DDX10 overexpression predicts worse prognosis in osteosarcoma and its deletion prohibits cell activities modulated by MAPK pathway.

Osteosarcoma (OS) is an invasive cancer in the skeletal system. The molecular mechanism of its etiology and pathogenesis are still not clear, so the effective treatment strategy of OS needs further research. First, we analyzed the expression level and prognostic ability of the RNA helicase DDX10 in OS patients based on the data obtained from GEO database. Next, we used CCK8 to test OS cell viability. Besides, we used wound-healing assay and transwell migration assay to detect cell migration of OS MG63 cell line. And the cell invasion was tested by transwell invasion assay. Moreover, we used QRT-PCR and western blot to analyze the mRNA and protein expression levels. We found that DDX10 was significantly over-expressed in OS patients and elevated level of DDX10 was associated with a poor prognosis. Silencing of DDX10 inhibited proliferation, invasion and migration of MG63 cells in vitro. Down-regulation of DDX10 inhibited MAPK signaling pathway. The expression of p-MEK and p-ERK were also decreased by silencing of DDX10. Therefore, Silencing of DDX10 inhibited proliferation, invasion and migration of MG63 cells, which might be regulated by suppression of MAPK pathway. In conclusion, our results unfold a novel area of studying for understanding how DDX10 functions in OS oncogenic and prognostic significance, accordingly implying a promising therapeutic target for OS treatment.

[Effect and mechanisms of TET on human gastric carcinoma cell line SGC7901 and SGC7901/ADR].

OBJECTIVE: To investigate the effect of tetrandrine (TET) on zinc finger protein 139 (ZNF139) and multidrug resistance (MDR) of human gastric carcinoma cell lines and possible mechanisms. METHODS: Cultured SGC7901 and SGC7901/ADR were treated with TET (0.5, 1.0, 1.5, 2.0, and 2.5 microg/mL), then inhibition rates were measured by MTT assay in vitro. The expressions of ZNF139, MRP-1, MDR1, and GST-pi were detected by RT-PCR. The correlation between ZNF139 and each multidrug resistance factor was analyzed using Spearman correlation analysis, and the coefficient correlation was calculated. RESULTS: The inhibition rate of TET (< or = 2.0 microg/mL) for SGC7901 and SGC7901/ADR was less than 10% with MTT assay. Expressions of ZNF139, MRP-1, MDR1, and GST-pi mRNA were higher in SGC7901/ADR than in SGC7901 (all P < 0.05). The expressions of ZNF139, MRP-1, MDR1, and GST--pi were down-regulated in SGC7901/ADR cells efficiently (all P < 0.01). Positive correlation existed between ZNF139 and MRP-1, ZNF139 and MDR1 before treated by TET in SGC7901/ADR, and this relationship also existed in SGC7901/ADR cells after treated by TET (all P < 0.05). CONCLUSION: TET could achieve MDR reversion in gastric cancer cells by down-regulating the expression of ZNF139, MRP-1, and MDR1.

Ginsenoside Rg1 relieves rat intervertebral disc degeneration and inhibits IL-1ß-induced nucleus pulposus cell apoptosis and inflammation via NF-κB signaling pathway.

