Pediatric cancer is one of the leading causes of death in children around the world.Although radiotherapy is an important means of treatment for pediatric cancer,it causes acute or chronic adverse events that may affect patients' survival time and quality of life.As a novel and advanced radiation technique,proton therapy allows for precise dose delivery in target volume,significantly reducing the irradiation to surrounding tissues and organs.Studies have shown that proton therapy is well tolerated in the treatment of pediatric cancer,and it achieves good tumor control;proton therapy is superior to traditional radiotherapy in improving quality of life,protecting intelligence,and reducing the risk of secondary cancer.This article reviews the research advances in the application of proton therapy in the treatment of pediatric cancer.

Objective To discuss the validity and the feasibility of modified specific immunotherapy of hypoglossis allergen in the treatment of children allergic asthma. Methods 100 children with allergic asthma were selected from October,2007 to April ,2008 in our hospital and divided into the observation group and the control group. The control group adopted routine method, the observation group made modifi-cation based upon routine nursing, placing emphasis on intervention of cognition and behavior of children and their parents, improvement of treatment compliance, whole- process, dynamic and continuous observa-tion of the treatment process, making individualized health education plan. The treatment compliance, total score of asthma control, and pulmonary function examination of impulse oscillation(IOS) were compared be-tween the two groups. Results The observation group was superior to the control group in treatment com-pliance, pulmonary function examination and the control results of asthma. Conclusions Specific im-munotherapy of hypoglossis allergen combined with modified nursing method can increase treatment com-pliance of children and lead to better results.

OBJECTIVEThe glucocorticoid dexamethasone (DEX) can induce palatal cleft; however, the mechanism involved remains unclear. E-cadherin is an important cell adhesion molecule, and it can significantly affect cell fate and embryonic development. Recent studies have indicated that E-cadherin expression in palatal epithelial cells is suppressed in normal palate fusion. This study aimed to determine whether the change in E-cadherin expression is related to the incidence of cleft palate in DEX-induced mice.

METHODSMice were divided into the experimental group and the control group. Pregnant mice were injected with DEX on E10.0-E12.0, whereas mice in the control group were injected with normal saline. Hematoxylin and eosin (HE) staining, immunohistochemistry, and real-time quantitative polymerase chain reaction were employed to evaluate the effect of DEX on fetal mouse palatal processes, particularly the changes in E-cadherin and β-catenin expression levels in the phases of the experimental and control groups.

RESULTSData indicated that the incidence of cleft palate in the DEX group was 43.59% (17/39), whereas that in the control group was only 3.03% (1/33). The results of HE staining showed that the obviously shortened palatal processes could not contact and fuse with one another in the DEX-treated mice model compared with those in the control group. The ectopic expression of E-cadherin in embryonic palatal mesenchymal cells was also analyzed. The expression levels of E-cadherin and β-catenin in the experimental group were higher than those in the control group.

CONCLUSIONThese findings indicated that DEX could induce E-cadherin gene upregulation and ectopic expression, as well as high β-catenin expression, thereby inhibiting the growth of mesenchyme cells and cleft palate.

Animals ; Cadherins ; genetics ; metabolism ; Cleft Palate ; chemically induced ; embryology ; Dexamethasone ; adverse effects ; Disease Models, Animal ; Epithelial Cells ; Female ; Glucocorticoids ; Immunohistochemistry ; Mice ; Pregnancy ; beta Catenin ; metabolism

A quality control (QC) strategy for quantitative and qualitative analysis of “common peaks” in chemical fingerprint was proposed to analyze Yuanhu Zhitong tablet (YZT), using high performance liquid chromatography with diode array detector and tandem mass spectrometry (HPLC-DAD-MS/MS). The chromatographic separation was achieved on an Agilent Eclipse plus C18 column with a gradient elution using a mixture of 0.4‰ ammonium acetate aqueous (pH 6.0 adjusted with glacial acetic acid) and acetonitrile. In chemical fingerprint, 40 peaks were assigned as the “common peaks”. For quantification of “common peaks”, the detection wavelength was set at 254 nm, 270 nm, 280 nm and 345 nm, respectively. The method was validated and good results were obtained to simultaneously determine 10 analytes (protopine, jatrorrhizine, coptisine, palmatine, berberine, xanthotoxin, bergapten, tetrahydropalmatine, imperatorin and isoimperatorin). For qualification of “common peaks”, 33 compounds including 10 quantitative analytes were identified or tentatively characterized using LC-MS/MS. These results demonstrated that the present approach may be a powerful and useful tool to tackle the complex quality issue of YZT.

