Objective A targeted nanopeptides(VEGF/TIE-2 targeted nanopeptides,VTN)that simultaneously inhibits vascu-lar endothelial growth factor(VEGF)/tyrosine kinase with immunoglobulin-like and EGF-like domains-2(TIE-2)signaling pathways were designed and synthesized,and explore its inhibitory effect on angiogenesis in renal clear cell carcinoma(ccRCC).Methods VTN and non-self-assembling control VTN-C were prepared by solid-phase peptide synthesis technology,and the molecular structures of VTN and VTN-C were analyzed by electrospray ionization mass spectrometry(ESI-MS).The CCK-8 method was used to evaluate the effect of VTN on the cell viability of human umbilical vein endothelial cells(HUVEC).The cell scratch assay,Transwell invasion assay and angiogenesis assay were used to detect the inhibitory effects of VTN on migration,invasion and angiogenesis of HUVEC.Western blot was used to detect the effect of VTN on the phosphorylation of downstream proteins of VEGF and TIE-2 signaling pathways.A 786-O cell mouse model was established,and the effects of VTN on tumor angiogenesis and tumor progression were observed through animal ex-periments.Results ESI-MS showed that the main charge state peaks of both synthesized VTN and VVTN-C pointed to the same molec-ular weight,which was highly consistent with the corresponding theoretical molecular mass.Immunofluorescence showed that VTN co-lo-calized with VEGF and TIE-2.VTN combined with MMP-2 could significantly inhibit the activity of HUVEC(P<0.001).The cell inva-sion rate and scratch closure rate in the VTN group were reduced by(78.30±1.35)%and(37.09±3.49)%compared those in the PBS group,respectively(P<0.001).Angiogenesis experiments showed that VTN could significantly inhibit the angiogenesis of HUVEC(P<0.001).Western blot showed that VTN significantly inhibited the phosphorylation of Akt and ERK(P<0.001).The results from animal experimentsshowed that tumor volume in the VTN group was decreased by(87.16±1.30)%compared with the control group,and the CD31-positive area was reduced(P<0.001).Conclusion VTN significantly blocks ccRCC angiogenesis and delays tumor progression by inhibiting VEGF and TIE-2 signaling pathways and downregulating Akt and ERK phosphorylation.

Objective A targeted nanopeptides(VEGF/TIE-2 targeted nanopeptides,VTN)that simultaneously inhibits vascu-lar endothelial growth factor(VEGF)/tyrosine kinase with immunoglobulin-like and EGF-like domains-2(TIE-2)signaling pathways were designed and synthesized,and explore its inhibitory effect on angiogenesis in renal clear cell carcinoma(ccRCC).Methods VTN and non-self-assembling control VTN-C were prepared by solid-phase peptide synthesis technology,and the molecular structures of VTN and VTN-C were analyzed by electrospray ionization mass spectrometry(ESI-MS).The CCK-8 method was used to evaluate the effect of VTN on the cell viability of human umbilical vein endothelial cells(HUVEC).The cell scratch assay,Transwell invasion assay and angiogenesis assay were used to detect the inhibitory effects of VTN on migration,invasion and angiogenesis of HUVEC.Western blot was used to detect the effect of VTN on the phosphorylation of downstream proteins of VEGF and TIE-2 signaling pathways.A 786-O cell mouse model was established,and the effects of VTN on tumor angiogenesis and tumor progression were observed through animal ex-periments.Results ESI-MS showed that the main charge state peaks of both synthesized VTN and VVTN-C pointed to the same molec-ular weight,which was highly consistent with the corresponding theoretical molecular mass.Immunofluorescence showed that VTN co-lo-calized with VEGF and TIE-2.VTN combined with MMP-2 could significantly inhibit the activity of HUVEC(P<0.001).The cell inva-sion rate and scratch closure rate in the VTN group were reduced by(78.30±1.35)%and(37.09±3.49)%compared those in the PBS group,respectively(P<0.001).Angiogenesis experiments showed that VTN could significantly inhibit the angiogenesis of HUVEC(P<0.001).Western blot showed that VTN significantly inhibited the phosphorylation of Akt and ERK(P<0.001).The results from animal experimentsshowed that tumor volume in the VTN group was decreased by(87.16±1.30)%compared with the control group,and the CD31-positive area was reduced(P<0.001).Conclusion VTN significantly blocks ccRCC angiogenesis and delays tumor progression by inhibiting VEGF and TIE-2 signaling pathways and downregulating Akt and ERK phosphorylation.