The study aimed to investigate the effect of ginsenoside Rg1 on intervertebral disc degeneration (IVDD) in rats and IL-1ß-induced nucleus pulposus (NP) cells, and explore its underlying mechanism. Forty IVDD rat models were divided into the IVDD group, low-dose (L-Rg1) group (intraperitoneal injection of 20 mg/kg/d ginsenoside Rg1), medium-dose (M-Rg1) group (intraperitoneal injection of 40 mg/kg/d ginsenoside Rg1), and high-dose (H-Rg1) group (intraperitoneal injection of 80 mg/kg/d ginsenoside Rg1). The pathological change was observed by HE and safranin O-fast green staining. The expression of IL-1ß, IL-6, TNF-α, MMP3, aggrecan, and collagen II was detected. The expression of NF-κB p65 in IVD tissues was detected. Rat NP cells were induced by IL-1ß to simulate IVDD environment and divided into the control group, IL-1ß group, and 20, 50, and 100 µmol/L Rg1 groups. The cell proliferation activity, the apoptosis, and the expression of IL-6, TNF-α, MMP3, aggrecan, collagen II, and NF-κB pathway-related protein were detected. In IVDD rats, ginsenoside Rg1 improved the pathology of IVD tissues; suppressed the expression of IL-1ß, IL-6, TNF-α, aggrecan, and collagen II; and inhibited the expression of p-p65/p65 and nuclear translocation of p65, to alleviate the IVDD progression. In the IL-1ß-induced NP cells, ginsenoside Rg1 also improved the cell proliferation and inhibited the apoptosis and the expression of IL-6, TNF-α, aggrecan, collagen II, p-p65/p65, and IκK in a dose-dependent manner. Ginsenoside Rg1 alleviated IVDD in rats and inhibited apoptosis, inflammatory response, and ECM degradation in IL-1ß-induced NP cells. And Rg1 may exert its effect via inhibiting the activation of NF-κB signaling pathway.

Tumor chemosensitivity is correlated with expression of multidrug resistance associated factors in variously differentiated gastric carcinoma tissues.

BACKGROUND/AIMS: To evaluate the relationship between chemosensitivities in vitro and expressions of multidrug resistance (MDR) associated factors in differentiated gastric carcinomas. METHODOLOGY: Gastric carcinomas tissues of varying degree of differentiation (65 cases) were collected and chemosensitivities to 5-FU, HCPT, PTX, L-OHP, CDDP and eADM were detected by sulphorhodamine B (SRB) assay, and expressions of P-gp, GST-π, Topo IIα, p53, Bcl-2, Bax and Survivin were tested by immunohistochemical staining. RESULTS: Inhibition rates of 5-FU, L-OHP and CDDP for well differentiated tumors were lower than those of poorly differentiated tumors (p<0.05). Expressions of P-gp, Bcl-2 and Survivin were higher in well differentiated than in poorly differentiated carcinomas (p<0.05); while expression of Topo IIα in well differentiated carcinomas was lower than in poorly differentiated carcinomas (p<0.05). The expression of MDR factors was different between well and poorly differentiated carcinomas. CONCLUSIONS: Different MDR characteristics were exhibited in well and poorly differentiated gastric carcinomas, which may be caused by different expressed MDR associated factors in these tissues.

[Application of CFP short-stem prosthesis in the treatment of osteonecrosis of the femoral head].

OBJECTIVE: To investigate the clinical outcome for the treatment of osteonecrosis of the femoral head (ONFH) in advanced stage by a short-stem prosthesis preserving femoral neck in total hip arthroplasty (THA). METHODS: From June 2008 to December 2009, 9 hips in 8 patients with advanced stage of ONFH were treated by a short-stem preserving femoral neck in THA. The mean age was 24.1 years (range: 20 - 36). There were 3 patients (3 hips) with alcohol-induced ONFH and 5 patients (6 hips) with steroid-induced ONFH. According to the classification of Association Research Circulation Osseous (ARCO), 7 hips were in stage III-C and 2 hips in stage IV respectively. The clinical outcomes were evaluated according to the Harris evaluation score and radiographic analysis. RESULTS: All patients were followed up for a mean duration of 18.1 months (range: 12 - 30). The mean Harris hip score improved from preoperative (42.8 ± 8.6) points to (92.8 ± 6.1) points at the time of final follow-up. The outcomes were excellent in 7 hips and better in 2 hips. Neither osteolysis of mortar and femur nor loose component was found from radiological films. The pain of all hips disappeared and no complications occurred. CONCLUSION: The short-term clinical outcome is satisfactory for treating young patients with advanced stage of ONFH by a short-stem prosthesis preserving femoral neck in THA.

Application of positive behavior management in patients after breast cancer surgery.

