Unconscious classification of quantitative electroencephalogram features from propofol versus propofol combined with etomidate anesthesia using one-dimensional convolutional neural network.

Objective: Establishing a convolutional neural network model for the recognition of characteristic raw electroencephalogram (EEG) signals is crucial for monitoring consciousness levels and guiding anesthetic drug administration. Methods: This trial was conducted from December 2023 to March 2024. A total of 40 surgery patients were randomly divided into either a propofol group (1% propofol injection, 10 mL: 100 mg) (P group) or a propofol-etomidate combination group (1% propofol injection, 10 mL: 100 mg, and 0.2% etomidate injection, 10 mL: 20 mg, mixed at a 2:1 volume ratio) (EP group). In the P group, target-controlled infusion (TCI) was employed for sedation induction, with an initial effect site concentration set at 5-6 µg/mL. The EP group received an intravenous push with a dosage of 0.2 mL/kg. Six consciousness-related EEG features were extracted from both groups and analyzed using four prediction models: support vector machine (SVM), Gaussian Naive Bayes (GNB), artificial neural network (ANN), and one-dimensional convolutional neural network (1D CNN). The performance of the models was evaluated based on accuracy, precision, recall, and F1-score. Results: The power spectral density (94%) and alpha/beta ratio (72%) demonstrated higher accuracy as indicators for assessing consciousness. The classification accuracy of the 1D CNN model for anesthesia-induced unconsciousness (97%) surpassed that of the SVM (83%), GNB (81%), and ANN (83%) models, with a significance level of p < 0.05. Furthermore, the mean and mean difference ± standard error of the primary power values for the EP and P groups during the induced period were as follows: delta (23.85 and 16.79, 7.055 ± 0.817, p < 0.001), theta (10.74 and 8.743, 1.995 ± 0.7045, p < 0.02), and total power (24.31 and 19.72, 4.588 ± 0.7107, p < 0.001). Conclusion: Large slow-wave oscillations, power spectral density, and the alpha/beta ratio are effective indicators of changes in consciousness during intravenous anesthesia with a propofol-etomidate combination. These indicators can aid anesthesiologists in evaluating the depth of anesthesia and adjusting dosages accordingly. The 1D CNN model, which incorporates consciousness-related EEG features, represents a promising tool for assessing the depth of anesthesia. Clinical Trial Registration: https://www.chictr.org.cn/index.html.

Pre-school children single inhalation anesthetic exposure and neuro-psychological development: a prospective study and Mendelian randomization analysis.

Background: For children who are unable to cooperate due to severe dental anxiety (DA), dental treatment of childhood caries under Dental General Anesthesia (DGA) is a safe and high-quality treatment method. This study aims to evaluate the impact on neurocognitive functions and the growth and development of children 2 years after dental procedure based on previous research, and further establish a causal relationship between general anesthesia (GA) and changes in children's neurocognitive functions by incorporating Mendelian Randomization (MR) analysis. Methods: Data were collected and analyzed from 340 cases of S-ECC procedures of preschool children conducted in 2019. This involved comparing the neurocognitive outcomes 2 years post-operation of preschool children receiving dental procedures under general anesthesia or local anesthesia. Physical development indicators such as height, weight, and body mass index (BMI) of children were also compared at baseline, half a year post-operation, and 2 years post-operation. We performed a Mendelian randomization analysis on the causal relationship between children's cognitive development and general anesthesia, drawing on a large-scale meta-analysis of GWAS for anesthesia, including multiple general anesthesia datasets. Results: Outcome data were obtained for 111 children in the general anesthesia group and 121 children in the local anesthesia group. The mean FSIQ score for the general anesthesia group was 106.77 (SD 6.96), while the mean score for the local anesthesia group was 106.36 (SD 5.88). FSIQ scores were equivalent between the two groups. The incidence of malnutrition in children in the general anesthesia group was 27.93% (p < 0.001) before surgery and decreased to 15.32% (p > 0.05) after 2 years, which was not different from the general population. The IVW method suggested that the causal estimate (p = 0.99 > 0.05, OR = 1.04, 95% CI = 5.98 × 10-4-1.82 × 103) was not statistically significant for disease prevalence. This indicates no genetic cause-and-effect relationship between anesthesia and childhood intelligence. Conclusion: There were no adverse outcomes in neurocognitive development in 2 years after severe early childhood caries (S-ECC) procedure under total sevoflurane-inhalation in preschool children. The malnutrition condition in children can be improved after S-ECC procedure under general anesthesia. Limited MR evidence does not support a correlation between genetic susceptibility to anesthesia and an increased risk for intelligence in children.

