Unraveling Key m6A Modification Regulators Signatures in Postmenopausal Osteoporosis through Bioinformatics and Experimental Verification.

OBJECTIVE: Bone marrow mesenchymal stem cells (BMSCs) show significant potential for osteogenic differentiation. However, the underlying mechanisms of osteogenic capability in osteoporosis-derived BMSCs (OP-BMSCs) remain unclear. This study aims to explore the impact of YTHDF3 (YTH N6-methyladenosine RNA binding protein 3) on the osteogenic traits of OP-BMSCs and identify potential therapeutic targets to boost their bone formation ability. METHODS: We examined microarray datasets (GSE35956 and GSE35958) from the Gene Expression Omnibus (GEO) to identify potential m6A regulators in osteoporosis (OP). Employing differential, protein interaction, and machine learning analyses, we pinpointed critical hub genes linked to OP. We further probed the relationship between these genes and OP using single-cell analysis, immune infiltration assessment, and Mendelian randomization. Our in vivo and in vitro experiments validated the expression and functionality of the key hub gene. RESULTS: Differential analysis revealed seven key hub genes related to OP, with YTHDF3 as a central player, supported by protein interaction analysis and machine learning methodologies. Subsequent single-cell, immune infiltration, and Mendelian randomization studies consistently validated YTHDF3's significant link to osteoporosis. YTHDF3 levels are significantly reduced in femoral head tissue from postmenopausal osteoporosis (PMOP) patients and femoral bone tissue from PMOP mice. Additionally, silencing YTHDF3 in OP-BMSCs substantially impedes their proliferation and differentiation. CONCLUSION: YTHDF3 may be implicated in the pathogenesis of OP by regulating the proliferation and osteogenic differentiation of OP-BMSCs.

METTL3-mediated m6A modification of SOX4 regulates osteoblast proliferation and differentiation via YTHDF3 recognition.

N6-methyladenosine (m6A), the most prevalent internal modification in mRNA, is related to the pathogenesis of osteoporosis (OP). Although methyltransferase Like-3 (METTL3), an m6A transferase, has been shown to mitigate OP progression, the mechanisms of METTL3-mediated m6A modification in osteoblast function remain unclear. Here, fluid shear stress (FSS) induced osteoblast proliferation and differentiation, resulting in elevated levels of METTL3 expression and m6A modification. Through Methylated RNA Immunoprecipitation Sequencing (MeRIP-seq) and Transcriptomic RNA Sequencing (RNA-seq), SRY (Sex Determining Region Y)-box 4 (SOX4) was screened as a target of METTL3, whose m6A-modified coding sequence (CDS) regions exhibited binding affinity towards METTL3. Further functional experiments demonstrated that knockdown of METTL3 and SOX4 hampered osteogenesis, and METTL3 knockdown compromised SOX4 mRNA stability. Via RNA immunoprecipitation (RIP) assays, we further confirmed the direct interaction between METTL3 and SOX4. YTH N6-Methyladenosine RNA Binding Protein 3 (YTHDF3) was identified as the m6A reader responsible for modulating SOX4 mRNA and protein levels by affecting its degradation. Furthermore, in vivo experiments demonstrated that bone loss in an ovariectomized (OVX) mouse model was reversed through the overexpression of SOX4 mediated by adeno-associated virus serotype 2 (AAV2). In conclusion, our research demonstrates that METTL3-mediated m6A modification of SOX4 plays a crucial role in regulating osteoblast proliferation and differentiation through its recognition by YTHDF3. Our research confirms METTL3-m6A-SOX4-YTHDF3 as an essential axis and potential mechanism in OP.

[Comparative study on posterior cruciate ligament reconstruction with autologous hamstring tendon and LARS artificial ligament in the treatment of KD-â ¢-M knee dislocation].

