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1.
OBJECTIVES--To determine whether the offspring of cancer survivors are at an increased risk of congenital anomalies and whether cancer therapy before conception is associated with such an increase. DESIGN--Case-control study using computerised record linkage. SETTING--Ontario, Canada. SUBJECTS--Parents of children born during April 1979 to December 1986 who had a congenital anomaly diagnosed within the first year of life (45,200 mothers and 41,158 fathers) and a matched sample of parents whose children did not have a congenital anomaly (45,200 mothers and 41,158 fathers). MAIN OUTCOME MEASURES--Cancer diagnosed in either parent before conception and radiotherapy to the pelvis or abdomen or chemotherapy with an alkylating agent. RESULTS--Among the mothers, 54 cases and 52 controls were identified as having had cancer diagnosed in Ontario (relative risk = 1.04, 95% confidence interval 0.7 to 1.5) and among the fathers, 61 cases and 65 controls were identified (0.9, 0.7 to 1.4). No significant associations were found between congenital anomalies in the offspring and any type of cancer treatment in either the mothers or the fathers. CONCLUSIONS--The risk of congenital anomalies among liveborn offspring whose parents have had cancer or been treated for cancer is not higher than that in the general population.  相似文献   

2.
Congenital anomalies associated with congenital hypothyroidism   总被引:2,自引:0,他引:2  
The French national neonatal screening program for congenital hypothyroidism (CH) was initiated in 1978. The purpose of this study was to ascertain the incidence of congenital extrathyroid anomalies (ETAs) among the infants with congenital hypothyroidism (CH) and to compare it with the Northeastern France Birth Defect Monitoring System data from 1979 to 1996. Among 129 CH infants on whom adequate data were available, 20 infants (15.5%) had associated congenital anomalies. Eight out of 76 infants with persistent CH had ETAs (10.5%) whereas 12 out of 53 children with transient hypothyroidism had ETAs (22.6%, p < 0.05). Some additional anomalies were considerably more common than in the general population. Nine infants had congenital cardiac anomalies (6.9%). This rises the question if teratogenic effects active during organogenesis may affect simultaneously many organs, including the developing thyroid, causing a relatively high percentage of CH infants with congenital ETAs.  相似文献   

3.
This article provides a broad overview of our earlier studies on the induction of tumors and congenital anomalies in the progeny of X-irradiated or chemically treated mice and our subsequent (published, hitherto unpublished and on-going) investigations aimed at identifying potential relationships between genetic changes induced in germ cells and the adverse effects manifest as tumors and congenital anomalies using cytogenetic and molecular approaches. The earlier studies document the fact that tumors and congenital anomalies can be induced by irradiation or treatment with certain chemicals such as urethane and that these phenotypes are heritable i.e., transmitted to generations beyond the first generation. These findings support the view that transmissible induced genetic changes are involved. The induced rates of congenital abnormalities and tumors are about two orders of magnitude higher than those recorded in the literature from classical mutation studies with specific locus mutations. The cytogenetic studies addressed the question of whether there were any relationships between induced translocations and induced tumors. The available data permit the inference that gross chromosomal changes may not be involved but do not exclude smaller induced genetic changes that are beyond the resolution of the techniques used in these studies. Other work on possible relationship between visible chromosomal anomalies (in bone marrow preparations) and tumors were likewise negative. However, there were indications that some induced cytogenetic changes might underlie induced congenital anomalies, i.e., trisomies, deletions and inversions were observed in induced and transmissible congenital anomalies (such as dwarfs, tail anomalies). Studies that explored possible relationships between induction of minisatellite mutations at the Pc-3 locus and tumors were negative. However, gene expression analysis of tumor (hepatoma)-susceptible offspring of progeny descended from irradiated male mice showed abnormal expression of many genes. Of these, only very few were oncogenes. This lends some support to our hypothesis that cumulative changes in gene expression of many genes, which perform normal cellular functions, may contribute to the occurrence of tumors in the offspring of irradiated or chemically treated mice.  相似文献   

