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1.
Zhonghua Xue Ye Xue Za Zhi ; 42(6): 502-507, 2021 Jun 14.
Artigo em Chinês | MEDLINE | ID: mdl-34384157

RESUMO

Objective: To observe the efficacy and safety of humanized anti-BCMA chimeric antigen receptor modified (BCMA CAR) -T cell therapy after disease progression with their murine BCMA CAR-T cell therapy in patients with relapsed/refractory multiple myeloma (MM) . Methods: Study participants underwent leukapheresis to collect T cells for BCMA CAR-T manufacturing. Patients were pretreated with intensive chemotherapy (fludarabine combined with cytarabine) before CAR-T therapy. Adverse events (AEs) , CAR DNA expansion, and cytokine were monitored. In vitro, transfection efficacy, specific cytotoxicity, and inflammatory response were detected when co-cultured with effector and target cells. Results: Patient (PT) 1 and 2 achieved complete remission (CR) and disease stability at 3 months post murine CAR-T therapy. However, 16 and 18 months later, they experienced progression of disease (PD) , and patient 1 presented with extramedullary disease at PD. Both of the patients received humanized CAR-T therapy and achieved partial remission (PR) and very good partial remission (VGPR) post humanized CAR-T therapy. PT1 achieved CR of the soft tissue masses at 4 months post humanized CAR-T therapy. Notably, the median peak of the BCMA CAR-T cells, copy of BCMA CAR gene, persistence of BCMA CAR-T, and the peak levels of IL-6, IL-8, IL-10, IFN-γ and TNF-α were higher in humanized CAR-T therapy than those in the murine CAR-T therapy. During the murine CAR-T therapy, both of the patients experienced grade 1 CRS and no ICANS. PT1 experienced grade 3 CRS and grade 2 ICANS during humanized CAR-T therapy, which were relieved by supportive care. Grade 2 CRS was observed for patient 2 during humanized CAR-T therapy. Humanized BCMA CAR-T cells showed a higher inflammatory response and in vitro cytotoxicity than that of murine BCMA CAR-T cells with effector/targets cells at 1∶1 over 48 hours (P<0.001) . The proportions of residual cells in humanized BCMA CAR-T and murine CAR-T were (17.38±5.18) % vs (28.27±4.58) %, (13.25±1.62) % vs (22.77±1.77) % for PT1 and PT2, respectively. Conclusions: The humanized BCMA CAR-T cell therapy was efficient and safe for patients who experienced progression of disease after the murine CAR-T therapy, especially for patients with extramedullary disease.


Assuntos
Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Animais , Antígeno de Maturação de Linfócitos B , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Imunoterapia Adotiva , Camundongos , Mieloma Múltiplo/terapia , Terapia de Salvação , Linfócitos T
3.
Eur Rev Med Pharmacol Sci ; 25(9): 3398, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34002807

RESUMO

The article "LINC00346 accelerates the malignant progression of colorectal cancer via competitively binding to miRNA-101-5p/MMP9, by W.-H. Tong, J.-F. Mu, S.-P. Zhang, published in Eur Rev Med Pharmacol Sci 2020; 24 (12): 6639-6646-DOI: 10.26355/eurrev_202006_21650-PMID: 32633353" has been withdrawn from the authors since they decided to perform further experiments. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21650.