OBJECTIVE: To observe the curative effect of one-stage reconstruction of anterior cruciate ligament(ACL), posterior cruciate ligament (PCL) and medial collateral ligament (MCL) in patients with KD-Ⅲ-M knee injury, and to compare the operation time, hospitalization cost and curative effect after arthroscopic reconstruction of PCL with LARS artificial ligament and autogenous hamstring tendon, ACL reconstruction with autogenous hamstring tendon and MCL repair combined with limited incision. METHODS: From March 2016 to January 2019, a total of 36 patients met the criteria of this study. Twenty patients in group A were treated with autogenous hamstring tendon reconstruction of ACL and PCL and repair of MCL, including 17 males and 3 females, with an average age of (34.7±9.2) years old. Sixteen patients in group B with LARS artificial ligament reconstruction of PCL, with an autogenous hamstring tendon reconstruction of PCL and MCL repair as before as group B, including 15 males and 1 female, with an average age of (36.8±8.6) years old. The operation time, hospitalization time and total hospitalization cost were compared between the two groups. The preoperative and postoperative functions of the two groups were evaluated by Hospital for Sepcial Surgery (HSS) score and Lysholm score respectively, and the curative effects were compared within and between groups. RESULTS: All the patients in the two groups were followed up for at least 1 year. There were no complications such as infection and poor wound healing in both groups. There was significant difference in operation time between (120.25±9.55) min in group A and (106.63±8.85) min in group B (P<0.01). The average hospitalization days in group A was (10.60±1.64) days, while that in group B was (10.38±1.59) days. There was no significant difference between the two groups (P>0.05). The HSS score of group A increased from preoperative 32.95±5.03 to postoperative 84.70±5.72 (P<0.01), and that of group B increased from preoperative 33.81±4.10 to postoperative 85.00±5.25 (P<0.01). The Lyshlom score in group A increased from preoperative 21.10±3.46 to postoperative 80.25±5.75 (P<0.01), and in group B increased from preoperative 21.56±3.01 to postoperative 80.00±4.30(P<0.01). There was no significant difference in preoperative and postoperative scores between the two groups(P>0.05). CONCLUSION: There was no significant difference in the average hospitalization days between the two groups, but the operation time in group A was longerthan that in group B, and the hospitalization cost in group B was higher than that in group A. There was no difference in HSS score and Lysholm score before and follow-up for a certain period of time after operation.

Application of Triggered EMG in the Intraoperative Neurophysiological Monitoring of Posterior Percutaneous Endoscopic Cervical Discectomy.

OBJECTIVE: To describe the rationale and application of triggered EMG (T-EMG) in intraoperative neurophysiological monitoring, and to explore the efficacy and safety of posterior percutaneous endoscopic cervical discectomy (PPECD) in the treatment of cervical spondylotic radiculopathy (CSR) under multimodal intraoperative neurophysiological monitoring (IOM). METHODS: This study was a retrospective cohort control study. The clinical data of 74 patients with single-segment CSR from June 2015 to August 2018 were analyzed retrospectively, of whom 35 underwent IOM-assisted PPECD with triggered EMG (T-EMG group), while 39 were subjected to IOM-assisted PPECD alone (IOM group). Operation time, hospital stay, and complications were recorded for both groups. The curative effect was evaluated according to the Visual Analog Scale (VAS) of neck and arm pain, Japanese Orthopaedic Association (JOA) score, and modified MacNab scale. RESULTS: Operations were successful and all patients were followed up for at least 24 (average 31.77 ± 9.51) months with no patient lost to follow-up. No significant difference was found in preoperative baseline data between the T-EMG and the IOM group (P > 0.05). Also, no significant difference was found in the operation time between the T-EMG (108.29 ± 11.44 min) and the IOM (110.13 ± 12.70 min) (P > 0.05) group, but the difference in hospital stay (T-EMG: 5.66 ± 0.99 days; IOM: 7.10 ± 1.43 days) was statistically significant (P < 0.05). The VAS for the neck and upper limbs in the two groups at 1 month post-operation (T-EMG: 2.09 ± 1.07, 2.26 ± 0.92; IOM:2.18 ± 1.05, 2.31 ± 0.77) and the last follow-up (T-EMG: 0.83 ± 0.62, 0.86 ± 0.55; IOM: 0.90 ± 0.50, 0.87 ± 0.61) were significantly different from the preoperative scores (T-EMG: 6.14 ± 1.09, 7.17 ± 1.04; IOM: 6.18 ± 1.28, 7.15 ± 1.23) (P < 0.05). However, no significant difference was found between the two groups (P > 0.05). The 1-month postoperative JOA scores for the two groups (12.69 ± 0.76; 12.59 ± 0.82) and those at the last follow-up (14.60 ± 0.77; 14.36 ± 0.78) were significantly different from the preoperative scores (11.09 ± 0.98; 11.05 ± 0.89) (P < 0.05), but the difference between the two groups was not significant (P > 0.05). One patient in the T-EMG group developed a transient aggravation of symptoms on the first day after surgery. In the IOM group, three patients had intraoperative cerebrospinal fluid leakage, and symptoms of C5 nerve root paralysis were presented in four patients following surgery. Compared with the IOM group, the T-EMG group had fewer complications (1/35; 7/39, P < 0.05). At the last follow-up, the modified MacNab criteria were 91.43% (32/35) and 89.7% (35/39) for the T-EMG group and IOM group, respectively. CONCLUSIONS: Triggered EMG prevents the occurrence of neurological complications, which not only aids PPECD for CSR treatment in achieving satisfactory results, but also reduces average hospital stay and complication rates.