4.
In humans, unpaired organs are placed in a highly ordered pattern along the left-right axis. As indicated by animal studies, a cascade of signaling molecules establish left-right asymmetry in the developing embryo. Some of the same genes are involved also in limb patterning. To provide a better insight into the connection between these processes in humans, we analysed the symmetry of limb deficiencies among infants with multiple congenital anomalies. The study was based on data collected by the International Clearinghouse for Birth Defects Monitoring Systems (ICBDMS). Registries of the ICBDMS provided information on infants who, in addition to a limb deficiency, also had at least one major congenital anomaly in other organ systems. We reviewed 815 such cases of which 149 cases (18.3 %) were syndromic and 666 (81.7 %) were nonsyndromic. The comparisons were made within the associated limb deficiencies, considering the information on symmetry, using a comparison group with malformations associated not involved in the index association. Among the non-syndromic cases, the left-right distribution of limb deficiencies did not differ appreciably between limb deficiency subtypes (e.g., preaxial, transverse, longitudinal). The left-right distribution of limb anomalies did not differ among most types of non-limb anomalies, though a predominance of left-sided limb deficiencies was observed in the presence of severe genital defects - odds ratio [OR], 2.6; 95 % CI, 1.1-6.4). Limb deficiencies (LDs) were more often unilateral than bilateral when accompanied by gastroschisis (OR, 0.1) or axial skeletal defects (OR, 0.5). On the contrary, LDs were more often bilateral than unilateral when associated with cleft lip with or without cleft palate (OR, 3.9) or micrognathia (OR, 2.6). Specifically, we found an association between bilateral preaxial deficiencies and cleft lip, bilateral amelia with gastroschisis and urinary tract anomalies, and bilateral transverse deficiencies and gastroschisis and axial skeleton defects. Of 149 syndromic cases, 62 (41.6 %) were diagnosed as trisomy 18. Out of the 30 cases of trisomy 18 with known laterality, 20 cases were bilateral. In the remainder the right and left sides were equally affected. Also, in most cases (74.4 %) only the upper limbs were involved. In conclusion the left-right distribution of limb deficiencies among some non-limb anomalies may suggest a relationship between the development of the limb and the left-right axis of the embryo.  相似文献   

5.
We examined clinical, genetic, and epidemiologic factors among 512 probands with nonsyndromal neural tube defects (NTDs). Data were analyzed after grouping the probands in four different ways with respect to pathological features and putative pathogenic mechanisms. Apparently unrelated congenital anomalies occurred more frequently among probands with craniorachischisis (62%), encephalocele (30%), or multiple NTDs (25%) than among probands with anencephaly (14.7%) or spina bifida (10.1%) (P much less than .0001). Unrelated congenital anomalies occurred less often among probands with low spina bifida (6.7%) than among probands with high spina bifida (19.5%). NTDs were seen in 7.8% of the siblings of probands with high spina bifida but in only 0.7% of the siblings of probands with low spina bifida, in 2.2% of the siblings of anencephalic probands, and in none of the siblings of probands with craniorachischisis, encephalocele, or multiple NTDS (P less than .001). In all 16 families in which two siblings had NTDs, both had either defects of the type associated with abnormal primary neurulation or defects of the type associated with abnormal canalization. High spina bifida and multiple NTDs were found more frequently than expected among the Sikh probands (P less than .02). The frequency of non-NTD congenital anomalies was higher among siblings of Sikh probands (8.8%) than among siblings of other probands (2.4%) (P less than .05). This excess was due to the occurrence of hydrocephalus without spina bifida in four of 68 siblings of Sikh probands.  相似文献   

6.
A total of 542 children under 10 years of age, admitted to the Seoul National University Children's Hospital, was examined for antibody titers of Toxoplasma gondii using indirect latex agglutination (ILA) test. Among them, 7.7% showed positive titers higher than 1:32, without significant difference between males (7.3%) and females (8.5%). The seropositive rate increased with age although the statistical significance was negligible (0.05 < P < 0.1). By residential areas, the prevalence appeared higher among children from southern provinces (Kyongsang-do and Cholla do) than those from other areas, but the statistical significance was also very low (0.05 < P < 0.1). When the seropositive cases were analyzed by coincidental diseases, the prevalence was significantly higher in patients with congenital diseases than in patients with non-congenital diseases (P < 0.05). The results showed that the seropositive rate of toxoplasmosis in children examined was not high compared with other endemic countries. Some correlations are suggested between toxoplasmosis and congenital anomalies in Korea.  相似文献   

