OBJECTIVETo observe the effect of sirolimus-based immunosuppression administered on heart transplant recipients with chronic renal dysfunction.

METHODSFrom June 2004 to December 2008, standard calcineurin inhibitors (CNI)-based immunosuppressive regimen was changed to reduced-dose CNI plus sirolimus due to CNI-related chronic renal dysfunction in 20 out of 138 cardiac transplant recipients at Fuwai Hospital. The standard immunosuppressive regimen included steroid, CNI (cyclosporine or tacrolimus), and mycophenolate mofetil or azathioprine. Sirolimus was started at 0.75 - 1.50 mg/d with titration to achieve levels of 5 - 15 µg/L, and CNI dose was reduced gradually to 1/2-2/3 of the baseline level. Patients were followed for changes in renal function, lipid level and clinical side effects related to immunosuppressive therapy. Endomyocardial biopsy (EMB) was performed routinely at 3 weeks, 3, 6 and 12 months after transplantation. EMB was also performed at 3 months after regimen change within 1 year post-transplantation or when rejections were suspected in patients beyond 1 year post-transplantation. Echocardiography was performed for monitoring purpose.

RESULTSThe mean follow-up after regimen change was (7.9 ± 6.3) months. Final sirolimus dose was (0.89 ± 0.22) mg/d and blood drug level was (7.6 ± 3.8)µg/L. Cyclosporine dose was reduced from (191.7 ± 60.0) mg/d to (123.6 ± 34.8) mg/d, with blood drug concentration reduced from (175.5 ± 58.0) µg/L to (111.9 ± 56.0) µg/L in 18 patients (P < 0.01). Tacrolimus average dose was reduced from 4.25 mg/d to 3.00 mg/d, with blood drug concentration reduced from 13.5 µg/L to 10.5 µg/L in 2 patients. Serum creatinine level fell from (160.4 ± 25.5) µmol/L to (134.4 ± 26.8) µmol/L (P < 0.01) and urea nitrogen fell from (13.8 ± 4.7) µmol/L to (10.4 ± 3.0) µmol/L (P < 0.01) at one month after regimen change. Twenty two EMBs were performed in 11 patients within 1 year post-transplant, there were 4 episodes of acute rejected (ISHLT grade 2). Twenty patients are all alive and cardiac function was normal. The most common side effect was hyperlipidemia, and triglycerides, total cholesterol and low density lipoprotein levels were significantly increased at 1 month post regimen change (P < 0.05 or P < 0.01). Leukocyte, hemoglobin and platelet as well as liver function remained unchanged at 1 month post regimen change (all P > 0.05).

CONCLUSIONOur results show that change from CNI-based immunosuppressive regimen to reduced-dose CNI plus sirolimus is an effective and safe approach for the management of patients with CNI-related chronic renal dysfunction, leading to an improvement in renal function without compromise in anti-rejection efficacy and with tolerable side effects.

Calcineurin Inhibitors ; Female ; Heart Transplantation ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Kidney Failure, Chronic ; drug therapy ; Male ; Middle Aged ; Retrospective Studies ; Sirolimus ; therapeutic use

OBJECTIVETo ascertain whether mouse c-Kit(+)Lin- bone marrow cells have the potential of hepatic stem cells.

METHODSc-Kit(+)lin- bone marrow cells were isolated and purified by magnetic-activated cell sorting (MACS) from BALB/C male donor mice, and immediately transplanted into age-matched BALB/C syngeneic female mice with 35-Gy total liver irradiation. The recipients were sacrificed 1 month after the transplantation for pathological observation of the liver morphology. The presence of Y-chromosome was examined in the liver cells of the recipient by in situ hybridization (ISH), and alpha-fetoprotein (AFP) and albumin in the cells were detected by immunohistochemistry.

RESULTSThe hepatocytes positive for Sry gene on Y-chromosome were identified 1 month after transplantation, and immunohistochemistry for AFP and albumin confirmed that the donor mice-derived cells were hepatocytes.

CONCLUSIONc-Kit(+)lin- bone marrow cells have the potential of hepatic stem cells, which can reside and differentiate into hepatocytes in the liver after transplantation. c-Kit(+)lin- bone marrow cells can be used as the source cells of cell transplantation for liver disease.

Animals ; Bone Marrow Transplantation ; methods ; Cell Differentiation ; Female ; Hepatocytes ; cytology ; metabolism ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred BALB C ; Multipotent Stem Cells ; metabolism ; transplantation ; Proto-Oncogene Proteins c-kit ; metabolism ; Random Allocation ; Whole-Body Irradiation ; alpha-Fetoproteins ; metabolism

OBJECTIVETo observe the efficacy of polyglycoside of Tripterygium wilfordii(GTW) in preventing postoperative recurrence of Crohn disease(CD).