A new strategy for overcoming drug resistance in liver cancer: Epigenetic regulation.

Drug resistance in hepatocellular carcinoma has posed significant obstacles to effective treatment. Recent evidence indicates that, in addition to traditional gene mutations, epigenetic recoding plays a crucial role in HCC drug resistance. Unlike irreversible gene mutations, epigenetic changes are reversible, offering a promising avenue for preventing and overcoming drug resistance in liver cancer. This review focuses on various epigenetic modifications relevant to drug resistance in HCC and their underlying mechanisms. Additionally, we introduce current clinical epigenetic drugs and clinical trials of these drugs as regulators of drug resistance in other solid tumors. Although there is no clinical study to prevent the occurrence of drug resistance in liver cancer, the development of liquid biopsy and other technologies has provided a bridge to achieve this goal.

Bibliometric analysis of pediatric dental sedation research from 1993 to 2022.

Statement of problem: Bibliometric analysis methods were used to evaluate pediatric dental sedation research and to identify topical hotspots using quantitative and qualitative methodologies. Purpose: To conduct bibliometric analysis on the retrieved data and to foresee the development of trends and hotspots in this research area. Material and methods: We retrieved appropriate research articles from the Web of Science Core Collection on January 1, 2023. VOSviewer, Citespace and the Bibliometrics website were used to conduct bibliometric analysis on the retrieved data. GraphPad Prism 10.0 (GraphPad, San Diego, CA, USA) was used to conduct the statistical analysis. Results: A total of 396 publications on pediatric sedation in dentistry, published between 1993 and 2022, were retrieved from online databases. The USA published most papers. Furthermore, the most frequent countries who cooperated were the USA and Canada. Six of the top ten publishing establishments were USA based. Papers on the research have appeared primarily in the journals of Dentistry and Anesthesiology. Keyword co-occurrence and co-citation cluster analysis revealed that the most common topics mainly were: dental anxiety; conscious sedation; dental caries; midazolam; propofol; hypoxemia. Conclusions: During the three decades, the focus of pediatric sedation research has been on drugs, dental anxiety and procedural sedation. Keyword burst detection indicated that procedural sedation; adverse event; respiratory depression is an emerging research hotspot.

Lnc-ZEB2-19 Inhibits the Progression and Lenvatinib Resistance of Hepatocellular Carcinoma by Attenuating the NF-κB Signaling Pathway through the TRA2A/RSPH14 Axis.

Long non-coding RNAs have been reported to play a crucial role in tumor progression in hepatocellular carcinoma (HCC). Lnc-ZEB2-19 has been validated to be deficiently expressed in HCC. However, the capabilities and underlying mechanisms of lnc-ZEB2-19 remain uncertain. In this study, we verified that the downregulation of lnc-ZEB2-19 was prevalent in HCC and significantly correlated with the unfavorable prognosis. Further in vitro and in vivo verified that lnc-ZEB2-19 notably inhibited the proliferation, metastasis, stemness, and lenvatinib resistance (LR) of HCC cells. Mechanistically, lnc-ZEB2-19 inhibited HCC progression and LR by specifically binding to transformer 2α (TRA2A) and promoting its degradation, which resulted in the instability of RSPH14 mRNA, leading to the downregulation of Rela(p65) and p-Rela(p-p65). Furthermore, rescue assays showed that silencing RSPH14 partially restrained the effect of knockdown expression of lnc-ZEB2-19 on HCC cell metastatic ability and stemness. The findings describe a novel regulatory axis, lnc-ZEB2-19/TRA2A/RSPH14, downregulating the nuclear factor kappa B to inhibit HCC progression and LR.