7.
In the last decade a high frequency of extrathyroidal congenital anomalies has been reported in infants with congenital hypothyroidism (CH) detected by neonatal screening. In the present study the occurrence of additional congenital malformations (CM) in a cohort of children with confirmed primary CH due to thyroid dysgenesis was investigated. A high prevalence of extrathyroidal major congenital anomalies (15.9%), more than 5-fold higher than that reported in the Egyptian population (2.7%), was found. The cardiac and musculoskeletal systems were the most commonly involved, comprising 9.09 and 47.72% of all anomalies, respectively. The high prevalence of musculoskeletal anomalies in this study was mostly due to minor anomalies as brachydactyly and digitalization of thumbs. The type of dysgenesis (i.e. aplastic, ectopic or hypoplastic) as well as the severity of hypothyroidism, as assessed by TSH and T(4) levels at diagnosis, had no relation with the occurrence of extrathyroidal abnormalities.  相似文献   

8.
At the Instituto Materno Infantil (IMI) in Bogotá (Colombia), 5,686 births (5,597 live births and 89 stillbirths) were analyzed during two periods: from October, 1997, to April, 1998, and from July to November, 2000 (12 months). Congenital anomalies were detected in 4.4% of live newborn babies and in 7.8% of stillbirths. Major anomalies corresponded to 69% and mild anomalies to 31% (3% and 1.4% of all live births, respectively). The newborn babies with major anomalies, in comparison to the normal controls, had higher mortality at hospital discharge (p = 0.0001), lower average birth weight (p = 0.003), and family history of congenital anomalies (p = 0.0001). The only significant association for mild anomalies was with family history of congenital anomalies (p = 0.0001). The frequency of congenital anomalies was similar to that in other studies, although certain kinds of anomalies showed noticeable frequency differences. This may be a consequence of differences in record keeping or in detection methods.  相似文献   

9.
The objectives of this study were to describe the impact of prenatal diagnosis on the birth prevalence of congenital anomalies over 21 years (1979-1999) in a well defined population in northeastern France (13,500 births per year). The material for this study came from the analysis of data from multiple sources on births and terminations of pregnancy after prenatal diagnosis of congenital anomalies in 279,642 consecutive pregnancies of known outcome. The study period was divided into three subgroups 1979-1988, 1989-1993 and 1994-1999. Between 1979-1988, 1989-1993 and 1994-1999, prenatal detection of congenital anomalies increased, respectively, from 12.0% to 25.5% and to 31.7%. Termination of pregnancy (TOP) increased in the same proportions during the three time periods. However, the increase of TOP was much higher for chromosomal anomalies than for nonchromosomal congenital anomalies. The birth prevalence of Down's syndrome fell by 80% from 1979-1988 to 1994-1999. Sensitivity of prenatal detection of congenital anomalies and TOPs were lower for isolated cases (only one malformation present in the fetus) than for multiple malformations in the same fetus. Sensitivity varied with the type of malformations: it was high for neural tube defect (79.7%) and urinary anomalies (50.7%) and low for congenital heart defects (16.4%). In conclusion, the introduction of routine prenatal diagnosis has resulted in a significant fall in the birth prevalence of children with congenital anomalies. However, this fall varied with the types of congenital anomalies.  相似文献   

10.
BACKGROUND: Few registry-based studies have investigated survival among infants with congenital anomalies. We conducted a registry-based study to examine patterns and probability of survival during the first year of life among infants with selected congenital anomalies. METHODS: Data from the Texas Birth Defects Monitoring Division were merged with linked birth-infant death files for 2,774 infants born January 1, 1995 to December 31, 1997, with at least 1 of 23 common anomalies. Deaths before the first birthday were assessed from infant death files. Kaplan-Meier was used to estimate first-year survival; first-year survival was assessed for specific anomalies and by the number of life-threatening anomalies. RESULTS: Overall, 80.8% of infants with these 23 anomalies survived the first year of life. We observed the highest survival rates for infants with gastroschisis (92.9%, 95% CI = 86.8, 96.3), trisomy 21 (92.3%, 95% CI = 89.5, 94.4) or cleft lip with or without cleft palate (87.6%, 95% CI = 84.0, 90.5). Infants with intermediate survival rates included those with microcephaly (79.7%; 95% CI = 73.6, 84.6), tetralogy of Fallot (75.0%; 95% CI = 65.5, 82.2), or with diaphragmatic hernia (72.8%; 95% CI = 61.8, 81.2). As expected, all infants with anencephaly and almost all infants with trisomy 13 or trisomy 18 died during the first year of life. First-year survival declined as the number of co-occurring life-threatening anomalies increased. CONCLUSIONS: Overall, first-year survival for infants with congenital anomalies was high. Additional population-based studies are needed to quantify improvements in first-year survival.  相似文献   

