An allele of rs619586 polymorphism in MALAT1 alters the invasiveness of meningioma via modulating the expression of collagen type V alpha (COL5A1).

The rs619586 polymorphism has been shown to alter the expression of MALAT1, which act as a competing endogenous RNA (ceRNA) against miR-145. And miR-145 was found to target COL5A1, the interaction between which was shown to be involved in the pathogenesis of invasive meningioma. In this study, we aimed to explore the effect of rs619586 polymorphism and its underlying molecular mechanism in invasive meningioma. Real-time PCR and Western Blot analysis were used to study the differentiated expression of miR-145, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) and COL5A1 (collagen alpha-1(V) chain) in tumour/serum samples genotyped as rs619586 AA, AG and GG. Computational analysis and luciferase reporter assay were also conducted to identify the regulatory relationship between miR-145 and MALAT1/COL5A1. Meanwhile, expression of miR-145 and COL5A1 in different cell treatment groups was measured to validate the results obtained from earlier experiments. As shown by the results and in tumour/serum samples genotyped as AA, AG and GG, the expression of both MALAT1 and COL5A1 was down-regulated in a stepwise fashion, while the expression of miR-145 was increased, suggesting a potential negative relationship between MALAT1/COL5A1 and miR-145. Meanwhile, miR-145 was shown to bind to MALAT1, while COL5A1 was identified as a virtual target gene of miR-145. As a consequence, a MALAT1/miR-145/COL5A1 molecular pathway was established based on the above results. In particular, with the presence of rs619586 A>G polymorphism, the expression of MALAT1 and COL5A1 was both reduced, leading to reduced invasiveness of meningioma.

Downregulation of microRNA-218 is cardioprotective against cardiac fibrosis and cardiac function impairment in myocardial infarction by binding to MITF.

OBJECTIVE: This study is intended to figure out the function of microRNA-218 (miR-218) together with microphthalmia-associated transcription factor (MITF) on the cardiac fibrosis and cardiac function impairment in rat models of myocardial infarction (MI). RESULTS: The rats with MI exhibited cardiac function impairment, cardiac fibrosis, oxidative stress, cardiomyocyte apoptosis, as well as inflammatory injury. Additionally, upregulated miR-218 and downregulated MITF were detected in cardiac tissues of MI rats. MI rats injected with miR-218 inhibitors or overexpressed MITF exhibited elevated MITF expression, improved cardiac function, and diminished pathological damages, infarct size, cardiomyocyte apoptosis, cardiac fibrosis, oxidative stress as well as inflammatory injury in cardiac tissues. Furthermore, downregulated miR-218 and MITF aggravated the conditions than downregulation of miR-218 alone in MI rats. METHODS: MI models were performed in rats, and then the rats were injected with miR-218 inhibitors and/or MITF overexpression plasmid to elucidate the role of miR-218 and/or MITF on the cardiac function, pathological damage, cardiac fibrosis, angiogenesis, oxidative stress and inflammatory injury of cardiac tissues in MI rats by performing a series of assays. CONCLUSION: Collectively, we found that the suppression of miR-218 alleviates cardiac fibrosis and cardiac function impairment, and stimulates angiogenesis in MI rats through inhibiting MITF.

Monolayer Colloidal Crystals by Modified Air-Water Interface Self-Assembly Approach.

Hexagonally ordered arrays of polystyrene (PS) microspheres were prepared by a modified air-water self-assembly method. A detailed analysis of the air-water interface self-assembly process was conducted. Several parameters affect the quality of the monolayer colloidal crystals, i.e., the colloidal microsphere concentration on the latex, the surfactant concentration, the polystyrene microsphere diameter, the microsphere polydispersity, and the degree of sphericity of polystyrene microspheres. An abrupt change in surface tension was used to improve the quality of the monolayer colloidal crystal. Three typical microstructures, i.e., a cone, a pillar, and a binary structure were prepared by reactive-ion etching using a high-quality colloidal crystal mask. This study provides insight into the production of microsphere templates with flexible structures for large-area patterned materials.

