Objective　To evaluate the technique and clinical outcomes of modified transperitoneal laparoscopic radical prostatectomy.　Methods　A total of 285 patients received the operation with mean age of 67 years (50-76 years) from January 2008 to April 2012.Mean level of PSA was 15.7 μg/L (1.8 -50.0 μg/L),and mean prostatic volume was 44 ml (26 -74 ml). No lymph node or seminal vesicle involvement was found by CT or MR and radionuclide bone scan revealed no metastasis.271 cases were confirmed diagnosis by prostatic biopsy and 14 were detected through pathological studies of TURP specimens.Gleason score ranged from 6 to 8.14 cases were in clinical stage T1b,29 cases in T1c,214 cases in T2 and 28 cases in T3a.Transperitoneal approach and modified technique involving bladder neck dissection,nervesparing technique and vesicoureteral anastomosis were applied on patients.　Results　Mean operative time was 105 min (55 -150 min).Mean intraoperative estimated blood loss was 240 ml (50-800 ml).Rectal injures occurred in 2 cases and were repaired under laparoscopy.Drainage tube and urinary catheter were removed 48 -72 h and 5 -8 d postoperatively.Postoperative hospital stay was 7 d (5 - 11 d).Positive surgical margin was present in 58 patients.Mean follow-up time was 29 months (3 -50 months).Complete continence were found in 208 patients immediately after catheter removal.68 patient recovered continence within 3 months and 9 patients remained incontinence 3 months after surgery. Normal erection presented in 42 of the 57 cases with nerve-sparing.　Conclusions　Transperitoneal laparoscopic radical prostatectomy is safe and efficient.Higher efficiency and lower complication rate have been achieved through modified laparoscopic technique involving bladder neck dissection,nerve-sparing technique and vesicoureteral anastomosis.

MicroRNAs (miRNAs) are important diagnostic markers and therapeutic targets for many diseases. However, the miRNAs that control the pathogenesis of idiopathic pulmonary fibrosis (IPF) and act as potential therapeutic targets for the disease are rarely studied. In the present study, we analyzed the function and regulatory mechanism of microRNA-708-3p (miR-708-3p) and evaluated this marker’s potential as a therapeutic target in IPF. The clinical and biological relevance of fibrogenesis for miR-708-3p was assessed in vivo and in vitro, specifically in matching plasma and tissue samples from 78 patients with IPF. The data showed that the miR-708-3p levels decreased during fibrosis and inversely correlated with IPF. The experiments showed that the decreased miR-708 promoter activity and primer-miR-708(pri-miR-708) expression were the potential causes. By computational analysis, a dual luciferase reporter system, rescue experiments and a Cignal Finder 45-Pathway system with siADAM17 and a miR-708-3p mimic, we identified that miR-708-3p directly regulates its target gene, a disintegrin and metalloproteinase 17 (ADAM17), through a binding site in the 3′ untranslated region, which depends on the GATA/STAT3 signaling pathway. Finally, an miR-708-3p agomir was designed and used to test the therapeutic effects of the miR-708-3p in an animal model. Small-animal imaging technology and other experiments showed that the dynamic image distribution of the miR-708-3p agomir was mainly concentrated in the lungs and could block fibrogenesis. In conclusion, the miR-708-3p–ADAM17 axis aggravates IPF, and miR-708-3p can serve as a potential therapeutic target for IPF.

Both cholinergic dysfunction and protein citrullination are the hallmarks of rheumatoid arthritis (RA), but the relationship between the two phenomena remains unclear. We explored whether and how cholinergic dysfunction accelerates protein citrullination and consequently drives the development of RA. Cholinergic function and protein citrullination levels in patients with RA and collagen-induced arthritis (CIA) mice were collected. In both neuron-macrophage coculture system and CIA mice, the effect of cholinergic dysfunction on protein citrullination and expression of peptidylarginine deiminases (PADs) was assessed by immunofluorescence. The key transcription factors for PAD4 expression were predicted and validated. Cholinergic dysfunction in the patients with RA and CIA mice negatively correlated with the degree of protein citrullination in synovial tissues. The cholinergic or alpha7 nicotinic acetylcholine receptor (α7nAChR) deactivation and activation resulted in the promotion and reduction of protein citrullination in vitro and in vivo, respectively. Especially, the activation deficiency of α7nAChR induced the earlier onset and aggravation of CIA. Furthermore, deactivation of α7nAChR increased the expression of PAD4 and specificity protein-3 (SP3) in vitro and in vivo. Our results suggest that cholinergic dysfunction-induced deficient α7nAChR activation, which induces the expression of SP3 and its downstream molecule PAD4, accelerating protein citrullination and the development of RA.