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1.
2.

Objective

In this study, we examined whether cyclosporine was effective when combined with everolimus in clinical heart transplantation (HT).

Patients and Methods

From August 2004 to July 2007, 108 adult patients underwent primary HT. The main exclusion criteria were: donors >60 years; cold ischemia times >6 hours; recipients of multiorgan transplantation or a previous transplantation; and panel-reactive antibodies ≥25%. The cyclosporine plus everolimus regimen (group CE, n = 32) was suggested first; upon refusal or if the recipient or donor was positive for hepatitis B surface antigen or PCR + hepatitis C infection, then patient was randomly assigned to success cyclosporine plus mycophenolate mofetil (MMF; group CM, n = 24) or tacrolimus plus MMF (group TM, n = 25). All patients underwent similar operative procedures and postoperative care with protocol endomyocardial biopsies.

Results

No 30-day mortality was noted in any group. The efficacy failure rates were 3%, 25%, and 16% in groups CE, CM, and TM, respectively (P = .04 between groups CE and CM). The 1-year survivals were 96.7% ± 18.1%, 89.7% ± 29.8%, and 81.0% ± 35.5% for groups CE, CM, and TM, respectively (P = .04 between groups CE and TM). The 3-year survival rates were 91.9% ± 28.3%, 79.8% ± 46.0%, and 81.0% ± 35.5% in groups CE, CM, and TM, respectively.

Conclusions

The 3 immunosuppressive regimens offered good efficacy after HT. The cyclosporine plus everolimus regimen showed a significantly better result with less efficacy failure (compared with cyclosporine plus MMF: 3% vs 25%) and better 1-year survival compared with tacrolimus plus MMF: 96.7% vs 81.0%.  相似文献   

3.

Objective

The aim of this study in renal transplant recipients was to compare a tacrolimus plus mycophenolate mofetil (MMF) immunosuppressive regimen with a combination of low dose of cyclosporine and everolimus.

Patients and Methods

Sixty consecutive patients were prospectively assigned to receive tacrolimus and MMF (TAC; n = 30) or everolimus and low-dose cyclosporine (EVL; n = 30). Tacrolimus was dosed seeking a trough blood level of 8 to 10 ng/mL by month 3 and 5 to 8 ng/mL thereafter. Everolimus was dosed seeking a trough blood level of 3 to 8 ng/mL by day 7. Cyclosporine was dosed aiming at a C2 blood level of 350 to 700 ng/mL in the first week and 150 to 400 ng/mL thereafter. All patients received induction with basiliximab and maintenance treatment with corticosteroids.

Results

At 6-months follow-up, patient survival rates (TAC 100% vs EVL 100%) and graft survival rates (TAC 96.7% vs EVL 93.3%) were not significantly different between the groups. Patients in the EVL group showed more acute rejection episodes, but serum creatinine concentrations and creatinine clearances were not significantly different from the TAC group. Among the observed side effects, hypercholesterolemia was significantly higher in the EVL group (total cholesterol: TAC 206 ± 38 vs EVL 250 ± 55 mg/dL; P < .003).

Conclusions

This study showed that the immunosuppressive association of tacrolimus and MMF produced similar acute rejection episodes, graft survivals, and renal function at 6 months after renal transplantation compared with an immunosuppressive combination of everolimus and low-dose cyclosporine. Dyslipidemia was significantly greater among patients who received everolimus.  相似文献   

4.

Introduction

The half-life of everolimus is approximately 28 hours, but everolimus is generally administered twice a day. The aim of this prospective, single-center, exploratory study was to compare the efficacy and safety of a once a day everolimus (OD) with the standard twice a day administration regimen (BID) as immunosuppressive therapy in renal transplantation.

Methods

Forty-one de novo renal transplant recipients prospectively assigned to OD (n = 21) or BID (n = 20) treatment were followed for 1 year. In the OD group, everolimus was orally administered targeting a trough blood level of 2 to 5 ng/mL. In the BID group, everolimus was given twice a day targeting a trough blood level of 3 to 12 ng/mL. All patients also received induction with basiliximab and low-dose calcineurin inhibitor immunosuppression.

