Oral azacitidine prolongs survival of patients with AML in remission independently of measurable residual disease status.

Measurable residual disease (MRD) in patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy is predictive of early relapse and poor survival. Postremission maintenance therapy that prolongs MRD negativity or converts MRD+ patients to MRD- status may delay or prevent relapse and improve overall survival (OS). In the phase 3 QUAZAR AML-001 trial, oral azacitidine (oral-AZA; formerly CC-486), a hypomethylating agent, significantly prolonged OS and relapse-free survival (RFS) compared with placebo in patients aged ≥55 years with AML in first remission after intensive chemotherapy who were not candidates for hematopoietic stem cell transplantation. In this trial, MRD (≥0.1% leukemic cells in bone marrow) was assessed by multiparameter flow cytometry in serial samples collected at baseline and on day 1 of every 3 cycles. As expected, baseline MRD status was significantly associated with both OS and RFS. Multivariate analyses showed oral-AZA significantly improved OS and RFS vs placebo independent of baseline MRD status. Oral-AZA treatment also extended the duration of MRD negativity by 6 months vs placebo and resulted in a higher rate of conversion from MRD+ at baseline to MRD- during treatment: 37% vs 19%, respectively. In the oral-AZA arm, 24% of MRD responders achieved MRD negativity >6 months after treatment initiation. Although presence or absence of MRD was a strong prognostic indicator of OS and RFS, there were added survival benefits with oral-AZA maintenance therapy compared with placebo, independent of patients' MRD status at baseline. Registered at clinicaltrials.gov as #NCT01757535.

Decreased expression of SRY-box containing gene 30 is related to malignant phenotypes of human bladder cancer and correlates with poor prognosis.

BACKGROUND: In human pulmonary malignancies, the SRY-box containing gene 30 (SOX30) is a known cancer-suppressing gene. Nevertheless, its molecular role and clinical effects remains unknown in bladder cancer. METHODS: SOX30 mRNA expression was quantified in bladder cancer tissue, paired adjacent normal tissue, and cell lines with qRT-PCR. SOX30 protein expression in BC tissue and cell lines was evaluated via western blotting and immunohistochemistry. In addition, the clinical and prognostic significance of SOX30 in BC were assessed using Kaplan-Meier analysis. Furthermore, we measured cell migration and invasion, cell proliferation and cell apoptosis by means of a Transwell assay, cell counting kit-8 along with flow cytometry, respectively. RESULTS: Expression levels of SOX30 were markedly lower in BC cells and tumor tissues than in adjacent noncancerous tissues. Moreover, clinicopathological analyses showed that low SOX30 expression was positively related to an advanced tumor, node, and metastasis (TNM) stage. Furthermore, low SOX30 expression conferred reduced survival rates (P < 0.05). Functional analyses revealed that SOX30 overexpression attenuated cell proliferation, invasion, and migration, while promoting apoptosis in BC cells. CONCLUSIONS: SOX30 displays tumor suppressive behavior, warranting future investigations into its therapeutic potential in the treatment of BC.

TMEM106a is a Novel Tumor Suppressor in Human Renal Cancer.

BACKGROUND/AIMS: In recent years the diagnosis and management of renal cancer has changed greatly, although the mechanism is still elusive. TMEM106a is a conserved type II transmembrane protein which is a key factor to regulate macrophage activation. Its inactivation in gastric cancer is frequently observed to be associated with poor prognosis. The role of TMEM106a in renal cancer remained unclear. METHODS: TMEM106a expression profiling was performed in a panel of renal cancer cell lines and primary renal tissue cells. Then TMEM106a was overexpressed by a viral system in a renal cancer cell line with low level of TMEM106a. This stable cell line was assessed in multiple cell growth and migration assays. The results from TMEM106a overexpressing cell line were then confirmed with primary renal cells by siRNA knockdown of TMEM106a. RESULTS: TMEM106a expression level was reduced in renal cancer cells compared to normal primary renal cells. Restoration of TMEM106a expression in TMEM106a-low renal cancer cells resulted in attenuated proliferation, reduced cell migration and enhanced caspase 3 dependent apoptosis compared to control cells. TMEM106a knockdown in primary renal cells led to increased colony formation compared to the control cells with scrambled siRNA transfection. CONCLUSION: TMEM106a is a novel tumor suppressor in renal cancer.