11.
The mortality and cancer incidence risks among males with Y polysomy are unknown because there have been no large long-term cohort studies carried out of such men. We conducted a cohort study of 667 men diagnosed with the abnormality in Britain since 1959 to compare their mortality and cancer incidence rates with those of the general population. Sixty deaths occurred during follow-up to December 2005, twice the number expected from general population rates (standardised mortality ratio (SMR) = 2.0 (95% confidence interval (CI) 1.5–2.6)). Significantly raised mortality was observed for diseases of the nervous system (SMR = 7.0, 95% CI: 2.3–16.4), circulatory system (SMR = 2.1, 95% CI: 1.3–3.2), respiratory system (SMR = 4.0, 95% CI: 1.8–7.5), genitourinary system (SMR = 10.2, 95% CI: 1.2–36.9), and congenital anomalies (SMR = 11.9, 95% CI: 3.2–30.5). Four of the five nervous system deaths were from epilepsy, the risk of death from this condition being more than 20-fold raised. The rates of cancer incidence and mortality among these men was not significantly different from those in the general population. This study provides evidence that mortality rates from several specific causes are raised among men with Y polysomy. The use of these data in genetic counselling should be cautious particularly for cases of Y polysomy that are detected prenatally. Further investigations are required to confirm these findings and to elucidate the possible role of genes on the Y chromosome in the aetiology of these causes of death.  相似文献   

12.
BackgroundHyperthyroidism affects about 0.2%-2.7% of all pregnancies, and is commonly managed with antithyroid drugs (ATDs). However, previous studies about the effects of ATDs on congenital anomalies are controversial. Therefore, the present meta-analysis was performed to explore the risk of congenital anomalies in children exposed to ATDs in-utero.MethodsEmbase, Pubmed, Web of Knowledge, and BIOSIS Citation Index were searched to find out studies about congenital anomalies in children exposed to ATDs in-utero reported up to May 2014. The references cited by the retrieved articles were also searched. The relative risks (RRs) and confidence intervals (CIs) for the individual studies were pooled by fixed effects models, and heterogeneity was analyzed by chi-square and I2 tests.ResultsEight studies met the inclusion criteria. Exposure to propylthiouracil (PTU), methimazole/carbimazole (MMI/CMZ), and PTU & MMI/CMZ was investigated in 7, 7 and 2 studies, respectively. The pooled RR was 1.20 (95%CI: 1.02-1.42), 1.64 (95%CI: 1.39-1.92), and 1.83 (95%CI: 1.30-2.56) for congenital anomalies after exposure to PTU, MMI/CMZ, and PTU & MMI/CMZ, respectively.ConclusionsThe meta-analysis suggests that exposure to ATDs in-utero increases the risk of congenital anomalies. The use of ATDs in pregnancy should be limited when possible. Further research is needed to delineate the exact teratogenic risk for particular congenital anomaly.  相似文献   

13.
14.
Variation in genes associated with serum levels of proteins may be useful for examining specific disease pathways. Using data from a large study of colon cancer, we examine genetic variants in insulin, inflammation, estrogen, metabolizing enzymes, and energy homeostasis genes to explore associations with microsatellite instability (MSI), CpG Island methylator phenotype (CIMP), mutations of p53 in exons 5 through 8, and mutations in codons 12 and 13 of Ki-ras. Insulin-related genes were associated with CIMP-positive and MSI tumors, with the strongest associations among aspirin users. The Fok1 vitamin D receptor (VDR) polymorphism was associated with CIMP-positive/Ki-ras-mutated tumors; the Poly A and CDX2 VDR polymorphisms were associated only with Ki-ras-mutated tumors. NAT2 was associated with CIMP-positive/Ki-ras-mutated tumors but not with MSI tumors. The TCF7L2 rs7903146 polymorphism was associated with p53 mutated tumors. Most associations varied by recent aspirin/NSAID use: IL6 rs1800796 and rs1800795 polymorphisms were associated inversely with tumor mutations in the presence of aspirin/NSAIDs; POMC significantly reduced risk of Ki-ras-mutated tumors when aspirin/NSAIDs were not used; the TCF7L2 rs7903146 was associated with reduced risk of Ki-ras-mutated tumors in the presence of aspirin and increased risk in the absence of aspirin. These data, although exploratory, identify specific tumor subsets that may be associated with specific exposures/polymorphism combinations. The important modifying effects of aspirin/NSAIDs on associations with genetic polymorphisms reinforce the underlying role of inflammation in the etiology of colon cancer.  相似文献   