METHODSThirty-nine post-operative CD patients in whom all of the diseased gut had been removed from January 2005 to December 2006 were enrolled in a randomized, placebo-controlled trial. The patients took GTW(21 cases) or SASP(18 cases) in two weeks after operation. Crohn disease activity index(CDAI), ESR and CRP were collected at week 0, 13, 26, 52 or at the onset of symptoms. Ileocolonoscopy was performed at the end of the trial or at the onset of symptoms.

RESULTSOne patient in GTW group and 2 patients in SASP group were lost and 2 patients in GTW were excluded from the trial for non-compliance. Clinical recurrence was ascertained in one patient (5.6%) received GTW and in four (25.0%) received SASP. Four of eighteen patients in GTW(22.2%) had endoscopic recurrence compared with nine of sixteen(56.2%) in SASP. There were significant differences between the two groups(P<0.05).

CONCLUSIONTripterygium wilfordii showed good efficacy in preventing recurrence of postoperative CD which can maintain remission and prevent recurrence.

Adult ; Crohn Disease ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Glycosides ; therapeutic use ; Humans ; Male ; Middle Aged ; Phytotherapy ; Postoperative Period ; Secondary Prevention ; Treatment Outcome ; Tripterygium

OBJECTIVEPrimary indications for endomyocardial biopsy (EMB) include heart transplant rejection surveillance and identifying cardiomyopathy or myocarditis. EMB procedures have not yet gained widespread acceptance because of concerns about possible complications associated with EMB procedures. In this single-center retrospective study, we analyzed the incidence of major and minor EMB procedure-related complications of 439 EMBs during the past 4.5 years.

METHODSFrom May 2004 to November 2008, 15 patients with cardiomyopathy and 1 patient with suspected cardiac tumor underwent 16 EMB procedures and 131 heart transplant recipients underwent 423 EMB procedures with the use of a modified Cordis bioptome. All EMB procedures were made via the right internal jugular vein approach and RV septum EMBs were performed under fluoroscopic guidance without additional echocardiographic monitoring. Operators were allowed to perform EMB procedure alone if a minimum of 50 EMB procedures had been previously supervised by a senior operator and all EMBs were performed by 4 operators. All patients underwent a 12-lead electrocardiogram (ECG), 12-hour continuous ambulatory ECG monitoring, chest X-ray and transthoracic echocardiography before and after EMB procedures to obtain a detailed evaluation of the incidence of conduction abnormalities, arrhythmias, pericardial effusions and worsening valve insufficiency.

RESULTSThere was no major complications like cardiac tamponade, hemothorax and pneumothorax. Minor complications such as conduction abnormalities including temporary RBBB (lasting < 24 h after EMB procedures) were found in 2 cases (0.47%) and sustained RBBB (> 24 h) was evidenced in 1 case (0.23%). There were no A-V block, complex ventricular arrhythmias or episodes of atrial fibrillation during and post procedure. In addition, 4 cases (0.91%)of EMB induced mild-moderate tricuspid regurgitation during the procedure were diagnosed by echocardiography.

CONCLUSIONThe EMB procedure via the right internal jugular vein approach under fluoroscopic guidance is safe and associated with a very low complication rate when performed by experienced operators.

Adolescent ; Adult ; Aged ; Biopsy ; adverse effects ; methods ; Endocardium ; pathology ; Humans ; Middle Aged ; Myocarditis ; pathology ; Retrospective Studies ; Safety ; Young Adult

OBJECTIVETo summarize and analyze clinical outcomes and experience about using extracorporeal membrane oxygenation (ECMO) in supporting heart transplant patients in the peri-operative period of in Fuwai Hospital retrospectively.

METHODSWe performed 131 orthotopic heart transplantations from June 2004 to December 2008. Fourteen cases used veno-artery ECMO (Medtronic Ltd) for mechanical circulatory support in the peri-operative period of heart transplantation. Active clotting time(ACT) was maintained between 160 - 200 seconds, mean blood flow was 1.8 - 3.3 L/min during ECMO assistant period.