4.
Zhonghua Xue Ye Xue Za Zhi ; 42(2): 140-145, 2021 Feb 14.
Artigo em Chinês | MEDLINE | ID: mdl-33858045

RESUMO

Objective: To investigate the characteristics and cytotoxicity in vitro of the residual leukemia cells in the culture system that caused the accidental transfer of CD19 chimeric antigen receptor (CAR) into leukemia cells during the preparation of autologous CD19 CAR-T cells of relapsed/refractory B-cell acute lymphoblastic leukemia. Methods: ①Peripheral blood mononuclear cells (PBMC) of 30 patients with relapsed/refractory B-cell acute lymphoblastic anemia (R/R B-ALL) who accepted CD19 CAR-T cell therapy and six healthy volunteers were collected. ②The residual leukemia cells were analyzed by flow cytometry in the system after the PBMCs of R/R B-ALL patients were sorted by CD3 magnetic beads. ③ CD3(+) T cells from patients and healthy volunteers were transfected with CD19 CAR and CD22 CAR lentivirus to prepare CD19 CAR-T and CD22 CAR-T cells. ④The Nalm-6 cell line was resuscitated and the Nalm-6 cells with CD19 CAR lentivirus were transfected to prepare CD19 CAR-Nalm-6 cells. The patient's primary ALL cells were transfected with CD19 CAR lentivirus at the same time. ⑤The transfection rates were analyzed by flow cytometer, the cell proliferation was analyzed by the CCK-8 method, and the cell-killing activities were detected by the lactate dehydrogenase method. Results: ① Among the 30 R/R B-ALL patients who received CD19 CAR-T cell therapy, two patients had 2.04% and 3.32% residual leukemia cells in CD3(+) T cells. After 4 days in culture, the residual leukemia cells disappeared and could not be detected by a flow cytometer with prolonged cultivation in vitro. ② The proliferation of CD19 CAR-Nalm-6 cells was higher than that of the Nalm-6 cells. ③ The killing activity of the CD19 CAR-T cells on Nalm-6 cells was higher than that of the CD19 CAR-Nalm6 cells at a target ratio of 1∶1 on 24, 48, 72 h, respectively. The cytotoxicity of CD22 CAR-T cells on CD19 CAR-Nalm-6 cells was significantly higher than that of CD19 CAR-T cells. ④ The cytotoxicity of CD22 CAR-T alone on CD19 CAR-Nalm-6 cells was higher than that of CD19 CAR-T combined with CD22 CAR-T at the same target ratio. Conclusion: The residual leukemia cells in the culture system in the preparation of CD19 CAR-T cells may lead to the introduction of CD19 CAR into leukemia cells and results in the failure of the CD19 CAR-T cell therapy. Detecting the residual leukemia cells in the culture system via flow cytometry before transfection with CD19 CAR lentivirus is needed. Thus, CD22 CAR-T cell therapy could be used as one of the salvage treatments.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Antígenos CD19 , Linfócitos B , Humanos , Imunoterapia Adotiva , Leucócitos Mononucleares , Linfócitos T
5.
Clin Radiol ; 76(6): 471.e17-471.e25, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33663913

RESUMO

AIM: To investigate the value of motion-corrected (MOCO) phase-sensitive inversion recovery (PSIR) late gadolinium enhancement (LGE) compared with single-shot balanced steady-state gradient echo ("TrueFISP", Siemens) PSIR in free breathing paediatric patients. MATERIALS AND METHODS: In this retrospective study, 238 paediatric patients underwent clinical contrast-enhanced cardiovascular magnetic resonance imaging (CMRI). Both the single-shot TrueFISP PSIR and MOCO PSIR sequences were performed on each child. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Two radiologists rated the quality of the images on a scale of 1-5 (1 = poor, 5 = very good). Bland-Altman, linear regression, and intraclass correlation coefficient were used to compared the extent of LGE of the single-shot TrueFISP PSIR and MOCO PSIR. Imaging artefacts were described and compared. RESULTS: Children ranged in age from 60 days to 17 years with an average age of 8.1 ± 3.8 years. MOCO PSIR had higher SNR and CNR than the single-shot TrueFISP PSIR (p<0.001). Mean quality ratings for short-axis imaging were 4 (interquartile range, 3-4) for single-shot TrueFISP PSIR and 4 (interquartile range, 4-5) for MOCO PSIR (p<0.001). The scan time was faster for single-shot TrueFISP PSIR than for MOCO PSIR. The myocardial LGE results were similar with high agreement between the single-shot TrueFISP PSIR and MOCO PSIR (ICC = 0.955-0.986). CONCLUSION: The MOCO PSIR sequence is feasible in children. MOCO PSIR is robust at high heart rates and can be performed without breath-holding with higher image-quality ratings than the single-shot TrueFISP PSIR.


