Integrative analysis of the efficacy and pharmacological mechanism of Xuefu Zhuyu decoction in idiopathic pulmonary fibrosis via evidence-based medicine, bioinformatics, and experimental verification.

Objective: We used evidence-based medicine, bioinformatics and experimental verification to comprehensively analyze the efficacy and pharmacological mechanism of Xuefu Zhuyu decoction (XFZYD) in the treatment of idiopathic pulmonary fibrosis (IPF). Methods: Major databases were retrieved for randomized controlled trials (RCTs) of XFZYD treating IPF to perform meta-analysis. Active ingredients and target genes of XFZYD were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). IPF-related differentially expressed genes (DEGs) were identified from the Gene Expression Omnibus (GEO) database. The RGUI software was utilized for Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The ingredient-target and protein-protein interaction (PPI) networks were achieved through Cytoscape software and the STRING database to identify the key compounds and target proteins. Molecular docking was performed using AutoDockTool and AutoDock Vina software. The effect between key compounds and target proteins was verified in animal experiments. Results: Six RCTs were included for meta-analysis, which uncovered that the total effective rate of clinical efficacy was higher in the experimental group than control group. Then, 156 active ingredients and 254 target genes of XFZYD, and 1,566 IPF-related DEGs were identified. The intersection analysis identified 48 target genes correlating with 130 active ingredients of XFZYD treating IPF. GO functional enrichment, KEGG pathway enrichment, ingredient-target network and PPI network were achieved. Following the identification of key compounds and target proteins, we performed molecular docking. Ultimately, our research focused on the key compound quercetin for experimental validation to assess its interactions with two key target proteins, JUN and PTGS2. Conclusion: The effectiveness of XFZYD on IPF has been substantiated through evidence-based medicine. The pharmacological mechanism of XFZYD for IPF treatment involves a complex interplay of various compounds and targets, with quercetin exerting pronounced impacts on JUN and PTGS2 proteins.

Evaluating psychological distress in Chinese patients with head and neck squamous cell carcinoma planned for radiotherapy: a cross-sectional study using the distress thermometer.

OBJECTIVE: We aim to estimate the prevalence of baseline clinically significant distress in Chinese patients with head and neck squamous cell carcinoma (HNSCC) before receiving the first radiotherapy and assess factors predictive of distress. METHODS: One hundred and sixty-eight patients were enrolled to complete a set of questionnaires including Distress Thermometer (DT) and Hospital Anxiety and Depression Scale (HADS). Of these, 131 questionnaires were available for the final analysis. The accuracy of DT was validated using HADS as the gold standard, and receiver operating characteristic (ROC) curves were employed to identify the optimal cutoff score of DT. RESULTS: Distress was reported in sixty-two patients (47%). Patients who were visited in the last week (p = 0.022) and those with medical-related occupations (p = 0.017) were less likely to suffer from psychological distress. Additionally, religious belief was negatively associated with both the DT and HADS-T scores, indicating that patients with religious beliefs were less likely to report high levels of distress (odds ratio (OR) for DT ≥ 4 = 0.291, p = 0.039; OR for HADS-T ≥ 15 = 0.316, p = 0.047). Factors such as age, gender, marital status, education and residency did not contribute to distress levels. DT was significantly correlated with HADS-T (Correlation coefficient (r) = 0.624, p < 0.001) and the best cutoff score of DT was 4 in screening distress. CONCLUSIONS: DT was a brief and effective tool to screen distress among HNSCC patients.

