Initial clinical experiences of the muscle-preserving double door cervical laminoplasty with adjustable mini plates.

Shirashi's double door laminoplasty method was a popular decompression procedure for cervical myelopathy. In this paper, we introduced a modified double door laminoplasty based on Shirashi's method with preliminary results. This study retrospectively analyzed 22 patients who underwent modified double door laminoplasty. During procedure, a single segment of the unilateral lamina was separated from the cervical semispinalis muscle and the multifidus muscle space for the preparation of lamina groove. A self-developed mini titanium plate was used to fix the inner side of the spinous process to complete the fixation after open-door process. The VAS, JOA scores and QoL scale were recorded for pain assessment, neurological and functional recovery. The overall curvature and range of motion of C2-C7 were measured with x-ray images. Changes in sagittal diameter of spinal canal were measured by CT scans. MRI was used to measure the cross-sectional area of cervical paravertebral muscles. All 22 patients successfully recovered with this procedure. The mean operation time, blood loss and follow-up durations were 117 ± 25 min, 149 ± 32 ml and 16.1 ± 3.6 months respectively. The preoperative, 3-month postoperative and 12-month postoperative JOA scores were 9.35 ± 3.25, 13.74 ± 4.86 and 15.73 ± 5.19 respectively. with improvement rates of 57.4% and 83.4%. Mean VAS scores before, 3 months after and 12 months after surgery were 1.81 ± 0.79, 2.82 ± 1.56 and 2.18 ± 1.34 respectively. The C2-7 lordotic angle and overall range of motion shows no statistical difference preoperatively and 12 post-surgery. The average sagittal diameter of the cervical spinal canal was enlarged from 9.15 ± 1.55 mm to 14.25 ± 1.46 mm. The average area of cervical paravertebral volume measured preoperatively and 3 months post operation was 84% of pre-operative value respectively. This value was improved to 93% of the preoperative value at 12 months post-surgery. This paper introduced initial experience on a modified posterior cervical double-door laminoplasty that was based on Shirashi's method, featuring creating bilateral laminar grooves on both sides and fixing central gap with self-developed mini plates. This procedure prevented obvious axial symptoms and improved patients' quality of life, which provided a baseline for further research with larger cohorts.

Replication and transcriptionomic analysis of human noroviruses in human intestinal enteroids.

Human noroviruses (HuNoVs) are a major cause of epidemic and sporadic cases of acute gastroenteritis worldwide. Recently, human intestinal enteroids (HIEs) have been shown to support the replication of HuNoVs, and be an excellent model to study HuNoV-host interactions. We implemented the HIE system in our laboratory and investigated the global molecular events associated with the mechanism of HuNoV-host interactions. Successful replication was observed for several norovirus GII genotypes, and totally 5,376 genes with different expression in HIEs were identified during infection. Bioinformatics analysis revealed that several important pathways, especially the "Signal transduction" and "Immune system" pathways, were involved in the HuNoV-host interaction. Quantitative PCR results validated that IFN-λ instead of IFN-ß was elevated in HIEs after infection. Our study showed the holistic understanding of the transcriptome events in the HIE model infected by HuNoVs, and highlighted the important role of IFN-λ signaling in the HuNoV-host interactions.

miR-185 suppresses progression of Ewing's sarcoma via inhibiting the PI3K/AKT and Wnt/ß-catenin pathways.

BACKGROUND: miRNAs are confirmed to play essential roles in tumorigenesis and progression of cancers, including Ewing's sarcoma. miR-185 has been reported to be downregulated in some tumors, whereas the role of miR-185 in Ewing's sarcoma remains unclear. PURPOSE: The objective of this study was to investigate the role of miR-185 in the progression and metastasis of Ewing's sarcoma and explore the associated mechanism. MATERIALS AND METHODS: Ewing's sarcoma cell line RD-ES was transfected with pCMV-MIR-miR185 vector to upregulate the expression of miR-185. Cell Counting Kit 8 and colony formation assays were used to assess the effect of miR-185 on cell proliferation. The effect of miR-185 on cell migration and invasion was detected by transwell assay. Flow cytometry assay was performed to detect apoptosis rate of RD-ES cells. The protein levels of apoptosis-related proteins was determined using Western blot assay or immunohistochemistry assay. Dual-luciferase reporter assay was used to validate the regulation between miR-185 and its target gene. RESULTS: Upregulation of miR-185 caused significant inhibition on cell growth capacity, migration and invasion of Ewing's sarcoma cell RD-ES. Besides, upregulation of miR-185 was observed to accelerate cell apoptosis in a mitochondrial pathway through regulating Bcl-2/Bax, Caspase 3, and Caspase 9 in Ewing's sarcoma in vitro. Moreover, upregulation of miR-185 was found to suppress the PI3K/Akt/mTOR and Wnt/ß-catenin pathways in RD-ES cells. Furthermore, we identified that E2F6 was a target gene for miR-185, and the suppression on cell proliferation caused by overexpression of miR-185 was significantly rescued by the upregulation of E2F6 in RD-ES cells. CONCLUSION: miR-185 is involved in cell growth, motility and survival of Ewing's sarcoma as a tumor suppressor via suppressing PI3K/Akt/mTOR and Wnt/ß-catenin pathways and targeting E2F6.

