Hub genes and gene functions associated with postmenopausal osteoporosis predicted by an integrated method.

Postmenopausal osteoporosis (PO) imposes great burden on individuals and society. This study predicted hub genes and gene functions for PO by an integration of the convergent evidence (CE) method, rank product (RP) algorithm and the combing of P-values. Using the gene expression data, genes were ranked by the CE method, RP algorithm and combing P-values, respectively. Subsequently, the top 100 genes were selected from each of the three gene lists, and then the common genes for two or three methods were denoted as informative genes of PO. A mutual information network (MIN) was constructed for the informative genes utilizing the context likelihood of relatedness algorithm. Topological centrality (degree) analysis was conducted on the MIN to investigate hub genes. Then we performed Gene Ontology (GO) enrichment analysis dependent upon the Biological Networks Gene Ontology tool (BiNGO) plugin of Cytoscape to investigate hub gene functions for PO patients. Consequently, a total of 82 informative genes were obtained by integrating the results of the three methods. There were 82 nodes and 1,741 edges in the MIN, of which 8 hub genes were identified, such as PFN1, EEF2 and S100A9. The result of GO enrichment analysis showed that 49 GO terms with P<0.001 were detected, especially the top 5 gene sets were defined as hub gene functions of PO, for instance, translational elongation, translation and cellular macromolecule biosynthetic process. In conclusion, we have predicted 8 hub genes and 5 hub gene functions associated with PO patients. The findings might help understand the molecular mechanism underlying PO.

[REPAIR OF ACUTE CLOSED ACHILLES TENDON RUPTURES BY CHANNEL-ASSISTED MINIMALLY INVASIVE REPAIR SYSTEM].

OBJECTIVE: To evaluate the effectiveness of channel-assisted minimally invasive repair (CAMIR) for acute closed Achilles tendon ruptures. METHODS: Between January 2011 and June 2012, 30 patients (30 sides) with acute closed Achilles tendon ruptures were treated with CAMIR technique. Among 30 patients, 18 were male and 12 were female with an average age of 30.4 years (range, 22-50 years); the locations were left side in 10 cases and right side in 20 cases. All the causes were sports injury. B-ultrasound was used to confirm the diagnosis, with the average distance from the rupture site to the Achilles tendon insertion of 4.4 cm (range, 2-8 cm). The time from injury to operation was 3 hours to 9 days (median, 4 days). All injuries were repaired by CAMIR technique. RESULTS: The average operation time was 17.0 minutes (range, 10-25 minutes), and the mean incision length was 2.0 cm (range, 1.5-2.5 cm). All the incisions healed by first intention. There was no complication of wound problem, deep vein thrombosis, re-rupture, or sural nerve injury. All cases were followed up 12-24 months with an average of 16 months. At last follow-up, the patients could walk normally with powerful raising heels and restored to normal activity level. MRI imaging suggested the continuity and healing of ruptured tendon. The circumference difference between affected leg and normal leg was less than 1 cm, and the ankle dorsi-extension was 20-30°, plantar flexion was 20-30°. Arner Lindholm score showed that the surgical results were excellent in 28 cases and good in 2 cases, with an excellent and good rate of 100%. CONCLUSION: CAMIR is a safe and reliable method to repair acute closed Achilles tendon rupture, with many advantages of minimal injury, low re-rupture and infection. Sural nerve injury can be minimized using CAMIR by carefully placing the suture channel with a stab incision and special trocar based on a modified Bunnel suture technique.

Early posterior spinal canal decompression and circumferential reconstruction of rotationally unstable thoracolumbar burst fractures with neurological deficit.