Construction of an artificial neural network diagnostic model and investigation of immune cell infiltration characteristics for idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a severe lung condition, and finding better ways to diagnose and treat the disease is crucial for improving patient outcomes. Our study sought to develop an artificial neural network (ANN) model for IPF and determine the immune cell types that differed between the IPF and control groups. METHODS: From the Gene Expression Omnibus (GEO) database, we first obtained IPF microarray datasets. To conduct protein-protein interaction (PPI) networks and enrichment analyses, differentially expressed genes (DEGs) were screened between tissues of patients with IPF and tissues of controls. Afterward, we identified the important feature genes associated with IPF using random forest (RF) analysis, and then constructed and validated a prediction ANN mode. In addition, the proportions of immune cells were quantified using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) analysis, which was performed on microarray datasets based on gene expression profiling. RESULTS: A total of 11 downregulated and 36 upregulated DEGs were identified. PPI networks and enrichment analyses were carried out; the immune system and extracellular matrix were the subjects of the enrichments. Using RF analysis, the significant feature genes LRRC17, COMP, ASPN, CRTAC1, POSTN, COL3A1, PEBP4, IL13RA2, and CA4 were identified. The nine feature gene scores were integrated into the ANN to develop a diagnostic prediction model. The receiver operating characteristic (ROC) curves demonstrated the strong diagnostic ability of the ANN in predicting IPF in the training and testing sets. An analysis of IPF tissues in comparison to normal tissues revealed a reduction in the infiltration of natural killer cells resting, monocytes, macrophages M0, and neutrophils; conversely, the infiltration of T cells CD4 memory resting, mast cells, and macrophages M0 increased. CONCLUSION: LRRC17, COMP, ASPN, CRTAC1, POSTN, COL3A1, PEBP4, IL13RA2, and CA4 were determined as key feature genes for IPF. The nine feature genes in the ANN model will be extremely important for diagnosing IPF. It may be possible to use differentiated immune cells from IPF samples in comparison to normal samples as targets for immunotherapy in patients with IPF.

Circulating micrornas as potential diagnostic biomarkers for cervical intraepithelial neoplasia and cervical cancer: a systematic review and meta-analysis.

BACKGROUND: Cervical cancer is a prevalent malignancy of the female reproductive system. Cervical intraepithelial neoplasia (CIN) is a precursor lesion for CC. Various studies have examined circulating microRNAs (miRNAs) as potential early diagnostic markers for CC and CIN. However, the findings have been inconclusive. Therefore, it is necessary to evaluate the diagnostic accuracy and identify potential sources of variability among these studies. METHODS: The PubMed, Cochrane Library, Embase, and Web of Science databases were searched to identify relevant literature. Then, Stata 14.0 was utilized to calculate summary estimates for diagnostic parameters, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic (ROC). To scrutinize the heterogeneity, the Cochran-Q test and I2 statistic were utilized. As significant heterogeneity was observed, the random effects model was chosen. To explore potential sources of the heterogeneity, subgroup and regression analyses were conducted. RESULTS: We analysed 12 articles reporting on 24 studies involving 1817 patients and 1731 healthy controls. The pooled sensitivity was 0.77 (95% CI 0.73-0.81), the specificity was 0.81 (95% CI 0.73-0.86), the PLR was 3.99 (95% CI 2.81-5.65), the NLR was 0.28 (95% CI 0.23-0.35), the DOR was 14.18 (95% CI 8.47-23.73), and the area under the curve (AUC) was 0.85 (95% CI 0.81-0.87). Subgroup analysis revealed that multiple miRNAs can improve diagnostic performance; the pooled sensitivity of multiple miRNAs was 0.78 (95% CI 0.68-0.86), the specificity was 0.85 (95% CI 0.78-0.90), and the AUC was 0.89 (95% CI 0.86-0.91). CONCLUSION: This study suggested that circulating microRNAs may be biomarkers for early CC diagnosis.

The prognostic value of LAYN in HPV-related head and neck squamous cell carcinoma and its influence on immune cell infiltration.