Shenfu Injection Protects Brain Injury in Rats with Cardiac Arrest through Nogo/NgR Pathway.

The effect of Shenfu injection on brain injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) along with the underlying mechanism of axonal regeneration was explored. CA/CPR model in rats was established for subsequent experiments. A total of 160 rats were randomly divided into sham group, model group, conventional western medicine (CWM) group, Shenfu group, and antagonist group (n = 32 per group). After 3 hours, 24 hours, 3 days, and 7 days of drug administration, the modified Neurological Severity Score tests were performed. The ultrastructure of the brain and hippocampus was observed by electron microscopy. Real-time quantitative polymerase chain reaction (PCR), western blotting, and immunohistochemistry were used to detect Nogo receptor (NgR) expression in the hippocampus and cerebral cortex, and Nogo-NgR expression in CA/CPR model. Neurological deficits in the model group were severe at 3 hours, 24 hours, 3 days, and 7 days after the recovery of natural circulation, whereas the neurological deficits in CWM, antagonist, and Shenfu group were relatively mild. The ultrastructure of neuronal cells in Shenfu group had relatively complete cell membranes and more vesicles than those in the model group. The results of PCR and western blotting showed lower messenger ribonucleic acid and protein expression of NgR in Shenfu group than the model group and CWM group. Immunohistochemical examination indicated a reduction of Nogo-NgR expression in Shenfu group and antagonist group. Our results suggested that Shenfu injection reduced brain injury by attenuating Nogo-NgR signaling pathway and promoting axonal regeneration.

Three-Dimensional Evaluation of Deformed Noses in Patients With Unilateral Cleft Lip and Palate: A Meta-Analysis.

ABSTRACT: Multiple surgeries for patients with cleft lip and palate may be required to repair secondary deformities after the completion of cleft repair. This meta-analysis aimed to evaluate the three-dimensional nasal morphology in patients with unilateral cleft palate who underwent cleft lip and palate repair but did not undergo terminal nasal repair. PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Data, and SINOMED databases were searched from inception until December 2020. Studies involving patients ages ≥6 years with cleft lip and palate who did not undergo terminal nasal repair were included. Quantitative data were obtained through three-dimensional evaluation. Mean weighted effect sizes with 95% confidence intervals, heterogeneities, and publication biases were assessed using raw data obtained from 13 studies. In general, patients with unilateral cleft lip and palate had a significantly wider nose; shorter bridge length and nasal height; larger forehead-nose angle, nasal tip angle, and alar slope angle; and smaller nasolabial angle. The number of studies that included patients with unilateral cleft lip, unilateral cleft lip and alveolus, and unclassified deformities was limited, and their results were similar to those involving patients with unilateral cleft lip and palate. Patients with unilateral cleft tend to have short, flat, and wide noses. Nasal tip elevation and alar base adduction should be prioritized during terminal nasal repair to achieve more normalized cleft-side nostrils.

Management of anticoagulants in delayed bleeding after endoscopic resection: A systematic review and meta-analysis.

Background and study aims Delayed bleeding and thrombotic events are uncontrolled adverse events that are hard to balance in patients receiving anticoagulants after endoscopic resection. The present study aims to assess the clinical effect of warfarin, when compared to direct oral anticoagulants (DOACs), in terms of delayed bleeding and thrombotic events. Methods A comprehensive electronic literature search was conducted for eligible literature. Pairwise meta-analyses were performed on outcomes of delayed bleeding and thrombotic events. Two networks within the Bayesian framework were established based on the management of anticoagulants and type of DOAC. Results Eight cohort studies with 2,046 patients were eligible for inclusion, including 1,176 patients treated with warfarin and 870 with DOACs. There was no significant difference between warfarin and DOACs, in terms of delayed bleeding (OR = 1.29, 95 % CI [0.99-1.69]) and thromboembolism (OR = 2.0, 95 % CI [0.32-12.39]). In the network meta-analyses for delayed bleeding, the rank probabilities revealed that the safest management was discontinuous warfarin without heparin bridge therapy (HBT). Rank probabilities for the types of DOACs demonstrated that the safest drug was dabigatran. Conclusions There was no significant difference in delayed bleeding and thromboembolism between warfarin and DOACs in patients receiving endoscopic treatment. In terms of delayed bleeding, discontinuous warfarin without HBT was suggested as the best management, and dabigatran was recommended as the best type of DOAC.