BACKGROUND: Among the various treatments of neurologically involved unstable thoracolumbar burst fractures, the combination of anterior and posterior instrumentation provides the most stable reconstruction. However, the use of both approaches on a trauma patient may increase the morbidity. This study is a retrospective matched cohort study to evaluate the advantages of a single stage posterior approach for spinal canal decompression in combination with circumferential reconstruction by comparing the clinical and radiographic results. METHODS: From March 2005 to September 2009, patients with matched type spinal fracture, ages at surgery, and involved levels in our institute underwent either a single stage posterior approach (group one, n = 12) or traditional combined approach (group two, n = 14) for spinal canal decompression and circumferential reconstruction were reviewed. Pre- and post-operative X-ray flms were reviewed and changes in Cobb angle of thoracolumbar spine were documented. Intra-operative, post-operative, and general complications were registered. RESULTS: The mean follow-up was (27.7 ± 9.6) months (range, 14 to 56 months) in group one and (29.2 ± 7.4) months (range, 20 to 60 months) in group two (P > 0.05). The mean operation time was 214 minutes (range, 186 ± 327 minutes) in group one and 284 minutes (range, 219 ± 423 minutes) in group two (P < 0.05). The average volume of intraoperative blood loss was 1856 ml (range, 1250 ± 3480 ml) in group one and 2453 ml (range, 1600 ± 3680 ml) in group two (P < 0.05). There was no statistical difference between the groups one and two in average vertebral body height loss at the injured level and the average Cobb angle in sagittal plane before and immediately after surgery. Postoperatively, there was an epidural hematoma in one patient in group one and two patients in group two. Bony union after stabilization was obtained in all patients, without loosening or breakage of screws. Loss of correction (5°) was seen in 1 patient in group one at the 6th month owing to the subsidence of the Titanium mesh cages into the vertebra. In group two, totally four patients suffered respiratory-related complication, including pneumonia in two, severe atelectasis in one and pleural effusions in one. Importantly, there were no intraoperative or postoperative deaths in any group. All patients with incomplete neurologic deficits improved at least 1 Frankel grade. CONCLUSION: Single-stage posterior vertebra resection in combination with circumferential reconstruction is a new option to manage severe thoracolumbar burst fractures.

Ethanol promotes chemically induced oral cancer in mice through activation of the 5-lipoxygenase pathway of arachidonic acid metabolism.

Alcohol drinking is a known risk factor for oral cancer in humans. However, previous animal studies on the promoting effect of ethanol on oral carcinogenesis were inconclusive. It is necessary to develop an animal model with which the molecular mechanism of ethanol-related oral carcinogenesis may be elucidated to develop effective prevention strategies. In this study, mice were first treated with 4-nitroquinoline-1-oxide (4NQO, 100 µg/mL in drinking water) for 8 weeks and then given water or ethanol (8%) as the sole drink for another 16 weeks. During the experiment, 8% ethanol was well tolerated by mice. The incidence of squamous cell carcinoma (SCC) increased from 20% (8/41) to 43% (17/40; P < 0.05). Expression of 5-lipoxygenase (5-Lox) and cyclooxygenase 2 (Cox-2) was increased in dysplasia and SCC of 4NQO-treated tongues and further enhanced by ethanol. Using this mouse model, we further showed that fewer cancers were induced in Alox5(-/-) mice, as were cell proliferation, inflammation, and angiogenesis in the tongue, as compared with Alox5(+/+) mice. Interestingly, Cox-2 expression was induced by ethanol in knockout mice, whereas 5-Lox and leukotriene A4 hydrolase (LTA4H) expression and leukotriene B4 (LTB4) biosynthesis were dramatically reduced. Moreover, ethanol enhanced expression and nuclear localization of 5-Lox and stimulated LTB4 biosynthesis in human tongue SCC cells (SCC-15 and SCC-4) in vitro. In conclusion, this study clearly showed that ethanol promoted 4NQO-induced oral carcinogenesis, at least in part, through further activation of the 5-Lox pathway of arachidonic acid metabolism.

Ultrasound biomicroscopy for the detection of early osteoarthritis in an animal model.

