Mechanism of the Notch1 signaling pathway regulating osteogenic factor influences lumbar disc calcification / 中国骨伤

OBJECTIVE@#To explore the mechanism of the Notch1 signaling pathway in regulating osteogenic factors and influencing lumbar disc calcification.@*METHODS@#Primary annulus fibroblasts from SD rats were isolated and subcultured in vitro. The calcification-inducing factors bone morphogenetic protein-2 (BMP-2) and basic fibroblast growth factor (b-FGF) were added to separate groups to induce calcification, which were referred to as the BMP-2 group and the b-FGF group, respectively. A control group was also set up, which was cultured in normal medium. Subsequently, cell morphology and fluorescence identification, alizarin red staining, ELISA, and quantitative real-time polymerase chain reaction (QRT-PCR) were performed to determine the effect of calcification induction. Cell grouping was performed again, including the control group, the calcification group (adding the inducer BMP-2), the calcification + LPS group(adding the inducer BMP-2 and the Notch1 pathway activator LPS), and the calcification + DAPT group (adding the inducer BMP-2 and the Notch1 pathway inhibitor DAPT). Alizarin red staining and flow cytometry were used to detect cell apoptosis, ELISA was used to detect the content of osteogenic factors, and Western blot was used to detect the expression of BMP-2, b-FGF, and Notch1 proteins.@*RESULTS@#The induction factor screening results showed that the number of mineralized nodules in fibroannulus cells in BMP-2 group and b-FGF group was significantly increased, and the increase was greater in the BMP-2 group Meanwhile, ELISA and Western blot results showed that BMP-2, b-FGF and mRNA expression levels of BMP-2, b-FGF and Notch1 in the induced group were significantly increased (P<0.01). The results of the mechanism of Notch1 signaling pathway affecting lumbar disc calcification showed that compared to calcified group, the number of fibroannulus cell mineralization nodules, apoptosis rate, BMP-2, b-FGF content, the expression levels of BMP-2, b-FGF, and Notch1 proteins were further increased significantly However, the number of mineralization nodules, apoptosis rate, BMP-2 and b-FGF levels, BMP-2, b-FGF and Notch1 protein expression levels were decreased in the calcified +DAPT group (P<0.05 or P<0.01).@*CONCLUSION@#Notch1 signaling pathway promotes lumbar disc calcification through positive regulation of osteogenic factors.

Clinical efficacy of posterior percutaneous endoscopic cervical discectomy for single level cervical spondylopathy with intraspinal ossification / 中国骨伤

OBJECTIVE@#To evaluate the effectiveness and security of posterior percutaneous endoscopic cervical discectomy (PPECD) in the treatment of single level cervical spondylopathy with intraspinal ossification.@*METHODS@#Twenty three patients with single level cervical spondylopathy with intraspinal ossification were treated by posterior percutaneous endoscopic cervical discectomy between August 2017 and July 2019. There were 16 males and 7 females, aged from 29 to 74 years old with an average of (50±13) years.The disease duration were 3 to 120 months with a median of 6 months. There were 9 cases of cervical spondylotic radiculopathy, 6 cases of cervical spondylotic myelopathy, and 8 cases of mixed cervical spondylopathy. According to the characteristics of ossification, 17 cases were osteophytes on the posterior edge of the vertebral body;3 cases were protrusion ossification;3 cases were posterior longitudinal ligament ossification. According to the position of ossification in spinal canal, 14 cases were medial and lateral type, 5 cases were central type, and 4 cases were mixed type. Posterior percutaneous cervical endoscopic cervical discectomy in patients performed by the same surgeon. Japanese Orthopaedic Association (JOA) score and visual analogue scale(VAS) were compared separately before and after operation. At 3 months after operation, clinical effect was assessed according to modified Macnab standard.@*RESULTS@#All operations were successful. The operative time was 30 to 155 (69.1±27.2) min. The bedridden time was 2 to 3(3.0±0.9) h, length of postoperative hospitalization was 2 to 7(4.1± 1.5) d. Three dimensional CT reconstruction of the cervical spine at 3 days after operation showed that ossified tissue of 13 cases were completely removed, and 10 cases were left after operation, and the residual was located at the posterior edge and/or center of the upper vertebral body. VAS score at discharge from hospital was significantly lower than that before operation (@*CONCLUSION@#For an experienced surgeon, percutaneous posterior cervical endoscopic discectomy is safe and reliable in treating single level cervical spondylopathy with intraspinal ossification, and can obtain good clinical results.

