The placement of percutaneous retrograde acetabular posterior column screw based on imaging anatomical study of acetabular posterior column corridor.

OBJECTIVE: To explore the entry point, orientation, and fixation range of retrograde acetabular posterior column screw. METHOD: The computed tomography data of 100 normal adult pelvises (50 males and 50 females, respectively) were collected and pelvis three-dimensional (3D) reconstruction was performed by using Mimics software and the 3D model was imported into Geomagic Studio software. The perspective of acetabular posterior column was carried out orienting from ischial tuberosity to iliac fossa in the Mimics software. Virtual screw was inserted perpendicular to the transverse section of acetabular posterior column corridor, and the maximum screw diameter, entry point, orientation, exit point were measured. The screw fixation range, the easy-to-penetrate sites, and intraoperative optimal fluoroscopic views were assessed. RESULTS: The acetabular posterior column corridor showed a triangular-prism shape. The virtual screw entry point was located at the midline between the medial and lateral edges of the ischial tuberosity. The distance between the entry point and the distal ischial tuberosity was around 13 mm. The distances between the exit point and the true pelvis rim, and ipsilateral anterior sacroiliac joint line were (19.33 ± 2.60) mm and (23.65 ± 2.42) mm in males, respectively. As for females, those two data were (17.63 ± 2.00) mm and (24.94 ± 2.39) mm, respectively. The maximum diameters of screws were (17.21 ± 1.41) mm in males and (15.54 ± 1.51) mm in females. The angle between the retrograde posterior column screw and the sagittal plane was lateral inclination (10.52 ± 3.04)° in males, and that was lateral inclination (7.72 ± 2.99)° in females. Correspondingly, the angle between the screw and the coronal plane was anterior inclination (15.00 ± 4.92)° in males, and that was anterior inclination (12.94 ± 4.72)° in females. Retrograde acetabular posterior column screw through ischial tuberosity can fix the acetabular posterior column fractures which were not 4 cm above the femoral head center. The easy-to-penetrate sites were located at the transition between the posterior acetabular wall and the ischium, the middle of the acetabulum, and 1 cm below the greater sciatic notch, respectively. The iliac oblique 10°, iliac oblique 60°, and obturator oblique 60° views were the intraoperative optimal fluoroscopic views to assess whether the screw was safely inserted. CONCLUSION: Retrograde acetabular posterior column screw entry point is located at the midline between the medial and lateral edges of the ischial tuberosity, which is 1.3 cm far from the distal ischial tuberosity. The screw direction is about 10° lateral inclination and 15° anterior inclination, which can fix the acetabular posterior column fractures which were not 4 cm above the femoral head center.

CT-scan based anatomical study as a guidance for infra-acetabular screw placement.

BACKGROUND: The infra-acetabular corridor is quite narrow, which makes a challenge for the orthopedists to insert the screw. This study aimed to explore the relationship between the infra-acetabular corridor diameter (IACD) and the minimum thickness of medial acetabular wall (MTMAW), and to clarify the way of screw placement. METHODS: The Computed tomography (CT) data of 100 normal adult pelvises (50 males and 50 females respectively) were collected and pelvis three-dimensional (3D) reconstruction was performed by using Mimics software and the 3D model was imported into Geomagic Studio software. The perspective of acetabulum was carried out orienting from iliopubic eminence to ischial tuberosity and the IACD was measured by placing virtual screws which was vertical to the corridor transverse section of "teardrop". The relationship between IACD and MTMAW was analyzed. When IACD was ≥5 mm, 3.5 mm all-in screws were placed. When IACD was < 5 mm, 3.5 mm in-out-in screws were placed. RESULTS: The IACD of males and females were (6.15 ± 1.24) mm and (5.42 ± 1.01) mm and the MTMAW in males and females were (4.40 ± 1.23) mm and (3.60 ± 0.81) mm respectively. The IACD and MTMAW in males were significantly wider than those of females (P < 0.05), and IACD was positively correlated with MTMAW (r = 0.859), the regression equation was IACD = 2.111 + 0.917 MTMAW. In the all-in screw group, 38 cases (76%) were males and 33 cases (66%) were females respectively. The entry point was located at posteromedial of the apex of iliopubic eminence, and the posterior distance and medial distance were (8.03 ± 2.01) mm and (8.49 ± 2.68) mm respectively in males. As for females, those were (8.68 ± 2.35) mm and (8.87 ± 2.79) mm respectively. In the in-out-in screw group, 12 cases (24%) were males and 17 cases (34%) were females, respectively. The posterior distance and medial distance between the entry point and the apex of iliopubic eminence were (10.49 ± 2.58) mm and (6.17 ± 1.84) mm respectively in males. As for females, those were (10.10 ± 2.63) mm and (6.63 ± 1.49) mm respectively. The angle between the infra-acetabular screw and the sagittal plane was medial inclination (0.42 ± 6.49) °in males, lateral inclination (8.09 ± 6.33) °in females, and the angle between the infra-acetabular screw and the coronal plane was posterior inclination (54.06 ± 7.37) °. CONCLUSIONS: The placement mode of the infra-acetabular screw (IAS) can be determined preoperatively by measuring the MTMAW in the CT axial layers. Compared with all-in screw, the in-out-in screw entry point was around 2 mm outwards and backwards, and closer to true pelvic rim.

