Objective To investigate the changes of somatosensory-evoked potential(SEP)during an mild impact spinal cord injury in rats 80 as to evaluate its potential value in prevention of such iatrogenic damage. Methods Twenty-four SD rats weighing(340±28)g were randomly divided into two groups,ie,sham control group(only exposure without impact at C6)and injury group(mild impact spihal cord injury at C6).SEP wss recorded in both groups.The changes of SEP in waveform,amplitude and latency were observed and compared between groups and between operations.The gross dissection and histologic analysis were performed after surgery for comparative study. Results SEP waveforms,amplitude and latency showed no significant change in the sham control group.In contrast,the SEP waveform and amplitude animals showed significant changes in the injury group after impact spinal cord injury and the amplitude was decreased from pre-injury(1.3±0.7)μV to post-injury(0.5±0.4)μV(P<0.05),while the latency showed no significant difference between(11.1±2.1)ms pre-injury and(10.7±1.3)ms post-injury(P>0.05).However,this abnormal change appeared in a temporary period at(5.7±3.2)minutes after impact and lasted for about(7.1±3.3)minutes.Diffused hemorrhagic nidus could be seen in the injured cord,which was not found in the sham control group. Condusions Mild impact spinal cord injury may induce transient abnormalities of SEP in waveform and amplitude,which requires careful monitoring in clinical practice.The sudden change in SEP may be associated with impact and vibration damage to the spinal cord,suggesting timely use of protection measures for spinal cord.

Objective To compare the biomechanical properties of mono-segTnent pedicle instru-mentation and its combination with bone cement fixation in treatment of thoracolumbar fractures. Meth-ods Eight fresh specimens of calf spines ( T11 -L3 ) were used for development of incomplete burst frac-ture models at the vertebral body of L1. Mono-segment pedicle instrumentation and its combination with vertebroplasty were respectively applied in each specimen subsequently to restore spinal stability. A cyclic loading with pure moment of 4 Nm was applied to specimens, with load frequency of 0.5 Hz for 2 000 cy-cles. Range of motion (ROM) at flexion/extension, left/right lateral bending and left/right axial rotation of the fixated segment at different status of intact, injury, fixation and cyclic loading was determined by spinal three-dimensional instability test system. Results ROM after treatment with two fixation tech-niques and that at different directions after cyclic loading were distinctly smaller than that of intact and fractured models (P <0.05 ). Under mono-segment pedicle instrumentation combined with bone cement fixation, ROM at flexion, extension, lateral bending and axial rotation was 0.40°, 0. 53°, 0.86° and 0.55° respectively and that after cyclic loading was 0.10°, 0.07°, 0.19° and 0.08°respectively, which were all lower than those of monosegmental fixation, especially at flexion and axial rotation, with statisti-cal difference (P <0.05 ). Conclusions Both fixation techniques can provide instant stabihty of the fractured spine and have good fatigue resistance effect. However, mono-segment pedicle instrumentation is inferior to mono-segment pedicle instrumentation plus bone cement fixation in treatment of fractured verte-bral body at flexion and axial rotation.

OBJECTIVETo establish a model bearing human lung cancer xenograft with bone metastasis in mice with normal immune function.

METHODSForty female C57BL/6J mice were randomly allocated into 4 equal groups, including a control group and 3 immunosuppression groups treated with low, moderate, and high doses of dexamethasone (50, 100, and 150 mg, respectively). Four days after immune suppression, the mice were subjected to percutaneous injection of1.0×10(9) L(-1) A549 cells into the tibial plateau, and the bone defects were assessed radiographically 28 days after modeling. HE staining and immunohistochemical staining were used to examine the tumor tissues and bone tissue damages.

RESULTSIn each of the 4 groups one mouse died during tumor cell injection. Only 1 mouse showed tumor formation in low-dose immunosuppression group, as compared to 7 and 4 in moderate- and high-dose immunosuppression groups. X-ray and microCT scan showed significant tibial bone destruction in moderate- and high-dose groups. The moderate- and high-dose groups showed similar ALP activities but both were significantly higher than those in the other two groups (P<0.05).

CONCLUSIONImmunosuppression with a moderate dose of dexamethasone results in longer survival time of the human lung cancer xenograft-bearing model mice as well as a higher tumor formation rate.

Animals ; Bone Neoplasms ; secondary ; Cell Line, Tumor ; Dexamethasone ; pharmacology ; Disease Models, Animal ; Female ; Humans ; Immunosuppression ; Lung Neoplasms ; pathology ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation

Sec61β, a subunit of the Sec61 translocon complex, is not essential in yeast and commonly used as a marker of endoplasmic reticulum (ER). In higher eukaryotes, such as Drosophila, deletion of Sec61β causes lethality, but its physiological role is unclear. Here, we show that Sec61β interacts directly with microtubules. Overexpression of Sec61β containing small epitope tags, but not a RFP tag, induces dramatic bundling of the ER and microtubule. A basic region in the cytosolic domain of Sec61β is critical for microtubule association. Depletion of Sec61β induces ER stress in both mammalian cells and Caenorhabditis elegans, and subsequent restoration of ER homeostasis correlates with the microtubule binding ability of Sec61β. Loss of Sec61β causes increased mobility of translocon complexes and reduced level of membrane-bound ribosomes. These results suggest that Sec61β may stabilize protein translocation by linking translocon complex to microtubule and provide insight into the physiological function of ER-microtubule interaction.
Animals ; COS Cells ; Caenorhabditis elegans Proteins ; genetics ; metabolism ; Cell Line, Tumor ; Cercopithecus aethiops ; Endoplasmic Reticulum ; metabolism ; Homeostasis ; Humans ; Microtubules ; metabolism ; SEC Translocation Channels ; deficiency ; genetics ; metabolism

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.