Testis expressed 19 is a novel cancer-testis antigen expressed in bladder cancer.

Bladder cancer exhibits high mortality as a result of limited therapeutic options and a high recurrence rate. Accordingly, novel treatments such as immunotherapy have emerged as promising therapeutic modalities to prolong overall patient survival and effect a disease cure, which has renewed enthusiasm for the identification of tumor-specific target antigens. Cancer-testis (CT) antigens are recognized as ideal targets for immunotherapy because of their expression features and high immunogenicity profiles. Here, we investigate the expression pattern of a novel CT antigen, testis-expressed 19 (TEX19), in patients with bladder carcinoma and among multiple human tissues. Six bladder cancer cell lines (T24, UM-UC-3, J82, 5637, SW780, and RT4) were also analyzed for TEX19 expression. Our results reveal that TEX19 expression in normal tissue is restricted to human testis. In addition, TEX19 mRNA expression was detected in 60 % (24/40) bladder cancer samples, whereas 58.20 % (110/189) were positive for TEXT19 protein expression. Compared to low-grade tumors, TEX19 exhibited increased expression in high-grade tumors, from 53.69 to 77.14 %, respectively (P = 0.011). TEX19 was also expressed in all six bladder cancer cell lines. Together, our findings suggest that TEX19 represents a novel CT gene and might play a role in the progression of bladder cancer and that this gene therefore provides a potential target for immunotherapy treatment strategies against bladder cancer.

Simultaneous-Fault Diagnosis of Gearboxes Using Probabilistic Committee Machine.

This study combines signal de-noising, feature extraction, two pairwise-coupled relevance vector machines (PCRVMs) and particle swarm optimization (PSO) for parameter optimization to form an intelligent diagnostic framework for gearbox fault detection. Firstly, the noises of sensor signals are de-noised by using the wavelet threshold method to lower the noise level. Then, the Hilbert-Huang transform (HHT) and energy pattern calculation are applied to extract the fault features from de-noised signals. After that, an eleven-dimension vector, which consists of the energies of nine intrinsic mode functions (IMFs), maximum value of HHT marginal spectrum and its corresponding frequency component, is obtained to represent the features of each gearbox fault. The two PCRVMs serve as two different fault detection committee members, and they are trained by using vibration and sound signals, respectively. The individual diagnostic result from each committee member is then combined by applying a new probabilistic ensemble method, which can improve the overall diagnostic accuracy and increase the number of detectable faults as compared to individual classifiers acting alone. The effectiveness of the proposed framework is experimentally verified by using test cases. The experimental results show the proposed framework is superior to existing single classifiers in terms of diagnostic accuracies for both single- and simultaneous-faults in the gearbox.

Electroacupuncture improves recovery after hemorrhagic brain injury by inducing the expression of angiopoietin-1 and -2 in rats.

