Neural Crest‐Specific TSC1 Deletion in Mice Leads to Sclerotic Craniofacial Bone Lesion

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in either TSC1 or TSC2. TSC has high frequency of osseous manifestations such as sclerotic lesions in the craniofacial region. However, an animal model that replicates TSC craniofacial bone lesions has not yet been described. The roles of Tsc1 and the sequelae of Tsc1 dysfunction in bone are unknown. In this study, we generated a mouse model of TSC with a deletion of Tsc1 in neural crest‐derived (NCD) cells that recapitulated the sclerotic craniofacial bone lesions in TSC. Analysis of this mouse model demonstrated that TSC1 deletion led to enhanced mTORC1 signaling in NCD bones and the increase in bone formation is responsible for the aberrantly increased bone mass. Lineage mapping revealed that TSC1 deficient NCD cells overpopulated the NCD bones. Mechanistically, hyperproliferation of osteoprogenitors at an early postnatal stage accounts for the increased osteoblast pool. Intriguingly, early postnatal treatment with rapamycin, an mTORC1 inhibitor, can completely rescue the aberrant bone mass, but late treatment cannot. Our data suggest that enhanced mTOR signaling in NCD cells can increase bone mass through enlargement of the osteoprogenitor pool, which likely explains the sclerotic bone lesion observed in TSC patients. © 2015 American Society for Bone and Mineral Research.     

Impact of gender on the clinicopathological features of patients with primary IgA nephropathy

Objective To explore the impact of gender on the clinicopathological features of patients with primary IgA nephropathy (IgAN). Methods All patients with IgAN who were biopsy-proven in The First Affiliated Hospital, Sun Yat-sen University from January 2006 to December 2011 were divided into two groups by gender: male group and female group. The clinical manifestations and pathological features of two groups were retrospectively investigated and compared. Results A total of 1512 primary IgAN patients were enrolled in the study, and the ratio of male to female was 1∶1.16, with a median age of 32(26, 39) years old at biopsy. Compared to female patients, male patients with IgAN exhibited more severe clinical manifestations including worse renal function, greater urinary protein excretion, and more frequent occurrence of hypertension, hypertriglyceridemia and hyperuricemia. Besides, male patients had worse histological lesions, including more severe segmental sclerosis, tubular-atrophy/interstitial fibrosis and interstitial infiltration. For female patients, hematuria, including gross and microscopic hematuria, was more frequent. Conclusion Male patients with IgAN were with worse clinicopathological changes than those of female.     

Time-average albumin predicts the long-term prognosis of IgA nephropathy patients achieved remission

Objective To clarify the long-term renal prognosis and related risk factors of progression for IgA nephropathy (IgAN) patients who achieved remission under current therapy. To identify the target value of the serum albumin level for Chinese patients with IgAN. Methods The patients with biopsy-proven primary IgAN in Nephrology Department of Renji Hospital in Shanghai were studied．The survival of renal and the relationships between clinical parameters and renal outcome were assessed. Results A total of 369 patients between Jan 2005 and Dec 2010 were included with a median follow-up time of 49.0 (38.0-65.8) months. All the subjects had achieved a complete remission (CR) or partial remission (PR) following six months’ therapy after diagnosis. Progressive renal disease had occurred in 61 cases at the end of follow-up. Three variables had a significant independent effect on renal outcome in patients achieving remission under current therapy regimen for IgAN, including time-average serum creatinine (TA-Scr) [HR(95%CI): 1.03(1.01-1.04)], time-average serum albumin (TA-Alb) [HR(95%CI): 0.83 (0.69-0.99)], and eGFR ratio within one year [HR(95%CI): 0.00(0.00-0.01)]. By multivariate Cox analyses, each 1 g/L drop of TA-Alb was related with 17.2% increase in the risk of renal progression. The ROC curve indicated that combination of serum albumin at baseline and during a long-term had a more significant value in prediction of renal outcome than independent predictor alone. By Kaplan-Meier analyses, patients with TA-Alb﹤38 g/L had a 10.4 fold sincreased risk of progressive disease compared with that of TA-Alb﹥38 g/L. Conclusions IgAN patients with lower eGFR ratio, higher TA-Scr and lower TA-Alb would progress to ESRD more quickly, and serum albumin during follow-up is important for predicting IgAN progression.     

Basilar artery on computed tomography angiography score and clinical outcomes in acute basilar artery occlusion

Journal of Neurology - This study aimed to evaluate the safety and efficacy of mechanical thrombectomy (MT) in patients with acute basilar artery occlusion (BAO) based on the baseline Basilar...     

Effectiveness and acceptability of a multidisciplinary approach in improving the care of patients with advanced chronic kidney disease: a pilot study

International Urology and Nephrology - This study aimed at determining the feasibility of conducting a large-scale pragmatic effectiveness study on the implementation of multidisciplinary care...