Multiregion sequencing reveals the intratumor heterogeneity of driver mutations in TP53-driven non-small cell lung cancer.

Intratumor heterogeneity (ITH) in non-small cell lung cancer (NSCLC) may account for resistance after a period of targeted therapies because drugs destroy only a portion of tumor cells. The recognition of ITH helps identify high-risk patients to make effective treatment decisions. However, ITH studies are confounded by interpatient heterogeneity in NSCLC and a large amount of passenger mutations. To address these issues, we recruited NSCLC patients carrying TP53 mutations and selected driver mutations within recurrently mutated genes in NSCLC. A total of 12-paired normal-tumor tissues were subjected to whole-genome/whole-exome sequencing. From these, 367 non-silent mutations were selected as driver mutations and deeply sequenced in 61 intratumoral microdissections. We identified a universal prevalence of heterogeneity in all 12 tumors, indicating branched evolution. Although TP53 mutations were observed in single biopsy of all 12 tumors, most tumors consist of both TP53 mutated and non-mutated cells in separate regions within the same tumor. This suggests the late molecular timing of the acquisition of TP53 mutations; therefore, the detection of TP53 mutations in a single biopsy may simply not reflect the early malignant potential. In addition, we identified regions of loss of heterozygosity surrounding TP53 and CDKN2A mutations in tumor 711, which also exhibited heterogeneity in different regional samples. Because the ITH of driver mutations likely has clinical consequences, further efforts are needed to limit the impact of ITH and to improve therapeutic efficiency, which will benefit NSCLC patients receiving targeted treatments.

Association between fat mass and obesity associated (FTO) gene rs9939609 A/T polymorphism and polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: Up to now, numerous case-control studies have reported the associations between fat mass and obesity associated (FTO) gene rs9939609 A/T polymorphism and polycystic ovary syndrome (PCOS), however, without a consistent result. Hence we performed current systematic review and meta-analysis to clarify the controversial results. METHODS: Case-control studies reporting the relationship of rs9939609 A/T polymorphism and PCOS published before April 2015 were searched in Pubmed database without language restriction. Data was analyzed by Review Manager 5.2. RESULTS: A total of five studies involving 5010 PCOS patients and 5300 controls were included for further meta-analysis. The results of meta-analysis showed that the FTO gene rs9939609 A/T polymorphism was significantly different between PCOS group and control group in different gene models (For AA + AT vs. TT: OR = 1.41, 95% CI = 1.28-1.55, P < 0.00001. For AA vs. AT + TT: OR = 1.54, 95% CI = 1.25-1.89, P < 0.0001. For AA vs. TT: OR = 1.74, 95% CI = 1.38-2.18, P < 0.00001. For A vs. T: OR = 1.36, 95% CI = 1.25-1.47, P < 0.00001, respectively) suggesting that A allele was a risk factor for PCOS susceptibility. Furthermore, subgroup analysis in Asian and Caucasian ethnicities also found significant association between rs9939609 A/T polymorphism and PCOS (In Asian subgroup: OR = 1.43, 95% CI = 1.29-1.59, P < 0.0001. In Caucasian subgroup: OR = 1.33, 95% CI = 1.08-1.64, P = 0.008) CONCLUSION: This meta-analysis suggests that rs9939609 A/T polymorphism of FTO gene is associated with PCOS risk, and that A allele is a risk factor for PCOS susceptibility simultaneously.

Genome-wide association study identifies a novel susceptibility gene for serum TSH levels in Chinese populations.