BACKGROUND: Angiopoietin (Ang) is one of the major effectors of angiogenesis, playing a critical role in neurovascular remodeling after stroke. Acupuncture has been widely used for treating stroke in China for a long time. Recently, we have demonstrated that electroacupuncture (EA) can accelerate intracerebral hemorrhage (ICH)-induced angiogenesis in rats. In the present study, we investigated the effect of EA on the expression of Ang-1 and Ang-2 in the brain after ICH. METHODS: ICH was induced by stereotactic injection of collagenase type VII into the right globus pallidus. Adult male Sprague-Dawley rats were randomized into the following four groups: sham-operation (SHAM), stroke-no electroacupuncture (SNE), stroke-EA at the Zusanli acupoint (SEZ), and stroke-EA at a nonacupoint (SEN). EA was applied to the bilateral Zusanli (ST36) acupoint in the SEZ group and a nonacupoint in the SEN group. The expression of Ang-1 and Ang-2 was evaluated by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Some Ang-1 and Ang-2 immunoreactive microvessels with a dilated outline were detected in the perihematomal tissues after ICH, and the vessels extended into the clot from the surrounding area since day 7. The expression of Ang-1 increased notably as long as 2 weeks after ICH, while Ang-2 immunoreactivity declined at about 7 days following a striking upregulation at 3 days. EA at the Zusanli (ST36) acupoint upregulated the expression of Ang-1 and Ang-2 at both the protein and mRNA levels. However, EA at a nonacupoint had little effect on the expression of Ang-1 and Ang-2. CONCLUSIONS: Our data suggest that EA at the Zusanli (ST36) acupoint exerts neuroprotective effects on hemorrhagic stroke by upregulation of Ang-1 and Ang-2.

Remaining Useful Life Prediction of Rolling Bearings Based on ECA-CAE and Autoformer.

In response to the need for multiple complete bearing degradation datasets in traditional deep learning networks to predict the impact on individual bearings, a novel deep learning-based rolling bearing remaining life prediction method is proposed in the absence of fully degraded bearng data. This method involves processing the raw vibration data through Channel-wise Attention Encoder (CAE) from the Encoder-Channel Attention (ECA), extracting features related to mutual correlation and relevance, selecting the desired characteristics, and incorporating the selected features into the constructed Autoformer-based time prediction model to forecast the degradation trend of bearings' remaining time. The feature extraction method proposed in this approach outperforms CAE and multilayer perceptual-Attention Encoder in terms of feature extraction capabilities, resulting in reductions of 0.0059 and 0.0402 in mean square error, respectively. Additionally, the indirect prediction approach for the degradation trend of the target bearing demonstrates higher accuracy compared to Informer and Transformer models, with mean square error reductions of 0.3352 and 0.1174, respectively. This suggests that the combined deep learning model proposed in this paper for predicting rolling bearing life may be a more effective life prediction method deserving further research and application.

PRAMEF12, a novel cancer/testis gene, regulates proliferation and apoptosis to promote progression of glioma.

Aim: To evaluate whether PRAMEF12 can serve as a diagnostic biomarker for glioma. Methods: We examined PRAMEF12 expression in multiple normal and glioma tissues. The diagnostic value of PRAMEF12 was evaluated using receiver operating characteristic curve analysis. The effect of PRAMEF12 ablation on proliferation, cell cycle and apoptosis was investigated. Database analyses were utilized for functional enrichment analysis. Results: PRAMEF12 expression in normal tissue was restricted to the human testis. PRAMEF12 displayed significant diagnostic value in glioma. PRAMEF12 knockdown inhibited cell proliferation, induced apoptosis and resulted in induction of S-phase cell cycle arrest. Pathway enrichment analysis indicated that PRAMEF12 may participate in cancer. Conclusion: PRAMEF12, a novel cancer/testis gene, may be a potential new diagnostic biomarker for glioma.

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Retroperitoneal neuroglial heterotopia: a case report and literature review.

Background: Neuroglial heterotopia is a rare lesion composed of differentiated neuroectodermal cells that manifest in extracranial locations, with the majority of cases predominantly occurring in the head and neck region. Retroperitoneal neuroglial heterotopia is exceptionally rare, with isolated cases published in the scientific literature. Case report: Here, we present the case of a 3-year-old girl who was admitted without clinical signs but presented with a palpable abdominal mass. Ultrasonography and computed tomography scans revealed a sizable cystic lesion within the retroperitoneal space. Subsequently, laparoscopic resection was performed. Histological examination unveiled neuroglial cell-lined cysts encompassing fibrous connective tissue, ganglia, glial tissue, and nerve bundles. Notably, distinct areas and cell types exhibited expression of S100, glial fibrillary acidic protein, and neuron-specific enolase. Follow-up assessments revealed no relapses or late complications. Conclusion: In cases of retroperitoneal neuroglial heterotopia, most children may remain asymptomatic without any congenital anomalies. Despite their detectability through imaging, accurate preoperative diagnosis is seldom achieved. Generally, a favorable prognosis follows complete surgical resection, although further cases are required to confirm its long-term efficacy, necessitating extended follow-up for verification.