Results

At 1 year follow-up patient and graft survivals were 100%. The intention-to-treat analysis showed similar renal function between the two regimens: serum creatinine values for OD 1.54 ± 0.6 versus BID 1.48 ± 0.53 mg/dL (P = NS). Also the occurrence of acute rejection episodes was not significantly different: 4.8% in the OD versus 15% in the BID group, (P = NS). The median trough blood levels were significantly lower among the OD group: OD 4.5 versus BID 7.2 ng/mL (P < .001).

Discussion

This study demonstrated that once a day administration of everolimus achieved excellent patient and graft survival and good renal function without an increased incidence of acute rejection episodes.  相似文献   

5.

Introduction

The reported incidences of de novo malignancy following orthotopic liver transplantation (OLT) are significantly greater than those in the general population. We have analyzed the efficacy of mammalian target of rapamycin inhibitor (mTORi) as immunosuppressant therapy in patients with de novo malignancies or those engrafted because of a primary liver cancer.

Methods

We performed a case-control study of patients with hepatocellular carcinoma (HCC; n = 119), cholangiocarcinoma (n = 1) or de novo malignancies (n = 73). Thirty-seven patients with these tumors were treated with mTORi, and 167, with calcineurin inhibitors (CNI). Switching to mTORi was performed progressively, withdrawing the CNI over 15 days, until obtaining levels of 5-10 ng/dL.

Results

No incidence of rejection, serious adverse events, or death was observed with an overall actuarial survival of 68.5% in the mTORi group versus 45.7% among the CNI group. Overall rates of tumor recurrence were 15.2% and 36.8%, respectively (P < .05). Among patients with HCC, survival was 100% of mTORi with and 61.5% among CNI patients, with tumor recurrence rates of 6.2% and 19.1%, respectively (P < .05).

Discussion

Surprising differences in survival and tumor recurrence rates were observed among the mTORi-treated group compared with controls. Switching from CNI to mTORi immunosuppressant therapy appeared to be safe. It seems to be reasonable to employ this strategy in liver transplant patients with primary hepatic or “de novo” neoplasms.  相似文献   

6.

Background

Inhibitors of mammalian target of rapamycin (mTORi) have been suggested as an alternative to calcineurin inhibitors (CNIs) to treat stable renal transplant recipients. However, their use has been significantly limited owing to a high incidence of side effects.

Objective

To compare the rate of dropout (mTORi elimination and CNI reintroduction) caused by side effects among renal transplant patients converted to everolimus (EVL) or sirolimus (SRL).

Methods

Between October 1999 and February 2010, 409 subjects were converted to an mTORi at least 3 months after transplantation, including 220 (53.8%) to EVL and 189 (46.2%) to SRL. Most patients were under CNI therapy. Patients were followed for a median of 35 months (interquartile range [IQR], 18-50 months).

Results

mTORi treatment was prematurely eliminated due to adverse events in 112 patients. The median time between the initiation of mTORi and discontinuation was 5.7 months (IQR, 1.9-15.7 months; range, 0.2-48 months): 5.5 (IQR, 1.6-16.3) in the EVL group and 7.4 (IQR, 2.6-15.6) in the SRL group. In the EVL group, the drug was stopped in 69 patients (31.4%), and in the SRL group in 43 patients (22.8%; P = .051). The most important causes of discontinuation were severe infections (2.3% in EVL group and 4.8% in SRL group; P = .17), pneumonitis (6.8 % in EVL group and 4.8 in SRL group; P = .38), acute rejection episode (4.1% in EVL group and 1.6% in SRL group; P = .13), proteinuria (4.1% in EVL group and 1.6% in SRL group; P = .13), renal function deterioration (2.3% in EVL group and 2.1% in SRL group; P = .91), and severe dermal eruption (2.3% in EVL group and 0.5% in SRL group; P = .14).

Conclusions

Although the overall incidence discontinuations due to side effects was higher in the EVL group, there was no greater frequency of severe side effects, such as pneumonitis, proteinuria, acute rejection episodes, renal function deterioration, or dermal eruptions.  相似文献   

7.

Introduction

Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been used in acute and chronic treatment of kidney and heart transplants. There is scarce information regarding its use in liver transplant recipients, although everolimus may be a useful alternative for selected cases.

Objective

The objective of this study was to study the clinical, biochemical, and pathological features of patients to whom everolimus was added based upon defined clinical profiles.