BACKGROUND: HPV-positive head and neck squamous cell carcinoma (HNSCC) exhibits different characteristics from HPV-negative tumors in terms of tumor development, clinical features, treatment response, and prognosis. Layilin (LAYN), which contains homology with C-type lectins, plays a critical role in tumorigenesis and cancer progression. However, the prognostic value of LAYN and the relationship between LAYN and immune infiltration levels in HPV-related HNSCC patients still require a comprehensive understanding. Herein, we aimed to assess the prognostic value of LAYN and to investigate its underlying immunological function in HPV-related HNSCC. METHODS: Through various bioinformatics methods, we analyzed the data from The Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to explore the potential underlying oncogenic impression of LAYN, including the relevance of LAYN to survival outcomes, clinicopathological factors, immune cell infiltration, and immune marker sets in HPV-related HNSCC. The expression levels of LAYN and HPV were also verified in HNSCC patient tissues. RESULTS: LAYN was differentially expressed in a variety of tumors. The expression of LAYN in HNSCC was significantly higher than that in adjacent normal tissues (P < 0.0001), and high expression of LAYN was correlated with poor overall survival (OS) in HNSCC patients (Hazard Ratio (HR) = 1.3, P = 0.035). Moreover, LAYN expression level in HPV-positive HNSCC patients was significantly lower than that in HPV-negative patients, with HPV-positive HNSCC patients displaying a trend of favorable prognosis. In addition, the relationship between LAYN expression and immune infiltration levels in HPV-positive HNSCC group was less tightly correlated than that in HPV-negative HNSCC group, and there was a strong relationship between LAYN expression and markers of M2 macrophage (P < 0.001) and exhausted T cells (P < 0.05) in HPV-negative HNSCC. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis suggested that LAYN potentially influenced tumor progression through HPV infection and other cancer-related pathways. CONCLUSIONS: LAYN might contribute to tumorigenesis via its positive correlation with immune checkpoint molecules and tumor-associated macrophages (TAMs). Our study might provide a novel prognostic biomarker and latent therapeutic target for the treatment of HPV-related HNSCC.

Transmembrane serine protease 2, a SARS-CoV-2 internalization protease, correlates with clinical outcome, molecular features, and immunotherapy response in colorectal cancer.

Background: Transmembrane serine protease 2 (TMPRSS2) mediates the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells. The relevant research indicates the intestine to be a target of SARS-CoV-2 infection, and thus we aimed to investigate the correlation between TMPRSS2 expression and the prognosis, molecular features, and immunotherapy response in patients with colorectal cancer (CRC). Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used in this study and a total of 1,385 patients were identified. The CIBERSORT algorithms were used to evaluate the relative infiltration levels of immune cell types in the tumor microenvironment (TME). The correlation between TMPRSS2 expression and immunotherapy response rate was assessed in another 2 independent cohorts. Results: TMPRSS2 expression was significantly downregulated in cancer tissue compared to the adjacent normal tissue, and patients with CRC with lower TMPRSS2 expression showed notably poorer prognosis. Functional enrichment analysis found that low TMPRSS2 expression was significantly associated with cancer metastasis-related pathways. Further analysis based on the miRWalk tool and JASPAR database identified a list of microRNAs (miRNAs) and transcriptional factors targeting TMPRSS2. Distinct differences in immune cell infiltration and tumor purity reflected by estimate and mutant-allele tumor heterogeneity score were observed between patients with low and high TMPRSS2 expression levels. Interestingly, patients with a low TMPRSS2 expression level showed a higher response rate to immunotherapy. Conclusions: CRC cells may be more resistant to SARS-CoV-2 infection due to the decreased expression of TMPRSS2, which could be a newly identified biomarker for prognosis and immunotherapy response prediction in patients with CRC.

3D-US and CBCT Dual-guided Radiotherapy for Postoperative Uterine Malignancy: A Primary Workflow Set-up.

