Creation of signatures and identification of molecular subtypes based on disulfidptosis-related genes for glioblastoma patients' prognosis and immunological activity.

BACKGROUND: In recent times, disulfidptosis, an intricate form of cellular demise, has garnered attention due to its impact on prognosis, tumor progression and treatment response. Nevertheless, the exact significance of disulfidptosis-related genes (DisRGs) in glioblastoma (GBM) remains enigmatic. METHODS: The GEO and TCGA databases provided transcriptional and clinically relevant data on tumor samples, while the GTEx database provided data on healthy tissues. Disulfidptosis-related genes (DisRGs) were procured from previous scholarly investigations. The expression profile of DisRGs was initially scrutinized among patients diagnosed with GBM, subsequent to which their prognostic value was explored. Through consensus clustering, we constructed DisRGs-related clusters and gene subtypes. Our results established that the DisRG-related clusters had differentially expressed genes, resulting in a DisulfidptosisScore model, which had a positive prognostic value. RESULTS: The differential expression profile of 24 DisRGs between GBM samples and healthy samples was acquired. Through consensus cluster analysis, two distinct disulfidptosis subtypes, namely DisRGcluster A and DisRGcluster B, were identified. Then, the DisulfidptosisScore model including 4 characteristic genes was constructed.Notably, patients with GBM assigned with lower score demonstrated a considerably longer overall survival (OS) compared to those with higher score. CONCLUSION: We have effectively devised a prognostic model associated with disulfidptosis, presenting autonomous prognostic predictions for patients with GBM. These findings serve as a valuable addition to the current comprehension of disulfidptosis and offer fresh theoretical substantiation for the development of enhanced treatment strategies.

Termination of convulsion seizures by destabilizing and perturbing seizure memory engrams.

Epileptogenesis, arising from alterations in synaptic strength, shares mechanistic and phenotypic parallels with memory formation. However, direct evidence supporting the existence of seizure memory remains scarce. Leveraging a conditioned seizure memory (CSM) paradigm, we found that CSM enabled the environmental cue to trigger seizure repetitively, and activating cue-responding engram cells could generate CSM artificially. Moreover, cue exposure initiated an analogous process of memory reconsolidation driven by mammalian target of rapamycin-brain-derived neurotrophic factor signaling. Pharmacological targeting of the mammalian target of rapamycin pathway within a limited time window reduced seizures in animals and interictal epileptiform discharges in patients with refractory seizures. Our findings reveal a causal link between seizure memory engrams and seizures, which leads us to a deeper understanding of epileptogenesis and points to a promising direction for epilepsy treatment.

A study on pharmaceutical text relationship extraction based on heterogeneous graph neural networks.

Effective information extraction of pharmaceutical texts is of great significance for clinical research. The ancient Chinese medicine text has streamlined sentences and complex semantic relationships, and the textual relationships may exist between heterogeneous entities. The current mainstream relationship extraction model does not take into account the associations between entities and relationships when extracting, resulting in insufficient semantic information to form an effective structured representation. In this paper, we propose a heterogeneous graph neural network relationship extraction model adapted to traditional Chinese medicine (TCM) text. First, the given sentence and predefined relationships are embedded by bidirectional encoder representation from transformers (BERT fine-tuned) word embedding as model input. Second, a heterogeneous graph network is constructed to associate words, phrases, and relationship nodes to obtain the hidden layer representation. Then, in the decoding stage, two-stage subject-object entity identification method is adopted, and the identifier adopts a binary classifier to locate the start and end positions of the TCM entities, identifying all the subject-object entities in the sentence, and finally forming the TCM entity relationship group. Through the experiments on the TCM relationship extraction dataset, the results show that the precision value of the heterogeneous graph neural network embedded with BERT is 86.99% and the F1 value reaches 87.40%, which is improved by 8.83% and 10.21% compared with the relationship extraction models CNN, Bert-CNN, and Graph LSTM.

A controlled lumbar puncture procedure improves the safety of lumbar puncture.