Assuntos
Meios de Contraste , Gadolínio , Cardiopatias/diagnóstico por imagem , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Coração/diagnóstico por imagem , Humanos , Lactente , Masculino , Respiração , Estudos Retrospectivos
6.
Zhonghua Gan Zang Bing Za Zhi ; 29(2): 137-142, 2021 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-33685082

RESUMO

Objective: To investigate the safety and efficacy of voriconazole in the patients with cirrhosis at Child-Pugh C stage complicated by invasive fungal infection(IFI). Methods: A retrospective collection of medical records of 76 patients with cirrhosis at Child-Pugh C stage complicated by IFI who were admitted to our hospital, from August 2014 to August 2017 was carried out. All the 76 patients who used voriconazole to treat IFI were divided into recommended dose group for hepatic insufficiency(56 cases) and routine dose group(20cases). The two groups were observed and compared in terms of the voriconazole's plasma concentrations, the outcomes of IFI and the rate of untoward reactions. The liver functional indicators were also compared between before and after treatment each group. We used Student's t test, Z test, chi-square test, or Fisher's exact test, as appropriate, for statistical analysis. Results: Both groups had good performance and low frequencies of side effects in the treatment of IFI, but there were also significant differences in the plasma concentrations of voriconazole and the incidence of untoward reactions between the two groups(P = 0.008 and P = 0.022). There commended dose group for hepatic insufficiency had lower adverse effect rate. The levels of direct bilirubin, alanine aminotransferase and aspartate aminotransferase were significantly lower after treatment of IFI in the recommended dose group for hepatic insufficiency(P < 0.05). Conclusion: In our research, it is relatively safe and effective to use voriconazole to treat IFI in the patients with cirrhosis at Child-Pugh C stage if according to the recommended dose regimen for cirrhosis at Child-Pugh A,B stage.


Assuntos
Antifúngicos , Infecções Fúngicas Invasivas , Antifúngicos/uso terapêutico , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Estudos Retrospectivos , Voriconazol/uso terapêutico
7.
Zhonghua Bing Li Xue Za Zhi ; 49(11): 1120-1125, 2020 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-33152815

RESUMO

Objective: To establish an artificial intelligence (AI)-assisted diagnostic system for lung cancer via deep transfer learning. Methods: The researchers collected 519 lung pathologic slides from 2016 to 2019, covering various lung tissues, including normal tissues, adenocarcinoma, squamous cell carcinoma and small cell carcinoma, from the Beijing Chest Hospital, the Capital Medical University. The slides were digitized by scanner, and 316 slides were used as training set and 203 as the internal test set. The researchers labeled all the training slides by pathologists and establish a semantic segmentation model based on DeepLab v3 with ResNet-50 to detect lung cancers at the pixel level. To perform transfer learning, the researchers utilized the gastric cancer detection model to initialize the deep neural network parameters. The lung cancer detection convolutional neural network was further trained by fine-tuning of the labeled data. The deep learning model was tested by 203 slides in the internal test set and 1 081 slides obtained from TCIA database, named as the external test set. Results: The model trained with transfer learning showed substantial accuracy advantage against the one trained from scratch for the internal test set [area under curve (AUC) 0.988 vs. 0.971, Kappa 0.852 vs. 0.832]. For the external test set, the transferred model achieved an AUC of 0.968 and Kappa of 0.828, indicating superior generalization ability. By studying the predictions made by the model, the researchers obtained deeper understandings of the deep learning model. Conclusions: The lung cancer histopathological diagnostic system achieves higher accuracy and superior generalization ability. With the development of histopathological AI, the transfer learning can effectively train diagnosis models and shorten the learning period, and improve the model performance.


