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1.
We have retrospectively evaluated 24 sepsis episodes caused by viridans streptococci in 23 neutropenic children during a 21 months period at the Pediatric Hematology Unit of St. Louis Hospital. The underlying malignancies included acute lymphoblastic leukemia, acute non lymphoblastic leukemia, aplastic anemia and solid tumor. In 17 children neutropenia, defined as a neutrophil count of less than 500 per cubic millimeter, was caused by cytotoxic chemotherapy. For 6 other children neutropenia was consequential to pretransplant treatment regimen for autologous bone marrow transplantation including cytotoxic chemotherapy and total body irradiation. All patients had a silicone rubber atrial catheter. In 9 patients sepsis was associated only with fever for less than 48 hours. In 5 other children fever was prolonged more than 72 hours in spite of specific antimicrobial therapy. No other organism was isolated. In 10 patients, however, the infectious syndrome was severe and the features included cardiac failure (7 patients), pneumonia (7 patients) resembling adult respiratory distress syndrome, encephalopathy (3 patients) without meningitis and proteinuria, 7 of these patients needed a management in a pediatric intensive care unit and 2 died in spite of adapted antibiotics. Streptococci were isolated in blood cultures in 23 children.  相似文献   

2.
BackgroundFebrile neutropenia is a common complication in children undergoing chemotherapy for malignancies. A microbial agent is only identified in 15–30% of the fever episodes and corresponds mostly to bacterial findings.ObjectiveTo investigate viral infections as possible etiologic agents in episodes of febrile neutropenia.Study designNasopharyngeal aspirates (NPAs) from patients presenting with neutropenic fever at two pediatric oncology wards in Sweden and Australia were analyzed with a conventional virus-diagnostic approach and RT-PCR. Coupled blood samples were analyzed for the detection of CMV, EBV, adenovirus and erythrovirus. Bacterial blood culture was performed routinely.ResultsConventional virus-diagnostic approach coupled to routinely performed bacterial analyzes revealed an infectious agent in 29% compared to 60% when using PCR. By adding PCR, a viral pathogen was detected in 46% of the NPAs and in 4% of the blood samples collected. In half of the patients with bacteremia, respiratory tract viruses were co-detected.ConclusionRespiratory viruses were frequently detected in NPAs suggesting a significant role of viral infections in children presenting with neutropenic fever. The meaning of these findings needs to be further evaluated but has the potential to individualize infection treatment and to reduce the extensive use of antibiotics in immunocompromised children with neutropenia.  相似文献   

3.
Febrile neutropenia is a common and potentially fatal problem encountered in cancer patients undergoing chemotherapy. We carried out an observational study to evaluate the possible risk factors of developing fever amongst neutropenic children with an underlying malignancy. We also looked at the microbiological profile of causative pathogens in patients with febrile neutropenia. During a study period of 1 year, a total of 90 neutropenic episodes were recorded amongst 57 patients who were on treatment and follow-up during the study period. Multivariate analysis showed that factors such as chemotherapy status, underlying disease, existing central venous catheters, presenting white blood cell counts at chemotherapy, use of steroid therapy or hospitalisation at the onset of neutropenia, were not significant risk factors for developing fever during neutropenic episodes. Although the presence of a central venous catheter was associated with a higher risk of developing fever, it did not reach statistical significance (p=0.11). Of the 90 neutropenic episodes, 59 (65.6%) developed fever and 25 of these had positive blood cultures. The causative organisms include gram-negative bacteria (64%), gram positive bacteria (16%) and fungus (20%). Of the gram-negative organisms, Klebsiella spp. predominated (28%) with the extended spectrum beta-lactamase producing strain forming the majority (16%). Amongst those with fungaemia, Candida spp. and Candida tropicalis formed the majority (8% each) of the isolates.  相似文献   