TIMP-1 suppressed by miR-138 participates in endoplasmic reticulum stress-induced osteoblast apoptosis in osteoporosis.

The aim of this study was to investigate the role of miR-138 in osteoporosis and its underlying mechanism. Hydrogen peroxide (H2O2) was used to induce osteoporotic injury of osteoblasts. The cell viability and apoptosis of MC3T3-E1 cells was assessed using MTT assay and flow cytometry, respectively. The cell transfection was carried out to modulate the expression levels of miR-138 and TIMP-1 in MC3T3-E1 cells. Luciferase reporter gene assay was performed to determine the interaction between miR-138 and TIMP-1 3'UTR. In the present study, H2O2 inhibited osteoblasts growth and induced intracellular endoplasmic reticulum (ER) stress accompanied by high expression of miR-138. We also confirmed that miR-138 promoted osteoblasts apoptosis in vitro and in vivo. MiR-138 was further indicated to inhibit osteoblast survival via negative regulating TIMP-1 expression. Moreover, the downregulated TIMP-1 also mediated the ER stress-induced apoptosis of osteoblasts. We confirmed that miR-138 and ER stress were induced in osteoporosis and then promoted the apoptosis of osteoblasts, at least in part, through TIMP-1.

Severe fracture-dislocation of the thoracic spine without any neurological deficit.

BACKGROUND: Fracture-dislocations of the thoracic spine without spinal cord injury are very rare. CASE PRESENTATION: A 35-year-old woman presented to our emergency department with complete T6-7 fracture-dislocation without any neurological loss had undergone a surgical reduction and fixation. CONCLUSIONS: The radiological severity of fracture-dislocation pattern doesn't correlate sometimes with the clinical manifestation.

Hydrogen bonding-promoted efficient Ru-catalyzed ring-closing metathesis of demanding homoallyl 2-(hydroxymethyl)acrylates.

An efficient hydrogen bonding-guided ring-closing metathesis (RCM) reaction of sterically demanding homoallyl 2-(hydroxymethyl)acrylates catalyzed by the Hoveyda-Grubbs 2nd generation catalyst was developed and the reaction mechanism was explored. Adding a substituent to the hydroxymethyl group in this scaffold resulted in a class of challenging RCM substrates, although usable yields could be obtained. However, substrates bearing a 1-oxygenated alkyl group on the homoallylic carbon gave excellent RCM yields, providing a practical solution. Experimental and computational evidence indicated an unusual directing effect of OHCl hydrogen bonding between the substrate and Ru catalyst, which guides Ru to interact with the electron-deficient, more hindered acrylic C[double bond, length as m-dash]C bond and thus triggers the RCM process.

Plumbagin protects against glucocorticoid-induced osteoporosis through Nrf-2 pathway.

Long-term and high-dose glucocorticoids (GCs) supplementation has been linked to osteoporosis. In this study, we studied the protective role of plumbagin against GC-induced cell damage in MC3T3-E1 cells. The effect of dexamethasone (DEX) and plumbagin on cell viability was determined. DEX showed as IC-50 value of 95 µM. Further, 10 µM plumbagin treatment effectively ameliorated DEX-induced cell death by increasing the cell viability to 92 %. A further effect of plumbagin on DEX-induced oxidative stress was determined through reactive oxygen species (ROS) level, lipid peroxide content, and antioxidant status. Nrf-2 nuclear localization was analyzed through immunofluorescence. Protein expression of redox regulator Nrf-2 and their target genes HO-1 and NQO1 and osteogenic markers (OCN, OPN Runx-2) were determined by Western blot. Apoptotic effect was analyzed by mitochondrial membrane potential and caspase activities (3, 8, and 9). The results showed that DEX treatment showed a significant increase in oxidative stress through increased ROS levels and downregulation of cytoprotective antioxidant proteins and antioxidant enzyme activities. Further DEX treatment downregulated the osteogenic markers and upregulated apoptosis through decreased mitochondrial membrane potential and upregulation of caspase activities. Plumbagin treatment significantly reversed the levels of oxidative stress and apoptotic markers and protected against DEX-induced cell damage. Further, plumbagin treatment significantly improved the expression of osteogenic markers compared to DEX treatment. In conclusion, the present study shows that plumbagin offers significant protective role against DEX-induced cellular damage via regulating oxidative stress, apoptosis, and osteogenic markers.