Effect of Oridonin on Experimental Animal Model of Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a serious disease that occurs in premature and low-birth-weight infants. In recent years, the incidence of BPD has not decreased, and there is no effective treatment for it. Oridonin (Ori) is a traditional Chinese medicine with a wide range of biological activities, especially pharmacological and anti-inflammatory. It is well known that inflammation plays a key role in BPD. However, the therapeutic effect of Ori on BPD has not been studied. Therefore, in the present study, we will observe the anti-inflammatory activity of Ori in an experimental animal model of BPD. Here, we showed that Ori could significantly decrease hyperoxia-induced alveolar injury, inhibit neutrophil recruitment, myeloperoxidase concentrations, and release inflammatory factors in BPD neonatal rats. Taken together, the experimental results suggested that Ori can significantly improve BPD in neonatal rats by inhibiting inflammatory response.

Binary Graph Convolutional Network With Capacity Exploration.

The current success of Graph Neural Networks (GNNs) usually relies on loading the entire attributed graph for processing, which may not be satisfied with limited memory resources, especially when the attributed graph is large. This paper pioneers to propose a Binary Graph Convolutional Network (Bi-GCN), which binarizes both the network parameters and input node attributes and exploits binary operations instead of floating-point matrix multiplications for network compression and acceleration. Meanwhile, we also propose a new gradient approximation based back-propagation method to properly train our Bi-GCN. According to the theoretical analysis, our Bi-GCN can reduce the memory consumption by an average of  âˆ¼ 31x for both the network parameters and input data, and accelerate the inference speed by an average of  âˆ¼ 51x, on three citation networks, i.e., Cora, PubMed, and CiteSeer. Besides, we introduce a general approach to generalize our binarization method to other variants of GNNs, and achieve similar efficiencies. Although the proposed Bi-GCN and Bi-GNNs are simple yet efficient, these compressed networks may also possess a potential capacity problem, i.e., they may not have enough storage capacity to learn adequate representations for specific tasks. To tackle this capacity problem, an Entropy Cover Hypothesis is proposed to predict the lower bound of the width of Bi-GNN hidden layers. Extensive experiments have demonstrated that our Bi-GCN and Bi-GNNs can give comparable performances to the corresponding full-precision baselines on seven node classification datasets and verified the effectiveness of our Entropy Cover Hypothesis for solving the capacity problem.

Investigating the prognostic and predictive value of the type II cystatin genes in gastric cancer.

BACKGROUND: Accumulating evidence indicates that type II cystatin (CST) genes play a pivotal role in several tumor pathological processes, thereby affecting all stages of tumorigenesis and tumor development. However, the prognostic and predictive value of type II CST genes in GC has not yet been investigated. METHODS: The present study evaluated the expression and prognostic value of type II CST genes in GC by using The Cancer Genome Atlas (TCGA) database and the Kaplan-Meier plotter (KM plotter) online database. The type II CST genes related to the prognosis of GC were then screened out. We then validated the expression and prognostic value of these genes by immunohistochemistry. We also used Database for Annotation, Visualization, and Integrated Discovery (DAVID), Gene Multiple Association Network Integration Algorithm (GeneMANIA), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), nomogram, genome-wide co-expression analysis, and other bioinformatics tools to analyze the value of type II CST genes in GC and the underlying mechanism. RESULTS: The data from the TCGA database and the KM plotter online database showed that high expression of CST2 and CST4 was associated with the overall survival (OS) of patients with GC. The immunohistochemical expression analysis showed that patients with high expression of CST4 in GC tissues have a shorter OS than those with low expression of CST4 (HR = 1.85,95%CI: 1.13-3.03, P = 0.015). Multivariate Cox regression analysis confirmed that the high expression level of CST4 was an independent prognostic risk factor for OS. CONCLUSIONS: Our findings suggest that CST4 could serve as a tumor marker that affects the prognosis of GC and could be considered as a potential therapeutic target for GC.

Clinical Study of Artificial Intelligence in Imaging Diagnosis of False Positive Lesions of Pulmonary Nodules.