Integrin ß3 Mediates the Endothelial-to-Mesenchymal Transition via the Notch Pathway.

BACKGROUND/AIMS: Neointimal hyperplasia is responsible for stenosis, which requires corrective vascular surgery, and is also a major morphological feature of many cardiovascular diseases. This hyperplasia involves the endothelial-to-mesenchymal transition (EndMT). We investigated whether integrin ß3 can modulate the EndMT, as well as its underlying mechanism. METHODS: Integrin ß3 was overexpressed or knocked down in human umbilical vein endothelial cells (HUVECs). The expression of endothelial markers and mesenchymal markers was determined by real-time reverse transcription PCR (RT-PCR), immunofluorescence staining, and western blot analysis. Notch signaling pathway components were detected by real-time RT-PCR and western blot analysis. Cell mobility was evaluated by wound-healing, Transwell, and spreading assays. Fibroblast-specific protein 1 (FSP-1) promoter activity was determined by luciferase assay. RESULTS: Transforming growth factor (TGF)-ß1 treatment or integrin ß3 overexpression significantly promoted the EndMT by downregulating VE-cadherin and CD31 and upregulating smooth muscle actin α and FSP-1 in HUVECs, and by enhancing cell migration. Knockdown of integrin ß3 reversed these effects. Notch signaling was activated after TGF-ß1 treatment of HUVECs. Knockdown of integrin ß3 suppressed TGF-ß1-induced Notch activation and expression of the Notch downstream target FSP-1. CONCLUSION: Integrin ß3 may promote the EndMT in HUVECs through activation of the Notch signaling pathway.

Comparison of Clinical Efficacy of Lateral and Lateral and Medial Double-plating Fixation of Distal Femoral Fractures.

The present study was performed to compare the clinical efficacy of lateral plate and lateral and medial double-plating fixation of distal femoral fractures and explore the indication of lateral and medial double-plating fixation of the distal femoral fractures. From March 2006 to April 2014, 48 and 12 cases of distal femoral fractures were treated with lateral plate (single plate) and lateral and medial plates (double plates), respectively. During the surgery, after setting the lateral plate for the distal femoral fractures, if the varus stress test of the knee was positive and the lateral collateral ligament rupture was excluded, lateral and medial double-plating fixation was used for the stability of the fragments. All the patients were followed up at an average period of 15.9 months. The average operation time, the intraoperative hemorrhage and the fracture union time of the two groups were compared. One year after operation, knee function was evaluated by the Kolmert's standard. There was no significant difference in the average operation time, intraoperative hemorrhage, fracture healing time and excellent and good rates of postoperative knee function between two groups. Positive Varus stress test during operation can be an indication for lateral and medial double-plating fixation of distal femoral fractures.

Anatomical evidence for the anterior plate fixation of sacroiliac joint.