Osthole, a Coumadin Analog from Cnidium monnieri (L.) Cusson, Ameliorates Nucleus Pulposus-Induced Radicular Inflammatory Pain by Inhibiting the Activation of Extracellular Signal-Regulated Kinase in Rats.

AIM: This study was aimed at assessing the role of extracellular signal regulated kinase (ERK) in mechanical allodynia resulting from lumbar disc herniation (LDH) and exploring the osthole's anti-nociceptive effect on ERK activation. METHODS: Radicular pain was generated by applying nucleus pulposus (NP) to the L5 dorsal root ganglion (DRG). Allodynia was measured using Von Frey filaments to calculate the mechanical pain threshold. Phosphorylated ERK and total ERK protein in the lumbar spinal dorsal horn was detected by using the Western blot technique. Cyclooxygenase 2 (COX-2) mRNA was assessed by real-time reverse-transcription polymerase chain reaction. RESULTS: The application of NP to L5 DRG induced mechanical hypersensitivity which lasted for at least 28 days, and a significant increase of ERK phosphorylation in the ipsilateral spinal dorsal horn from postoperative day (POD) 1 to POD 21. ERK inhibitor attenuated NP-induced hyperalgesia compared to the dimethyl sulfoxide-(vehicle control) administered group (p < 0.05). Epidural treatment with osthole could ameliorate NP-evoked hyperalgesia by suppressing the activation of ERK rather than decreasing the expression of ERK protein. Osthole could also inhibit the increased expression of COX-2 mRNA in spinal dorsal horn, which was a known downstream effect of ERK signaling pathway. CONCLUSIONS: Our results suggest that ERK activation in the spinal dorsal horn plays a vital role in NP-evoked hyperalgesia. Osthole exerts analgesic effect on radicular inflammatory pain in LDH rat model, by down-regulating the mRNA expression of the target gene of COX-2 via inhibiting ERK activation in the spinal dorsal horn.

Predictors for Surgical Outcome of Laminoplasty for Cervical Spondylotic Myelopathy.

BACKGROUND: There were no precise researches showing which parameters with regard to degree of cervical stenosis and sagittal cervical alignment are the most crucial for surgical outcomes after laminoplasty for cervical spondylotic myelopathy (CSM). The objectives of this study were to investigate to what extent the preoperative parameters may have a direct influence on postoperative neurologic recovery, and to determine the crucial determinants of prognosis. METHODS: A retrospective review of 83 patients with CSM after laminoplasty was conducted. Magnetic resonance imaging parameters evaluation included presence/absence of signal change on T1 and T2 and anatomic measurements, including cervical canal compromise and cervical alignment. Data analysis involved logistic regressions and Spearman rank correlation coefficients. Receiver operator characteristic (ROC) curves were computed to evaluate the contribution of the original model. RESULTS: Univariate logistic regression showed that age (odds ratio = 0.822; 95% confidence interval, 0.729-0.927; P = 0.001), baseline Japanese Orthopedic Association (JOA) score (odds ratio = 1.700; 95% confidence interval, 1.158-2.496; P = 0.007), cervical curvature index (Ishihara) score (CCI) (odds ratio = 1.123; 95% confidence interval, 1.030-1.225; P = 0.008), maximum canal compromise (MCC) (odds ratio = 0.940; 95% confidence interval, 0.885-0.998; P = 0.041), and signal intensity (odds ratio = 0.139; 95% confidence interval, 0.033-0.580; P = 0.007) were independent prognostic indicators after laminoplasty. A ROC curve was computed based on the probability of the five predictors, with an area under the curve of 0.929 ± 0.028. CONCLUSIONS: Age and baseline JOA scores were crucial clinical predictors of outcome after laminoplasty for patients with CSM. Regarding the predictive value, CCI, MCC, and patterns of signal intensity changes on T1-/T2-weighted images were crucial determinants of prognosis of neurologic outcome.

