SP1-induced overexpression of LINC00520 facilitates non-small cell lung cancer progression through miR-577/CCNE2 pathway and predicts poor prognosis.

Long noncoding RNAs (lncRNAs) have gained much attention in the past few years. Long intergenic non-protein coding RNA 520 (LINC00520) was one of the newly discovered lncRNA which has been demonstrated to be dysregulated in several cancers. So far, the function and mechanism of LINC00520 in non-small cell lung cancer (NSCLC) are unclear. In this paper, our group first showed that LINC00520 level was elevated in non-small cell lung cancer (NSCLC) tissue and cells. In addition, SP1 could bind directly to the promoter region of LINC00520 and thus promote its transcription. Increased LINC00520 was distinctly correlated with advanced tumor stage and shorter survival time in NSCLC patients. Further functional investigations provided evidences that forced down regulation of LINC00520 inhibited NSCLC cell proliferation, invasion, metastasis and EMT, while contributing to cells apoptosis. Mechanistically, we found that LINC00520 serving as a competing endogenous RNA to be involved in the modulation of miR-577 expressions, and thus affected the expression of CCNE2 which was a target gene of miR-577. Moreover, in NSCLC cells with si-LINC00520, up regulation of CCNE2 led to an increase of cell growth and invasion. Taken together, LINC00520 displayed its tumor-promotive roles through modulating the miR-577/CCNE2 axis, highlighting a potential therapeutic strategy for NSCLC patients.

Correction to: A combination of omega-3 and plant sterols regulate glucose and lipid metabolism in individuals with impaired glucose regulation: a randomized and controlled clinical trial.

Following publication of the original article [1], the Authors' Contributions statement need to be changed.

A combination of omega-3 and plant sterols regulate glucose and lipid metabolism in individuals with impaired glucose regulation: a randomized and controlled clinical trial.

BACKGROUND: Lipid metabolism imbalance has been recognized as one of the major drivers of impaired glucose metabolism in the context of type 2 diabetes mellitus (T2DM), the rates of which are steadily increasing worldwide. Impaired glucose regulation (IGR) plays a vital role in the prevention and treatment of T2DM. The goal of this study was to further clarify whether the combination of plant sterols (PS) and omega-3 fatty acids yields any synergistic effect that enhances the prevention and treatment of IGR. METHODS: A total of 200 participants were randomized to receive PS and omega-3 fatty acids (n = 50), PS alone (n = 50), omega-3 fatty acids alone (n = 50), or placebo soy bean powder plus placebo capsules (n = 50) for 12 weeks. Patient characteristics including body composition, blood pressure, glucose metabolism (Fasting plasma glucose (FPG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)), lipid metabolism (TG, TC, HDL-C, LDL-C) and inflammatory factors (Hs-CRP, IL-6) were all monitored in these IGR individuals. RESULTS: Compared to the placebo group, the group receiving the combined intervention exhibited significantly decreased TG, HDL-C, FBG, HOMA-IR and HbA1c. Omega-3 fatty acids alone were associated with significant reductions in waistline, TG, FBG, HOMA-IR and Hs-CRP. PS alone was only associated with decreased TG and Hs-CRP. No interventions produced significant changes in body weight, BMI, blood pressure, FINS, body fat percentage, visceral fat rating, TC, LDL-C or IL-6. CONCLUSIONS: In summary, this study has demonstrated for the first time that PS, omega-3 fatty acids or the combination thereof significantly improved inflammation, insulin resistance, as well as glucose and lipid metabolism in IGR individuals. These findings may provide a scientific basis for the development of nutritional products incorporating PS and omega-3 fatty acids, and also for the development of nutritional supplement strategies aimed at preventing the development of disease in the IGR population.

[Technology of finite-element analysis and its application in the field of acetabular prosthesis].