MiR-503 suppresses cell proliferation and invasion of gastric cancer by targeting HMGA2 and inactivating WNT signaling pathway.

BACKGROUND: Abnormal expression of microRNAs (miRNAs) is related to human carcinogenesis. Although previous studies have shown that miR-503 expression in gastric cancer (GC) is downregulated, however, the underlying molecular mechanism for miR-503 involved in gastric cancer development is still largely unknown. METHODS: The relative expression of miR-503 in GC tissues and adjacent normal tissues was examined using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analyses. In vitro, cell proliferation and invasion were evaluated by using CCK8, cell colony and transwell invasion assays. In vivo, xenograft tumor model was constructed to assess miR-503 expression whether affects tumor growth or not. Luciferase reporter assay, qRT-PCR and western blot assay were used to demonstrate HMGA2 is a target of miR-503. RESULTS: We demonstrated that miR-503 expression was significantly downregulated in GC tissues and cell lines compared to adjacent normal tissues and normal gastric mucosa cell lines, respectively. Lower miR-503 expression associated with tumor size, lymph node metastasis, and predicted a poor overall survival (OS) time in GC patients. Subsequently, in vitro, gain-function and loss-function assays confirmed that miR-503 overexpression significantly suppressed GC cell proliferation, colony formation and cell invasion, while decreased miR-503 expression had an adverse effect in GC cells. Furthermore, we found that miR-503 specifically targeted the 3'-UTR regions of HMGA2 mRNA and suppressed its protein expression. Overexpression of HMGA2 could reverse the miR-503 mediated inhibition of GC cell proliferation and invasion. In vivo, miR-503 overexpression dramatically reduced tumor growth. Moreover, we demonstrated that miR-503 suppressed WNT/ß-catenin signaling by elevating GSK-3ß and p-ß-catenin expression, but decreased p-GSK-3ß and ß-catenin expression in GC cells. CONCLUSION: These results provide that miR-503 expression acts as a predictor for GC prognosis and may have a potential application in GC therapy.

Overexpression of amplified in breast cancer 1 (AIB1) gene promotes lung adenocarcinoma aggressiveness in vitro and in vivo by upregulating C-X-C motif chemokine receptor 4.

BACKGROUND: We previously found that overexpression of the gene known as amplified in breast cancer 1 (AIB1) was associated with lymph node metastasis and poor prognosis in patients with lung adenocarcinoma. However, the role of AIB1 in that malignancy remains unknown. The present study aimed to investigate the function of AIB1 in the process of lung adenocarcinoma cell metastasis. METHODS: A series of in vivo and in vitro assays were performed to elucidate the function of AIB1, while real-time PCR and Western blotting were utilized to identify the potential downstream targets of AIB1 in the process of lung adenocarcinoma metastasis. Rescue experiments and in vitro assays were performed to investigate whether the invasiveness of AIB1-induced lung adenocarcinoma was mediated by C-X-C motif chemokine receptor 4 (CXCR4). RESULTS: The ectopic overexpression of AIB1 in lung adenocarcinoma cells substantially enhanced cell migration and invasive abilities in vitro and tumor metastasis in vivo, whereas the depletion of AIB1 expression substantially inhibited lung adenocarcinoma cell migration and invasion. CXCR4 was identified as a potential downstream target of AIB1 in lung adenocarcinoma. The knockdown of AIB1 greatly reduced CXCR4 gene expression at both the transcription and protein levels, whereas the knockdown of CXCR4 in cells with AIB1 ectopic overexpression diminished AIB1-induced migration and invasion in vitro and tumor metastasis in vivo. Furthermore, we found a significant positive association between the expression of AIB1 and CXCR4 in lung adenocarcinoma patients (183 cases), and the co-overexpression of AIB1 and CXCR4 predicted the poorest prognosis. CONCLUSIONS: These findings suggest that AIB1 promotes the aggressiveness of lung adenocarcinoma in vitro and in vivo by upregulating CXCR4 and that it might be usable as a novel prognostic marker and/or therapeutic target for this disease.