Prediction of incomplete decompression after cervical laminoplasty on magnetic resonance imaging: The modified K-line.

OBJECTIVES: The original K-line was developed on plain radiograph to predict incomplete indirect decompression for the patients with ossification of the posterior longitudinal ligament. The current study modified the K-line on magnetic resonance imaging (MRI) to determine risk factors for incomplete decompression after laminoplasty and to provide a guide for predicting incomplete decompression after laminoplasty and making decisions regarding the surgical approach in patients with cervical spondylotic myelopathy (CSM). PATIENTS AND METHODS: A retrospective review of 47 patients with CSM after laminoplasty was conducted. The modified K-line was defined as a line connecting both anterior points of the spinal cord at the level of the inferior vertebrae endplates of C2 and C7 on sagittal T1-weighted MR image. Quantitative analysis of the interval between the maximal anterior compression factor and the modified K-line (IAK) was performed to investigate the efficiency and practicality of this modified K-line. Data analysis involved logistic regression and Spearman rank correlation coefficient. RESULTS: Thirteen patients (27.7%) had postoperative residual anterior compression of the spinal cord (ACS). Univariate logistic regression with backward stepwise procedure showed that only IAK (odds ratio: 0.301; 95% confidence interval: 0.134-0.673, P=0.003) was a significant risk factor for the occurrence of postoperative ACS. Incidence of ACS was 80% in patients with an IAK of less than 1.5mm and 96.2% in those whose IAK is 0mm. CONCLUSION: The modified k-line can provide a guide for predicting poor clinical outcome after laminoplasty and making decisions regarding the surgical approach in patients with CSM.

Decreased miRNA-146a in glioblastoma multiforme and regulation of cell proliferation and apoptosis by target Notch1.

OBJECTIVE: The primary purpose of this paper is to investigate the relationship between the microRNA 146a (miR-146a) and the proliferation of cells occurring in glioblastoma multiforme. The secondary purpose of the paper is to investigate abnormalities of expression in miR-146a. METHODS: A real-time PCR assay was used to investigate the abnormal expression of miR-146a in glioma and adjacent tissue. Lipofection was used to transfect a mimic of miR-146a and induce the upregulation of miR-146a. Real-time PCR was used to observe the expression level of miR-146a. A cell viability analysis was conducted using MTT. A luciferase report vector was used to identify potential targets for miR-146a. RESULTS: The miR-146a component was found to be downregulated in glioma tissue compared with adjacent nontumor tissue (p<0.05). The upregulation of miR-146a in glioma cells through miR-146a mimic transfection led to reduction of cell viability and to an increase in the percentage of apoptosis. Notch1 was the name of the potential targeted gene for miR-146a in glioma. CONCLUSIONS: The study found that the presence of miR-146a potentially affected the proliferation of glioma cells by regulating the rate of Notch1 expression.

[Research on the Pre-Processing Methods of Wheat Hardness Prediction Model Based on Visible-Near Infrared Spectroscopy].