Objective:To investigate the differences in electroencephalographic (EEG) microstate characteristics between children with autism spectrum disorder (ASD) and typically developing (TD) children, and to explore the correlation between irritability and EEG microstate features in ASD children.Methods:A total of 104 children with ASD [ASD group, 83 boys, 21 girls; aged 4-13 years, mean age (9.47±1.74)years] from the Autism Cohort of Nanjing Medical University and 60 TD children [TD group; 50 boys, 10 girls; aged 5-13 years, mean age(9.86±1.78) years ]from the IEEE Dataport database were enrolled. Irritability severity was assessed using the Affective Reactivity Index-Parent (ARI-P). Resting-state EEG data with eyes closed were recorded using a 24-channel dry-electrode EEG cap. Group-level EEG microstate topographic maps and microstate parameters, including mean duration, frequency, and time coverage, were extracted and compared between groups using nonparametric tests. In the ASD group, Spearman correlation analysis was used to examine the associations between microstate features and ARI-P in ASD children. Multiple linear regression was used to identify predictors of irritability.Results:Four group-level microstates (A, B, C, D) were identified in both groups. Compared to TD children, ASD children exhibited significantly longer mean duration for all microstates, in microstates A[ M(Q1, Q3)]: 0.060 (0.054,0.070) vs 0.091 (0.0530, 0.155) s, microstate B: 0.059 (0.050, 0.066) vs 0.087 (0.057,0.149) s, microstate C: 0.059 (0.050, 0.066) vs 0.095 (0.056, 0.183) s and microstate D: 0.055 (0.049,0.075) vs 0.095 (0.053,0.162) s ( Z=-3.51, -4.89, -4.71, -4.21; all P<0.001); However, microstate occurrence frequencies were significantly lower in the ASD group: A: 5.423 (3.640,21.024) vs 1.834 (1.327,3.395) Hz, microstate B: 4.949 (3.439,20.038) vs 2.146 (1.314,3.834) Hz, microstate C: 5.888 (3.998,22.078) vs 2.234 (1.441,3.768) Hz and microstate D: 5.371 (3.170,15.208) vs 2.074 (1.147,3.582) Hz ( Z=-7.72, -6.41, -7.85, -6.60; all P<0.001). In the ASD group, ARI-P scores were positively correlated with the mean duration of microstates B, C, and D ( r=0.28, 0.26, 0.33; all P<0.05) and negatively correlated with the occurrence frequency of microstates A, C, and D ( r=-0.26, -0.27, -0.21; all P<0.05). Multiple linear regression analysis revealed that the mean duration of microstate B was a significant predictor of irritability severity ( β=0.436, 95% CI: 1.260-4.202, P<0.001). Conclusion:Resting-state EEG microstate characteristics in Children with ASD differ from those in TD children and are associated with the severity of irritability. Prolonged duration of microstate B may serve as a risk factor for increased irritability in children with ASD.