Thyroid-stimulating hormone (TSH) is a sensitive indicator of thyroid function. High and low TSH levels reflect hypothyroidism and hyperthyroidism, respectively. Even within the normal range, small differences in TSH levels, on the order of 0.5-1.0 mU/l, are associated with significant differences in blood pressure, BMI, dyslipidemia, risk of atrial fibrillation and atherosclerosis. Most of the variance in TSH levels is thought to be genetically influenced. We conducted a genome-wide association study of TSH levels in 1346 Chinese Han individuals. In the replication study, we genotyped four candidate SNPs with the top association signals in an independent isolated Chinese She cohort (n = 3235). We identified a novel serum TSH susceptibility locus within XKR4 at 8q12.1 (rs2622590, Pcombined = 2.21 × 10(-10)), and we confirmed two previously reported TSH susceptibility loci near FOXE1 at 9q22.33 and near CAPZB at 1p36.13, respectively. The rs2622590_T allele at XKR4 and the rs925489_C allele near FOXE1 were correlated with low TSH levels and were found to be nominally associated to patients with papillary thyroid carcinoma (PTC) (OR = 1.41, P= 0.014 for rs2622590_T, and OR = 1.61, P= 0.030 for rs925489_C). The rs2622590 and rs925489 genotypes were also correlated with the expression levels of FOXE1 and XKR4, respectively, in PTC tissues (P = 2.41 × 10(-4) and P= 0.02). Our findings suggest that the SNPs in XKR4 and near FOXE1 are involved in the regulation of TSH levels.

Identification of BACH2 as a susceptibility gene for Graves' disease in the Chinese Han population based on a three-stage genome-wide association study.

The BACH2 gene regulates B cell differentiation and function and has been reported to be a shared susceptibility gene for several autoimmune diseases. Our previous genome-wide association study (GWAS) indicated that several single nucleotide polymorphisms (SNPs) in the BACH2 gene are associated with Graves' disease (GD) in the Chinese Han population; however, the association did not achieve genome-wide significance levels. Recently, this association of BACH2 with GD was confirmed in Caucasians in the UK population, but fine mapping in this region has not yet been reported. Here, we provide a refined analysis of a 331-kb region in the BACH2 gene, which harbors 359 SNPs, using GWAS data from 1,442 GD patients and 1,468 controls. The SNPs rs2474619 and rs9344996 were implied as the independent variants associated with GD by forward and two-locus logistic regression analysis. We genotyped eight out of 10 tagSNPs with P < 1 × 10(-3) in 3,508 GD patients and 3,209 controls, the results also showed that rs2474619 was independently associated with GD in the combined population from GWAS and the second stage (P = 1.81 × 10(-5)). The rs2474619 and rs9344996 were further genotyped in the third stage cohorts, and rs2474619 showed evidence of association with GD at genome-wide significance levels in the combined population (P = 3.28 × 10(-8), odds ratio = 1.13). The association of rs9344996 with GD can be explained by its linkage to rs2474619 in the combined population. Our study clearly demonstrated that BACH2 is a susceptibility gene for GD in the Chinese Han population and further supported rs2474619, in intron 2 of BACH2, is the best association signal with GD. However, the mechanism by which BACH2 confers increased risk of GD requires further study.

The association between androgen receptor gene CAG polymorphism and polycystic ovary syndrome: a case-control study and meta-analysis.

PURPOSE: Many studies have been carried out to confirm the relationship between androgen receptor gene CAG repeat polymorphism and polycystic ovary syndrome (PCOS), without consistent results. Hence we conducted the current study to research this relationship. METHODS: 224 Chinese Han women with PCOS and 223 in vitro fertilization and embryo transplantation (IVF-ET) infertile women with tubal factor or male infertility served as the controls were recruited in our study. PCR-based assays were applied to genotype the (CAG)n repeat alleles. A meta-analysis including 1,536 PCOS patients and 1,807 controls was conducted to produce a pooled estimate. RESULTS: We observed that the CAG bi-allelic mean lengths were similar in PCOS patients and controls (22.65 ± 2.5 vs. 23.09 ± 2.1, P = 0.116). When CAG bi-allelic were divided into two categories (mean repeats ≤22, >22), the short AR-CAG bi-allelic showed more frequent in PCOS group than in controls (56.25% vs 29.14%, P < 0.001). Further analysis presented that, in PCOS, there was a lower mean CAG repeat lengths in mean bi-allelic lengths (22.3 ± 2.5 vs. 23.9 ± 2.2, P = 0.008) and long bi-allelic lengths (24.3 ± 1.4 vs. 25.9 ± 1.6, P = 0.05) among patients with testosterone less than 0.7 ng/ml compared with those whose testosterone was more than 0.7 ng/ml. Besides, the testosterone were positively correlated with the CAG polymorphism (r = 0.237, P = 0.008), which accorded with our meta-analysis results. CONCLUSIONS: The distribution of AR-CAG allele differed between PCOS patients and controls, and polymorphism of CAG repeat lengths may contribute to hyperandrogenism in PCOS.