4.
Neopterin, a pteridine group compound that is secreted from macrophages is shown to be increased in adult leukemia; however there are few studies in childhood leukemia. This study aimed to investigate neopterin levels during childhood leukemia treatment and neutropenic fever episodes for the possibility of using as a marker for disease activity and differentiation of infections. A total of 44 children with acute leukemia, 19 children with infection (control group 1) and 21 healthy children (control group 2) were studied. Median serum neopterin level before induction chemotherapy (day 0) in 25 children (patient group 1) was significantly higher (27.7 nmol/L) than those at the beginning of 30 febrile episodes in 19 children in bone marrow remission (2.2 nmol/L) (patient group 2) and in control group 2 (0.4 nmol/L) (p< 0.05). It was (27.7 nmol/L) also significantly higher in control group 1 than in patient group 2 and control group 2 (p< 0.05). Serum neopterin levels at day 15 (2.1 mmol/L) and day 33 (0.4 mmol/L) of induction were significantly lower than day 0 of ALL subgroup at patient group 1. There were no significant difference in neopterin levels between days 0, 3 and 5 of neutropenic fever as well as between patients with microbiologically and/or clinically documented infections and those with fever of unknown origin in patient group 2 (p> 0.05). Serum neopterin did not show significant correlation with absolute neutrophil count and absolute monocyte count (p> 0.05). In conclusion, elevated neopterin at diagnosis of leukemia with decrement during induction therapy suggest that it might be an indicator of leukemic process; however larger studies for its role in identifying infections are warranted.  相似文献   

5.
Abstract Neutropenia as a state of immunosuppression is probably the major problem in patients suffering from acute lymphoblastic leukaemia undergoing intensive chemotherapy. Fever is frequent in neutropenic patients and often related to infection. Clinically, the presence of infection in patients with neutropenia may be difficult to establish, because there are usually few signs of infection. The aim of this work was to study sensitive markers for early diagnosis of microbial infection in neutropenic children undergoing intensive chemotherapy as a treatment for acute lymphoblastic leukaemia. The study included three groups (A, B and C) of children with acute lymphoblastic leukaemia and neutropenia. Group A consisted of 29 children with febrile neutropenia and microbial infection, aged 1–14 years (5.8±2.9), 11 boys and 18 girls; Group B of 38 children with febrile neutropenia without microbial infection, aged 2–14 years (6.8±3.1), 14 boys and 24 girls; and Group C of 53 children with neutropenia without fever and without infection, aged 1–14 years (5.9±2.1), 21 boys and 32 girls. Blood samples were collected upon admission and before the start of any antimicrobial treatment. The samples were used for blood culture, serological tests, leukocyte count and analysis of levels of C–reactive protein, procalcitonin, total adenosine deaminase (ADA) activity and its isoenzymes, ADA–1 and ADA–2. According to our results the procalcitonin levels and total ADA activity discriminated best between neutropenic febrile (Groups A and B) and neutropenic afebrile episodes (Group C). In conclusion, this study suggests procalcitonin and total ADA activity as two easily measurable and cost effective markers for the assessment of immune response in febrile neutropenic patients with acute lymphoblastic leukaemia.  相似文献   

6.
This study reviews the clinical manifestations, causes and frequency of Stomatococcus mucilaginosus bacteremia in neutropenic cancer patients. We analyzed retrospectively all clinical and microbiological records of patients with S. mucilaginosus bacteremia. The incidence was compared with that of other pathogens causing bacteremia during neutropenia for the same period. S. mucilaginosus represented 5.9% of bacteremias in our neutropenic patients. Seven patients with hematologic malignancies and one with breast cancer are described. The common clinical presentation was one of sepsis. All patients presented with damaged mucosal barriers as the probable portal of entry, from either stomatitis or enterocolitis. All patients survived.  相似文献   

7.
Objective: To prospectively evaluate serum neopterin, a marker of cellular immune activation, in relation to blood culture findings and cytokine levels (tumor necrosis factor-α (TNF-α), interleukin (IL)-1 receptor antagonist, interferon-γ (IFN-γ), IL-6, and IL-10) at start of fever in neutropenic patients with hematologic malignancies.
Methods: Serum samples were obtained during the first 24 h after start of fever in 27 episodes of febrile neutropenia seen in 22 patients.
Results: Neopterin levels increased significantly at start of fever (time 0) compared to baseline values (samples obtained within 72 h before start of fever). Neopterin levels peaked at 2–4 h after start of fever and returned to baseline levels after 12 h. At start of fever no differences in neopterin values were seen with regard to blood culture findings (i.e. blood-culture-negative (BCN) fever episodes versus Gram-positive bacteria versus Gram-negative bacteremia). In five of seven BCN fever episodes, in patients without other clinical evidence of infection, a high neopterin/low TNF-α value was observed and the correlation ( r -value) between neopterin/TNF-α was negative in BCN fever episodes (-0.9; p <0.04), as opposed to the bacteremic episodes, where the correlation was positive (0.7; p <0.04).
Conclusion: The results of this study show that febrile neutropenic patients are able to react with increased neopterin values, and that some BCN fever episodes are characterized by high neopterin/low cytokine values which may be due to an occult non-bacterial infection.  相似文献   