Objective:To investigate the differences in electroencephalographic (EEG) microstate characteristics between children with autism spectrum disorder (ASD) and typically developing (TD) children, and to explore the correlation between irritability and EEG microstate features in ASD children.Methods:A total of 104 children with ASD [ASD group, 83 boys, 21 girls; aged 4-13 years, mean age (9.47±1.74)years] from the Autism Cohort of Nanjing Medical University and 60 TD children [TD group; 50 boys, 10 girls; aged 5-13 years, mean age(9.86±1.78) years ]from the IEEE Dataport database were enrolled. Irritability severity was assessed using the Affective Reactivity Index-Parent (ARI-P). Resting-state EEG data with eyes closed were recorded using a 24-channel dry-electrode EEG cap. Group-level EEG microstate topographic maps and microstate parameters, including mean duration, frequency, and time coverage, were extracted and compared between groups using nonparametric tests. In the ASD group, Spearman correlation analysis was used to examine the associations between microstate features and ARI-P in ASD children. Multiple linear regression was used to identify predictors of irritability.Results:Four group-level microstates (A, B, C, D) were identified in both groups. Compared to TD children, ASD children exhibited significantly longer mean duration for all microstates, in microstates A[ M(Q1, Q3)]: 0.060 (0.054,0.070) vs 0.091 (0.0530, 0.155) s, microstate B: 0.059 (0.050, 0.066) vs 0.087 (0.057,0.149) s, microstate C: 0.059 (0.050, 0.066) vs 0.095 (0.056, 0.183) s and microstate D: 0.055 (0.049,0.075) vs 0.095 (0.053,0.162) s ( Z=-3.51, -4.89, -4.71, -4.21; all P<0.001); However, microstate occurrence frequencies were significantly lower in the ASD group: A: 5.423 (3.640,21.024) vs 1.834 (1.327,3.395) Hz, microstate B: 4.949 (3.439,20.038) vs 2.146 (1.314,3.834) Hz, microstate C: 5.888 (3.998,22.078) vs 2.234 (1.441,3.768) Hz and microstate D: 5.371 (3.170,15.208) vs 2.074 (1.147,3.582) Hz ( Z=-7.72, -6.41, -7.85, -6.60; all P<0.001). In the ASD group, ARI-P scores were positively correlated with the mean duration of microstates B, C, and D ( r=0.28, 0.26, 0.33; all P<0.05) and negatively correlated with the occurrence frequency of microstates A, C, and D ( r=-0.26, -0.27, -0.21; all P<0.05). Multiple linear regression analysis revealed that the mean duration of microstate B was a significant predictor of irritability severity ( β=0.436, 95% CI: 1.260-4.202, P<0.001). Conclusion:Resting-state EEG microstate characteristics in Children with ASD differ from those in TD children and are associated with the severity of irritability. Prolonged duration of microstate B may serve as a risk factor for increased irritability in children with ASD.

Objective The purpose of this study is to explore the efficacy and predictors of second?line chemotherpy in advanced non?small cell lung cancer patients and suggest optimal protocols suitable for differently characterized patients. Methods The clinical data of 178 advanced NSCLC patients second?line?treated in Tianjin Cancer Hospital from 2009.1.1 to 2013.12.31 were retrospectively analyzed. According to the different second?line treatments, the patients were divided into standard mono?drug therapy group ( 46 cases), endostar combined with standard mono?drug therapy group (42 cases), and platinum?based doublet chemotherapy group ( 90 cases) . Kaplan?Meier and Log?rank analyses were used to estimate and compare the survival rates in the groups, and Cox′s hazard regression model was used to determine the prognostic factors. Chi?square test was used to analyze the differences among different groups. Results The median progression?free survivals ( mPFS) were 50 days, 54 days, and 79 days ( P=0.042) for the standard mono?drug therapy group, endostar combined with standard mono?drug therapy group, and platinum?based doublet chemotherapy group, respectively. The differences between the mono?drug therapy group and doublet chemotherapy group were statistically significant ( P=0. 011 ) . The disease control rate ( DCR ) for each group was 26.1%, 47.6% and 46.7% (P=0.041), and the DCR were statistically significantly different between the mono?drug therapy group and doublet chemotherapy group ( P=0.016) , and between the mono?drug therapy group and endostar combined with standard mono?drug therapy group (P=0.041). The overall response rate (ORR) for each group was 2.2%, 0, and 4.4% (P>0.05 for all). Multivariate analysis showed that the period from the begining of first?line to second?line chemotherapy ( progression?free time) , base?line clinical stage, neuron specific enolase ( NSE) before second?line therapy, the cycles of second?line chemotherapy and the response to second?line therapy were independent predictors for PFS ( P<0. 005 for all) . Subgroup analysis indicated that the patients obtained more clinical benefit from doublet chemotherapy rather than mono?drug therapy, with following factors: age<60 years, paclitaxel plus cisplatin for first?line treatment, chemotherapy cycles≤4, CR, PR and SD for response, progression time within 3?6 months from the begining of first?line to second?line chemotherapy, performance status score≤1 at the begining of second?line therapy,Ⅳ stage, and mild leukopenia ( P<0.05 for all) . The patients whose progression?free survival time within 3?6 months from the begining of the first?line to second?line chemotherapy got more clinical benefit from endostar combined with standard mono?drug chemotherapy than mono?drug therapy ( P=0.006) . Conclusions The period from the begining of first?line to second?line chemotherapy, base?line TNM stage, NSE before second?line chemotherapy, the cycles of second?line chemotherapy and the response to second?line therapy were independent predictors for PFS. Platinum?based doublet chemotherapy and endostar plus standard second?line regimen can improve the efficacy in some characterized advanced NSCLC as compared with the patients by standard mono?drug therapy, wherein the platinum?based chemotherapy revealed the best efficacy.