BACKGROUND: The iatrogenic injuries to the lumbar nerves during the fixation the sacroiliac (SI) joint fractures with anterior plates were often reported. No specific method had been reported to avoid it. This study was done to find a safer way of placing the anterior plates and screws for treating the sacroiliac (SI) joint fracture and/or dislocation. METHODS: The research was performed using 8 male and 7 female normal corpse pelvic specimens preserved by 10% formalin solution. Try by measuring the horizontal distance from L4, L5 nerve roots to the sacroiliac joint and perpendicular distance from L4, L5 nerve roots to the ala sacralis, the length of L4, L5 nerve roots from intervertebral foramen to the edge of true pelvis, the diameter of L4, L5 nerve roots. The angles between the sacroiliac joint and sagittal plane were measured on the CT images. RESULTS: The horizontal distance between the lateral side of the anterior branches of L4, L5 nerve roots and the sacroiliac joint decreased gradually from the top to the bottom. The widest distances for L4,5 were 2.1 cm (range, 1.74-2.40) and 2.7 cm (range, 2.34-3.02 cm), respectively. The smallest distances for L4, 5 were 1.2 cm (range, 0.82-1.48 cm) and 1.5 cm (range, 1.08-1.74 cm), respectively. On CT images, the angle between the sacroiliac joint and sagittal plane was about 30°. CONCLUSIONS: If we use two anterior plates to fix the sacroiliac joint, It is recommended to place one plate on the superior one third part of the joint, with exposing medially no more than 2.5 cm and the other in the middle one third part of the joint, with elevating periosteum medially no more than 1.5 cm. The screws in the sacrum are advised to incline medially about 30° directing to the true pelvis.

Serum Glucocorticoid-Regulated Kinase 1 Blocks CKD-Induced Muscle Wasting Via Inactivation of FoxO3a and Smad2/3.

Muscle proteolysis in CKD is stimulated when the ubiquitin-proteasome system is activated. Serum glucocorticoid-regulated kinase 1 (SGK-1) is involved in skeletal muscle homeostasis, but the role of this protein in CKD-induced muscle wasting is unknown. We found that, compared with muscles from healthy controls, muscles from patients and mice with CKD express low levels of SGK-1. In mice, SGK-1-knockout (SGK-1-KO) induced muscle loss that correlated with increased expression of ubiquitin E3 ligases known to facilitate protein degradation by the ubiquitin-proteasome, and CKD substantially aggravated this response. SGK-1-KO also altered the phosphorylation levels of transcription factors FoxO3a and Smad2/3. In C2C12 muscle cells, expression of dominant negative FoxO3a or knockdown of Smad2/3 suppressed the upregulation of E3 ligases induced by loss of SGK-1. Additionally, SGK-1 overexpression increased the level of phosphorylated N-myc downstream-regulated gene 1 protein, which directly interacted with and suppressed the phosphorylation of Smad2/3. Overexpression of SGK-1 in wild-type mice with CKD had similar effects on the phosphorylation of FoxO3a and Smad2/3 and prevented CKD-induced muscle atrophy. Finally, mechanical stretch of C2C12 muscle cells or treadmill running of wild-type mice with CKD stimulated SGK-1 production, and treadmill running inhibited proteolysis in muscle. These protective responses were absent in SGK-1-KO mice. Thus, SGK-1 could be a mechanical sensor that mediates exercise-induced improvement in muscle wasting stimulated by CKD.

Protective role of insulin-like growth factor-1 receptor in endothelial cells against unilateral ureteral obstruction-induced renal fibrosis.