RATIONALE AND OBJECTIVES: Osteoarthritis (OA) is a common disease, and early diagnosis is essential for preventing further cartilage destruction and decreasing severe complications. Ultrasound biomicroscopy (UBM) is sensitive for detecting minute lesions in tissue because of its higher resolution, but its B-mode characterization of the early stage of OA has not been widely studied. The aim of this study was to determine the usefulness of UBM for detecting the early stage of OA using a rabbit model of early OA. MATERIALS AND METHODS: Eighteen adult New Zealand White female rabbits were used in this study, which included 12 rabbits that underwent transections of the left anterior cruciate ligament and six control rabbits. At 2, 4, and 6 weeks after surgery, four experimental rabbits and two control rabbits were euthanized. UBM was performed to evaluate the articular cartilage surfaces of the left knee, using a 55-MHz transducer. All the articular cartilage surfaces were independently assessed in blinded fashion by two radiologists for the severity of OA. The value of UBM, interobserver reliability, and the concordance between UBM and pathologic grades were determined. RESULTS: For the first radiologist, the sensitivity, specificity, positive predictive value, and negative predictive value of UBM for the diagnosis of OA were 91%, 83%, 89%, and 86%, respectively. For the second radiologist, the sensitivity, specificity, positive predictive value, and negative predictive value of UBM were 93%, 86%, 91%, and 89%, respectively. The concordance between UBM and pathologic grades for both radiologists was high (κ = 0.72 and 0.76), and the interobserver agreement was high (κ = 0.80). CONCLUSIONS: UBM can be used to evaluate cartilage defects in an animal model, and further study is needed to determine whether this technique can be valuable for detecting early OA in humans.

Quantitative evaluation of the peripheral nerve blood perfusion with high frequency contrast-enhanced ultrasound.

RATIONALE AND OBJECTIVES: The blood perfusion of peripheral nerves plays an important role in regeneration after nerve injury. Previous studies have shown that it is possible to quantitatively assess the blood perfusion of the tissue using contrast-enhanced ultrasound (CEUS). The aim of this study was to evaluate the feasibility of CEUS for quantitative assessment of the blood perfusion of the sciatic nerve in normal New Zealand white rabbits and to compare these parameters to those of surrounding skeletal muscle and the main artery in the thigh. MATERIALS AND METHODS: CEUS of the bilateral sciatic nerves was performed in 12 normal New Zealand white rabbits after a bolus injection of SonoVue (0.13 mL/kg). Pulse-inversion harmonic imaging was used for real-time CEUS. The blood perfusion of the left sciatic nerve was compared to that of its surrounding muscle, the arterial branch in the thigh, and the contralateral side. RESULTS: The supplying arteries in the sciatic nerve could be demonstrated during the early phase of CEUS, followed by the homogeneous enhancement of the whole nerve. The area under the curve and the perfusion index of the sciatic nerve were higher than those of the surrounding muscle and lower than those of the arterial branch in the thigh (both P values = .000). The maximum intensity of the sciatic nerve was similar to that of skeletal muscle and lower than that of the arterial branch. The time to peak was not significantly different among the sciatic nerve, skeletal muscle, and arterial branch (P = .551). There were no differences in area under the curve, mean transit time, perfusion index, maximum intensity, and time to peak between the left and right sciatic nerves (P > .05). CONCLUSIONS: CEUS may be a feasible method for the quantitative assessment of blood perfusion of the peripheral nerves.

[Surgical treatment of compound fracture of the ankle].