Grain hardness is an important quality parameter of wheat which has great influence on the classification, usage and composition research of wheat. To achieve rapid and accurate detection of wheat hardness, radial basis function (RBF) neural network model was built to predict the hardness of unknown samples on the basis of analyzing the absorptive characteristics of the composition of wheat grain in infrared, besides, the effects of different spectral pretreatment methods on the predictive accuracy of models were emphatically analyzed. 111 wheat samples were collected from major wheat-producing areas in China; then, spectral data were obtained by scanning samples. Mahalanobis distance method was used to identify and eliminated abnormal spectra. The optimized method of sample set partitioning based on joint X-Y distance (SPXY) was used to divide sample set with the number of calibration set samples being 84 and prediction set samples being 24. Successive projections algorithm (SPA) was employed to extract 47 spectral features from 262. SPA, first derivatives, second derivatives, standard normal variety (SNV) and their combinations were applied to preprocess spectral data, and the interplay of different prediction methods was analyzed to find the optimal prediction combination. Radial basis function (RBF) was built with preprocessed spectral data of calibration set being as inputs and the corresponding hardness data determined via hardness index (HI) method being as outputs. Results showed that the model got the best prediction accuracy when using the combination of SNV and SPA to preprocess spectral data, with the discriminant coefficient (R2), standard error of prediction (SEP) and ratio of performance to standard deviate (RPD) being 0.844, 3.983 and 2.529, respectively, which indicated that the RBF neural network model built based on visible-near infrared spectroscopy (Vis-NIR) could accurately predict wheat hardness, having the advantages of easy, fast and nondestructive compared with the traditional method. It provides a more convenient and practical method for estimating wheat hardness.

Epigenetic Regulation of miR-129-2 Leads to Overexpression of PDGFRa and FoxP1 in Glioma Cells.

miR-129-2 is frequently downregulated in multiple cancers. However, how it is silenced in cancers remains unclear. Here we investigated the expression profile and potential biological function of miR-129-2 in glioblastoma (GBM), the most common and lethal form of brain tumors in adults. We showed that miR-129-2 is lost in GBM patient specimens and cultured cell lines. miR-129-2 expression could be restored upon treatment with a histone deadetylase inhibitor (trichostatin A) but not a DNA methylation inhibitor (5-Aza-2'-deoxycytidine), and more profound effect was observed with the treatment of these two drugs in combination. Furthermore, forced expression of miR-129-2 repressed the expression of major oncogenic genes such as PDGFRa and Foxp1 in GBMs. Consistently, expression of miR-129-2 significantly inhibits GBM cell proliferation in vitro. These results reveal that miR-129-2 is epigenetically regulated and functions as a tumor suppressor gene in GBMs, suggesting it may serve as a potential therapeutic target for GBM treatment.

[China's rice field greenhouse gas emission under climate change based on DNDC model simulation].

In contrast to a large body of literature assessing the impact of agriculture greenhouse gas (GHG) emissions on climate change, there is a lack of research examining the impact of climate change on agricultural GHG emissions. This study employed the DNDC v9.5, a state-of-art biogeochemical model, to simulate greenhouse gas emissions in China' s rice-growing fields during 1971-2010. The results showed that owing to temperature rising (on average 0.49 °C higher in the second 20 years than in the first 20 year) and precipitation increase (11 mm more in the second 20 years than in the first 20 years) during the rice growing season, CH4 and N2O emissions in paddy field increased by 0.25 kg C . hm-2 and 0.25 kg N . hm-2, respectively. The rising temperature accelerated CH4 emission and N2O emission increased with precipitation. These results indicated that climate change exerted impact on the mechanism of GHG emissions in paddy field.

Elevated expression of Notch-1 and EGFR induced apoptosis in glioblastoma multiforme patients.

OBJECTIVE: The Notch signaling pathway has been well recognized as important adjuster in glioma tumorigenesis and could regulate the glioma cell proliferation through downstream factors such as epidermal growth factor receptor (EGFR). Our current study was aim to investigate the clinical association between Notch-1 gene and EGFR gene as well as cell survival rate in human glioblastoma multiforme (GBM) samples. PATIENTS AND METHODS: Samples from 90 patients with GBMs and 20 normal brain tissues were analyzed in our study. Western blot and immunohistochemistry was used to detect Notch and EGFR protein expression. RT-PCR was used to detect Notch and EGFR mRNA expression. Apoptosis was detected with flow cytometry. RESULTS: Results demonstrated that the Notch and EGFR gene mRNA and protein levels were dramatically higher in GBM tissues compared to normal brain. Further analysis found these increased mRNA levels were only associated with patient survival period, but not related to patient age, gender and tumor size. A positive correlation was observed between Notch and EGFR protein expression. The positive correlations were also exhibited between Notch-1, EGFR gene expression and apoptosis percentage. CONCLUSION: Our study verified both Notch-1 and EGFR involved in GBM tumorigenesis and may provide important information for GBM clinical treatment and prognosis.