Introduction: The consistency of clinical target volume is essential to guiding radiotherapy with precision for postoperative uterine malignancy patients. By introducing a three-dimensional ultrasound system (3D-US) into image-guided radiation therapy (IGRT), this study was designed to investigate the initial workflow set-up, the therapeutic potential, and the adverse events of 3D-US and cone-beam computed tomography (CBCT) dual-guided radiotherapy in postoperative uterine malignancy treatment. Methods: From April 2021 to December 2021, postoperative uterine malignancy patients were instructed to follow the previously standard protocol of daily radiation treatment, particularly a 3D-US (Clarity system) guiding was involved before CBCT. Soft-tissue-based displacements resulting from the additional US-IGRT were acquired in the LT (left)/RT (right), ANT (anterior)/POST (posterior), and SUP (superior)/INF(inferior) directions of the patient before fractional treatment. Displacement distributions before and after treatment either from 3D-US or from CBCT were also estimated and compared subsequently, and the urinary and rectal toxicity was further evaluated. Results: All the patients completed radiation treatment as planned. The assessment of 170 scans resulted in a mean displacement of (0.17 ± 0.24) cm, (0.19 ± 0.23) cm, (0.22 ± 0.26) cm for bladder in LT/RT, ANT/POST, and SUP/INF directions. A mean deviation of (0.26 ± 0.22) cm, (0.58 ± 0.5) cm, and (0.3 ± 0.23) cm was also observed for the bladder centroid between the CBCT and computed tomography -simulation images in three directions. Paired comparison between these two guidance shows that the variations from 3D-US are much smaller than those from CBCT in three directions, especially in ANT/POST and SUP/INF directions with significance (P = 0.000, 0.001, respectively). During treatment, and 0, 3, 6, 9, and 12 months after treatment, there was no severe urinary and rectal toxicity happened. Conclusion: A primary workflow of 3D-US and CBCT dual-guided radiotherapy has been established, which showed great therapeutic potential with mild to moderate urinary and rectal toxicity for postoperative uterine malignancy patients. But the clinical outcomes of this non-invasive technique need to be investigated further.

Molecular characteristics of natural organic matter in the groundwater system with geogenic iodine contamination in the Datong Basin, Northern China.

Natural organic matter (NOM) plays an important role in the iodine mobilization in the groundwater system. In this study, the groundwater and sediments from iodine affected aquifers in the Datong Basin were collected to perform chemistry analysis and molecular characteristics of NOM by Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR-MS). Total iodine concentrations in groundwater and sediments ranged from 1.97 to 926.1 µg/L and 0.001-2.86 µg/g, respectively. A positive correlation was observed between DOC/NOM and groundwater/sediment iodine. FT-ICR-MS results showed that the DOM in the high-iodine groundwater system is characterized by less aliphatic and more aromatic compounds with higher NOSC, indicating the features of more unsaturated larger molecule structures and more bioavailability. Aromatic compounds could be the main carriers of sediment iodine and were easily absorbed on amorphous iron oxides to form the NOM-Fe-I complex. More aliphatic compounds, especially those containing N/S, experienced a higher degree of biodegradation, which further mediated the reductive dissolution of amorphous iron oxides and the transformation of iodine species, thereby causing the release of iodine into groundwater. The findings of this study provide some new insights into the mechanisms of high-iodine groundwater.

Double-Network Polymer Electrolytes with Ionic Liquids for Lithium Metal Batteries.

Solid-state polymer electrolytes have become promising candidates for high-energy-density lithium metal batteries (LMBs). However, they suffer from low ionic conductivities at room temperature. In this work, two types of composite polymer electrolytes based on a double-network polymer, an ionic liquid (IL) of 1-butyl-1-methylpyrrolidinium bis(trifluoromethanesulfonyl) imide (Pyr14TFSI) or 1-ethyl-3-methylimidazolium bis((trifluoromethyl)sulfonyl) imide (EmimTFSI), and bis(trifluoromethane)sulfonamide lithium salt (LiTFSI) were prepared by a facile one-pot method. The two types of CPEs possess good mechanical properties, excellent thermal stability, and high ionic conductivities greater than 10-4 S cm-1 at 20 °C with 26 wt% IL. The performance diversity of the CPEs was also carefully investigated through a series of electrochemical measurements. Although the CPEs containing EmimTFSI show higher ionic conductivities than those of CPEs with Pyr14TFSI, the latter ones have wider electrochemical stability windows and better resistance to the growth of lithium dendrites. Moreover, CPE with 34 wt% Pyr14TFSI leads to Li/LiFePO4 batteries with favorable rate capability and cycling stability and a columbic efficiency of 98.8% at 20 °C, which suggests that CPEs are promising for practical application in solid-state LMBs.

