YY1-induced lncRNA XIST inhibits cartilage differentiation of BMSCs by binding with TAF15 to stabilizing FUT1 expression.

Introduction: The functional roles and mechanism of the XIST in osteoarthritis and the chondrogenic differentiation of BMSCs were clarified. Methods: The expression levels of XIST, TAF15, FUT1 and YY1 were detected through quantitative RT-PCR. The protein expression of Sox9, ACAN, COL2A1 and FUT1 were detected by western blot and immunohistochemistry. The damage of cartilage tissue was detected by HE staining, and Safranin O-fast green. Alcian-Blue and Alizarin red S staining were performed to evaluate BMSCs chondrogenic differentiation. The relationship between XIST and TAF15, XIST and TAF15 were analyzed by RNA immunoprecipitation assay. Luciferase reporter assays and chromatin immunoprecipitation were performed to detect the interaction relationship between XIST and YY1. In addition, osteoarthritis mice were built to assess the function of XIST in vivo. Results: The levels of XIST, TAF15 and FUT1 were upregulated in cartilage tissues from osteoarthritis patient. The level of XIST was decreased in BMSCs during chondrogenic differentiation. XIST overexpression inhibited the chondrogenic differentiation of BMSCs. Moreover, silencing of FUT1 reversed the effects of XIST overexpression on BMSCs chondrogenic differentiation. Mechanistically, in BMSCs, YY1 induced the expression of XIST in BMSCs, and XIST regulated FUT1 mRNA stability through targeting TAF15. Furthermore, silencing of XIST alleviated the symptoms of cartilage injury in OA mice. Conclusion: Taken together, these results suggested that YY1 induced XIST was closely related to the chondrogenic differentiation of BMSCs and the progression of osteoarthritis by TAF15/FUT1 axis, and may be a new OA therapeutic target.

Stress analysis of the thoracolumbar junction in the process of backward fall: An experimental study and finite element analysis.

The aim of the present study was to evaluate the biomechanical mechanism of injuries of the thoracolumbar junction by the methods of a backward fall simulation experiment and finite element (FE) analysis (FEA). In the backward fall simulation experiment, one volunteer was selected to obtain the contact force data of the sacrococcygeal region during a fall. Utilizing the fall data, the FEA simulation of the backward fall process was given to the trunk FE model to obtain the stress status of local bone structures of the thoracolumbar junction during the fall process. In the fall simulation test, the sacrococcygeal region of the volunteer landed first; the total impact time was 1.14±0.58 sec, and the impact force was up to 4,056±263 N. The stress of thoracic (T)11 was as high as 42 MPa, that of the posterior margin and the junction of T11 was as high as 70.67 MPa, and that of the inferior articular process and the superior articular process was as high as 128 MPa. The average stress of T12 and the anterior margin of lumbar 1 was 25 MPa, and that of the endplate was as high as 21.7 MPa, which was mostly distributed in the back of the endplate and the surrounding cortex. According to the data obtained from the fall experiment as the loading condition of the FE model, the backward fall process can be simulated to improve the accuracy of FEA results. In the process of backward fall, the front edge of the vertebral body and the root of vertebral arch in the thoracolumbar junction are stress concentration areas, which have a greater risk of injury.

A Prediction Rule for Overall Survival in Non-Small-Cell Lung Cancer Patients with a Pathological Tumor Size Less Than 30 mm.

