Author Correction: Transplanted miR-219-overexpressing oligodendrocyte precursor cells promoted remyelination and improved functional recovery in a chronic demyelinated model.

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Transplanted miR-219-overexpressing oligodendrocyte precursor cells promoted remyelination and improved functional recovery in a chronic demyelinated model.

Oligodendrocyte precursor cells (OPCs) have the ability to repair demyelinated lesions by maturing into myelin-producing oligodendrocytes. Recent evidence suggests that miR-219 helps regulate the differentiation of OPCs into oligodendrocytes. We performed oligodendrocyte differentiation studies using miR-219-overexpressing mouse embryonic stem cells (miR219-mESCs). The self-renewal and multiple differentiation properties of miR219-mESCs were analyzed by the expression of the stage-specific cell markers Nanog, Oct4, nestin, musashi1, GFAP, Tuj1 and O4. MiR-219 accelerated the differentiation of mESC-derived neural precursor cells (NPCs) into OPCs. We further transplanted OPCs derived from miR219-mESCs (miR219-OPCs) into cuprizone-induced chronically demyelinated mice to observe remyelination, which resulted in well-contained oligodendrocyte grafts that migrated along the corpus callosum and matured to express myelin basic protein (MBP). Ultrastructural studies further confirmed the presence of new myelin sheaths. Improved cognitive function in these mice was confirmed by behavioral tests. Importantly, the transplanted miR219-OPCs induced the proliferation of endogenous NPCs. In conclusion, these data demonstrate that miR-219 rapidly transforms mESCs into oligodendrocyte lineage cells and that the transplantation of miR219-OPCs not only promotes remyelination and improves cognitive function but also enhances the proliferation of host endogenous NPCs following chronic demyelination. These results support the potential of a therapeutic role for miR-219 in demyelinating diseases.

GluR3B Ab's induced oligodendrocyte precursor cells excitotoxicity via mitochondrial dysfunction.

Studies have indicated that glutamate receptor subunit 3 peptide B antibodies (GluR3B Ab's) by directing against a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype glutamate receptors (AMPARs) subunit 3 (GluR3B) was involved in the hippocampal neuron damage in the pathogenesis of epilepsy. Glutamate accumulation is critical for oligodendrocyte precursors (OPCs) excitotoxic injury. However, remarkably little is known about whether GluR3B Ab's causes OPCs excitotoxicity, and the underlying mechanisms remain unclear. In this study, we found that the survival rate of OPCs decreased, apoptosis increased and the release of LDH increased with GluR3B Ab's treatment. GluR3B Ab's enhanced the level of intracellular Ca2+ and reactive oxygen species (ROS), caused mitochondrial potential collapse measured by JC-1 and promoted mitochondrial cytochrome C release. AMPARs antagonist NBQX reversed OPCs apoptosis caused by GluR3B Ab's. Taken together, these data suggests that AMPAR was involved in GluR3B Ab's-induced OPCs toxicity by mitochondrial dysfunction. The study revealed a new mechanism for OPCs excitotoxicity in many central nervous system diseases such as epilepsy.

RRM1, TUBB3, TOP2A, CYP19A1, CYP2D6: Difference between mRNA and protein expression in predicting prognosis of breast cancer patients.

