The purpose of this study was to investigate the molecular mechanism by which miR-21 and its target genes mediate radiation resistance of glioblastoma cells. Real-time PCR was employed to detect miR-21 expression in normal brain tissues, glioblastoma tissues and glioblastoma cell lines (A172, T98G and U87MG). T98G cells were transfected with anti-miR-21 oligonucleotides, or plasmids containing PDCD4 or hMSH2 (PDCD4-pcDNA3 and hMSH2-pcDNA3). The survival curve was obtained to investigate the sensitivity of T98G cells to radiation. Cell apoptosis was measured by using the Caspase-3/7 kit and cell cycle by flow cytometry. Western blotting was performed to detect the expression of hMSH2 and PDCD4 in miR-21-inhibiting T98G cells. The results showed that miR-21 expression in glioblastoma cells and tissues was conversely associated with the radiation sensitivity. Over-expression of miR-21 resulted in radiation resistance, while knockdown of miR-21 led to higher sensitivity of glioblastma cells to radiation. After miR-21 knockdown, the apoptosis of T98G cells was significantly increased and the G(2) phase arrest was more significant. In addition, miR-21 knockdown increased the expression of endogenous PDCD4 and hMSH2, which contributed to the apoptosis and G(2) arrest of T98G cells. The findings suggested that miR-21 may mediate the resistance of glioblastoma cells against radiation via its target genes PDCD4 and hMSH2. MiR-21 and its target genes may be used as potential molecular targets for clinical radiotherapy sensitization in the future.
Apoptosis Regulatory Proteins ; genetics ; Cell Line, Tumor ; Glioblastoma ; genetics ; Humans ; MicroRNAs ; genetics ; MutS Homolog 2 Protein ; genetics ; RNA-Binding Proteins ; genetics ; Radiation Tolerance ; genetics

OBJECTIVETo study the application of three-dimensional reconstruction technique based on CT-MRI fusion in skull base surgery.

METHODSTo acquire the thin layer CT scan and MRI scanned images, to achieve image registration, fusion, segmentation and 3D visualization by using self-preparation software, to operate, observe and measure models by using methods of endoscopic observation, volume rendering segmentation, automatically and manually measure.

RESULTSThe center of the eye and foramen magnum in CT-MRI were used as point registration. Good coincidence of important anatomic landmarks were formed in the image fusion. The boundary of spotted graphical was clear and complete. The models showed a complete, continuous, smooth surface. Virtual endoscopy could display the inside three-dimensional structures of skull from nasal with fluent operations of rotation and transparency. The boundary of skull stump segmented after volume rendering segmentation was clear and smooth, and it could show bone signs and soft tissue models together. Cooperation of automatic measurement method [(32.007 ± 15.311) mm] and the manual measurement method [(30.240 ± 15.169) mm] for measuring the maximum diameters of the tumor model, the difference was significant (t = 8.409, P < 0.05).

CONCLUSIONSThe method of selecting the center of the eye and foramen magnum in point matching is scientific, simple and easy to operate. The models reconstructed based on CT-MRI fusion images can accurately reflect the size of the soft tissue and be better measured through the automatic measurement. Reconstruction models can be observed through the way of virtual endoscopic within the nasal cavity or volume rendering segmentation from outside to inside to frustrate the relationship of skull structures. Three-dimensional reconstruction techniques based on CT-MRI fusion in skull base surgery can be used to plan surgical approach, to assess the risk of surgery and to achieve space measurements, and it laid the foundation for the three-dimensional navigation.

Adult ; Aged ; Endoscopy ; Female ; Humans ; Image Processing, Computer-Assisted ; Imaging, Three-Dimensional ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Skull Base ; surgery ; Software ; Tomography, Spiral Computed ; Tomography, X-Ray Computed

Objective: To evaluate the associative role of depression and apolipoprotein E epsilon 4 allele (APOEε4) in subjective cognitive decline (SCD) and its progression to objective cognitive decline. Methods: After literature search in electronic databases, studies were selected by following precise eligibility criteria. Meta-analyses were performed to examine the role of APOEε4 and depression in SCD or its progression to mild cognitive impairment (MCI) or dementia. Results: APOEε4 positivity was not different between SCD and normal individuals but was significantly higher in individuals with SCD plus than in normal individuals [odds ratio: 2.39 (95% CI: 1.87, 3.05); p<0.00001] and in SCD converters than in non-converters [odds ratio: 5.19 (95% CI: 2.36, 11.42); p<0.00001]. Depression was significantly higher in individuals with SCD [standardized mean difference: 0.63 (0.45, 0.82); p<0.00001] and SCD plus [standardized mean difference: 0.83 (0.43, 1.22); p<0.0001] than in normal individuals. However, depression was not different between SCD and MCI or between SCD converters and non-converters. Age of SCD converters was higher than non-converters [mean difference: 2.95 years (0.58, 5.31)]. Conclusion Whereas APOEε4 positivity was higher in SCD plus and SCD converters, depression was higher in SCD and SCD plus but was not different between SCD and MCI.

