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1.
J Exp Clin Cancer Res ; 42(1): 234, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37684630

RESUMO

BACKGROUND: Neoadjuvant radiotherapy has been used as the standard treatment of colorectal cancer (CRC). However, radiotherapy resistance often results in treatment failure. To identify radioresistant genes will provide novel targets for combined treatments and prognostic markers. METHODS: Through high content screening and tissue array from CRC patients who are resistant or sensitive to radiotherapy, we identified a potent resistant gene SUMO specific peptidase 5 (SENP5). Then, the effect of SENP5 on radiosensitivity was investigated by CCK8, clone formation, comet assay, immunofluorescence and flow cytometric analysis of apoptosis and cell cycle to investigate the effect of SENP5 on radiosensitivity. SUMO-proteomic mass spectrometry combined with co-immunoprecipitation assay were used to identify the targets of SENP5. Patient-derived organoids (PDO) and xenograft (PDX) models were used to explore the possibility of clinical application. RESULTS: We identified SENP5 as a potent radioresistant gene through high content screening and CRC patients tissue array analysis. Patients with high SENP5 expression showed increased resistance to radiotherapy. In vitro and in vivo experiments demonstrated that SENP5 knockdown significantly increased radiosensitivity in CRC cells. SENP5 was further demonstrated essential for efficient DNA damage repair in homologous recombination (HR) dependent manner. Through SUMO mass spectrometry analysis, we characterized H2AZ as a deSUMOylation substrate of SENP5, and depicted the SUMOylation balance of H2AZ in HR repair and cancer resistance. By using PDO and PDX models, we found targeting SENP5 significantly increased the therapeutic efficacy of radiotherapy. CONCLUSION: Our findings revealed novel role of SENP5 in HR mediated DNA damage repair and cancer resistance, which could be applied as potent prognostic marker and intervention target for cancer radiotherapy.


Assuntos
Neoplasias Colorretais , Proteômica , Humanos , Reparo de DNA por Recombinação , Recombinação Homóloga , Neoplasias Colorretais/genética , Neoplasias Colorretais/radioterapia , Dano ao DNA
2.
J Cell Mol Med ; 27(23): 3839-3850, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37723905

RESUMO

Radiation-induced lung injury (RILI), divided into early radiation pneumonia (RP) and late radiation-induced pulmonary fibrosis (RIPF), is a common serious disease after clinical chest radiotherapy or nuclear accident, which seriously threatens the life safety of patients. There has been no effective prevention or treatment strategy till now. Epithelial-mesenchymal transition (EMT) is a key step in the occurrence and development of RILI. In this study, we demonstrated that emetine dihydrochloride (EDD) alleviated RILI through inhibiting EMT. We found that EDD significantly attenuated EMT-related markers, reduced Smad3 phosphorylation expression after radiation. Then, for the first time, we observed EDD alleviated lung hyperaemia and reduced collagen deposit induced by irradiation, providing protection against RILI. Finally, it was found that EDD inhibited radiation-induced EMT in lung tissues. Our study suggested that EDD alleviated RILI through inhibiting EMT by blocking Smad3 signalling pathways. In summary, our results indicated that EDD is a novel potential radioprotector for RILI.


Assuntos
Lesão Pulmonar , Fibrose Pulmonar , Lesões por Radiação , Humanos , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/etiologia , Lesão Pulmonar/metabolismo , Emetina/farmacologia , Pulmão/patologia , Lesões por Radiação/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/metabolismo , Transição Epitelial-Mesenquimal
3.
BMC Cancer ; 23(1): 130, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36755223