Study Design

This study was prospective observational ongoing study to evaluate the effectiveness and safety of everolimus alone or in combination with low doses of a calcineurin inhibitor (CNI). Chronic liver transplant recipients without contraindications to everolimus were defined based upon 7 profiles of complications. The initial everolimus dose (0.25 mg every 12 hours) was overlapped during conversion, measuring blood levels and evaluating clinical tolerance. Routine monitoring was performed to obtain immunosuppressant blood levels near the lower limit of the therapeutic range.

Results

The 35 patients' including 17 men and 18 women, had an overall mean age of 61 ± 10 years with a mean follow-up of 34 months. The everolimus treatment lasted 20 months (range, 6-60). The indication for everolimus conversion were as follows: renal insufficiency (45.7%), no response to hepatitis C virus (HCV) treatment (42.9%), autoimmune hepatitis associated with interferon (8.5%), de novo autoimmune hepatitis (25.5%), de novo tumor (37.1%), neurotoxicity (14.3%), or side effects to rapamycin treatment (5.7%). Patients may have presented more than one indication. Effectiveness was assessed based upon improved liver (48.6%) or renal function (31.25% with renal insufficiency) or withdrawal of prednisone (100% of 10 patients receiving prednisone). CNI was withdrawn from 48.6% of patients due to de novo tumors or neurotoxicity. The side effect were as follows: anemia, leukopenia, or thrombocytopenia (11.4%) or dyslipidemia (27.3%). The survival rate was 94.3%.

Conclusions

Administration of everolimus to chronic liver transplants enhanced therapeutic options in the long term recipients when applied for predefined clinical indications and administrated with dose adjustments based on serial monitoring of exposure.  相似文献   

8.

Study Objective

To investigate the effect of intravenous (IV) landiolol, a novel β1-adrenergic blocker, on the minimum alveolar concentration (MAC) of sevoflurane in adult women.

Design

Prospective, randomized study.

Setting

University hospital.

Patients

42 ASA physical status 1 and 2 women, aged 24-57 years, who were scheduled to undergo elective abdominal surgery.

Interventions

Anesthesia was induced in all patients by vital capacity rapid inhalation induction of sevoflurane. In the landiolol group, administration of landiolol began when patients took a vital-capacity breath: 0.125 mg/kg/min for one minute and then 0.04 mg/kg/min. Normal saline was administered in the control group.

Measurements

MAC was determined by a technique adapted from the conventional up-down method.

Main Results

The MAC of sevoflurane was 2.2% ± 0.2% in the control group and 1.7% ± 0.2% in the landiolol group, a statistically significant difference (P = 0.0005).

Conclusions

IV landiolol reduces the MAC of sevoflurane in women by approximately 20%.  相似文献   

9.

Objectives

The functional outcome after midforearm transplantation (HT) is believed to be similar to the outcome after replantation. However, the few existing reports comparing functional outcomes are based on amputations at the level of the distal forearm. This report provides a comparative analysis of the functional results after midforearm replantation (HR) versus HT.

Materials and Methods

Transplantation of a dominant right forearm performed in a 32-year-old man was compared to the outcomes after five dominant (right) forearm replantations (four men and one woman) in patients ranging from 22 to 38 years of age. Cold ischemia time ranged from 6 to 12.5 hours in all cases. We used similar operative technique and rehabilitation protocol. At 26 (±2) months after replantation/transplantation, we recorded, bony union (x-ray), arterial flow (ultrasonography), range of motion, grip strength, sensation (2 PD Weisensten's filaments), quality of life (DASH, 30-150 points), general evaluation of function according to Chen's or the IRHCTT scoring system.

Results

A complication of wound infection was observed in one HR patient; Marginal skin necrosis accompanied by prolonged wound healing, in one HT patient. Unification of bones was achieved faster after forearm replantation when compared with transplantation. Grip strength was 17% greater after replantation, but ranges of motion were comparable in both groups. Sensitivity was superior after forearm transplantation (2 PD 15 mm) and overall patient satisfaction was comparable (90 points of DASH questionnaire for HR versus 108 points for HT patients). None of the patients returned to their previous occupations.

Conclusion

The functional outcome after HT was comparable, and in some respects superior, to the outcome after replantation performed at the midforearm level.  相似文献   

10.
11.