Difference in the alveolar bone remodeling between the adolescents and adults during upper incisor retraction: a retrospective study.

The purpose of this study was to compare the difference of alveolar bone remodeling between the adolescents and adults in the maxillary incisor area during retraction. This retrospective study included 72 female patients who needed moderate anchorage to correct the bimaxillary protrusion. Subjects were further divided into the minor group (n = 36, 11-16 years old) and adult group (n = 36, 18-35 years old). Digital lateral cephalography and cone beam CT scanning were taken in each patient before (T0) and after treatment (T1). Cephalometry was conducted to assess incisor retraction, while alveolar bone thickness (ABT), alveolar bone distance (ABD), and alveolar bone area (ABA) were detected to assess changes in the alveolar bone. No difference in the inclination of upper incisors was observed at both T0 and T1 between two groups. Changes in the alveolar bone showed a similar tendency with bone apposition on the labial side and bone resorption on the palatal side in both groups. Less increase in the labial ABT (T1-T0) and more decrease in the palatal ABT (T1-T0) was found in the adult group, leading to less total ABT in the adult group. Higher reduction in ABD (T1-T0) was found in the adult group. Moreover, more decrease in the ABA (T1-T0) was found in the adult group. Adult patients have less alveolar bone support after treatment when compared with young adolescents. Orthodontists should take the age into consideration to reduce the potential periodontal risks during the treatment planning.

Hydrogeochemical processes controlling the mobilization and enrichment of fluoride in groundwater of the North China Plain.

Fluoride enrichment in groundwater at the North China Plain (NCP) is posing a potential health risk to human being. To better understand the enrichment mechanism of fluoride in the groundwater systems, the groundwater, sediments samples and pore water compacted from clayey sediments were collected to perform the chemistry analysis and geochemical inverse modeling. The results showed that fluoride concentration in groundwater from the NCP has a range of 0.38-7.35 mg/L, and 67.8% of groundwater samples have the fluoride concentration higher than 1.5 mg/L. High fluoride groundwater was mainly distributed in the central plain and coastal area of the NCP, and characterized by the Na-HCO3 or Na-Cl type water, lower Ca and higher TDS concentrations. Along groundwater flow-path from the mountainous to coastal areas, several hydrogeochemical processes control the mobilization and enrichment of fluoride in groundwater, including cation exchange between Ca and Na on the surface of clay minerals, precipitation/dissolution of carbonates, dissolution of fluorite, marine transgressions, and release of pore water trapped in clayey sediments caused by land subsidence. The fluoride concentrations in the pore water compacted from the sediments ranged from 2.92 to 4.48 mg/L. At the central plain and coastal area, the wide occurrence of land subsidence resulted from the groundwater over-exploration leads to the release of pore water rich in fluoride into surrounding aquifers, thereby elevating the concentration of groundwater fluoride. The resulted groundwater environment with high salinity and some newly-introduced ions, such as Mg, promote the dissolution of fluorite, which was under-saturated in the groundwater samples from the NCP, further enhancing the fluoride enrichment in the groundwater at the coastal area. The findings of this study will provide new insights on the generation of high fluoride groundwater.

Evaluation of Contrast-Enhanced Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) in the Detection of Retropharyngeal Lymph Node Metastases in Nasopharyngeal Carcinoma Patients.