We sought to develop and validate a clinical nomogram model for predicting overall survival (OS) in non-small-cell lung cancer (NSCLC) patients with resected tumors that were 30 mm or smaller, using clinical data and molecular marker findings. We retrospectively analyzed 786 NSCLC patients with a pathological tumor size less than 30 mm who underwent surgery between 2007 and 2017 at our institution. We identified and integrated significant prognostic factors to build the nomogram model using the training set, which was subjected to the internal data validation. The prognostic performance was calibrated and evaluated by the concordance index (C-index) and risk group stratification. Multivariable analysis identified the pathological tumor size, lymph node metastasis, and Ki-67 expression as independent prognostic factors, which were entered into the nomogram model. The nomogram-predicted probabilities of OS at 1 year, 3 years, and 5 years posttreatment represented optimal concordance with the actual observations. Harrell's C-index of the constructed nomogram with the training set was 0.856 (95% CI: 0.804-0.908), whereas TNM staging was 0.814 (95% CI: 0.742-0.886, P = 5.280221e - 13). Survival analysis demonstrated that NSCLC subgroups showed significant differences in the training and validation sets (P < 0.001). A nomogram model was established for predicting survival in NSCLC patients with a pathological tumor size less than 30 mm, which would be further validated using demographic and clinicopathological data. In the future, this prognostic model may assist clinicians during treatment planning and clinical studies.

Prognostic value of mutant p53, Ki-67, and TTF-1 and their correlation with EGFR mutation in patients with non-small cell lung cancer.

INTRODUCTION: The clinical characteristics of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation have been well studied. However, the correlation of EGFR mutation with mutant p53, Ki-67, and thyroid transcription factor 1 (TTF-1) and their prognostic value remain indistinct. MATERIAL AND METHODS: Clinical and pathological characteristics and overall survival were analysed retrospectively in 523 surgically resected NSCLC patients. The expression levels of p53, Ki-67, and TTF-1 protein were detected by immunohistochemistry, and an amplification refractory mutation system was used to access the status of EGFR mutations. RESULTS: Of 523 patients with surgically resected NSCLC, 210 patients (38.4%) harboured EGFR mutations. Compared to the EGFR wild-type lung cancer, mutated EGFR harboured significantly increased mutant p53-positive or TTF-1-positive tumors (P<0.001 and<0.001, respectively). Former or current smokers, pathological stage and mutant p53-or TTF-1-positive status were independent predictors of EGFR mutation (P=0.001, 0.014, 0.014 and <0.001, respectively). Patients with p53 under expression had significantly better overall survival in the whole cohort and wild-type EGFR cohort (P=0.0010 and 0.0020, respectively) as well as in Ki-67-negative and TTF-1-positive patients (P<0.0001 and 0.0009, and P<0.0001 and 0.0004, respectively). Interestingly, in patients harbouring EGFR mutations, p53-under expression and Ki-67-negative cases still had better survival than positive cases, whereas there was no obvious difference between TTF-1-negative and TTF-1-positive cases (P=0.0198, 0.0068 and 0.3684, respectively). Finally, in NSCLC patients with wild-type EGFR, positive Ki-67 expression was the independent predictor for the worst survival (P=0.022). CONCLUSION: The expression levels of mutant p53, Ki-67, and TTF-1 were correlated with EGFR mutation. High expression of mutant p53 and Ki-67 correlated with poor survival in the entire cohort, EGFR mutation or wild-type cohort. In addition, Ki-67 might have an impact on the prognosis for patients with NSCLC with wild-type EGFR.

Post-stroke gastrodin treatment ameliorates ischemic injury and increases neurogenesis and restores the Wnt/ß-Catenin signaling in focal cerebral ischemia in mice.

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide, and the only available drug treatment is limited to a short window following the ischemic event. Gastrodin is the major bioactive constituent extracted from thetuberGastrodia elata, and is currently used to treat dizziness in the clinic. "Early" application of gastrodin (before modeling or immediately after ischemic injury) has shown antioxidative and neuroprotective effects in a transient focal brain ischemia model in rodents; however, it is not known whether the delayed administration of gastrodin after permanent focal cerebral ischemia ameliorates neural injury and increases neurogenesis. In this study, we performed a permanent middle cerebral artery occlusion (MCAO) model for the study of cerebral ischemic stroke in adult male mice to examine the effects of gastrodin. Gastrodin treatment that was started "late" (one day after the ischemic injury) significantly improved neural function, reduced infarct volume and apoptosis, and increased the number of DCX/BrdU double-positive cells in permanent MCAO mice. Moreover, gastrodin treatment markedly preserved the Wnt/ß-Catenin signaling pathway, which could promote neurogenesis and provide neuroprotection brain injury. Our findings suggest that gastrodin treatment following ischemic injury can induce neuroprotection, promote neurogenesis and restored the Wnt /ß-Catenin signaling pathway.