BACKGROUND: As a radical treatment, breast cancer surgery has a positive psychological impact on most patients. However, some patients do not have a clear understanding of the disease, which requires a more scientific and comprehensive consideration during clinical intervention and are based on cognition. The positive behavior management model is based on this kind of background-derived new interventions, which can better serve the clinical rehabilitation process of patients. The positive behavior management model based on cognitive architecture is a new type of intervention derived from this background, which can better serve the clinical rehabilitation process of patients. AIM: To analyze the influence of a positive behavior management model based on cognitive framework on the degree of hope and self-efficacy of patients with breast cancer surgery. METHODS: Eighty-four patients with breast cancer who underwent surgical treatment in our hospital from August 2016 to December 2018 were included in the study. The patients were divided into the experimental group (n = 42) and control group (n = 42) by random number table grouping. The control group received traditional nursing intervention, while the experimental group received a positive behavior management model based on cognitive framework based on the traditional intervention of the control group. General Self-efficacy Scale, Herth Hope Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale and Cancer Patient Specific Scale were used to evaluate the two groups before and 1 wk after intervention. RESULTS: After the intervention, self-efficacy and hope level of the experimental group were significantly higher than those of the control group (P < 0.05). The Self-Rating Anxiety Scale and Self-Rating Depression Scale scores in the experimental group were significantly lower than those in the control group (P < 0.05). There was no significant difference in the quality of life scores between the two groups before intervention (P > 0.05). The quality of life scores in all aspects in the experimental group after intervention were significantly higher than those in the control group (P < 0.05). CONCLUSION: The positive behavior management model based on cognitive framework applied to patients with breast cancer surgery improved hope for treatment and self-efficacy, reduced negative emotion, and improved quality of life.

Trans-upper-sternal approach to the cervicothoracic junction.

UNLABELLED: From August 1999 to February 2006, 11 patients with cervicothoracic lesions (eight males, three females; age range, 17-77 years) were surgically treated using the trans-upper-sternal approach. Combined cervicothoracic incision and upper sternotomy facilitated exposure for tumor resection, partial or subtotal removal of the involved vertebrae, and spinal cord decompression. The spinal column then was stabilized. Neurologic status was assessed using the Frankel classification. Followup for a minimum of 10 months (mean, 31 months; range, 10-56 months) revealed one patient had a chyle leak (50 mL) 1 day after surgery, which resolved after 2 days of drainage. One patient had a transient vocal cord paresis, which recovered within 3 months of surgery. All the patients had improved neurologic function. No nonunions or instrument-related complications developed. Stability of the vertebral column was maintained during followup in all patients. The trans-upper-sternal approach can provide excellent exposure for reconstruction of the cervicothoracic junction. Special care must be taken to avoid injury to the recurrent laryngeal nerve and the thoracic duct. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Downregulation of annexin A7 decreases proliferation, migration, and invasion of gastric cancer cells by reducing matrix metalloproteinase 1 and 9 expression.

High annexin A7 expression is a potential indicator of lymphatic metastasis and poor prognosis in patients with gastric cancer (GC). The mechanism underlying the effects of annexin A7 on GC cells remains unclear. In patients with GC, primary adenocarcinoma tissues had higher annexin A7 expression than adjacent non-cancerous tissues (P < 0.05). Among three human GC cell lines with high, moderate, and low levels of differentiation, respectively, the cell line with the lowest level of differentiation displayed the highest level of annexin A7 expression. We transfected cells of the human GC cell line BGC823 with short interfering RNAs (siRNAs) targeting annexin A7 and investigated the effects on signaling pathways related to cancer progression by quantitative real-time PCR and western blot. The silencing of endogenous annexin A7 suppressed the proliferation, migration, and invasion abilities of the BGC823 cells. In the cells treated with annexin A7 siRNA, the expression of p16, p21, and p27 was significantly upregulated while that of proliferating cell nuclear antigen (PCNA), cyclin A, cyclin D1, cyclin E1, matrix metalloproteinase-2 (MMP-2), MMP-9, and intercellular cell-adhesion molecule-1 (ICAM-1) was significantly downregulated compared with that in control cells. Our results suggest that the downregulation of endogenous annexin A7 inhibits GC cell proliferation, migration, and invasion by impacting cell cycle regulators and the expression of MMP-1, MMP-2, and ICAM-1. Targeting annexin A7 may represent a valuable strategy for the diagnosis and clinical treatment of GC.