Assuntos
Aprendizado Profundo , Neoplasias Pulmonares , Inteligência Artificial , Bases de Dados Factuais , Humanos , Neoplasias Pulmonares/diagnóstico , Redes Neurais de Computação
8.
Eur Rev Med Pharmacol Sci ; 24(21): 11105-11113, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33215427

RESUMO

OBJECTIVE: Previous studies have shown that the function of miR-141 has tissue specificity. However, the role of miR-141-3p has not been reported in nasopharyngeal carcinoma (NPC). Therefore, this study explored the function of miR-141-3p in NPC. PATIENTS AND METHODS: MiR-141-3p expression in NPC tissues was examined via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay. Cell Counting Kit-8 (CCK-8) and transwell assays were used to explore the function of miR-141-3p. The relationship between miR-141-3p and DLC1 was verified by Dual-Luciferase assay. Protein expression was observed by immunocytochemical assay and Western blot analysis. RESULTS: Upregulation of miR-141-3p associated with poor prognosis was detected in NPC patients. Moreover, overexpression of miR-141-3p promoted cell proliferation, migration, and invasion in NPC cells. It was also found that miR-141-3p promoted EMT and activated the mTOR signaling pathway in NPC. Furthermore, DLC1 was indicated as a direct target of miR-141-3p and miR-141-3p negatively correlated with DLC1 expression in NPC. In particular, upregulation of DLC1 could impair the promoted effect of miR-141-3p in NPC. CONCLUSIONS: MiR-141-3p promotes the progression of NPC by targeting DLC1 and activating the mTOR pathway.


Assuntos
Proteínas Ativadoras de GTPase/metabolismo , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Células Cultivadas , Feminino , Proteínas Ativadoras de GTPase/genética , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Proteínas Supressoras de Tumor/genética
9.
Zhonghua Wai Ke Za Zhi ; 58(9): 697-706, 2020 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-32878417

RESUMO

Objective: To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China. Methods: This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to Ⅰ, whereas 1 059 (30.02%) in stage Ⅱ to Ⅲ, 1 874 (53.12%) in stage Ⅳ, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed. Results: Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn't be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage ⅣB tumor without surgery was 5.4%, and for patients with stage ⅣB tumor underwent palliative surgery was 4.7%. Conclusions: More than half GBC patients in China are diagnosed in stage Ⅳ.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.


Assuntos
Neoplasias da Vesícula Biliar/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
10.
Eur Rev Med Pharmacol Sci ; 24(17): 9030-9040, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32964993

RESUMO

OBJECTIVE: Arterial stiffness may be an early marker for vascular changes associated with hypertension in young adults. Individuals with a family history of hypertension are at high risk of developing hypertension. We investigated whether arterial stiffness measured, such as mean arterial pressure (MAP) and brachial to ankle pulse wave velocity (baPWV), were increased in normotensive offspring with a parental history of hypertension. PATIENTS AND METHODS: We compared MAP and baPWV in a sample of 1953 non-hypertensive participants (974 men, mean age 42±3 years) recruited in the previous Hanzhong adolescent hypertension cohort study. Standardized questionnaires, physical examinations and laboratory tests were used to obtain information, with a particular focus on family hypertension history, anthropometric, hemodynamic, and biochemical factors. RESULTS: A total of 1039, 759, 155 participants had 0, 1, and 2 parents with hypertension, respectively. Parental hypertension was associated with elevated offspring MAP (in multivariable-adjusted models, B=1.5 mm Hg, 95% CI 0.8-2.2 for 1 parent with hypertension; B=3.0 mm Hg, 95% CI 1.8-4.3, for 2 parents with hypertension; p<0.001 for each). A significant positive correlation was also observed between MAP and baPWV (r=0.543, p<0.001). BaPWV displayed a similar correlation with parental hypertension in age-adjusted, sex-adjusted and body mass index (BMI)-adjusted models (B=23.1 cm/s, 95% CI 8.0-38.1, for 1 parent with hypertension, p<0.01; B=53.0 cm/s, 95% CI 25.8-80.2, p<0.001 for 2 parents with hypertension), but associations were attenuated in multicovariate models after adjustment for MAP. In multivariable-adjusted models, logistic regression analysis showed that the risk of belonging to the upper quartile of MAP was significantly increased for offspring whose parents had hypertension (OR=1.5, 95% CI 1.2-1.9, for 1 parent with hypertension; OR=2.3, 95% CI 1.6-3.4, for 2 parents with hypertension; p<0.001 for each). Similarly, the odds ratios of belonging to the upper quartile of baPWV increased (OR=1.3, 95% CI 1.1-1.6, for 1 parent with hypertension, p<0.05; OR=2.1, 95% CI 1.5-3.0, for 2 parents with hypertension, p<0.001, in age-sex-BMI-adjusted models), and were then brought down in the fully adjusted models including MAP, but the increase remained significant for 2 parents with hypertension (OR=1.6, 95% CI 1.0-2.3, p<0.05). CONCLUSIONS: These findings provide evidence that arterial stiffness is higher in young-to middle-aged normotensive subjects with a family history of hypertension, suggesting that increased arterial stiffness may occur in the early stages during the pathogenesis of hypertension.