INTRODUCTION: We performed this study to explore the diagnostic accuracies and cutoff values of contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) for the detection and diagnosis of metastatic retropharyngeal lymph nodes (RLNs) in patients with nasopharyngeal carcinoma (NPC). METHODS: One hundred and twenty-eight patients with a total of 159 RLNs were included in the study. The sizes of maximal and minimal axial diameters of each node on both contrast-enhanced CT and MRI images were measured. The characteristics of the RLNs (malignant or benign), as well as the survival of patients, were classified based on the results of follow-up MRI. RESULTS: RLN size cutoffs of 4-11 mm for minimal axial diameter were used. We found that MRI showed higher sensitivity while CT demonstrated higher specificity. The reasonable criterion for the diagnosis of metastatic RLNs in MRI was a minimal axial diameter of ≥6 mm, which yielded a sensitivity, specificity and diagnostic odds ratio (DOR) of 0.71, 0.82 and 10.88. CONCLUSION: The radiologic criteria that should be used for the assessment of RLN metastases in NPC patients are nodes with a minimal axial diameter of ≥6 mm on MR images.

The Oncogenic and Tumor Suppressive Functions of the Long Noncoding RNA MALAT1: An Emerging Controversy.

Long noncoding RNAs are recently emerging as critical factors of tumorigenesis. Originally regarded as a pre-messenger RNA (mRNA) splicing regulator, the long noncoding RNA MALAT1 has been demonstrated to regulate gene transcription by binding histone modification enzymes and transcription factors, and to regulate mRNA and protein expression post-transcriptionally by binding microRNAs (miRNAs) and acting as a sponge. Early studies consistently report that MALAT1 is up-regulated in human cancer tissues of various organ origins, particularly metastatic cancer tissues, that high levels of MALAT1 expression in cancer tissues are associated with poor patient prognosis, and that MALAT1 induces cancer cell proliferation, migration, and invasion in vitro and tumor metastasis in mice. By contrast, by analyzing multiple independent large datasets, MALAT1 have very recently been found to be down-regulated in human colorectal and breast cancer tissues, and low MALAT1 expression is associated with decreased patient survival. By binding to the transcription factor TEAD, MALAT1 suppresses metastasis gene expression, colorectal and breast cancer cell migration, invasion, and metastasis in vitro and in mice. MALAT1 has therefore been proposed to function as a tumor suppressor in colorectal and breast cancers. More comprehensive studies with multiple independent cohorts of human cancer tissues of various organ origins, in vitro and in vivo function, and mechanism studies with rescue experiments are required to confirm the oncogenic or tumor suppressive role of MALAT1 in other cancers.

Plasma Long Non-Coding RNA RP11-438N5.3 as a Novel Biomarker for Non-Small Cell Lung Cancer.

BACKGROUND: Lung cancer is one of the most common malignancies around the world. The lack of early diagnosis and effective treatment strategies contributes to the poor prognosis of patients with lung cancer. Recent studies have implied the role of long non-coding RNAs (lncRNAs) in oncogenesis. The purpose of our study was to identify specific lncRNAs which were correlated with non-small cell lung cancer (NSCLC) and their potential functions. MATERIALS AND METHODS: The global plasma lncRNA profiling was performed using LncPathTM Human Cancer Array, and 11 lncRNAs were then selected for quantitative reverse transcription PCR (qRT-PCR) validation in 138 plasma samples from 69 NSCLC patients and 69 healthy controls (HCs). A noteworthy lncRNA, RP11-438N5.3, the function of which was previously unknown, was further explored on the aspect of the correlation of its expression level with clinicopathological factors. RESULTS: The results revealed that plasma level of RP11-438N5.3 was significantly lower in NSCLCs than that in HCs (p <0.01). Receiver operating characteristic (ROC) analyses showed that the area under the ROC curve (AUC) for plasma RP11-438N5.3 was 0.814 (95% CI, 0.743-0.885; p<0.01). High expression of RP11-438N5.3 in plasma correlated with favorable prognosis for NSCLC patients (Hazard ratio = 2.827; 95% CI: 1.036 to 7.718; p = 0.024; Cox regression analysis). Moreover, we found that the plasma level of stromal interaction molecule 1 (STIM1) mRNA was remarkably higher in NSCLC compared with HC (p<0.01), and the AUC for STIM1 was 0.753 (95% CI, 0.673-0.833; p<0.01), RP11-438N5.3 and STIM1 were inversely correlated with each other. CONCLUSION: Our results indicated that RP11-438N5.3 and STIM1 might provide a new strategy for NSCLC diagnosis. Furthermore, increased circulating RP11-438N5.3 level holds great potential in indicating a beneficial prognosis in NSCLC patients.