The hip with distinctive anatomical structure and complicated function plays an important role in normal standing and activity. The clinical doctors have paid attention to studies on hip biomechanics of normal structure and reconstruction. It was difficult for us to analyze hip in vivo because of its complex structure. Many examinations were preformed on animal models, but the reliability of results was unavoidably affected. Technology of finite-element analysis as one of the main methods of mechanics had been successfully applied in many fields, especially in analyzing on irregular bodies. The application in the field of orthopaedic surgery, for example the optimal design for prosthesis, stress analysis of grafts etc, had made great progress. The method could help us to improve current thoughts on study of biomechanics and make continuous advance in the future.

[Design of ABC damage variable and positioning system for acetabular fractures and 1122 cases multi-center statistic analysis].

OBJECTIVE: To design ABC damage variable and positioning system for acetabular fracture and explore the feasibility and clinical practical value of the system through the multi-center analysis of 1122 acetabular fractures. METHODS: According to acetabular three-column conception, and pelvic ring lesions damage direction caused by acetabular fracture domino effect and injury degree of proximal femur joint, it defined class A as any column acetabular fracture; class B as any two-column acetabular fracture; class C as front, dome and posterior mixture acetabular fracture. Lower case English letters a, m, p represented front, dome, posterior fracture, respectively. Acetabular damage variables: 1 was simple displaced fractures; 2 was comminuted fractures; 3 was compression fractures. Pelvic ring lesions damage variables: alpha was sacroiliac joints or sacroiliac fracture horizontal separation deflection; beta was sacroiliac joints or sacroiliac fracture vertical separation deflection; gamma was pubic symphysis separation/superior and inferior ramus of pubis fracture deflection; alpha beta gamma delta was compound floating damage. Proximal humerus joint damage variables: I was femoral head fracture; II was femoral neck fracture; II was intertrochanteric fractures of femur; IV was I to III compound fracture. The ABC damage variable positioning system for acetabular fracture was made up by the above-mentioned variables. The statistics from March 1997 to February 2010 showed 1122 cases acetabular fractures with 18 cases of double side acetabular fracture and 1140 cases of acetabular fractures. The pelvics anterior-posterior view, ilium and obturator oblique view, and 2/3D-CT materials were analyzed and researched. RESULTS: Each damage variables distribution situation in 1140 cases of acetabular fracture involved A in 237 cases (20.8%), B in 605 cases (53.1%), C in 298 cases (26.1%);front column fracture in 808 cases(70.9%), dome fracture in 507 cases (44.5%), posterior fracture in 1026 cases (90%). Acetabular variables: variabe 1 in 203 cases of simple displaced fracture (17.8%); variabe 2 in 516 cases of comminuted fracture(45.3%); variabe 3 in 421 cases of compression fracture (36.9%); 249 cases of pelvic ring lesions damage (21.8%), 75 cases femoral head fracture (6.6%); 18 cases of double side acetabular fracture and relative pelvic ring and proximal humerus joint variables (1.58%). Key part and curative effect elements of 1140 cases acetabular fracture: 507 cases of dome or posterior acetabular fracture (44.5%); 421 cases of compression fracture (36.9%); 249 cases of pelvic ring variables (21.8%); 75 cases of proximal humerus joint variables (6.6%); 486 cases of simple Aa/pl/2,Bapl/2 acetabular fracture (42.6% ). CONCLUSION: Compression fracture, especially defected compression fracture, takes important part in acetabular damage variables, and also presents that acetabular fracture with pelvic ring and proximal femoral damage variables are not rare at all. The relationship of the acetabular fracture damage variables, and its percentage shows the key points and elements in clinical treatment: weight-bearing to dome accounts for 44.5%; compression to defects account for 36.9%, pelvic ring to float accounts for 21.8%; dome fracture to double side fracture account for 6.6%. The system has significant guiding effects on clinic in terms of evaluation of injury severity, anatomic localization, difficulty index, alternative strategy, operative approach, effect of treatment,and prognosis. And the most important thing is that the system creates the comparison of damage variables in same type of fracture and the communication of homo-language and explores a new method.

Effects of aquaporin4 deficiency on opioid receptors characteristics in naive and chronic morphine-treated mice.