BackgroundThe quick Sequential Organ Failure Assessment (qSOFA) score emerged recently. We investigated its contribution to risk stratification in acute pulmonary embolism (PE) by combining with electrocardiography (ECG).

MethodsAcute PE patients diagnosed in Beijing Chao-Yang Hospital, Capital Medical University, from 2008 to 2018 were retrospectively studied and divided into high- and low - risk groups by imaging and biomarkers. The ECG scores consisted of tachycardia, McGinn-White sign (SQT), right bundle branch block, and T-wave inversion of leads V-V. A new combination of qSOFA scores and ECG scores by logistic regression for predicting high-risk stratification patients with acute PE was evaluated by a receiver operating characteristic curve.

ResultsTotally 1318 patients were enrolled, including 271 in the high-risk group and 1047 in the low-risk group. A combination predictive scoring system named qSOFA-ECG = qSOFA score + ECG score was created. The optimal cutoff value for qSOFA-ECG was 2, and the sensitivity, specificity, positive predictive value, and negative predictive value were 81.5%, 72.3%, 43.2%, and 93.8%, respectively. For predicting high-risk stratification and reperfusion therapy, the qSOFA-ECG is superior to PE Severity Index (PESI) and simplified PESI.

ConclusionsThe qSOFA score contributes to identify acute PE patients with potentially hemodynamic decompensation that need monitoring and possible reperfusion therapy at the emergency department arrival when used in combination with ECG score.

Objective To analyze the epidemic tendency of Microtus fascus plague during 2000-2008 in Sichuan province. Methods To investigate the plague each year according to "overall Plan of the Plague in the Whole Nation" and "Surveillance Program of Sichuan Province Plague". Results There were plague epidemic from 2000 to 2008, with the average density as 312.41/ha. 42.57% of the Microtus fuscus were infected by body Fleas. The Fleas Index was 0.88 and the Index for nest Fleas of Microtas fuscus was 55.89. Six kinds of animals were infected by not only the Microtus fuscus but also herd-dog, sand fox, Tibetan sheep, domestic cats and Cricetulus longicaulatus as well. The positive rate of live Microtus fuscus was 0.32% but 22.99% in the dead Microtus fuscus. The overall positive rate on serological test was 6.70%. There were 4 Sections, 11 species and 19 kinds Fleas identified and carrying 3 kinds of fleas, Callopsylla sparsilis, Amphipsylla tntua tutua and Rhadinopsylla dahurica vicina, with the overall infection rate as 0.054%. Conclusion Plague among Microtus fuscus showed a continuous epidemic in Sichuan province during 2000-2008.

Objective To analyzed the variant information on the indices regarding fleas from natural foci of Microtus plague in Sichuan epidemic area during 2000 to 2008.Methods Statistical and analytical methods were used on the surveillance data regarding Microtus fuscus plague.Results There were 19 flea species identified and the share of Callopsylla sparsilis was 62.79 percent while the share of Amphipsylla tuta tuta was 30.90 percent on Microtus fuscus plague.The infection rate of fleas and the flea index were the highest in October and the lowest in December and March.Species as Callopsylla sparsilis,Amphipsylla tuta tuta and Rhadinopsylla dahurica vicina could naturally infect the Yersinia pestis.Conclusion Microtus fuscus plague could become epidemic when animals and flea species were infected.We should emphasis on plague monitoring program so as to prevent the occurrence of the disease.

OBJECTIVETo detect the expression of CBX7 in human glioma and investigate the potential regulatory effect of abnormally expressed microRNAs on CBX7 expression.

METHODSSemi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot were applied to detect the expression pattern of CBX7 in 2 human normal brain tissues, 9 glioma tissues, and 3 glioma cell lines. Miranda algorithm and Ensemble Machine Learning algorithm were combined to predict miRNAs that target human CBX7. The expression of miR-9 in those tissues and cell lines were detected by real-time PCR. After miR-9 overexpression in 293ET and miR-9 knock-down in T98G, luciferase assay and Western blot were used to confirm the effect of miR-9 on CBX7 expression. MTT assay and flow cytometry were applied to detect the effect of miR-9 knock-down on T98G cells.

RESULTSNo obvious difference in the CBX7 mRNA level between normal and tumor tissues was observed, while the protein level of CBX7 was abrogated or markedly reduced in glioma tissues and cell lines. Several miRNAs including miR-9 may target CBX7 by bioinformatics prediction. MiR-9 was up-regulated in glioma tissues and cell lines. In 293ET cell, luciferase activity of CBX7-3'UTR reporter was decreased to 24% after miR-9 overexpression. After miR-9 knock-down in T98G cell, the luciferase activity was increased by 1.8 fold and there was no change of CBX7 mRNA, while the protein level of endogenous CBX7 was significantly increased. The number of survival T98G cells increased and cells in G1 phase decreased after miR-9 knock-down.