Effects of Yangzheng Sanjie Decoction-containing serum mediated by microRNA-7 on cell proliferation and apoptosis in gastric cancer.

Gastric cancer (GC) is one of the most common types of cancer and a leading cause of cancer-associated mortality. MicroRNAs (miRNAs/miRs) are demonstrated to function as oncomiRs or tumor-suppressor-miRs in GC. miR-7 has been identified to be a tumor suppressor of GC by targeting epidermal growth factor receptor (EGFR). In our previous study, Yangzheng Sanjie Decoction (YZSJD), a traditional Chinese formula, was identified to be effective in alleviating the symptoms and even postponing turnover of precancerous lesions. To elucidate the mechanism of YZSJD, the present study evaluated the effects of YZSJD of the GC MKN-45 cell line and investigated the underlying molecular mechanisms using YZSJD-containing serum (YCS). The expression of miR-7 in GC, normal and adjacent tissue samples was examined. The results demonstrated that YCS inhibited proliferation by inducing cell cycle arrest at the S phase, and significantly induced apoptosis compared with the control group. miR-7 was significantly downregulated in GC tissues compared with the matched ones. Using reverse transcription-quantitative polymerase chain reaction and western blot analysis, the expression of miR-7 was inversely associated with EGFR. This indicates that YCS inhibits proliferation and induces apoptosis of GC cells mediated by miR-7 targeting EGFR, which may be one of the mechanisms whereby YZSJD exerts its effects on GC.

Yangzheng Sanjie decoction regulates proliferation and apoptosis of gastric cancer cells by enhancing let-7a expression.

AIM: To explore the let-7a-mediated anti-cancer effect of Yangzheng Sanjie decoction (YZSJD) in gastric cancer (GC) cells. METHODS: YZSJD-containing serum (YCS) was prepared using traditional Chinese medicine serum pharmacology methods. After YCS treatment, cell proliferation and apoptosis were assessed by cell counting kit-8 assay and flow cytometry, respectively, and miRNA expression profiles were determined using qPCR arrays. Let-7a expression was examined by in situ hybridization in GC tissues and by qPCR in GC cells. c-Myc protein expression was detected by immunohistochemistry in GC tissues, and by Western blot in cell lines. RESULTS: YZSJD significantly inhibited proliferation and induced apoptosis in AGS and HS-746T GC cells. After treatment with YCS, the miRNA expression profiles were altered and the reduced let-7a levels in both cell lines were up-regulated, accompanied by a decrease in c-Myc expression. Moreover, decreased let-7a expression and increased c-Myc expression were observed during the progression of gastric mucosa cancerization. CONCLUSION: YZSJD inhibits proliferation and induces apoptosis of GC cells by restoring the aberrant expression of let-7a and c-Myc.

MicroRNA-144 modulates oxidative stress tolerance in SH-SY5Y cells by regulating nuclear factor erythroid 2-related factor 2-glutathione axis.

