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Abstract Natural killer (NK) cells play essential roles in the tumor development, diagnosis, and prognosis of tumors. In this study, we aimed to establish a reliable signature based on marker genes in NK cells, thus providing a new perspective for assessing immunotherapy and the prognosis of patients with gastric cancer (GC). We analyzed a total of 1560 samples retrieved from the public database. We performed a comprehensive analysis of single-cell RNA-sequencing (scRNA-seq) data of gastric cancer and identified 377 marker genes for NK cells. By performing Cox regression analysis, we established a 12-gene NK cell-associated signature (NKCAS) for the Cancer Genome Atlas (TCGA) cohort, that assigned GC patients into a low-risk group (LRG) or a high-risk group (HRG). In the TCGA cohort, the areas under curve (AUC) value were 0.73, 0.81, and 0.80 at 1, 3, and 5 years. External validation of the predictive ability for the signature was then validated in the Gene Expression Omnibus (GEO) cohorts (GSE84437). The expression levels of signature genes were measured and validated in GC cell lines by real-time PCR. Moreover, NKCAS was identified as an independent prognostic factor by multivariate analysis. We combined this with a variety of clinicopathological characteristics (age, M stage, and tumor grade) to construct a nomogram to predict the survival outcomes of patients. Moreover, the LRG showed higher immune cell infiltration, especially CD8+ T cells and NK cells. The risk score was negatively associated with inflammatory activities. Importantly, analysis of the independent immunotherapy cohort showed that the LRG had a better prognosis and immunotherapy response when compared with the HRG. The identification of NK cell marker genes in this study suggests potential therapeutic targets. Additionally, the developed predictive signatures and nomograms may aid in the clinical management of GC.

Background/Aim: Irritable Bowel Syndrome (IBS) is a common chronic functional bowel disorder and the evidence shows most drug therapies in the treatment of IBS are weak. Recently, some studies showed probiotics may have a positive effect in IBS and they are widely used to improve the symptom of IBS, which indicate probiotics may play an important role in the treatment of IBS. However, the exact effectiveness and safety of probiotics are largely unknown. This systematic review focuses on identifying the efficacy and safety of probiotics in the treatment of IBS. Materials and Methods: Data sources were searched up to February 2019. Databases included MEDLINE, CENTRAL, CINAHL, and Embase. Randomized controlled trials (RCTs) comparing probiotics including complex or individual probiotics with placebo or no therapy were screened, extracted, and appraised by two independent reviewers. The data were pooled using a random-effects model. The methodological quality of all RCTs was assessed using the Cochrane risk of bias and Jadad scale. Outcomes included symptom-relevant and patient-relevant characteristics, such as symptom relief, abdominal pain, bloating, flatulence, quality of life, and adverse event. Results: This review includes 28 studies with a total of 3606 participants. Particular combinations of probiotics, or specific species and strains, showed probiotics have beneficial effect on overall IBS symptoms (22 studies, n = 3144, RR of improvement in overall IBS symptoms = 1.5, CI 1.23 to 1.83) or overall IBS symptom and abdominal pain scores (18 studies, n = 2766, SMD = -0.31, CI -0.45 to -0.17). In addition, adverse events were not significantly higher with probiotics (8 studies, n = 923, RR = 1.05; 95% CI 0.85-1.31). However, there was no significant benefit on individual IBS symptom scores and quality of life. Conclusion: Current evidence shows particular combinations, species or strains of probiotics are effective for overall IBS symptoms. However, it is hard to derive a definite conclusion due to high heterogeneity and unclear risk of bias of some trials. Large well-designed and rigorous trials are warranted.

Hepatocellular carcinoma (HCC) is one of the most common types of malignancy and is associated with high mortality. Prior research suggests that long non-coding RNAs (lncRNAs) play a crucial role in the development of HCC. Therefore, it is necessary to identify lncRNA-associated therapeutic biomarkers to improve the accuracy of HCC prognosis. Transcriptomic data of HCC obtained from The Cancer Genome Atlas (TCGA) database were used in the present study. Differentially expressed RNAs (DERNAs), including 74 lncRNAs, 16 miRNAs, and 35 mRNAs, were identified using bioinformatics analysis. The DERNAs were subsequently used to reconstruct a competing endogenous RNA (ceRNA) network. A lncRNA signature was revealed using Cox regression analysis, including LINC00200, MIR137HG, LINC00462, AP002478.1, and HTR2A-AS1. Kaplan-Meier plot demonstrated that the lncRNA signature is highly accurate in discriminating high- and low-risk patients (P < 0.05). The area under curve (AUC) value exceeded 0.7 in both training and validation cohort, suggesting a high prognostic potential of the signature. Furthermore, multivariate Cox regression analysis indicated that both the TNM stage and the lncRNA signature could serve as independent prognostic factors for HCC (P < 0.05). Then, a nomogram comprising the TNM stage and the lncRNA signature was determined to raise the accuracy in predicting the survival of HCC patients. In the present study, we have introduced a ceRNA network that could contribute to provide a new insight into the identification of potential regulation mechanisms for the development of HCC. The five-lncRNA signature could serve as a reliable biosignature for HCC prognosis, while the nomogram possesses strong potential in clinical applications.

