Increasing the angle between caudal screw and the transverse plane may aggravate the risk of femoral head necrosis by deteriorating the fixation stability in patients with femoral neck fracture.

Necrosis of the femoral head is the main complication in femoral neck fracture patients with triangle cannulated screw fixation. Instant postoperative fixation instability is a main reason for the higher risk of femoral head necrosis. Biomechanical studies have shown that cross screw fixation can effectively optimize fixation stability in patients with proximal humerus fractures and pedicle screw fixation, but whether this method can also effectively optimize the fixation stability of femoral neck fractures and reduce the corresponding risk of femoral head necrosis has yet to be identified. In this study, a retrospective review of imaging data in femoral neck fracture patients was performed. The cross angle between the femoral neck and the caudal cannulated screw was reported; if the angle between the screw and the transverse plane increased, it was recorded as positive; otherwise, it was recorded as negative. Angle values and their corresponding absolute values were compared in patients with and without femoral head necrosis. Regression analysis identified potential risk factors for femoral head necrosis. Moreover, the biomechanical effect of the screw-femoral neck angle on fixation stability was also verified by numerical mechanical simulations. Clinical review presented significantly larger positive angle values in patients with femoral head necrosis, which was also proven to be an independent risk factor for this complication. Moreover, fixation stability progressively deteriorated with increasing angle between the caudal screw and the transverse plane. Therefore, increasing the angle between the caudal screw and the transverse plane may aggravate the risk of femoral head necrosis by deteriorating the fixation stability in patients with femoral neck fracture.

Portfolio Analysis of Research Grants in Data Science Funded by the National Heart, Lung, and Blood Institute.

Leveraging emerging opportunities in data science to open new frontiers in heart, lung, blood, and sleep research is one of the major strategic objectives of the National Heart, Lung, and Blood Institute (NHLBI), one of the 27 Institutes/Centers within the National Institutes of Health (NIH). To assess NHLBI's recent funding of research grants in data science and to identify its relative areas of focus within data science, a portfolio analysis from fiscal year 2008 to fiscal year 2017 was performed. In this portfolio analysis, an efficient and reliable methodology was used to identify data science research grants by utilizing several NIH databases and search technologies (iSearch, Query View Reporting system, and IN-SPIRE [Pacific Northwest National Laboratory, Richland, WA]). Six hundred thirty data science-focused extramural research grants supported by NHLBI were identified using keyword searches based primarily on NIH's working definitions of bioinformatics and computational biology. Further analysis characterized the distribution of these grants among the heart, lung, blood, and sleep disease areas as well as the subtypes of data science projects funded by NHLBI. Information was also collected for data science research grants funded by other NIH institutes/centers using the same search and analysis methodology. The funding comparison among different NIH institutes/centers highlighted relative data science areas of emphasis and further identified opportunities for potential data science areas in which NHLBI could foster research advances.

[Study on development and biomechanics test of plastic rod-hook plate].

OBJECTIVE: To develop a new type of internal fixation device which can be used to treat the minor avulsion fracture of the medial malleolus, lateral malleolus, the base of the fifth metatarsal, and the ulnar styloid process, and investigate the reliability and effectiveness of the device through biomechanical test. METHODS: Eighty human's bone specimens with complete medial malleolus, lateral malleolus, the base of the fifth metatarsal, and the ulnar styloid process were selected and measured the anatomic indexes (the height, width, and thickness of medial malleolus, lateral malleolus, the base of the fifth metatarsal, and the ulnar styloid process). The CT three-dimensional reconstruction data of 200 healthy adults which including medial malleolus, lateral malleolus, the base of the fifth metatarsal, and the ulnar styloid process was also selected and measured the anatomic indexes by Mimics software. The plastic rod-hook plate was designed according to the measured results and prepared. Forty fresh porcine lower limb specimens were randomly divided into groups A and B (20 in each group), and 8 adult lower limb specimens including 4 left and 4 right were also randomly divided into groups A and B (4 in each group). All specimens were prepared for avulsion fracture of medial malleolus. Then, the fractures were fixed with plastic rod-hook plate in group A and wire anchor in group B. The load and axial torsion test of ankle joint were carried out by universal biomechanical testing machine. RESULTS: According to the anatomical characteristics, a plastic rod-hook plate was designed successfully. The biomechanical test results between animal and human specimens were consistent. There was a linear relationship between load and displacement in the ankle distal load test. The displacement when loaded to the maximum load was significantly lower in group A than in group B ( P<0.05). The torsion angle and torque were significantly higher in group A than in group B when the internal fixation failed in the axial torsion test of the ankle joint ( P<0.05), and the torsion angle was significantly smaller in group A than in group B when the torque was 1 N·m ( P<0.05), and the maximum torque was also significantly higher in group A than in group B ( P<0.05). However, there was no significant difference in torsion angle between the two groups in the maximum torque ( P>0.05). CONCLUSION: The biomechanical properties of plastic rod-hook plate is obviously better than wire anchor, and the fixation of avulsion fracture with plastic rod-hook plate is easy to operate, which is expected to be used in the clinical treatment of minor avulsion fractures such as medial malleolus, lateral malleolus, base of the fifth metatarsal, and ulna styloid process.