Our previous study indicated that aquaporin4 (AQP4) deficiency potentiated morphine analgesia, but attenuated tolerance and physical dependence induced by chronic exposure to morphine. However, the mechanisms remained to be explored. In the present study, effects of AQP4 deficiency on opioid receptor characteristics were investigated by [(3)H]-diprenorphine binding assays. In basal condition, the K(d) values of opioid receptors increased from 0.27+/-0.03 nM in wild-type mice to 0.44+/-0.04 nM in AQP4 deficient mice. Meanwhile, the density (B(max) values) of opioid receptors increased from 0.40+/-0.04 pmol/mg protein in wild-type mice to 0.66+/-0.04 pmol/mg protein in AQP4 deficient mice. After chronic morphine treatment, the affinity of opioid receptors decreased in wild-type mice, in which the K(d) value increased from 0.27+/-0.03 nM to 0.40+/-0.04 nM, while no change in the density of opioid receptors was observed. In AQP4 knockout mice, the effects of chronic morphine treatment on opioid receptors were similar to that in wild-type mice, in which the K(d) values increased from 0.44+/-0.04 nM to 0.64+/-0.08 nM, whereas the density had no significant change. Taken together, at the first time, we found that AQP4 deficiency decreased the affinity and increased the density of opioid receptors. Additionally, AQP4 deficiency did not affect chronic morphine-induced alterations of opioid receptor characteristics.

Development, characterization, and validation of porous carbonated hydroxyapatite bone cement.

Carbonated hydroxyapatite (CHA) bone cement is capable of self-setting and forming structures similar to mineralized bone. Conventional CHA leaves little room for new bone formation and delays remodeling. The purposes of this study were to develop porous CHA (PCHA) bone cement and to investigate its physicochemical properties, biocompatibility, biodegradation, and in vivo bone repair potential. Vesicants were added to modify CHA, and the solidification time, porosity, and pore size of the PCHA cements were examined. The cytotoxicity and bone repair potential of PCHA were tested in a rabbit bone defect model and assessed by x-ray, histological examination, and mechanical testing. The porosity of the modified PCHA was 36%; 90.23% of the pores were greater than 70 mum, with a calcium/phosphate ratio of 1.64 and a solidification time of 15 minutes. The PCHA did not affect bone cell growth in vitro, and the degrading time of the PCHA was two and four times faster in vitro and in vivo when compared to CHA. In the bone defect model, the amount of new bone formation in the PCHA-treated group was eight times greater than that of the CHA group; the compressive strength of the PCHA setting was relatively weak in the first weeks but increased significantly at 8 to 16 weeks compared to the CHA group. The PCHA has stable physicochemical properties and excellent biocompatibility; it degrades faster than CHA, provides more porous spaces for new bone ingrowths, and may be a new form of bone cement for the management of bone defects.

[Impacted cancellous autograft for reconstructing bone defects of tibial plateau in total knee arthroplasty].

OBJECTIVE: To observe the effects of a newly developed technique to transform the dish-like bone defect into contained bone defect and adopt the cancellous bone obtained from bone cut to make parvula impacted bone graft to repair the bone defect of tibial plateau in total knee arthroplasty (TKA) for osteoarthritis (OA) patients with severe varus or valgus. METHODS: 54 OA patients (74 knees) with severe varus or valgus (> 25 degrees ) received TKA. The average depth of the bone defect at the tibial plateau measured in the operation was 18.23 mm and the average thickness of the bone cut was 9.97 mm. The average depth of the dish-like bone defect left after bone cutting was 8.78 mm and the defect occupied averagely 31.5% of the total section area. The sclerotic bone layer was removed to the depth of the cancellous bone by saw blade or reamer, which made the defect to be contained. Small holes were drilled in the contained bone defect. Fragments 5-8 mm in diameter were made from the cancellous bone osteotomized from the femur and tibia were impacted into the bone defect. The defect was finally covered by a bone slice to make a flat tibial section allowing the tibia prosthesis to be firmly seated on it by routine technique. Follow-up was conducted for 32.2 months on average. RESULTS: The tibial deformity was repaired effectively and reliable support for the prosthesis at the tibia side was provided. Subsequent X ray films showed that no bone defect was seen under the prosthesis and the position of the prosthesis was fine. No autograft resorption and complete radiolucency between the graft and the tibial host bone appeared during the follow-up. The average KSS score raised from 45.6 preoperatively up to 94.5 postoperatively. CONCLUSION: In comparison with other techniques, the impacted autografting technique more effectively reconstructs the bone defects of tibial plateau in TKA. The cancellous bone obtained from the bony end can be used fully, thus over-cutting can be avoided and the mechanical characteristics of the knee joint would not be disturbed.