ObjectiveToinvestigatethecorrelationbetween-2578C>Apolymorphismofvascular endothelium grow th factor (VEGF) gene and carotid atherosclerosis in Chinese Han population in Shandong, China. Methods A total of 384 subjects aged 45-85 in Chinese Han population in Shandong, China w ere enroled. They were divided into either an increased intima-media thickness (IMT) group ( n=248) or a control group (n=136) according to the vascular ultrasound results. The baseline clinical data, such as the demographic data, vascular risk factors, and blood biochemical indicators in both groups were colected. Polymerase chain reaction w as used to detect the VEGF gene -2578C>A polymorphism genotype and alele. Multivariate logistic regression analysis was used to identify the independent risk factors for increased carotid IMT. Results The proportions of hypertension ( 70.6%vs.59.6%;χ2 =4.793, P=0.032), diabetes (18.4%vs.29.0%; χ2 =5.281, P=0.027), hyperlipidemia ( 45.2%vs.33.1%; χ2 =7.883, P=0.006), previous previous stroke or transient ischemic attack (29.0%vs.16.9%;χ2 =6.294, P=0.009), smoking (35.9%vs.19.9%;χ2 =10.708, P=0.001), as w el as total cholesterol ( 4.82 ±1.25 mmol/L vs.4.57 ± 0.94 mmol/L; t= -2.072, P= 0.039 ), triglyceride ( median, interquartile range; 1.71[0.84-2.22] mmol/L vs.1.53[1.08-2.59] mmol/L;Z= -2.560 P=0.010), low-density lipoprotein cholesterol (2.86 ±1.01 mmol/L vs.2.64 ±0.85 mmol/L; t= -2.407, P= 0.033 ), and high-density lipoprotein cholesterol (1.58 ±0.72 mmol/L vs.1.43 ±0.46 mmol/L;t= -2.183, P=0.030) in the increased IMT group, and there w ere significant differences compared w ith the control group. There w as significant difference in genotype frequency betw een the 2 groups (χ2 =10.131; P=0.006). There w as significant difference in C alele frequency between the increased IMT group and the control group (78.2% vs. 70.2%;χ2 =6.068, P=0.014). Multivariate logistic regression analysis showed that CC genotype (odds ratio 1.132, 95%confidence interval 1.021-2.141;P=0.029) w as an independent risk factor for increased carotid IMT. In 248 patients w ith increased IMT, 213 had at least 1 plaque, 76 (39.6%) of them w ere 1-2, 107 (43.15%) w ere 3-4, and 30 (12.1%) w ere 5-8 in plaque index. There w ere no significant differences in frequencies of genotypes (χ2 =6.766, P=0.149) and alele (χ2 =0.185, P=0.667) in the different plaque index groups. Conclusions -2578 single nucleotide polymorphism in the VEGF gene promoter is associated w ith carotid atherosclerosis, and C al ele may be its genetic susceptibility factor in Chinese Han population in Shandong, China.

Objective To investigate associations of UC with the polymorphisms of TRAIL receptors.Methods From January 2008 to December 2012, 380 consecutive UC patients [215 males and 165 females, the average age was (42.63 ±14.61) years] as well as 539 sex-and age-matched healthy individuals [290 males and 249 females, the average age was (41.29 ±15.86) years] were recruited from four large scale comprehensive hospitals in Wenzhou city.Five single nucleotide polymorphisms of DR4 (rs20575, rs13278062), DR5(rs1047266), DcR2(rs1133782) and OPG (rs3102735) were detected by a SNaPshot technique.Distributions of mutant alleles and genotypes for targeted polymorphisms in TRAIL receptors were analyzed by Chi-square test or Fisher′s exact test. By means of unconditional Logistic regression analysis, it evaluated associations between the polymorphisms and the risk of UC attack as well as the clinical features of UC patients.Furthermore, an unconditional Logistic multiple regression analysis was employed to investigate the independent risk factors of UC and their multiplicative interaction effects on UC.Results The frequencies of mutant allele (G) and genotype (CG+GG) of DR4(rs20575) were higher in UC patients than those in the controls (3.55%vs 1.95%,χ2 =4.512, P=0.034;6.58%vs 3.71%,χ2=3.938, P=0.047, respectively).However, the frequeucies of mutant allele ( A) and genotype ( GA+AA) of DcR2(rs1133782) were decreased in UC patients compared to the controls(6.18%vs 9.09%,χ2=5.183, P=0.023; 11.32% vs 17.44%, χ2 =6.589, P=0.010, respectively).The frequencies of mutant allele (T) and homozygote (TT) of OPG(rs3102735) were significantly higher in UC patients than in the controls (86.32% vs 81.54%, χ2 =7.385, P=0.007;75.26% vs 66.98%, χ2 =7.346, P=0.007, respectively) .Furthermore, the genotype (GG) of DcR2 (rs1133782) was found to be the independent risk factor for UC attack (OR=4.937, 95%CI:2.320-10.504, P<0.001).Moreover, the (GG) of DcR2(rs1133782) and (CC) of DR4(rs20575) had an interactive effect on UC (OR=0.322, 95%CI:0.164-0.633, P=0.001).The same conclusion was drawn for the ( GG) of DR4( rs20575) and (TT) of OPG(rs3102735) (OR=1.580, 95%CI:1.165-2.144, P=0.003).Conclusions The genetic polymorphisms of DR4 ( rs20575 ) , DcR2 ( rs1133782 ) and OPG ( rs3102735 ) were associated with UC. The mutation of DcR2(rs1133782) might play a protective role in UC.Moreover, the DcR2(rs1133782) and DR4(rs20575) gene had a collaborative effect on UC.So did the DR4(rs20575) and OPG(rs3102735) genes.