Changes of microstructure and mineralized tissue in the middle and late phase of osteoporotic fracture healing in rats.

BACKGROUND: With osteoporosis emerged as one of the most important health issues, more and more investigations are focusing on osteoporotic fracture healing. However, there are few studies on the changes of microstructure and mineralized tissue of newly formed callus. OBJECTIVE: We established an osteoporotic fracture rat model to evaluate the changes of microstructure and mineralized tissue during osteoporotic fracture healing. MATERIALS AND METHODS: A mid-shaft femur fracture model was established 12 weeks after ovariectomy as an osteoporotic fracture group (OPF group). Femurs were then harvested at 4 weeks, 8 weeks and 12 weeks after fracture for peripheral quantitative computed tomography (pQCT), micro-computed tomography (MicroCT), histology and biomechanical test. A sham-operated group was used for comparison, i.e. the normal fracture group (NF group). RESULTS: The pQCT-derived total external callus area in the OPF group was smaller than that in the NF group at 4 weeks after fracture (P<0.05), whereas it was 21% larger in the OPF group than that in the NF group at 12 weeks after fracture (P<0.01). The pQCT-derived bone mineral density in the OPF group was significantly inferior to the NF group at all the time points (P<0.05 for all the time points, respectively). MicroCT data, at 12 weeks after fracture, showed the total callus, bony callus, and newly formed bone was approximately 20% lower in the OPF group than that in the NP group, and the total connectivity was 56% lower in the OPF group as compared to the NF group. Biomechanical test data, at 12 weeks after fracture, showed that the failure load of the left femur of OPF group was 17% less compared to that of the NF group (P<0.01), and 15% lower bending stiffness (P<0.05), 20% lower bending stress (P<0.01), and 28% lower energy at failure (P<0.01) were observed in the OPF group as compared to the NF group. CONCLUSION: The decrease in mineralized tissue and the not well connected microstructure in newly formed callus may explain the decline of mechanical impairment of fracture healing in the ovariectomized rats.

Gastrointestinal stromal tumor (GIST) with liver metastases: An 18-year experience from the GIST cooperation group in North China.

Approximately 40% to 50% of gastrointestinal stromal tumor (GIST) patients will have recurrence or metastases after resection of the primary lesion, and the most common affected sites will be liver and peritoneum. Imatinib has been considered as the first-line therapy of metastatic GIST. Surgery for metastases is proposed when possible. Furthermore, there are controversies concerning hepatic resection and systemic tyrosin kinase inhibitors (TKIs). The therapeutic conditions and long-term outcome of GIST patients with liver metastases in northern China remain unknown.The clinical, pathological, and follow-up data of 144 GIST patients, who had liver metastases between June 1996 and June 2014 from 3 tertiary cancer centers in northern China, were reviewed.Thirty-two cases (22.2%) had hepatectomy with 23 (23/32, 71.9%) R0 resections and 9 (9/32, 28.1%) R1/R2 resections, respectively. Twenty-three patients were given imatinib postoperatively. Furthermore, 98 (68.1%) patients were given TKIs only to control disease progression, and sunitinib was considered after imatinib failure in 12 patients. The 1-, 3- and 5-year survival rate was 82%, 51%, and 24%, with a median overall survival of 48 months for all patients. Patients who had hepatic resection combined with TKIs had a tendency of improved outcome, and the median survival time was 89 months. This was in contrast to patients who received TKIs only, in which median survival time was 53 months. Patients who received imatinib plus sunitinib had a tendency of longer survival time, compared with patients who received imatinib only (not reached vs 50 months).TKIs combined with hepatic resection had a role in improving the outcome of GIST patients with liver metastases.

Role of RNA-interference-induced zinc finger protein 139 suppression in gastric cancer cell sensitivity to chemotherapeutic agents.