A dual MET/AXL small-molecule inhibitor exerts efficacy against gastric carcinoma through killing cancer cells as well as modulating tumor microenvironment.

The receptor tyrosine kinases MET and AXL have been implicated in tumorigenesis and aggressiveness of multiple malignancies. We performed this study to evaluate the antitumor impact of LY2801653, a dual MET and AXL inhibitor on gastric cancer and to elucidate the underlying mechanisms. In the present study, tissue microarrays containing gastric cancer tissues were stained with MET and AXL antibodies, which showed the prognostic values of MET and AXL. Administration of LY2801653 inhibited cell proliferation, migration, epithelial-mesenchymal transition, induced apoptosis, and cell cycle arrest. Xenograft mouse models showed suppressed cell proliferation of tumors in high MET and AXL expression cells. LY2801653 also inhibited the growth of MET and AXL-independent cells at higher but clinically relevant doses through decreased angiogenesis and M2 macrophages in the tumor microenvironment. In conclusion, our study provides evidence for MET and AXL as prognostic biomarkers and potential therapeutic targets in gastric cancer. The dual MET/AXL inhibitor LY2801653 represents a promising therapeutic strategy for the treatment of patients with gastric carcinoma.

The prognostic association of SPAG5 gene expression in breast cancer patients with systematic therapy.

BACKGROUND: Despite much effort on the treatment of breast cancer over the decades, a great uncertainty regarding the appropriate molecular biomarkers and optimal therapeutic strategy still exists. This research was performed to analyze the association of SPAG5 gene expression with clinicopathological factors and survival outcomes. METHODS: We used a breast cancer database including 5667 patients with a mean follow-up of 69 months. Kaplan-Meier survival analyses for relapse free survival (RFS), overall survival (OS), and distant metastasis-free survival (DMFS) were performed. In addition, ROC analysis was performed to validate SPAG5 as a prognostic candidate gene. RESULTS: Mean SPAG5 expression value was significantly higher with some clinicopathological factors that resulted in tumor promotion and progression, including poor differentiated type, HER2 positive or TP53 mutated breast cancer. Based on ROC-analysis SPAG 5 is a suitable prognostic marker of poor survival. In patients who received chemotherapy alone, SPAG5 had only a moderate and not significant predictive impact on survival outcomes. However, in hormonal therapy, high SPAG5 expression could strongly predict prognosis with detrimental RFS (HR = 1.57, 95% CI 1.2-2.06, p = 0.001), OS (HR = 2, 95% CI 1.05-3.8, p = 0.03) and DMFS (HR = 2.36, 95% CI 1.57-3.54, p <  0.001), respectively. In addition, SPAG5 could only serve as a survival predictor in ER+, but not ER- breast cancer patients. Patients might also be at an increased risk of relapse despite being diagnosed with a lower grade cancer (well differentiated type). CONCLUSIONS: SPAG5 could be used as an independent prognostic and predictive biomarker that might have clinical utility, especially in ER+ breast cancer patients who received hormonal therapy.

AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications.