Objective

Our aim was to assess our experience with the use and management of everolimus after orthotopic liver transplantation (OLT).

Materials and Methods

Among the 759 patients who underwent transplantation from 1988 to 2008, 25 (3.2%) received immunosuppression with everolimus. Their mean age was 55.6 years. We analyzed indications for use, time between transplantation and introduction of everolimus, as well as its efficacy, side effects, and patient survival.

Results

The indications for everolimus treatment were: extended hepatocellular carcinoma (HCC) in the explanted liver (n = 6; 24%); HCC recurrence during follow-up (n = 4; 16%); de novo tumor (n = 6; 24%); refractory rejection (n = 3; 12%); side effects of calcineurin inhibitors (CNI; n = 3; 12%); and other causes (n = 3; 12%). Mean time between OLT and everolimus treatment was 40 ± 33 months (range, 10 days-178 months). Mean follow-up after conversion was 10 ± 9 months (range, 1.5-25 months). More than half of the patients resolved the event for which the drug was indicated: 75% of patients with refractory rejection; 60% of those with renal insufficiency; and 100% of those converted for neurotoxicity or hepatotoxicity. Two patients with recurrent HCC and 1 with extended HCC died at a mean time of 10.5 months. The 6 cases of de novo tumors were operated and are healthy. Side effects were dyslipidemia in 8 and infection in 2. Five patients (20%) discontinued the drug.

Conclusions

In the early posttransplantation period, everolimus is indicated for refractory rejection or as prophylaxis for recurrence of extended tumors. In any time but especially in the late period, everolimus is indicated for patients with serious side effects due to a CNI or to a de novo tumor.  相似文献   

12.

Background

The mammalian target of rapamycin inhibitors (mTORi) sirolimus (Si) and everolimus (Ev) induce pneumonitis, an unusual but potentially fatal adverse effect. We report 8 cases of suspected mTORi-induced pneumonitis over a 9-years experience from 2000 to 2009.

Methods

The switch from a calcineurin inhibitor (CNi) was made due to chronic transplant nephropathy, tumors, nephrotoxicity, or for rejection prophylaxis.

Results

One hundred six patients were switched from CNi to Si (n = 29) or Ev (n = 134). Twenty-five additional patients were treated de novo with mTORi. The 8 patients (3 Si, 5 Ev) who developed pneumonitis included 5 females and 3 males of median age, 59.1 years (range, 40-68). The median time from switch to pneumonitis onset was 292 days (range, 60-982). The clinical presentation included fatigue (n = 6), fever (n = 7), dyspnea (n = 6), dry cough (n = 6), and weight loss (n = 5). In most cases, imaging tests (chest radiograph, computerized tomography) revealed bilateral lower lobe involvement. Bronchoalveolar lavage showed a lymphocytic alveolitis in 5 subjects with negative cultures. All patients recovered after mTORi withdrawal. All patients were treated with antibiotics and five with steroids.

Conclusion

mTORi associated pneumonitis is not a rare disease. It is equally induced by Si or Ev. Pneumonitis was not apparently dependent on the drug dose or the blood levels. Discontinuation of mTORi seems to be the safest treatment option to avoid pulmonary fibrosis or a fatal outcome.  相似文献   

13.

Background/Purpose

Symptomatic pancreatic pseudocysts have traditionally been managed with surgical, percutaneous, and, more recently, endoscopic drainage. Although the role of the latter is well defined in the adult population, its utility in children needs to be clarified. The authors reviewed their experience with endoscopic drainage of pancreatic pseudocyst (EDPP).

Methods

A retrospective chart review was conducted, and relevant demographic and clinical data were obtained for all patients with pancreatic pseudocysts managed with endoscopic drainage in the period from 1997 through 2001, inclusive.

Results

Three children had successful endoscopic drainage of pancreatic pseudocysts. They were 9, 13, and 14 years old, and were all boys. The etiology of the pancreatitis was idiopathic related to anomalous pancreatic divisum ducts in the first 2 and azathioprine induced in the latter. The first 2 patients had endoscopic transpapillary drainage, whereas the third had an endoscopic cystduodenostomy. All patients had complete resolution of the pseudocyst clinically and radiologically after follow-up periods of 3, 31, and 21 months, respectively. The first needed a subsequent pancreaticojejunostomy for persistent symptoms related to chronic pancreatitis. A successful endoscopic drainage of a posttraumatic pancreatic pseudocyst has previously been reported from our institution.

