3 cells / 临床与实验病理学杂志

Purpose To investigate the effect of anti-HER-2 engineered antibody chA21 on the angiogenesis in nude mice xenografts of human ovarian cancer SKOV3 cells that overexpresses HER-2.Methods An animal model with SKOV3 cells involved in nude mice was established and the mice were randomized into control group and chA21 group;chA21 was administrated via caudal vein for 5 weeks, meanwhile the same volume of chA21 buffer was injected in control group.The mice were terminated after 5 weeks and the xenografts dislodged,VEGF and DLL4 expression in two groups were quantitatively analyzed by immunohistochemistry on tissue microarray sections combined with a micro-image analyzing system, and microvessel density (MVD) values were compared between the two groups by immunohistochemical staining of CD31.Results The expression of VEGF, DLL4 and MVD values in chA21 group were lower than those in control group (P<0.05).Conclusion chA21 inhibits the angiogenesis of transplantations of human ovarian cancer SKOV3 cells effectively.

Review of the role of Dll4-Notch signaling pathway in angiogenesis / 基础医学与临床

Angiogenesis is regulated by complex interactions of multiple activators and inhibitors.Vascular endothelial growth factor(VEGF)and Notch signaling pathway are involved in such process.Recent studies have demonstrated that Notch signaling pathway plays a key role in the embryonic development and tumour angiogenesis,and identified the role of Dll4-Notch signaling during vascular development and the mechanism of the vascular defects which result from reduction of Notch signaling,thus Dll4-Notch became regarded as novel and important drug targets for disrupting tumour angiogenesis.This review emphasizes on introduction of the constitution of Notch signaling pathway,the role of Dll4-Notch in angiogenesis and the significance of Dll4-Notch for tumour therapy.

The clinical significance and correlation of Notch1/DLL4 pathway and VEGF in invasion and metastasis of gastric carcinoma / 中国普通外科杂志

Objective To investigate the expression of Notch1 and its ligand DLL4 in human gastric carcinoma tissues and its correlation with tumor angiogenic metastasis.Methods Immunohistochemical SP method was used to detect the expression of Notch1,DLL4 and VEGF in 45 gastric carcinoma tissues and paired adjacent normal gastric mucosa,and the relationship between them and clinico-pathological parameters were analyzed.Results The positive expression rate of Notch1,DLL4 and VEGF in gastric carcinoma were higher than that in normal gastric mucosa(P

The design and implementation of interface software between HIS and MIS of social medical insurance / 医疗卫生装备

The interface software between HIS and MIS of social medical insurance makes it possible to interchange data between the two systems and apply HIS to medical insurance management. Usually, the social medical insurance center offers a standard method of interface, which is called the upper interface. The interface between the upper interface and HIS, called the lower interface, requires specific design based on specific HIS. This article discusses a case in which a HIS client computer can transmit data to the server at the insurance center and receive real-time processing results. The upper interface consists of two dynamic link libraries (DLL). Three tasks have to be accomplished to program the lower interface, which are to create a table in HIS database and arrange every item in HIS price list with its corresponding item in the insurance list, to create tables or fields in HIS database to store proper data for medical insurance business, and to design a special HIS application module and alter several existing modules for medical insurance business. There are some key points in programming such as invoking a function in the DLL properly, gathering data to form a character storing variables for the function and parsing the returned character string to extract result data.