Molecular targeted therapy for cancer has been a research hotspot for decades. AXL is a member of the TAM family with the high-affinity ligand growth arrest-specific protein 6 (GAS6). The Gas6/AXL signalling pathway is associated with tumour cell growth, metastasis, invasion, epithelial-mesenchymal transition (EMT), angiogenesis, drug resistance, immune regulation and stem cell maintenance. Different therapeutic agents targeting AXL have been developed, typically including small molecule inhibitors, monoclonal antibodies (mAbs), nucleotide aptamers, soluble receptors, and several natural compounds. In this review, we first provide a comprehensive discussion of the structure, function, regulation, and signalling pathways of AXL. Then, we highlight recent strategies for targeting AXL in the treatment of cancer.AXL-targeted drugs, either as single agents or in combination with conventional chemotherapy or other small molecule inhibitors, are likely to improve the survival of many patients. However, future investigations into AXL molecular signalling networks and robust predictive biomarkers are warranted to select patients who could receive clinical benefit and to avoid potential toxicities.

Application of Contrast-Enhanced Ultrasound (CEUS) in Lymphomatous Lymph Nodes: A Comparison between PET/CT and Contrast-Enhanced CT.

Purpose: We described imaging characteristics of different types of lymphomas using contrast-enhanced ultrasound (CEUS) and summarized some simple criteria to distinguish between normal lymph nodes and lymphomatous lymph nodes for clinical diagnosis. Materials and methods: Sixty-one lymphoma patients from 2014 to 2015 with 140 suspicious lymph nodes, who had been confirmed by histology and underwent chemotherapy, were enrolled in our study. The responses to chemotherapy were recorded by PET/CT, contrast-enhanced CT, or CEUS. Results: We summarized the CEUS enhancement patterns as two types when detecting lymphomatous lymph nodes, which could be the specific diagnostic criteria: (1) rapid well-distributed hyperenhancement, with 83.1% lesions exhibiting a fast-in hyperenhancement pattern in the arterial phase, and (2) rapid heterogeneous hyperenhancement, with 16.9% lesions exhibiting heterogeneous in the arterial phase. Particularly, we found that all the suspicious lesions of indolent lymphomas were rapid well-distributed hyperenhancement. CEUS successfully identified 117 lymphomatous lymph nodes, while PET/CT and contrast-enhanced CT detected 124 and 113 lymphomatous lymph nodes, respectively. CEUS had an accuracy of 83.57%, and the accuracy of PET/CT and contrast-enhanced CT was 88.57% and 80.71%, respectively (p=0.188). The false-negative rate was 16.43%, 11.43%, and 19.29%, respectively (p=0.188). Conclusion: CEUS could be a useful tool in detecting lymphomatous nodes. A rapid well-distributed hyperenhancement pattern in CEUS could be a useful diagnostic criterion in both aggressive lymphoma and indolent lymphoma. These results can help us distinguish between lymphomatous and benign lymph nodes and make better diagnostic and therapeutic decisions.

Prevalence and relationship of malnutrition and distress in patients with Cancer using questionnaires.

BACKGROUND: Negative feelings, such as anxiety and depression, are common in patients with cancer. Our aim was to investigate the prevalence of malnutrition and distress in cancer patients and to examine the relationship between them. MATERIALS AND METHODS: We did a cross-sectional study in West China hospital, China, using adapted questionnaires derived from Patient-Generated Subjective Global Assessment (PG-SGA), Nutritional Risk Screening 2002 (NRS2002) and Distress Thermometer (DT). We also focused on the factors associated with distress. RESULTS: We found that psychological distress in cancer patients was common, with 39.5% patients suffering from distress. The mean score of PG-SGA was 3.37 (0-6), and 39.1% patients had malnutrition when using 4 as a cut-off value. Meanwhile, the mean score of NRS2002 was 1.91 (0-11), and 25.8% patients presented with malnutrition when using 3 as the cut-off value. Higher scores of nutritional risks confirmed by PG-SGA (r = 0.148, p < 0.001) and NRS2002 (r = 0.142, p < 0.001) were significantly correlated with higher levels of psychological stress. CONCLUSION: Malnutrition was correlated with psychological stress in cancer patients. Early intervention in the mental problems and nutrition was meaningful, which could improve the psychological statuses of cancer patients.