RESUMO

BACKGROUND: Radiotherapy is an important treatment for lung cancer, mainly by triggering DNA double-strand breaks to induce cell death. Blocking DNA damage repair can increase the radiosensitivity of tumor cells. Recent studies have identified long noncoding RNAs as key regulators in DNA damage repair. The lncRNA ANRIL was previously shown to be involved in homologous recombination (HR) repair, but its specific mechanism has not been fully elucidated. METHODS: The downstream interacting miRNAs of ANRIL were predicted according to miRanda software. Fluorescence quantitative PCR was used to detect the expression levels of ANRIL and candidate miRNAs. Clone formation experiment and cell viability assays detect cell viability after ionizing radiation. Apoptosis assay was used to detect the apoptosis of cells after 8 h of ionizing radiation. Western blot analysis and immunofluorescence assays verified the protein expression levels of the downstream target molecule PARP1 of miR-7-5p and key molecules in the HR pathway. Fluorescent reporter gene experiments were used to verify the interaction between ANRIL and miR-7-5p and between miR-7-5p and PARP1. RESULTS: Bioinformatics analysis and qPCR validation suggested that miR-7-5p might be a downstream molecule of ANRIL. The expression of miR-7-5p was up-regulated after knockdown of ANRIL, and the expression of miR-7-5p was down-regulated after overexpression of ANRIL. Meanwhile, there was a negative correlation between ANRIL and miR-7-5p expression changes before and after ionizing radiation. The luciferase reporter gene assay confirmed the existence of ANRIL binding site with miR-7-5p, and found that transfection of miR-7-5p inhibitor can reduce the radiation sensitivity of ANRIL-KD cells. A downstream target molecule of miR-7-5p related to HR repair, PARP1, was screened through website prediction. Subsequently, it was confirmed by Western blot and luciferase reporter assays that miR-7-5p could down-regulate the expression of PARP1, and there was a miR-7-5p binding site on the 3'UTR of PARP1 mRNA. This suggests that ANRIL may act as a competitive endogenous RNA to bind miR-7-5p and upregulate the expression of PARP1. Western blot and immunofluorescence staining were used to detect the expression changes of HR repair factors in ANRIL-KD cells after ionizing radiation, and it was found that knockdown of ANRIL can inhibit the expression of PARP1, BRCA1 and Rad51, hinder radiation-induced HR repair, and eventually result in resensitizing ANRIL-KD cells to ionizing radiation. CONCLUSIONS: Our findings provide evidence that ANRIL targets the miR-7-5p/PARP1 axis to exert its regulatory effect on HR repair, suggesting that altering ANRIL expression may be a promising strategy to overcome radiation resistance.


Assuntos
Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Reparo do DNA/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , MicroRNAs/metabolismo , Poli(ADP-Ribose) Polimerase-1/genética , Poli(ADP-Ribose) Polimerase-1/metabolismo , Reparo de DNA por Recombinação , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
4.
J Gene Med ; 25(3): e3470, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36537017

RESUMO

DNA double-strand breaks can seriously damage the genetic information that organisms depend on for survival and reproduction. Therefore, cells require a robust DNA damage response mechanism to repair the damaged DNA. Homologous recombination (HR) allows error-free repair, which is key to maintaining genomic integrity. Long non-coding RNAs (lncRNAs) are RNA molecules that are longer than 200 nucleotides. In recent years, a number of studies have found that lncRNAs can act as regulators of gene expression and DNA damage response mechanisms, including HR repair. Moreover, they have significant effects on the occurrence, development, invasion and metastasis of tumor cells, as well as the sensitivity of tumors to radiotherapy and chemotherapy. These studies have therefore begun to expose the great potential of lncRNAs for clinical applications. In this review, we focus on the regulatory roles of lncRNAs in HR repair.


Assuntos
RNA Longo não Codificante , Reparo de DNA por Recombinação , RNA Longo não Codificante/genética , Reparo do DNA , Dano ao DNA , Recombinação Homóloga , DNA
5.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(6): 665-670, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34296683