Analysis of clinical efficacy of C expanded half lamina excision combined with unilateral open-door laminoplasty for multiple segmental cervical spinal cord compression syndrome / 中国骨伤

OBJECTIVE@#To explore the clinical efficacy of C expanded half lamina excision combined with unilateral open door laminoplasty for multiple segmental cervical spinal cord compression syndrome.@*METHODS@#The clinical data of 58 patients with multiple segmental cervical spinal cord compression syndrome underwent surgical treatment between September 2014 and May 2018 were retrospectively analyzed. There were 34 males and 24 females with a mean age of 64.4 years old (ranged from 46 to 78 years old). Among them, 28 cases received the surgery of C expanded half lamina excision combined with C-C unilateral open-door laminoplasty (improvedgroup), and 30 cases received a single C-C unilateral open-door laminoplasty (traditional group). Operation time, intraoperative blood loss, complications including C nerve root palsy and axial symptoms were compared between two groups. To evaluate the situation of the imaging indicators by measuring the space available for the spinal cord through cross sectional MRI of cervical spine at the narrowest segment of C (including intervertebral disc levels of C). Pre- and post-operative Japanese Orthopedic Association(JOA) score, Neck Disability Index(NDI) score, and improvement rate of neurological function, were recorded and analyzed between the two groups.@*RESULTS@#All the patients were followed up for 12 to 18 months with an average of(14.5±1.8) months for improved group and (14.5±1.9) months for traditional group, and no significant difference was found between the two groups (>0.05). There was no significant difference in intraoperative blood loss and C nerve root palsy between the two groups (>0.05). The operation time (119±10) min vs (126±12) min and axial symptoms 7.1%(2/28) vs 26.6%(8/30) was significant difference between the two groups (0.05).@*CONCLUSION@#C expanded half lamina excision combined with unilateral open-door laminoplasty is an effective method to treat multiple segmental cervical spinal cord compression syndrome, for it can not only fully relieved spinal cord compression, but also achievedgood effect in preventing complications such as axial symptoms by reducing stripping of muscles from C2 spinous process.

Unilateral pedicle screw fixation and intervertebral fusion for the treatment of far lateral lumbar disc herniation / 中国骨伤

<p><b>OBJECTIVE</b>To explore the feasibility and clinical efficacy of unilateral pedicle screw fixation with transforaminal lumbar interbody fusion (TLIF) for the treatment of far lateral lumbar disc herniation.</p><p><b>METHODS</b>From January 2007 to January 2011, 18 patients with far lateral lumbar disc herniation underwent a unilateral TLIF procedure in conjunction with posterior unilateral pedicle screw fixation. There were 13 males and 5 females,ranging in age from 42 to 73 years (means 58.5 years). All cases had single segment involved 5 cases in L3, 4, 10 cases in L4,5,3 cases in LSS. The visual analog scale (VAS) of low back pain and leg pain and Oswestry Disability Index scores were observed in postoperative and followed-up period, and compared with preoperative.</p><p><b>RESULTS</b>The operation of 18 patients was successful,there were no severe complication. The average operative time was 105 min (85 to 125 min), the average amount of blood loss was 145 ml (90 to 340 ml). During the followed-up, the visual analog scale and Oswestry disability index scores were significant improved compared with preoperative (P < 0.05). All patients were followed up from 12 to 48 months with an average of 23 months, there was no implant break and displacement in postoperative X-ray.</p><p><b>CONCLUSION</b>The surgical procedure of unilateral pedicle screw fixation with transforaminal lumbar interbody fusion had the advantage including less invasion, quickly recovery, short operative time, and saving fixation cost, it may provide an alternative treatment for patients with far lateral lumbar disc herniation.</p>

