TMEM43-S358L mutation enhances NF-κB-TGFβ signal cascade in arrhythmogenic right ventricular dysplasia/cardiomyopathy

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a genetic cardiac muscle disease that accounts for approximately 30% sudden cardiac death in young adults. The Ser358Leu mutation of transmembrane protein 43 (TMEM43) was commonly identified in the patients of highly lethal and fully penetrant ARVD subtype, ARVD5. Here, we generated TMEM43 S358L mouse to explore the underlying mechanism. This mouse strain showed the classic pathologies of ARVD patients, including structural abnormalities and cardiac fibrofatty. TMEM43 S358L mutation led to hyper-activated nuclear factor κB (NF-κB) activation in heart tissues and primary cardiomyocyte cells. Importantly, this hyper activation of NF-κB directly drove the expression of pro-fibrotic gene, transforming growth factor beta (TGFβ1), and enhanced downstream signal, indicating that TMEM43 S358L mutation up-regulates NF-κB-TGFβ signal cascade during ARVD cardiac fibrosis. Our study partially reveals the regulatory mechanism of ARVD development.

The recovery of the renal function in the severe hydronephrosis children after percutaneous nephrostomy / 中华泌尿外科杂志

Objective To analyze the recovery of the renal function in the severe hydronephrosis children after percutaneous nephrostomy.Methods 50 cases of uretero-pelvic junction obstruction (UPJO) children were retrospectively studied from January 2013 to January 2016.There were 25 boys and 25 girls,and the mean age was 3.0 years (ranged from 2 months to 9 years and 7 months).The children were taken the percutaneous nephrostomy in the first stage and pyeloplasty or nephrectomy in the second stage according to the recovery of renal function.Split renal function,urine osmotic pressure,urine pH and urine β2-microglobulin (β32-MG) were compared between pre-operation and post-operation.The recovery of the renal function after the operation were evaluated by the single photon emission computed tomography (SPECT) and superb micro-vascular imaging (SMI) to analysis the feasibility of the pyeloplasty surgery in the severe hydronephrosis children.Result The postoperative renal function of 49 patients in the group recovered after percutaneous nephrostomy,only one child showed unrecoverable.After the first stage management,the renal cortical thickness [(5.9 ± 1.0)mm vs.(2.9 ± 0.9) mm,P =0.03],the separate renal function mmo]/L vs.(126.5 ± 100.5) mmol/L,P ＜ 0.001] were significantly improved compared with preoperation,andRI [(0.72 ±0.03) vs.(0.79 ±0.04),P=0.021],urine pH [(6.18±0.21) vs.(7.38 ± 0.32),P =0.039] and urine β2-MG [(562.16 ± 49.78) mg/L vs.(954.28 ± 69.45) mg/L,P ＜0.001] significantly reduced.Conclusions The renal function of the severe hydronephrosis children could be recoverable after the surgery of the percutaneous nephrostomy and pyeloplasty.Most children's kidneys suffered the severe hydronephrosis could be spared by surgery.SMI technology could provide reliable quantitative basis to evaluate renal function.

Tumor necrosis factor-related apoptosis-inducing ligand and its receptors in lung cancer therapy / 国际肿瘤学杂志

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a newly discovered apoptosis-inducing ligand that can induce apoptosis of cancer cells, but not of normal cells, through the activation of multiple signaling transduction pathways. By sensitizing lung cancer cells but not normal cells to apoptosis,TRAIL may become a new strategy for the treatment of lung cancer.

Minimally invasive surgical procedures treated urinary calculi caused by melamine in infants / 中华泌尿外科杂志

Objective To report experience of minimally invasive surgery of urinary calculi caused by melamine in infants. Methods Retrospectively reviewed the treatments and outcomes of 36 cases with urinary calculi caused by melamine from November 2007 to October 2008. 13 girls and 23 boys aged 8 to 36 months after daily consumption for six month or more of milk products tainted with melamine. These infants underwent MPCNL, ureteroscopic lithotripsy and placement of ureteral stent, respectively. Results The operations were performed successfully in all patients. Five cases underwent MPCNL. Ureteroscopic lithotripsy were performed in fourteen cases. Seventeen cases were placed of ureteral stents. No major complications like hemorrhea, perforation and organic injury were noted. The postoperative hospital stays were 3 to 10 days. All cases were followed up for 1 to 12 months. Calculus had no recurrence. Hydronephrosis and hydroureterosis disappeared or lightened. Growth and development were normal. Conclusions Various kinds of minimally invasive surgical procedures is safe and effective treatments for urinary calculi caused by melamine in infants, applicable in calculi with urinary obstruction especially.