Assuntos
Hipertensão/diagnóstico , Rigidez Vascular , Adolescente , Adulto , Pressão Sanguínea , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pais , Análise de Onda de Pulso
11.
Zhonghua Yan Ke Za Zhi ; 56(8): 608-614, 2020 Aug 11.
Artigo em Chinês | MEDLINE | ID: mdl-32847336

RESUMO

Objective: To explore the short-term effects of ambient PM2.5 on the outpatient visits of allergic conjunctivitis among children in Shenzhen. Methods: It was a ecological study. Data on daily visits including date of visit, sex and age from children with allergic conjunctivitis were collected from Shenzhen Eye Hospital and Shenzhen Children's Hospital in 2018. Related data on air pollution (PM2.5, PM10, SO2, NO2, CO and O3) and meteorology (atmospheric pressure, temperature and relative humidity) were also collected. Pearson correlation analysis was used for normal distribution data and Spearman rank correlation analysis was used for non-normal distribution data. Generalized additive model was used to estimate the impact of PM2.5 pollution on allergic conjunctivitis outpatients and the lagging effects. Results: In 2018, there were 16 133 allergic conjunctivitis outpatients in the two hospitals. The maximum age was 18 years and the minimum age was 2 months. Males accounted for 49.3%. The daily average concentration of PM2.5 was 22 (15, 31) µg/m3. Changes of the concentration of PM2.5 had a positive correlation with the amount of allergic conjunctivitis visits, and the Spearman correlation coefficient was 0.150 (P=0.004). The single pollutant model showed that the strongest effect appeared at 3 days (RR=1.111, 95%CI:1.071-1.152). A 10 µg/m3 increase of PM2.5 would result in an excessive number of allergic conjunctivitis outpatients as much as 11.112% (95%CI:7.011%-15.212%). In the multiple air pollutants models, after the introduction of NO2, O3 and CO, the concentration of PM2.5 showed an enhanced effect on the number of hospital visits due to allergic conjunctivitis on the same day, and the difference was statistically significant (P<0.05). Conclusion: Changes of the concentration of PM2.5 had a positive correlation with daily outpatient visits of allergic conjunctivitis among children in Shenzhen. (Chin J Ophthalmol, 2020, 56: 608-614).