Percutaneous Endoscopic Unilateral Laminotomy and Bilateral Decompression for Lumbar Spinal Stenosis.

To introduce a new surgery, percutaneous endoscopic unilateral laminotomy and bilateral decompression (Endo-ULBD) using visual trepan, and investigate its efficacy and safety in elderly patients with lumbar spinal stenosis. In our retrospective study, a total of 69 patients were enrolled between March 2018 and September 2018; 31 patients were treated with Endo-ULBD and 38 patients were treated with posterior lumbar interbody fusion surgery (PLIF). The operation time, intraoperative blood loss, and hospitalization duration were compared between the two groups. A visual analog scale (VAS) was used to evaluate the degree of pain. The Oswestry Disability Index (ODI) and European Quality of Life-5 Dimensions (EQ-5D) were used to evaluate lumbar function and quality of life, respectively. Lumbar X-ray, computed tomography (CT) and magnetic resonance imaging (MRI) were performed postoperatively at different time points. MacNab's outcome assessment and perioperative complications were also documented. The surgeon completed all surgeries successfully, and all 69 patients were followed up. The operative time of the Endo-ULBD group was 60.68 ± 0.47 min, while that of the PLIF group was 120.23 ± 10.24 min. The operative time of the Endo-ULBD group was shorter than that of the PLIF group, and the difference was statistically significant (P < 0.001). The volume of intraoperative blood loss was 47.25 ± 0.43 mL in the Endo-ULBD group and 256.90 ± 20.83 mL in the PILF group (P < 0.001). The length of hospital stay in the Endo-ULBD group was 5.12 ± 1.60 days and that in the PILF group was 10.54 ± 1.82 days (P < 0.001). The VAS scores at postoperative 1 day, 3 months, 6 months, final follow-up (Endo-ULBD: 6.58 ± 0.65, 4.55 ± 0.54, 2.78 ± 0.24, 1.31 ± 0.78; PLIF: 7.19 ± 1.14, 4.80 ± 0.13, 2.71 ± 0.83, 1.29 ± 0.56) were significantly improved compared with those before surgery (Endo-ULBD: 8.63 ± 0.37; PLIF: 8.31 ± 1.34). The ODI and EQ-5D scores of lumbar function and quality of life at each time point after surgery (Endo-ULBD ODI: 30.29% ± 0.47%, 23.35% ± 0.95%, 19.45% ± 0.81%, 10.84% ± 0.36%; EQ-5D: 0.38 ± 0.15, 0.45 ± 0.17, 0.63 ± 0.14, 0.71 ± 0.20; PLIF ODI: 33.56% ± 1.58%, 25.69% ± 2.69%, 20.01% ± 1.49%, 10.72% ± 0.29%; EQ-5D: 0.33 ± 0.03, 0.39 ± 0.05, 0.62 ± 0.07, 0.72 ± 0.10) were significantly improved compared with those before surgery (Endo-ULBD: 44.56 ± 1.32, 0.33 ± 0.07; PLIF: 43.79 ± 1.91, 0.31 ± 0.09, respectively), with statistically significant differences (P < 0.05); however, there was no significant difference between the two groups at the last follow-up (P > 0.05). At the last follow-up, the excellent and good efficacy rate was 90.3% (28/31) in the Endo-ULBD group and 89.4% (34/38) in the PILF group (χ2 = 0.089, P = 0.993). No mortality, irreversible nerve injury, or even paralysis occurred in either group. Endo-ULBD for lumbar spinal stenosis has the advantages of less trauma, a shortened operation time, and rapid recovery and is an effective alternative for the treatment of lumbar spinal stenosis. Strict surgical indications, reasonable surgical plans, and experienced surgeons are important factors to ensure safety and satisfactory postoperative efficacy.