Background: In order to improve the safety of lumbar puncture (LP), we designed a new type of LP needle, that is, an integrated and controlled LP needle, which can actively and accurately control the flow rate and retention of cerebrospinal fluid (CSF) during puncture, so as to achieve a controlled LP procedure. Objective: To evaluate whether a controlled LP procedure can improve the comfort of LP and reduce the risk of complications associated with LP. Methods: Patients requiring LP (n = 63) were pierced with an integrated and controlled LP needle or a conventional LP needle. The differences in vital signs, symptom score, comfort, operation time, CSF loss, CSF pressure fluctuation and back pain before and after puncture were analyzed. Results: An integrated and controlled LP needle (n = 35) significantly improved patients' headache symptoms before and after puncture. In addition, a controlled LP procedure significantly reduced the amount of unnecessary CSF loss (p < 0.001), shortened the time of puncture (p < 0.001), improved patient comfort (p = 0.001) and reduced the incidence of back pain (p < 0.001). For patients with high intracranial pressure (HICP), the fluctuations in pressure of the CSF were also reduced while obtaining similar amounts of CSF (p = 0.009). Conclusion: A controlled LP procedure avoids unnecessary CSF loss, prevents rapid fluctuations in CSF pressure in patients with HICP, and reduces the risks associated with LP.

Altitude measurement method of VHF radar based on spatial smoothing of correlation matrix.

For very high frequency (VHF) phased array radar, the key problem to be solved in altitude measurement is the super-resolution spatial spectrum estimation under the condition of coherent sources. The spatial smoothing algorithm is a kind of decorrelation algorithm with excellent properties, but the decorrelation process is at the expense of the effective array aperture. Because it only uses the autocorrelation information of the subspace, its performance is significantly reduced, when the positions of the coherent sources are very close. In order to solve the above problems, this paper proposes an altitude measurement method of VHF radar based on the space smoothing of autocorrelation and cross-correlation matrix, which is used to realize the correlation and super-resolution processing of echo signals and multipath signals. The proposed method does not need to construct a weighting matrix, and can make full use of the received data, enhance the signal components in the equivalent spatial smoothing matrix, reduce the impact of noise, and improve the resolution of coherent sources. The simulation results show that the weighted spatial smoothing method proposed in this paper is correct and effective.

Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma.

BACKGROUND: Despite recent progress, multiple myeloma remains incurable. Mezigdomide is a novel cereblon E3 ubiquitin ligase modulator with potent antiproliferative and tumoricidal activity in preclinical models of multiple myeloma, including those resistant to lenalidomide and pomalidomide. METHODS: In this phase 1-2 study, we administered oral mezigdomide in combination with dexamethasone to patients with relapsed and refractory myeloma. The primary objectives of phase 1 (dose-escalation cohort) were to assess safety and pharmacokinetics and to identify the dose and schedule for phase 2. In phase 2 (dose-expansion cohort), objectives included the assessment of the overall response (partial response or better), safety, and efficacy of mezigdomide plus dexamethasone at the dose and schedule determined in phase 1. RESULTS: In phase 1, a total of 77 patients were enrolled in the study. The most common dose-limiting toxic effects were neutropenia and febrile neutropenia. On the basis of the phase 1 findings, investigators determined the recommended phase 2 dose of mezigdomide to be 1.0 mg, given once daily in combination with dexamethasone for 21 days, followed by 7 days off, in each 28-day cycle. In phase 2, a total of 101 patients received the dose identified in phase 1 in the same schedule. All patients in the dose-expansion cohort had triple-class-refractory multiple myeloma, 30 patients (30%) had received previous anti-B-cell maturation antigen (anti-BCMA) therapy, and 40 (40%) had plasmacytomas. The most common adverse events, almost all of which proved to be reversible, included neutropenia (in 77% of the patients) and infection (in 65%; grade 3, 29%; grade 4, 6%). No unexpected toxic effects were encountered. An overall response occurred in 41% of the patients (95% confidence interval [CI], 31 to 51), the median duration of response was 7.6 months (95% CI, 5.4 to 9.5; data not mature), and the median progression-free survival was 4.4 months (95% CI, 3.0 to 5.5), with a median follow-up of 7.5 months (range, 0.5 to 21.9). CONCLUSIONS: The all-oral combination of mezigdomide plus dexamethasone showed promising efficacy in patients with heavily pretreated multiple myeloma, with treatment-related adverse events consisting mainly of myelotoxic effects. (Funded by Celgene, a Bristol-Myers Squibb Company; CC-92480-MM-001 ClinicalTrials.gov number, NCT03374085; EudraCT number, 2017-001236-19.).