Genome-wide analysis of miRNA expression has revealed increased levels of miR-144 in the brains of Alzheimer's disease (AD) patients. Nuclear factor erythroid 2-related factor 2 (NRF2), a potential target of miR-144, is a central regulator of antioxidant response, and plays an important role in glutathione (GSH) biosynthesis and recycling. In this study, miR-144 mimic was used to over express miR-144. Aß (1-42) was used to induce oxidative stress in SH-SY5Y cells. Cell viability and intracellular reactive oxygen species (ROS) were assessed to identify the effects of miR-144 on oxidative stress status. GSH and glutathion peroxidase (GPX) activities were detected to reveal the effect of miR-144 on GSH accumulation. To understand the effects of miR-144 on GSH biosynthesis and recycling, intracellular GPX1, glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM), glutathione reductase (GR), and NRF2 expression were detected by western blot and Real-time PCR. In oxidative stress conditions, miR-144 increased the intracellular accumulation of ROS, reduced cell viability, reduced the activities of GSH and antioxidant enzymes, GPX1, and decreased the expression of GCLC, GCLM, GR and NRF2. In conclusion, miR-144 modulates oxidative stress tolerance by regulating NRF2 expression and GSH generation, which may contribute to the pathogenesis of AD.

Role of microRNA-7 in digestive system malignancy.

There are several malignancies of the digestive system (including gastric, pancreatic and colorectal cancers, and hepatocellular carcinoma), which are the most common types of cancer and a major cause of death worldwide. MicroRNA (miR)-7 is abundant in the pancreas, playing an important role in pancreatic development and endocrine function. Expression of miR-7 is downregulated in digestive system malignancies compared with normal tissue. Although there are contrasting results for miR-7 expression, almost all research reveals that miR-7 is a tumor suppressor, by targeting various genes in specific pathways. Moreover, miR-7 can target different genes simultaneously in different malignancies of the digestive system. By acting on many cytokines, miR-7 is also involved in many gastrointestinal inflammatory diseases as a significant carcinogenic factor. Consequently, miR-7 might be a biomarker or therapeutic target gene in digestive system malignancies.

Macrophage migration inhibitory factor as a potential prognostic factor in gastric cancer.

AIM: To investigate macrophage migration inhibitory factor (MIF) expression and its clinical relevance in gastric cancer, and effects of MIF knockdown on proliferation of gastric cancer cells. METHODS: Tissue microarray containing 117 samples of gastric cancer and adjacent non-cancer normal tissues was studied for MIF expression by immunohistochemistry (IHC) semiquantitatively, and the association of MIF expression with clinical parameters was analyzed. MIF expression in gastric cancer cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Two pairs of siRNA targeting the MIF gene (MIF si-1 and MIF si-2) and one pair of scrambled siRNA as a negative control (NC) were designed and chemically synthesized. All siRNAs were transiently transfected in AGS cells with Oligofectamine(TM) to knock down the MIF expression, with the NC group and mock group (Oligofectamine(TM) alone) as controls. At 24, 48, and 72 h after transfection, MIF mRNA was analyzed by RT-PCR, and MIF and proliferating cell nuclear antigen (PCNA) proteins were detected by Western blot. The proliferative rate of AGS cells was assessed by methylthiazolyl tetrazolium (MTT) assay and colony forming assay. RESULTS: The tissue microarray was informative for IHC staining, in which the MIF expression in gastric cancer tissues was higher than that in adjacent non-cancer normal tissues (P < 0.001), and high level of MIF was related to poor tumor differentiation, advanced T stage, advanced tumor stage, lymph node metastasis, and poor patient survival (P < 0.05 for all). After siRNA transfection, MIF mRNA was measured by real-time PCR, and MIF protein and PCNA were assessed by Western blot analysis. We found that compared to the NC group and mock group, MIF expression was knocked down successfully in gastric cancer cells, and PCNA expression was downregulated with MIF knockdown as well. The cell counts and the doubling times were assayed by MTT 4 d after transfection, and colonies formed were assayed by colony forming assay 10 d after transfection; all these showed significant changes in gastric cancer cells transfected with specific siRNA compared with the control siRNA and mock groups (P < 0.001 for all). CONCLUSION: MIF could be of prognostic value in gastric cancer and might be a potential target for small-molecule therapy.

MicroRNA-374b Suppresses Proliferation and Promotes Apoptosis in T-cell Lymphoblastic Lymphoma by Repressing AKT1 and Wnt-16.