Norcantharidin induces growth inhibition and apoptosis of glioma cells by blocking the Raf/MEK/ERK pathway.

BACKGROUND: Malignant gliomas represent the most common primary brain tumors. The prognosis of patients with malignant gliomas is poor in spite of current intensive therapy and novel therapeutic modalities are needed. Here we report that norcantharidin is effective in growth inhibition of glioma cell lines in vitro. METHODS: Glioma cell lines (U87 and C6) were treated with norcantharidin. The effects of norcantharidin on the proliferation and apoptosis of glioma cells were measured by 3-[4,5-dimethylthiazol-2-thiazolyl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and flow cytometry. Western blotting was employed to determine the signaling pathway changes. RESULTS: The results showed that norcantharidin effectively inhibited cell growth and induced apoptosis in glioma cells, which was concurrent with inhibition of the expression of phospho-MEK and phospho-ERK. Furthermore, the expression anti-apoptotic proteins Bcl-2 and Mcl-1 significantly reduced, but no changes in Bcl-xL and Bax. CONCLUSIONS: Our findings demonstrate that norcantharidin is effective for growth inhibition of glioma cell lines and suggest that norcantharidin may be a new therapeutic option for patients with glioma.

Does intraoperative ulinastatin improve postoperative clinical outcomes in patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

INTRODUCTION: The systematic meta-analysis of randomized controlled trials (RCTs) evaluated the effects of intraoperative ulinastatin on early-postoperative recovery in patients undergoing cardiac surgery. METHODS: RCTs comparing intraoperative ulinastatin with placebo in cardiac surgery were searched through PubMed, Cochrane databases, Medline, SinoMed, and the China National Knowledge Infrastructure (1966 to May 20th, 2013). The primary endpoints included hospital mortality, postoperative complication rate, length of stay in intensive care unit, and extubation time. The physiological and biochemical parameters illustrating postoperative cardiac and pulmonary function as well as inflammation response were considered as secondary endpoints. RESULTS: Fifteen RCTs (509 patients) met the inclusion criteria. Ulinastatin did not affect hospital mortality, postoperative complication rate, or ICU length of stay but reduced extubation time. Ulinastatin also increased the oxygenation index on postoperative day 1 and reduced the plasma level of cardiac troponin-I. Additionally, ulinastatin inhibited the increased level of tumor necrosis factor-alpha, polymorphonuclear neutrophil elastase, interleukin-6, and interleukin-8 associated with cardiac surgery. CONCLUSION: Ulinastatin may be of value for the inhibition of postoperative increased inflammatory agents and most likely provided pulmonary protective effects in cardiac surgery. However, larger adequately powered RCTs are required to define the clinical effect of ulinastatin on postoperative outcomes in cardiac surgery.

Prediction of prognosis in patients with cervical spinal cord injury without radiologic evidence of trauma using MRI.