OBJECTIVE: To report the clinical outcome of the treatment of compound ankle fractures by vacuum sealing drainage and spanning external fixator. METHODS: From April 2005 to April 2009, 19 cases of Gustilo type III compound ankle fractures were treated, with type IIIA in 10 cases, Type IIIB in 7 and Type IIIC in 2. All cases underwent emergency debridement, and had the fractures fixed with spanning external fixator following indirect reduction, the wound closed with vacuum sealing drainage and repaired through direct suture, split-thickness skin graft or flap transposition. RESULTS: In this series, following VSD of 5.0 to 18.0 d (mean 10.3 d), 2 cases had their wounds closed by direct suture, 12 by skin graft and 3 by flap transposition. The other 2 cases had repeated wound debridement and multiple use of VSD, and had their wounds repaired by flap transposition. All the 19 cases were followed up for 8 to 36 months with an average of 26 months. All the fractures united 3.0 to 10.0 (mean 3.8) months. At the final follow-up functional evaluation of the affected ankle joints was performed only to find excellent in 9 cases, good in 5, fair in 4 and poor in 1. CONCLUSION: Gustilo type III compound ankle fracture can effectively be treated with VSD and spanning external fixator.

[Comparison of effectiveness of three operations in treatment of displaced femoral neck fractures in the elderly patients].

OBJECTIVE: To compare the effectiveness of internal fixation, hemiarthroplasty, and total hip arthroplasty in the treatment of displaced femoral neck fractures in elderly patients so as to provide the evidence for the selection of therapeutic methods. METHODS: Between May 2005 and April 2008, 108 elderly patients with displaced femoral neck fractures were treated by internal fixation with compression screw (IF group, n = 31), hemiarthroplasty (HA group, n = 37), and total hip arthroplasty (THA group, n = 40). In IF group, there were 8 males and 23 females with an average age of 73 years (range, 65-80 years); fractures were caused by tumbling (25 cases) and traffic accident (6 cases), including 17 cases of Garden type III and 14 cases of Garden type IV; and the time from injury to operation ranged from 8 hours to 13 days with an average of 4.2 days. In HA group, there were 10 males and 27 females with an average age of 74 years (range, 65-80 years); fractures were caused by tumbling (29 cases) and traffic accident (8 cases), including 21 cases of Garden type III and 16 cases of Garden type IV; and the time from injury to operation ranged from 1 to 14 days with an average of 4.4 days. In THA group, there were 11 males and 29 females with an average age of 73 years (range, 66-80 years); fractures were caused by tumbling (32 cases) and traffic accident (8 cases), including 23 cases of Garden type III and 17 cases of Garden type IV; and the time from injury to operation ranged from 2 to 14 days with an average of 5.6 days. There was no significant difference in general data among 3 groups (P > 0.05). RESULTS: There were significant differences in operation time and blood loss among 3 groups (P < 0.05), and IF group was less than other 2 groups. All patients were followed up 1 year and 4 months to 2 years and 3 months with an average of 1 year and 8 months. In IF group, HA group, and THA group, the rates of early postoperative complications were 19.4% (6/31), 8.1% (3/37), and 7.5% (3/40), respectively; the rates of late postoperative complications were 29.0% (9/31), 13.5% (5/37), and 7.5% (3/40), respectively; and the reoperation rates were 29.0% (9/31), 10.8% (4/37), and 5.0% (2/40), respectively. The rates of the early postoperative complication, late postoperative complication, and reoperation rate were significantly higher in IF group than in HA group and THA group (P < 0.05), but there was no significant difference between HA group and THA group (P > 0.05). The mortality rates were 16.1% (5/31), 13.5% (5/37), and 15.0% (6/40) in IF group, HA group, and THA group, respectively; showing no significant difference (P > 0.05). According to Harris hip score, the excellent and good rates were 65.4% (17/26), 81.3% (26/32), and 85.3% (29/34) in IF group, HA group, and THA group, respectively; showing significant differences among 3 groups (P < 0.05). CONCLUSION: According to patient's age, life expectancy, and general conditions, THA is a reasonable choice for the patients aged 65-80 years with displaced femoral neck fracture.

[Effectiveness of acetabular transverse and posterior wall fractures by Kocher-Langenbeck approach].