Advances in Sol-Gel-Based Superhydrophobic Coatings for Wood: A Review.

As the focus of architecture, furniture, and other fields, wood has attracted extensive attention for its many advantages, such as environmental friendliness and excellent mechanical properties. Inspired by the wetting model of natural lotus leaves, researchers prepared superhydrophobic coatings with strong mechanical properties and good durability on the modified wood surface. The prepared superhydrophobic coating has achieved functions such as oil-water separation and self-cleaning. At present, some methods such as the sol-gel method, the etching method, graft copolymerization, and the layer-by-layer self-assembly method can be used to prepare superhydrophobic surfaces, which are widely used in biology, the textile industry, national defense, the military industry, and many other fields. However, most methods for preparing superhydrophobic coatings on wood surfaces are limited by reaction conditions and process control, with low coating preparation efficiency and insufficiently fine nanostructures. The sol-gel process is suitable for large-scale industrial production due to its simple preparation method, easy process control, and low cost. In this paper, the research progress on wood superhydrophobic coatings is summarized. Taking the sol-gel method with silicide as an example, the preparation methods of superhydrophobic coatings on wood surfaces under different acid-base catalysis processes are discussed in detail. The latest progress in the preparation of superhydrophobic coatings by the sol-gel method at home and abroad is reviewed, and the future development of superhydrophobic surfaces is prospected.

Internal carotid artery stenosis: hemodynamics in the ipsilateral ACA affects CT angiography manifestations.

Objective: This study aimed to evaluate whether CT angiography (CTA) manifestations in anterior cerebral artery a1 segment (A1) were related to the hemodynamics in patients with internal carotid artery stenosis (ICAS). Methods: A total of 97 cases were selected. The degree of ICAS and symmetry of A1 were evaluated by CTA examination. Hemodynamic indexes were detected by transcranial Doppler (TCD). The differences in CTA presentations of A1 and hemodynamics between the vessels on the stenotic and contralateral sides were analyzed according to the different degrees of stenosis. The degree of ICAS according to the different manifestations of A1 and the hemodynamics of A1's adjacent vessels were also analyzed. Results: In the case of unilateral ICAS, the difference in Vm of A1 between the stenotic and the contralateral side was the most significant relative to the stenosis degree. When unilateral ICAS was ≥70%, the presentation of A1 on the stenotic side was more slender or non-visualized compared to that on the contralateral side, while in cases with unilateral stenosis <70% or bilateral stenosis with a similar degree of stenosis, A1 were mainly symmetrical. When A1 on the side of ICAS was slender or non-visualized, the Vm of A1 was significantly slower than that on the contralateral side (P < 0.001). Conclusion: The CTA manifestations of A1 on the side of ICAS embodied the overall changes of the intracranial hemodynamics after ICAS. A combination of TCD and CTA examination of A1 can assist in judging the location and degree of ICAS.

CEBPB upregulates P4HA2 to promote the malignant biological behavior in IDH1 wildtype glioma.

Temozolomide (TMZ), the primary drug for glioma treatment, has limited treatment efficacy. Additionally, considerable evidence shows that isocitrate dehydrogenase 1 mutation-type (IDH1 mut) gliomas have a better response to TMZ than isocitrate dehydrogenase 1 wildtype (IDH1 wt) gliomas. Here, we aimed to identify potential mechanisms underlying this phenotype. Herein, the Cancer Genome Atlas bioinformatic data and 30 clinical samples from patients were analyzed to reveal the expression level of cytosine-cytosine-adenosine-adenosine-thymidine (CCAAT) Enhancer Binding Protein Beta (CEBPB) and prolyl 4-hydroxylase subunit alpha 2 (P4HA2) in gliomas. Next, cellular and animal experiments, including cell proliferation, colony formation, transwell, CCK-8, and xenograft assays, were performed to explore the tumor-promoting effects of P4HA2 and CEBPB. Then, chromatin immunoprecipitation (ChIP) assays were used to confirm the regulatory relationships between them. Finally, a co-immunoprecipitation (Co-IP) assay was performed to confirm the effect of IDH1-132H to CEBPB proteins. We found that CEBPB and P4HA2 expression was significantly upregulated in IDH1 wt gliomas and associated with poor prognosis. CEBPB knockdown inhibited the proliferation, migration, invasion, and temozolomide resistance of glioma cells and hindered the growth of glioma xenograft tumors. CEBPE, as a transcription factor, exerted its function by transcriptionally upregulating P4HA2 expression in glioma cells. Importantly, CEBPB is prone to ubiquitin-proteasomal degradation in IDH1 R132H glioma cells. We also demonstrated that both genes are related to collagen synthesis, as confirmed by in vivo experiments. Thus, CEBPE promotes proliferation and TMZ resistance by inducing P4HA2 expression in glioma cells and offers a potential therapeutic target for glioma treatment.