OBJECTIVE: To determine the accuracy of diagnosis of pulmonary nodules using artificial intelligence method. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Thoracic Surgery, Jinan Central Hospital, Jinan, China, from January 2020 to May 2021. METHODOLOGY: An analysis of clinical characteristics exhibited by 32 patients initially diagnosed with malignant tumours through imaging (LDCT) and artificial intelligence (AI), was reclassified as having benign lesions following surgical intervention. Quantitative parameters were assessed, including CT mean value, kurtosis, skewness, solid ratio, and the ratio of length to short diameter, within a cohort of 32 benign patients juxtaposed with 58 patients diagnosed with lung cancer during the same time frame. The AI-derived parameters were subjected to Mann-Whitney U non-parametric test. RESULTS: A total of 32 benign pulmonary lesions were evaluated that were initially misdiagnosed as malignant prior to surgery. These lesions displayed an average length of (18.56 ± 12.16) mm, with the majority characterised as solid (68.8%). Notably, a substantial proportion of these lesions exhibited imaging features akin to malignant growths. The AI-derived quantitative parameters of the 32 benign cases and the 58 malignant cases revealed statistical significance in average CT value and solid ratio. However, statistical significance was not established for kurtosis, skewness, or the ratio of length to short diameter. The area under the Receiver Operating Characteristic (ROC) curve for average CT value and solid ratio stood at 0.71 and 0.705, respectively. CONCLUSION: Among the cases initially misdiagnosed as malignant yet subsequently identified as benign, a notable number of these instances were solid nodules, often resembling malignant lesions in imaging characteristics. There was moderate discriminatory capacity for average CT value and solid ratio, rendering them valuable tools for distinguishing between benign and malignant lesions within this particular cohort. This underscores their high diagnostic significance. KEY WORDS: Artificial intelligence, Benign lesions of lung, Lung cancer, Quantitative parameters, Postoperative.

Stratifin Promotes Hepatocellular Carcinoma Progression by Modulating the Wnt/ß-Catenin Pathway.

Abnormal stratifin (SFN) expression is closely related to the progression of several human cancers, but the potential roles of SFN in hepatocellular carcinoma (HCC) remain largely unknown. In this study, we found that SFN was upregulated in HCC cell lines and tissues and was positively associated with tumor size, poor differentiation, Tumor Node Metastasis (TNM) stage, and vascular invasion. In addition, high expression levels of SFN were associated with poor overall survival and disease-free survival. Biologically, downregulation of SFN suppressed tumor cell proliferation, epithelial-mesenchymal transition (EMT), invasion, and migration in vitro and tumor growth in vivo. However, overexpression of SFN promoted cell proliferation, EMT, invasion, and migration in vitro and tumor growth in vivo. Mechanistically, overexpression of SFN activated the Wnt/ß-catenin pathway by promoting Glycogen synthase kinase-3 beta (GSK-3ß) phosphorylation, decreasing ß-catenin phosphorylation, promoting ß-catenin transport into the nucleus, and enhancing the expression of c-Myc, whereas depletion of SFN inhibited the Wnt/ß-catenin pathway. In addition, TOPFlash/FOPFlash reporter assays showed that overexpression or downregulation of SFN obviously increased or decreased, respectively, the activity of the Wnt/ß-catenin pathway. Our results indicated that SFN plays an important role in HCC, possibly providing a prognostic factor and therapeutic target for HCC.

Ligustrazine Inhibits the Migration and Invasion of Renal Cell Carcinoma.

Ligustrazine is a Chinese herb (Chuanxiong) approved for use as a medical drug in China. Recent evidence suggests that ligustrazine has promising antitumor properties. Our preliminary results showed that ligustrazine could inhibit the growth of human renal cell carcinoma (RCC) cell lines. However, the complicated molecular mechanism has not been fully revealed. Therefore, the purpose of this study to investigate the mechanism of ligustrazine resistance in human RCC cells. Cell proliferation, migration, invasion, and colony-formation ability of RCC cells A498 were detected by MTT assay, clonal formation rates, and transwell chamber assay in vitro. The expression of epithelial-mesenchymal transition (EMT)-related proteins were analyzed using western blot test. The effect of ligustrazine on the growth of A498 cells in nude mice was investigated in vivo. Our results showed that ligustrazine could significantly inhibit the proliferation, migration, and invasion of A498 both in vivo and vitro. Western blot analysis showed that the expressions of EMT-related, N-cadherin, snail, and slug proteins were significantly decreased in A498 in the ligustrazine treatment group. This study indicated that ligustrazine could significantly inhibit the malignant biological behaviors of RCC cell lines, possibly by inhibiting the EMT process.