Conclusions

This experience would indicate that endoscopic drainage of pancreatic pseudocyst is an effective and relatively safe option of managing this problem in children.  相似文献   

14.

Purpose

We aimed at determining whether osseous grafts engineered from amniotic mesenchymal stem cells (aMSCs) could be used in postnatal sternal repair.

Methods

Leporine aMSCs were isolated, identified, transfected with green fluorescent protein (GFP), expanded, and seeded onto biodegradable electrospun nanofibrous scaffolds (n = 6). Constructs were dynamically maintained in an osteogenic medium and equally divided into 2 groups with respect to time in vitro as follows: 14.6 or 33.9 weeks. They were then used to repair full-thickness sternal defects spanning 2 to 3 intercostal spaces in allogeneic kits (n = 6). Grafts were submitted to multiple analyses 2 months thereafter.

Results

Chest roentgenograms showed defect closure in all animals, confirmed at necropsy. Graft density as assessed by microcomputed tomographic scans increased significantly in vivo, yet there were no differences in mineralization by extracellular calcium measurements preimplantation and postimplantation. There was a borderline increase in alkaline phosphatase activity in vivo, suggesting ongoing graft remodeling. Histologically, implants contained GFP-positive cells and few mononuclear infiltrates. There were no differences between the 2 construct groups in any comparison.

Conclusions

Engineered osseous grafts derived from amniotic mesenchymal stem cells may become a viable alternative for sternal repair. The amniotic fluid can be a practical cell source for engineered chest wall reconstruction.  相似文献   

15.

Background

Wound infection after median sternotomy for cardiac or thoracic surgery is a serious complication. A variety of treatment plans have been advocated, and there is lack of agreement regarding the best treatment method. We present our results in patients with mediastinitis who have been treated in a simple, consistent manner.

Methods

We reviewed our experience with 40 consecutive patients with mediastinitis who were treated between January 1995 and May 2003 with a single-stage treatment consisting of sternal and soft tissue debridement and wound closure over mediastinal tubes with continuous irrigation and drainage. Tubes were placed posterior to the sternum in all patients and were irrigated continuously for at least 7 days with antibiotic or antibacterial solution. Systemic antibiotics were selected based on culture and sensitivity data and were administered for 2 to 6 weeks.

Results

All patients with mediastinitis treated in this manner survived. Of the 40 patients, 38 achieved complete healing of the wound without further operative intervention or major complication. One patient had recurrent infection and required sternal resection and advancement of muscle flaps. One patient had a residual localized focus of chondritis and underwent limited resection of cartilage.

Conclusions

In this series of patients with postoperative mediastinitis, a simplified approach consisting of wound debridement, reclosure over drains, and anterior mediastinal irrigation has been an effective treatment. The results we have achieved suggest that this technique may be a suitable option for treating this condition.  相似文献   

16.

Background

In conventional conduit operations, longevity has been essentially limited by the inevitable need for conduit replacement. This study was undertaken to compare long-term results of the use of equine pericardial conduits, autologous pericardial conduits, and direct anastomosis repair.

Methods

Between 1982 and 2001, 366 patients underwent primary establishment of right ventricle-pulmonary artery continuity at our institution. The mean age at the time of operation was 6.2 years (range, 4 days to 28 years) and mean weight was 17.2 kg (range, 1.6 to 61 kg). Three different repair techniques were used for connection: hand-made valved equine pericardial conduits (n = 179), autologous pericardial conduits (n = 71), and direct anastomosis without a conduit (n = 116). Mean follow-up period for early survivors was 8.6 years in the equine group, 6.1 years in the direct anastomosis group, and 5.1 years in the autologous pericardium group.

Results

Direct anastomosis repair (p = 0.0002) was associated with significantly better freedom from late events (conduit replacement or late death) than equine pericardial conduits. The hazard ratio was less with the autologous pericardium conduit than with the equine pericardium, but the difference was not statistically significant (p = 0.2122). Younger age at operation, and postoperative pressure ratio from right to left ventricle were also predictors of conduit longevity.