8.
The Platelia Candida-specific antigen and antibody assays (Bio-Rad Laboratories) were used to test serial serum samples from seven neutropenic adult patients with hematological malignancies who had developed systemic Candida tropicalis infections. The diagnosis of candidiasis was based on a positive blood culture (all seven patients) and the isolation of C. tropicalis from a normally sterile site (six patients). All patients received early antifungal therapy with amphotericin B and/or an azole derivative and had successful outcomes. When the combined assays were applied to sera collected at different time points before and after the first positive blood culture, all patients tested positive. In six patients, at least one positive test was obtained with sera collected, on average, 5 days (range, 2 to 10 days) prior to the first positive blood culture, while blood cultures were constantly negative. High and persistent mannanemias were detected in all patients during the neutropenic period. In five patients, an increased antibody response was detected when the patients recovered from aplasia. Controls consisted of 48 serum samples from 12 febrile neutropenic patients with aspergillosis (n = 4), bacteremia (n = 4), or no evidence of infection (n = 4). A low level of mannanemia was detected in only one serum sample, and none showed significant Candida antibody titers. Our data thus confirm the value of the combined detection of mannanemia and antimannan antibodies in individuals at risk of candidemia and suggest that in neutropenic patients, an approach based on the regular monitoring of both markers could contribute to the earlier diagnosis of C. tropicalis systemic infection.  相似文献   

9.
Objective  To investigate the appearance of cytomegalovirus (CMV) DNA, human herpesvirus-6 (HHV-6) DNA and human herpesvirus-7 (HHV-7) DNA in plasma as a sign of reactivation and possible causes of fever of unknown origin (FUO) during neutropenia.
Methods  From 134 patients with febrile neutropenia following cytotoxic chemotherapy during the years 1996–2000, 20 severely neutropenic patients (granulocyte count < 0.1 × 109/L) were selected. Ten were patients with bacteremia and ten were patients with FUO. Five samples from each patient were selected at the start of chemotherapy, at the time of blood culture and fever, after 24 and 48 hours of fever, and, finally, after two to three days without fever. Virus DNA was detected by real-time quantitative and nested polymerase chain reaction (PCR).
Results  CMV-DNA was detected in two out of ten FUO-patients in all samples drawn during fever. From another FUO and during two bacteremia episodes, CMV-DNA was detected after 48 hours of fever. DNA from HHV-6 and HHV-7 was not detected in any of the 20 febrile episodes.
Conclusions  HHV-6 and HHV-7 as a possible explanation for FUO in severely neutropenic patients treated with cytotoxic chemotherapy seems not be very likely. However, CMV was identified in 5/20 patients and the febrile episodes in the two FUO-patients with constant DNA-emia may have been caused by a reactivation of CMV. This implies that CMV infection can be expected not only in transplant patients but also in chemotherapy-treated neutropenic patients.  相似文献   

10.
The incidence of mucocutaneous herpes simplex virus infection confirmed by culture and occurring during febrile neutropenic episodes was determined in 43 patients with haematological malignancy. The outcome of 72 episodes of neutropenic fever was determined and correlated with the presence or absence of herpes simplex virus (HSV) infection. Twenty four patients had mucocutaneous HSV infection during at least one episode. In 24 episodes in which HSV was isolated only 12.5% of fevers responded to antibiotics and 75% of fevers were otherwise unexplained. Conversely, in 48 episodes of neutropenic fever in which HSV was not isolated 67% of fevers responded to antibiotics and only 8.3% were unexplained. The difference in incidence of antibiotic resistant fever in the two groups was significant. There was, therefore, a strong association between mucocutaneous HSV infection and antibiotic resistant fever in immunosuppressed neutropenic patients. As most HSV infections are the result of virus reactivation, establishing the HSV serological state of patients would identify those at risk of infection and hence those in whom the prophylactic use of acyclovir would be indicated.  相似文献   