The study investigated the clinical significance of RRM1 (ribonucleoside reductase subunit M1), TUBB3 (tubulin-ß-III), TOP2A (DNA topoisomerase II), CYP19A1 (cytochrome P450, family 19, subfamily A, polypeptide 1) and CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) for the diagnosis and possible predictive roles in breast cancer. Tissue microarray detected the expression of RRM1, tubulin-ß-III, Topo IIα, CYP19A1 and CYP2D6 protein in breast cancer tissue and tissue adjacent to tumors (TATs). In addition, a publically available tool, was used to assess the prognostic value of their gene expression in breast cancer (http://kmplot.com). Analysis for relapse-free survival (RFS), disease-free survival (DFS) and overall survival (OS) was performed. Cytoplasmic RRM1, tubulin-ß-III, CYP19A1 and Topo IIα staining were significantly higher in breast cancer tissues compared with TATs (P<0.050). Significant correlation occurred between RRM1 expression with pathological classification (P=0.018), lymph node involvement (P=0.035) and ER status (P=0.003). Tubulin-ß-III and CYP2D6 expression correlated significantly with tumor grade (P=0.021 for tubulin-ß-III and P=0.029 for CYP2D6, respectively). Cox analysis showed that the protein expression of CYP2D6, CYP19A1, RRM1, Topo IIα or tubulin-ß-III was not an independent prognostic factor. A significant association occurred between RFS and TUBB3, TOP2A, CYP19A1, and CYP2D6 mRNA expression. With CYP19A1 (P<0.001) and CYP2D6 (P<0.001), a high expression was associated with good clinical outcome. Conversely, a low expression of TUBB3 (P<0.001) and TOP2A (P<0.001) was associated with good clinical outcome. TUBB3 (P=0.0004) and TOP2A (P<0.001) were significant prognostic factors in predicting the patient OS. The expression of RRM1, tubulin-ß-III, Topo IIα and CYP19A1 in tumor tissues was significantly higher than that in TATs. TUBB3, TOP2A, CYP19A1 and CYP2D6 gene expression, but not protein expression, was associated with patient survival.

Successful treatment of a patient with congenital kyphoscoliosis associated with tethered cord.

Tethered cord is a common finding in congenital scoliosis. The most frequently advocated approach for this condition is to perform prophylactic detethering of the cord before scoliosis corrective surgery. The authors report on a 14-year-old patient with congenital thoracic kyphoscoliosis associated with a tethered cord, who developed progressive paraparesis and was successfully treated by posterior spine shortening osteotomy alone without prophylactic untethering. The patient had a 103° scoliotic curve together with a 93° kyphotic curve with an apical vertebra of T-7. Furthermore, he developed a significant progression of neurological deficits, including weakness of both legs and urinary and bowel incontinence. Preoperative MRI revealed that the spinal cord was entrapped by the apical vertebra and the low-placed conus medullaris was at approximately L-5. A posterior vertebral column resection of T-7 was performed for the purpose of simultaneously correcting the kyphoscoliosis and releasing tension on the tethered cord without a true detethering surgery. The patient's spinal cord function recovered completely from Frankel D to Frankel E by 6 months after the procedure. Evaluation at 31 months after surgery showed maintenance of good curve correction and normal neurological function.

Salvianolic acid B attenuates spinal cord ischemia-reperfusion-induced neuronal injury and oxidative stress by activating the extracellular signal-regulated kinase pathway in rats.

BACKGROUND: Salvianolic acid B (SalB), the main bioactive compound isolated from the traditional Chinese medicinal herb broad Radix Salviae Miltiorrhizae exerts a spectrum of pharmacologic activities. We investigated the effects of SalB treatment in a rat model of spinal cord ischemia and reperfusion (I/R) injury and the underlying mechanism. MATERIALS AND METHODS: SalB was administered at 1, 10, or 50 mg/kg after spinal cord ischemia. The potential protective effects on spinal cord injury were determined by spinal cord edema, infarct volume, and motor function assessment of the hind limbs. RESULTS: SalB treatment significantly decreased spinal cord edema and infarct volume and preserved motor function of the hind limbs in a dose-dependent manner. SalB administration ameliorated the generation of oxidative products and preserved antioxidant defense activities in the injured spinal cord at both 4 and 24 h after I/R injury. Moreover, SalB prolonged the I/R injury-induced activation of extracellular signal-regulated kinase (ERK), and blocking ERK activation with PD98059 partially prevented the neuroprotective effects of SalB. CONCLUSIONS: These findings demonstrate the neuroprotective effects of SalB in a spinal cord I/R injury model and suggest that SalB-induced neuroprotection was mediated by ERK activation.

Incidence, risk factors and clinical outcomes of peripherally inserted central catheter spontaneous dislodgment in oncology patients: a prospective cohort study.