Biosafety evaluation of bacteriophages for treatment of diarrhea due to intestinal pathogen Escherichia coli 3-2 infection of chickens.

Intestinal Escherichia coli caused diarrhea in chicken makes serious damage directly to the chicken culture industry. Bacteriophage therapy is able to control the diarrhea in chickens effectively. In this study, the biosafety of bacteriophages was evaluated for treating intestinal pathogenic E. coli, which induced diarrhea in chickens. Ten bacteriophages were isolated from feces of chickens with diarrhea using the ill-chicken intestinal pathogenic E. coli 3-2 as target organism. Three bacteriophages propagated on E. coli 3-2 with relative big and clear plaques were selected and used together for toxicity experiment and evaluating the effect of therapy on chicken weight gain. In 3 weeks of trial, no mice given with or without mixed bacteriophages died, and the weight of mice of the experimental group did not show significant difference to the control group after 3 weeks infection. Besides remarkable decreasing the death rate of chickens with diarrhea, treatment of mixed bacteriophages also promoted the weight gain and saved the diet consumption as the utilize rate of diet increased 11% compared with the control group. These observations indicated that a mixture of three bacteriophages would be biosafe for rapid and effective preventing pathogenic E. coli infections.

Significance of elevated levels of collagen type IV and hyaluronic acid in gastric juice and serum in gastric cancer and precancerous lesion.

BACKGROUND AND AIMS: Collagen type IV and hyaluronic acid (HA) are the major components of basement membrane and extracellular matrix, respectively. Cathepsin D is an aspartyl lysosomal protease involved in the degradation of the basement membrane and extracellular matrix. The aim of this study is to investigate the clinical significance of collagen type IV and hyaluronic acid in gastric juice and serum in diagnosis of gastric cancer and the degrading effect of cathepsin D on collagen type IV and HA. METHODS: Fifty gastric cancer patients were enrolled in our study compared with 41 patients with precancerous lesion and 30 control subjects. Collagen type IV and HA in gastric juice and serum were analyzed by radioimmunoassay. Expression of cathepsin D and collagen type IV in tissue were analyzed by immunohistochemical staining with monoclonal antibodies. RESULTS: The contents of collagen type IV and HA in gastric juice and HA in serum were significantly higher in patients with gastric cancer than those in patients with precancerous lesion and control group (p < 0.05, p < 0.0001). Gastric cancer patients with lymph node metastasis had a higher level of collagen type IV and HA in gastric juice than those in patients without metastasis (p = 0.049, p = 0.043). The expression of cathepsin D had significantly increased in patients with gastric cancer compared to the control group (p < 0.0001). The continuous expression of collagen type IV in basement membrane in gastric cancer group was lower than that in the precancerous lesion group and control group (p < 0.0001). CONCLUSIONS: The analysis of collagen type IV and HA in gastric juice and serum may provide a simple aid in diagnosing gastric cancer and evaluating whether metastasis is occurring or not.

[Seasonal Removal Efficiency and Degradation Products of Two Typical PPCPs in Subsurface Flow Constructed Wetlands].