11.
Hemophagocytic lymphohistiocytosis is a potentially fatal condition characterized by pathologic immune activation, which can complicate infections, childhood systemic rheumatologic diseases and malignancies. Here we report a case of reactive hemophagocytic lymphohistiocytosis [macrophage activation syndrome] complicating systemic onset juvenile idiopathic arthritis, which was treated successfully with dexamethasone and cyclosporine. Reactive hemophagocytic lymphohistiocytosis or macrophage activation syndrome should be considered in patients of juvenile idiopathic arthritis with prolonged fever of unknown origin and cytopenias. Early diagnosis with high index of suspicion and prompt, aggressive treatment are needed for successful outcomes.  相似文献   

12.
PURPOSE OF REVIEW: A decade after the availability of hematopoietic growth factors, the long-term outcome of severe congenital neutropenia has dramatically changed. The prolonged survival of neutropenic patients receiving hematopoietic growth factors has drawn attention to the heterogeneity of this disease and to the complications of treatment. The dose of granulocyte colony stimulating factor that is required to obtain normal levels of circulating neutrophils and to prevent fever and infections is quite variable among patients, but is higher in children with severe congenital neutropenia than in those with other conditions of neutropenia. Moreover, leukemic transformation during treatment is not observed in all patients, but is more typical of severe congenital neutropenia and Shwachman-Diamond patients. RECENT FINDINGS: In recent years, the converging efforts of hematologists, immunologists and geneticists have led to the discovery of the genetic and biochemical basis of severe congenital neutropenia; cyclic neutropenia; warts, hypogammaglobulinemia, immunodeficiency, myelokathexis or WHIM syndrome and other rarer conditions associated to neutropenia. SUMMARY: Although the diagnosis of congenital neutropenia includes many disorders of distinct origin and variable prognosis, their treatment is still based on granulocyte colony stimulating factor administration. Understanding the pathogenesis of these forms of neutropenia and their evolution will focus future studies on the mechanisms of normal and pathological myelopoiesis and on the development of the most appropriate treatment for each type of neutropenia.  相似文献   

13.
Patients undergoing stem cell transplant (SCT) for the treatment of hematologic malignancy are at increased risk for central line–associated bloodstream infections (CLABSIs). The use of prophylactic antibiotics to prevent CLABSIs in the setting of autologous SCT is of unclear benefit. We aimed to evaluate the impact of levofloxacin prophylaxis on reducing CLABSIs in this high-risk population. Patients undergoing autologous SCT at a tertiary care hospital received levofloxacin prophylaxis from January 13, 2016 to January 12, 2017. Levofloxacin was administered from autologous SCT (day 0) until day 13, absolute neutrophil count > 500/mm3, or neutropenic fever, whichever occurred first. Clinical outcomes were compared with a baseline group who underwent autologous SCT but did not receive antibacterial prophylaxis during the previous year. The primary endpoint was incidence of CLABSIs assessed using Cox proportional hazards regression. A total of 324 patients underwent autologous SCT during the entire study period, with 150 receiving levofloxacin prophylaxis during the intervention period. The rate of CLABSIs was reduced from 18.4% during the baseline period to 6.0% during the intervention period. On multivariable analysis levofloxacin prophylaxis significantly reduced CLABSI incidence (hazard ratio, .33; 95% confidence interval [CI], .16 to .69; P = .003). There was also a reduction in the risk of neutropenic fever (odds ratio [OR], .23; 95% CI, .14 to .39; P < .001) and a trend toward a reduction in intensive care unit transfer for sepsis (OR, .33; 95% CI, .09 to 1.24; P = .10) in patients receiving levofloxacin prophylaxis. Notably, there was no increase in Clostridium difficile infection in the levofloxacin group (OR, .66; 95% CI, .29 to 1.49; P = .32). Levofloxacin prophylaxis was effective in reducing CLABSIs and neutropenic fever in patients undergoing autologous SCT. Further studies are needed to identify specific patient groups who will benefit most from antibiotic prophylaxis.  相似文献   