Early prediction of drug-resistant epilepsy using clinical and EEG features based on convolutional neural network.

OBJECTIVE: Machine learning utilization in electroencephalogram (EEG) analysis and epilepsy care is fast evolving. Thus, we aim to develop and validate two one-dimensional convolutional neural network (CNN) algorithms for predicting drug-resistant epilepsy (DRE) in patients with newly-diagnosed epilepsy based on EEG and clinical features. METHODS: We included a total of 1010 EEG signal epochs and 15 clinical features from 101 patients with epilepsy. Each patient had 10 epochs of EEG signal data, with each signal recorded for 90 s. The ratio of development set and validation set was 80:20, and ten-fold cross validation was performed. First, a CNN algorithm was used to extract EEG features automatically. Then, Two one-dimensional CNNs were crafted.. Accuracy, specificity, precision, sensitivity, F1-score, kappa statistics, mean square error (MSE) and area under the curve (AUC) were calculated to evaluate the classifiers performance. RESULTS: The clinical-EEG model showed good performance and clinical practical value, with the accuracy, specificity, precision, sensitivity, F1-score, kappa statistics, best MSE and AUC in test set were 0.99, 0.72, 0.82, 0.96, 0.89, 0.83, 32.00, 0.81, respectively, and the accuracy in validation set was 0.84. In the EEG model, the accuracy, specificity, precision, sensitivity, F1-score, kappa statistics, best MSE and AUC in test set were 0.99, 0.59, 0.82, 0.90, 0.86, 0.72, 181.76, 0.76, respectively, and the accuracy in validation set was 0.81. CONCLUSION: We constructed a clinical-EEG model showed good potential for predicting DRE in patients with newly-diagnosed epilepsy, which could help identify patients at high risk of developing DRE at earlier stages.

Advanced multifunctional hydrogels for diabetic foot ulcer healing: Active substances and biological functions.

AIM: Hydrogels with excellent biocompatibility and biodegradability can be used as the desirable dressings for the therapy of diabetic foot ulcer (DFU). This review aimed to summarize the biological functions of hydrogels, combining with the pathogenesis of DFU. METHODS: The studies in the last 10 years were searched and summarized from the online database PubMed using a combination of keywords such as hydrogel and diabetes. The biological functions of hydrogels and their healing mechanism on DFU were elaborated. RESULTS: In this review, hydrogels were classified by their active substances such as drugs, cytokines, photosensitizers, and biomimetic peptide. Based on this, the biological functions of hydrogels were summarized by associating the pathogenesis of DFU, including oxidative stress, chronic inflammation, cell phenotype change, vasculopathy, and infection. This review also pointed out some of the shortcomings of hydrogels in present researches. CONCLUSIONS: Hydrogels were classified into carrier hydrogels and self-functioning hydrogels in this review. Besides, the functions and components of existing hydrogels were clarified to provide assistance for future researches and clinical applications.

Fault Diagnosis of Planetary Gearbox Based on Dynamic Simulation and Partial Transfer Learning.