Insulin-like growth factor-1 receptor (IGF-1R) can regulate vascular homeostasis and endothelial function. We studied the role of IGF-1R in oxidative stress-induced endothelial dysfunction. Unilateral ureteral obstruction (UUO) was performed in wild-type (WT) mice and mice with endothelial cell (EC)-specific IGF-1R knockout (KO). After UUO in endothelial IGF-1R KO mice, endothelial barrier dysfunction was more severe than in WT mice, as seen by increased inflammatory cell infiltration and vascular endothelial (VE)-cadherin phosphorylation. UUO in endothelial IGF-1R KO mice increased interstitial fibroblast accumulation and enhanced extracellular protein deposition as compared with the WT mice. Endothelial barrier function measured by transendothelial migration in response to hydrogen peroxide (H2O2) was impaired in ECs. Silencing IGF-1R enhanced the influence of H2O2 in disrupting the VE-protein tyrosine phosphatase/VE-cadherin interaction. Overexpression of IGF-1R suppressed H2O2-induced endothelial barrier dysfunction. Furthermore, by using the piggyBac transposon system, we expressed IGF-1R in VE cells in mice. The expression of IGF-1R in ECs also suppressed the inflammatory cell infiltration and renal fibrosis induced by UUO. IGF-1R KO in the VE-cadherin lineage of bone marrow cells had no significant effect on the UUO-induced fibrosis, as compared with control mice. Our results indicate that IGF-1R in the endothelium maintains the endothelial barrier function by stabilization of the VE-protein tyrosine phosphatase/VE-cadherin complex. Decreased expression of IGF-1R impairs endothelial function and increases the fibrosis of kidney disease.

Migration of smooth muscle cells from the arterial anastomosis of arteriovenous fistulas requires Notch activation to form neointima.

A major factor contributing to failure of arteriovenous fistulas (AVFs) is migration of smooth muscle cells into the forming neointima. To identify the source of smooth muscle cells in neointima, we created end-to-end AVFs by anastomosing the common carotid artery to the jugular vein and studied neural crest-derived smooth muscle cells from the carotid artery, which are Wnt1-positive during development. In Wnt1-cre-GFP mice, smooth muscle cells in the carotid artery but not the jugular vein are labeled with GFP. About half of the cells were GFP-positive in the neointima, indicating their migration from the carotid artery to the jugular vein in AVFs created in these mice. As fibroblast-specific protein-1 (FSP-1) regulates smooth muscle cell migration, we examined FSP-1 in failed AVFs and polytetrafluoroethylene grafts from patients with end-stage kidney disease or from AVFs in mice with chronic kidney disease. In smooth muscle cells of AVFs or polytetrafluoroethylene grafts, FSP-1 and activation of Notch1 are present. In smooth muscle cells, Notch1 increased RBP-Jκ transcription factor activity and RBP-Jκ stimulated FSP-1 expression. Conditional knockout of RBP-Jκ in smooth muscle cells or general knockout of FSP-1 suppressed neointima formation in AVFs in mice. Thus, the artery of AVFs is the major source of smooth muscle cells during neointima formation. Knockout of RBP-Jκ or FSP-1 ameliorates neointima formation and might improve AVF patency during long-term follow-up.

Impaired integrin ß3 delays endothelial cell regeneration and contributes to arteriovenous graft failure in mice.

OBJECTIVE: Neointima formation is associated with stenosis and subsequent thrombosis in arteriovenous grafts (AVGs). A role of integrin ß3 in the neointima formation of AVGs remains poorly understood. APPROACH AND RESULTS: In integrin ß3(-/-) mice, we found significantly accelerated occlusion of AVGs compared with the wild-type mice. This is caused by the development of neointima and lack of endothelial regeneration. The latter is a direct consequence of impaired functions of circulating angiogenic cells (CACs) and platelets in integrin ß3(-/-) mice. Evidence suggests the involvement of platelet regulating CAC homing to and differentiation at graft sites via transforming growth factor-ß1 and Notch signaling pathway. First, CACs deficient of integrin ß3 impaired adhesion activity toward exposed subendothelium. Second, platelets from integrin ß3(-/-) mice failed to sufficiently stimulate CACs to differentiate into mature endothelial cells. Finally, we found that transforming growth factor-ß1 level was increased in platelets from integrin ß3(-/-) mice and resulted in enhanced Notch1 activation in CACs in AVGs. These results demonstrate that integrin ß3 is critical for endothelial cell homing and differentiation. The increased transforming growth factor-ß1 and Notch1 signaling mediates integrin ß3(-/-)-induced AVG occlusion. This accelerated occlusion of AVGs was reversed in integrin ß3(-/-) mice transplanted with the bone marrow from wild-type mice. CONCLUSIONS: Our results suggest that boosting integrin ß3 function in the endothelial cells and platelets could prevent neointima and thrombosis in AVGs.