Early Clinical Evaluation of Percutaneous Full-endoscopic Transforaminal Lumbar Interbody Fusion with Pedicle Screw Insertion for Treating Degenerative Lumbar Spinal Stenosis.

OBJECTIVE: To compare the clinical efficacy of percutaneous full-endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) with percutaneous pedicle screws (PPSs) performed by using a visualization system with that of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for the treatment of degenerative lumbar spinal stenosis (LSS). METHODS: From June 2017 to May 2018, the data of a total of 78 patients who met the selection criteria were retrospectively reviewed and were divided into the Endo-TLIF group (40 cases) and the MIS-TLIF group (38 cases) according to the surgical method used. The visual analog scale (VAS) and the Japanese Orthopaedic Association (JOA) scale were administered preoperatively and at the 1-week, 3-month, and 1-2-year follow-ups. The fusion rate and major complications, including revision, were also recorded. RESULTS: All the patients were followed up for 24 to 34 months, with an average follow-up of 30.7 months. The intraoperative blood loss and length of hospital stay for the Endo-TLIF group (60.56 ± 0.36 mL, 8.12 ± 0.92 days, respectively) were statistically significantly lower than those for the MIS-TLIF group (65.47 ± 0.91 mL, 9.66 ± 1.34 days, respectively) (P < 0.05). The VAS and JOA scores of the patients in the two groups at postoperative 1 week, 3 months, 1 year, 2 years (Endo-TLIF VAS: 4.16 ± 0.92, 3.72 ± 1.54, 1.32 ± 0.45, 1.29 ± 0.34; JOA:16.71 ± 0.99, 19.86 ± 0.24, 24.91 ± 0.97, 25.88 ± 0.52; MIS-TLIF VAS: 4.17 ± 1.41, 2.98 ± 0.91, 1.54 ± 0.32, 1.33 ± 0.18; JOA: 16.67 ± 0.67, 19.58 ± 0.65, 25.33 ± 0.73, 25.69 ± 0.33) were statistically significantly improved from the preoperative scores (Endo-TLIF: 8.45 ± 1.44, 14.36 ± 0.56; MIS-TLIF: 8.11 ± 0.93, 14.45 ± 0.34, respectively) (P < 0.01). The VAS and JOA scores of the Endo-TLIF group were statistically significantly better than those of the MIS-TLIF group at 3 months and 1 year after surgery (P < 0.05). There were no statistically significant differences in the scores between the two groups at any of the other time points (P > 0.05). There was no significant difference in the intervertebral altitude between the two groups at the 3-month (11.36 ± 0.23, 11.21 ± 0.42, respectively) or final follow-up (10.88 ± 0.64, 10.81 ± 0.39, respectively) (P > 0.05). Dural tears, cerebrospinal fluid leakage, infection, and neurologic injury did not occur. Both groups showed good intervertebral fusion at the last follow-up. The intervertebral fusion rate was 97.5% (39/40) in the Endo-TLIF group and 94.7% (36/38) in the MIS-TLIF group, with no statistically significant difference between the two groups (χ2 = 0.118, P = 0.731). At the final follow-up, the modified MacNab's criteria were 92.5% and 89.5% between the two groups. CONCLUSION: Endo-TLIF with percutaneous pedicle screws (PPS) performed by using a visualization system for lumbar degenerative disease may be regarded as an efficient alternative surgery for degenerative lumbar spinal stenosis. It is a safe and minimally invasive way to perform this surgery and has shown satisfactory clinical outcomes.

Knockdown of Ski decreased the reactive astrocytes proliferation in vitro induced by oxygen-glucose deprivation/reoxygenation.