PURPOSE: Peripherally inserted central catheter (PICC) spontaneous dislodgment is insidious in onset and prone to cause complications. We performed a prospective cohort study to examine the incidence, risk factors and clinical results of PICC spontaneous dislodgment in oncology patients to facilitate successful early diagnosis, prophylaxis and management. PATIENTS AND METHODS: Consecutive oncology patients, undergoing placement of PICCs, were enrolled and prospectively followed up until their catheters were removed or PICC spontaneous dislodgment presented. The patients with PICC spontaneous dislodgment or catheter-associated thrombosis (CRT) were followed up for an extra three months from the date of diagnosis. The main endpoint was PICC spontaneous dislodgment, and the sub-endpoints were CRT and catheter in-place time. The PICC insertion team, nurses, interventional radiologists and oncology doctors collected longitudinal data. RESULTS: Over a total of 60,894 days of cumulative follow-up, 21 out of 510 PICCs presented spontaneous dislodgment, leading to an incidence rate of 4.12%. The CRT rate of the group with PICC spontaneous dislodgment was much higher than that of the group without PICC spontaneous dislodgment (RR=17.46, 95% CI: 8.29-36.82, p=1.09×10(-17)). Five baseline exposure factors, including primary lung cancer, metastatic lung cancer, chest radiotherapy, vigorous coughing and severe vomiting, were significant risk factors of PICC spontaneous dislodgment. Basilic vein access (odds ratio [OR]=0.39, 95% CI: 0.16-0.95, P=0.04) was a protective factor against PICCSD in univariate analysis. Among these factors, the independent significant risk factors were vigorous coughing (OR=6.14, 95% CI: 1.70-22.16, P=0.01) and severe vomiting (OR=3.70, 95% CI: 1.28-10.68, P=0.02). CONCLUSION: The incidence rate of PICC spontaneous dislodgment is 4.12% (0.34 per 1000 catheter-days); PICC spontaneous dislodgment significantly increases the risk of CRT and shortens catheter in-place time. Vigorous coughing and severe vomiting were independent risk factors of PICC spontaneous dislodgment among oncology patients.

Anatomic assessment of femoral tunnel by transtibial drilling technique in double-bundle anterior cruciate ligament reconstruction: an in vivo study.

OBJECTIVE: To evaluate the anatomy of femoral tunnels created by simulated transtibial technique in double-bundle anterior cruciate ligament (ACL) reconstruction. METHODS: Two tibial tunnels, anteromedial (AM) and posterolateral (PL), were drilled 45?and 55?to tibial plateau respectively. On the femoral side, the AM and PL tunnels were drilled through anteriomedial portal. After the four tunnels were established, the shaft of a reamer was introduced into the joint through tibial tunnel and reached against the lateral wall of intercondylar notch. The position that the reamer shaft can reach was marked and recorded. RESULTS: Neither femoral AM nor PL tunnel opening can be fully or partially reached by the reamer shaft through the tibial AM tunnel in all cases. The evaluation through the tibial PL tunnel showed that only in 8 of 50 cases (16%) the femoral AM tunnel opening and in 4 cases (8%) the PL opening can be fully reached. On the other hand, in 12 cases (24%) the femoral AM tunnel opening and in 10 cases (20%) the PL opening can be partially reached by the shafts through the tibial PL tunnel. CONCLUSION: The result strongly suggests that transtibial technique is not well competent for femoral tunnel drilling in anatomic double-bundle ACL reconstruction as we have hypothesized.

Safety and efficacy of 1-stage surgical treatment of congenital spinal deformity associated with split spinal cord malformation.

STUDY DESIGN: Retrospective clinical study. OBJECTIVE: The aim of this study was to evaluate retrospectively the safety and efficacy of 1-stage surgical treatment of 45 consecutive patients, who had progressive congenital spinal deformity associated with split spinal cord malformation (SSCM). SUMMARY OF BACKGROUND DATA: For correction of progressive congenital spinal deformity with SSCM, it has been reported that all SSCM should be operated on before any orthopedic intervention, and then surgery for correction and stabilization of the spinal deformity should be performed 3 to 6 months later. Recently, different viewpoints have been approved, and the common treatment of these 2 associated conditions needs to be re-evaluated. METHODS: Patients had 1-stage surgery. After exposure of the determined levels and placement of instruments, bony spur was resected in the patients of type 1; in patients of type 2, we did nothing to the SSCM. In the corrective stage of surgery, posterior fusion surgery was performed in 38 patients; nonfusion surgery was performed in 7 patients. RESULTS: Thirty-six female patients and 9 male patients formed the basis of the study. The mean age was 14 years, and the mean follow-up period was 31 months. Type 1 SSCM was in 15 patients, and type 2 SSCM was in 30 patients. Seven patients had progressive neurological deteriorations preoperatively. The mean major curves were corrected from an average of 73.7° to 33.5°, with a correction rate of 54.5%. The overall complication was transient, including 2 patients of neurological compromise and 1 patient of cerebrospinal fluid leakage. The average loss of correction at final follow-up was 2.5° for major curves. CONCLUSION: The 1-stage surgical treatment of congenital spinal deformity associated with SSCM provides a satisfactory option to improve the spinal deformity without significant complications effectively. Neurosurgical interventions are recommended to patients with type 1 SSCM before spinal deformity surgery; however, patients with type 2 SSCM can be treated safely without a need of neurosurgical intervention.

