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BACKGROUND: Pancreatic cancer (PC) is one of the most lethal malignant tumors with no valid biomarkers for early diagnosis. We evaluated the value of PD-1, PD-L1, PD-L2, CD28, B7-1, and B7-H5 for diagnosing PC. METHODS: We measured serum soluble PD-1, PD-L1, PD-L2, CD28, B7-1, and B7-H5, and serum carbohydrate antigen (CA)19-9 levels in 87 patients with PC, 27 patients with benign pancreatic disease, and 20 healthy volunteers. We evaluated the diagnostic value of CA19-9, PD-1, PD-L1, PD-L2, CD28, B7-1, B7-H5. RESULTS: Patients with PC had significantly higher serum CA19-9, PD-L1, PD-L2, and B7-H5. Combined detection (CA19-9 + PD-L1 + PD-L2 + B7-H5) had much higher sensitivity than single CA19-9 detection. CONCLUSIONS: Serum soluble PD-L1, PD-L2, and B7-H5 might be novel potential biomarkers for diagnosing PC; their combination with serum CA19-9 might improve diagnostic sensitivity and specificity.
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Antígeno B7-H1 , Neoplasias Pancreáticas , Biomarcadores Tumorais , Antígeno CA-19-9 , Humanos , Neoplasias Pancreáticas/diagnóstico , Prognóstico , Sensibilidade e EspecificidadeRESUMO
BACKGROUND/AIMS: Co-stimulating molecule B7-H4 regulates T cell-mediated immune responses, participates in tumor immune escape, and promotes the proliferation and metastasis of pancreatic cancer cells. However, the specific mechanisms are unclear. MicroRNAs (miRNAs) participated in the pathogenesis and progression of cancer. METHODS: In this study, a microarray technique was used to screen B7-H4-related differentially expressed miRNAs in a pancreatic cancer cell line find those associated with pancreatic cancer. Using a miRCURYTM LNA Array approach, we compared the miRNA expression profiles of L3.6p1 pancreatic cancer cells transfected with B7-H4 siRNA for 72 h with those transfected with non-target siRNAs. RESULTS: B7-H4 siRNA significantly up-regulated 57 miRNAs and down-regulated 14 miRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis of predicted miRNA targets showed that these genes were mainly involved in protein binding, pathways in cancer, mitogen-activated protein kinase (MAPK) signaling pathway, and phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway. CONCLUSIONS: This is the first description of target genes of B7-H4, showing that miRNAs participate in the B7-H4 mediated regulation of oncogenicity and pathogenesis of pancreatic cancer. These results may help us better understand the role of B7-H4 in the progression of pancreatic cancer and its possible mechanisms. We also provide novel biomarkers for potential treatments of pancreatic cancer.
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MicroRNAs/metabolismo , Inibidor 1 da Ativação de Células T com Domínio V-Set/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Regulação para Cima , Inibidor 1 da Ativação de Células T com Domínio V-Set/antagonistas & inibidores , Inibidor 1 da Ativação de Células T com Domínio V-Set/genéticaRESUMO
Background: It has been shown that autoimmune diseases are associated with psychiatric disorders in epidemiological studies. The acute psychiatric disorder patients have higher frequency of autoantibodies in the blood, including antinuclear antibodies, anti-thyroid peroxidase, and thyroglobulin [thyroid antibody carriers]. However, large clinical studies with more relevant control groups in China are few. Methods: This was a retrospective study. A total of 1669 sera were tested for autoantibodies in the clinical laboratory of the Fourth Affiliated Hospital, Zhejiang University School of Medicine from October 2016 to March 2021. All data available during this time period were analyzed. Only the first entry for each patient from inpatient care units was used for analysis. The clinical information and laboratory data of patients were retrospectively collected and analyzed. Results: A significantly lower prevalence of antinuclear antibodies was observed in the healthy control group than in the patient group (21.7% vs 28.8%, P < .05). There was a significant difference in the prevalence of antinuclear antibodies between thyroglobulin-antibody carriers and thyroid peroxidase-antibody- and thyroglobulin-antibody-seronegative individuals in the unipolar depressive disorder group (P < .05). A positive anti-thyroid peroxidase test was significantly associated with patients having nonaffective psychoses (P < .05). Conclusion: The results showed that psychiatric disorders were associated with antinuclear antibodies and thyroid autoantibodies in our large sample of patients admitted to acute psychiatric hospitalization, and autoimmune autoantibodies were potential biomarkers of psychotic disorders. The results might lead to new research directions for the study of psychiatric disorders in the future.