Glia scar is a pathological marker in late phase of brain ischemia disease, which constitutes a major physical biochemical barrier to impede axonal regrowth. Astrocytes are known to be critically involved in the formation of glial scar. However, their response to ischemia and their role in neuroprotection after central nervous system (CNS) injury are not completely clear. Recently, we have demonstrated for the first time that Ski was up-regulated in reactive astrocytes after spinal cord injury in vivo and in vitro, which indicates Ski may be a new molecule that control astrocytes biologic properties after CNS injury. However, its role in the process of reactive astrogliosis after cerebral ischemia and its definite mechanism still remains unknown. This study is to elucidate the role of Ski in reactive astrocytes induced by oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro. The expression of Ski was proved to be up-regulated in OGD/R model. Meanwhile, Up-regulation of Ski was accompanied with high ratio of EdU (+) cells and up-expression of related proteins including GFAP, PCNA, CDK4, and CyclinD1, which demonstrated the distinct activation and proliferation of astrocytes after stimulation by OGD/R. Astrocytes were transfected with Ski-specific siRNA to knockdown Ski expression and subsequently attenuated OGD-induced astrocyte proliferation. Our results also showed that Ski down-regulation could suppress the activity of the Ras-Raf-ERK1/2 signaling pathway. Together, knockdown of Ski can effectively inhibit the proliferation of reactive astrogliosis via suppressing the Ras-Raf-ERK1/2 pathway. These findings indicated that maybe Ski is a promising therapeutic target for cerebral ischemic injury.

Comparison of Early Functional Recovery After Total Hip Arthroplasty Using a Direct Anterior or Posterolateral Approach: A Randomized Controlled Trial.

BACKGROUND: Controversy exists as to whether early functional outcomes differ after total hip arthroplasty performed using the direct anterior approach (DAA) or the posterolateral approach (PLA). METHODS: One hundred twenty patients were enrolled in this study and were divided into 2 groups based on surgical approach. Group A included patients who had a total hip arthroplasty with a DAA, whereas group B included those with a PLA. Patients were randomized into the DAA or PLA groups (n = 60), and perioperative and postoperative outcomes were recorded. RESULTS: When compared with the PLA, the DAA had a shorter incision length (9.1 vs 13.1 cm; P < .01), shorter hospital stay (2.8 vs 3.3 days, P = .04), and lower self-reported pain. Both serum inflammatory and muscle damage markers were lower in the DAA group. However, the PLA had shorter operative times (65.5 vs 83.3 min, P = .03) and less intraoperative blood loss (123.8 vs 165.9 mL, P = .04). The DAA had significantly lower variance in cup inclination and anteversion. Similar rates of intraoperative complications were identified in the 2 groups. The DAA was associated with better functional recovery at 3 months based on the Harris hip score, University of California Los Angeles activity score, and gait analysis; however, functional recovery at 6 months was similar between the 2 groups. CONCLUSION: We found functional advantages in early recovery after the DAA compared with the PLA. The DAA can offer rapid functional recovery with less muscle damage, greater pain relief, and lower variance in cup inclination and anteversion. However, no functional difference was found at 6 months follow-up.

Does Arthroplasty Provide Better Outcomes Than Internal Fixation At Mid- and Long-term Followup? A Meta-analysis.

BACKGROUND: Arthroplasty has been shown to be superior regarding low risk of reoperation and better function score to internal fixation for treatment of displaced femoral neck fractures at short-term followup. However, there are unanswered questions regarding the efficacy of arthroplasty in the longer term compared with internal fixation. QUESTIONS/PURPOSES: We performed a meta-analysis comparing arthroplasty (hemiarthroplasty or THA) with internal fixation in patients with displaced femoral neck fractures with respect to (1) mortality, (2) reoperation, (3) functional recovery, and (4) complications, including only randomized trials with a minimum of 4 years followup. METHODS: Computerized databases, including PubMed (MEDLINE), EMBASE, Cochrane Register of Controlled Trials databases, and Web of Science™ were searched for studies published from the inception date for each database to March 2014. Eleven randomized controlled trials that compared arthroplasty (either hemiarthroplasty or THA) with internal fixation for treatment of patients with a femoral neck fracture were included in our analysis. The quality of the trials was assessed according to the Cochrane Handbook and meta-analyses were conducted using RevMan 5.2 software from the Cochrane Collaboration. The heterogeneity among studies was evaluated by the I-squared index (I2) and publication bias was assessed using forest plots. RESULTS: There were no differences between the internal fixation and arthroplasty groups for patient mortality at mid-term (48.4% vs 46.8%) or long-term followup (83.2% vs 81.5%). Arthroplasty was associated with a lower risk of reoperation at mid-term (7.2% vs 39.8%; relative risk [RR]=0.10; 95% CI, 0.06-0.07) and at long-term followup (14.3% vs 43.8%; RR=0.10; 95% CI, 0.06-0.07). Arthroplasty was associated with better functional recovery at mid-term followup (standard mean difference [SMD]=0.55; 95% CI, 0.02-1.09), whereas function at long-term followup (SMD=0.14; 95% CI, -0.35 to 0.62) was not different between the arthroplasty and internal fixation groups. There were no significant differences in subsequent ipsilateral fractures (1.5% vs 1.2%; RR=2.18; 95% CI, 0.32-14.67; p=0.42) and deep infections (2.7% vs 2.9%; RR=0.89; 95% CI, 0.40-2.01; p=0.78) between patients treated with arthroplasty and internal fixation. CONCLUSIONS: Based on our results, we found that compared with internal fixation, arthroplasty may result in a lower rate of subsequent reoperation at mid- and long-term followup, and better mid-term functional recovery. Future studies should investigate the mid- and long-term results of THAs compared with hemiarthroplasty.

