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1.

Background

A number of studies have assessed ages of parents of children with autistic spectrum disorders (ASD), and reported both maternal and paternal age effects. Here we assess relationships with grandparental ages.

Methods and Findings

We compared the parental and grandparental ages of children in the population-based Avon Longitudinal Study of Parents and Children (ALSPAC), according to their scores in regard to 4 autistic trait measures and whether they had been given a diagnosis of ASD. Mean maternal and paternal ages of ASD cases were raised, but this appears to be secondary to a maternal grandmother age effect (P = 0.006): OR = 1.66[95%CI 1.16, 2.37] for each 10-year increase in the grandmother''s age at the birth of the mother. Trait measures also revealed an association between the maternal grandmother''s age and the major autistic trait–the Coherence Scale (regression coefficient b = 0.142, [95%CI = 0.057, 0.228]P = 0.001). After allowing for confounders the effect size increased to b = 0.217[95%CI 0.125, 0.308](P<0.001) for each 10 year increase in age.

Conclusions

Although the relationship between maternal grandmother''s age and ASD and a major autistic trait was unexpected, there is some biological plausibility, for the maternal side at least, given that the timing of female meiosis I permits direct effects on the grandchild''s genome during the grandmother''s pregnancy. An alternative explanation is the meiotic mismatch methylation (3 M) hypothesis, presented here for the first time. Nevertheless the findings should be treated as hypothesis generating pending corroborative results from other studies.  相似文献   

2.
Water hyacinth (Eichhornia crassipes (Mart.) Solms) and salvinia (Salvinia auriculata Aubl.) were exposed to toxic levels of Cd with the objective of evaluating its effect on sulphate uptake and metabolism. Plants were treated with 0 and 5 μmol L−1 Cd for 3 days and, then sulphate uptake, ATP sulfurylase activity, soluble thiol content and Cd-binding complexes were determined. Water hyacinth showed a lower sulphate uptake, but its kinetic parameters were not affected by Cd. In salvinia, however, both Vmax and affinity to sulphate (1/Km) decreased with Cd treatment. The ATP sulfurylase activity increased in Cd-treated plant of both species, except in the roots of salvinia. In the presence of Cd water hyacinth always exhibited higher activity of this enzyme. The total soluble thiol content was always higher in water hyacinth. In Cd treated plants it increased in the leaves of water hyacinth, but decreased in salvinia. Cysteine content increased only in water hyacinth leaves, while γ-glutamylcysteine content increased in the two parts of the plants of both species after Cd treatment, especially in water hyacinth. Glutathione contents, on the contrary, after Cd treatment, reduced in both parts of the plants of water hyacinth but only in the leaves of salvinia. The unidentified thiol fraction content increased with Cd treatment in both species, especially in water hyacinth. Root and leaf extracts of both species showed peaks with maxima at A265/A280. In treated plants these peaks coincided with Cd content peaks indicating the formation of Cd-binding peptides. It was estimated that in the presence of Cd about 97% of Cd was associated with these complexes and water hyacinth had 28% more Cd-binding peptides than salvinia. Despite its lower sulphate uptake, water hyacinth showed higher rates of sulfur reduction and assimilation into soluble thiols. Possibly, glutathione is used in water hyacinth roots to synthesize hitherto unidentified Cd-binding peptides.  相似文献   

3.
CysQ is a 3'-phosphoadenosine-5'-phosphatase that dephosphorylates intermediates from the sulfate assimilation pathway of Mycobacterium tuberculosis (Mtb). Here, we demonstrate that cysQ disruption attenuates Mtb growth in vitro and decreases the biosynthesis of sulfated glycolipids but not major thiols, suggesting that the encoded enzyme specifically regulates mycobacterial sulfation.  相似文献   