Objective The purpose of this study is to explore the efficacy and predictors of second?line chemotherpy in advanced non?small cell lung cancer patients and suggest optimal protocols suitable for differently characterized patients. Methods The clinical data of 178 advanced NSCLC patients second?line?treated in Tianjin Cancer Hospital from 2009.1.1 to 2013.12.31 were retrospectively analyzed. According to the different second?line treatments, the patients were divided into standard mono?drug therapy group ( 46 cases), endostar combined with standard mono?drug therapy group (42 cases), and platinum?based doublet chemotherapy group ( 90 cases) . Kaplan?Meier and Log?rank analyses were used to estimate and compare the survival rates in the groups, and Cox′s hazard regression model was used to determine the prognostic factors. Chi?square test was used to analyze the differences among different groups. Results The median progression?free survivals ( mPFS) were 50 days, 54 days, and 79 days ( P=0.042) for the standard mono?drug therapy group, endostar combined with standard mono?drug therapy group, and platinum?based doublet chemotherapy group, respectively. The differences between the mono?drug therapy group and doublet chemotherapy group were statistically significant ( P=0. 011 ) . The disease control rate ( DCR ) for each group was 26.1%, 47.6% and 46.7% (P=0.041), and the DCR were statistically significantly different between the mono?drug therapy group and doublet chemotherapy group ( P=0.016) , and between the mono?drug therapy group and endostar combined with standard mono?drug therapy group (P=0.041). The overall response rate (ORR) for each group was 2.2%, 0, and 4.4% (P>0.05 for all). Multivariate analysis showed that the period from the begining of first?line to second?line chemotherapy ( progression?free time) , base?line clinical stage, neuron specific enolase ( NSE) before second?line therapy, the cycles of second?line chemotherapy and the response to second?line therapy were independent predictors for PFS ( P<0. 005 for all) . Subgroup analysis indicated that the patients obtained more clinical benefit from doublet chemotherapy rather than mono?drug therapy, with following factors: age<60 years, paclitaxel plus cisplatin for first?line treatment, chemotherapy cycles≤4, CR, PR and SD for response, progression time within 3?6 months from the begining of first?line to second?line chemotherapy, performance status score≤1 at the begining of second?line therapy,Ⅳ stage, and mild leukopenia ( P<0.05 for all) . The patients whose progression?free survival time within 3?6 months from the begining of the first?line to second?line chemotherapy got more clinical benefit from endostar combined with standard mono?drug chemotherapy than mono?drug therapy ( P=0.006) . Conclusions The period from the begining of first?line to second?line chemotherapy, base?line TNM stage, NSE before second?line chemotherapy, the cycles of second?line chemotherapy and the response to second?line therapy were independent predictors for PFS. Platinum?based doublet chemotherapy and endostar plus standard second?line regimen can improve the efficacy in some characterized advanced NSCLC as compared with the patients by standard mono?drug therapy, wherein the platinum?based chemotherapy revealed the best efficacy.