[Clinical effect of one-stage arthroscopically assisted repair and reconstruction for posterolateral dislocation of knee joint with multiple ligament injuries].

OBJECTIVE: To evaluate clinical outcomes of anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) reconstruction under arthroscopy and repair of the injured posteromedial complex structure of the knee joint in the treatment of posterolateral knee dislocation with multiple ligament injuries. METHODS: From March 2008 to August 2012,22 patients (16 males and 6 females, ranging in age from 20 to 53 years old, with an average of 30.5 years old) with posterolateral dislocation of the knee were treated with primary reconstruction of ACL and PCL, combined with the repair of injuries in the posteromedial complex and soft-tissue. Eight patients had injuries caused by sports,5 patients road accidents and 9 patients falling down. The ACL was reconstructed using the gracilis and semitendinosus tendons. The PCL was reconstructed using LARS artificial ligaments (14 cases), or gracilis and semitendinosus tendons (8 cases). Suture repair was performed in 17 patients with posteromedial ligament injuries,and self-semitendinosus strengthening operations were performed in 5 patients. Continuouspassive montion (CPM) and active exercises were executed after operation at early stage. The IKDC and Lysholm system were used to evaluate therapeutic effects. RESULTS: All the patients were regularly followed up, and the duration ranged from 11 to 56 months (averaged, 39 months). According to the IKDC scale,9 patients got a grade A result, 10 got a grade B result, and 3 got a grade C result. The IKDC subject score was 89.6±3.1 and the Lysholm scores was 90.7±1.8 at the latest follow-up, which were both better than those before operation. CONCLUSION: Reconstructing the ACL and PCL and repairing injured posteromedial complex of the knee followed by an active rehabilitation is an effective method to treat posterolateral knee dislocation.

The MEK5/ERK5 pathway mediates fluid shear stress promoted osteoblast differentiation.

The aim of this study was to determine the role of the mitogen-activated protein kinase kinase (MEK) 5/extracellular signal-regulated kinase (ERK) 5 pathway in osteoblast differentiation promoted by intermittent fluid shear stress (FSS). MC3T3-E1 osteoblastic cells were subjected to 12 dyn/cm(2) intermittent FSS, and the phenotypic markers for osteoblast differentiation, such as alkaline phosphatase (ALP) activity and expression of osteopontin (OPN) and osteocalcin (OCN), were then examined. The results showed that intermittent FSS could stimulate ERK5 phosphorylation, ALP activity and the expression of OPN and OCN. When the MEK5/ERK5 pathway was selectively inhibited by BIX02189, ALP activity was suppressed, and the expression of OPN and OCN was downregulated. Intermittent FSS induce the expression of Runt-related transcription factor-2 (Runx-2), which is involved in osteoblast differentiation by promoting the transcription of the above genes. Furthermore, the expression of Runx-2 was also reduced after treatment with BIX02189. Finally, we found that intermittent FSS was a more intense stimulus than steady FSS for promoting osteoblast differentiation. In summary, our results suggest that the MEK5/ERK5 pathway mediates osteoblast differentiation promoted by intermittent FSS, which was more effective than steady FSS in the differentiation process. The MEK5/ERK5 pathway also mediates FSS-induced Runx-2 expression in osteoblast differentiation.