RESUMO

OBJECTIVE: To evaluate the clinical value of neutrophil/lymphocyte ratio (NLR) in early prediction of the incidence of sepsis-induced organ dysfunction and 28-day mortality. METHODS: A retrospective study was conducted in 815 adult patients with sepsis admitted to the department of critical care medicine of the First Affiliated Hospital of China Medical University from January 2017 to December 2019. The clinical data including age, gender and complication were collected, and the peripheral blood routine indexes at 24, 48 and 72 hours after the diagnosis of sepsis were collected, and the NLR was calculated. The primary endpoint of the study was the incidences of sepsis related acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC) and acute liver failure (ALF); the secondary endpoint was the 28-day in-hospital mortality in septic patients with organ dysfunction. Univariate and multivariate Logistic regression were used to analyze the risk factors of organ dysfunction and 28-day mortality in patients with sepsis, the receiver operating characteristic curve (ROC curve) was drawn and the area under the ROC curve (AUC) was calculated to evaluate the predictive value of NLR for organ dysfunction and 28-day mortality in patients with sepsis. RESULTS: A total of 714 patients with sepsis were enrolled for final statistical analysis. There was no significant difference in NLR at 24, 48 and 72 hours in patients with or without organ dysfunction (such as AKI, ARDS, DIC and ALF). Logistic regression analysis showed that there was no significant difference in NLR at 24 hours with 28-day in-hospital mortality [odds ratio (OR) = 1.006, 95% confidence interval (95%CI) was 0.994-1.019, P = 0.323]. However, NLR at 48 hours and 72 hours had a significant difference with 28-day mortality (48 hours: OR = 1.026, 95%CI was 1.013-1.040, P = 0.000; 72 hours: OR = 1.021, 95%CI was 1.005-1.037, P = 0.010), which suggested that NLR at 48 hours and 72 hours after diagnosis were independent risks factor for 28-day mortality in patients with sepsis. ROC curve showed that the AUC of NLR at 48 hours was 0.598, 95%CI was 0.540-0.658, P = 0.02; when the cut-off value was 10.1, the sensitivity and specificity for predicting 28-day mortality was 75.2% and 58.0%, respectively; the AUC of NLR at 72 hours was 0.595, 95%CI was 0.536-0.655, P = 0.03; when the cut-off value was 9.24, the sensitivity and specificity for predicting 28-day mortality was 75.3% and 59.9%, respectively. CONCLUSIONS: NLR cannot predict the occurrence of AKI, ARDS, DIC and ALF in sepsis in early stage. NLR has a certain clinical value in predicting 28-day mortality in patients with sepsis, but its predictive efficiency is low.


Assuntos
Neutrófilos , Sepse , Adulto , China/epidemiologia , Humanos , Incidência , Linfócitos , Insuficiência de Múltiplos Órgãos , Prognóstico , Curva ROC , Estudos Retrospectivos
6.
J Cancer ; 11(13): 3834-3845, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32328188

RESUMO

Background: Many indicators of peripheral blood in routine blood test (BRT) results of colorectal cancer (CRC) patients are related to prognosis. Currently, indexes such as NLR (Neutrophil-to- Lymphocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio) and LMR (Lymphocyte-to-Monocyte ratio) evaluate the survival risk of patients by assessing the inflammatory - immune status of CRCs. These indexes are more comprehensive and accurate than independent estimates. We hope to design more effective indexes through fully considering the correlation and significance between BRT indicators and prognosis, so as to play a guiding role in clinical malignant estimation of CRCs. Methods: 701 CRCs in training set and 256 CRCs in test set were included in the study samples, and their clinical data, tumor pathology results and peripheral blood routine results were collected. The prognosis, progression, and survival status of all patients were determined after follow-up. Above data were used for statistical analysis and designing new indexes. Results: It was found that high NE, MONO, RDW-CV/SD and PLT in peripheral blood indicated poor prognosis of DFS and OS. Conversely, CRCs with postoperative tumor progression or death had lower LY, EO, RBC, HGB, HCT, MCV, MCH, MCHC, PDW, and P-LCR. IRR, ARR and CRR related to infection, anemia and coagulation were designed respectively using the largest AUC indicators (P<0.05) selected by ROC curve. The formula: IRR= (NE*MONO)/(LY*EO); ARR= (HGB*MCHC)/RDW-CV; CRR=PLT/PDW. Results of Kaplan­Meier survival analysis and multivariate COX proportional hazard analysis adjusted for age, gender, TNM stage, infiltration, adhesion showed IRR, ARR, CRR were all able to be used as the evaluation standard of survival of CRC. The result was also authenticated in the test set. Conclusion: We designed three different prognostic indexes of colorectal cancer, IRR, ARR and CRR, which could be used as risk indicators of CRC prognosis, tumor progression and survival.