Zinc finger proteins (ZNFs) are a class of proteins widely distributed in the human genome, which have been found to play a role in the regulation of gene transcription and the occurrence and development of gastric cancer (GC). ZNF139 was found to be associated with GC in our previous experiments. The present study aimed to analyse the differences in ZNF139 protein expression in SGC7901 GC cells and in situ grafted GC tumors in nude mice prior to and following RNA interference inhibition, and to investigate the mechanisms underlying ZNF139 involvement in the occurrence, development and chemosensitivity of GC. A ZNF139-targeted small interfering (si)RNA plasmid was constructed and transfected into the cancer cells and in situ grafted tumors. The MTT assay was used to investigate the alterations in chemosensitivity prior to and following transfection of siRNA-ZNF139. The two-dimensional difference gel electrophoresis and liquid chromatography-mass spectrometry techniques were used to identify the different protein points prior to and following siRNA-ZNF139 transfection. Western blot analysis was performed to confirm the identified proteins. In the siRNA-ZNF139 group, the growth of the cancer cells and in situ grafted tumors significantly decreased. However, the post-interference chemosensitivity to 5-fluorouracil, cisplatin and mitomycin C significantly increased. In the in vivo and in vitro experiments, the expression of pyridoxal kinase (PDXK) was upregulated, whereas the expression levels of annexin A2 (ANXA2) and fascin were downregulated following transfection. Western blot analysis confirmed the results for PDXK, ANXA2 and fascin by proteomics. Therefore, ZNF139 may participate in the occurrence, development and chemosensitivity of GC by promoting the expression of ANXA2 and fascin, while inhibiting the expression of PDXK.

Sternal tumor resection and reconstruction with titanium mesh: a preliminary study.

OBJECTIVE: To explore the clinical efficacy and complications of treating sternal tumors by resection and titanium mesh thoracic reconstruction. METHODS: This retrospective analysis of eight patients with sternal tumors treated in the Department of Orthopedic Surgery at the First Affiliated Hospital of Zhengzhou University from January 2008 to June 2012 included five men and three women aged 37-66 years (mean, 50.4 years). The histological diagnoses were chondrosarcoma (two cases), osteosarcoma (one), malignant fibrous histiocytoma (two), eosinophilic granuloma (one) and sternal metastasis from breast cancer (two). The tumors were invading the manubrium sterni (three cases), manubrium sterni and body (three) and sternal body (two). All patients underwent needle or incisional biopsy prior to sternal tumor resection and titanium mesh thoracic reconstruction. RESULTS: All patients were followed for 9 months to 4 years. There were no intraoperative complications or operative or postoperative deaths. One patient developed a deep wound hematoma 1 week postoperatively; incisional drainage and debridement resulting in healing within 2 weeks. There was no loosening or exsertion of the titanium mesh and no patients developed respiratory complications or thoracic deformity. One patient with malignant fibrous histiocytoma died of lung metastases 9 months postoperatively, another with malignant fibrous histiocytoma died of liver metastases 14 months postoperatively; the remaining patients survived without tumor recurrence. CONCLUSION: Titanium mesh chest reconstruction after sternal tumor resection has the advantages of simplifying the procedure, achieving a good shape and having few complications. Titanium mesh is an ideal material for reconstruction of the sternum.

Surgical treatment of cervical vertebral hemangioma associated with adjacent cervical spondylotic myelopathy.