OBJECTIVE: To investigate the surgical treatment effectiveness of acetabular transverse and posterior wall fractures by Kocher-Langenbeck approach. METHODS: Between January 2002 and February 2009, 17 patients with acetabular transverse and posterior wall fractures were treated with Kocher-Langenbeck approach and fracture reduction and fixation. There were 12 males and 5 females with an average age of 33.4 years (range, 20-65 years). The disease causes were traffic accident in 16 cases and falling from height in 1 case. The disease duration was 6 hours to 11 days. According to Letournel classification, all fractures were rated as acetabular transverse and posterior wall fractures. Concomitant injuries included posterior hip dislocation in 3 cases, fracture of extremities in 8 cases, injury of sciatic nerve in 3 cases, craniocerebral injury in 1 case, and lienal rupture in 1 case. RESULTS: The incisions healed primarily and no complication of infection and deep venous thrombosis occurred after operation. All patients were followed up 12 to 36 months with an average of 19 months. The X-ray films showed that fracture healed 3 to 5 months after operation. After operation, anatomic reduction was found in 9 cases, satisfactory reduction in 5 cases, and unsatisfactory reduction in 3 cases according to Matta et al criterion. According to modified grading system of Merle D'Aubigne and Postel, the results were excellent in 4 cases, good in 9, fair in 3, and poor in 1 at last follow-up with an excellent and good rate of 76.5%. The nerve function was recovered in patients with sciatic nerve injury at 12 months after symptomatic treatment. Traumatic arthritis occurred in 5 cases, avascular necrosis of the femoral head in 1, and heterotopic ossification in 5 between 9 weeks and 12 months after operation. CONCLUSION: For acetabular transverse and posterior wall fractures, it is important to make adequate preoperative preparation, to get the imaging data, and to perform open reduction and internal fixation with Kocher-Langenbeck approach as early as possible.

[A comparisive study between intramedullary interlocking nail and plate-screw fixation in the treatment of tibial shaft fractures].

OBJECTIVE: To evaluate the effects of tibial shaft fractures treatment with plate-screw or intramedullary interlocking nail. METHODS: Thirty-five fractures were treated with intramedullary interlocking nail. Tape A, B and C were 11, 18 and 6 cases respectively according to AO classification. Forty-five fractures were treated with plate-screw system. Type A,B and C were 10,22 and 13 cases respectively. The mean time between injury and operation was 3 days and 3.5 days respectively. The patients were evaluated with operation time,range of motion,time of bone union,and complications after a mean followup of 13 months(range 8 to 26 months). RESULTS: The mean operation time and the mean range of motion of the ankle and knee were found similar in both groups. The average dorsiflexion angle of ankle was 13 Degrees (0 degrees to 20 degrees) in locked intramedullary nailing group and 11 degrees (0 degree to 20 degrees) in plate group. The average plantar flextion angle of ankle was 41 degrees (30 degrees to 50 degrees) in locked intramedullary nailing group and 47 degrees (30 degrees to 50 degrees) in plate-screw group. The mean time of bone union was 3.3 months with intramedullary nailing and 3.5 months with plate-screw fixation. Length discrepancy occurred in only two patients (2 and 2.5 cm) with intramedullary interlocking nail. One patient treated by intramedullary interlocking nail for a type III open fracture occured osteomyelitis. Plain radiographs showed rotation in two patients with intramedullary interlocking nail and angulation in 3 patients with plate-screw fixation, which were distal-third tibial fractures. CONCLUSION: Plate-screw osteosynthesis could attain satisfactory results in uncomminuted tibia shaft fractures, and locked intramedullary nailing is more appropriate in comminuted fractures.

[Minimally invasive technique treatment of postoperative recurrent bone cysts in juvenile patients].