To address the problem of insufficient real-world data on planetary gearboxes, which makes it difficult to diagnose faults using deep learning methods, it is possible to obtain sufficient simulation fault data through dynamic simulation models and then reduce the difference between simulation data and real data using transfer learning methods, thereby applying diagnostic knowledge from simulation data to real planetary gearboxes. However, the label space of real data may be a subset of the label space of simulation data. In this case, existing transfer learning methods are susceptible to interference from outlier label spaces in simulation data, resulting in mismatching. To address this issue, this paper introduces multiple domain classifiers and a weighted learning scheme on the basis of existing domain adversarial transfer learning methods to evaluate the transferability of simulation data and adaptively measure their contribution to label predictor and domain classifiers, filter the interference of unrelated categories of simulation data, and achieve accurate matching of real data. Finally, partial transfer experiments are conducted to verify the effectiveness of the proposed method, and the experimental results show that the diagnostic accuracy of this method is higher than existing transfer learning methods.

Research on the biological mechanism and potential application of CEMIP.

Cell migration-inducing protein (CEMIP), also known as KIAA1199 and hyaluronan-binding protein involved in hyaluronan depolymerization, is a new member of the hyaluronidase family that degrades hyaluronic acid (HA) and remodels the extracellular matrix. In recent years, some studies have reported that CEMIP can promote the proliferation, invasion, and adhesion of various tumor cells and can play an important role in bacterial infection and arthritis. This review focuses on the pathological mechanism of CEMIP in a variety of diseases and expounds the function of CEMIP from the aspects of inhibiting cell apoptosis, promoting HA degradation, inducing inflammatory responses and related phosphorylation, adjusting cellular microenvironment, and regulating tissue fibrosis. The diagnosis and treatment strategies targeting CEMIP are also summarized. The various functions of CEMIP show its great potential application value.

Research on fault diagnosis method of planetary gearbox based on dynamic simulation and deep transfer learning.

To address the issue of not having enough labeled fault data for planetary gearboxes in actual production, this research develops a simulation data-driven deep transfer learning fault diagnosis method that applies fault diagnosis knowledge from a dynamic simulation model to an actual planetary gearbox. Massive amounts of different fault simulation data are collected by creating a dynamic simulation model of a planetary gearbox. A fresh deep transfer learning network model is built by fusing one-dimensional convolutional neural networks, attention mechanisms, and domain adaptation methods. The network model is used to learn domain invariant features from simulated data, thereby enabling fault diagnosis on real data. The fault diagnosis experiment is verified by using the Drivetrain Diagnostics Simulator test bench. The validity of the proposed means is evaluated by comparing the diagnostic accuracy of various means on various diagnostic tasks.

Pachymic Acid Ameliorates Pulmonary Hypertension by Regulating Nrf2-Keap1-ARE Pathway.

OBJECTIVE: Pulmonary hypertension (PH) is a severe pulmonary vascular disease that eventually leads to right ventricular failure and death. The purpose of this study was to investigate the mechanism by which pachymic acid (PA) pretreatment affects PH and pulmonary vascular remodeling in rats. METHODS: PH was induced via hypoxia exposure and administration of PA (5 mg/kg per day) in male Sprague-Dawley rats. Hemodynamic parameters were measured using a right ventricular floating catheter and pulmonary vascular morphometry was measured by hematoxylin-eosin (HE), α-SMA and Masson staining. MTT assays and EdU staining were used to detect cell proliferation, and apoptosis was analyzed by TUNEL staining. Western blotting and immunohistochemistry were used to detect the expression of proteins related to the Nrf2-Keap1-ARE pathway. RESULTS: PA significantly alleviated hypoxic PH and reversed right ventricular hypertrophy and pulmonary vascular remodeling. In addition, PA effectively inhibited proliferation and promoted apoptosis in hypoxia-induced pulmonary artery smooth muscle cells (PASMCs). Moreover, PA pretreatment inhibited the expression of peroxy-related factor (MDA) and promoted the expression of antioxidant-related factors (GSH-PX and SOD). Furthermore, hypoxia inhibited the Nrf2-Keap1-ARE signaling pathway, while PA effectively activated this pathway. Most importantly, addition of the Nrf2 inhibitor ML385 reversed the inhibitory effects of PA on ROS generation, proliferation, and apoptosis tolerance in hypoxia-induced PASMCs. CONCLUSION: Our study suggests that PA may reverse PH by regulating the Nrf2-Keap1-ARE signaling pathway.

