Tauopathies, including Alzheimer's disease (AD), are a series of neurodegenerative diseases characterized by pathological accumulation of the microtubule-associated protein tau. Since the abnormal modification and deposition of tau in nerve cells are crucial for tauopathy etiology, methods for reducing tau levels, such as promoting tau degradation, may become effective strategies for disease treatment. Herein, we identified that sorafenib significantly reduced total tau and phosphorylated tau levels through screening FDA-approved drugs. We showed that sorafenib treatment attenuated cognitive deficits and tau pathologies in PS19 tauopathy model mice. Mechanistically, we found that sorafenib inhibited multiple kinases involved in tau phosphorylation and promoted autophagy. Importantly, we further demonstrated that sorafenib also promoted the expression of the E3 ubiquitin ligase FBXW7, which could bind tau and mediate tau degradation through the ubiquitin-proteasome pathway. Finally, we showed that FBXW7 expression decreased in the brains of AD patients and tauopathy model mice, and that overexpression of FBXW7 in the hippocampus attenuated cognitive deficits and tau pathologies in PS19 mice. These results suggest that sorafenib may be a promising treatment option for tauopathies by promoting tau degradation and reducing tau phosphorylation, and that targeting FBXW7 could also serve as an alternative therapeutic strategy for tauopathies.

Mutations in the triggering receptor expressed in myeloid 2 (TREM2) gene have recently been found to be closely related to the development of Alzheimer's disease (AD) and other neurodegenerative diseases. However, the detailed mechanism underlying TREM2's participation in the pathogenesis of AD and other diseases has yet to be fully elucidated. In this review, we discuss current understanding on the structure and function of TREM2, the relevance between TREM2 and AD, and the possible causes of AD by TREM2 mutations.

Objective To explore the effect of bladder muscle flaps for long segment defect of ureter middle-lower segment and reconstruction method in laparoscopic surgery. Methods Clinical data of 3 patients with long segment defect of ureter middle-lower segment, all of whom underwent laparoscopic surgery from May 2014 to April 2016 was retrospectively evaluated. There were 1 male and 2 females, in 2 cases with history of ureteroscopy holmium laser lithotripsy in ureter middle-lower segment, in 2 cases with history of repeated ESWL. Preoperative urinary tract ultrasound, CT and intravenous urography imaging showed severe hydronephrosis, ureter middle-upper segment severe hydroureter, ureter middle-lower segment severe stricture. Results Operations were successful in 3 cases. After reconstruction bladder muscle flaps average length of is 9.6 cm, The average operation time of 180 min, The average length of hospital stay for 10 d, Postoperative eighth weeks extracted the double J tube and used ureteroscopy showed anastomotic unobstructed, it may smooth Through 8.5 F ureteroscopy, and no infection and urinary leakage occurred, Follow-up ranged from 3 to 18 months. 3 cases hydronephrosis and hydroureter significantly reduce, ureter unobstructed, no narrow in ureter and muscle flap of tube joint, serum creatinine valueswere in normal range. Conclusions The bladder muscle flaps for the treatment of long segment defect of ureter middle-lower segment in laparoscopic surgery was a safe and effective therapy, but it must be accomplished by seasoned doctors.

Objective To explore the efficacy and safety of Transurethral vaporization of the prostate using 1 470 nm diode laser in treatment of BPH.Methods 58 cases BPH patients underwent transurethral vaporization of the prostate using 1 470 nm diode laser from Dec. 2015 to Apr. 2016 were retrospectively analyzed, including the mean operation time and compared hemoglobin, electrolyte, urinary symptoms, before and after surgery.Result Operations were successfully performed in all the 58 cases, with average operation time of (48.2 ± 16.3) min. No difference was found in either hemoglobin decrease or electrolyte decrease before and after surgery. The patients were followed up for 1~3 months, which revealed a signiifcant reduction in IPSS and improvement in Qmaxand PVR (P < 0.05), compared with pre-operation. No severe complications were reported, including transurethral resection (TUR) syndrome, urinary incontinence and impaired erectile function.Conclusion Transurethral vaporization of the prostate using 1 470 nm diode laser is a safe and effective therapy for BPH. It has advantages of short learning curve, very little blood loss, high efifcacy. It has promising broad prospects.

ObjectiveTo understand the pathological and physiological roles of Presenilin 1 (PS1) in Alzheimer's disease (AD) recurrence, and the interaction between PSI and carhoxyl terminus of Hsc70 interacting protein (CHIP). MethodsThe yeast two-hybrid system was applied to identify a novel PS1 interacting protein as CHIP. After pGBKT7-PS1-C203 bait plasmid and full fragement CHIP of pACT2-CHIP expression vector were constructed, the interaction between PSI and CHIP was tested by β-galactosidase assay, pGBKT7-PS1-C203 was co-transfected with pACT2-CHIP into 293T cells and the interaction between PS1 and CHIP was tested by co-immunoprecipitation and Western blot. ResultsSpecificity of the interaction between PS1 and CHIP was identified by β-galactosidase assay and co- immunoprecipitation. ConclusionsCHIP is able to modulate chaperone functions and the pathway of protein ubiquitination/degradation. CHIP may regulate a proper assembly of the γ-secretase complex through its interaction with PSI, which is helpful to elucidate the mechanism of AD pathology.