The pollution of surface waters by pharmaceuticals and personal care products (PPCPs) has aroused widespread concern. Constructed wetlands (CWs) have outstanding advantages in the removal of PPCPs; however, few studies have focused on the interaction of different types of PPCPs in CWs. In this study, two typical PPCPs[broad-spectrum antimicrobial agents triclosan (TCS) and non-steroidal anti-inflammatory drug diclofenac (DCF)] were selected as target pollutants and their removal behavior in subsurface flow CWs was analyzed. The effects of different seasons and influent conditions (i.e., single and combined addition of TCS and DCF) on removal efficiency was also examined. The main parameters of the CW system were as follows:the up-flow subsurface CW had a hydraulic load of 0.20 m·d-1 and a hydraulic residence time of 3 d with a continuous flow inlet. The initial influent concentration of PPCPs was 80 g·L-1 for TCS and 25 g·L-1 for DCF. The results showed that the average removal efficiencies for TCS and DCF in summer (91.72% and 85.86%, respectively) were significantly higher than in winter (52.88% and 32.47%, respectively). Independent sample t-tests confirmed that there was no significant difference in the removal efficiency of TCS and DCF under the different influent conditions (single and combined addition). The degradation products of TCS and DCF were also no different between the influent systems, and the representative degradation products of TCS were not detected in all systems. The main degradation products of DCF in the different systems were 3,5-dichlorobenzoic acid and m-dichlorobenzene. The two studied PPCPs showed no significant antagonism and competition effects at trace levels.

Compelling Evidence Linking CD40 Gene With Graves' Disease in the Chinese Han Population.

Mutations in CD40 have been widely reported to be risk factors for Graves' disease (GD). The gene, along with its cognate ligand CD40L, may regulate pro-inflammatory and immune responses. Rs1883832, located at the -1 position of the Kozak sequence, is the most well-studied single nucleotide polymorphism (SNP) of CD40, and has been confirmed to predispose those with the alteration to GD, regardless of ethnicity. Our genome-wide association study (GWAS) indicated that several SNPs, including rs1883832 located within the vicinity of CD40 were associated with GD in the Han Chinese population. Aiming at identifying the most consequential SNP and its underlying pathogenic mechanism, we performed a two-stage refined study on 8,171 patients with GD and 7,906 controls, and found rs1883832 was the most significantly GD-associated SNP in the CD40 gene region (PCombined = 9.17×10-11, OR = 1.18). Through searching the cis-expression quantitative trait locus database and using quantitative RT-PCR, we further discovered that the rs1883832 genotype can influence CD40 gene transcription. Furthermore, we demonstrated that rs1883832 is a susceptibility locus for pTRAb+ GD patients. In conclusion, the current study provides robust evidence that rs1883832 can regulate CD40 gene expression and affect serum TRAb levels, which ultimately contributes to the development of GD.

Effects of long-term addition of Cu(II) and Ni(II) on the biochemical properties of aerobic granules in sequencing batch reactors.

Copper (Cu(II)) and nickel (Ni(II)) are often encountered in wastewaters. This study investigated the individual toxic effects of long-term addition of Cu(II) and Ni(II) on the biochemical properties of aerobic granules in sequencing batch reactors (SBRs). The biochemical properties of aerobic granules were characterized by extracellular polymeric substances (EPS) content, dehydrogenase activity, microbial community biodiversity, and SBR performance. One SBR was used as a control system, while another two received respective concentration of Cu(II) and Ni(II) equal to 5 mg/L initially and increased to 15 mg/L on day 27. Results showed that the addition of Cu(II) drastically reduced the biomass concentration, bioactivity, and biodiversity of aerobic granules, and certainly deteriorated the treatment performance. The toxic effect of Ni(II) on the biodiversity of aerobic granules was milder and the aerobic granular system elevated the level of Ni(II) toxicity tolerance. Even at a concentration of 15 mg/L, Ni(II) still stimulated the biomass yield and bioactivity of aerobic granules to some extent. The elevated tolerance seemed to be owed to the concentration gradient developed within granules, increased biomass concentration, and promoted EPS production in aerobic granular systems.

[Microbial Diversity and Physicochemical Properties of Rhizosphere Microenvironment in Saline-alkali Soils of the Yellow River Delta].