RESULTSTwelve survivals discharged with NYHAI, two patients died of multiple orgen failure with severe infection and complication of central nervous system. The ECMO time was 75 - 824 h and mean time 149 h. 12 survivals with ECMO assistance decreases the dose of vasoactive drugs, after bedside UCG evaluating heart function recovery with stable circulation, ECMO could be weaned off uneventfully after 100 h. Five patients with seven times bleeding complication and one patient with catheter-associated arterial thrombosis of distal limb, all ECMO patients with low-albuminemia and hyperbilirubinemia at some degree, eleven patients with increasing blood creatine and five patients were treated with continous renal replacement therapy, one patient with pertinacious hyperbilirubinemia was treated with plasma exchange and molecular absorbent recirculating system. Seven patients were extension incision healing and six patients were tracheotomy.

CONCLUSIONSECMO can bridge patients with end-stage heart failure to heart transplant, and extend the use of marginal donors, grasp the ECMO indication and timing of application, avoiding irreversible dysfunction of the vital organs and preventing complication during ECMO, ECMO may decrease mortality of severe patients in the peri-operative period of heart transplantation.

Extracorporeal Membrane Oxygenation ; adverse effects ; methods ; Heart Failure ; therapy ; Heart Transplantation ; mortality ; Hospital Mortality ; Humans ; Perioperative Care ; methods ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo access the prevalence and risk factors for hypertension after heart transplantation (HT), and the impact of post-transplant hypertension on medium-term survival among HT patients.

METHODSData from 265 consecutive patients underwent HT between June 2004 and May 2012 in Fuwai hospital and survived for at least 6 months were retrospectively analyzed. Hypertension was defined as systolic pressure ≥ 140 mm Hg (1 mm Hg = 0.133 kPa) and/or diastolic pressure ≥ 90 mm Hg or current treatment with antihypertensive drugs. Patients were divided into post-HT hypertension group and non-hypertension group. Logistic regression analysis was used to determine preoperative and postoperative risk factors for hypertension after HT. Kaplan-Meier method and log rank test were used for survival analysis.

RESULTSHypertension was present in 17.4% (46/265) patients before HT and in 57.4% (152/265) patients post HT. The median follow-up time was 37 months (20 - 57 months). Logistic regression analysis showed that male gender (OR: 2.27, 95%CI: 1.16 - 4.42, P < 0.05), history of pre-HT hypertension (OR: 2.22, 95%CI: 1.05 - 4.71, P < 0.05), and cyclosporine A based immunosuppressive therapy (OR: 2.54, 95%CI: 1.51 - 4.29, P < 0.01) were independent risk factors for the development of post-HT hypertension. At the end of 1, 3, 5 years, the survival rate of heart transplant patients by Kaplan-Meier method estimation were 100%, 97.2%, 86.7% in post-HT hypertension group; 98.1%, 93.8%, 93.8% in non-hypertension group. Log rank test displayed that there was no significant difference between the two survival curves (P > 0.05).

CONCLUSIONSHypertension is a frequent comorbidity after HT. Male gender, pre-HT hypertension together with cyclosporine A based immunosuppressive therapy are independent predictors for the development of post-HT hypertension. By adjusting the controllable risk factors and active control of blood pressure, the medium-term survival is similar between patients with or without postoperative hypertension in this cohort.

Adult ; Female ; Heart Transplantation ; Humans ; Hypertension ; etiology ; Logistic Models ; Male ; Middle Aged ; Postoperative Complications ; etiology ; Prognosis ; Retrospective Studies ; Risk Factors

Castleman's disease is a slowly progressive and rare lymphoproliferative disorder. Here, we report a 55-year-old woman with superior mediastinal Castleman's disease being misdiagnosed for a long term. We found a 4.3 cm mass localized in the superior mediastinum accompanied with severe clinical symptoms. The patient underwent an exploratory laparotomy, but the mass failed to be totally excised. Pathologic examination revealed a mediastinal mass of Castleman's disease. After radiotherapy of 30 Gy by 15 fractions, the patient no longer presented previous symptoms. At 3 months after radiotherapy of 60 Gy by 30 fractions, Computed tomography of the chest showed significantly smaller mass, indicating partial remission. Upon a 10-month follow-up, the patient was alive and free of symptoms.
Antigens, CD20 ; metabolism ; Castleman Disease ; diagnosis ; immunology ; pathology ; radiotherapy ; surgery ; Female ; Follow-Up Studies ; Humans ; Mediastinal Diseases ; diagnosis ; immunology ; pathology ; radiotherapy ; surgery ; Mediastinum ; diagnostic imaging ; pathology ; Middle Aged ; Multimodal Imaging ; Positron-Emission Tomography ; Radiotherapy, Intensity-Modulated ; Tomography, X-Ray Computed

Gastrointestinal Tract ; Humans ; Lymphoproliferative Disorders ; T-Lymphocytes

ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.