14.
Hepatic Candida infection (HCI; known as chronic disseminated candidosis or CDC) is a distinct form of disseminated Candida infection with predominant involvement of the liver. Diagnosis of HCI is usually made on clinical suspicion together with multiple lesions in liver on ultrasound (US), CT and/or MRI scan. Fungal elements may not always be visible in liver tissue and mycological culture is frequently negative, making the evidence for proven fungal disease difficult. We studied a novel commercially available low-cost and density-array (LCD) chip technique for a molecular diagnosis of HCI. This is a two-step procedure with PCR amplification after DNA extraction followed by hybridization on a small chip provided by the manufacturer (Fungi 2.1, Chipron GmbH). The analysis of DNA from 45 fungal control strains showed an excellent specificity and sensitivity. The DNA from 11 liver biopsies of patients with haematological malignancies suffering from CDC was analysed on the LCD chip and overall 11 fungal pathogens could be detected in eight liver biopsies, supporting the clinical diagnosis of HCI/CDC. Analysis of liver biopsies from controls was negative for fungal DNA in all samples studied. In conclusion, the novel LCD chip technique examined in our study was able to detect fungal pathogens in liver biopsies from patients with haematological malignancies and suspected HCI/CDC but was negative in control biopsies.  相似文献   

15.
This study was prospectively conducted in 11 haematology divisions over a 2-year period to evaluate the efficacy of caspofungin in 24 neutropenic patients with haematological malignancies (HM) and candidaemia. These patients had received chemotherapy for HM and were neutropenic (PNN < 0.5 × 109/L) for a median of 12 days (2–41) before candidaemia. The patients received caspofungin for a median duration of 12 days (range 6–26), obtaining a favourable overall response of 58%. At 30 days, 11 patients had died (46%); candidaemia was responsible for mortality in six patients (25%). These results suggest that treatment of candidaemia with caspofungin in neutropenic HM was efficacious, as it is in non-haematological subgroups.  相似文献   

16.
Blood samples were drawn daily from 72 patients who had hematological malignancies, neutropenia, and fever and who had failed to respond to broad-spectrum antibiotics. Each sample was used for conventional fungal blood cultures and for detection and identification of Candida DNA by a PCR method with subsequent restriction enzyme analysis (REA) recently developed in our laboratory. The PCR method was able to detect five CFU of Candida spp. per ml of blood, and subsequent REA of the amplicons allowed the identification of the Candida species most commonly implicated in cases of candidiasis. Thirty-one patients were PCR-REA positive, and four of these patients were also culture positive. The ultimate diagnosis for 13 of these patients and 1 patient who was PCR-REA negative was disseminated candidiasis (confirmed by clinical data, multiple cultures, histology, autopsy, and/or ultrasonographic evidence of hepatosplenic candidiasis). The molecular method is significantly more sensitive than conventional fungal blood cultures and has a high negative predictive value (97.5%) for the development of disseminated candidiasis in neutropenic patients.  相似文献   

17.
Since neutropenic patients with hematological malignancies are at high risk of contracting life-threatening infections, specific markers of infection are needed in cases of febrile neutropenia. The study presented here assessed serum concentrations of C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) in samples obtained from 31 febrile neutropenic patients. A total of 53 episodes were evaluated, and 18 of these were associated with positive blood culture results. Procalcitonin and IL-6 concentrations differed significantly between bacteremic and non-bacteremic episodes. Procalcitonin values were 0.22 ng/ml [interquartile range (IR), 0.15–1.9] for patients with pneumonia without bacteremia, 0.22 ng/ml (IR, 0.16–0.55) for patients with fever of unknown origin, 0.2 ng/ml (IR, 0.13–0.57) for patients with non-microbial fever and 1.8 ng/ml (IR, 0.35–5.3) for patients with bacteremia. The differences between bacteremic and non-bacteremic episodes had a P-value of 0.003 using the Mann–Whitney test. For IL-6 the median values were 301 pg/ml (IR, 152–1,879) for patients with pneumonia without bacteremia, 207 pg/ml (IR, 94–445) for patients with fever of unknown origin, 177 pg/ml (IR, 142–208) for patients with non-microbial fever and 942 pg/ml (IR, 181–2,807) for patients with bacteremia. Using the Mann–Whitney test, the differences between bacteremic and non-bacteremic episodes were P=0.006. No differences were found in CRP concentrations. Cutoff levels to distinguish between bacteremic and non-bacteremic episodes were chosen using receiver operating characteristic curves: 0.62 ng/ml for PCT and 297 pg/ml for IL-6. Negative predictive values were 84% for PCT and 70% for IL-6. The results indicate that PCT and IL-6 are more reliable markers than CRP for predicting bacteremia in patients with febrile neutropenia.  相似文献   