The purpose of this study was to investigate whether pre- to postoperative changes of increased signal intensity (ISI) of the spinal cord as seen on T2-weighted magnetic resonance imaging (MRI) reflect the surgical outcome in patients with cervical spinal cord injury without radiologic evidence of trauma (SCIWORET). In this study, 54 patients with SCIWORET who underwent expansive laminoplasty were retrospectively analyzed. All patients underwent MRI at an average of 1.9 days (range, 1-5 days) after injury and 7.9 days (range, 6-10 days) postoperatively. The pre- and postoperative range and degree of ISI were measured on computer software using the same sagittal view on T2-weighted MRI. Then, the post-preoperative ratio of range and degree of ISI were calculated. Pre- and postoperative neurologic evaluations were performed according to the criteria proposed by the Japanese Orthopedic Association (JOA). A significant negative correlation existed between the ratio of range of ISI and the recovery rate (r=-0.504, P<.01). The ratio of degree of ISI negatively correlated with the recovery rate, but this was not statistically significant. Patients were divided into 2 groups according to the ratio of degree of ISI: group A included patients with a ratio of degree of ISI of ≤1 (n=24) and group B included patients with a ratio of degree of ISI of >1 (n=30). Patients' mean recovery rate was 65.0%±6.3% in group A and 52.4%±7.4% in group B. A significant difference was found between the 2 groups (P<.001, Student's t test) when comparing recovery rate. The pre- to postoperative changes of the range and degree of ISI significantly reflected prognosis for surgical outcome in patients with SCIWORET.

A new recipient artery for reconstruction of soft-tissue defects in the lower limb with a free anterolateral thigh flap: the reversed descending branch of the lateral femoral circumflex artery.

BACKGROUND: Complex and severe leg defects remain a persistent challenge in reconstructive surgery, especially when no feasible local or regional flaps are available. An operative solution is yet to be found. The descending branch of the lateral circumflex femoral artery of the injured leg was used as the recipient artery in a reverse-flow fashion in these difficult wounds. METHODS: From March of 2005 to May of 2010, 11 male and four female patients with soft-tissue defects in the lower leg were treated. Causes of injury were industrial machinery injuries in six patients and traffic accidents in nine patients. Mean patient age at surgery was 36.6 years. The mean soft-tissue defect size was 17.6 × 7.4 cm, and the mean anterolateral thigh flap was 19.3 × 8.7 cm. The mean length of flap pedicles was 11.8 cm, and the mean length of recipient pedicles was 15.7 cm. RESULTS: Fourteen flaps survived completely. Partial necrosis at the distal edge of the flap occurred in one case. No patient needed operative revision due to postoperative thrombosis of the vessels. At the mean follow-up period of 10.5 months, wound coverage was achieved in all patients. CONCLUSIONS: The reverse descending branch of the lateral circumflex femoral artery is a reliable recipient artery for the free anterolateral thigh flap taken from the opposite thigh. The technique can be used to reconstruct defects in the lower leg when use of local or regional flaps is not feasible and commonly used recipient arteries are not available. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Modification of rat model of sciatica induced by lumber disc herniation and the anti-inflammatory effect of osthole given by epidural catheterization.

One of the most treatable causes of lower back pain and associated sciatica is lumbar disc herniation (LDH), which is characterized by rupture of the hard outer wall (annulus fibrosis) in a lumbar intervertebral disc. In the current study, we aimed to: (1) develop and characterize a rat model of sciatica induced by LDH, while introducing a novel method of epidural catheterization; (2) use this model to evaluate the effect of osthole on pain due to LDH, and (3) gain insight into the mechanisms through which osthole affects sciatica induced by LDH. The results indicate that our newly developed rat model maintained mechanical allodynia for 28 days without reduction. Moreover, cyclooxygenase-2 (COX-2) and nitric oxide synthase (NOS) were overexpressed in the associated inflammatory response, which is consistent with clinical manifestations of the disease. We then used this model to study the effect and mechanisms through which osthole affected pain due to LDH. Our study suggests that osthole is capable of reversing hyperalgesia due to LDH, potentially through modulation of activity of COX-2 and NOS, two important proteins for the exacerbation of pain due to LDH. Finally, a molecular modeling simulation showed that osthole has unique binding capabilities to both NOS and COX-2. As the model-induced mechanical hyperalgesia response was consistent, and the position of the catheter tip and the extension/spreading of the drug in the epidural space were reliable, this study developed an improved model to study remedies for sciatic pain. Moreover, our studies demonstrate that osthole may be a feasible treatment for the reduction of pain due to hyperalgesia.