Overexpression of OsNF-YB4 leads to flowering early, improving photosynthesis and better grain yield in hybrid rice.

For cereal crops, such as rice, the grain yield mainly comes from the accumulation of carbohydrates in the seed, which depends ultimately on photosynthesis during the growth period. To create early ripen variety, higher efficiency of photosynthesis is thus necessary to get higher grain yield with shorter growth period. In this study, flowering early was observed in the hybrid rice with overexpression of OsNF-YB4. Along with the flowering early, the hybrid rice also was shorter in plant height with less of leaves and internodes, but no changes of panicle length and leaf emergence. The grain yield was kept or even increased in the hybrid rice with shorter growth period. Transcription analysis revealed that Ghd7-Ehd1-Hd3a/RFT1 was activated early to promote the flowering transition in the overexpression hybrids. RNA-Seq study further showed that carbohydrate-related pathways were significantly altered in addition to circadian pathway. Notably, up-regulation of three pathways related to plant photosynthesis was observed, as well. Increased carbon assimilation with alteration of chlorophyll contents was subsequently detected in the following physiological experiments. All these results demonstrate that overexpression of OsNF-YB4 in the hybrid rice activates flowering early and improves photosynthesis resulting in better grain yield with shorter growth period.

Ginsenoside Rh2 inhibits CBP/p300-mediated FOXO3a acetylation and epilepsy-induced oxidative damage via the FOXO3a-KEAP1-NRF2 pathway.

Epilepsy is a chronic disease that affects a wide range of people. Furthermore, a third of patients suffering from epileptic seizures do not respond to antiepileptic drugs. In recent years, increasing attention has focused on the role of oxidative stress in acquired epilepsy, and adjuvant antiepileptic drugs to reduce oxidative stress may be a new therapeutic strategy. In this study ginsenoside Rh2 was resistant to oxidative stress induced by epileptic activity in vivo and in vitro. Using online databases, we identified forkhead box O3a (FOXO3a) overexpression in epilepsy tissue and validated this in vitro, in vivo, and in clinical tissues of patients with epilepsy. An in vitro epilepsy model revealed that the overexpression of FOXO3a led to more severe oxidative stress, while the knockdown of FOXO3a had a protective effect on SH-SY5Y cells. Moreover, our results showed that the positive effect of FOXO3a on oxidative stress was caused by the transcriptional activation of Kelch-like ECH-associated protein 1 (KEAP1), a negative regulator of nuclear factor erythroid 2-related factor 2 (NRF2). We also found that ginsenoside Rh2 can directly inhibit the activation of FOXO3a by selectively blocking CREB-binding protein (CBP)/p300-mediated FOXO3a acetylation and play a role in regulating the KEAP1-NRF2 pathway to resist oxidative stress.

CircRNA SRRM4 affects glucose metabolism by regulating PKM alternative splicing via SRSF3 deubiquitination in epilepsy.