Conclusions

To decrease the probability of late events, direct anastomosis is an encouraging technique compared with traditional equine pericardium extracardiac conduit repair. An autologous pericardial conduit, because of its benefits, would be an alternative when direct anastomosis is not suitable.  相似文献   

17.

Background

Sternal dehiscence with or without mediastinitis is a devastating complication of median sternotomy. Various techniques of sternotomy closure including ‘figure of eight’ wire sutures, nylon bands, and custom-made titanium-H plates have been described. We have devised and tested a new method of sternal closure to prevent sternal wound complications in patients at high risk of sternal dehiscence.

Methods

1336 patients underwent sternotomy for various cardiac operations from January 1996 to January 2002. Patients were divided into two groups. Group I consisted of 560 patients who did not have any high risk factors for sternal dehiscence and received a standard six wire closure. Group II comprised of patients at high risk of sternal dehiscence and were divided randomly into subgroup II A (n = 390), which included patients who had conventional sternal closure. While in subgroup II B (n = 386) patients had a modified parasternal wire closure according to the finalized protocol.

Results

Sternal instability was noticed in 1/560 and none had sternal dehiscence in group I, but 16/390 patients had sternal instability and 3/390 had sternal dehiscence in subgroup II A, whereas only one patient in high risk subgroup II B developed sternal dehiscence with mediastinitis and required a pectoral flap advancement for sternal closure.

Conclusions

Use of modified parasternal wire closure in patients with a high risk of sternal dehiscence is a safe, effective, technically easily reproducible, as well as economical, method of preventing and treating sternal dehiscence.  相似文献   

18.
Caecal volvulus     

Background

Caecal volvulus accounts for 30% of all cases of volvulus of the colon.

Methods

We recorded clinical data and accurate images of volvulus of the cecum.

Results

A detorsion with resection and primary anastomosis was performed. We reviewed the management and surgical strategies for cecal volvulus.

Conclusions

Caecal volvulus is an uncommon entity with potentially severe outcomes and requires surgical management.  相似文献   

19.

Purpose

Few studies address the surgical correction of pectus excavatum (PE) in patients with connective tissue disease (CTD). We have identified the preoperative characteristics, postoperative complications, and outcomes of patients with CTD undergoing bar repair of PE and compared these outcomes to a control group without CTD.

Methods

A retrospective review of patients undergoing primary repair of PE with a bar procedure from 1997 to 2006 identified 22 patients with CTD. Of those, 20 (90.9%) had their bars removed. We identified 223 patients of similar age without CTD whose bars were removed. Data collected included demographics, preoperative symptoms, operative characteristics, and postoperative outcomes.

Results

Among those with CTD, the median age at repair was 15.5 years, with a mean pectus index of 4.0 ± 1.4. Three patients (13.6%) experienced bar displacement or upper sternal depression requiring surgical revision. Only 1 patient recurred after bar removal. Rates of bar displacement, upper sternal depression, and recurrence were not statistically different than those in the comparison group.

Conclusions

Patients with CTD benefit from primary bar repair of PE and experience excellent operative outcomes after repair, with complication rates being no different than those found in similarly aged control patients.  相似文献   

20.

Purpose

The aim of the study is to review the surgical experiences with pectus excavatum (PE) chest deformities at the Department of Pediatric Surgery, West China Hospital of Sichuan University (Sichuan, PR China), during a 30-year period.

Method

Records of 398 PE patients (396 congenital, 2 acquired) who underwent surgical repair between 1975 and 2005 were reviewed. Modified sternal elevation was applied in all patients. Repair was performed with subperiosteal resection of the abnormal cartilages, transverse wedge osteotomy of the anterior sternum, and internal support with a metal strut for 1 year. Five technical details were strictly followed for each case. Three hundred twelve patients (78.39%) were followed up from 1 to 16 years.

Result

There were no deaths. Normal contour of the costal cage was constructed postoperatively in 98.74% (393/398) of the patients. Exercise tolerance was improved, and cardiac function recovered to the healthy level of same age. But pulmonary function recovered slowly after surgery.

Conclusions

The 5 technical details are key principles for sternal elevation. Normal appearance of chest wall can be recovered; normal cardiopulmonary function can be restored by the modified sternal elevation with excellent long-term physiologic, cosmetic results and low rate of complications.  相似文献   

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