Aim: Osteosarcoma is one of the most prevalent primary bone malignancies in children and adolescents. Magnetic resonance imaging (MRI) has been considered a very critical tool to provide anatomical information of tumor and surrounding main blood vessels. To evaluate the prognostic significance of the radiological vascular involvement according to the pre-treatment MRI in patients with Enneking IIB osteosarcoma. Methods: In this retrospective study, we included 482 patients younger than 50 years old with Enneking IIB primary osteosarcoma of the extremities with complete clinical records from 2005 to 2015.Univariate and multivariable analyses were conducted to identify the risk factors for OS (Overall survival) and EFS (Event-free survival). The correlations between the risk factors was performed using Spearman analysis. The Kaplan-Meier method was used to calculate survival curves. Based on the radiological relationship between the tumor lesion and the surrounding reactive area with the main blood vessels as shown on pretreatment MRI findings. Results: Radiological vascular involvement assessed via pretreatment MRI is an important risk factor for Enneking IIB primary patients with osteosarcoma (HROS=2.32/HREFS=1.81 P<0.01) according to the univariate and multivariable analyses. Enneking IIB patients with osteosarcoma were assigned to three subtypes based on the radiological relationship between the main blood vessels and the lesion or reactive area. The 5-year cumulative OS of patients classified by the three types were 81.6% (type I), 67.1% (type II) and 44.8% (type III)(P<0.01). The 5-year cumulative EFS of the three types were 60.2% (type I), 46.7% (type II) and 30.2% (type III)(P<0.05). The total 5-year cumulative OS and EFS for all patients were 68.3% and 48.3%, respectively. Conclusion: Vascular involvement according to radiological findings from pretreatment MRI is an independent risk factor for cumulative OS and EFS in patients with Enneking IIB primary osteosarcoma of the extremities. The new subtyping based on the relationship between the tumors and surrounding reactive area with the main blood vessels based on pretreatment MRI can predict the prognosis of patients with osteosarcoma and provide certain directive information for selecting the appropriate surgical procedure for individual patients.
Postmenopausal osteoporosis (OPM) is a common type of osteoporosis in females. It is a systemic, chronic bone disease that presents as microstructure degradation of osseous tissue, decreased bone mineral density and increased osteopsathyrosis caused by hypoovarianism and reduced estrogen levels in the body following menopause. In the present study, the role of microRNA (miR)‑214‑5p in the regulation of the expression of bone marrow stem cells (BMSCs) was investigated, and its molecular mechanism of osteogenic induction in vitro was assessed. When dexamethasone‑induced adipogenic differentiation was performed, miR‑214‑5p expression was increased compared with the control group, as determined by RT‑qPCR. Furthermore, oil red O staining, RT‑qPCR and western blot analysis demonstrated that overexpression of miR‑214‑5p promoted adipogenic differentiation, inhibited alkaline phosphatase (ALP), runt‑related transcription factor 2 (Runx2), osteocalcin (OC) and collagen α‑1 (I) chain (COL1A1) mRNA expression, and suppressed transforming growth factor (TGF)‑β, phosphorylated (p)‑Smad2 and collagen type IV α1 chain (COL4A1) protein expression in BMSCs. Additionally, downregulation of miR‑214‑5p increased the ALP, Runx2, OC and COL1 mRNA expression and increased TGF‑β, Smad2 and COL4A1 protein expression in BMSCs. Furthermore, a TGF‑β inhibitor was employed to inhibit TGF‑β expression in BMSCs following miR‑214‑5p downregulation, which led to reduced Smad2, TGF‑β and COL4A1 protein expression, and ALP, Runx2, OC and COL1 mRNA expression was also reduced, compared with the miR‑214‑5p downregulation only group. It was demonstrated that miR‑214‑5p may weaken osteogenic differentiation of BMSCs through regulating COL4A1. In conclusion, the results of the present study indicated that miR‑214‑5p may promote the adipogenic differentiation of BMSCs through regulation of the TGF‑β/Smad2/COL4A1 signaling pathway, and potentially may be used to develop a novel drug for postmenopausal osteoporosis.