Aquaporin 4 deficiency modulates morphine pharmacological actions.

Acute administration of opioids produces analgesia, while chronic administration induces tolerance and dependence. Aquaporin 4 (AQP4) is most strongly expressed in astrocytes throughout central nervous system, and plays an important role in some pathophysiological processes in brain. However, whether AQP4 modulates opioid analgesia, tolerance and dependence or not remains unknown. In the present study, the effects of AQP4 deficiency on morphine analgesia, tolerance and physical dependence were investigated. (1) In hot-plate tests, ED(50) values of morphine analgesia were 3.77 and 3.96 mg/kg in male and female AQP4 knockout mice, which were lower than that in wild-type mice (5.23 and 5.20mg/kg in males and females). (2) Repeated treatment with morphine resulted in analgesic tolerance to morphine in wild-type mice, whereas the morphine tolerance was attenuated in AQP4 knockout mice treated as the same schedule. (3) After repeated morphine administration, naloxone precipitation induced significant abstinent jumping in wild-type mice, whereas naloxone-induced abstinent jumping was not observed in AQP4 knockout mice. This suggested that AQP4 deficiency inhibited the development of morphine physical dependence. (4) Repeated morphine administration down-regulated cerebral glutamate transporter 1 (GLT-1) expression in wild-type mice. However, the down-regulation of GLT-1 expression diminished in AQP4 knockout mice. Taken together, these results demonstrated that AQP4 deficiency potentiated morphine analgesia, attenuated morphine tolerance and physical dependence. The suppression of down-regulation of cerebral GLT1 expression might mediate the attenuation of AQP4 deficiency to morphine tolerance and dependence.

[Clinical experience of treating infection after total hip arthroplasty].

OBJECTIVE: To present the experience in the management of the infected total hip arthroplasty (THA). METHODS: Forty-three cases (44 hips) of infection after THA were reviewed. Eighteen women and 25 men with a mean age of 54 years (range, 24-81 years) were studied. Follow-up ranged from 5 months to 16 years (mean, 3.2 years). Treatment strategies included: one-stage revision (n = 7), two-stage revision (n = 15), resection arthroplasty (n = 13), debridement and retain prosthesis (n = 5), and others (n = 3). RESULTS: Forty cases had positive culture result with 59 organisms including 19 staphylococcus epidermidis and 10 staphylococcus aureus. Thirty-six cases had been followed up, and no case had infection recurrence. Twenty-nine cases had postoperative Harris hip score averaged 78.5 (45-98). CONCLUSIONS: The diagnosis and treatment of infection after hip replacement is very difficult. The violence and antibiotic resistant rate of the organisms is high. Two-stage reconstruction of the infected hip is useful and effective because of higher eradication rate of the infection and good postoperative functional result.

Inhibitory effect of agmatine on proliferation of tumor cells by modulation of polyamine metabolism.