Schizandrin A protects against cerebral ischemia-reperfusion injury by suppressing inflammation and oxidative stress and regulating the AMPK/Nrf2 pathway regulation.

Inflammation and oxidative stress are considered major factors in the pathogenesis of ischemic stroke. Increasing evidence has demonstrated that Schizandrin A (Sch A), a lignin compound isolated from Schisandra chinesnesis, exhibits prominent anti-inflammatory and antioxidant activities. In this study, we investigated the anti-inflammatory and antioxidant effects of Sch A against cerebral ischemia/reperfusion (I/R) injury as well as the underlying molecular mechanisms. Sch A treatment significantly improved the neurological score and reduced infarct volume 24 h after reperfusion. It dose-dependently inhibited the expression of cyclooxygenase-2 and inducible nitric oxide synthase, reduced the release of pro-inflammatory cytokines (tumor necrosis factor-α interleukin [IL]-1ß and IL-6), and increased anti-inflammatory cytokines (transforming growth factor-ß and interleukin-10). Furthermore, it increased the activity of superoxide dismutase and catalase, decreased reactive oxygen species production and 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine levels. Transcription of nuclear factor erythroid 2-related factor 2 (Nrf2) and downstream genes (heme oxygenase-1 and NAD[P]H: quinone oxidoreductase 1) increased. Knockdown of Nrf2 by siRNA inhibited the neuroprotective effects of Sch A. In addition, Sch A increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) both in vivo and in vitro. Activation of the Nrf2 pathway as well as the protective effects of Sch A in an oxygen and glucose deprivation-induced injury model was abolished by AMPK knockdown. Our study indicates that Sch A protects against cerebral I/R injury by suppressing inflammation and oxidative stress, and that this effect is regulated by the AMPK/Nrf2 pathway.

[Application of three-dimensional printing technology in treatment of internal or external ankle distal avulsed fracture].

Objective: To explore the effectiveness and advantage of three-dimensional (3D) printing technology in treatment of internal or external ankle distal avulsed fracture. Methods: Between January 2015 and January 2017, 20 patients with distal avulsed fracture of internal or external ankle were treated with the 3D guidance of shape-blocking steel plate fixation (group A), and 18 patients were treated with traditional plaster external fixation (group B). There was no significant difference in gender, age, injury cause, disease duration, fracture side, and fracture type between 2 groups ( P>0.05). Recording the fracture healing rate, fracture healing time, the time of starting to ankle functional exercise, residual ankle pain, and evaluating ankle function recovery of both groups by the American Orthopaedic Foot and Ankle Society (AOFAS) score. Results: All patients were followed up 8-24 months, with an average of 15.5 months. In group A: all incisions healed by first intention, the time of starting to ankle functional exercise was (14±3) days, fracture healing rate was 100%, and the fracture healing time was (10.15±2.00) weeks. At 6 months, the AOFAS score was 90.35±4.65. Among them, 13 patients were excellent and 7 patients were good. All patients had no post-operative incision infection, residual ankle pain, or dysfunction during the follow-up. In group B: the time of starting to ankle functional exercise was (40±10) days, the fracture healing rate was 94.44%, and the fracture healing time was (13.83±7.49) weeks. At 6 months, the AOFAS score was 79.28±34.28. Among them, 15 patients were good, 2 patients were medium, and 1 patient was poor. During the follow-up, 3 patients (16.67%) had pain of ankle joint with different degrees. There were significant differences in the postoperative fracture healing rate, fracture healing time, the time of starting to ankle functional exercise, and postoperative AOFAS score between 2 groups ( P<0.05). Conclusion: Application of 3D printing technology in treatment of internal or external ankle distal avulsed fracture is simple, safe, reliable, and effective. In particular, it is an ideal treatment for avulsed fracture.