Management of adverse events in patients with acute myeloid leukemia in remission receiving oral azacitidine: experience from the phase 3 randomized QUAZAR AML-001 trial.

BACKGROUND: Most older patients with acute myeloid leukemia (AML) who attain morphologic remission with intensive chemotherapy (IC) will eventually relapse and post-relapse prognosis is dismal. In the pivotal QUAZAR AML-001 trial, oral azacitidine maintenance therapy significantly prolonged overall survival by 9.9 months (P < 0.001) and relapse-free survival by 5.3 months (P < 0.001) compared with placebo in patients with AML in first remission after IC who were not candidates for transplant. Currently, the QUAZAR AML-001 trial provides the most comprehensive safety information associated with oral azacitidine maintenance therapy. Reviewed here are common adverse events (AEs) during oral azacitidine treatment in QUAZAR AML-001, and practical recommendations for AE management based on guidance from international cancer consortiums, regulatory authorities, and the authors' clinical experience treating patients in the trial. METHODS: QUAZAR AML-001 is an international, placebo-controlled randomized phase 3 study. Patients aged ≥ 55 years with AML and intermediate- or poor-risk cytogenetics at diagnosis, who had attained first complete remission (CR) or CR with incomplete blood count recovery (CRi) within 4 months before study entry, were randomized 1:1 to receive oral azacitidine 300 mg or placebo once-daily for 14 days in repeated 28-day cycles. Safety was assessed in all patients who received ≥ 1 dose of study drug. RESULTS: A total of 469 patients received oral azacitidine (n = 236) or placebo (n = 233). Median age was 68 years. Patients received a median of 12 (range 1-80) oral azacitidine treatment cycles or 6 (1-73) placebo cycles. Gastrointestinal AEs were common and typically low-grade. The most frequent grade 3-4 AEs during oral azacitidine therapy were hematologic events. AEs infrequently required permanent discontinuation of oral azacitidine (13%), suggesting they were effectively managed with use of concomitant medications and oral azacitidine dosing modifications. CONCLUSION: Oral azacitidine maintenance had a generally favorable safety profile. Prophylaxis with antiemetic agents, and blood count monitoring every other week, are recommended for at least the first 2 oral azacitidine treatment cycles, and as needed thereafter. Awareness of the type, onset, and duration of common AEs, and implementation of effective AE management, may maximize treatment adherence and optimize the survival benefits of oral azacitidine AML remission maintenance therapy. Trial registration This trial is registered on clinicaltrials.gov: NCT01757535 as of December 2012.

Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes.

PURPOSE: Treatment options are limited for patients with lower-risk myelodysplastic syndromes (LR-MDS). This phase III, placebo-controlled trial evaluated CC-486 (oral azacitidine), a hypomethylating agent, in patients with International Prognostic Scoring System LR-MDS and RBC transfusion-dependent anemia and thrombocytopenia. METHODS: Patients were randomly assigned 1:1 to CC-486 300-mg or placebo for 21 days/28-day cycle. The primary end point was RBC transfusion independence (TI). RESULTS: Two hundred sixteen patients received CC-486 (n = 107) or placebo (n = 109). The median age was 74 years, median platelet count was 25 × 109/L, and absolute neutrophil count was 1.3 × 109/L. In the CC-486 and placebo arms, 31% and 11% of patients, respectively, achieved RBC-TI (P = .0002), with median durations of 11.1 and 5.0 months. Reductions of ≥ 4 RBC units were attained by 42.1% and 30.6% of patients, respectively, with median durations of 10.0 and 2.3 months, and more CC-486 patients had ≥ 1.5 g/dL hemoglobin increases from baseline (23.4% v 4.6%). Platelet hematologic improvement rate was higher with CC-486 (24.3% v 6.5%). Underpowered interim overall survival analysis showed no difference between CC-486 and placebo (median, 17.3 v 16.2 months; P = .96). Low-grade GI events were the most common adverse events in both arms. In the CC-486 and placebo arms, 90% and 73% of patients experienced a grade 3-4 adverse event. Overall death rate was similar between arms, but there was an imbalance in deaths during the first 56 days (CC-486, n = 16; placebo, n = 6), most related to infections; the median pretreatment absolute neutrophil count for the 16 CC-486 patients was 0.57 × 109/L. CONCLUSION: CC-486 significantly improved RBC-TI rate and induced durable bilineage improvements in patients with LR-MDS and high-risk disease features. More early deaths occurred in the CC-486 arm, most related to infections in patients with significant pretreatment neutropenia. Further evaluation of CC-486 in MDS is needed.