18.
 In an attempt to determine the actual relevance of Pseudomonas aeruginosa as a target of empiric antimicrobial first-line therapy in febrile cancer patients, 44 reports of clinical trials on antimicrobial treatment regimens and 53 reports on the epidemiology of microbiologically documented infections in cancer patients were reviewed. The incidence of infections due to Pseudomonas aeruginosa was 1–2.5% among all patients presenting with first fever during neutropenia, and 5–12% among patients with microbiologically documented infections. The proportion of Pseudomonas aeruginosa infections among cases of gram-negative bacteremia has not generally declined during the past 2 decades. There were marked local and regional differences regarding the incidence of documented Pseudomonas aeruginosa infections. No clear differences between neutropenic and non-neutropenic cancer patients, between patients with solid tumors and those with hematologic malignancies, or between inpatients and outpatients presenting with fever and neutropenia were detected with respect to the likelihood of Pseudomonas aeruginosa involvement. The mortality rate in patients with Pseudomonas aeruginosa bacteremia, particularly with polymicrobial bacteremia or bacteremic pneumonia with Pseudomonas aeruginosa involvement, is considerably high. The beneficial impact on mortality of an empiric antimicrobial treatment regimen with high antipseudomonal activity has not yet been demonstrated unequivocally. Additional factors such as the quality of intensive care management, effective second-line antimicrobial regimens, local resistance patterns, and patient-related cofactors are very likely to influence the outcome of Pseudomonas aeruginosa infections in cancer patients.  相似文献   

19.
BackgroundFebrile neutropenia is generally recognised as a complication of myelosuppressive chemotherapy. Recombinant human granulocyte colony stimulating factor (G-CSF) is commonly used as a primary or secondary prophylaxis to reduce the degree and duration of neutropenia in patients at risk of developing chemotherapy-induced neutropenic fever and infectious complications. G-CSF is known to decrease mortality and increase the possibility of maintaining adequate chemotherapy dose intensity and density, which is essential in curable malignancies. Common side effects are generally mild. However, potentially fatal adverse events have also been reported.Case presentationHerein, we summarise previously reported and report two new independent cases of G-CSF-induced aortitis, both in patients treated with chemotherapy for breast cancer. The two cases, identified only a few months apart, share several common characteristics including type of cancer, gender, age, chemotherapy, G-CSF treatment regimen, and time span from G-CSF initiation to aortitis manifestation. The two cases were both diagnosed by CT scan and successfully treated with corticosteroids along with discontinuation of G-CSF.ConclusionThis case report highlights that although aortitis is a rare adverse event of G-CSF treatment, it should be considered in cases of unexplained fever and/or clinical and laboratory findings that do not respond to antibiotics.  相似文献   

20.
AIM: To evaluate a newly developed aspergillus mitochondrial gene PCR-ELISA assay for the early diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients. METHODS: The aspergillus mitochondrial gene was chosen for the amplification target for use with a solution hybridisation assay with colorimetric end stage detection in microtitre plate format (PCR-ELISA). The study group comprised neutropenic patients undergoing febrile episodes not responding to standard antibacterial antibiotics. Patients underwent computed tomography and bronchoscopy. Bronchoalveolar lavage (BAL) fluids were examined by culture and PCR. RESULTS: The aspergillus mitochondrial gene PCR-ELISA was both sensitive (100%) and specific (100%) for IPA in neutropenic patients. All 12 patients with definite or probable IPA had PCR positive BAL fluids. None of the patients with undiagnosed or confirmed infections of other aetiologies were mitochondrial PCR positive. Speciation based upon amplicon size difference was possible. CONCLUSIONS: Aspergillus mitochondrial DNA PCR-ELISA on BAL fluid is useful in the early diagnosis of IPA in neutropenic patients alone or, potentially, as an indication for thoracic computed tomography.  相似文献   

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