7.
World J Gastroenterol ; 25(32): 4739-4748, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31528098

RESUMO

BACKGROUND: Severe acute pancreatitis (SAP) is a common condition in the intensive care unit (ICU) and has a high mortality. Early evaluation of the severity and prognosis is very important for SAP therapy. Recently, red blood cell distribution (RDW) was associated with mortality of sepsis patients and could be used as a predictor of prognosis. Similarly, RDW may be associated with the prognosis of SAP patients and be used as a prognostic indicator for SAP patients. AIM: To investigate the prognostic value of RDW for SAP patients. METHODS: We retrospectively enrolled SAP patients admitted to the ICU of the First Affiliated Hospital of China Medical University from June 2015 to June 2017. According to the prognosis at 90 d, SAP patients were divided into a survival group and a non-survival group. RDW was extracted from a routine blood test. Demographic parameters and RDW were recorded and compared between the two groups. The receiver operator characteristic (ROC) curve was constructed and Cox regression analysis was performed to investigate the prognostic value of RDW for SAP patients. RESULTS: In this retrospective cohort study, 42 SAP patients were enrolled, of whom 22 survived (survival group) and 20 died (non-survival group). The baseline parameters were comparable between the two groups. The coefficient of variation of RDW (RDW-CV), standard deviation of RDW (RDW-SD), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Sequential Organ Failure Assessment (SOFA) score were significantly higher in the non-survival group than in the survival group (P < 0.05). The RDW-CV and RDW-SD were significantly correlated with the APACHE II score and SOFA score, respectively. The areas under the ROC curves (AUCs) of RDW-CV and RDW-SD were all greater than those of the APACHE II score and SOFA score, among which, the AUC of RDW-SD was the greatest. The results demonstrated that RDW had better prognostic value for predicting the mortality of SAP patients. When the RDW-SD was greater than 45.5, the sensitivity for predicting prognosis was 77.8% and the specificity was 70.8%. Both RDW-CV and RDW-SD could be used as independent risk factors to predict the mortality of SAP patients in multivariate logistic regression analysis and univariate Cox proportional hazards regression analysis, similar to the APACHE II and SOFA scores. CONCLUSION: The RDW is greater in the non-surviving SAP patients than in the surviving patients. RDW is significantly correlated with the APACHE II and SOFA scores. RDW has better prognostic value for SAP patients than the APACHE II and SOFA scores and could easily be used by clinicians for the treatment of SAP patients.


Assuntos
Índices de Eritrócitos , Pancreatite/mortalidade , Adulto , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pancreatite/sangue , Pancreatite/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença
8.
J Cancer ; 10(5): 1162-1170, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30854125