Clinicopathological and Prognostic Significance of PRAME Overexpression in Human Cancer: A Meta-Analysis.

Numerous studies have demonstrated that preferentially expressed antigen in melanoma (PRAME) is abnormally expressed in various solid tumours. However, the clinicopathological features and prognostic value of the PRAME expression in patients with cancer remain unclear. Accordingly, we performed a meta-analysis to accurately assess the association of the expression level of PRAME with clinicopathological features and cancer prognosis. Relevant study collection was performed in PubMed, Web of Science, and Embase until 28 February 2020. A total of 14 original studies involving 2,421 patients were included. Our data indicated that the PRAME expression was significantly associated with tumour stage (OR = 1.99, 95% CI: 1.48-2.67, P < 0.001) and positive lymph node metastasis (OR = 3.14, 95% CI: 1.99-4.97, P < 0.001). Pooled results showed that overexpression of PRAME is positively correlated with poor disease-free survival (HR = 1.60, 95% CI: 1.36-1.88, P < 0.001), progression-free survival (HR = 1.88, 95% CI: 1.02-3.46, P = 0.042), metastasis-free survival (HR = 1.86, 95% CI: 1.05-3.31, P = 0.034), and overall survival (HR = 1.75, 95% CI: 1.53-1.99, P < 0.001). In summary, these data are suggesting that PRAME is tumorigenic and may serve as a prognostic biomarker for cancer.

Buyang Huanwu Decoction () Attenuates Glial Scar by Downregulating the Expression of Leukemia Inhibitory Factor in Intracerebral Hemorrhagic Rats.

OBJECTIVE: To evaluate the effect of Buyang Huanwu Decoction (, BYHWD) on glial scar after intracerebral hemorrhage (ICH) and investigate the underlying mechanism. METHODS: Collagenase type VII (0.5 U) was injected stereotaxically into right globus pallidus to induce ICH model. One hundred and twenty Sprague-Dawley rats were randomly divided into 3 groups according to a random number table, including normal group (n=40), ICH model group (n=40) and BYHWD group (n=40), respectively. After ICH, the rats in the BYHWD group were intragastrically administered with BYHWD (4.36 g/kg) once a day for 21 days, while the rats in ICH group were administered with equal volume of distilled water for 21 days, respectively. Double immunolabeling was performed for proliferating cell nuclear antigen (PCNA)+/glial fibrillary acidic protein (GFAP)+ nuclei. The expression of GFAP and leukemia inhibitory factor (LIF) was evaluated by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The astrocytes with hypertrophied morphology around the hematoma was observed on day 3 after ICH. The number of GFAP positive cells and GFAP mRNA levels increased notably on day 3 and reached the peak on day 14 post-ICH (P<0.01). PCNA+/GFAP+ nuclei were observed around the hematoma and reached the peak on day 14 post-ICH (P<0.01). In addition, LIF-positive astrocytes and LIF mRNA level in the hemorrhagic region increased significantly till day 14 post-ICH (P<0.01). However, BYHWD not only reduced the number of PCNA+/GFAP+ nuclei, but also decreased GFAP and LIF levels (P<0.05). CONCLUSIONS: BYHWD could attenuate ICH-induced glial scar by downregulating the expression of LIF in the rats.