OBJECTIVES: Several reports suggest that epigenetic therapy may be a potential method for treating epilepsy, and circular RNAs (circRNAs) play important roles in mediating the epigenetic mechanisms associated with epilepsy; however, currently there are no effective treatment methods to prevent the progression of epileptogenesis. The circRNA serine/arginine repetitive matrix 4 (circSRRM4) was found to exert regulatory effects in temporal lobe epilepsy (TLE); however, the mechanisms involved are still unknown. MATERIALS AND METHODS: To elucidate the molecular mechanism of circSRRM4, we investigated human epileptic brain tissue, epileptic rats, neuron and astrocyte cell lines using RT-qPCR, western blot, fluorescence in situ hybridisation, immunofluorescence staining, Nissl stain, micro-PET-CT, RNA-pulldown, liquid chromatography-mass spectrometry, and RBP immunoprecipitation techniques. Furthermore, we evaluated the pyruvate kinase M1/2 (PKM) expression patterns in the human and rat models of TLE. RESULTS: We detected the increased circSRRM4 expression in the hypometabolic lesions of patients with TLE and discovered that circSrrm4 has specific spatiotemporal characteristics in rats with kainic acid-induced epilepsy. The decreased PKM1 expression and increased PKM2 expression were similar to the Warburg effect in tumours. Notably, circSrrm4 silencing reduced the incidence and frequency of epilepsy, improved local hypometabolism, and prevented neuronal loss and astrocyte activation. CONCLUSION: PKM2 promotes lactic acid production in the astrocytes by inducing glycolysis, thereby contributing to the energy source for epileptic seizures. Notably, circSRRM4 combines with and inhibits serine and arginine rich splicing factor 3 (SRSF3) from joining the ubiquitin-proteasome pathway, improving the SRSF3-regulated alternative splicing of PKM, and consequently stimulating glycolysis in cells.

Near-infrared toroidal dipole response supported by silicon metasurfaces.

The dielectric metasurfaces supporting non-radiative toroidal dipole resonances play important roles in nanophotonics. In this paper, toroidal dipole resonances using a double-axe nanostructure array in the near-infrared region are theoretically investigated by the characterization of the near-field distribution and far-field scattering. An experimental quality factor of 261 is obtained at the resonant wavelength of 1498 nm.

Multi-Sensor Fusion by CWT-PARAFAC-IPSO-SVM for Intelligent Mechanical Fault Diagnosis.

A new method of multi-sensor signal analysis for fault diagnosis of centrifugal pump based on parallel factor analysis (PARAFAC) and support vector machine (SVM) is proposed. The single-channel vibration signal is analyzed by Continuous Wavelet Transform (CWT) to construct the time-frequency representation. The multiple time-frequency data are used to construct the three-dimension data matrix. The 3-level PARAFAC method is proposed to decompose the data matrix to obtain the six features, which are the time domain signal (mode 3) and frequency domain signal (mode 2) of each level within the three-level PARAFAC. The eighteen features from three direction vibration signals are used to test the data processing capability of the algorithm models by the comparison among the CWT-PARAFAC-IPSO-SVM, WPA-PSO-SVM, WPA-IPSO-SVM, and CWT-PARAFAC-PSO-SVM. The results show that the multi-channel three-level data decomposition with PARAFAC has better performance than WPT. The improved particle swarm optimization (IPSO) has a great improvement in the complexity of the optimization structure and running time compared to the conventional particle swarm optimization (PSO.) It verifies that the proposed CWT-PARAFAC-IPSO-SVM is the most optimal hybrid algorithm. Further, it is characteristic of its robust and reliable superiority to process the multiple sources of big data in continuous condition monitoring in the large-scale mechanical system.

Effect of KLF17 overexpression on epithelial-mesenchymal transition of gastric cancer cells.

OBJECTIVE: To investigate Krüppel-like factor 17 (KLF17) expression in normal and gastric cancer tissues and cell lines. METHODS: Levels of KLF17 mRNA and protein in GES-1 normal gastric mucosal cells, and NCI-N87, SGC-7901, BGC-823 and HGC-27 gastric cancer cells were analysed by quantitative polymerase chain reaction (qPCR) and western blot. Differences in KLF17 expression between gastric cancer and adjacent tissues were analysed by qPCR and immunohistochemistry. Invasion/migration effects of KLF17 overexpression in BGC-823 and HGC-27 cells were analysed by wound-healing and Transwell chamber assays. Changes in expression of KLF17 and epithelial-mesenchymal transition (EMT)-related genes (matrix metalloproteinase [MMP]-9, vimentin and E-cadherin) were analysed in BGC-823 and HGC-27 cells before and after transfection using qPCR and western blot. Transforming growth factor (TGF)-ß1, Smad family member (Smad)2/3 and phosphorylated-Smad2/3 levels in BGC-823 and HGC-27 cells were assessed by qPCR and western blot. RESULTS: KLF17 expression was lower in gastric cancer versus adjacent tissues, and in gastric cancer cell lines versus GES-1 normal gastric mucosal cells, and was positively correlated with degree of cancer-cell differentiation. Wound-healing and Transwell assays showed decreased migration and invasion ability of BGC-823 and HGC-27 cells transfected to overexpress KLF17. KLF17 overexpression was associated with decreased MMP-9 and vimentin in BGC-823 and HGC-27 cancer cells, and increased KLF17 and E-cadherin. KLF17 overexpression also resulted in decreased levels of TGF-ß1 and p-Smad2/3 in BGC-823 and HGC-27 cancer cells. CONCLUSION: KLF17 is poorly expressed in gastric cancer tissues and cell lines. KLF17 overexpression might inhibit EMT via the TGF-ß/Smad pathway, thereby reducing gastric cancer cell invasion and migration. Therefore, KLF17 may become a novel target for treating gastric cancer.