BackgroundAlternative splicing (AS) is a molecular event that drives protein diversity through the generation of multiple mRNA isoforms. Growing evidence demonstrates that dysregulation of AS is associated with tumorigenesis. However, an integrated analysis in identifying the AS biomarkers attributed to esophageal carcinoma (ESCA) is largely unexplored.MethodsAS percent-splice-in (PSI) data were obtained from the TCGA SpliceSeq database. Univariate and multivariate Cox regression analysis was successively performed to identify the overall survival (OS)-associated AS events, followed by the construction of AS predictor through different splicing patterns. Then, a nomogram that combines the final AS predictor and clinicopathological characteristics was established. Finally, a splicing regulatory network was created according to the correlation between the AS events and the splicing factors (SF).ResultsWe identified a total of 2389 AS events with the potential to be used as prognostic markers that are associated with the OS of ESCA patients. Based on splicing patterns, we then built eight AS predictors that are highly capable in distinguishing high- and low-risk patients, and in predicting ESCA prognosis. Notably, the area under curve (AUC) value for the exon skip (ES) prognostic predictor was shown to reach a score of 0.885, indicating that ES has the highest prediction strength in predicting ESCA prognosis. In addition, a nomogram that comprises the pathological stage and risk group was shown to be highly efficient in predicting the survival possibility of ESCA patients. Lastly, the splicing correlation network analysis revealed the opposite roles of splicing factors (SFs) in ESCA.ConclusionIn this study, the AS events may provide reliable biomarkers for the prognosis of ESCA. The splicing correlation networks could provide new insights in the identification of potential regulatory mechanisms during the ESCA development.

Objective: To explore the key targets and mechanism of Shengjiang Xiexin Decoction in the treatment of chemotherapy-induced diarrhea based on network pharmacological methods. Methods: The effective components and corresponding target proteins of Shengjiang Xiexin Decoction were screened by TCMSP, and the target of chemotherapy-induced diarrhea were screened by the GeneCards. R software was used to obtain the common targets of drugs and diseases, and the "component-target-disease" network diagram was constructed by Cytoscape3.8.0 software. The string datebase was used to draw the protein interaction (PPI) network, and the Bioconductor software was used to perform GO function and KEGG pathway enrichment analysis on effective targets. Result: The result showed that 216 components were screened and 276 effective targets were screened. There were 1764 chemotherapy-induced diarrhea targets. The 173 common targets were obtained through venn diagram. The GO function analysis found 2427 items of biological process, 168 items of molecular function and 79 items of cellular component. The KEGG pathway analysis found 169 items. Conclusion: The PPI network found that STAT3, AKT1, MAPK3, JUN, MAPK1, RELA, IL6, etc. may be the key targets for Shengjiang Xiexin Decoction in treatment of chemotherapyinduced diarrhea. GO biological processes include DNA-binding transcription factor activity, cytokine receptor binding, cytokine activity, response to lipopolysaccharide, cellular response to chemical stress and so on. The KEGG pathways involved mainly include Toll-like receptor signaling pathway, TNF signaling pathway, inlfuenza A signaling pathway, hepatitise B signaling pathway and other pathways, that Play the role of anti-inflammatory and repair barrier. [ABSTRACT FROM AUTHOR]

Acute promyelocytic leukemia (APL) is a common subtype of acute myeloid leukemia in China. Since the application of arsenic trioxide and all-trans retinoic acid in the treatment of APL, the prognosis has greatly improved. However, ~20% of patients with APL relapse upon completing chemotherapy. Decreasing the relapse rate and incidence of early mortality may pose the greatest challenges for the future management of APL. Recently, Ets variant 6 (ETV6) was reported to be involved in a variety of translocations associated with hematological malignancies of myeloid and lymphoid origin. To date, little is known about the clinical implication of ETV6 rearrangement in APL. In the present study, ETV6 rearrangement was examined by split-signal fluorescence in situ hybridization in 258 adults with APL, and its association with the clinical features and outcomes of the patients was analyzed. The data suggested that ETV6 rearrangement may be an independent unfavorable prognostic factor for overall survival in APL patients. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumors (GISTs) originate from the mesenchymal tissue of the gastrointestinal tract. The pathogenesis of GIST is associated with the mutational activation of the receptor tyrosine kinase cluster of differentiation (CD)117 or platelet-derived growth factor receptor-a. Overall, ~60% of GISTs occur in the stomach. Clinically, GISTs may coexist with various types of cancer, including liver cancer, pancreatic tumors and lymphoma, either synchronously or metachronously. The present study reports the case of a patient with the synchronous occurrence of a CD117-positive GIST and acute myeloid leukemia. A 69-year-old man was hospitalized for heart palpitations and dizziness, and was diagnosed with acute myeloid leukemia (AML) by bone marrow aspiration and flow cytometry analysis. An abdominal computed tomograpy and gastroscopy revealed the presence of GIST. The patient received chemotherapy in combination with imatinib (400 mg/day), and the mass was removed 2 months later. To the best of our knowledge, the present study is the first reported case of the synchronous development of a CD117-positive GIST and AML. Additional studies are required in order to understand the association between GIST and hematological malignancies. [ABSTRACT FROM AUTHOR]