ITGA5 Promotes Tumor Progression through the Activation of the FAK/AKT Signaling Pathway in Human Gastric Cancer.

Background: ITGA5 is an adhesion molecule that integrates the intracellular structures with the extracellular matrix to perform biological functions. However, ITGA5 is highly expressed in a variety of tumors and is involved in tumor progression by promoting cell proliferation and metastasis. Nevertheless, little research has been performed on its function in gastric cancer. Therefore, the aim of this study was to investigate the role of ITGA5 in gastric cancer, focusing on the mechanism regulating the proliferation, invasion and migration. Methods: The expression of ITGA5 in gastric cancer tissues was assessed by the use of molecular bioinformatics databases and high-throughput sequencing of gastric cancer tissues from patients. Western blot, qPCR, and immunohistochemistry were performed to detect the expression of ITGA5 in samples from gastric cancer patients and gastric cancer cell lines. Furthermore, the ITGA5 gene was silenced and overexpressed in gastric cancer cells, and the effect on proliferation, invasion, migration, and tumorigenic ability was assessed. Results: ITGA5 mRNA and protein expression were upregulated in gastric cancer cell lines and tissues from patients, and its expression was closely associated with tumor size, lymph node metastasis, and TNM stage. In vitro and in vivo experiments showed that ITGA5 silencing resulted in the inhibition of proliferation, invasion, migration, and graft growth of gastric cancer cells; conversely, the overexpression resulted in the promotion of these cell functions. Our results finally showed that the effect of ITGA5 on proliferation, invasion, and migration of gastric cancer cells was performed through the activation of the FAK/AKT pathway. Conclusions: ITGA5 promotes proliferation, invasion, and migration of gastric cancer cells through the activation of FAK/AKT signaling pathway, suggesting that ITGA5 may be potentially considered as a new target in gastric cancer therapy.

An Application of ITO Analysis in Secondary Kinship Identification.

Objective: As the methods of the paternity and kinship testing have been developed, the second-degree and more distant relationships remain challenging in forensic science. Currently, the ITO method is the mainstream method to clarify the kinship between two individuals. Methods: In this study, the ITO algorithm was used to calculate the uncle-nephew index based on 55 autosomal short tandem repeats (STRs) loci that were universally used for forensic identification. 19 STRs loci in Y chromosome were used for verification of the kinship. Results: The cumulative uncle-nephew index between A and B was calculated to 0.993 by the analysis of the genotyping results of 21 STRs. When genotyping results of the other 34 STRs were added to the calculation algorithm, the cumulative uncle-nephew index between A and B was promoted to 227.928. Meanwhile, genotyping results of 17 Y-STRs loci showed that A and B shared the same Y-STRs haplotype that was in accord with the paternal inheritance law. Conclusion: The biological uncle-nephew relationship between A and B are identified by applying the statistical principles and genetic technologies.

A high-performance SERS imprinted membrane based on Ag/CNTs for selective detection of spiramycin.

In this test, the eggshell membrane (ESM) is selected as the support membrane for the biocompatibility and anchors CNTs on the surface to increase the mechanical properties. Then Ag NPs are decorated on CNTs-ESM substrate as SERS substrate by twice in-situ reduction. Finally, a layer of imprinted polymers is coated on the surface of the substrate to synthesize the imprinted membrane for selective detection of spiramycin. It is exhibited from the characteristic results that the CNTs significantly increase the mechanical properties and the detection sensitivity, simultaneously. When the concentration of SP changes between 10-6 âˆ¼ 10-11 M, there is a linear relationship between SERS intensity and SP concentration. The detection limit is 10-11 M, and the correlation coefficient R2 is 0.9864. The SERS imprinted membrane can be applied into the detection of antibiotics in practical sample, which broadens the research field of antibiotics detection.

Synthesis of PVDF membrane loaded with wrinkled Au NPs for sensitive detection of R6G.

