LDC000067 suppresses RANKL-induced osteoclastogenesis in vitro and prevents LPS-induced osteolysis in vivo.

Bone homeostasis requires a dynamic balance between osteogenesis and osteoclastogenesis, and osteolytic disorders are mainly attributed to aberrant osteoclastogenesis and bone resorption. Accumulating evidence has demonstrated that cyclin-dependent kinase 9 (CDK9) regulates some inflammatory diseases without affecting the cell cycle. Whether the specific inhibitor of CDK9, LDC000067 (abbreviated as LDC067), helps to prevent from osteolytic disorders has not been fully elucidated. Interestingly, this study demonstrated that LDC067 inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption in vitro, and suppressed the expression of osteoclast-related marker genes such as cathepsin K (CTSK), tartrate-resistant acid phosphatase (TRAP), dendrite cell-specific transmembrane protein (DC-STAMP), V-ATPase D2, calcitonin receptor (CTR) and nuclear factor of activated T cells cytoplasmic 1 (NFATc1). The bone protective effects of LDC067 can be partly explained by its suppression of nuclear factor-kappa B (NF-κB)-mediated NFATc1 activation via AKT signalling pathway. In keeping with the results obtained in vitro, inhibition of CDK9 with LDC067 was observed to delay subchondral osteolysis and substantially ameliorate LPS-induced osteolysis in murine calvaria. Collectively, these results highlight the positive effects of LDC067 in preventing osteolytic disorders and indicate that this CDK9 inhibitor may a promising therapeutic agent.

[Failure of internal fixation on displaced femoral neck fractures in adults under fifty-five years old].

OBJECTIVE: To investigate the failure of internal fixation on displaced femoral neck fractures in adults under fifty-five years old retrospectively inorder to pay more attention to the treatment of these fractures. METHODS: From Junary 2007 to June 2010,18 failed cases of internal fixation on displaced femoral neck fractures in adults under fifty-five years old were treated,there were 13 males and 5 females with an average age of (48.0 +/- 6.0) years old ranging from 27 to 55. Among them, 17 patients were treated with cannulated screws and 1 patient was treated with intramedullary nail; 16 patients were diagnosed as osteonecrosis and 2 patients as osteonecrosis associated with nonunion. RESULTS: The average time from internal fixation to failure was 23 months (ranged, 8 to 32 months). The quality of fracture reduction in Garden index was poor. The Harris Hip Score was (56.0 +/- 12.5) (ranged,33 to 80). Eight cases of osteonecrosis and 2 cases of nonunion combinated osteonecrosis were received total hip arthroplasty. Hip resurfacing arthroplasty were performed for other 5 osteonecrosis. Because of no evident clinical symptoms,the other 3 cases received conservative treatment. The patients with total hip arthroplasty and hip resurfacing arthroplasty were followed-up for 34 months ranging from 12 to 53 months. After operation,the Harris score was (94.0 +/- 3.0) ranged 89 to 96. CONCLUSION: Osteonecrosis is a common complication after internal fixation on displaced femoral neck fracture in adults under fifty-five years old. More attention should be paid to the treatment of displaced femoral neck fracture in those patients.

Differences in portal hemodynamics between whole liver transplantation and living donor liver transplantation.