Smooth muscle cells from the anastomosed artery are the major precursors for neointima formation in both artery and vein grafts.

Accumulation of smooth muscle cells (SMC) results in neointima formation in injured vessels. Two graft models consisting of vein and artery grafts were created by anastomosing common carotid arteries to donor vessels. To identify the origin of the neointima cells from anastomosed arteries, we use Wnt1-Cre/reporter mice to label and track SMCs in the common carotid artery. The contribution of SMCs in the neighboring arteries to neointima formation was studied. On evaluating the artery grafts after 1 month, >90 % of the labeled neointima cells were found to have originated from the anastomosing host arteries. Most of the neointima cells were also smooth muscle α-actin positive (SMA-α(+)) and expressed the smooth muscle myosin heavy chain (SMMHC), the SMC terminal differentiation marker. In vein grafts, about 60 % SMA-α-positive cells were from anastomosing arteries. Bone marrow cells did not contribute to neointima SMCs in vein grafts, but did co-stain with markers of inflammatory cells. Wnt1 expression was not detected in the neointima cells in the vein or artery grafts, or the injured femoral arteries. Neointima SMCs showed the synthetic phenotype and were positively labeled with BrdU in vitro and in vivo. Treatment with the IGF-1 receptor inhibitor suppressed SMC proliferation and neointima formation in vein grafts. Our results indicate that SMCs from the neighboring artery are predominantly present in the neointima formed in both vein and artery grafts and that Wnt1-Cre mice can be used to explore the role of SMCs originating from neighboring vessels in vascular remodeling.

Blocking Notch in endothelial cells prevents arteriovenous fistula failure despite CKD.

Neointima formation causes the failure of 60% of arteriovenous fistulas (AVFs) within 2 years. Neointima-forming mechanisms are controversial but possibly linked to excess proinflammatory responses and dysregulated Notch signaling. To identify how AVFs fail, we anastomosed the carotid artery to the internal jugular vein in normal and uremic mice and compared these findings with those in failed AVFs from patients with ESRD. Endothelial cells (ECs) of AVFs in uremic mice or patients expressed mesenchymal markers (FSP-1 and/or α-SMA) and exhibited increased expression and nuclear localization of Notch intracellular domain compared with ECs of AVFs in pair-fed control mice. Furthermore, expression of VE-Cadherin decreased, whereas expression of Notch1 and -4, Notch ligands, the downstream transcription factor of Notch, RBP-Jκ, and Notch target genes increased in ECs of AVFs in uremic mice. In cultured ECs, ectopic expression of Notch ligand or treatment with TGF-ß1 triggered the expression of mesenchymal markers and induced endothelial cell barrier dysfunction, both of which were blocked by Notch inhibition or RBP-Jκ knockout. Furthermore, Notch-induced defects in barrier function, invasion of inflammatory cells, and neointima formation were suppressed in mice with heterozygous knockdown of endothelial-specific RBP-Jκ. These results suggest that increased TGF-ß1, a complication of uremia, activates Notch in endothelial cells of AVFs, leading to accelerated neointima formation and AVF failure. Suppression of Notch activation could be a strategy for improving AFV function in uremia.

Chronic kidney disease accelerates endothelial barrier dysfunction in a mouse model of an arteriovenous fistula.