A novel SERS membrane is synthesized by combining metal lattice and surface enhanced Raman scattering (SERS) technology. Since R6G is a carcinogenic and harmful pollutant, and traditional detection methods have many drawbacks and have research value, this paper selects R6G as the detection target. The SERS substrates are synthesized by loading Au nanoparticles (Au NPs) on the surface of polyvinylidene fluoride (PVDF) membrane. The Au NPs are synthesized through a controllable hydrothermal method. The synthesized AuNPs are covered by some gold particles, forming a fold pattern. Finally, the synthesized structure is immobilized on the surface of the PVDF membrane by the phase inversion method. It is suggested that the prepared Au NPs@PVDF membrane exhibits adjustable cavity structure, strong plasmon coupling, tunable magnetic plasmon resonance, prominent SERS performances. The prepared Au NPs@PVDF membrane showed sensitive SERS activity, good mechanical strength and reusability, expanding the application field of SERS detection. Overall, this study establishes a novel technique for the synthesis of SERS membrane with excellent SERS property and expands the application field of SERS detection.

DEAD-box helicase 56 functions as an oncogene promote cell proliferation and invasion in gastric cancer via the FOXO1/p21 Cip1/c-Myc signaling pathway.

DEAD-box helicase (DDX) family exerts a critical effect on cancer initiation and progression through alternative splicing, transcription and ribosome biogenesis. Increasing evidence has demonstrated that DEAD-box helicase 56 (DDX56) is over-expressed in several cancers, which plays an oncogenic role. Till the present, the impact of DDX56 on gastric cancer (GC) remains unclear. We conducted high-throughput sequencing (RNA-seq) to demonstrate aberrant DDX56 levels within 10 GC and matched non-carcinoma tissue samples. DDX56 levels were detected through qRT-PCR, western blotting (WB) and immunochemical staining in GC patients. We conducted gain- and loss-of-function studies to examine DDX56's biological role in GC development. In vitro, we carried out 5­Ethynyl­2­deoxyuridine (EdU), scratch, Transwell, and flow cytometry (FCM) assays for detecting GC cell growth, invasion, migration and apoptosis. Additionally, gene set enrichment analysis (GSEA), WB assay, and Encyclopedia of RNA Interactomes (ENCORI) were carried out for analyzing DDX56-regulated downstream genes and signaling pathways. In vivo, tumor xenograft experiment was performed for investigating how DDX56 affected GC development within BALB/c nude mice. Functionally, DDX56 knockdown arrested cell cycle at G1 phase, invasion and migration of AGS and MKN28 cells, and enhanced their apoptosis. Ectopic DDX56 expression enhanced the cell growth, migration and invasion, and inhibited apoptosis. Knockdown of DDX56 suppressed GC growth in the tumor models of BALB/c nude mice. Mechanistically, DDX56 post-transcriptionally suppressed FOXO1/p21 Cip1 protein expression, which could activate its downstream cyclin E1/CDK2/c-Myc signaling pathways. This sheds lights on the GC pathogenic mechanism and offers a potential anti-cancer therapeutic target.

Screening of Serum Exosomal miRNAs as Diagnostic Biomarkers for Gastric Cancer Using Small RNA Sequencing.

Background/Aim: Exosomal miRNAs are promising tumor biomarkers. This research explored the diagnostic value of serum exosomal miRNAs by analyzing the exosomal miRNAs derived from the serum of gastric cancer patients. Methods: Deep sequencing of exosomal miRNAs was performed using an Illumina HiSeq2500 sequencer on serum samples from three healthy subjects in the normal control group (group N) and six gastric cancer patients in the gastric cancer treatment group (group T). Bioinformatics analysis was performed on exosomal miRNA profiles to screen differentially expressed miRNA. In addition, target gene prediction, GO, and KEGG pathway enrichment analyses were performed. Finally, the serum exocrine bodies of 24 patients with gastric cancer and 24 normal controls were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to confirm the findings. The receiver operating characteristic (ROC) curve of the subjects was plotted, and the area under the curve (AUC) was calculated with a 95% confidence interval (CI). Results: The exosomes were successfully extracted from the serum of gastric cancer patients, which showed a form of goblet vesicles or irregular circles, with an average particle size of approximately 102.3 nm. The exosomal marker proteins, CD9, CD63, TSG101, and calnexin, were positively expressed. Small RNA sequencing detected 15 different types of RNA components in the serum exosomes, and the most abundant one was miRNA. In the screened cohort, the downregulation of seven existing miRNAs and the upregulation of one existing miRNA were observed. Four of them were selected for confirmation, revealing that the expression of miR-10401-3p, miR-1255b-5p, and miR-6736-5p declined significantly in group T (P < 0.05). In addition, the ROC curve showed that the AUC values for these three miRNAs were 0.8333, 0.8316, and 0.8142, respectively; all of them are statistically significant (P < 0.05). Conclusions: The above three miRNAs found in the serum exosomes from gastric cancer patients might serve as diagnostic biomarkers for gastric cancer.