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare malignant tumor of the hemopoietic system that arises from plasmacytoid dendritic cell precursors with a highly aggressive course. BPDCN frequently involves the skin, lymph nodes, peripheral blood and bone marrow. BPDCN is known to develop leukemic dissemination as a feature of myelomonocytic leukemia in the late phase of the disease, which leads to a poorer prognosis. In the present study, a case of BPDCN with leukemic manifestation without cutaneous involvement was reported. In addition, ETS variant gene 6 (ETV6) gene rearrangement was detected in the patient. The patient relapsed soon after complete remisson and had no response to further treatment. To the best of our knowledge, this is the first reported case of BPDCN with ETV6 rearrangement. Following chemotherapy treatment, the patient suffered from severe headache in the complete remission stage; however, brain CT scans showed no significant abnormalities. Several lumbar punctures and intrathecal chemotherapy were performed, and the patient recovered gradually. Therefore, the patient was considered to suffer from central nervous system leukemia. In conclusion, implementation of lumbar punctures and preventive intrathecal chemotherapy are required in BPDCN patients with leukemic manifestation during the remission stage. [ABSTRACT FROM AUTHOR]

Evolutions of defects and helium contained defects produced by atomic displacement and helium deposition with helium implantation at different temperatures in novel high silicon (NHS) steel are investigated by a slow positron beam. Differences of the defect information among samples implanted by helium to a fluence of 1 × 1017 ions/cm2 at room temperature, 300°C, 450°C and 750°C are discussed. It is found that the mobility of vacancies and vacancy clusters, a recombination of vacancy-type defects and the formation of the He-V complex lead to the occurrence of these differences. At high temperature irradiations, a change of the diffusion mechanism of He atoms/He bubbles might be one of the reasons for the change of the S-parameter. [ABSTRACT FROM AUTHOR]

We report on cavity swelling at peak damage regions of three ferritic-martensitic (FM) steels (NHS, RAFM and T91) irradiated by 196 MeV Kr ions at different temperatures (450/550°C). Cavity configurations of the irradiated specimens are investigated by transmission electron microscopy with cross-section technique. For home-made reduced activation ferritic-martensitic (RAFM) and T91 steels irradiated at 450°C, both large size and bimodal size distribution of the cavity are found in their peak damage regions, whereas novel high silicon (NHS) steel exhibits good swelling resistance at different irradiation temperatures. Temperature relativity of the cavity swelling in NHS, RAFM and T91 steels is discussed briefly. [ABSTRACT FROM AUTHOR]

Ti3AlC2 samples are irradiated in advance by 3.5MeV Fe-ion to the fluence of 1.0×1016ion/cm2, and then are implanted by 500 keV He-ion with the fluence of 1.0×1017ion/cm2at room temperature. The irradiated samples are investigated by grazing incidence x-ray diffraction (GIXRD) and transmission electron microscopy (TEM). GIXRD results show serious structural distortion, but without amorphization in the irradiated samples. Fe-ion irradiation and He-ion implantation create much more serious structural distortion than single Fe-ion irradiation. TEM results reveal that there are a large number of defect clusters in the damage region, and dense spherical He bubbles appear in the He depositional region. It seems that the pre-damage does not influence the growth of He bubbles, but He-ion implantation influences the pre-created defect configurations. [ABSTRACT FROM AUTHOR]

Radiation-induced defect annealing in He+ ion-implanted 4H-SiC via H+ ion irradiation is investigated by Raman spectroscopy. There are 4H-SiC wafers irradiated with 230 keV He+ ions with fluences ranging from cm−2 to cm−2 at room temperature. The post-implantation samples are irradiated by 260 keV H+ ions at a fluence of cm−2 at room temperature. The intensities of Raman lines decrease after He implantation, while they increase after H irradiation. The experimental results present that the magnitude of Raman line increment is related to the concentration of pre-existing defects formed by He implantation. A strong new peak located near 966 cm−1, which is assigned to 3C-SiC LO () phonon, is found in the He-implanted sample with a fluence of cm−2 followed by H irradiation. However, for the He-implanted sample with a fluence of cm−2 followed by H irradiation, no 3C-SiC phonon vibrations are found. The detailed reason for H irradiation-induced phase transformation in the He-implanted 4H-SiC is discussed. [ABSTRACT FROM AUTHOR]