[Clinical observation of microsurgial repairing for the treatment of soft tissue defection of heel].

OBJECTIVE: T o summarize the clinical effects of the repairing methods for skin and soft tissue defection of heel. METHODS: From June 1998 to June 2009,42 patients with skin and soft tissue defection of heel underwent the repairing treatment,including 23 males and 19 females, with an average age of 37 years old ranging from 18 to 65. The causes of injuries included mangled injury in 22 cases, high fall injury in 10 cases, cut injury in 5 cases,melanoma in 3 cases, decubital ulcer in 2 cases. Of the 42 cases, 27 were on left side and 15 on right side. The defect area of skin ranged from 3 cm x 2 cm to 18 cm x 16 cm. The time between the injury and surgery ranged from 8 hours to 10 years. The wounds were repaired separately by medial plantar flap in 13 cases, lesser saphenous sural nerve vascular island flap in 18 cases, saphenous neurocutaneous vascular flap in 11 cases. The patients' outcome were evaluated with appearance,blood supply, texture, resilience and two points discrimination of the flaps. RESULTS: All of the 42 flaps were survived. The distal skin necrosis occurred in 2 flaps, but healing occurred after debridement and intermediate thickness skin grafting. Three patients with sinus formation healed after 5 to 12 months of dressing change. All patients were follow-up for 8 months to 6 years. The flaps of all patients gained a satisfied shape after operation. The patients had a normal gait, the flaps had a good sense and a resistance to wearing,and no ulcer occurred. The two point discrimination of the flap was 4 to 12 mm. CONCLUSION: It is convenient and effective to repair the heel skin and soft tissue defects using medial plantar island skin flap when the defects is less then 8 cmx6 cm. As reliable blood supply,major artery preservation and high survival, the lesser saphenous sural nerve vascular island flap and saphenous neurocutaneous vascular flap can be transferred to repair the large soft tissue defect of heel.

[Treatment of tibial intercondylar eminence fracture under arthroscopy through patellofemoral joint space].

OBJECTIVE: To evaluate the clinical outcome of arthroscopy techniques for the treatment of tibial intercondylar eminence fractures through patellofemoral joint space. METHODS: From September 2008 to September 2012,45 patients (32 males, 13 females; ranging in age from 15 to 22 years old) with intercondylar eminence fractures (29 left knees and 16 right knees) were treated with reduction and fixation through patellofemoral joint space under arthroscopy. All fractures were fresh fracture and were treated within 10 days after trauma. The fractures were confirmed by X-ray. According to Meyers and McKeever classification, 27 patients had fractures with type III and 18 patients had fractures with type II. After operation, X-ray films were taken to evaluate fracture heal,and Lysholm criteria was used to evaluate therapeutic effects. RESULTS: All the patients were followed up, and all fractures healed at 3 months after operation. During the follow-up period, all the patients had excellent or good results,without complications such as nonunion, limit extension caused by intercondyloid fossa knocking of knee joint, strengthening pain and anterior instability of knee joint. The mean Lysholm score was 92 (ranged, 85 to 96) of patients with type II fractures,and 93 (ranged, 83 to 96) of patients with type II fractures. CONCLUSION: Treatment of tibial intercondylar eminence fractures under arthroscopy through patellofemoral joint space has follow advantages: simple reduction and fixation, easy operation and good clinical outcome.

[Reconstruciton of medial patellofemoral ligament (MPFL) for the treatment of recurrent patellar dislocation].

OBJECTIVE: To evaluate the middle term effectiveness of medial patellofemoral ligament (MPFL) reconstruction for the treatment of recurrent patellar dislocation. METHODS: From February 2007 to January 2010, 65 patients including 6 males and 59 females with recurrent patellar dislocation received the MPFL reconstruction. The reconstruction was performed using ipsilateral semitendinosis tendon to restore the damaged MPFL. Patients were evaluated pre-operatively and post-operatively by physical and subjectively with the IKDC (International Knee Documentation Committee), Tegner, and Lysholm questionnaires and radiographic examination. RESULTS: The average follow-up duration was 20 months (ranged, 15 to 23 months). No recurrent episodes of dislocation or subluxation occurred. A firm endpoint to lateral patellar translation was noted in all patients at most recent follow-up. The Lysholm subjective knee evaluation score improved from (60.6 +/- 3.7) preoperatively to (89.8 +/- 4.6) postoperatively; and Tegner scores improved from (3.6 +/- 0.4) to (5.6 +/- 0.3), IKDC from (40.0 +/- 3.5) to (82.0 +/- 3.6). Radiographic evaluation demonstrated improvements in the congruence and sulcus femoral angles. CONCLUSION: MPFL reconstruction is an effective surgical procedure for the treatment of recurrent patellar dislocation.