Biomimetic Metal-Organic Framework Nanoparticles for Synergistic Combining of SDT-Chemotherapy Induce Pyroptosis in Gastric Cancer.

In recent years, sonodynamic therapy (SDT) has been widely developed for cancer research as a promising non-invasive therapeutic strategy. Here, we synthesized zeolitic imidazole frameworks-8 (ZIF-8) and utilized its properties to encapsulate hydrophobic Chlorin e6 (Ce6) and hydrophilic tirapazamine (TPZ) for a synergistic sonodynamic chemotherapy, which was also accompanied by the modification of cytomembrane of gastric cancer (GC) cells. Thus, we enabled the biomimetic property to achieve targeted delivery. Ce6-mediated SDT, in combination with ultrasound irradiation, could target the release of reactive oxygen species (ROS) to aggravate further hypoxia and activate TPZ. Combining these effects could induce the pyroptosis of GC cells and play the anti-tumor function, which could provide a potential therapeutic method for cancer therapy.

A review of BMP and Wnt signaling pathway in the pathogenesis of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive elevation in mean pulmonary arterial pressure. This occurs due to abnormal remodeling of small peripheral lung vasculature resulting in progressive occlusion of the artery lumen that eventually causes right heart failure and death. Current therapeutic options for PAH are limited and focused mainly on reversal of pulmonary vasoconstriction and proliferation of vascular cells. Although these treatments can relieve disease symptoms, PAH remains a progressive lethal disease.Bone morphogenetic proteins (BMPs) and their receptors were required for PAH-induced right ventricular hypertrophy. Emerging data suggest that restoration of BMP type II receptor (BMPR2) signaling in PAH is a promising alternative that could prevent and reverse pulmonary vascular remodeling. BMPR2 mutations have been identified in >70% of familial and roughly 15% of sporadic PAH cases. Wingless (Wnt) are a family of secreted glycoproteins with varying expression patterns and a range of functions, Wnt signaling pathway is divided into canonical signaling pathway and non-canonical signaling pathway. A recent study reports that interaction between BMP and Wnt closely associated with lung development, those cascade coordination regulation stem cell fate which determine lung branching morphogenes. The promoting effect of BMPR2 on proliferation, survival, and motility of endothelial cells was through recruiting Wnts signaling pathway, the interaction between BMP and Wnt closely associated with lung development.Therefore, in this review, we outline the latest advances of BMP and Wnt signaling pathway in the pathogenesis of PAH and disease progression.

Hydrophilic modification of PVDF-based SERS imprinted membrane for the selective detection of L-tyrosine.

The polyvinylidene difluoride (PVDF) membrane has received considerable attention as a flexible surface enhanced Raman scattering (SERS) substrate due to its excellent mechanical and physicochemical properties. However, the poor fouling resistance of PVDF membrane due to its intrinsic hydrophobic property limits its practical application. To address this, in this investigation, a SERS imprinted membrane is synthesized based on W18O49/Ag composites. Firstly, to promote hydrophilicity, N-vinyl-2-pyrrolidone (NVP) and triethoxyvinylsilane (VTES) are copolymerized by hydrolysis condensation and linked with engineered polyvinypyrrolidone (PVP) chains exposed on the surface of membrane. Furthermore, W18O49/Ag composites are dispersed on the membrane under the assistance of polydopamine (pDA) to promote the pollution resistance. Subsequently, in order to demonstrate the practical detection property, W18O49/Ag/PVDF membrane is selected as the SERS substrate to synthesize SERS imprinted membrane by precipitation polymerization for the selective detection of L-tyrosine. The characteristic results reveal that the SERS-imprinted membrane exhibits satisfactory hydrophilicity, and it can effectively degrade the pollutant molecules absorbed on its surface under ultraviolet light illumination. It is proved from the detection results that the LOD of WADP-MIMs for L-tyrosine reached 10-9 mol L-1 when the concentration of L-tyrosine changed between 10-3-10-9 mol L-1. The correlation coefficient (R2) is 0.994 and the limit of detection is 10-9 mol L-1. Meanwhile, it can be applied for the selective detection of L-tyrosine in mixture samples. Overall, this study presents a novel approach for the hydrophilic modification and pollution resistance enhancement of PVDF-based SERS imprinted membrane, which can be effectively utilized for the selective detection of practical samples.

