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1.
BMC Med Genomics ; 16(1): 106, 2023 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-37198621

RESUMO

BACKGROUND: Pancreatic adenocarcinoma (PDAC) is a malignant tumor with high heterogeneity and poor prognosis. In this study, we sought to identify the value of platelet-related genes in prognosis and heterogeneity of PDAC through multiple transcriptomic methods. METHODS: Based on datasets from Gene Expression Omnibus and The Cancer Genome Atlas (TCGA), platelet-related genes were screened out, and the TCGA cohort (n = 171) was identified into two subtypes by unsupervised clustering. The platelet-related risk score model (PLRScore) was constructed by univariate Cox and LASSO regression, and the predictive ability was evaluated by Kaplan-Meier test and time-dependent receiver operating characteristic (ROC) curves. The results were validated in two other external validation sets, ICGC-CA (n = 140) and GSE62452 (n = 66). Furthermore, predictive nomogram containing clinical characteristics and PLRScore was established. In addition, we determined the possible correlation between PLRScore and immune infiltration and response of immunotherapy. Finally, we analyzed the heterogeneity of our signature in various types of cells using single-cell analysis. RESULTS: Platelet-related subtypes that have significant difference of overall survival and immune states (p < 0.05) were identified. PLRScore model based on four-gene signature (CEP55, LAMA3, CA12, SCN8A) was constructed to predict patient prognosis. The AUCs of training cohort were 0.697, 0.687 and 0.675 for 1-, 3-and 5-year, respectively. Further evaluation of the validation cohorts yielded similar results. In addition, PLRScore was associated with immune cell infiltration and immune checkpoint expression, and had promising ability to predict response to immunotherapy of PDAC. CONCLUSIONS: In this study, the platelet-related subtypes were identified and the four-gene signature was constructed and validated. It may provide new insights into the therapeutic decision-making and molecular targets of PDAC.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/genética , Neoplasias Pancreáticas/genética , Prognóstico , Plaquetas , Proteínas de Ciclo Celular , Neoplasias Pancreáticas
2.
Biol Direct ; 18(1): 1, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631876

RESUMO

BACKGROUND: Pancreatic cancer (PC) is a highly lethal malignancy that requires effective novel therapies. M2 macrophages are abundant in the PC microenvironment and promote cancer progression. Exosomes are emerging mediators of the crosstalk between cancer cells and the microenvironment. This study was conducted to explore the role of M2 macrophage-derived exosomes in PC. METHODS: Exosomes derived from M2 macrophages were extracted. miR-193b-3p and TRIM62 were overexpressed or silenced to examine their function in PC. Luminescence assays were used to investigate the interaction between miR-193b-3p and TRIM62. Cell proliferation was examined by EdU staining. Would healing and transwell assays were applied to evaluate cell migration and invasion. Co-immunoprecipitation was used to assess the interaction between TRIM62 and c-Myc. Gene and protein expressions were analyzed by quantitative RT-PCR and immunoblotting, respectively. RESULTS: M2 macrophage-derived exosomal miR-193b-3p promoted the proliferation, migration, invasion, and glutamine uptake of SW1990 cells. Mechanism study revealed that TRIM62 is a target of miR-193b-3p. TRIM62 inhibited the proliferation, migration, invasion, and glutamine uptake of SW1990 cells by promoting c-Myc ubiquitination. Our data also suggested that TRIM62 expression negatively correlated with miR-193b-3p and c-Myc expression. High-expression of miR-193b-3p and c-Myc predicts poor prognosis, whereas low-expression of TRIM62 predicts poor prognosis in patients with PC. CONCLUSION: M2 macrophage-derived exosomal miR-193b-3p enhances the proliferation, migration, invasion, and glutamine uptake of PC cells by targeting TRIM62, resulting in the decrease of c-Myc ubiquitination. This study not only reveals the mechanism underlying the crosstalk between M2 macrophages and PC cells but also suggests a promising therapeutic target for PC.