RESUMO

Background: Colorectal cancer is one of the common tumors that seriously threaten human health worldwide. Serum tumor markers, including CEA and CA19-9, have become the focus of research on colorectal cancer in recent years. As one of the classic blood test results, RDW is related to the pathological features, diagnosis and prognosis of various cancers in recent studies. We hope to search the correlation between RDW and the pathological features of colorectal cancer through the following studies, explore the potential relationship between RDW and the prognosis of colorectal cancer, and find a more effective prognostic evaluation method by combining other blood markers. Methods: We retrospectively analyzed 168 patients with colorectal cancer included in this study, collected their clinical data, tumor pathological features and their preoperative blood test results including RDW value and tumor markers, and grouped them. After 3 and 5 years of follow-up, the recurrence and survival status were defined, and the above data were statistically analyzed. Results: The distribution frequency/rate of abnormal RDW-CV in colorectal cancer patients was significantly increased in the elderly (>62), colon cancer, serosal permeability, lymph node metastasis, stage III and IV, peripheral adhesion (P < 0.05). Furthermore, RDW-CV was significantly positively correlated with abnormal high values of tumor serum markers CEA and CA19-9 (P < 0.05). More importantly, ROC curve analysis found that the abnormal increase in RDW-CV in colorectal cancer was associated with the shortening of DFS and OS in patients who were followed up for 3 and 5 years (P < 0.05). Further combined with CEA, it was found that the prognosis and survival of patients with colorectal cancer in 3 and 5 years were more accurate and effective than independent prediction (AUC of DFS in 3/5years=0.630/0.635, AUC of OS in 3/5 years=0.692/0.652). Conclusion: RDW-CV is correlated with the pathological features of colorectal cancer, indicating a worse malignant tendency of tumor. RDW-CV can independently evaluate the prognosis of colorectal cancer patients, and combined with the high value of CEA, it can effectively indicate the adverse recurrence and survival prognosis.

9.
Oncol Rep ; 40(3): 1706-1724, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30015936

RESUMO

The expression levels of microRNA­31 (miR­31) and LOC554202 have been previously investigated in colorectal cancer (CRC) and their oncogenic and/or tumor suppressive roles have been described. The aim of the present study was to examine the role of miR­31 and its host gene LOC554202 in the prognosis of patients with CRC. Patients with CRC treated with oxaliplatin­based chemotherapy between June 2005 and March 2010 were recruited to the First Affiliated Hospital of China Medical University. Tumor and adjacent mucosal tissues were collected. The detection of miR­31 and/or LOC554202 was performed with probe hybridization targeting. Correlation analysis was performed among the expression levels of miR­31, LOC554202, and their association with clinicopathological parameters and/or survival rates. miR­31 and LOC554202 were expressed at high levels in CRC (P<0.01) compared with adjacent intestinal mucosa. A linear correlation was noted for the two markers in CRC tissues (P<0.01). The expression of miR­31 was significantly higher in adenocarcinoma than in the adjacent intestinal mucosa (P<0.01), whereas the expression of LOC554202 was significantly higher in the adenocarcinoma and the rectal cancer tissue regions (P<0.01). The high expression levels of miR­31 and LOC554202 were associated with high disease­free survival (DFS) and overall survival (OS) rates (P<0.05). Associations between the increase in DFS and OS and the elevated expression levels of miR­31 and LOC554202 were present in patients with colon cancer but not in patients with rectal cancer (P<0.05). These data indicated that miR­31 and LOC554202 may be potential markers for evaluation of the prognosis of patients treated with oxaliplatin­based chemotherapy.


Assuntos
Adenocarcinoma/mortalidade , Biomarcadores Tumorais/genética , Neoplasias Colorretais/mortalidade , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , Compostos Organoplatínicos/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina , Prognóstico , Taxa de Sobrevida , Adulto Jovem
10.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 29(8): 752-755, 2017 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-28795678

RESUMO

OBJECTIVE: Neutrophil extracellular traps (NETs) are net-like structure composed of DNA and nuclear proteins, which are produced by activated neutrophils under the circumstances of a variety of pathogens or drugs. As part of defensive mechanism, NETs have been proved to restrict the spread of pathogens and release of antimicrobial molecules. NETs can not only strengthen the adhesion between neutrophils and platelets, promote platelet mediated procoagulant reaction, but also lead to endothelial cell damage and coagulopathy in sepsis. In addition, NETs also plays an important role in pathophysiological processes of venous thrombosis. Therefore, NETs may become the biomarkers of evaluating coagulation dysfunction and potential therapy target in sepsis.