OBJECTIVEThis study was designed to investigate the correlation factors for occurrence and progression-free survival of patients with cavitating lung cancer.

METHODSWe collected the clinical data of 947 lung cancer patients. Tumor cavitation was observed in 51 patients at baseline and in 23 patients after treatment, while was not discovered in other 873 patients. Multifactor logistic regression was performed to analyze the correlation factors for occurrence. The independent predictors of PFS were analyzed with Cox proportional regression. Survival curves were constructed with the Kaplan-Meier product limit method and compared using the log-rank test.

RESULTSIn the 947 cases, the proportion of cases with baseline cavitation was 5.4% and the incidence of cavitation after treatment was 2.6%. Multivariate logistic regression analysis revealed that the occurrence of baseline cavitation is related to age, history of diabetes, history of drinking, pathologic types, tumor location, tumor diameter and distant metastasis (P < 0.05). Multifactor logistic regression analysis revealed that the occurrence of post-therapeutic cavitation is related to sex, pathologic types and tumor diameter (P < 0.05).The median PFS of patients with baseline cavitation (7.3 months) was significantly longer than the cases without it (5.2 months) (P = 0.002). While there was no significant difference between the median PFS of patients with post-therapeutic cavitation and patients without it (5.1 months vs. 5.3 months, P = 0.060). Cox proportional regression analysis revealed that cyfra21-1 is related to PFS of patients with baseline cavitaion (P < 0.05) and smoking history is related to PFS of patients with post-therapeutic cavitaion (P < 0.05).

CONCLUSIONSPatients with baseline and post-therapeutic cavitation present different clinical features and progression-free survivals. The PFS of patients with baseline cavitation is longer than that of the cases without it. On the contrary, PFS of patients with post-therapeutic cavitation is shorter than the patients without it.

Antigens, Neoplasm ; metabolism ; Disease-Free Survival ; Humans ; Kaplan-Meier Estimate ; Keratin-19 ; metabolism ; Lung Neoplasms ; mortality ; pathology ; therapy ; Regression Analysis ; Retrospective Studies ; Risk Factors ; Time Factors

Objective This study was designed to investigate the correlation factors for occurrence and progression?free survival of patients with cavitating lung cancer. Methods We collected the clinical data of 947 lung cancer patients. Tumor cavitation was observed in 51 patients at baseline and in 23 patients after treatment, while was not discovered in other 873 patients. Multifactor logistic regression was performed to analyze the correlation factors for occurrence. The independent predictors of PFS were analyzed with Cox proportional regression. Survival curves were constructed with the Kaplan?Meier product limit method and compared using the log?rank test. Results In the 947 cases, the proportion of cases with baseline cavitation was 5.4% and the incidence of cavitation after treatment was 2.6%. Multivariate logistic regression analysis revealed that the occurrence of baseline cavitation is related to age, history of diabetes, history of drinking, pathologic types, tumor location, tumor diameter and distant metastasis ( P<0. 05 ) . Multifactor logistic regression analysis revealed that the occurrence of post?therapeutic cavitation is related to sex, pathologic types and tumor diameter (P<0.05).The median PFS of patients with baseline cavitation (7.3 months) was significantly longer than the cases without it (5.2 months) (P=0.002). While there was no significant difference between the median PFS of patients with post?therapeutic cavitation and patients without it (5.1 months vs. 5.3 months, P=0.060 ) . Cox proportional regression analysis revealed that cyfra21?1 is related to PFS of patients with baseline cavitaion ( P<0.05) and smoking history is related to PFS of patients with post?therapeutic cavitaion ( P<0. 05 ) . Conclusions Patients with baseline and post?therapeutic cavitation present different clinical features and progression?free survivals. The PFS of patients with baseline cavitation is longer than that of the cases without it. On the contrary, PFS of patients with post?therapeutic cavitation is shorter than the patients without it.