Functional Assays to Screen and Dissect Genomic Hits: Doubling Down on the National Investment in Genomic Research.

The National Institutes of Health have made substantial investments in genomic studies and technologies to identify DNA sequence variants associated with human disease phenotypes. The National Heart, Lung, and Blood Institute has been at the forefront of these commitments to ascertain genetic variation associated with heart, lung, blood, and sleep diseases and related clinical traits. Genome-wide association studies, exome- and genome-sequencing studies, and exome-genotyping studies of the National Heart, Lung, and Blood Institute-funded epidemiological and clinical case-control studies are identifying large numbers of genetic variants associated with heart, lung, blood, and sleep phenotypes. However, investigators face challenges in identification of genomic variants that are functionally disruptive among the myriad of computationally implicated variants. Studies to define mechanisms of genetic disruption encoded by computationally identified genomic variants require reproducible, adaptable, and inexpensive methods to screen candidate variant and gene function. High-throughput strategies will permit a tiered variant discovery and genetic mechanism approach that begins with rapid functional screening of a large number of computationally implicated variants and genes for discovery of those that merit mechanistic investigation. As such, improved variant-to-gene and gene-to-function screens-and adequate support for such studies-are critical to accelerating the translation of genomic findings. In this White Paper, we outline the variety of novel technologies, assays, and model systems that are making such screens faster, cheaper, and more accurate, referencing published work and ongoing work supported by the National Heart, Lung, and Blood Institute's R21/R33 Functional Assays to Screen Genomic Hits program. We discuss priorities that can accelerate the impressive but incomplete progress represented by big data genomic research.

[COMPARATIVE STUDY ON FIXATION WITH PERCUTANEOUS CANNULATED SCREWS ASSISTED BY ROBOT NAVIGATION AND CONVENTIONAL SURGERY WITH MANUAL POSITIONING FOR FEMORAL NECK FRACTURES].

OBJECTIVE: To investigate the effectiveness and the advantage of fixation with percutaneous cannulated screws assisted by robot navigation in the treatment of femoral neck fractures by comparing with the conventional surgery. METHODS: Between January 2013 and December 2014, 20 patients with femoral neck fracture were treated by internal fixation with percutaneous cannulated screws assisted by robot navigation (navigation group), another 18 patients undergoing conventional surgery with manual positioning were chosen as the control group. There was no significant difference in gender, age, cause of injury, the injury side, time from injury to operation, and the classification of fractures between 2 groups (P > 0.05). The operation time, X-ray fluoroscopy time, blood loss, frequency of guide pin insertion, and healing time were recorded. At 1 week after operation, the parallel degree of screws was measured on the anteroposterior and lateral X-ray films; the Harris score was used to evaluate the hip function. RESULTS: All incisions of 2?groups healed by first intention after operation. There was no significant difference in operation time between 2?groups (t= -1.139, P=0.262). The blood loss, frequency of guide pin insertion, and X-ray fluoroscopy time of navigation group were significantly less than those of control group (P < 0.05). There were 2 screws penetrating into the joint cavity in control group. The patients were followed up 12-24 months with an average of 18 months. The navigation group got significantly better parallel degree of screws than control group on the anteroposterior and lateral X-ray films (t=25.021, P=0.000; t=18.659, P=0.000). Fractures healed in all patients of navigation group (100%), and the healing time was (21.8±2.8) weeks; fracture healed in 16 patients of control group (88.9%), and the healing time was (24.0 ± 3.7) weeks. There was no significant difference in healing rate and healing time between 2 groups (χ2=2.346, P=0.126; t=1.990, P=0.055). The Harris score of navigation group (87.1±3.7) was significantly higher than that of control group (79.3±4.7) at last follow-up (t= -5.689, P=0.000). CONCLUSIONS: Cannulated screw fixation assisted by robot navigation is a good method to treat femoral neck fractures, which has the advantages of more accurate positioning, better hip function recovery, less surgical trauma, and shorter X-ray exposure time.