DIO3OS as a potential biomarker of papillary thyroid cancer.

BACKGROUND: Papillary thyroid carcinoma (PTC) is one of the common clinical tumors, where LncRNA plays an important role in tumorigenesis and its development. The purpose of this study was to explore the role of DIO3OS in PTC. METHOD: Firstly, this study verified the expression of DIO3OS in PTC through the public database. Then, the differences in DIO3OS expression between the PTC group and paracancerous tissues were verified using the qRT-PCR. A series of in vitro experiments were conducted to verify the function of DIO3OS in PTC, while its involvement in possible pathways was analyzed by the GSEA. The ssGSEA algorithm estimated the immune status using the queue transcriptome graph derived from the TCGA database. Further, the correlation analysis was used to confirm the relationship between DIO3OS and the immune genes. RESULT: The results showed that the expression of DIO3OS was low in PTC. The same results were also confirmed by qRT-PCR analysis (P= 0.0077). In vitro, DIO3OS was localized within the cytoplasm and exosomes. Overexpression of DIO3OS hindered the proliferation, invasion, and migration of PTC cells. According to the degree of immune cell infiltration, the tumor group was divided into high immune cell infiltration group, medium immune cell infiltration group, and low immune cell infiltration group. The results showed that the DIO3OS was highly expressed in the high immune cell infiltration group (P < 0.001), which was positively correlated with the immune cell infiltration and also correlated with multiple immune genes. CONCLUSION: In summary, this study illustrated the expression pattern of DIO3OS in PTC, which may be involved in the immune-inflammatory pathway. Hence, our results may provide new diagnostic biomarkers and therapeutic targets for PTC.

α-Actinin1 promotes tumorigenesis and epithelial-mesenchymal transition of gastric cancer via the AKT/GSK3ß/ß-Catenin pathway.

α-Actinin1 (ACTN1), an actin cross-linking protein, is implicated in cytokinesis, cell adhesion, and cell migration. In addition, it is involved in the tumorigenesis and development of certain cancers, such as breast cancer. We explored the function of ACTN1 in gastric cancer (GC), which has largely remained unclear. High-throughput sequencing and public microarray datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) revealed the upregulation of ACTN1 in gastric cancer with a poor prognosis. These results were further verified by western blotting (WB), Real-Time Quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry. We constructed loss and gain of function gastric cancer cells, which revealed the effect of ACTN1 over-expression on promoting GC cell proliferation, invasion, migration, and inhibited apoptosis. Mechanistic studies revealed that ACTN1 regulates the epithelial-mesenchymal transition (EMT) and tumorigenesis of gastric cancer via the AKT/GSK3ß/ß-catenin pathway, confirmed by the inhibitor of AKT MK2206. Altogether, these results demonstrated that ACTN1 could be a promising candidate for gastric cancer treatment.

Correlation between Circulating Tumor Cells and Plasma D-dimer and Clinicopathological Characteristics of Patients with Non-small Cell Lung Cancer.

OBJECTIVE:  To study the relationship between circulating tumor cells (CTCs) and plasma D-dimer (D-D) and their correlation with clinicopathological characteristics of patients with non-small cell lung cancer (NSCLC). STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Department of Thoracic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, China, from December 2015 to August 2019. METHODOLOGY: Seventy-five patients with NSCLC were selected as the research subjects. The contents of CTCs and D-D were determined and the results were analysed as per objective. Data was analysed quantitatively, using SPSS Version 24.0. RESULTS: Forty-five patients with NSCLC were positive for CTCs. The level of D-D in NSCLC patients was significantly increased. The D-D level in CTCs-positive patients was 0.79 (0.43-1.80) mg/L. The levels of CTCs and D-D in NSCLC patients were not affected by gender and pathological subtypes and other factors (p>0.05). CTCs and D-D in peripheral blood of NSCLC patients were significantly correlated with the total stage of lung cancer patients (p <0.05). CONCLUSION: The levels of CTCs and D-D in peripheral blood of NSCLC patients are significantly correlated with clinicopathological features, and the positive CTCs and high levels of D-D may indicate the late stage of the disease and poor prognosis, and there is a correlation between the two. The combined detection of the two is of great significance in predicting the progress and poor prognosis of NSCLC patients, and can guide the clinical diagnosis and treatment. Key Words: Non-small cell lung cancer (NSCLC), Circulating tumor cells (CTCs), D-dimer (D-D), Clinicopathologic features.