Soil salinity and alkalinity are major problems that limit agricultural development across the world. The planting of halophytes and salt-tolerant plants could improve saline-alkaline soil character, while the microorganisms in saline-alkali soils play an important role in the growth of halophytes and salt-tolerant plants. In this study, four representative plants of maize, cotton, Phragmites australis (Cav.) Trin. ex Steud, and Suaeda salsa were selected in saline-alkali soil. Soil samples were collected to explore the relationship between the main bacterial communities of roots and non-roots and the physical and chemical properties and soil microbial diversity of saline-alkali soil. The results showed that the root microorganisms of Suaeda salsa affect the pH of the soil to some extent, and the soil salinity is negatively correlated with the soil nutrient content. The top five bacterial gates with higher relative abundance in all soil samples were α-Proteobacteria, Actinobacteria, Bacteroides, Chloroflexi, and Acidobacteria. Cotton, Phragmites australis(Cav.) Trin. ex Steud, and Suaeda salsa have large differences in salt-tolerant bacteria between root soils and non-root soils. High-throughput sequencing results show that salt tolerance is different between the three plant roots and non-root soils. Bacterial genus, such as Actinophytocola and Lechevalieria, differ greatly in cotton soil, Bacillus and Filobacillus differ greatly in Phragmites australis (Cav.) Trin. ex Steud. soil, and Echinicola differ greatly in the soil of Suaeda salsa. This research can provide a theoretical basis for promoting plant growth in saline-alkali soil.

Genetic Study in a Large Cohort Supported Different Pathogenesis of Graves' Disease and Hashimoto's Hypothyroidism.

CONTEXT: Hashimoto's thyroiditis (HT) and Graves' disease (GD) are the 2 main autoimmune thyroid diseases that have both similarities and differences. Determining the genetic basis that distinguishes HT from GD is key for a better understanding of the differences between these closely related diseases. OBJECTS: To identify the susceptibility genes for HT in the Chinese cohort and compare susceptibility genes between GD and HT. DESIGN: In the current study, 18 SNPs from 18 established GD risk loci were selected and then genotyped in 2682 patients with HT, 4980 patients with GD, and 3892 controls. The association analysis between HT and controls and heterogeneity analysis between HT and GD were performed on SPSS, with the logistic regression analysis adjusted for sex and age. RESULTS: We identified 11 susceptibility loci for HT in the Chinese Han population, with 4 loci, including the rs1265883 in SLAMF6 locus, rs1024161 in CTLA4, rs1521 in HLA-B, and rs5912838 in GPR174/ ITM2A at X chromosome, reaching genome-wide significance of 5 × 10-8. Five loci were reported to be associated with HT for the first time. We also identified 6 susceptibility loci with heterogeneity between GD and HT. Out of them, 4 loci were associated with GD but not with HT, including HLA-DPB1, CD40, TSHR, and TG; the association of HLA-B with GD was stronger than that with HT, but the association of SLAMF6 was reversed. CONCLUSION: Our findings suggested that the pathogenesis of HT and GD was different.

[Evolution pattern of impervious surface in the Yuqiao Reservoir Watershed, Tianjin, China during the process of urbanization.] / åŸŽé•‡åŒ–è¿‡ç¨‹ä¸­æµåŸŸä¸é€æ°´é¢æ¼”å˜æ ¼å±€­­ä»¥å¤©æ´¥äºŽæ¡¥æ°´åº“流域为例.

Imperviousness in watershed is a key index to measure urbanization status which exerts an important impact on both eco-hydrological process and spatio-temporal pattern. Taking Yuqiao Reservoir Watershed as a case study area, based on the ENVI 5.1 software, the basic impervious surface information was extracted from remote sensing images taken in 1984, 1994, 2004 and 2013. The linear spectral mixture analysis (LSMA) model was applied to extract the impervious surface area (ISA) in nine coverage classes of watershed in order to analyze its spatio-temporal varying trend in terms of the landscape pattern metrics. Results showed that the RMSE and IS pixel accuracy of all samples were 0.005 and 85.4% respectively, which indicated that the method of extracting impervious surface on a basin scale was feasible. The average of ISA showed a linear growth, from 0.16 to 0.23, the impervious surface area increased by 4.9% in the whole watershed, and the total impervious surface area increased by 1 time. In the sub-basin road network, the impervious surface area increased gradually with the density of the road network, and its expansion pattern was of infilling growth. The patch shape of the middle coverage degree was irregular, and its fragmentation degree was the highest. The fragmentation degree and diversity of the landscape in the whole river basin increased year by year due to increasing human disturbance.