[Effect of reformative acetabular centralization technology on leg-length inequality in total hip arthroplasty].

OBJECTIVE: To investigate the application value of acetabular centralization technology for correction of leg-length inequality in total hip arthroplasty (THA). METHODS: Between June 2001 and January 2012, 147 cases of abnormal acetabular center were treated. Of them, 68 cases underwent routine THA (control group), and 79 cases underwent acetabular reconstruction by fossae ovalis oriented centralized technology in THA (test group). There was no significant difference in gender, age, side, pathogeny, acetabular rotation center indexs, difference of relative and absolute leg-length, and Harris score between 2 groups before operation (P > 0.05). The hip joint function was evaluated by Harris score; the difference of relative leg-length was measured by tape; the difference of absolute leg-length and the horizontal and vertical distances of actual and true rotation center were also measured on the X-ray films by software. RESULTS: The patients were followed up 8-26 months (mean, 8.3 months) in the test group, and 6-33 months (mean, 9.7 months) in the control group. Sciatic nerve injury occurred in 2 cases (1 in each group, respectively), lower extremity deep venous thrombosis in 7 cases (3 in test group and 4 in control group), and hip joint dislocation in 2 cases (control group); the other patients had no related complications. The difference of relative leg-length and Harris score in test group were significantly better than in control group (P < 0.05), and significant difference was also found when compared with preoperative one in 2 groups (P < 0.05). The horizontal and vertical distances of actual and the true rotation center in test group was significantly better than those in control group at immediate after operation on the X-ray films (P < 0.05); and significant differences were also found when compared with preoperative ones in 2 groups (P < 0.05). At 6 months after operation, the absolute leg-length difference in test group was significantly better than that in control group (P < 0.05); and significant difference was also found when compared with preoperative one in 2 groups (P < 0.05). CONCLUSION: The fossae ovalis oriented acetabular centralized technology in THA can significantly correct abnormal hip center of rotation, thus reduce the relative and absolute leg-length inequality and improve the life quality of the patients.

Temporal-spatial interaction between reactive oxygen species and abscisic acid regulates rapid systemic acclimation in plants.

Being sessile organisms, plants evolved sophisticated acclimation mechanisms to cope with abiotic challenges in their environment. These are activated at the initial site of exposure to stress, as well as in systemic tissues that have not been subjected to stress (termed systemic acquired acclimation [SAA]). Although SAA is thought to play a key role in plant survival during stress, little is known about the signaling mechanisms underlying it. Here, we report that SAA in plants requires at least two different signals: an autopropagating wave of reactive oxygen species (ROS) that rapidly spreads from the initial site of exposure to the entire plant and a stress-specific signal that conveys abiotic stress specificity. We further demonstrate that SAA is stress specific and that a temporal-spatial interaction between ROS and abscisic acid regulates rapid SAA to heat stress in plants. In addition, we demonstrate that the rapid ROS signal is associated with the propagation of electric signals in Arabidopsis thaliana. Our findings unravel some of the basic signaling mechanisms underlying SAA in plants and reveal that signaling events and transcriptome and metabolome reprogramming of systemic tissues in response to abiotic stress occur at a much faster rate than previously envisioned.

Linking genes of unknown function with abiotic stress responses by high-throughput phenotype screening.

Over 13% of all genes in the Arabidopsis thaliana genome encode for proteins classified as having a completely unknown function, with the function of >30% of the Arabidopsis proteome poorly characterized. Although empirical data in the form of mRNA and proteome profiling experiments suggest that many of these proteins play an important role in different biological processes, their functional characterization remains one of the major challenges in modern biology. To expand the annotation of genes with unknown function involved in the response of Arabidopsis to different environmental stress conditions, we selected 1007 such genes and tested the response of their corresponding homozygous T-DNA insertional mutants to salinity, oxidative, osmotic, heat, cold and hypoxia stresses. Depending on the specific abiotic stresses tested, 12-31% of mutants had an altered stress-response phenotype. Interestingly, 832 out of 1007 mutants showed tolerance or sensitivity to more than one abiotic stress treatment, suggesting that genes of unknown function could play an important role in abiotic stress-response signaling, or general acclimation mechanisms. Further analysis of multiple stress-response phenotypes within different populations of mutants revealed interesting links between acclimation to heat, cold and oxidative stresses, as well as between sensitivity to ABA, osmotic, salinity, oxidative and hypoxia stresses. Our findings provide a significant contribution to the biological characterization of genes with unknown function in Arabidopsis and demonstrate that many of these genes play a key role in the response of plants to abiotic stresses.

