miR-210 Participates in Hepatic Ischemia Reperfusion Injury by Forming a Negative Feedback Loop With SMAD4.

BACKGROUND AND AIMS: Hepatic ischemia-reperfusion (IR) injury is a major complication of liver transplantation, resection, and hemorrhagic shock. Hypoxia is a key pathological event associated with IR injury. MicroRNA-210 (miR-210) has been characterized as a micromanager of hypoxia pathway. However, its function and mechanism in hepatic IR injury is unknown. APPROACH AND RESULTS: In this study, we found miR-210 was induced in liver tissues from patients subjected to IR-related surgeries. In a murine model of hepatic IR, the level of miR-210 was increased in hepatocytes but not in nonparenchymal cells. miR-210 deficiency remarkably alleviated liver injury, cell inflammatory responses, and cell death in a mouse hepatic IR model. In vitro, inhibition of miR-210 decreased hypoxia/reoxygenation (HR)-induced cell apoptosis of primary hepatocytes and LO2 cells, whereas overexpression of miR-210 increased cells apoptosis during HR. Mechanistically, miR-210 directly suppressed mothers against decapentaplegic homolog 4 (SMAD4) expression under normoxia and hypoxia condition by directly binding to the 3' UTR of SMAD4. The pro-apoptotic effect of miR-210 was alleviated by SMAD4, whereas short hairpin SMAD4 abrogated the anti-apoptotic role of miR-210 inhibition in primary hepatocytes. Further studies demonstrated that hypoxia-induced SMAD4 transported into nucleus, in which SMAD4 directly bound to the promoter of miR-210 and transcriptionally induced miR-210, thus forming a negative feedback loop with miR-210. CONCLUSIONS: Our study implicates a crucial role of miR-210-SMAD4 interaction in hepatic IR-induced cell death and provides a promising therapeutic approach for liver IR injury.

Surgery for thoracic myelopathy caused by ossification of the ligamentum flavum.

Between January 1996 and December 2003, our department treated 16 patients (10 men and 6 women; average age 57.5 years) by performing a laminectomy for thoracic myelopathy caused by ossification of the ligamentum flavum (OLF). We followed up all patients for 36 to 86 months (mean follow-up time, 57.3 months). The mean (+/-standard deviation) Japanese Orthopaedic Association score increased from 5.0+/-1.4 points before the operation to 7.7+/-1.9 points at the last follow-up (p<0.01). The average values for pre-operative and post-operative kyphosis of the involved vertebrae were 5.8 degrees +/-4.1 degrees and 8.8 degrees +/-6.0 degrees , respectively; the mean increase in kyphosis was only 3.0 degrees +/-2.4 degrees . An intraoperative dural tear was the main complication and none of the patients developed severe neurological complications. We conclude that laminectomy was both effective and safe in the treatment of thoracic OLF, but it must be performed with great care because of frequent dural adhesions to the OLF. The increase in kyphosis after the laminectomy was minimal when most of the facet joints were left intact and when the patient followed a back extensor exercise program post-operatively.

Cancer testis antigen 55 deficiency attenuates colitis-associated colorectal cancer by inhibiting NF-κB signaling.

Colitis-associated cancer (CAC), a prototype of inflammation-associated cancer, is one of the most common gastrointestinal tumors. As a potential cancer testis antigen (CT antigen), cancer testis antigen 55 (CT55) is expressed in different tumors and normal testes. However, its role in CAC remains unknown. Here, we identified CT55 as a new potent promoter of CAC. We discovered that Ct55 deficiency alleviated inflammatory responses, decreased cell proliferation and colitis-associated tumorigenesis in an azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model. Mechanistically, CT55 acts as an accelerator of tumor necrosis factor (TNF)-α-induced nuclear factor-κB (NF-κB) signaling. Upon stimulation with TNF-α, CT55 interacts with the IκB kinase (IKK) complex, which increases the phosphorylation of IKKα/ß and activates IKK-p65 signaling, while knockout of CT55 blocks IKK-p65 signaling. Notably, inhibition of IKK abolished the positive effect of CT55 on NF-κB activation. Collectively, our findings strongly indicate that CT55 deficiency suppresses the development of CAC and that the CT55-TNF-α-induced NF-κB axis may represent a promising target for CAC therapy.

[Case-control study on two different approaches for the treatment of thoracolumbar fracture without neurological symptoms].

OBJECTIVE: To investigate the clinical effects of two surgical approaches for the treatment of thoracolumbar fracture without neurological symptoms. METHODS: From January 2008 to December 2009, 40 cases with thoracolumbar fractures without neurological symptoms treated by surgery were respectively analyzed. Among the patients, there were 13 males and 27 females, with an average age of 46 years (ranged, 26 to 61 years). Twenty patients in group A treated through posterior median approach; twenty patients in group B were treated through paraspinal muscle approach. All the patients were received the same posterior spinal internal fixation (Sofamor Inc (Basis)). Operating time, blood loss, postoperative drainage, postoperative bed time, VAS score 24 and 72 hours after operation, postoperative Cobb angle correction rate, correction rate of vertebral collapse were analyzed. RESULTS: There were no significant difference in postoperative Cobb angle correction rate and vertebral collapse rate (P < 0.05); while the index such as operating time, blood loss, postoperative drainage, postoperative bed time and VAS score 24 h and 72 h after operation in group B is better than group A. CONCLUSION: Treatment of thoracolumbar fracture through posterior median approach has an advantage of minimal invasive, less bleeding and rapidly recovery, but the patients with neural symptoms and intraspinal occupying more than 1/3 is not suggested.

Comparison of the mini-midvastus with the mini-medial parapatellar approach in primary TKA.

A prospective randomized study was performed to compare the clinical and radiological results of primary total knee arthroplasties (TKAs) using a mini-midvastus approach or a mini-medial parapatellar approach in 134 patients. The mini-midvastus approach was used on 68 patients (group A) and the mini-medial parapatellar approach on 66 patients (group B). All knees were implanted with the same posterior-stabilized prosthesis by the same surgeon (T.-S.T.) with the same set of downsized instruments. Mean follow-up in both groups was 30.5 months (range, 24-48 months). Patients in group A achieved an active straight-leg raise and 90° of flexion significantly earlier (P=.017 and P=.025, respectively). However, no significant difference was detected between the groups with respect to range of movement and Knee Society scores at all the postoperative visits and at final follow-up (all, P>.05). In contrast, the tourniquet time was significantly longer in group A (P=.015), with a higher incidence of medialized tibial component (P=.031). We believe that the early clinical results are similar between the mini-midvastus and mini-medial parapatellar approach. The mini-medial parapatellar approach is easier to initially apply and provides better visualization for TKA.