Assuntos
Transtornos da Coagulação Sanguínea , Armadilhas Extracelulares , Sepse/fisiopatologia , Plaquetas , Humanos , Neutrófilos
11.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 29(2): 122-126, 2017 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-28625258

RESUMO

OBJECTIVE: To investigate the changes of neutrophil extracellular traps (NETs) level in plasma of sepsis patients and judge its clinical value for early diagnosing of sepsis. METHODS: A prospective observational study was conducted. The patients after surgery aged > 18 years and expected to stay in the ICU > 24 hours admitted to intensive care unit (ICU) of the First Affiliated Hospital of China Medical University from November 2014 to February 2015 were enrolled. According to the criteria of sepsis diagnosis in 1991, patients were divided into non-sepsis group and sepsis group. The healthy people who taken a physical examination were enrolled in the healthy control group. 3 mL peripheral venous blood was collected at 1 hour after admission to ICU. A fasting blood was collected in the healthy control group in the morning. The plasma free DNA (cf-DNA/NETs) was determined by using the fluorescence microplate reader, white blood cell (WBC), neutrophil ratio (NEU), procalcitonin (PCT), C-reactive protein (CRP) in peripheral blood of the patients were detected, and acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores were calculated. The correlation between plasma NETs and the risk factors in sepsis patients was analyzed by Spearman correlation analysis. The value of cf-DNA/NETs and WBC level in the diagnosis of sepsis was analyzed by using the receiver operating characteristic curve (ROC). RESULTS: Twenty-three sepsis patients, 20 non-sepsis patients, and 22 healthy persons were enrolled. There were no differences in baseline variables including gender and age among three groups, which indicated baseline data equalization. The plasma concentration of cf-DNA/NETs in sepsis group was significantly higher than that in non-sepsis group and healthy control group (µg/L: 453.44±185.37 vs. 188.35±29.66, 203.83±43.25, both P < 0.05), and there was no significant difference between last two groups (P > 0.05). WBC, NEU, PCT, CRP, APACHE II and SOFA score in sepsis group were significantly higher than those of non-sepsis group [WBC (×109/L): 9.52±5.51 vs. 5.97±2.28, NEU: 0.787±0.110 vs. 0.655±0.067, PCT (mg/L): 7.14 (3.60, 13.29) vs. 6.07 (3.57, 7.91), CRP (mg/L): 64.44±13.14 vs. 27.00±19.47, APACHE II: 10.25±4.92 vs. 6.00±1.22, SOFA: 6.0±5.1 vs. 5.0±1.2, all P < 0.05]. Correlation analysis showed that the level of NETs had no obvious correlation with gender, age, WBC, NEU, PCT, CRP, APACHE II and SOFA scores (r value was 0.322, 0.262, 0.194, 0.312, 0.227, 0.454, 0.433, 0.333, respectively, all P > 0.05). The area under the ROC curve (AUC) of plasma cf-DNA/NETs for the diagnosis of sepsis was 0.981. When the cut-off value of plasma cf-DNA/NETs was > 257.96 µg/L, the sensitivity was 91.3%, specialty was 95.2%, and Youden index was 0.865. AUC of WBC in the diagnosis of sepsis was 0.663. When the cut-off value of WBC was > 6.0×109/L, the sensitivity was 78.3% and specificity was 25.0%. CONCLUSIONS: The plasma cf-DNA/NETs levels increased significantly in sepsis patients. In the diagnosis of sepsis, plasma NETs levels had better advantages over WBC. NETs can be used as a biomarker for early diagnosis of sepsis.


Assuntos
Armadilhas Extracelulares , Proteína C-Reativa , Calcitonina , Peptídeo Relacionado com Gene de Calcitonina , China , Humanos , Prognóstico , Estudos Prospectivos , Precursores de Proteínas , Curva ROC , Sepse
12.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 29(4): 337-341, 2017 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-28420468