Objective This study was designed to investigate the correlation factors for occurrence and progression?free survival of patients with cavitating lung cancer. Methods We collected the clinical data of 947 lung cancer patients. Tumor cavitation was observed in 51 patients at baseline and in 23 patients after treatment, while was not discovered in other 873 patients. Multifactor logistic regression was performed to analyze the correlation factors for occurrence. The independent predictors of PFS were analyzed with Cox proportional regression. Survival curves were constructed with the Kaplan?Meier product limit method and compared using the log?rank test. Results In the 947 cases, the proportion of cases with baseline cavitation was 5.4% and the incidence of cavitation after treatment was 2.6%. Multivariate logistic regression analysis revealed that the occurrence of baseline cavitation is related to age, history of diabetes, history of drinking, pathologic types, tumor location, tumor diameter and distant metastasis ( P<0. 05 ) . Multifactor logistic regression analysis revealed that the occurrence of post?therapeutic cavitation is related to sex, pathologic types and tumor diameter (P<0.05).The median PFS of patients with baseline cavitation (7.3 months) was significantly longer than the cases without it (5.2 months) (P=0.002). While there was no significant difference between the median PFS of patients with post?therapeutic cavitation and patients without it (5.1 months vs. 5.3 months, P=0.060 ) . Cox proportional regression analysis revealed that cyfra21?1 is related to PFS of patients with baseline cavitaion ( P<0.05) and smoking history is related to PFS of patients with post?therapeutic cavitaion ( P<0. 05 ) . Conclusions Patients with baseline and post?therapeutic cavitation present different clinical features and progression?free survivals. The PFS of patients with baseline cavitation is longer than that of the cases without it. On the contrary, PFS of patients with post?therapeutic cavitation is shorter than the patients without it.

BACKGROUNDSporadic fundic gland polyps (FGPs) are common gastric polyps. Some studies reported that FGPs dramatically increased due to proton pump inhibitors (PPIs) use and a decreased prevalence of Helicobacter pylori (H. pylori) infection in Western countries. However, data are still controversial. This study aimed to identify the relationships between these two factors and FGPs in China.

METHODSConsecutive patients with FGPs detected were retrospectively analyzed. Data including patients' age, sex, symptoms, H. pylori infection, history of PPIs use, and the polyps were documented. Each patient was compared with two randomly selected age- and sex-matched controls with similar symptoms in the same period.

RESULTSDuring the period from March 2011 to March 2012, a total of 328 patients were diagnosed as FGPs in 23 047 patients who underwent routine esophagogastroduodenoscopy and 656 patients without FGPs as controls. The mean age was (55.12±12.61) years, and 75.91% were women. The prevalence of H. pylori in patients with FGPs was significantly lower than in those without FGPs (22.30% (64/287) vs. 42.26% (224/530), P < 0.001, OR 0.392, 95% CI 0.283-0.544). Overall, a total of 54 patients with FGPs (54/328, 16.46%) and 136 patients without FGPs (136/656, 20.73%) received PPIs therapy (P = 0.110). According to the different duration of PPIs use, no significant differences of PPIs use were found between the cases and controls among all subgroups. Moreover, the PPIs use was also similar, regardless of age, sex, H. pylori infection, and the number of polyps.

CONCLUSIONSporadic FGPs may not be induced by PPIs therapy but negatively correlate with H. pylori infection in China, which is not the same with the data in Western countries.

Adenomatous Polyps ; epidemiology ; Adult ; Aged ; China ; epidemiology ; Endoscopy, Digestive System ; Female ; Gastric Fundus ; drug effects ; pathology ; Helicobacter Infections ; epidemiology ; Humans ; Male ; Middle Aged ; Proton Pump Inhibitors ; adverse effects ; Retrospective Studies ; Stomach Neoplasms ; epidemiology