PURPOSE: Deregulation of microRNA (miRNA) has been extensively investigated in both Hodgkin and non-Hodgkin lymphomas (NHL); however, little is known about the roles of miRNAs in T-cell lymphoblastic lymphoma (T-LBL). The aim of the present study was to investigate the potential roles of miR-374b in the development and treatment of T-LBL. EXPERIMENTAL DESIGN: MiRCURY LNA array was used to generate a miRNA-expressing profile. Real-time quantitative PCR and immunohistochemistry (IHC) were applied to detect the expression of miR-374b, AKT1, and Wnt16 in T-LBL samples. The dual-luciferase reporter assay was conducted to confirm target associations of miR-374b. The tumor-suppressive effect of miR-374b was determined by both in vitro and in vivo studies. RESULTS: The expression of 380 miRNAs was evaluated in five human T-LBL tissues and five infantile thymus samples by microRNA microarrays. Downregulation of miR-374b was frequently detected in primary T-LBL tissues, which was significantly associated with worse overall survival and increased risk of recurrence of the 58 patients enrolled in this study. miR-374b suppressed T-LBL cell proliferation in vitro and in vivo and sensitized cells to serum starvation- and chemotherapeutic agent-induced apoptosis. Furthermore, we characterized two AKT pathway-associated molecules, AKT1 and Wnt16, as direct targets of miR-374b. Consistently, in T-LBL patient tissues, AKT1 and Wnt16 expression was inversely correlated with miR-374b levels, and was an independent predictor of recurrence and survival. CONCLUSIONS: Our data highlight the molecular etiology and clinical significance of miR-374b in T-LBL. Targeting miR-374b may represent a new therapeutic strategy to improve therapy and survival for T-LBL patients.

Overexpression of NKX6.1 is closely associated with progressive features and predicts unfavorable prognosis in human primary hepatocellular carcinoma.

The homeobox gene NKX6.1 was recently identified in cervical tumors. This study was designed to explore the clinical and prognostic significance of NKX6.1 further in patients with primary hepatocellular carcinoma (HCC). The expression levels of NKX6.1 were examined using real-time PCR, Western blotting, and immunohistochemistry in HCC cell lines and HCC tissues. The invasion capability of cell lines following silencing or overexpression of NKX6.1 was investigated by Transwell assay. Cells proliferation was tested by MTT assays. Epithelial-mesenchymal transition (EMT) marker expression levels were detected in relation to NKX6.1 expression. Correlation between NKX6.1 immunohistochemical staining, clinicopathologic parameters, and follow-up data of HCC patients was analyzed statistically. NKX6.1 expression was higher in HCC tissues compared to the adjacent noncancerous tissue. NKX6.1 overexpression was significantly correlated with tumor size, tumor differentiation, clinical stage, metastasis, and relapse. Kaplan-Meier analysis revealed that NKX6.1 overexpression was related to unfavorable 5-year disease-free survival and overall survival. Importantly, multivariate analysis indicated that NKX6.1 overexpression was an independent unfavorable marker for overall survival. Moreover, a significant relationship was observed between NKX6.1 and EMT marker expression levels, and NKX6.1 knockdown inhibited cell invasion, and overexpression of NKX6.1 promotes cell proliferation in vitro. NKX6.1 is upregulated in HCC and is a reliable prognostic marker for patients with HCC.

Low expression of BARX2 in human primary hepatocellular carcinoma correlates with metastasis and predicts poor prognosis.

AIM: The homeobox gene Barx2 was recently identified as a regulator of ovarian and breast cancer; however, the expression level of BARX2 and its significance in hepatocellular carcinoma (HCC) remain unknown. METHODS: Protein and mRNA expression levels of Barx2 were examined using Western blotting and real-time PCR respectively, in paired HCC tissue and matched adjacent non-cancerous tissue from 12 patients. The expression levels of epithelial-mesenchymal transition (EMT) markers were also detected in relation to BARX2 expression. Lastly, immunohistochemistry for BARX2 was also performed on a tissue microarray containing 231 HCC tissue samples. RESULTS: We observed that BARX2 expression was lower in HCC tissues compared to matching adjacent non-cancerous tissue. The low expression level of BARX2 was significantly correlated with metrics of tumor size, tumor differentiation, clinical stage, metastasis and relapse. Furthermore, the patients with low BARX2 expression had adverse survival outcomes. Importantly, multivariate Cox regression analysis revealed that low BARX2 expression was an independent marker for lower overall survival (P = 0.007). Moreover, a significant negative relationship was observed between the expression of BARX2 and markers of EMT. CONCLUSION: These findings provide evidence that the low expression level of BARX2 in HCC is significantly correlated with tumor metastasis, and that BARX2 may be an independent prognostic biomarker for patients with HCC.

