Structure-based design, synthesis, and biological evaluation of novel pyrimidinone derivatives as PDE9 inhibitors

The pathological processes of Alzheimer's disease and type 2 diabetes mellitus have been demonstrated to be linked together. Both PDE9 inhibitors and PPAR agonists such as rosiglitazone exhibited remarkable preclinical and clinical treatment effects for these two diseases. In this study, a series of PDE9 inhibitors combining the pharmacophore of rosiglitazone were discovered. All the compounds possessed remarkable affinities towards PDE9 and four of them have the IC values <5 nmol/L. In addition, these four compounds showed low cell toxicity in human SH-SY5Y neuroblastoma cells. Compound , the most effective one, gave the IC of 1.1 nmol/L towards PDE9, which is significantly better than the reference compounds PF-04447943 and BAY 73-6691. The analysis of putative binding patterns and binding free energy of the designed compounds with PDE9 may explain the structure-activity relationships and provide evidence for further structural modifications.

Progress on pain control during the perioperative period of shoulder arthroscopy / 中国骨伤

Successful pain management of perioperative shoulder arthroscopy may allow patients to go home earlier, improve the quality of life in perioperative period, and facilitate rehabilitation. A comprehensive method to perioperative pain control has three stages including preoperative, intraoperative and postoperative phase. Successful pain reduction should begin preoperatively because of an excellent communication between patient and physician, moreover, preoperative analgesia also should be administered. Intraoperative efforts should include local wound infiltration and the administration of anesthetic medication intra-articularly. Postoperative management should include oral analgesics, constant infusion devices, Patient Controlled Analgesia (PCA), sedative-hypnotic drug, continuous cryotherapy and vicarious treatment.

Arthroscopic rotator cuff repair using a suture-bridge technique in late middle-aged adults / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate the clinical results after arthroscopic rotator cuff repair using a suture-bridge technique in late middle-aged adults.</p><p><b>METHODS</b>A retrospective analysis of 30 patients with rotator cuff tears, who were treated consecutively between December 2012 and December 2013 at our clinic, was carried out to evaluate the outcome of arthroscopic suture-bridge technique. The visual analogue scale (VAS), the range of motion (ROM), the rating scale of the University of California at Los Angeles (UCLA), and the shoulder index of the American Shoulder and Elbow Surgeons (ASES) were determined as the evaluation criteria.</p><p><b>RESULTS</b>The mean follow-up period was 13 months. The follow-up rate was 100%. The study included 0 small, 16 medium, 12 large and 2 massive rotator cuff tears. At the latest follow-up, the VAS score decreased significantly from preoperative 6.3±3.2 to 0.8±1.4 at rest,and from preoperative 7.7±2.1 to 1.7±1.6 during motion. The UCLA score improved significantly from 15.1±4.6 preoperatively to 31.2±5.0 at follow-up. The ASES shoulder index improved significantly from 30.2±16.0 preoperatively to 80.4±13.0 at follow-up. The ROM improved significantly. The satisfactory rate was 94%. There were no complications.</p><p><b>CONCLUSION</b>The results of this study indicate that the arthroscopic suture-bridge technique is an effective and reliable treatment for patients with rotator cuff tear in late middle-aged adults.</p>