Cyclic fluid shear stress promotes osteoblastic cells proliferation through ERK5 signaling pathway.

Fluid shear stress plays an important role in bone remodeling, however, the mechanism of mechanotransduction in bone tissue remains unclear. Recently, ERK5 has been found to be involved in multiple cellular processes. This study was designed to investigate the potential involvement of ERK5 in the proliferative response of osteoblastic cells to cyclic fluid shear stress. We reported here that cyclic fluid shear stress promoted ERK5 phosphorylation in MC3T3-E1 cells. Inhibition of ERK5 phosphorylation attenuated the increased expression of AP-1 and cyclin D1 and cell proliferation induced by cyclic fluid flow, but promoted p-16 expression. Further more, we found that cyclic fluid shear stress was a better stimuli for ERK5 activation and cyclin D1 expression compared with continuous fluid shear stress. Moreover, the pharmacological ERK5 inhibitor, BIX02189, which inhibited ERK5 phosphorylation in a time-dependent manner and the suppression lasted for at least 4 h. Taken together, we demonstrate that ERK5/AP-1/cyclin D1 pathway is involved in the mechanism of osteoblasts proliferation induced by cyclic fluid shear stress, which is superior in promoting cellular proliferation compared with continuous fluid shear stress.

In vitro and in vivo biocompatibility investigation of diamond-like carbon coated nickel-titanium shape memory alloy.

OBJECTIVE: To investigate the biocompatibility of diamond-like carbon (DLC) coated nickel-titanium shape memory alloy (NiTi SMA) in vitro and in vivo. METHODS: The in vitro study was carried out by co-culturing the DLC coated and uncoated NiTi SMA with bone marrow mesenchymal stem cells (MSCs), respectively, and the in vivo study was carried out by fixing the rabbits' femoral fracture model by DLC coated and uncoated NiTi SMA embracing fixator for 4 weeks, respectively. The concentration of the cells, alkaline phosphatase (AKP), and nickel ion in culture media were detected, respectively, at the first to fifth day after co-culturing. The inorganic substance, osteocalcin, alkaline phosphatase (ALP), and tumor necrosis factor (TNF) in callus surrounding fracture and the Ni(+) in muscles surrounding fracture site, liver and brain were detected 4 weeks postoperatively. RESULTS: The in vitro study showed that the proliferation of MSCs and the expression of AKP in the DLC-coated group were higher than the uncoated group (P < 0.05), while the uncoated group released more Ni(2+) into the culture media than that in the coated group (P < 0.05). The in vivo study revealed that the inorganic substance and AKP, osteocalcin, and TNF expression were significantly higher in the DLC coated NiTi SMA embracing fixator than that in the uncoated group (P < 0.05). Ni(2+) in liver, brain, and muscles surrounding the fracture were significantly lower in the DLC coated groups than that in the uncoated group (P < 0.05). CONCLUSION: Nickel-titanium shape memory alloy coated by diamond-like carbon appears to have better biocompatibility in vitro and in vivo compared to the uncoated one.

[Prevention effects of sodium hyaluronate on nerve root adhesion after lumbar intervertebral disc protrusion].

OBJECTIVE: To observe the effects of sodium hyaluronate on nerve root adhesion after operation of lumbar disc protrusion (LDP). METHODS: From April 1996 to June 2001, 152 cases with LDP were performed the removal of nucleus pulposus under endoscope. After operation, 2 ml of sodium hyaluronate were injected. The clinical results were evaluated by clinical symptom, straight leg raising test, patient's satisfaction degree and back pain. RESULTS: All the patients were followed for 1 month to 3 years. The average angle of straight leg raising test increased from 26 degree preoperatively to 62 degree postoperatively. The patient's pain were markedly relieved. Patient's satisfactory degree were 86.8%. CONCLUSION: The injection of sodium hyaluronate after operation of LDP has effect on preventing postoperative nerve root adhesion.