Unplanned Reoperation of Lumbar Spinal Surgery During the Primary Admission: A Multicenter Study Based on a Large Patient Population.

STUDY DESIGN: A retrospective study. OBJECTIVE: The purpose of this study was to identify the rates and reasons, and the risk factors for unplanned reoperation of lumbar spinal surgery during the primary admission in terms of a multicenter and a large patient population study. SUMMARY OF BACKGROUND DATA: Unplanned reoperation is suggested to be a useful quality indicator for spinal surgery. However, the rates of unplanned reoperation in patients underwent lumbar spinal surgery during the primary admission are not well established. METHODS: This study was performed to review all the patients who underwent lumbar spinal surgery at three institutions from January 2010 to April 2015. Patients with unplanned reoperations after primary surgery during the same admission were included in this study. The demographics, diagnosis, surgical procedure, and complications of patients were reviewed and statistical analysis was performed to investigate the incidences and risk factors of unplanned revision. RESULTS: A total of 3936 patients who underwent lumbar spinal surgery from three institutions were reviewed, and 82 (2.08%) required unplanned reoperation during the primary admission because of wound infection (0.94%), screw misplacement (0.53%), cerebrospinal fluid leakage (0.27%), wound hematoma (0.18%), and neurologic deficit (0.15%). For the diagnosis, patients with lumbar spinal spondylolisthesis had a much higher rate of reoperation (4.3%) than those of lumbar stenosis (2.3%), vertebral tumor (2.2%), vertebral fracture (1.2%), and disc herniation (1.1%) with a significant difference (P < 0.001). The revision rate was significantly higher in patients underwent posterior lumbar interbody fusion than those received transforaminal lumbar interbody fusion (P = 0.007). CONCLUSION: Unplanned reoperation rate of lumbar spinal surgery was 2.08% and the most common reasons for it were wound infection and screw misplacement. Patients with a diagnosis of lumbar spinal spondylolisthesis or who underwent posterior lumbar interbody fusion were more likely to required unplanned reoperation during the primary admission. LEVEL OF EVIDENCE: 4.

Knockdown of Aurora-B alters osteosarcoma cell malignant phenotype via decreasing phosphorylation of VCP and NF-κB signaling.

The aim of this study is to investigate the effects of inhibiting Aurora-B on osteosarcoma (OS) cell malignant phenotype, phosphorylation of valosin-containing protein (VCP), and the activity of NF-κB signaling in vitro. The expressions of Aurora-B and p-VCP proteins were detected by immunohistochemistry in 24 OS tissues, and the relationship between Aurora-B and p-VCP was investigated. The results showed that there was a positive correlation between Aurora-B and p-VCP proteins. The expression of Aurora-B in human OS cell lines U2-OS and HOS cells was inhibited by specific short hairpin RNA (shRNA) lentivirus (AURKB-shRNA lentivirus, Lv-shAURKB) which targeted Aurora-B. The results showed that the phosphorylation of VCP, the activity of NF-κB signaling pathway and the malignant phenotype of OS cells were all suppressed by knockdown of Aurora-B. It indicated that the inhibition of Aurora-B alters OS cells malignant phenotype by downregulating phosphorylation of VCP and activating of the NF-κB signaling pathway in vitro.

Tim-3 expression by peripheral natural killer cells and natural killer T cells increases in patients with lung cancer--reduction after surgical resection.