Elevated levels of plasma D-dimer predict a worse outcome in patients with nasopharyngeal carcinoma.

BACKGROUND: Hemostatic alterations occur during the development of cancer. Plasma D-dimer is a hypercoagulability and fibrinolytic system marker that is increased in patients with various solid tumours. The aim of this study was to evaluate the hemostatic status of nasopharyngeal carcinoma (NPC) patients by assessing plasma D-dimer levels to investigate its value as a prognostic marker. METHODS: We retrospectively analysed 717 patients with nasopharyngeal carcinoma, and we applied Cox regression and log-rank tests to assess the association of D-dimer levels with disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS). D-dimer levels were measured using a quantitative D-dimer latex agglutination assay. RESULTS: Using the 3rd quartile values (0.8 µg/L) as the optimal cut-offs, we found that patients with high D-dimer levels have a shorter 3-year DFS, (79%, 95%CI (73.1-84.9)) vs. (69%, 95%CI (59.2-78.8)), DMFS (87%, 95%CI (83.1-90.9)) vs. (77%, 95%CI (69.2-84.8)), and overall survival (82%, 95%CI (76.1-87.9)) vs. (76%, 95%CI (66.2-85.8)). Multivariate analysis revealed that pre-treatment D-dimer levels and EBV DNA were significant independent factors for DFS, DMFS, and OS in NPC patients. Subgroup analyses indicated that the plasma D-dimer levels could effectively stratify patient prognosis for early cancer, advanced stage cancer, and patients with EBV DNA ≥4000 copies/ml. CONCLUSIONS: High D-dimer levels were associated with poor disease-free survival, distant metastasis-free survival, overall survival, and increased risk of mortality in NPC patients. Prospective trials are required to assess the prognostic value of D-dimer levels.

Duplication and differentiation of common carp (Cyprinus carpio) myoglobin genes revealed by BAC analysis.

Two distinct myoglobin (mb) transcripts have been reported in common carp, Cyprinus carpio, which is a hypoxia-tolerant fish living in habitats with greatly fluctuant dissolved oxygen levels. Recombinant protein analysis has shown functional specialization of the two mb transcripts. In this work, analysis for mb-containing bacterial artificial chromosome (BAC) clones indicated different genome loci for common carp myoglobin-1 (mb-1) and myoglobin-2 (mb-2) genes. Fluorescence in situ hybridization (FISH) revealed that mb-1 and mb-2 are located on separate chromosomes. In both of the mb-1 and mb-2 containing BAC clones, gene synteny was well conserved with the homologous region on zebrafish chromosome 1, supporting that the common carp specific mb-2 gene originated from the recent whole genome duplication event in cyprinid lineage. Transcription factor binding sites search indicated that both common carp mb genes lacked specificity Protein 1 (Sp1) and myocyte enhancer factor-2 (MEF2) binding sites, which mediated muscle-specific and calcium-dependent expression in the well-studied mb promoters. Potential hypoxia response elements (HREs) were predicted in the regulatory region of common carp mb genes. These characteristics of common carp mb gene regulatory region well interpreted the hypoxia-inducible, non-muscle expression pattern of mb-1. In the case of mb-2, a 10 bp insertion to the binding site of upstream stimulatory factor (USF), which was a co-factor of hypoxia inducible factor (HIF), might cause the non-response to hypoxia treatment of mb-2. The case of common carp mb gene duplication and subsequent differentiation in expression pattern and protein function provided an example for adaptive evolution toward aquatic hypoxia tolerance.