Silencing of osteopontin promotes the radiosensitivity of breast cancer cells by reducing the expression of hypoxia inducible factor 1 and vascular endothelial growth factor / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Osteopontin (OPN) is a secreted phosphoglycoprotein (SSP) that is overexpressed in a variety of tumors and was regarded as a molecular marker of tumors. In this study, we intended to demonstrate the role of OPN in human breast cancer cell line MDA-MB-231.</p><p><b>METHODS</b>Recombinant plasmid expressing small interfering RNA (siRNA) specific to OPN mRNA was transfected into MDA-MB-231 cells to generate the stable transfected cell line MDA-MB-343, and the empty plasmid tansfected cells (MDA-MB-neg) or wildtype MDA-MB-231 cells were used as control cells respectively. Expression of OPN, hypoxia inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) proteins was analyzed by Western blotting analysis. The radiosensitivity of cells was determined by detecting cell apoptosis, cell proliferation and cell senescence.</p><p><b>RESULTS</b>HIF-1 and VEGF proteins in MDA-MB-343 cells were significantly downregulated upon the efficient knockdown of OPN expression under either hypoxia or normoxia environment. Moreover, expression of OPN protein was upregualted upon hypoxic culture. Stable OPN-silencing also decreased cell invasion, increased cell apoptosis and cell senescence, as well as reduced clonogenic survival, resulting in increase radiation tolerance.</p><p><b>CONCLUSIONS</b>Suppression of OPN gene expression can enhance radiosensitivity and affect cell apoptosis in breast cancer cells. OPN seems to be an attractive target for the improvement of radiotherapy.</p>

Clinical study of open vertebroplasty in treating thoracolumbar metastatic tumor / 中国骨伤

<p><b>OBJECTIVE</b>To explore the clinical application and therapeutic effect of open vertebroplasty for thoracolumbar metastatic tumor.</p><p><b>METHODS</b>From September 2003 to December 2009, 21 patients with thoracolumbar metastatic tumor underwent the surgical procedure of posterior spinal cord decompression and open vertebroplasty combined with short-segmental pedicle screw fixation during the same intervention. There were 14 males and 7 females, ranging in age from 48 to 73 years with the mean of 59.5 years and ranging in course of disease from 1 to 4 months with an average of 2.5 months. The primary focus of the tumor of 19 cases were established, lung carcinoma was in 8 cases, breast cancer in 4 cases, prostate carcinoma in 4 cases, hepatocarcinoma in 2 cases and thyroid carcinoma in 1 case. The primary focus of 2 cases could not be established. The spinal function according to Frankel grade, grade B was in 4 cases, C in 6, D in 5, E in 6. The lumbar-back pain, height of anterior and posterior vertebral body, Cobb angle and spinal function were recorded before and after operation.</p><p><b>RESULTS</b>The operation of all patients was successful, there were no severe complications and aggravation of spinal function. The VAS score of lumbar-back pain decreased from 8.78 +/- 0.45 preoperatively to 2.25 +/- 0.36 postoperatively. Among 16 cases combined with pathological fracture, the height of anterior spinal vertebral body increased from (12.7 +/- 2.1) mm preoperatively to (19.5 +/- 3.9) mm postoperatively; the height of posterior spinal vertebral body increased from (14.1 +/- 1.8) mm preoperatively to (20.3 +/- 2.3) mm postoperatively; Cobb angle decreased from (26.0 +/- 8.9) degrees preoperatively to (6.0 +/- 0.9) degrees postoperatively. There was significant difference above items between before and after operation (P < 0.05). The spinal function according to Frankel grade at final follow up, grade C was in 2 cases, D in 4, E in 15. All patients were followed up from 5 to 28 months with an average of 14 months, there was no loosening and breakage of internal fixity, 15 cases died during follow-up period.</p><p><b>CONCLUSION</b>The surgical intervention can effectively preserve spinal instability and alleviate the spinal cord symptoms, improve the life quality of patients. It may provide an alternative treatment for patients in poor general health and shorter life expectancy.</p>