BACKGROUND: The purpose of this study was to investigate Tim-3 expression on peripheral CD3-CD56+ natural killer (NK) cells and CD3+CD56+ natural killer T (NKT) cells in lung cancer patients. MATERIALS AND METHODS: We analyzed Tim-3+CD3-CD56+ cells, Tim-3+CD3-CD56dim cells, Tim-3+CD3-CD56bright cells, and Tim- 3+CD3+CD56+ cells in fresh peripheral blood from 79 lung cancer cases preoperatively and 53 healthy controls by flow cytometry. Postoperative blood samples were also analyzed from 21 members of the lung cancer patient cohort. RESULTS: It was showed that expression of Tim-3 was significantly increased on CD3-CD56+ cells, CD3- CD56dim cells and CD3+CD56+ cells in lung cancer patients as compared to healthy controls (p=0.03, p=0.03 and p=0.04, respectively). When analyzing Tim-3 expression with cancer progression, results revealed more elevated Tim-3 expression in CD3-CD56+ cells, CD3-CD56dim cells and CD3+CD56+ cells in cases with advanced stages (III/IV) than those with stage I and II (p=0.02, p=0.04 and p=0.01, respectively). In addition, Tim-3 expression was significantly reduced on after surgical resection of the primary tumor (p<0.01). CONCLUSIONS: Tim-3 expression in natural killer cells from fresh peripheral blood may provide a useful indicator of disease progression of lung cancer. Furthermore, it was indicated that Tim-3 might be as a therapeutic target.

Differential expression of miR-125a-5p and let-7e predicts the progression and prognosis of non-small cell lung cancer.

Aberrant expression of various microRNAs (miRNA) has shown diagnostic and prognostic significance in non-small cell lung cancer (NSCLC). qRT-PCR analysis confirmed altered expression of miR-125a-5p, let-7e, miR-30a, miR-30e and miR-30e-3p in 70 paired tissue and serum samples from NSCLC patients. The reduced expression of miR-125a-5p, let-7e and miR-30e was strongly associated with NSCLC dedifferentiation. The lost expression of miR-125a-5p and let-7e was associated with shorter overall survival and let-7e was an independent prognostic factor for NSCLC patients. These five miRNA expressions should be further evaluated as biomarkers for the early detection and prognosis of NSCLC patients.

Evaluation of dynamic change of serum miR-21 and miR-24 in pre- and post-operative lung carcinoma patients.

Although circulating microRNAs (miRNAs) were frequently detected in sera of cancer patients, there is still a lack of analysis of the dynamic changes of miRNAs expression in sera of pre- and post-operative lung carcinoma patients. Thus, we conducted quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to examine the expression of four miRNAs (miR-21, miR-205, miR-30d, and miR-24) in the sera of a set of 82 pre-operative lung carcinoma patients and paired 10 days post-operative patients, as well as in 50 normal volunteers. We showed that, compared to that in normal volunteers, the expression of miR-21, miR-205, miR-30d, and miR-24 was increased in lung cancer sera samples, as well as in sera of early stage lung cancer patients according to their clinical-pathological characteristics. The area under roc curves (AUCs) for levels of miR-21, miR-205, miR-30d, and miR-24 in sera were significantly higher than those for Carcinoma embryonic antigen (CEA) (P < 0.05), whereas the AUC for combination of serum levels of miRNA with serum CEA showed no significant difference from that for serum levels of miRNAs only (P > 0.05). The expression levels of miR-21 and miR-24 were significantly decreased in post-operative sera compared with levels in paired pre-operative sera (P = 0.0004 and <0.0001, respectively). In addition, high expressions of miR-21 and miR-30d in pre-operative sera were independently correlated with shorter overall survival in lung cancer patients (log-rank test: P = 0.0498, 0.0019). In summary, our results suggest that miR-21, miR-205, miR-30d, and miR-24 may serve as potential novel non-invasive biomarkers for diagnosis of lung cancer. In addition, miR-21 and miR-24 serum levels were lower in post-operative samples than those in pre-operative samples, suggesting they can potentially be used as biomarkers for disease recurrence after surgery operation.

miRNAs expression profiling to distinguish lung squamous-cell carcinoma from adenocarcinoma subtypes.