AIM: To assess the inhibitory effect of agmatine on tumor growth in vivo and tumor cell proliferation in vitro. METHODS: The transplanted animal model, [3H]thymidine incorporation assay,3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium assay, and lactate dehydrogenase (LDH) release assay were performed. RESULTS: Agmatine, at doses of 5-40 mg/kg, suppressed the S180 sarcoma tumor growth dose-dependently in mice in vivo and the highest inhibitory ratio reached 31.3% in Kunming mice and 50.0% in Balb/c mice, respectively. Similar results were obtained in the transplanted B16 melanoma tumor model. Agmatine (1-1000 micromol/L) was able to attenuate the proliferation of cultured MCF-7 human breast cancer cells in vitro in a concentration-dependent manner and the highest inhibitory ratio reached 50.3% in the [3H]thymidine incorporation assay. Additionally, in the LDH release assay, spermine (20 micromol/L) and spermidine (20 micromol/L) increased the LDH release significantly, but agmatine (1-1000 micromol/L) did not, indicating that the inhibitory effect of agmatine on the proliferation of MCF was not related to cellular toxicity. In the [3H]thymidine incorporation assay, putrescine (12.5-100.0 micromol/L) could reverse the inhibitory effect of agmatine on the proliferation of MCF concentration-dependently, suggesting that the inhibitory effect of agmatine on the proliferation of MCF might be associated with a decreased level of the intracellular polyamines pool. CONCLUSION: Agmatine had significant inhibitory effect on transplanted tumor growth in vivo and proliferation of tumor cells in vitro, and the mechanism might be a result of inducing decrease of intracellular polyamine contents.

[Analysis on causes of death of childhood leukemia from 1981 to 2000 in the city of Tianjin].

OBJECTIVE: Leukemia is a major cause of death of children in China, which accounts for 50 % of all cancers of children. Data from Tianjin Cancer Hospital was analyzed for mortality of leukemia in children under 20 years from 1981 to 2000 in the city of Tianjin. METHODS: All physicians and medical staff of the hospitals and clinics in the registry area were responsible for filling out the report forms for every new case diagnosed as malignant tumors. Death certificates for malignant tumors have been registered at the local police station and the residential files were checked. All cancer cases with insufficient information were traced to his/her family and relevant persons worked in the clinic. Tianjin Cancer Registry Center periodically conducted an active re-checking program to review all patient records on cancers that was not registered in this period. Tumors diagnosed in this study were coded according to the International Classification of Diseases for Oncology (ICD-O). Mortality rates were calculated by age, sex and date of death. RESULTS: The types of acute lymphoid leukemia, acute myeloid leukemia and chronic myeloid leukemia were the most common types of childhood leukemia in Tianjin, comprised 69.3%, 20.9 % and 8.0%, respectively. The mortality for childhood leukemia decreased slowly during the period of 1981 to 2000 in Tianjin. Mortality and morbidity ratios were 0.51. CONCLUSION: Combined with characteristics of individual forms of childhood leukemia mortality, further epidemiological research is needed to prevent childhood leukemia.

[Long-term clinical observation on the repair of large articular cartilage defects of the hip and the knee with free autogeneous periosteum].

OBJECTIVE: To observe the long-term clinical results of repairing large articular cartilage defects of the hip and the knee with free autogeneous periosteum. METHODS: Based on the results of experimental studies, the authors used free autogeneous periosteum transplantation and postoperative continuous passive motion (CPM) to repair large articular cartilaginous defects in 52 patients from February 1987 to August 1995. Of 37 patients with complete follow-up data, 16 had congenital dislocation of the hip, 6 traumatic arthritis of hip, 1 femoral head destruction following mild infection, 2 ankylosing spondylitis, 6 intra-articular fracture of the knee, 4 arthritis of the knee and 2 stiff knee following joint infection. The patients with dislocation of hip were given relieving traction before operation. The cartilages of pathological changes were excised to bleeding bone. The defects were repaired with periosteum removing from tibia. CPM were immediately applied for 4-6 weeks and no bearing was allowed 6 months after discharge. The silicon membrane was taken out in the 6th month. RESULTS: Thirty-seven patients (17 males, 20 females) were followed up 7-15 years with an average of 10.5 years. The functional evaluation referred to joint pain degree, joint mobile range, daily activity and X ray findings. The results were excellence in 11 patients, good in 18 patients, poor in 8 patients. CONCLUSION: The method to repair articular cartilage defect with free autogeneous periosteum is effective and may be applied clinically.