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Background: Colorectal cancer (CRC)is the third most common cancer in the world and the second leading cause of cancer-related deaths, and over the past two decades, many of these researchers have provided a substantial amount of important information on the role of gut microbes in the development and progression of CRC. A causal relationship between the presence of specific microorganisms and CRC development has also been validated. Although a large number of papers related to this area have been published, no bibliometric study has been conducted to review the current state of research in this area and to highlight the research trends and hotspots in this area. This study aims to analyze the current status and future research trends of gut microbiota and CRC through bibliometric analysis. Methods: Publications from 2001 to 2022 were retrieved from the Web of Science Core Collection database and screened according to inclusion criteria. VOSviewer and CiteSpace software were used to visualize the research trends in this field, including the analysis of title, country, institution, author, number of publications, year of publication, number of citations, journal, and H-index. Results: A total of 863 studies were eventually identified, and the articles retrieved were cited an average of 44.85 times each. The number of publications on this topic has been increased steadily since 2011. China and the USA have made the largest contribution in the field. FRONTIERS IN MICROBIOLOGY is the top productive journal with 26 papers, and Gut journal has the highest average citation (167.23). Shanghai Jiao Tong University is the most contributive institution. Professor Yu J, Sung, Joseph J. Y and Fang JY are the most productive authors in this field. Keyword co-occurrence analysis showed that the terms of "Gut Microbiota", "Colorectal Cancer", "Inflammation", "Probiotic" and "Fusobacterium Nucleatum" were the most frequent, which revealed the research hotpots and trends in this field. Conclusions: There has been a growing number of publications over the past two decades according to the global trends. China and the USA still maintained the leading position in this field. However, collaboration between institutions needs to be strengthened. It's commended to pay attention to the latest hotspots, such as "F. nucleatum" and "probiotics". This bibliometric analysis evaluates the scope and trends of gut microbiota and CRC, providing a useful perspective on current research and future directions for studying the link between the gut microbiota and CRC.
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Neoplasias Colorretais , Microbioma Gastrointestinal , Humanos , China , Bibliometria , Bases de Dados FactuaisRESUMO
The H7N9 virus mutated in 2017, resulting in new cases of highly pathogenic avian influenza (HPAI) H7N9 virus infection. H7N9 was found in a viraemic patient in Guangdong province, China. The present study aimed to clarify the pathogenic characteristics of HPAI H7N9. Virus was isolated from the plasma and sputum of the patient with HPAI H7N9. Liquid phase chip technology was used to detect the plasma cytokines from the infected patient and healthy controls. Mice were infected with strains A/Guangdong/GZ8H002/2017(H7N9) and A/Zhejiang/DTID-ZJU01/2013(H7N9) to observe the virus's pathogenic characteristics. Serum and brain tissue were collected at 2, 4, and 6 days after infection. The viruses in serum and brain tissue were detected and isolated. The two strains were infected into A549 cells, exosomes were extracted, and virus genes in the exosomes were assessed. Live virus was isolated from the patient's plasma. An acute cytokine storm was detected during the whole course of the disease. In animal experiments, A/Guangdong/GZ8H002/2017(H7N9) was more pathogenic than A/Zhejiang /DTID-ZJU01/2013(H7N9) and resulted in the death of mice. Live virus was isolated from infected mouse serum. Virus infection was also detected in the brain of mice. Under viral stress, A549 cells secreted exosomes containing the entire viral genome. The viraemic patient was confirmed to have an HPAI H7N9 infection. A/Guangdong/GZ8H002/2017(H7N9) showed significantly enhanced toxicity. Patient deaths might result from cytokine storms and brain infections. Extrapulmonary tissue infection might occur via the exosome pathway. The determined pathogenic characteristics of HPAI H7N9 will contribute to its future treatment.
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Exossomos/virologia , Subtipo H7N9 do Vírus da Influenza A , Influenza Aviária/virologia , Influenza Humana/virologia , Animais , Aves , Sangue/virologia , Encéfalo/virologia , Linhagem Celular , Citocinas/sangue , Genoma Viral , Humanos , Subtipo H7N9 do Vírus da Influenza A/genética , Subtipo H7N9 do Vírus da Influenza A/imunologia , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Camundongos , ViremiaRESUMO
B7-H4 belongs to the immune costimulatory B7 family and is thought to negatively regulate T-cell-mediated immunity, and may contribute an important role in tumor immune evasion. Although the expression of B7-H4 has been observed in human pancreatic cancer, the prognostic significance of this expression is poorly understood. This present study explored the prognostic value of B7-H4 in pancreatic cancer. Patients with pancreatic cancer and healthy controls were recruited at the Second Affiliated Hospital to Zhejiang University from January 2011 to December 2014. Expression of B7-H4 was assessed by immunohistochemistry. Immunohistochemical analysis indicated that B7-H4 was expressed in 100% (188/188) of the pancreatic cancer tumor tissue samples, while only in 68% (17/25) of normal pancreatic tissue samples. Furthermore, the expression levels of B7-H4 in pancreatic cancer patients were significantly higher than in controls (P<.01). A significant difference in B7-H4 expression was observed between patients with late tumor-node-metastasis (TNM) stage (III and IV) and early TNM stage (I and II) (P<.01). The expression of B7-H4 was associated with distant metastasis (P<.01) and differentiation (P<.01). In addition, B7-H4 expression (P<.01), distant metastasis (P<.01), TNM stage (P<.01), differentiation (P<.01) and chemotherapy treatment (P<.05) were indicators of poor overall survival time. Multivariate survival analysis indicated that B7-H4 expression, distant metastasis, and chemotherapy treatment (P<.05) were independent prognostic indicators of poor overall survival. In conclusion, B7-H4 is highly expressed in pancreatic cancer, and is an independent predictor of poor prognosis in patients with pancreatic cancer. B7-H4 may represent an immunotherapeutic target in pancreatic cancer.