Purpose:The aim of this study is to identify factors influencing BK viral clearance and graft outcomes for Polyomavirus BK-associated nephropathy (BKVAN). Methods:Between 2006 and 2013, we diagnosed BKVAN in 39 (7.9%) of 491 patients with transplant biopsies by simian virus 40 (SV40) staining and quantitative polymerase chain reaction(PCR) assay for BKV DNA load in urine and plasma and quantitative assay of urine cytology. At diagnosis, we either reduced cyclosporine A by 30%(n=1), or reduced tacrolimus(Tac) by 30%-50%(n=22), or switched from Tac to cyclosporine A (n=13), or switched from Tac to Rapamycin(n=3). Data from these 39 patients were analyzed for graft functional decline, graft loss, graft survival rate, the time for viral PCR reduction in plasma by 1 log(90%) (≤7weeks or >7weeks), and influence factors. Results:During 28.5 ± 25.3 months follow-up, the frequencies of any short-term(3 months after diagnosis) functional decline, any long-term functional decline, and graft loss were 25.6%, 33.3%, and 25.6% respectively.The 1-, 3-, 5- graft survival rate were 100%, 77.4%, and 61.2%. More extensive interstitial inflammation(OR 9.020, p=0.027), but not viral load in blood and urine, nor the creatinine at diagnosis correlated with worse creatinine at 3 months. Viral reduction by 1 log was rapid in 51.4% (≤7 weeks) and slow in 48.6% (>7 weeks). On long-term follow-up, rapid viral reduction was associated with stable graft function(94.7%), compared with slow viral reduction (44.4%, p=0.001). Tac treatment had a negative influence on viral reduction time(OR 8.20, p=0.023). Defining 1-log viral load reduction as an event, Tac compared with non- Tac was associated with slow viral reduction (P=0.044).Multivariate analysis showed that extensive interstitial inflammation (HR 19.0, p=0.020) at diagnosis and slow viral reduction(HR 30.3, p=0.009) were associated with long-term functional decline. Clearance of viremia(78.4%) was associated with better graft survival at 3 years (89.2% versus 15.0%, p<0.001).Conclusions:Tac treatment prolongs BK viral reduction time. The extent of interstitial inflammation and viral reduction time influence short and long-term graft outcomes in patients with BKVAN.
The purpose of this study was to investigate the effect of BK polyomavirus (BKPyV infection of glomerular parietal epithelial cells (GPECs) on graft outcome in kidney transplant recipients with BKPyV-associated nephropathy (BKPyVAN). A total of 152 kidney transplant recipients with BKPyVAN were divided into 31 with (GPEC-positive group) and 121 without (GPEC-negative group) BKPyV-infected GPECs. Clinicopathological characteristics and allograft survival were compared between the groups. The GPEC-positive group had more patients with advanced-stage BKPyVAN than the GPEC-negative group (P < .001). At the last follow-up, the GPEC-positive group had a significantly higher serum creatinine level than the GPEC-negative group. The graft loss rate in the GPEC-positive group was higher than that in the GPEC-negative group (32.3% vs 12.4%; P = .008). Kaplan-Meier analysis showed that the graft survival rate in the GPEC-positive group was lower than that in the GPEC-negative group (log-rank test, P = .004). Multivariate Cox regression analysis demonstrated that BKPyV infection of GPECs was an independent risk factor for graft survival (hazard ratio, 3.54; 95% confidence interval, 1.43–8.76; P = .006). GPEC infection in patients with BKPyVAN indicates more-severe pathological damage and a rapid decline in renal function. BKPyV infection of GPECs is an independent risk factor for allograft loss.
Background:A 1-year, single-center trial demonstrated that monitoring and preemptive of immunosuppression reduction were associated with resolution of viremia.Our 5-year prospective subsequent study was conducted to determine the long-term patient/graft survival and outcome of BK viremia and BK virus-associated nephropathy (BKVAN) in renal transplant recipients under the impact of intensive monitoring and reduction of maintenance immunosuppression. Methods:Quantitative BK virus (BKV) DNA surveillance in plasma/urine and cytological test in urine were performed at 1, 3, 6, 9, and 12 months after transplantation in 229 kidney recipients.Patients with BK viremia and BKVAN treated with 30% to 50% reduction in doses of tacrolimus (Tac) or/and mycophenolate mofetil(MMF) without antiviral therapy and were monitored for BKV every 3-6 months. All the patients were followed for 5 years. Results:Overall 5-year patient survival was 95.6% and graft survival was 92.1%. There were no differences in patient/graft survival, renal function, and rejection rate by presence of decoy cells, BK-viruria, viremia, or BKVAN. Multivariate analysis showed that Tac(OR, 2.9; P=0.032)and deceased kidney donation(OR, 2.1; P=0.071) were risk factors for BK viremia. After reduction of immunosuppression, viremia (n=38) resolved in 100%, without increased acute rejection. In the duration of follow-up 2-5 posttransplant years, BK viremia was not observed again in the BK viremic patients (n=30) without BKVAN. BKVAN was diagnosed in 7 cases(3.1%). The treatment of immunosuppression reduction was effective. All the BKVAN patients cleared viremia with a mean time of 5.9 months (range 1-15 months). Three of 7 BKVAN patients cleared viruria. A repeated renal biopsy was performed in two patients and revealed resolving BKVAN. There was no decline in estimated glomerular filtration rate over time from1 month(53.1mL/min) to 5 years(58.5mL/min) after transplantation (P=0.960). Conclusions:Monitoring and preemptive of immunosuppression reduction resulted in the successful resolution of BK viremia, showed effective in BKVAN recipients at the early stage with excellent graft survival and renal function at 5-years.