Hemodialysis patients depend on arteriovenous fistulas (AVF) for vascular access. Unfortunately, their 2-yr primary patency rate is only 60% because of AVF clog due to intimal hyperplasia at the venous anastomosis. Chronic kidney disease (CKD) can increase neointima formation by unknown mechanisms. A new AVF mouse model was created, and the mechanisms of CKD on neointima formation in AVFs were investigated. We created AVFs in mice by anastomosing the common carotid artery to the internal jugular vein. CKD was induced [BUN (blood urea nitrogen) in control and CKD mice, 33.3 ± 3.9 vs. 114.2 ± 12.1 mg/dl, P < 0.05]. After 1 day, there was endothelial cell loss and CD41-positive platelet aggregation, especially in the venous anastomosis. An invasion of macrophages and neutrophils peaked at 1 wk after surgery. Neointima formation (smooth muscle cell accumulation and extracellular matrix deposition) increased progressively over 4 wk. Mice with CKD had ~45% (P < 0.05) more neointima formation than control mice. CKD decreased vascular endothelial-cadherin expression in endothelial cells and delayed regeneration of the endothelium. CKD also increased inflammatory cells (Mac-2-positive or CD45-positive) in AVFs at 2 wk. Finally, AVFs were "leakier" (increased accumulation of Evans blue) in CKD mice at 7 and 14 days than control mice. We find that CKD increases neointima formation and endothelial barrier dysfunction. We have created a mouse model of AVF with characteristics similar to failed AVFs in patients. The model will allow testing of strategies directed at improving AVF function in CKD patients.

Loss of glutathione S-transferase A4 accelerates obstruction-induced tubule damage and renal fibrosis.

Glutathione transferase isozyme A4 (GSTA4) exhibits high catalytic efficiency to metabolize 4-hydroxynonenal (4-HNE), a highly reactive lipid peroxidation product that has been implicated in the pathogenesis of various chronic diseases. We investigated the role of 4-HNE in the mechanisms of unilateral ureteral obstruction (UUO)-induced fibrosis and its modulation by GSTA4-4 in a mouse model. Our data indicate that after UUO, accumulation of 4-HNE and its adducts were increased in renal tissues, with a concomitant decrease in the expression of GSTA4-4 in mice. As compared to wild-type (WT) mice, UUO caused an increased expression of fibroblast markers in the interstitium of GSTA4 KO mice. Additionally, increased autophagy and tubular cell damage were more severe in UUO-treated GSTA4 KO mice than in WT mice. Furthermore, GSK-3ß phosphorylation and expression of Snail, a regulator of E-cadherin and Occludin, was found to be significantly higher in UUO-inflicted GSTA4 KO mice. GSTA4 over-expression prevented 4-HNE-induced autophagy activation, tubular cell damage and Snail nuclear translocation in vitro. The effects of long-term expression of GSTA4 in restoration of UUO-induced damage in mice with the GSTA4 inducible transposon system indicated that release of obstruction after 3 days of UUO resulted in the attenuation of interstitial SMAα and collagen I expression. This transposon-delivered GSTA4 expression also suppressed UUO-induced loss of tubular cell junction markers and autophagy activation. Together, these results indicate that 4-HNE significantly contributes to the mechanisms of tubule injury and fibrosis and that these effects can be inhibited by the enhanced expression of GSTA4-4.

FSP-1 silencing in bone marrow cells suppresses neointima formation in vein graft.

RATIONALE: Fibroblast-specific protein 1 (FSP-1) plays multiple roles in promoting cell proliferation and motility. Increased FSP-1 expression in smooth muscle cells (SMCs) has been associated with their enhanced proliferation. OBJECTIVE: To study how FSP-1 contributes to neointima formation of vein grafts. METHODS: Arteriovenous grafts were created in wild-type or FSP-1-GFP mice (green fluorescent protein expression regulated by FSP-1 promoter). The effects of FSP-1 on bone marrow (BM) cell migration and on SMC proliferation were studied in vivo and in vitro. RESULTS: On creation of a vein graft, there was rapid deposition of platelets on the denuded surface leading to secretion of the chemokine stromal cell-derived factor-1α (SDF-1α). This was followed by recruitment of BM-derived cells expressing the SDF-1α receptor CXCR4; homing of FSP-1-positive cells was found to be dependent on platelet-derived SDF-1α. FSP-1 was expressed in 8% of the BM cells, and 20% of these express CD45; 85% of FSP-1-positive cells express CD11b. We found that the FSP-1-positive cells migrated into the vein graft in a Rac-1-dependent fashion. FSP-1 expression was also found to stimulate proliferation of SMCs through a MEK5-ERK5 signaling pathway that can be suppressed by a dominant-negative Rac1. Consequently, knocking down FSP-1 expression in BM cells prevented neointimal formation. CONCLUSIONS: BM-derived FSP-1(+) cells enhance neointima formation through an increase in transendothelial invasion with stimulation of SMC proliferation. The Rac1 and ERK5 signaling cascade mediate FSP-1-induced responses in SMCs and BM cells. This novel pathophysiology suggests a new therapeutic target, FSP-1, for preventing the development of neointima in vein grafts.