Krüppel-like factor 1 serves as a facilitator in gastric cancer progression via activating the Wnt/ß-catenin pathway.

Krüppel-like factor 1 (KLF1) is a transcription factor that exhibits promoting effect in cervical cancer, but its correlation with gastric cancer (GC) has not been reported yet. In this study, we explored the role and potential mechanism of KLF1 in GC progression by using a series of experimental methods including RT-qPCR, Western blot, CCK-8 assay, EdU staining, and cell cycle analysis. KLF1 was found to be elevated in GC tissues (n=415) compared with the normal tissues by applying UALCAN to analyze datasets from The Cancer Genome Atlas (TCGA). The upregulation of KLF1 was also validated in GC cell lines. Functional studies proved that RNA interference-mediated silencing of KLF1 inhibited GC cell growth, as evidenced by the decreased cell viability, DNA synthesis, and arrested cell cycle in G1 phase. Moreover, KLF1 knockdown exerted the inhibitory effects on cell migration and invasion as well as the epithelial-mesenchymal transition (EMT) in GC cells. Conversely, overexpression of KLF1 had the opposite effects on GC progression. Furthermore, we proved that the activation of Wnt/ß-catenin pathway was markedly inhibited by KLF1 knockdown and promoted by KLF1 overexpression. The blockade of Wnt/ß-catenin pathway rescued the effects of KLF1 overexpression. These results suggested that KLF1 promoted the growth, migration, invasion, and EMT process in GC cells, and this promotion was achieved by activating the Wnt/ß-catenin pathway. This work will be helpful for searching the potential therapeutic targets for treatment of GC.

Improvements in Nerve Dissection Surgery Methodology for Spasmodic Torticollis Treatment.

Spasmodic torticollis is the most common focal dystonia and is characterized by aberrant involuntary contraction of muscles of the neck and shoulders, which greatly affects patients' quality of life. Consequently, patients with this condition often desire treatment to alleviate their symptoms. The common clinical treatments for spasmodic torticollis include interventions such as drug therapy, botulinum toxin injections, and surgery. Surgical treatment is feasible for patients who do not respond well to other treatments or who are resistant to drugs. The gradual improvement of surgeons' understanding of anatomy and the ongoing developments in surgical techniques since their advent in the 1640s have resulted in many innovative surgical approaches that have led to improvements in the treatment of spasmodic torticollis. Previously used surgical treatments that result in uncertain outcomes, various postoperative complications, and serious damage to motor functions of the head and neck have gradually been discontinued. Nerve dissection surgery is the most common surgical treatment for spasmodic torticollis. This article reviews existing research on nerve dissection surgery for the treatment of spasmodic torticollis and the history of its development, along with the advantages and disadvantages of various surgical improvements. This article aims to provide clinicians with practical advice.

Up-regulation of KLF17 expression increases the sensitivity of gastric cancer to 5-fluorouracil.

It has been reported that the expression of Krüppel-like factor 17 (KLF17) was associated with the occurrence, development, invasion, metastasis and chemotherapy resistance of various tumors. However, the detailed mechanisms by which KLF17 promotes chemotherapy resistance in gastric cancer (GC) have not been fully investigated. In the present study, we collected the GC tissues and non-tumor tissues (matched adjacent normal tissues with corresponding GC tissues) of 60 GC patients, used qRT-PCR, Western blot and immunohistochemistry assay to analyze the relationship between the expression of KLF17 and the clinical pathological data of the patients. The effect of KLF17 on the sensitivity of GC cell lines to 5-fluorouracil (5-FU), and the potential mechanism were detected by MTS assay, Flow cytometry assay, and Western blot. Compared with non-tumor tissues, the expression level of KLF17 in GC tissue was significantly down-regulated, and the expression level of KLF17 in GES-1 cell line and GC cell lines also had a similar trend. Down-regulated expression of KLF17 is related to tumor size, invasion, regional lymph node metastasis, and TNM staging. Furthermore, through upregulating the expression of KLF17, the sensitivity of BGC-823 and SGC-7901 cell lines to 5-FU was obviously increased. Mechanistically, upregulation the expression of KLF17 can inhibit the expressions of P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and B-Cell lymphoma-2 (BCL-2), which have been reported to be associated with drug resistance and cell proliferation. Collectively, these data implied that KLF17 has the biological effect of inhibiting chemotherapy resistance of GC, and it could be a potential strategy for the GC chemotherapy resistance.