Screening and identification of the levoglucosan kinase gene (lgk) from Aspergillus niger by LC-ESI-MS/MS and RT-PCR.

A protein of 75,000 Daltons with levoglucosan kinase activity was purified from Aspergillus niger. After in-gel digestion by trypsin, a 14-mer peptide was sequenced and analyzed by LC-ESI-MS/MS. Using a primer derived from the 14-mer peptide in combination with Oligo-(dT)18, a cDNA fragment was obtained by RT-PCR. A search of the GenBank database indicated that the protein had not been identified before. A similar protein named hypothetical protein FG07802.1 (EAA77996.1) was found to exist in Gibberella zeae by Blastx search. Using a primer derived from the protein, a cDNA fragment of second RT-PCR was cloned into plasmid pAJ401, which was transformed to Saccharomyces cerevisiae H158 and expressed. Two positive levoglucosan assimilating recombinants were selected. The lgk gene was screened and identified.

[Effect of Ferric Iron on Nitrogen Immigration and Transformation and Nitrous Oxide Emission During Simultaneous Nitrification Denitrification Process].

Effect of Fe(III) concentration on nitrogen immigration and transformation and nitrous oxide emission during the simultaneous nitrification denitrification (SND) process was investigated. Higher nitrogen removal efficiency was obtained when the Fe(III) concentration was 20 mg x L(-1), while lower nitrogen removal efficiency was observed when the Fe (III) concentration turned to 60 mg x L(-1). In addition, higher Fe(III) concentration significantly enhanced the N2O emission, as well as the N2O conversion ratio. This was mainly attributed to (1) the high concentration of nitrite accumulation during the oxic stage, which was caused by lower dehydrogenase activity at high Fe(III) concentration; (2) less PHB production during the anoxic stage, which would led to shortage of carbon source for denitrification in the following oxic stage. The results also showed that Fe(III) addition could improve the TP removal efficiency. TP removal efficiency increased with increasing Fe(III) concentration, mainly because of extra chemical reaction.

Tanshinone IIA Prevents Rat Basilar Artery Smooth Muscle Cells Proliferation by Inactivation of PDK1 During the Development of Hypertension.

Basilar vascular smooth muscle cells (BASMCs) hyperplasia is a prominent feature of cerebrovascular remodeling and stroke during the development of hypertension. Tanshinone IIA (Tan) has been reported to exhibit a protective effect against the pathological features of hypertension. Previous studies have shown that phosphoinostitide-3 kinase (PI3K)/3'-phosphoinostitide dependent kinase (PDK1)/AKT pathway is involved in the regulation of proliferation of various cell types. Therefore, there may be a crosstalk between Tan antihypertension processes and PI3K/PDK1/AKT proliferative effect in BASMCs. To test this hypothesis, we used a 2-kidney, 2-clip hypertension model to examine the effect of Tan on PI3K/PDK1/AKT pathway by cellular, molecular, and biochemical approaches. Our results revealed that the abundance of PDK1 in plasma was paralleled with an increase in blood pressure and the cross-sectional area of basilar artery in hypertensive rats. Tan decreased blood pressure and hypertension-induced PDK1 phosphorylation but produced no effect on the phosphorylation of PI3K. Moreover, Tan attenuated endothelin 1 induced the activation of PDK1/AKT pathway in rat BASMCs. Tan could inhibit cell cycle transition by regulating the expression of cyclin D1 and p27, in turn, prevent proliferation of BASMCs. Our study provides a novel mechanism by which Tan prevents cerebrovascular cell proliferation during hypertension, and thus Tan may be a potential therapeutic agent for cerebrovascular remodeling and stroke.