Assuntos
Exossomos , MicroRNAs , Neoplasias Pancreáticas , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Glutamina/metabolismo , Neoplasias Pancreáticas/genética , Linhagem Celular Tumoral , Exossomos/genética , Exossomos/metabolismo , Exossomos/patologia , Proliferação de Células , Macrófagos/metabolismo , Microambiente Tumoral , Neoplasias Pancreáticas
3.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-921875

RESUMO

Computed tomography (CT) examination is the major measure for detecting and diagnosis of foreign bodies in human body. Although CT has high sensitivity in diagnosis of foreign body, some interference factors may still lead to missed diagnosis or misdiagnosis. Here we report a rare case that a bamboo stick accidentally pierced into the left chest of a young man who was drunk and unware of this hurt. The patient experienced cough, chest pain, fever, hemoptysis, and was misdiagnosed as primary and secondary tuberculosis based on chest CT examinations at a local hospital, although no tubercular bacillus detected by sputum smear. He subsequently received anti-tuberculous treatments in the following three years, but no improvement of his symptoms was observed. Until one month before his death, the bamboo stick was detected by spiral CT examination as well as three-dimensional image reconstruction at another hospital. Postmortem examination revealed pneumonia, pulmonary infarction, and abscess as the causes of his death. We analyze the potential reasons of misdiagnosis in this case, aiming to provide reference for the diagnosis and treatment of pulmonary inflammation associated with foreign body in the future.


Assuntos
Humanos , Masculino , Abscesso , Erros de Diagnóstico , Pneumonia , Infarto Pulmonar , Tuberculose Pulmonar
4.
Journal of Forensic Medicine ; (6): 384-384, 2018.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-984948

RESUMO

OBJECTIVES@#To study the epidemiological and pathological features of sudden death (SD) in Yunnan Province and to provide scientific evidence for prevention and forensic identification of sudden death.@*METHODS@#Totally 363 SD cases were collected from the autopsies between 2009 and 2017 in the Forensic Centre of Kunming Medical University. The related factors such as etiology, age, inducing factor, time interval between the onset of disease and death, morbidity season and pathological change were retrospectively analysed.@*RESULTS@#The incidence of SD in males was significantly higher than that of females. The peak age was ≥35-55 years. The mortality rate was relatively high within 6 h after the onset of disease. The season order with descending number of deaths was spring, summer, winter and autumn. The top ten causes of SD were coronary heart disease, sudden unexplained death (SUD), cerebral hemorrhage, acute hemorrhagic necrotic pancreatitis, aortic dissection rupture, cardiomyopathy, pneumonia, pulmonary thromboembolism, amniotic fluid embolism and allergy. Exercise, infusion, surgery, medication and minor injury were the most common predisposing factors of sudden coronary death. Consciousness disorder or coma, chest pain or chest tightness, and abdominal pain were the most common premortem symptoms of sudden coronary death.@*CONCLUSIONS@#The SD is more common in middle-aged males, which is the key population for the prevention of SD. For the forensic identification and prevention of SD, the attention on SUD should be paid.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ruptura Aórtica , Autopsia , Causas de Morte , China/epidemiologia , Morte Súbita/patologia , Morte Súbita Cardíaca/patologia , Patologia Legal , Incidência , Embolia Pulmonar , Estudos Retrospectivos , Estações do Ano
5.
Journal of Forensic Medicine ; (6): 253-256, 2018.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-984932

RESUMO

OBJECTIVES@#To analyze the relationship between the suicide method and the sex, age, education background and cause of suicide to provide reference for the forensic identification of suicide.@*METHODS@#After scene investigation, external body examination, autopsy and case investigation, 124 identified suicide cases which happened in recent three years in Wuhua district in Kunming were collected. Analytical methods as chi-square test and descriptive statistics were performed by SPSS 22.0.@*RESULTS@#In all the suicide cases, male to female ratio was 1.53∶1. The suicide methods were mainly fatal fall, hanging and drowning. The ratio of local to non-native residents was 1∶1. The suicide rate in the people with primary school or junior middle school education level was highest. The group of >10-50 years tended to choose fatal fall suicide and people over 60 years were more likely to choose hanging. People with different academic background tended to choose fatal fall suicide. The suicide methods as fatal fall and hanging were chosen because of mental and physical diseases and economic problems, while the suicides with emotional problems were more likely to choose fatal fall and poisoning.@*CONCLUSIONS@#Suicide belongs to a kind of complex cases. For the cases of suspected suicide, complete exploration and overall consideration should be done to determine the nature of cases based on comprehensive analysis of all the influence factors.


Assuntos
Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Distribuição por Idade , Autopsia , Causas de Morte , China/epidemiologia , Afogamento/psicologia , Incidência , Transtornos Mentais/psicologia , Distribuição por Sexo , Suicídio/estatística & dados numéricos
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