RIP1 mediates the protection of geldanamycin on neuronal injury induced by oxygen-glucose deprivation combined with zVAD in primary cortical neurons.

Caspase-dependent apoptosis is considered one of the most important cell death pathways. When the apoptotic process is blocked, a form of programmed necrosis called necroptosis occurs. Apoptosis and necroptosis may share some regulatory mechanisms. Recent studies indicated that receptor interacting protein 1 (RIP1), an Hsp90-associated kinase, is an important regulatory switch between apoptosis and necroptosis. In this study, we showed that oxygen-glucose deprivation (OGD) combined with a caspase inhibitor zVAD (OGD/zVAD)-induced RIP1 protein expression in a time-dependent manner. We found that geldanamycin (GA), a benzoquinone ansamycin, protected against neuronal injury induced by OGD/zVAD treatment in cultured primary neurons. More importantly, GA decreased RIP1 protein level in a time- and concentration-dependent manner. In this study, we found that GA also decreased the Hsp90 protein level, which caused instability of RIP1 protein, resulting in decreased RIP1 protein level but not RIP1 mRNA level after GA treatment. We concluded that the GA-mediated protection against OGD/zVAD-induced neuronal injury was associated with enhanced RIP1 protein instability by decreasing Hsp90 protein level. GA and its derivatives may be promising for the prevention of neuronal injury during ischemic injury.

[The clinical study of epithelioid angiosarcoma in deep soft tissue].

OBJECTIVE: To analyze the histopathology of, surgery for, and prognosis (survival rate, local recurrence rate, metastases rate, function) of epithelioid angiosarcoma (EA). METHODS: Seven patients diagnosed as EA were received treatment in our department from May 2001 to May 2011. According Enneking staging, 3 patients were classified as IIA, 3 for IIB, and 1 for III. Wide excision was performed in 3 patients and amputation in 4 patients. Seven patients were followed up from 3 to 20 months. RESULTS: One patient had local recurrence 3 months after wide excision. Five patients had metastases at 4 to 20 months postoperatively. The cumulative survival rate at 0.5, 1 and 2 years postoperatively were 67%, 22% and 0. The function of 3 patients after limb salvage operation was good in 2 cases and poor in 1 case. The tumor site, surgical staging, and safe margin were crucial factors affecting survival rate. CONCLUSIONS: The prognosis of EA in deep soft tissue was poor. Customized, multimodality treatment and safe margin in operation may increase the survival rate as well as decrease recurrence and metastasis.

[Researched of PJ34 which is protective effect on the glutamate-induced HT-22 cell damage].

AIM: To poly ADP ribose polymerase inhibitors PJ34 on glutamate neurotoxicity induced protective effect, as PJ34 in ischemic cerebrovascular disease provide a reference for clinical applications. METHODS: After the cultured HT-22 cells were treated with 5 mmol/L Glu induction treatment, divided into the PJ34 group subsequently given 50 micromol/L PARP inhibitor PJ34 protection effects processing. Inhibition rate of each group and the PARP activity of changes. RESULTS: PJ34 group after 24 h, inhibition rate of HT-22 cells were markedly decreased (P<0.05). PJ34 PARP activity than the control group was significantly lower (P<0.05). CONCLUSION: PJ34 PARP activity by reducing increased glutamate-induced HT-22 cell viability, and thus play a protective effect on cells.

Salvage of amputated thumbs by temporary ectopic implantation.