[Risk factors of lung cancer in Tianjin].

OBJECTIVE: To investigate the risk factors of lung cancer in Tianjin and to provide evidence for further monitor there of. METHODS: A case-control study involving interviews with 193 new cases and 259 controls aged 30 - 76 years was carried out. Structured questionnaires were used to collect information on general condition, living environment, living style, disease and family history, etc. Logistic regression model univariate and multivariate analysis were used to pick out the significant lung cancer risk factors. RESULTS: By monovariate analysis, risk factors such as smoking, passive smoking, drinking, history of malignancy in family and occupation were found. By multivariate analysis, smoking, passive smoking, higher body mass index (BMI) and average income and living space per capita ten years earlier were ascertained, their operations research (OR) values were 3.302, 1.193, 1.003, 1.067 and 0.913. CONCLUSION: Smoking and passive smoking are independent risk factors of lung cancer. Monthly income per person and living space per person 10 years earlier are associated with elevated risk of lung cancer. Higher body mass index has protective effects on lung cancer risk.

[An experimental study of demineralized bone matrix to repair bone defects as a scaffold of tissue engineering].

OBJECTIVE: To evaluate application of the sponge of demineralized bone matrix (SDBM) in tissue engineering of bone. METHODS: SDBM was prepared from long bone of rabbits. Bone marrow cells were flushed from the bone shaft of femurs of a two-month-old New Zealand white rabbit. After the cells were cultured for 9 days, the flasks were added into dexamethasone (10(-8) mol/L), beta-glycerophosphate sodium (10 mmol/L) and L-ascorbic acid (50 micrograms/ml). After 5 weeks, the cultured cells were collected and marked by 5-Bromo-2'-dexyouridine (BrdU). The grand sum of cells seeded on a piece of SDBM was about (4-6) x 10(6). The composites of cells and SDBM (tissue engineered chip, TEC) were implanted into muscles and bone defects of radius in rabbits. A standard procedure was applied to make a 10 mm long defect bilaterally in the radius of nine skeletally mature male New Zealand white rabbits. All of the 18 defects were randomly divided into three groups: group I, six defects were grafted by TEC; group II, six defects were grafted with SDBM alone; group III, six defects were empty. RESULTS: The results of radiographic and histological evaluation showed that all of the defects were repaired in group I and group II at 6 weeks, none of the defects was repaired in group III. The results of BrdU staining showed that the staining was positive in group I, but negative in group II. Biomechanical test showed that the compressive ultimate strength (CUS) of new bone in TEC implanted group was comparable with normal radius (P = 0.623) and in SDBM implanted group was significant lower than normal radius (P = 0.038). CONCLUSIONS: The TEC can form cartilage and bone tissue in muscles and repair segmental bone defects. SDBM is a kind of effective natural scaffold in tissue engineering of bone.

[Experimental study on repair of articular cartilage defect in large area with chondrocytes cultured on fascia].

OBJECTIVE: To study the biological characteristic and potential of chondrocytes grafting cultured on fascia in repairing large defect of articular cartilage in rabbits. METHODS: Chondrocytes of young rabbits were isolated and sub-cultured on fascia. The large defect of articular cartilage was repaired by grafts of freeze-preserved and fresh chondrocytes cultured on fascia, and free chondrocytes respectively; the biological characteristic and metabolism were evaluated by macroscopic, histological and immunohistochemical observations, autoradiography method and the measurement of nitric oxide content 6, 12, 24 weeks after grafting. RESULTS: The chondrocytes cultured on fascia maintained normal growth feature and metabolism, and there was no damage to chondrocytes after cryopreservation; the repaired cartilage was similar to the normal cartilage in cellular morphology and biological characteristics. CONCLUSION: Chondrocytes could be cultured normally on fascia, which could be used as an ideal carrier of chondrocytes.