15.
BACKGROUND: Limited data is available concerning the sex distribution of various congenital anomaly subtypes. This study investigated sex differences in the prevalence of congenital anomalies, overall and by subtype, using high quality population‐based data from the North of England. METHODS: Information on congenital anomalies occurring among singleton pregnancies during 1985–2003 were extracted from the Northern Congenital Abnormality Survey (NorCAS). Anomalies were categorized by groups, subtypes, and syndromes according to the European Surveillance of Congenital Anomalies guidelines. Relative risks (RRs) comparing the prevalences in males to that in females were calculated for a range of congenital anomaly subtypes. RESULTS: A total of 12,795 eligible cases of congenital anomaly were identified during the study period, including 7019 (54.9%) males and 5776 (45.1%) females. Overall, male fetuses were significantly more prevalent in pregnancies affected by a congenital anomaly than female fetuses (RR, male vs. female = 1.15; 95% confidence interval [CI], 1.11–1.19), but there was significant heterogeneity between subtypes (p < 0.001). Forty‐four of 110 (40%) unique subtypes were at least 40% more prevalent in males than females, with affected subtypes occurring across all major anomaly groups. Thirteen of 110 (12%) unique subtypes were at least 40% more prevalent in females than males, but the female‐biased RR of a neural tube defect was less pronounced than previously reported (RR = 0.84; 95% CI, 0.73–0.95). CONCLUSION:This study adds to the growing evidence of sex‐specific differences in the prevalence of a wide range of congenital anomaly subtypes. Birth Defects Research (Part A), 2011. © 2011 Wiley‐Liss, Inc.  相似文献   

16.
A survey of all anaesthetists in the West Midlands region--that is, 10% of all the anaesthetists in England and Wales--showed that one in 10 of their children had been referred to a consultant because of a congenital or nonacquired anomaly. Abortions among anaesthetists'' families were also common but more so when the mother was an anaesthetist. The anomalies were concentrated particularly in the central nervous system and musculoskeletal system, and girls were worst affected. The mean birth weights were below normal, more so when the mothers were anaesthetists. Girls with anomalies were particularly underweight. Other effects observed were unexpected infertility, cancer both in the adults and in the children, and, possibly, impaired intellectual development in the children. Many anaesthetising areas were inadequately ventilated, and scavenging devices despite their inefficiency are recommended as a stopgap measure. The results of the study closely resemble those of other studies with similar high response rates to requests for information.  相似文献   

17.
BACKGROUND: Although birth defects are a leading cause of death in infancy and early childhood, the proportion of all deaths to children with clinically diagnosed birth defects is not well documented. The study is intended to measure the proportion of all deaths to infants and children under age 10 occurring to children with birth defects and how and why this proportion differs from the proportion of deaths due to an underlying cause of congenital anomalies using standard mortality statistics. METHODS: A linked file of Michigan livebirths and deaths was combined with data from a comprehensive multisource birth defects registry of Michigan livebirths born during the years 1992 through 2000. The data were analyzed to determine the mortality rate for infants and children with birth defects and for children with no reported birth defect. Mortality risk ratios were calculated. The underlying causes of death for children with birth defects were also categorized and compared to cause- specific mortality rates for the general population. RESULTS: Congenital anomalies were the underlying cause of death for 17.8% of all infant deaths while infants with birth defects were 33.7% of all infant deaths in the study. Almost half of all Michigan deaths to children aged 1 to 2 were within the birth defects registry, though only 15.0% had an underlying cause of death of a congenital anomaly based upon standard mortality statistics. The mortality experience among children with birth defects was significantly higher than other children throughout the first 9 years of life, ranging from 4.6 for 5 year olds to 12.8 for children 1 to 2. Mortality risk ratios examined by cause of death for infants with birth defects were highest for other endocrine (28.1), other CNS (28.1), and heart (21.9) conditions. For children 1 through 9, the highest differential risk was seen for other perinatal conditions (39.0), other endocrine (29.7), other CNS (24.5), and heart (21.4). CONCLUSIONS: Childhood mortality analyses that incorporate birth defects registry data provide a more comprehensive picture of the full burden of birth defects on mortality in infant and children and can provide an effective mechanism for monitoring the survival and mortality risks of children with selected birth defects on a population basis.  相似文献   