PURPOSE: We investigated whether miRNA expression profiles can distinguish and predict outcome of non-small-cell lung carcinoma (NSCLC) patients with different histological subtypes. METHODS: High-throughput microarray was used to measure miRNA expression levels in six NSCLC samples. Subsequently, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to verify findings in an independent set of 54 squamous-cell lung carcinomas (SCC), 51 lung adenocarcinomas (AD), and paired adjacent non-neoplastic lung tissue. RESULTS: We showed that, compared to adjacent non-neoplastic lung tissues, the expressions of miR-125a-5p and let-7e were decreased in AD and SCC samples, while increased expressions of miR-93, miR-205, and miR-221 were observed in SCC samples. In addition, miR-205 expression was significantly higher in SCC patients with lymph node metastasis. Lower let-7e expression was associated with lymph node metastasis, >3 cm tumor size, and differentiation of the NSCLC AD subtype. High levels of miR-100 expression also correlated with the AD subtype in current smokers. Moreover, induction of miR-93 and miR-205 expressions and reduction of let-7e were strongly associated with shorter overall survival in SCC patients, whereas AD patient survival was only associated with reduced let-7e. CONCLUSIONS: We identified differential expression profiles of miRNAs in AD and SCC. More importantly, in addition to morphology and immunocytochemistry approaches, we report that miR-93, miR-205, miR-221, and let-7e may represent novel biomarkers for differential diagnosis and prognosis of certain NSCLC subtypes or be new targets of histology-specific treatments. Furthermore, our results suggest a strong correlation between high expression of miR-100 and AD patients with history of heavy smoking.

Prognostic evaluation of CapG, gelsolin, P-gp, GSTP1, and Topo-II proteins in non-small cell lung cancer.

Metastasis and multidrug resistance (MDR) are the main reasons for the poor prognosis of non-small cell lung cancer (NSCLC) patients. The use of biomarkers may contribute to a more accurate prediction of tumor metastasis, a better response to chemotherapy, and better patient survival. Gelsolin-like actin-capping protein (CapG) and gelsolin have been identified as playing important roles in tumor invasion and metastasis. Permeability glycoprotein (P-gp), glutathione S-transferase pi (GSTP1), and topoisomerase-II (Topo-II) are proteins that are closely related to MDR. In this study, we assessed the prognostic significance of CapG and gelsolin (both markers of tumor motility), and of P-gp, GSTP1, and Topo-II (markers of MDR) in NSCLC patients. One hundred and twenty-one patients with pathologically confirmed, resectable NSCLC were included in the study. The expression levels of the five kinds of proteins mentioned above were determined by immunohistochemistry (IHC). The correlation between the clinical characteristics and IHC findings were analyzed. Expression of CapG, gelsolin, and P-gp was found to be associated with an increased risk of death (Hazard Ratio (HR) = 2.799, 95% Confidence Interval (CI) = 1.2705-6.169, P = 0.011; HR = 3.968, 95% CI = 1.811-8.693, P = 0.001; HR = 3.251, 95% CI = 1.456-7.260, P = 0.004, respectively), whereas expression of GSTP1 and Topo-II was not. These results suggest that higher tumor motility and MDR may be important in NSCLC prognosis.

[An epidemiological study of the neoplasm mortality in Gejiu residents from 1996 to 2005].

OBJECTIVE: To assessment the trend of the mortality of the neoplasm among the residents in Gejiu city of Yunnan province and to provide scientific evidences for the neoplasm prevention. METHODS: Data of mortality of the neoplasm from 1996 to 2005 was collected and analyzed through a retrospective survey. RESULTS: The mortality was going up in the recent epidemiological surveys. The increase trend was showed on the mortality from 1996 to 2005. The mortality was 53.25 per 100,000 of 1996 increased to 70.58 per 100,000 in 2005. The mortality in female was 23.76 per 100,000 in 1996 increased to 50.57 per 100,000 of 2005. CONCLUSION: The neoplasm is still a leading disease in Gejiu city. The main cancer was lung cancer in the neoplasms. The mortality of the neoplasma in the town residents was higher than the countryside. It is necessary to enhance neoplasm prevention.