RESUMO

OBJECTIVE: To investigate the influence of heparin pretreatment on serum and lung tissue level of neutrophil extracellular traps (NETs) in septic mice model and its molecular mechanism. METHODS: Ninety male C57BL/6J mice were randomly divided into control group (n = 30), lipopolysaccharides (LPS) group (n = 30, 30 mg/kg LPS in 100 ?L normal saline was intraperitoneally injected) and LPS+heparin group (n = 30, 8 U of heparin in 20 ?L normal saline was subcutaneously injected 30 minutes before the injection of LPS). Six hours later of LPS injection, blood was collected and lung tissue was harvested. Enzyme linked immunosorbent assay (ELISA) was used to assess the concentration of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and histones 2AX (H2AX), neutrophil elastase (NE), which reflected NETs concentration. PicoGreen fluorescent dyes was used to detect serum circulating free DNA (cf-DNA/NETs) concentration. The protein expression levels of H2AX and NE in lung tissue were examined by Western Blot. RESULTS: The serum concentrations of TNF-α, IL-6, H2AX, NE, cf-DNA/NETs, and the protein expression levels of H2AX and NE in lung tissue of septic mice were significantly higher than those of control group [TNF-α (ng/L): 133.0±14.1 vs. 2.7±1.0, IL-6 (ng/L): 3 911.2±189.2 vs. 298.9±52.5, H2AX (ng/L): 545.5±40.0 vs. 21.9±8.3, NE (µg/L): 6.48±0.12 vs. 0.47±0.15, cf-DNA/NETs (µg/L): 846.3±137.5 vs. 152.7±36.4, H2AX protein (gray value): 1.14±0.09 vs. 0.68±0.04, NE protein (gray value): 0.56±0.03 vs. 0.32±0.04, all P < 0.05]. After heparin pretreatment, levels of serum TNF-α, H2AX, NE, cf-DNA/NETs, and protein expression levels of H2AX and NE in lung tissue were significantly reduced [TNF-α (ng/L): 83.2±7.6 vs. 133.0±14.1, H2AX (ng/L): 435.0±39.0 vs. 545.5±40.0, NE (µg/L): 4.26±0.17 vs. 6.48±0.12, cf-DNA/NETs (µg/L): 606.5±73.9 vs. 846.3±137.5, H2AX protein (gray value): 0.91±0.03 vs. 1.14±0.09, NE protein (gray value): 0.42±0.03 vs. 0.56±0.03, all P < 0.05], but no significant change was found in IL-6 (ng/L: 3 919.9±166.6 vs. 3 911.2±189.2, P > 0.05). CONCLUSIONS: Heparin pretreatment could significantly decrease the level of NETs in serum and lung tissue, and can be the potential mechanism of its organ protection in sepsis.


Assuntos
Armadilhas Extracelulares , Animais , Heparina , Interleucina-6 , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa
13.
Front Psychol ; 7: 660, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27242579

RESUMO

People have a greater desire to date highly attractive partners, which induces intrasexual competition between same-sex individuals. The present study used functional magnetic resonance imaging to explore whether and how intrasexual competition modulates pain empathy for a same-sex rival and the underlying neural mechanism. Participants were scanned while processing the pain of a same-sex 'lucky guy' who had an attractive partner and one with a plain partner. The results revealed that participants reported lower pain intensity for the lucky guy. Neurally, reduced pain-related activations in anterior insula and anterior mid-cingulate cortex and increased activations in right superior frontal gyrus (SFG) and medial prefrontal gyrus (MPFC) were found for the lucky guy compared to the one with a plain partner. Right SFG and MPFC activations could predict participants' subsequent pain intensity ratings for the lucky guy. These findings suggest intrasexual competition can modulate normal empathic responses.

14.
Exp Ther Med ; 10(4): 1293-1296, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26622480

RESUMO

Nitrogen mustards are chemical agents that are similar to sulfur mustards, with similar toxicities. The present study describes a case of nitrogen mustard-induced acute respiratory failure and myelosuppression in a 33-year-old man. The patient, who was accidentally exposed to nitrogen mustard hydrochloride in a pharmaceutical factory, exhibited severe inhalation injury and respiratory symptoms. Laboratory tests revealed reduced white blood cell counts and lowered platelet levels during the first 6 days after the skin exposure to nitrogen mustard. Following treatment with mechanical ventilation, immunity-enhancing agents and nutritional supplements for 1 month, the patient successfully recovered and was released from hospital.

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