Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

Objective A finite element analysis was conducted on the biomechanics of the locking plate and intramedullary nail fixation for the treatment of distal tibial fractures,and the resuhs were verified combined with clinical cases,so as to provide references for clinical treatment.Methods (1) Finite element analysis:the three-dimensional CT data of the lower limbs of a healthy male volunteer were used to establish a finite element model.The internal stress distribution of the tibial plateau was set to 60％ of the total load by intramedullary nail and locking plate respectively,and the tibia end was fixed effectively.400 N axial pressure load which equaled to that of adult knee joint during single axis standing was simulated.The equivalent stress and displacement of the model by different fixations were compared.(2) Clinical verification:a retrospective case control study was performed on the clinical data of 37 cases of distal tibia1 fractures treated with internal fixation from June 2015 to December 2016,including 17 cases in intramedullary nail group and 20 in locking plate group.The operation time,intraoperative blood loss,postoperative fracture healing time,and postoperative Johner-Wruhs score of patients were recorded for comprehensive assessment of recovery.Results (1) The finite element analysis results:the maximum stress value was 5.907 MPa for intramedullary nail and 5.821 MPa for locking plate model (P ＞0.05),respectively.The maximum displacement of intramedullary nail model was 2.313 mm,lower than that of locking plate fixation system (3.854 rmm) (P ＜ 0.05).(2) Clinical verification:the operation time and intraoperative blood loss of intramedullary nail were both lower than those of locking plate [(114.1 ±21.6)minutes):(129.8±21.4)minutes and (152.9 ±64.88)ml:(212.5 ±98.5)ml](P ＜0.05).The average fracture healing time was (17.7 ± 2.8)weeks for intramedullary nail and (20.6 ± 4.1) weeks for locking plate (P ＜ 0.05),respectively.In the intramedullary nail group,the Johner Wruhs score was excellent in 13 cases and good in four cases,with excellent and good rate of 100％,while in the locking plate group,nine cases were excellent,eight were good,and three were fair,with excellent and good rate of 85％ (P ＞ 0.05).Conclusions In terms of biomechanics and clinical effect,intramedullary nail fixation is superior than the medial locking plate fixation for the treatment of the distal tibial fractures.Intramedullary nail fixation can reduce surgical trauma and bone displacement after fixation and promote fracture healing.

Objective:To observe the efficacy of saiga horn capsule combining with benazapril on blood pressure variability,pulse pressure and left ventricular mass in elderly patients with isolated systolic hypertension (ISH).Methods:78 elderly patients with ISH were treated with saiga horn capsule combining with benazapril for 4 months.We compared the change of 24hours systolic blood pressure (SBP),24hours diastolic blood pressure (DBP),pulse pressure (PP) and left ventricular mass.Results:After four months treatment,reduction of 24 hour SBP variability,day SBP variability,DBP variability,night SBP variability day,24 hour and day average BP variability,pulse pressure and left ventricular mass had statistical signifi cance (P0.05).Conclusion:The elderly patients with ISH treated with saiga horn capsule and benazapril can lower blood pressure,pulse pressure more effective,therefore protect target organ better than with benazapril only.

In this paper, the implementation scheme for a hospital's data backup and recovery is introduced. It analyzes the goal of system design: to build a centralized, policy-based administration, automatic and high efficient data backup system.
Hospital Information Systems ; organization & administration ; Humans ; Medical Records Systems, Computerized ; organization & administration ; Work Simplification