Molecular imaging of epidermal growth factor receptor in glioma-bearing rats / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the value of 11C-PD153035 as an EGFR imaging agent in C6 tumor-bearing rat.</p><p><b>METHODS</b>The tumor-bearing rats were generated by subcutaneous injection of glioma C6 cells. Positron emission tomography/computer tomography (PET/CT) scans started as soon as intravenous injection of 11C-PD153035 (15-20 MBq/0.3 ml) was completed, images were collected continuously. The region of interest (ROI) was used to study the percentage of radioactivity in major organs and implanted tumors in the rats. The accumulation and blocking study in vitro was completed.</p><p><b>RESULTS</b>There were significant differences in 11C-PD153035 uptake among major organs. The maximum uptake in the organs ranked in the following order: liver > gastrointestinal tract > kidney > lung > brain > muscle. Radioactivity could be also observed in the tumors. The radioactivity ratio (T/NT, target/non-target) peaked (4.15) at 40 - 50 min post injection. The in vitro blocking study showed that 11C-PD153035 uptaken by C6 cells could be blocked by PD153035.</p><p><b>CONCLUSION</b>The results of this study show that 11C-PD153035 can be uptaken by EGFR-expressing tumors. 11C-PD153035 has a potential as a bioprobe to yield useful information for both diagnosis and therapy of tumors. However, the high concentration of 11C-PD153035 in the gastrointestinal tract is unfavorably affecting the tumor detection in these organs.</p>

Further characterization of the epidermal growth factor receptor ligand 11C-PD153035 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>(11)C-4-N-(3-bromoanilino)-6,7-dimethoxyquinazoline ((11)C-PD153035) has been reported as a tracer for imaging human tumors that overexpress epidermal growth factor receptor (EGFR). However it is still unclear whether (11)C-PD153035 uptake correlates with EGFR expression levels. The objective of this study was to investigate the relationship between (11)C-PD153035 accumulation and EGFR expression levels.</p><p><b>METHODS</b>Synthesis of (11)C-PD153035 was performed in the Tracerlab FXc system. Accumulation of (11)C-PD153035 by MDA-MB-468, A549 and MDA-MB-231 cells was measured in vitro. There were six tumor-bearing mice in each group. (11)C-PD153035 uptake in tumors was determined by positron emission tomography/computed tomography (PET/CT). Tumor/normal muscle tissue (T/NT) analysis in PET images was applied to quantify the PET data. Sixty minutes after PET/CT scanning, the nude mice were sacrificed and the tumors were excised. The (11)C-PD153035 accumulation in different tumors was determined by a gamma counter.</p><p><b>RESULTS</b>Close correlation existed between the uptake and the level of EGFR expression both in vitro and ex vivo (r(2) = 0.72, P < 0.001; r(2) = 0.63, P = 0.003). When the static T/NT analysis method was applied to analyze the PET data, the observed correlation was again excellent (r(2) = 0.70, P = 0.001).</p><p><b>CONCLUSIONS</b>The uptake of PET tracer (11)C-PD153035 closely correlates with the EGFR expression levels in tumor cells. (11)C-PD153035 has the potential to yield useful information for both cancer diagnosis and therapy.</p>

Advance in the Post-stroke Depression(review) / 中国康复理论与实践

@#Post-stroke depression(PSD) is one of the most common complications after stroke,and seriously influenced the quality of life of hemiplegic patients.The article would review the associated factors and mechanism of PSD.

Flow cytometric quantitative analysis of multiple tumor suppressor gene 1 (MTS1) and cyclooxygenase-2 (COX-2) gene expressions in invasive breast cancers and their clinical significance / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The purpose of the present study was to explore the expression and clinical significance of multiple tumor suppressor gene 1 (MTS1) and cyclooxygenase-2 (COX-2) gene in invasive breast cancers.</p><p><b>METHODS</b>Flow cytometry was used to analyze the expression level of MTS1 and COX-2 in cancer tissues and corresponding para-cancer tissues from 66 cases of primary invasive breast cancers.</p><p><b>RESULTS</b>In breast cancer tissues, the expression of MTS1 and COX-2 assessed by relative fluorescence intensity were 0.84 and 10.54, respectively, and were 1.61 and 4.00 in corresponding para-cancer tissues, respectively. There was a significant difference between MTS1 and COX-2 expressions in cancer and corresponding para-cancer tissues (P <0.05). The differences of MTS1 and COX-2 expression of different ages, pathological types, tumor sizes or clinical stages of the breast cancer patients were not significant (P > 0.05). The MTS1 and COX-2 expressions were 1.12 and 5.94, respectively, in lymph node metastasis positive patients, and 0.79 and 13.05, respectively, in lymph node metastasis negative patients. The differences were significant (P <0.05).</p><p><b>CONCLUSION</b>The preliminary research results suggest that MTS1 and COX-2 gene expressions play fairly important role in tumorigenesis and progression of breast cancers. MTS1 and COX-2 protein expressions have correlation with lymph node metastasis. This study provides theoretical basis for use of COX-2 selective inhibitors in prevention and treatment for breast cancer patients.</p>