Prognostic significance of expression of cyclooxygenase-2 and vascular endothelial growth factor in human gastric carcinoma.

AIM: To investigate the role of cyclooxygenase-2(COX-2) and vascular endothelial growth factor (VEGF) in the development of gastric carcinoma and correlation between expression of COX-2 and VEGF and clinicopathologic features in tissues from patients with gastric carcinoma. METHODS: 281 patients with gastric carcinoma who underwent surgical resection between 1990 and 1999 at the First Affiliated Hospital, Anhui Medical University, PRC, were followed up. Expression of COX-2 and VEGF was investigated retrospectively in 232 gastric carcinoma tissues and 60 noncancerous specimens by using immunohistochemistry. RESULTS: The 5-year survival rates of early gastric carcinoma (EGC) and advanced gastric carcinoma (AGC) were 93.4 % and 59.0 %, respectively. Survival time was highly correlated with lymph node metastasis, vascular invasion, depth of invasion and treatment with chemotherapy. Compared with paired noncancerous tissues, expression of COX-2 and VEGF and microvessel density (MVD) value in carcinoma tissue were significantly higher. The MVD value was much higher in COX-2-positive group and VEGF-positive group than that in COX-2-negative group and VEGF-negative group. Expression of COX-2 and VEGF, as well as MVD value were highly correlated with lymph node metastasis and vascular invasion. The 5-year survival rate of patients with expression of COX-2 or VEGF was significantly lower than that of patients without COX-2 or VEGF expression. Multivariate analysis revealed that VEGF overexpression, lymph node metastasis, COX-2 overexpression, depth of invasion and vascular invasion were all independent prognostic factors of gastric carcinoma. CONCLUSION: Overexpression of COX-2 and VEGF in patients with gastric carcinoma can enhance the possibility of invasion and metastasis, implicating a poor prognosis. They may serve as the fairly good prognostic factors to indicate biologic behaviors of gastric carcinoma.

[The alpha-synuclein gene microsatellite polymorphism and late-onset sporadic Parkinson's disease susceptibility].

OBJECTIVE: To explore the association of the microsatellite polymorphisms in the promoter region of alpha-synuclein gene with the late-onset sporadic Parkinson's disease (PD) susceptibility. METHODS: The microsatellite polymorphism of alpha-synuclein gene was analyzed with amplified fragment length polymorphism (Amp-FLP) and semiautomatic fluorescent labeled genotyping technique. Association analysis was performed in 135 unrelated late-onset sporadic PD patients and 170 age-matched healthy controls. RESULTS: The distribution of the alleles of the dinucleotide repeats variants of alpha-synuclein gene promoter region in PD cases was significantly different from that in the healthy controls. The most frequent allele in PD patients was allele 269 bp, but in controls it was the 271 bp allele. Alleles of

[Dopamine beta hydroxylase gene polymorphism and Parkinson's disease].

OBJECTIVE: To investigate the correlation between the polymorphism of dopamine beta hydroxylase(DBH) gene and the susceptibility of Shanghai Chinese Han population to Parkinson's disease(PD). METHODS: Association study was performed in 144 PD patients and 188 healthy control subjects matched for age, sex and origin. Polymorphism of DBH gene was analyzed with polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The allelic frequency of A2 allele of DBH gene was significantly higher in PD patients than in controls(P<0.01).The risk of suffering from PD increased (OR=1.82) in the individual with A2 allele. And the genotypic frequency of A2/A2 was significantly higher in PD patients(OR=2.11, P<0.01),too. On the other hand, the allelic frequency of A1 allele and the genotypic frequency of A1/A2 genotype of DBH gene in PD patients were significantly lower(A1 alleles: OR=0.54, P<0.01; A1/A2 genotypes: OR=0.45, P<0.01). CONCLUSION: The polymorphism in DBH gene might play an important role in the susceptibility of Shanghai Chinese Han population to PD.