BACKGROUND CONTEXT: Symptoms may vary from simple vertebral pain to progressive neurologic deficit because of cervical vertebral hemangioma associated with adjacent cervical spondylotic myelopathy (CVHAWACSM). Often resistant to conservative medical treatment, surgery has been the treatment of choice for these patients, but the optimal surgical strategy for CVHAWACSM has not been defined. PURPOSE: This study aimed to investigate the methods and efficacy in the treatment of CVHAWACSM. STUDY DESIGN: Retrospective review of patients enrolled in prospective randomized trial. PATIENT SAMPLE: Procedure was performed in 18 patients (11 men and 7 women) with CVHAWACSM, who were enrolled between January 2006 and September 2011. OUTCOME MEASURES: Radiographic examinations were carried out to assess total filling of polymethylmethacrylate in the vertebral body, fusion rates, implant failure, and general complications. The recovery of neurologic function and neck and shoulder pain relief were measured based on the Japanese Orthopedic Association (JOA) and the visual analog scale (VAS) scores. METHODS: Eighteen patients had single vertebral hemangioma, including one case at C3, three at C4, six at C5, five at C6, and three at C7. The X-ray films showed a typical "palisade" change. According to the clinical and imaging features, there were 12 cases of Type II and 6 of Type IV cervical hemangioma. Standard anterior cervical decompression and fusion with a stand-alone polyetheretherketone cage (filled with autologous cancellous iliac bone) was performed, followed by vertebroplasty. Clinical and radiologic follow-ups were performed. RESULTS: The mean follow-up was 24.1 months, with a range of 18 to 36 months. The symptoms of all 18 patients were improved, by varying degrees, and the lesion vertebra did not show anterior bone cement leakage or injuries in the spinal cord and nerves. The forming vertebra did not show fracture or collapse, and there was no recurrence of the hemangioma. During the follow-up, there was no implant loosening, displacement, or breakage. The JOA and the VAS scores were significantly recovered at 3 months after the operation and in the last follow-up, compared with the preoperative level (p<.05). The JOA scores in the last follow-up showed 13 excellent, 4 good, 1 fair, and 0 poor cases. CONCLUSIONS: This procedure seems to be a safe efficient method to treat symptomatic CVHAWACSM. It seems to serve the purpose of providing vertebral augmentation, cord decompression, and rigid fusion at the same sitting. Although the present outcomes are promising, long-term follow-up studies with larger patient numbers are required to confirm this effect.

Different doses of nitric oxide donor prevent osteoporosis in ovariectomized rats.

Nitric oxide has important effects on bone cell function. To verify that nitric oxide can protect against bone loss associated with estrogen deficiency, which is dependent on different concentrations of nitric oxide, we applied different doses of nitric oxide to ovariectomized rats. Fifty 12-week-old Sprague-Dawley female rats had ovariectomies, and 10 rats had sham operations. The ovariectomized rats were randomized into five groups: ovariectomized only; 17-beta-estradiol; low-dose nitroglycerin; middle-dose nitroglycerin; and high-dose nitroglycerin. After 12 weeks, the bone mineral density, dry weight, ash weight, calcium content, and nitric oxide concentration were determined. Compared with these same measurements in the sham-operated group, the bone mineral density, dry weight, ash weight, calcium content, and nitric oxide concentration decreased in the control group. Treatment with low-dose nitroglycerin, middle-dose nitroglycerin, and 17-beta-estradiol maintained bone mineral density and reversed the effects of ovariectomy on dry weight, ash weight and calcium content when compared with those in the control group. There were no differences in the bone mineral density, dry weight, ash weight, or calcium concentration between the ovariectomized-only rats and the rats treated with high-dose nitroglycerin. Results of this study suggest that nitric oxide treatment can counteract bone loss in ovariectomized rats. Furthermore, supplementation with a similar or slightly greater than physiologic concentration of nitric oxide has a potentially positive impact on osteoporosis.

[Nitrogen bio-cycle in the alpine tundra ecosystem of Changbai Mountain and its comparison with arctic tundra].

The nitrogen bio-cycle was discussed in the alpine tundra ecosystem of Changbai Mountain through compartment model. The alpine tundra of Changbai Mountain was compared with Arctic tundra by the common ratio of genus and species in this paper. It was found that the 89.3% of genus and 58.6% of species was the common between Changbai alpine tundra and Arctic tundra while 95.5% of lichen genus and 58.7% lichen species, 82.1% of moss genus and 76.3% of moss species, 93.1% of vascular bundle genus and 40.5% of vascular bundle species were the common, respectively, which made vegetation type or community to be similar between Changbai alpine tundra and Arctic tundra. The total storage of nitrogen was 65220.6 t in the vegetation-plant system of Changbai Mountain, of which soil pool amounted to 99.3%. The nitrogen storage of each compartment was as follows: the vegetation pool, litterfall pool and soil pool were 237.4 t, 145.3 t and 64837.9 t respectively. The transferable amounts of nitrogen were 131.7 t x a(-1), 58 t/a and 73.7 t x a(-1) in the aboveground plant, belowground root system and litterfall of alpine tundra ecosystem of Changbai Mountain.