Expression of MDR1 and GST-pi in osteosarcoma and soft tissue sarcoma and their correlation with chemotherapy resistance / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the expression of multidrug resistance gene 1 ( MDR1), glutathione-S-transferases-pi (GST-pi) in osteosarcoma and soft tissue sarcoma tissues from 34 patients and their correlation with chemotherapy resistance.</p><p><b>METHODS</b>MDR1 and GST-pi expressions were analyzed by real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) and flow cytometry (FCM) at mRNA and protein levels, respectively. Chemotherapy sensitivity on adriamycin, cisplatinum, fluorouracil, mitomycin C, dacarbazine, vincristine, methotrexate in tumor tissues were detected by MTT assay.</p><p><b>RESULTS</b>The nonsensitive rates on adriamycin, cisplatinum, fluorouracil, mitomycin C, dacarbazine, vincristine, methotrexate in tumor tissues were 41.18%, 17.7%, 47.1%, 50.0%, 76.5%, 61.8% and 52.9%, respectively. The expression of P-glycoprotein (P-gp) and GST-pi in tumor tissues was 1.54 and 2.58 (relative fluorescence intensity). Chi2 analysis showed that there was a positive correlation between P-gp expression and drug resistance on ADM, GST-pi expression and resistance on ADM, DDP and MMC (P < 0.05). There was not seen obvious correlation between expression of MDR1, GST-pi and age, gender, pathological type, tumor size in osteosarcoma and soft tissue sarcoma patients (P > 0.05). The expression of GST-pi was increased in patients receiving preoperative chemotherapy. The rate of postoperative recurrence was higher in patients with higher GST-pi expression level than those with lower GST-pi expression level before operation (P < 0.05).</p><p><b>CONCLUSION</b>Individual differences exist in chemotherapy sensitivity and expression of MDR1 and GST-pi in osteosarcoma and soft tissue sarcomas patients. Chemotherapy can induce up-regulation of GST-pi protein expression. Primary high expression of GST-pi is the main mechanism of resistance of osteosarcoma and soft tissue sarcomas to chemotherapy and is related to poor prognosis.</p>

Experimental study of sensitivity to chemotherapeutic agents for human endometrial carcinoma cell line / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To screen the sensitive chemotherapeutic agents to human endometrial carcinoma cell line-1 (HECCL-1) and study its mechanism.</p><p><b>METHODS</b>MTT method was used to examine the relative inhibition ratios (RIRs) of various concentrations of 18 chemotherapeutic agents to HECCL-1. Cell cycle, apoptosis and expression of MDR1 protein were detected by FCM.</p><p><b>RESULTS</b>Nine of the chemotherapeutic agents studied obviously inhibited the proliferative activity of HECCL-1 in a dose-dependent manner. The order of sensitivity was as follows: adriamycin (ADM), oxaliplatin (L-OHP), carboplatin (CBP), cisplatin (DDP), taxol (TAL), epirubicin (EPI), mitoxantrone (MIT), dactomycin (ACTD) and 5-fluorouracil (5-Fu). FCM showed these agents could significantly reduce the proportion of cells in G0-G1 phase, and increase the proportion of cells in S and G2-M phase (P < 0.05). Cell apoptosis was observed in 11 chemotherapeutic agents at their peak concentration. MDR expression was induced after using EPI, 5-Fu, hydroxycamptothecin (HCPT) and MIT.</p><p><b>CONCLUSION</b>HECCL-1 is sensitive to a number of the chemotherapeutic agents studied. Induced apoptosis may be the major mechanism of drug sensitivity, and acquired drug-resistance may be the critical reason against continued administration.</p>