Non-small cell lung cancer (NSCLC), although considered non-immunogenic, is often resistant to chemotherapy agents during the course of treatment in clinical patients. Melittin (C
To explore the clinical diagnosis of BK virus (BKV) infection in renal transplant recipients.Urine and peripheral blood samples were taken from 234 renal transplant recipients for BKV detection with cytological test and real-time PCR.The occurrence rate of urine decoy cells, BKV viruria and viremia in these patients was 33.3 %, 33.3% and 16.2%, respectively, and the median level of urine decoy cells was 6/10 HPF, with the median level of urine and peripheral blood BKV of 7.62 x 10(3) copy/ml and 7.61 x 10(3) copy/ml, respectively. The positivity rate of BKV in the urine samples were significantly higher than that in peripheral blood samples (P=0.000). The amount of decoy cells was related to BKV load in the urine samples (gamma=0.59, P=0.000), but the BKV load in the urine samples was not related to that in peripheral blood samples (P=0.14).Renal transplantation is associated with increased BKV shedding, indicating the necessity of BKV monitoring in renal transplant recipients with urine cytology, which is convenient and sensitive and indicates renal histological changes indirectly. Urine and peripheral blood BKV DNA detection is of value in identifying BKV activation to prevent irreversible graft damage of BKV-associated nephropathy.
BK virus-associated nephropathy (BKVN) is an important cause of chronic allograft dysfunction. The objective of our study was to evaluate the prognosis of BKVN.We retrospectively reviewed the data of 133 renal transplant recipients with BKVN treated at the First Affiliated Hospital of Sun Yat-Sen University between July 2007 and July 2017. BK viral loads, graft function, and pathologic indexes were compared between initial diagnosis and last follow-up.After a mean follow-up period of 14.4 (range, 0.3-109.6) months after diagnosis of BKVN, BK viruria, and BK viremia become negative in 19.5% and 90.2% of patients, respectively. The mean estimated glomerular filtration rate (eGFR) at last follow-up was lower than at diagnosis of BKVN (18.3 ± 9.2 vs. 32.8 ± 20.6 mL·min·1.73 m, t = 7.426, P < 0.001). Eight (6.0%) patients developed acute rejection after reducing immunosuppression. At last follow-up, the eGFR was significantly lower in patients with subsequent rejection than those without (21.6 ± 9.8 vs. 33.5 ± 20.9 mL·min·1.73 m, t = 3.034, P = 0.011). In 65 repeat biopsies, SV40-T antigen staining remained positive in 40 patients and became negative in the other 20 patients. The eGFR (42.6 ± 14.3 vs. 26.5 ± 12.3 mL·min·1.73 m), urine viral loads (median, 1.3 × 10vs. 1.4 × 10 copies/mL), and plasma viral load (median, 0 vs. 0 copies/mL) were all significantly lower in patients with negative SV40-T antigen staining than those with persistent BK involvement (all, P < 0.05). Five (3.8%) recipients lost their graft at diagnosis of BKVN, and 13 (9.8%) lost their graft during the follow-up period. The 1-, 3-, and 5-year graft survival rates after diagnosis of BKVN were 99.2%, 90.7%, and 85.7%, respectively. Higher pathologic stage correlated with lower allograft survival rate (χ = 6.341, P = 0.042).Secondary rejection and persistent histologic infection in BKVN lead to poor prognosis.
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