[Comparison study on locking compress plate external fixator and standard external fixator for treatment of tibial open fractures].

OBJECTIVE: To compare the clinical results of locking compress plate (LCP) as an external fixator and standard external fixator for treatment of tibial open fractures. METHODS: Between May 2009 and June 2012, 59 patients with tibial open fractures were treated with LCP as an external fixator in 36 patients (group A), and with standard external fixator in 23 patients (group B). There was no significant difference in gender, age, cause of injury, affected side, type of fracture, location, and interval between injury and surgery between 2 groups (P > 0.05). The time of fracture healing and incision healing, the time of partial weight-bearing, the range of motion (ROM) of knee and ankle, and complications were compared between 2 groups. RESULTS: The incidence of pin-track infection in group A (0) was significantly lower than that in group B (21.7%) (P=0.007). No significant difference was found in the incidence of superficial infection and deep infection of incision, and the time of incision healing between 2 groups (P > 0.05). Deep vein thrombosis occurred in 5 cases of group A and 2 cases of group B, showing no significant difference (Chi(2)=0.036, P=0.085). All patients were followed up 15.2 months on average (range, 9-28 months) in group A, and 18.6 months on average (range, 9-47 months) in group B. The malunion rate and nonunion rate showed no significant difference between groups A and B (0 versus 13.0% and 0 versus 8.7%, P > 0.05); the delayed union rate of group A (2.8%) was significantly lower than that of group B (21.7%) (Chi(2)=5.573, P=0.018). Group A had shorter time of fracture healing, quicker partial weight-bearing, greater ROM of the knee and ankle than group B (P < 0.05). CONCLUSION: The LCP external fixator can obtain reliable fixation in treating tibial open fracture, and has good patients' compliance, so it is helpful to do functional exercise, improve fracture healing and function recovery, and reduce the complication incidence.

[Experimental study of tissue engineered bone with cryopreservation on healing of bone defects].

OBJECTIVE: To investigate the effect of tissue engineered bone with cryopreservation on healing of bone defects and to explore feasibility of cryopreservation for tissue engineered bone. METHODS: Tissue engineered bones were constructed with osteoblasts being seeded onto bio-derived materials made from fresh human bones,and they were preserved at 4 degrees C and - 196 degrees C for 3 months and 6 months respectively. They were applied to repair segmental bone defects of rabbit's radius while the tissue engineered bone without cryopreservation and bio-derived materials were brought into control groups. The experiment was divided into groups A3, A6, B3, B6, C and D (group A3: tissue engineered bones were preserved at 4 degrees C for 3 months; group A6: tissue engineered bones were preserved at 4 degrees C for 6 months; group B3:tissue engineered bones were preserved at --196 degrees C for 3 months; group B6:tissue engineered bones were preserved at - 196 degrees C for 6 months; group C: tissue engineered bones without cryopreservation; group D: bio-derived materials). Macroscopical and histological examination were done at the 2nd, 4th, 6th, 12th weeks, X-ray examination was done at the 6th, 12th weeks and biomechanics were determined at 12th weeks after operation respectively. RESULTS: Macroscopical observation showed no significant differences among group A3, A6, B3, B6 and C, but less new bone formation and more obvious boundary in group D were observed. Histological observation showed more collagen and new bone around the edge of implant of group A3, A6, B3, B6 and C than group D, and histological evaluation showed significant differences between group D and other groups (P <0.05). Radiographic observation showed no absorbability of the implant cortex and less new bone formation in group D, but the unity between implant and host bone, medullary cavity reopened, disappearance of fracture line and fine bone modelling were observed in other groups at 12 weeks after operation. Biomechanics between group D and other groups showed significant differences (P< 0. 05). CONCLUSION: Cryopreservation (4 degrees C and - 196 degrees C) were capable of preserving tissue engineered bone for long time, and tissue engineered bone with cryopreservation has significant effect on healing of bone defects. The methods fit clinical application.