Background and purpose:Promoter methylation ofPCDH10, a gene encoding protocadherin 10, has been found to be correlated to poor prognosis in gastric cancer (GC) patients. However, the relationship between the expression of PCDH10 and prognosis in GC remained unknown. This study aimed to explore the relationship be-tween the expression of PCDH10 and clinicopathological features and prognosis of GC, and to identify biomarker for predictions of recurrence and survival of GC.Methods:mRNA expressions of PCDH10 in 115 pairs of GC tissues and adjacent normal tissues were detected by real-time lfuorescence quantitative polymerase chain reaction (RTFQ-PCR). The correlation between PCDH10 expression level and clinicopathological features and prognosis of GC was analyzed. Prediction models for 5-year recurrence and 5-year survival were established using logistic regression method.Results:Progression-free survival (PFS) and overall survival (OS) were signiifcantly prolonged in patients with PCDH10 low expression compared to patients without PCDH10 low expression (P=0.046 andP=0.033 respectively). PCDH10 low expression signiifcantly correlated with less lymph node metastasis (P=0.001) and earlier TNM staging (P=0.001), and was more common in female than in male (P=0.040). The mRNA expression of PCDH10 did not correlate with age, Lauren classiifcation, T stage, neural invasion or vascular invasion. Univariate Cox analysis showed Lauren classiifca-tion, T stage, N stage, M stage and PCDH10 expression signiifcantly correlated with PFS and OS. Logistic regression models for the prediction of 5-year recurrence or 5-year survival based on clinicopathological features included Lauren classiifcation, T stage, N stage and M stage as variables. Logistic regression models for the prediction of 5-year recur-rence or 5-year survival based on PCDH10 expression included Lauren classiifcation, T stage, M stage and PCDH10 expression level but not N stage as variables. The models based on PCDH10 expression had the same effciencies as models based on clinical parameters in predicting 5-year recurrence or 5-year survival for GC patients.Conclusion:PCDH10 low expression correlated with better prognosis, less lymph node metastasis and earlier TNM stage in GC patients. Low expression of PCDH10 may be a biomarker of better survival for GC patients. Logistic regression model based on PCDH10 mRNA expression may serve as a prediction model when patients have unknown lymph node metas-tasis status.

Objective To compare the adjuvanticity of type-A,B and C CpG-ODN in mice.Methods Three types of CpG-ODN were identified through in vitro stimulation of murine splenocytes with various CpG-ODN.BALB/c mice were immunized with HBsAg,together with different types of CpG-ODN,and antigen-specific IgG.IgG1 and IgG2a titers were measured 4 weeks later by indirect ELISA.Resuits Compared with the control group.all 3 types of CpG-ODN enhanced humoral immune response to HBsAg.However,type-B and C CpG-ODN induced much higher levels of antigen-specific IgG and IgG2a than type A CpG-ODN.Type-C CpG-ODN induced a similar TH 1-biased immune response as type-B CpG-ODN,revealed by decreased IsG1 to IgG2a ratio.In contrast,although type-A CpG-ODN increased IgG titers,it did not switch the balance between TH1 and TH2 immune responses.Conclusion All 3 types of CpG-ODN can enhance the humoral immune response to vaccines,but their aaiuvanticity could be mediated through different mechanisms.

Purpose To study the malignant transformation after treating rat oval cell line ( WB-F344 ) with chemical carcinogen N-methyl-N′-nitro-N-nitrosoguanidine ( MNNG) . Methods WB-F344 cells were cultured with MNNG for severe times. The biological characteristics of induced cells were detected through the following methods:to check proliferation activity by flow cytometry analysis, to examine malignant transformation degree of induced cells by soft agar assay and tumor formation in NOD/SCID mice, and to investi-gate the transcriptional and protein levels of hepatocellular carcinoma marker GGT, GST-P by real time-PCR. Results Oval cells in-duced by MNNG showed changes in biological characteristics and malignant molecular markers. Conclusion Hepatic oval cells model is successfully established, which can be confirmed by tumor formation in NOD/SCID mice.

Polyhexamethylene guanidine (PHMG) is a high molecular guanidine compound with a broad spectrum of antibacterial effects. Since the outbreak of the 'humidifier disinfectant-induced lung injury’ event in South Korea, the respiratory toxicity of PHMG had become a public concern. An epidemiological survey in Korea found that PHMG-containing disinfectants were an important risk factor for pulmonary fibrosis. Animal experiments also showed that the exposure to PHMG through the respiratory tract could cause irreversible fibrosis in the lungs. TGF-β signaling pathway, epithelial-mesenchymal transition and pulmonary inflammation might be the main pathways that could mediate PHMG-induced pulmonary fibrosis. This article provided an overview of the characteristics of population exposure to PHMG and research progress in the field of respiratory toxicology and recommendations for the rational and standard of using PHMG-related products in China.