OBJECTIVE: To study the effect of minimally invasive treatment of postoperative recurrent bone cysts in juvenile patients. METHODS: From December 1984 to December 2003, 36 cases of postoperative recurrent bone cysts after focal curettage and bone graft included 19 males and 17 females, aging 9-21 years with an average of 15 years. The size of bone cyst ranged from 2.5 cm x 6.0 cm to 3.5 cm x 13.0 cm with an average of 3.0 cm x 8.0 cm. The locations were proximal humerus in 18 cases, humeral shaft in 10 and femoral trochanteric region in 8. The focal curette and bone graft were given once in 23 cases, twice in 10 cases and 3 times in 3 cases. The interval between recurrence and minimally invasive treatment was 5-13 months (6.5 months on average). The posteroanterior and lateral X-ray films were taken to determine the location, range and feature of the focus. Under local anesthesia, 2 canulated needles were used; one was used to aspirate the contents of the cyst, the other was used to inject hydrocortisone acetate. The dose was determined according to the range of the focus. The treatment was repeated every 3. 5-4 months until the focus healed. RESULTS: All patients were followed up from 3 to 18 years with an average of 5 years. The minimally invasive treatment was repeated 3-11 times with an average of 6 times. Twenty-six cases healed completely, 6 cases healed significantly, and 4 cases healed partially. No local or general complications occurred during the treatment. CONCLUSION: This minimally invasive method for the treatment of postoperative recurrent bone cyst in juvenile patients has following advantages : less pain, easy manipulation, no hospitalization, low cost and definite effect.

[Clinical research of hemiprosthesis arthroplasty for the treatment of unstable intertrochanteric fractures in elderly patients].

OBJECTIVE: To report the clinical results of hemiprosthesis for unstable intertrochanteric fractures in elderly patients. METHODS: 86 cases (male 35 and females 51) of unstable intertrochanteric fractures in elderly patients were treated with hemiprosthesis arthroplasty in our hospital. The average age was 87 years old (range from 80 to 98 years old). According to the Evans classification of intertrochanteric fractures, there were 31 cases in type IIIA, 35 cases in IIIB and 20 cases in type IV. Most of the patients fell in the room and fractured, with concomitant diseases. After admitted to the hospital, the patients were consulted and treated for the concomitant diseases, and after the general conditions got stable and no absolute contraindications were found, the hemiprosthesis arthroplasty was performed. Almost all of the patients were operated on within 3 days with general anesthesia under the multi-function monitoring. The greater trochanter was reconstructed with figure of 8 wire fixation, the lesser trochanter with figure of 8 wire fixation, the lesser trochanter was fixed with circular wire around proximal femur. The defect within the femoral calcar was filled with bone cement and in a part of the patients, the intertrochanteric fracture was transformed into femoral neck fracture and the femoral calcar was fixed with femoral prosthesis stem. RESULTS: All operations were successful and the duration of the operation was 45 to 70 minutes with an average of 55 minutes. Blood was transfused in 73 patients during the operation between 400-800 ml with an average 450 ml. The patients got out of the bed within 3 days in 33 cases, 4-7 days in 43 cases, more than 8 days in 8 cases, and 2 patients couldn't get out of the bed. The period of hospitalization was between 13 to 27 days with an average of 16.8 days. COMPLICATIONS: 2 patients got slight deep phlebitis, 5 patients showed psychological disorders, and disorders in bacterial spectrum appeared in 3 patients, and after appropriate treatments, the complications gradually recovered and had no effect on the function of the affected extremity. 2 cases died of multiple organ failure during the hospitalization. 59 patients were followed up for 6 to 48 months with an average 16 months. The result was excellent in 17 cases who resumed their activities as before they got fractured, good in 35 cases who could walk with walking aid, fair in 5 cases who could walk with others help, and poor in 2 cases who could not walk. 1 patient died of other diseases 5 months after discharged. No dislocation, loosening or late infections occurred. 88.1% showed excellent or good result. CONCLUSION: It's an effective method to treat the unstable intertrochanteric fractures in elderly patients with hemiprosthesis arthroplasty. The result was satisfactory. It can decrease the complications, reduce the mortality, improve the patient's the living quality, and reduce the burden of the patient's family.