The FDP/FIB Ratio and Blood FDP Level May Be Related to Seizures After Fever in Young Children.

Objective: To evaluate the relationship of the blood fibrinogen (FIB) degradation product (FDP) level and FDP/FIB ratio with seizure in young children with fever. Methods: A total of 35 children with simple febrile seizures and 80 children with fever but no seizure were selected. First, the differences in white blood cell (WBC), platelets (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), FIB, FDP, FDP/FIB ratio, and C-reactive protein (CRP) between 35 children with simple febrile seizures and 40 randomly selected children with fever but no seizure were retrospectively analyzed. Then, an ROC curve was used to determine the diagnostic utility of the FDP level, FDP/FIB ratio, and FDP+FDP/FIB ratio, and the best diagnostic cutoff points were selected. Finally, the diagnostic specificities of the three diagnostic indicators were verified by comparison with the results of all 80 children with fever but no seizure. Results: The FDP level and FDP/FIB ratio were significantly different between the two groups (P < 0.0001) and there was a positive correlation between the FDP and FIB levels. Both the FDP level and FDP/FIB ratio had good diagnostic value. An FDP ≥ 2.0 mg/L and FDP/FIB ratio ≥ 0.5 had good diagnostic specificities. Combined application of an FDP ≥ 2.0 mg/L and FDP/FIB ratio ≥ 0.5 improved the diagnostic power. Conclusions: The blood FDP level and FDP/FIB ratio may be related to seizures after fever, and an FDP ≥ 2.0 mg/L + FDP/FIB ratio ≥ 0.5 has good diagnostic specificity.

Comprehensive Transcriptomic Analysis and Experimental Validation Identify lncRNA HOXA-AS2/miR-184/COL6A2 as the Critical ceRNA Regulation Involved in Low-Grade Glioma Recurrence.

PURPOSE: The recurrence and metastasis of glioma are closely related to complex regulatory networks among protein-coding genes, lncRNAs and microRNAs. The aim of this study was to investigate core genes, lncRNAs, miRNAs and critical ceRNA regulatory mechanisms, which are involved in lower-grade glioma (LGG) recurrence. MATERIALS AND METHODS: We employed multiple datasets from Chinese Glioma Genome Atlas (CGGA) database and The Cancer Genome Atlas (TCGA) to perform comprehensive transcriptomic analysis. Further in vitro experiments including cell proliferation assay, luciferase reporter assay, and Western blot were performed to validate our results. RESULTS: Recurrent LGG and glioblastoma (GBM) showed different transcriptome characteristics with less overlap of differentially expressed protein-coding genes (DEPs), lncRNAs (DELs) and miRNAs (DEMs) compared with primary samples. There were no overlapping gene in ontology (GO) terms related to GBM recurrence in the TCGA and CGGA databases, but there were overlaps associated with LGG recurrence. GO analysis and protein-protein interaction (PPI) network analysis identified three core genes: TIMP1, COL1A1 and COL6A2. By hierarchical cluster analysis of them, LGGs could be clustered as Low_risk and High_risk group. The High_risk group with high expression of TIMP1, COL1A1, and COL6A2 showed worse prognosis. By coexpression networks analysis, competing endogenous RNA (ceRNA) network analysis, cell proliferation assay and luciferase reporter assay, we confirmed that lncRNA HOXA-AS2 functioned as a ceRNA for miR-184 to regulate expression of COL6A2, which induced cell proliferation of low-grade glioma. CONCLUSION: In this study, we revealed a 3-hub protein-coding gene signature to improve prognostic prediction in LGG, and identified a critical ceRNA regulation involved in LGG recurrence.