4.
污染区域大气环境质量生物监测的数学模式   总被引:2,自引:0,他引:2  
以常规标准取样法、静态挂片吸收取样法分别测定了深圳南山区范围内大气二氧化硫、硫酸盐化速率和氟化物的含量,并同步测定了植物叶片的污染物含量。利用回归方法分析了3种测定结果的相互关系,并以植物叶片污染物含量为基础建立大气环境质量生物监测的数学模型,其中以叶片含硫量评价大气硫酸盐化速率的模型为夏季y=0.781x-0.754,冬季y=1.88x-2.283;以叶片含氟量评价大气氟化物的模型为夏季y=0.363x-7.511,冬季y=0.175x-3.461,这些模型均有很高的可信度(p<0.001)。  相似文献   

5.
In the developing mammalian brain, inhibition of NMDA receptor can induce widespread neuroapoptosis, inhibit neurogenesis and cause impairment of learning and memory. Although some mechanistic insights into adverse neurological actions of these NMDA receptor antagonists exist, our understanding of the full spectrum of developmental events affected by early exposure to these chemical agents in the brain is still limited. Here we attempt to gain insights into the impact of pharmacologically induced excitatory/inhibitory imbalance in infancy on the brain proteome using mass spectrometric imaging (MSI). Our goal was to study changes in protein expression in postnatal day 10 (P10) rat brains following neonatal exposure to the NMDA receptor antagonist dizocilpine (MK801). Analysis of rat brains exposed to vehicle or MK801 and comparison of their MALDI MS images revealed differential relative abundances of several proteins. We then identified these markers such as ubiquitin, purkinje cell protein 4 (PEP-19), cytochrome c oxidase subunits and calmodulin, by a combination of reversed-phase (RP) HPLC fractionation and top-down tandem MS platform. More in-depth large scale study along with validation experiments will be carried out in the future. Overall, our findings indicate that a brief neonatal exposure to a compound that alters excitatory/inhibitory balance in the brain has a long term effect on protein expression patterns during subsequent development, highlighting the utility of MALDI-MSI as a discovery tool for potential biomarkers.  相似文献   

6.

Background

Chronic inflammation from recurring trauma is an underlying pathophysiological basis of numerous diseases. Furthermore, it may result in cell death, scarring, fibrosis, and loss of tissue function. In states of inflammation, subsequent increases in oxidative stress and cellular division may lead to the accelerated erosion of telomeres, crucial genomic structures which protect chromosomes from decay. However, the association between plasma inflammatory marker concentrations and telomere length has been inconsistent in previous studies.

Objective

The purpose of this study was to determine the longitudinal association between telomere length and plasma inflammatory biomarker concentrations including: CRP, SAA, sICAM-1, sVCAM-1, VEGF, TNF-α, IL-1β, IL-2, IL-6, IL-8, and IL-10.

Methods

The longitudinal study population consisted of 87 subjects. The follow-up period was approximately 2 years. Plasma inflammatory biomarker concentrations were assessed using highly sensitive electrochemiluminescent assays. Leukocyte relative telomere length was assessed using Real-Time qPCR. Linear mixed effects regression models were used to analyze the association between repeated-measurements of relative telomere length as the outcome and each inflammatory biomarker concentration as continuous exposures separately. The analyses controlled for major potential confounders and white blood cell differentials.

Results

At any follow-up time, each incremental ng/mL increase in plasma CRP concentration was associated with a decrease in telomere length of −2.6×10−2 (95%CI: −4.3×10−2, −8.2×10−3, p = 0.004) units. Similarly, the estimate for the negative linear association between SAA and telomere length was −2.6×10−2 (95%CI:−4.5×10−2, −6.1×10−3, p = 0.011). No statistically significant associations were observed between telomere length and plasma concentrations of pro-inflammatory interleukins, TNF-α, and VEGF.