18.
BACKGROUND: Infants that develop congenital anomalies may also have an excess prevalence of macrosomia (birth weight > or =4,000 g). This may indicate that abnormalities of glycemic control play a role in the etiology of birth defects. This study was undertaken to determine whether all infants with congenital anomalies have an excess of macrosomia and whether it is confined to specific types of anomalies. METHODS: A case-control study was conducted, comparing the birth weights of 8,226 infants with congenital anomalies ascertained by the Texas Birth Defects Monitoring Division with those of 965,965 infants without birth defects. Odds ratios were calculated to determine the association between birth weight and congenital anomalies, for 45 specific defects, and for all these defects combined. RESULTS: For all 45 defects combined, a significant association occurred only in the highest birth weight category. Infants with congenital anomalies were more likely than infants without birth defects to have a birth weight > or =4,500 g (OR = 1.65; 95% CI = 1.39-1.96). Infants born with ventricular septal defects, atrial septal defects, ventricular hypertrophy, or anomalies of the great vessels were 1.5-2.5 times more likely to weigh > or =4,000 g than were infants without birth defects. Based on small numbers, a stronger excess of macrosomia was observed for infants with encephalocele, holoprosencephaly, anomalies of the corpus callosum, preaxial polydactyly, and omphalocele. CONCLUSIONS: Our data suggest that infants with specific congenital anomalies are more likely to be macrosomic than are infants without an anomaly. If these findings are confirmed, associations between macrosomia and specific types of birth defects may help to identify birth defects that are caused by alterations in glycemic control.  相似文献   

19.
BackgroundCancer in children is increasingly recognized as a major and growing health problem in different developed and developing countries. In Yemen, it is still difficult to know the extent of cancer and its determinants among children. This study was conducted to determine the magnitude of childhood cancer in Aden and provide the preliminary baseline data by age and sex.MethodsBasic epidemiologic data was retrieved from all paediatric cancer <15 years age registered in Aden Caner Registry (ACR), Yemen, from 1997 to 2006.ResultsThe results showed a total of 483 childhood cancers <15 years age comprising12.7% of all registered malignancies with a male to female ratio of 1.5:1. The predominant age affected was 5–9 years in (38.3%) children. The most frequent cancer among Yemeni children was leukaemia 160 (33.1%) followed by lymphoma 152 (31.5%), CNS tumors 35 (7.2%) and bone tumours 25 (5.2%). An interesting and unusual finding was the frequency of acute myeloid leukaemia twice more common in female (66.7%) than male (33.3%). Lymphoma was the most common cancer in children >5 years. An interesting comparison was the preponderance of non-Hodgkins's lymphoma over Hodgkin's disease (1.6:1) stronger in female (3:1) than male (1.25:1). Medulloblastoma was the most common CNS tumour followed by astrocytoma, an infrequent finding in childhood cancer. Osteosarcoma was the most frequent bone tumour (male:female ratio of 1.8:1). A female preponderance was noticed in chondrosarcoma that was not yet documented. The blastoma group was common in younger age group. Retinoblastoma and nephroblastoma predominated in female while neuroblastoma, hepatoblastoma and soft tissue sarcomas in male.ConclusionIt is concluded that there is a lower frequency of childhood cancer in Aden when compared with developed countries. It may explained by the fact that a large number of childhood cancers remain undiagnosed due to limitations of diagnostic facilities or under registration. Central paediatric hospitals should be provided with essential diagnostic and therapeutic services that should be freely available to all children with cancer.  相似文献   

20.
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