NKCC1 promotes proliferation, invasion and migration in human gastric cancer cells via activation of the MAPK-JNK/EMT signaling pathway.

Aims: This study aimed to explore the function of NKCC1 in the proliferation, migration and invasion of Gastric cancer (GC) cells. Materials and Methods: GC data extracted from the database was analyzed using molecular bioinformatics. The expression levels of NKCC1 in tissue samples from GC patients and GC cell lines were determined by Western blotting, qRT-PCR, and immunohistochemistry. Immunofluorescence was used to detect protein localization. The GC cell lines were transfected with NKCC1-shRNA or expression plasmid, and in vitro proliferation, invasion and migration were analyzed by the CCK8, wound healing and transwell tests. Results: The NKCC1 mRNA level was significantly increased in GC tissues than that in normal gastric tissues (P = 0.0195). This phenomenon was further confirmed by the analysis of the TCGA-GTEx database that includes 408 gastric cancer tissues and 211 normal gastric tissues (P < 0.01). Furthermore, the increased level of NKCC1 was significantly correlated with Tumor size (P = 0.039), lymphatic node metastasis (P = 0.035) and tumor stage (P = 0.034). In vitro experiments confirmed that NKCC1 expression was higher in GC cells compared to that in GES-1 cells, and was mainly localized to the cytoplasm and membrane. NKCC1 silencing inhibited GC cell proliferation, invasion, migration and EMT, whereas its overexpression had the opposite effects. Furthermore, NKCC1 overexpression upregulated and activated JNK, and the targeted inhibition of JNK by SP600125 abrogated the pro-metastatic effects of NKCC1. Conclusions: NKCC1 promotes migration and invasion of GC cells by MAPK-JNK/EMT pathway and can be a potential therapeutic target.

The role of MMP-2 and MMP-9 in the metastasis and development of hypopharyngeal carcinoma.

INTRODUCTION: The role of matrix metalloproteinase-2 and 9 in the metastasis and development of hypopharyngeal carcinoma has not been clarified. OBJECTIVES: To observe the relationship between matrix metalloproteinase-2, matrix metalloproteinase-9 and the metastasis, development of hypopharyngeal carcinoma. METHODS: This study included 42 hypopharyngeal cancer patients. The mRNA and protein expression levels of matrix metalloproteinase-2 and 9 in hypopharyngeal carcinoma and paracancerous tissues were detected by reverse transcription-polymerase chain reaction and Western blot. RESULTS: Reverse transcription-polymerase chain reaction detection showed that the mRNA of matrix metalloproteinase-2 and 9 was expressed in both cancer and pericarcinoma tissues, but was almost not expressed in polypoid control tissues. The expression intensity in the cancer tissue was significantly higher than that in the pericarcinoma tissue (matrix metalloproteinase-2: t ＝ 2.529, p = 0.015; matrix metalloproteinase-9: t ＝ 4.781, p ＜ 0.001). The mRNA expression in the cancer tissue was enhanced with the increase of the tumor clinical stage (matrix metalloproteinase-2: F = 4.003, p = 0.026; matrix metalloproteinase-9: F = 5.501, p = 0.008). Its expression intensity was associated with the metastasis of lymph nodes (N staging) and increased with the degree of lymphatic metastasis (matrix metalloproteinases-2: F = 8.965, p = 0.005; matrix metalloproteinase-9: F = 5.420, p = 0.025). There was no significant change in T staging of tumor. With the increase of tumor pathological stage, the mRNA expression of matrix metalloproteinase-2 and 9 was strengthened (matrix metalloproteinase-2: F = 3.884, p = 0.029; matrix metalloproteinase-9: F = 3.783, p = 0.032). The protein expression level of matrix metalloproteinase-2 and 9 was the same as that of mRNA. CONCLUSION: The expression of matrix metalloproteinase-2 and 9 in hypopharyngeal carcinoma was significantly higher than that in pericarcinoma tissue, and it was enhanced with the increase of clinical stage. The expression level was related to lymph node metastasis and tumor pathological stage. Thus, matrix metalloproteinase-2 and 9 may be involved in the occurrence, development, invasion and metastasis of hypopharyngeal carcinoma through a variety of mechanisms.