Conclusions

Findings from this study suggest that increased systemic inflammation, consistent with vascular injury, is associated with decreased leukocyte telomere length.  相似文献   

7.
寻找客观标记物是精神医学研究最重要的课题之一,近期融合了循证医学的神经电生理研究为此提供了重要的途径,并取得了较为可观的研究成果,然而现有的研究结果仍然存在较多争议,难以取得一致共识.本文全面总结和归纳了结合以元分析(meta-analysis)为代表的循证医学方法和以脑电图(electroencephalography)为代表的神经电生理技术的精神障碍相关脑电研究成果,将事件相关电位划分为早期和晚期成分,并结合定量EEG分析,从感知加工、认知控制、情绪反应和社会认知等不同认知过程出发,系统分析和评述了精神障碍患者及高危人群的神经认知功能异常情况.我们发现:精神分裂症患者存在从早期到晚期的各种感知、情感和社会认知方面的缺陷,注意缺陷/多动障碍(ADHD)患者存在从早期到晚期的认知控制缺陷,焦虑和强迫障碍患者则存在早期的认知控制缺陷,而孤独症谱系障碍(ASD)患者则存在早期的感知加工和社会认知缺陷.此外,反映注意资源分配和认知加工速度的P300异常特征跨越了多个诊断类型,这表明该脑电成分可能反映了精神障碍的一般性认知缺陷.未来研究可利用多中心大样本数据库探寻精神疾病的神经电生理客观标记物...  相似文献   

8.
铬对重金属去除菌影响的研究   总被引:1,自引:0,他引:1  
考察了Cr^6 浓度和培养时间对4株重金属去除菌致死率的影响、重金属去除菌除铬性能的稳定性、吸附铬前后胞内外的变化、Cr^6 对胞内可溶性还原糖含量的影响以及多种因素对重金属去除菌毒性,初步探讨了重金属去除菌的抗Cr^6 机理。实验结果表明,4株实验菌的致死率随培养时间的变化趋势都是先升高后降低,最后再升高;假丝酵母的可驯化性较好;掷孢酵母7-3对高浓度Cr^6 的耐受性最好;Cr^6 对4株实验菌的各种代谢过程有一定影响;扫描电镜,透射电镜及原子力显微镜等实验结果表明:产朊假丝酵母的除铬机理是表面吸附和胞内积累并存;在正交实验中,Cr^6 浓度、pH、培养时间、N源、C源、吸附时间等6个因素对4株实验菌的影响各不相同。  相似文献   

9.
The relationship between structural changes in grey matter and treatment response in patients with late-life depression remains an intriguing area of research. This magnetic resonance imaging (MRI) study compares the baseline grey matter volume of elderly people with and without major depression (according to the DSM-IV-TR criteria) and assesses its association with antidepressant treatment response. Brain MRI scans were processed using statistical parametric mapping and voxel-based morphometry. The sample consisted of 30 patients with depression and 22 healthy controls. We found a significant volumetric reduction in the orbitofrontal cortex bilaterally in patients in comparison with controls. According to their remission status after antidepressant treatment, patients were classified as remitted or not remitted. Compared with controls, remitted patients showed a volumetric reduction in the orbitofrontal cortex bilaterally and in another cluster in the right middle temporal pole. Non-remitted patients showed an even greater volumetric reduction in the orbitofrontal cortex bilaterally compared with controls. To investigate predictive factors of remission after antidepressant treatment, we used a logistic regression. Both baseline Mini Mental State Examination score and baseline left superior lateral orbitofrontal cortex volume (standardized to the total grey matter volume) were associated with remission status. Our findings support the use of regional brain atrophy as a potential biomarker for depression. In addition, baseline cognitive impairment and regional grey matter abnormalities predict antidepressant response in patients with late-life depression.  相似文献   

10.

Background

Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance.

Methods

We studied children with WHO-defined clinical pneumonia (n = 155) within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30), other infiltrates (n = 31), or normal chest x-ray (n = 94). Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis.

Results

Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5–98.8), 80.8% specificity (72.6–87.1), positive likelihood ratio 4.9 (3.4–7.1), negative likelihood ratio 0.083 (0.022–0.32), and misclassification rate 0.20 (standard error 0.038).