PURPOSE: To determine the indications and benefits of ectopic implantation in the salvage of amputated thumb. BASIC PROCEDURES: Two cases of avulsed amputated thumbs were temporarily ectopically implanted onto the forearm and foot, with microvascular anastomoses. When the stump condition allowed, and the soft-tissue defects were repaired, the ectopic implanted thumbs were replanted to their anatomic positions. RESULTS: Both thumbs survived the temporary ectopic implantation and second-stage replantation. The length of the thumbs was maintained, and the thumbs regained their function in 16- and 10-week follow-ups. CONCLUSIONS: Temporary ectopic implantation of amputated parts provides an innovative procedure for the salvage of amputated thumbs under special circumstances. Although this procedure is very demanding, it does deserve special consideration in reconstructive microsurgery, since it offers the possibility to salvage amputated thumbs with extensive soft tissue loss of the hand, by preserving the anatomy and restoring the function of severely injured hands.

A novel arthroscopic procedure for fixation of avulsion fracture of tibial attachment of anterior cruciate ligament guided by meniscal stitching needle.

OBJECTIVE: To introduce a novel technique in which meniscal stitching needle is used as a puller to induct steel wire to secure the tibial eminence avulsion under arthroscopic visualization, and evaluate the clinical results. METHODS: From 1999 to 2005, fifteen cases of tibial eminence avulsion were treated with this new technique. Lysholm scoring scale system was used to assess knee function before and after surgery. Regular plain anteroposterior and lateral X-ray films were undertaken to detect the bony healing of avulsed fragment. RESULTS: The operating time could be controlled within 30 minutes. No complications such as intraarticular infection, iatrogenic injury, fibroarthritis or nonunion of fracture occurred in this group. X-ray film revealed that bony healing in all 15 cases was achieved from 6 weeks to 12 weeks postoperatively. Lysholm score was improved from 19.1+/-15.2 (ranging from 10 to 56) preoperatively to 97.5+/-3.7 (ranging from 91 to 100) postoperatively on average in 12-54 months follow up (mean 23 months). The statistically significant difference was shown in Student's t test (t equal to 18.483, P equal to 3.100 x 10(-11), P < 0.01). Wire breakage was found in two patients whose wires were removed 8 months and 14 months after initial operation, respectively. CONCLUSION: This technique has many advantages, such as simplicity, wide indications from type II to type IV fractures, minimal invasion, short operating time and predictable satisfactory results.

Histological comparison of fate of ligamentous insertion after reconstruction of anterior cruciate ligament: autograft vs allograft.

OBJECTIVE: To analyze the histological results and the biological remodeling of ligamentous insertion after the reconstruction of anterior cruciate ligament (ACL) with autograft or allograft tendon. METHODS: Extensor digitorum tendon was harvested from hind limb as graft material and transplanted to reconstruct the resected ACL in 12 mongrel dogs. Each free tendon end was secured by holding sutures and then the sutures were tied to the post screw at the femoral and tibial bony tunnel outlet after transplantation respectively. Autograft was randomly performed on one side of knee while allograft on the other side of knee. After transplantation, the histological analysis was undertaken at the 6th, 12th weeks and the 6th month using hematoxylin-eosin (HE) stain under light microscope. RESULTS: The insertion structure of normal ACL typically consisted of four layers, i.e., dense connective tissue, fibrocartilage, mineralized fibrocartilage and bone. There was a distinct regular tidemark line between fibrocartilage and mineralized fibrocartilage. At the 6th week postoperatively, loose connective tissue presented in the interspace between graft and bony tunnel wall in both autograft and allograft groups. At the 12th week postoperatively, the collagenous fibers between autograft and tunnel wall became well organized and the four layers of insertion with discontinuous tidemark line were demonstrated indistinctly in autograft group but not in allograft group. At the 6th month postoperatively, both of a clear and continuous tidemark line and distinct four layers could be seen in autograft group. In allograft group, only a waved discontinuous tidemark line was shown and either the anatomic morphology or the maturity of insertion was inferior to that of autograft group. CONCLUSIONS: At the 6th month postoperatively, although the ligament-cartilage insertion is primarily formed after ACL reconstruction with autograft or allograft tendon, the histological morphology and the maturation of insertion of autograft tendon are better than those of allograft group, which suggests that postoperative rehabilitation should be paid more attention and could be safer if little delayed during ACL reconstruction with allograft tendon.