The aim of this study was to investigate the differences in portal hemodynamics between whole liver transplantation and living donor liver transplantation (LDLT). Twenty patients who underwent LDLT (the L group) and 42 patients who underwent whole liver transplantation (the W group) were enrolled, and colored Doppler ultrasonography was performed preoperatively and on postoperative days (PODs) 1, 3, 5, 7, 30, and 90. The changes in the portal blood flow velocity (PBV) and portal blood flow volume (PBF) were monitored. The graft and spleen sizes were measured with angiographic computed tomography, and upper endoscopy was used to measure esophageal varices on PODs 14, 30, and 90. Although the portal venous pressure (PVP) decreased after graft implantation, it was higher in the L group with a smaller graft size ratio (25.7 ± 5.1 cm H2O for the L group and 18.5 ± 4.6 cm H2O for the W group, P < 0.05). PBF and PBV increased in both the W and L groups on POD 1 after transplantation; however, the PBF and PBV peaks were significantly higher in the W group. The postoperative PVP and graft volume were greatly related to PBF on POD 1. Grafts in the L group regenerated rapidly after the operation, and the volume increased from 704 ± 115 to 1524 ± 281 mL as early as 1 month after transplantation. A rapid improvement in splenomegaly was observed in both groups. An improvement in esophageal varices was observed in the W group on POD 14 after transplantation, whereas no change was observed in the L group. The portal venous flow in patients with portal hypertension showed a high perfusion state after LDLT, but in contrast to whole liver transplantation, the PVP elevation after LDLT postponed the closing time of the collateral circulation and affected the recovery from splenomegaly.

Treatment of aseptic diaphyseal nonunion of the lower extremities with exchange intramedullary nailing and blocking screws without open bone graft.

OBJECTIVE: To report the preliminary results of the treatment of aseptic diaphyseal nonunion of the lower extremities with exchange nailing plus blocking screws. METHODS: Between June 2005 and September 2008, twelve patients with diaphyseal nonunion in the lower extremities (femur in five patients and tibia in seven; hypertrophic nonunion in eight patients and atrophic nonunion in four) were treated by reaming, exchanging the original intramedullary nail with a larger one, and using blocking screws, and the therapeutic effect assessed. RESULTS: All patients were followed up for 1-2 years (average, 1.5 years) to assess union. Bony union was achieved in all patients within 4.7-13.5 months (average, 7.8 months). All patients were pain free without any complications by the last follow-up. CONCLUSION: The therapeutic method of exchanging the nail combined with blocking screws is effective for aseptic nonunion of the lower extremity after intramedullary nailing.

[Comparison of nitrogen loss via surface runoff from two agricultural catchments in semi-arid North China].

Nitrogen loss characteristics via surface runoff from two typical agricultural catchments into Yuqiao Reservoir--the important drinking water source area for Tianjin city in semi-arid North China were investigated through two-year in-situ monitoring and indoor chemical analysis. The results showed that annual nitrogen export mainly concentrated in the rainy period between June to September. About 41% of the annual water output and 52% of the annual total nitrogen output took place in two rainfall events with rainfall> 60 mm in Taohuasi catchment (T catchment), while the distribution of water and nitrogen export among various rainfalls in Caogezhuang catchment (C catchment) was smooth. The rainfall thresholds for the appearance of water and nitrogen export from the outlet of T catchment and C catchment were 20 mm and 10 mm. The mean annual runoff coefficients of C and T catchments were 0.013 2 and 0.001 6, respectively. The mean annual total nitrogen exports from C catchment and T catchment were 1.048 kg x (hm2 x a)(-1) and 0.158 kg x (hm2 x a)(-1) respectively. The difference of micro-topography, landscape pattern and hydrological pathway between two catchments could explain the nitrogen export gap. Micro-topographical features created by long-term anthropological disturbance decrease the runoff generation ability. The distance between nitrogen source area and the outlet in T catchment was around 1 500 m, while such distance in C catchment was just around 200 m. The short distance added the nitrogen export risk via surface runoff. Road-type hydrological pathway in C catchment could transfer nitrogen into the receiving water via surface runoff directly, while nitrogen could be detained within the pathway by many sink structures such as small stones, vegetated buffer strip and dry ponds in T catchment.

Size-dependent surface tension and Tolman's length of droplets.

A model for the size-dependent surface tension gammalv(D) of liquid droplets, free of any adjustable parameter, is presented in terms of the size-dependent surface energy gammasv(D). It is found that gammalv(D) drops monotonically with the size of the droplet in the nanometer region. Modeling predictions agree with computer simulations for sodium, aluminum, and water droplets. Meanwhile, the Tolman's equation is found to be valid for small particles, and the Tolman's length is always positive and becomes longer when the droplet size is decreased.