Conclusions

In Tanzanian children with WHO-defined clinical pneumonia, combinations of host biomarkers distinguished between end-point pneumonia, other infiltrates, and normal chest x-ray, whereas clinical variables did not. These findings generate pathophysiological hypotheses and may have potential research and clinical utility.  相似文献   

11.
Hell R  Jost R  Berkowitz O  Wirtz M 《Amino acids》2002,22(3):245-257
Summary. Among the amino acids produced by plants cysteine plays a special role as a mediator between assimilatory sulfate reduction and provision of reduced sulfur for cell metabolism. Part of this characteristic feature is the presence of cysteine synthesis in plastids, mitochondria and cytosol. Plants are the major source of reduced sulfur for human and animal nutrition. Cysteine biosynthesis deserves special attention, since reduced sulfur is channelled from cysteine into many sulfur-containing compounds in food and feed. Recent investigations are reviewed that focus on structure and regulation of cysteine synthesis in the model plant Arabidopsis thaliana. These data indicate that cysteine synthesis is not just an intermediate reaction step but that it is part of a regulatory network that mediates between inorganic sulfur supply and the demand for reduced sulfur during plant growth and in response to environmental changes. Received December 3, 2001 Accepted December 21, 2001  相似文献   

12.
13.
Heavy metal binding complexes found in the cytoplasm of plant cells are widely reported to be responsible fox metal resistance. It is believed that these metal binding complexes may play an important role in the accumulation of heavy metal and preventing them from entering the ptant metabolic pathways. This review summarizes information on purification, characterization and properties of these molecules. In view of their inducibility, low molecular weight, specific optical characteristics (high absorption at 254nm and low absorption at 280 nm), high cysteine content and high capacity for binding heavy metal, these complexes were once proposed to be metallothionein-like molecules. However differing from metallothionein of animal system, heavy metal binding complexes in plants are comprised mainly of three amino acids with a unique structure of (γ-Glu-Cys)n-Gly ((γ-EC)nG) (n=2—11). With the presence of γ-carboxyl group peptide linkage, the complexes are thought not to be synthesized via mRNA but the product of biosynthetic pathway using glutatkione as precursor.  相似文献   

14.

Objective

The aim was to examine if long-term psychiatric sickness absence was associated with all-cause and diagnosis-specific (cardiovascular disease (CVD), cancer and suicide) mortality for the period 1990–2007. An additional aim was to examine these associations for psychiatric sickness absence in 1990 and 2000, with follow-up on mortality during 1991–1997 and 2001–2007, separately.

Methods

Employees within municipalities and county councils, 244,990 individuals in 1990 and 764,137 individuals in 2000, were followed up to 2007 through register linkages. Analyses were conducted with flexible parametric survival models comparing sickness absentees due to psychiatric diagnoses (>90 days) with those not receiving sick leave benefit.

Results

Long-term sickness absence for psychiatric disorders was associated with an increased risk of mortality due to all causes; CVD; cancer (smoking and non-smoking related); and suicide during the period 1990–2007. After full adjustment for socio-demographic covariates and previous inpatient care due to somatic and psychiatric diagnoses, these associations remained significant for all-cause mortality (Hazard ratios (HR) and 95% confidence interval (CI)): HR 1.56, 95% CI 1.3–1.8; CVD: HR 1.35, 95% CI 1.0–1.9, and suicide: HR 3.84, 95% CI 2.4–6.1. For both cohorts 1990 and 2000 estimates point in the same direction. For the time-period 2000–2007, we found increased risks of mortality in the fully adjusted model due to all causes: HR 1.47, 95% CI 1.2–1.7; CVD: HR 1.83, 95% CI 1.2–2.7; overall cancer: HR 1.33, 95% CI 1.0–1.7; and suicide: HR 2.15, 95% CI 1.3–3.7.