The mechanical stress-activated serum-, glucocorticoid-regulated kinase 1 contributes to neointima formation in vein grafts.

RATIONALE: Mechanical stress plays an important role in proliferation of venous smooth muscle cells (SMCs) in neointima, a process of formation that contributes to failure of vein grafts. However, it is unknown what intracellular growth signal leads to proliferation of venous SMCs. OBJECTIVE: The objective of this study is to identify mechanisms of mechanical stretch on neointima formation. METHODS AND RESULTS: By a microarray analysis, we found that mechanical cyclic stretch (15% elongation) stimulated the transcription of SGK-1 (serum-, glucocorticoid-regulated kinase-1). Mechanical stretch-induced SGK-1 mRNA expression was blocked by actinomycin D. The mechanism for the SGK-1 expression involved MEK1 but not p38 or JNK signaling pathway. SGK-1 activation in response to stretch is blocked by insulin-like growth factor (IGF)-1 receptor inhibitor and mammalian target of rapamycin complex (mTORC)2 inhibitor (Ku-0063794) but not mTORC1 inhibitor (rapamycin). Mechanical stretch-induced bromodeoxyuridine incorporation was reduced by 83.5% in venous SMCs isolated from SGK-1 knockout mice. In contrast, inhibition of Akt, another downstream signal of PI3K resulted in only partial inhibition of mechanical stretch-induced proliferation of venous SMCs. Mechanical stretch also induced phosphorylation and nuclear exportation of p27(kip1), whereas knockout of SGK-1 attenuated this effect of mechanical stretch on p27(kip1). In vivo, we found that placement of a vein graft into artery increased SGK-1 expression. Knockout of SGK-1 effectively prevented neointima formation in vein graft. There is significant lower level of p27(kip1) located in the nucleus of neointima cells in SGK-1 knockout mice compared with that of wild-type vein graft. In addition, we also found that wire injury of artery or growth factors in vitro increased expression of SGK-1. CONCLUSIONS: These results suggest that SGK-1 is an injury-responsive kinase that could mediate mechanical stretch-induced proliferation of vascular cells in vein graft, leading to neointima formation.

Hip and pelvic fractures and sciatic nerve injury.

OBJECTIVE: To investigate the influence of hip and pelvic fracture, especially acetabular fracture complicated by sciatic nerve injury on clinical features and prognosis of sciatic nerve injury. METHODS: From January 1987 to January 2000, 17 patients (14 male and 3 female) who had hip and pelvic fractures complicated by sciatic nerve injury were treated with operative reduction and internal fixation and followed up from 10 months to 5 years. The average age was 38 years (ranging 23-56 years). The left extremities were involved in 11 patients and the right in 6. Twelve patients underwent primary exploration and neurolysis and 5 patients underwent secondary operation. RESULTS: Preoperatively, 8 patients were treated with large doses of oral narcotics to control their severe sciatic pain. Three of the 8 patients underwent patient-controlled analgesia and epidural analgesia. After operation, excellent and good rates of reduction and functional recovery of sciatic nerve were 94.1% and 88% respectively. Four patients still had sciatic pain and 2 patients failed to recover. Sciatic nerve function improved within 3-6 months after surgery in 11 patients. CONCLUSIONS: Hip and pelvic fractures can result in sciatic nerve injury, especially common peroneal nerve injury and prognosis is poor. Open reduction and internal fixation combined with nerve exploration and neurolysis should be used as early as possible for severe sciatic pain.