CONCLUSIONIn human glioma, CBX7 is down-regulated by the inhibition of miR-9 at posttranscriptional level.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Algorithms ; Blotting, Western ; Brain ; metabolism ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Child ; Female ; Flow Cytometry ; Glioma ; genetics ; metabolism ; Humans ; In Vitro Techniques ; Male ; MicroRNAs ; genetics ; physiology ; Middle Aged ; Polycomb Repressive Complex 1 ; Repressor Proteins ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Young Adult

BACKGROUNDMicroRNAs (miRNAs) are small noncoding regulatory RNAs whose aberrant expression may be observed in many malignancies. However, few data are yet available on human primary medulloblastomas. This work aimed to identify that whether miRNAs would be aberrantly expressed in tumor tissues compared with non-tumorous cerebellum tissues from same patients, and to explore a possible role during carcinogenesis.

METHODSA high throughput microRNA microarray was performed in human primary medulloblastoma specimens to investigate differentially expressed miRNAs, and some miRNAs were validated using real-time quantitative RT-PCR method. In addition, the predicted target genes for the most significantly down- or up-regulated miRNAs were analyzed by using a newly modified ensemble algorithm.

RESULTSNine miRNA species were differentially expressed in medulloblastoma specimens versus normal non-tumorous cerebellum tissues. Of these, 4 were over expressed and 5 were under expressed. The changes ranged from 0.02-fold to 6.61-fold. These findings were confirmed using real-time quantitative RT-PCR for most significant deregulated miRNAs (miR-17, miR-100, miR-106b, and miR-218) which are novel and have not been previously published. Interestingly, most of the predicted target genes for these miRNAs were involved in medulloblastoma carcinogenesis.

CONCLUSIONSMiRNAs are differentially expressed between human medulloblastoma and non-tumorous cerebellum tissue. MiRNAs may play a role in the tumorigenesis of medulloblastoma and maybe serve as potential targets for novel therapeutic strategies in future.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Medulloblastoma ; genetics ; MicroRNAs ; genetics ; metabolism ; Oligonucleotide Array Sequence Analysis ; Reverse Transcriptase Polymerase Chain Reaction

Objective To analyze clinicopathological characteristics and the potential risk-related factors of female breast hyperplasia in different age groups.Method From Jan 2015 to Dec 2016,patients diagnosed with breast hyperplasia in 12 hospitals were evaluated.All patients completed the self-designed questionnaires on women'health,including basic demographic information,clinic examination information,radiologic information and pathologic results.The patients were divided into a young group (＜ 45 years old) and an elderly group (from 45 to 75 years old).Results There were 3 684 cases of breast hyperplasia,including 2 291 cases in young group and 1 393 cases in elder group,respectively Clinically breast pain type were most commonly observed in both young and older groups (50.3％ vs.42.7％,P ＜ 0.001).While pathological research based on biopsy showed that breast adenopathy were the most common changes in both groups (67.9％ vs.61.7％,P ＜0.001).More breast cancer cases were identified in elder group than that in young group,especially in clinically lump type patients (9.4％ vs.4.2％,P ＜ 0.001).Compared with elder group,patients in young group have different distribution characteristics regarding to fertility factors,lifestyle factors and psychology scale including anxiety and depression.Conclusion Distributions of clinicopathological characteristics and risk factors of female breast hyperplasia differ across different age groups.

OBJECTIVETo investigate the roles of the mammalian target of rapamycin-1 and -2 (mTORC1 and TORC2) in the proliferation and apoptosis of prostate cancer 22RV1 cells.

METHODSAfter silencing mTORC1 and TORC2, we examined the proliferation and apoptosis of prostate cancer 22RV1 cells by methylthiazol tetrazolium (MTT) assay and flow cytometry, respectively, and detected the expressions of the androgen receptor (AR) and Akt phosphorylation in the prostate cancer 22RV1 cells by Western blot after transfecting Raptor-siRNA and Rictor-siRNA to the 22RV1 cells.

RESULTSMTT showed that the prostate cancer 22RV1 cells had no significant change in the growth rate after mTORC1 silence (P > 0.05), but their proliferation was markedly inhibited after mTORC2 silence (P < 0.01). Flow cytometry revealed a dramatic increase in the apoptosis of the 22RV1 cells after mTORC1 silence (P < 0.01), but no obvious change after mTORC2 silence (P > 0.05). Western blot exhibited that mTORC1 silence significantly increased the expression of AR and Akt phosphorylation (P < 0.05), while mTORC2 silence markedly decreased them (P < 0.05).

CONCLUSIONmTORC2 is not only required for the survival of prostate cancer 22RV1 cells, but also a promising therapeutic target of prostate cancer.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Male ; Mechanistic Target of Rapamycin Complex 1 ; Mechanistic Target of Rapamycin Complex 2 ; Multiprotein Complexes ; metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; metabolism ; Receptors, Androgen ; metabolism ; Sirolimus ; pharmacology ; TOR Serine-Threonine Kinases ; metabolism