Conclusion

Long-term sickness absence for psychiatric disorders predicted premature mortality from all-causes, cardiovascular disease, cancer, and suicide.  相似文献   

15.
近海海域易于受到城市工业等人类活动的污染,重金属污染是其中之一,持续的低度污染也会造成近海生物体内污染物累积,影响海域渔业和生态环境。通过对大连周边6个海区内采集的牡蛎壳体分析测定发现,壳体中重金属的含量与该海区海水中重金属含量线性相关,其中Zn、Cd、Pb和Cu的相关系数分别为0.9430、0.9822、0.9930、0.9815,生物富集系数在1000左右。实验分析手段采用二阶微分阳极溶出伏安极谱,支持电解液为pH4.0~4.5的Hac-NaAc缓冲溶液,标准偏差RSD=0.11~1.16,实验回收率93~105%。研究结果表明,(1)牡蛎壳体可以替代贝类软组织作为监测海域环境的载体,指示海域环境重金属的变化情况; (2)牡蛎壳体层状的生长过程与同时期水质的状况密切相关,层状物理结构便于分层分析,通过本实验相关性的验证,完全有可能建立一种海水水质短期历史追溯的技术方法。  相似文献   

16.
铜陵铜尾矿凤丹种植基地重金属污染初探   总被引:8,自引:0,他引:8  
通过对安徽铜陵凤凰山铜尾矿凤丹种植基地土壤和凤丹中重金属污染状况进行采样分析.结果表明,在尾矿空白地和凤丹种植地土壤中Cu、Cd、Pb、Zn元素含量、存在形态差异明显,说明凤丹对尾矿土壤的修复效果明显;尾矿土壤中的Cu、Cd元素总量分别是国家土壤环境质量二级标准的436~1443倍和3.67~3.86倍,凤丹种植地重金属元素的CPI指数达到5.607,表明尾矿土壤中重金属元素污染仍相当严重.研究发现,4种元素在凤丹各部位含量明显不同:叶和根心为Cu>Zn>Pb>Cd,茎和根皮为Zn>Cu>Pb>Cd,根皮中Zn含量最高;土壤中重金属元素各形态的变化与凤丹体内相应元素总量无显著相关;丹皮内Cu、Cd、Pb元素含量与丹龄之间相关系数分别为0.842、0.993、0.992,Cu、Cd元素在凤丹体内含量约是出口药用植物绿色行业限量指标的1.43~2.53倍和1.17~3.17倍,可见缩短栽种时间可有效减少重金属元素对丹皮药效的影响.  相似文献   

17.

Objective

Four types of antipsychotic-induced movement disorders: tardive dyskinesia (TD), parkinsonism, akathisia and tardive dystonia, subtypes of TD (orofacial and limb truncal dyskinesia), subtypes of parkinsonism (rest tremor, rigidity, and bradykinesia), as well as a principal-factor of the movement disorders and their subtypes, were examined for association with variation in 7 candidate genes (GRIN2B, GRIN2A, HSPG2, DRD3, DRD4, HTR2C, and NQO1).

Methods

Naturalistic study of 168 white long-stay patients with chronic mental illness requiring long-term antipsychotic treatment, examined by the same rater at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. The authors genotyped 45 tag SNPs in 7 candidate genes, associated with movement disorders or schizophrenia in previous studies. Genotype and allele frequency comparisons were performed with multiple regression methods for continuous movement disorders.

Results

Various tag SNPs reached nominal significance; TD with rs1345423, rs7192557, rs1650420, as well as rs11644461; orofacial dyskinesia with rs7192557, rs1650420, as well as rs4911871; limb truncal dyskinesia with rs1345423, rs7192557, rs1650420, as well as rs11866328; bradykinesia with rs2192970; akathisia with rs324035; and the principal-factor with rs10772715. After controlling for multiple testing, no significant results remained.

Conclusions

The findings suggest that selected tag SNPs are not associated with a susceptibility to movement disorders. However, as the sample size was small and previous studies show inconsistent results, definite conclusions cannot be made. Replication is needed in larger study samples, preferably in longitudinal studies which take the fluctuating course of movement disorders and gene-environment interactions into account.  相似文献   

18.
BackgroundThe clinical management of pancreatic cancer is severely hampered by the absence of effective screening tools.MethodsSixty-seven biomarkers were evaluated in prediagnostic sera obtained from cases of pancreatic cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).ResultsThe panel of CA 19-9, OPN, and OPG, identified in a prior retrospective study, was not effective. CA 19-9, CEA, NSE, bHCG, CEACAM1 and PRL were significantly altered in sera obtained from cases greater than 1 year prior to diagnosis. Levels of CA 19-9, CA 125, CEA, PRL, and IL-8 were negatively associated with time to diagnosis. A training/validation study using alternate halves of the PLCO set failed to identify a biomarker panel with significantly improved performance over CA 19-9 alone. When the entire PLCO set was used for training at a specificity (SP) of 95%, a panel of CA 19-9, CEA, and Cyfra 21-1 provided significantly elevated sensitivity (SN) levels of 32.4% and 29.7% in samples collected <1 and >1 year prior to diagnosis, respectively, compared to SN levels of 25.7% and 17.2% for CA 19-9 alone.ConclusionsMost biomarkers identified in previously conducted case/control studies are ineffective in prediagnostic samples, however several biomarkers were identified as significantly altered up to 35 months prior to diagnosis. Two newly derived biomarker combinations offered advantage over CA 19-9 alone in terms of SN, particularly in samples collected >1 year prior to diagnosis. However, the efficacy of biomarker-based tools remains limited at present. Several biomarkers demonstrated significant velocity related to time to diagnosis, an observation which may offer considerable potential for enhancements in early detection.  相似文献   

19.
BackgroundThe incidence of Metabolic Syndrome (MetS) has been growing rapidly and is rising to pandemic proportions. Although obesity is a primary risk factor for the enhancement of these conditions, not all obese individuals develop metabolic syndrome, indicating that the risk for developing MetS is impacted by other genetic and/or environmental factors such as heavy metals. Therefore, the present study focused on the association between exposures to heavy metal and MetS.MethodsUrine samples were collected from 150 participants (75 patients with MetS and 75 healthy participants), which were used from Hoveyzeh Cohort center. To make a quantitative comparison between the two groups, Man-Whitney nonparametric test was used. The logistic regression was performed adjusted for age, demographic, lifestyle factor, physical activity, occupational history and urine creatinine.ResultsThe results of logistic regression showed that OR and 95 % CI for Cd, Pb, Sr, As and Fe concentration were still significant after adjusting for urine creatinine. Moreover, there was a relationship between Cd and Pb levels and waist circumstance (WC). After adjusting for urine creatinine, age, sex, occupation, smoking status, education and place of residence, only Pb concentration was showed a significant association with systolic blood pressure (SBP). The subjects with high urine level of Cd had the high odds (OR: 6.273; 95 % Cl: 1.783–22.070) of MetS and low high-density lipoprotein (HDL-C). The relationship between As concentration and high fasting blood sugars confirmed the previous evidence suggesting that high As level can cause diabetes.ConclusionThese results indicated that outbreak of MetS and its component are associated with heavy metal concentrations in urine.  相似文献   

20.
The heavy metal resistant ciliate, Stylonychia mytilus, isolated from industrial wastewater has been shown to be potential bioremediator of contaminated wastewater. The ciliate showed tolerance against Zn2+ (30 μg/mL), Hg2+ (16 μg/mL) and Ni2+ (16 μg/mL). The metal ions slowed down the growth of the ciliate as compared with the culture grown without metal stress. The reduction in cell population was 46% for Cd2+, 38% for Hg2+, 23% for Zn2+, 39% for Cu2+ and 51% for Ni2+ after 8 days of metal stress. S. mytilus reduced 91% of Cd2+, 90% of Hg2+ and 98% of Zn2+ from the medium after 96 h of incubation in a culture medium containing 10 μg/mL of the respective metal ions. Besides this, the ciliate could also remove 88% of Cu2+ and 73% Ni2+ from the medium containing 5 μg/mL of each metal after 96 h. The ability of Stylonychia to take up variety of heavy metals from the medium could be exploited for metal detoxification and environmental clean-up operations.  相似文献   

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