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Conjuntivite Alérgica , Criança , China/epidemiologia , Humanos , Masculino , Pacientes Ambulatoriais , Material Particulado/efeitos adversos , Material Particulado/análise
12.
Eur Rev Med Pharmacol Sci ; 24(12): 6639-6646, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32633353

RESUMO

OBJECTIVE: To clarify the promotive effect of LINC00346 on the malignant progression of colorectal cancer (CRC) by mediating miRNA-101-5p/MMP9 axis. PATIENTS AND METHODS: Expression pattern of LINC00346 in 46 paired CRC tissues and adjacent normal tissues was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlation between LINC00346 level and prognosis of CRC patients was analyzed, and the LINC00346 level in CRC cell lines was examined as well. Subsequently, potential influences of LINC00346 on cellular behaviors of CRC cells were evaluated through cell counting kit-8 (CCK-8), colony formation, transwell, and wound healing assays. Finally, Dual-Luciferase reporter gene assay was conducted to verify the binding relationship between LINC00346 and miRNA-101-5p/MMP9. RESULTS: LINC00346 was upregulated in CRC tissues and cell lines. Compared with CRC patients with low level of LINC00346, those with high level suffered a poorer prognosis, and higher metastatic rates (lymph node metastasis and distant metastasis). Transfection of sh-LINC00346 attenuated proliferative, migratory, and invasive abilities of CRC cells. In addition, LINC00346 was confirmed to bind to miRNA-101-5p, and the latter was binding to MMP9. Moreover, the overexpression of miRNA-101-5p decreased colony number, viability, and numbers of migratory and invasive cells. CONCLUSIONS: LINC00346 is upregulated in CRC and correlated with metastasis and poor prognosis of CRC. LINC00346 accelerates the malignant progression of CRC via targeting miRNA-101-5p/MMP9.


Assuntos
Ligação Competitiva/fisiologia , Neoplasias Colorretais/metabolismo , Progressão da Doença , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/biossíntese , Idoso , Neoplasias Colorretais/patologia , Feminino , Células HCT116 , Células HT29 , Humanos , Masculino , Pessoa de Meia-Idade
13.
Hum Exp Toxicol ; 39(12): 1725-1736, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32672070

RESUMO

Tripartite motif-containing protein 24 (TRIM24) has currently emerged as a crucial cancer-related gene present in a wide range of human cancer types. However, the involvement of TRIM24 in acute myeloid leukemia (AML) has not been well investigated. The present study aims to investigate the significance, cellular function, and potential regulatory mechanism of TRIM24 in AML. We found that TRIM24 expression was significantly upregulated in AML compared with normal tissues. AML patients with low expression of TRIM24 had higher survival rates than those expressing TRIM24 at higher levels. High expression of TRIM24 was also detected in AML cells and its knockdown markedly restricted proliferation and promoted apoptosis in AML cells. Further investigation revealed that TRIM24 contributed to the regulation of Wnt/ß-catenin signaling, which was associated with modulating the phosphorylation status of glycogen synthase kinase-3ß (GSK-3ß). Inactivation of GSK-3ß partially reversed the TRIM24 knockdown-mediated antitumor effects observed in AML cells. Furthermore, knockdown of TRIM24 retarded the growth of AML-derived xenograft tumors in nude mice in vivo. Overall, these findings demonstrate that knockdown of TRIM24 impedes the AML tumor growth through the modulation of Wnt/GSK-3ß/ß-catenin signaling. These findings highlight the potential TRIM24 as an attractive anticancer target to treat AML.


Assuntos
Proteínas de Transporte/metabolismo , Leucemia Mieloide Aguda/metabolismo , Animais , Apoptose , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Regulação para Baixo , Técnicas de Silenciamento de Genes , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Camundongos Endogâmicos BALB C , Camundongos Nus , Prognóstico , Via de Sinalização Wnt , beta Catenina/metabolismo
14.
Zhonghua Bing Li Xue Za Zhi ; 49(6): 562-567, 2020 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-32486533

RESUMO

Objective: To investigate the clinicopathological features of non-tuberculosis mycobacterial lung disease and the role of molecular pathology in diagnosis. Methods: Forty-five formalin-fixed, paraffin embedded (FFPE) specimens were collected from the Department of Pathology, Beijing Chest Hospital from February 2016 to August 2019. The clinical, imaging and histopathologic features, bacteriologic data and morphologic characteristics of acid fast bacilli (AFB) were analyzed retrospectively. Specific gene sequence IS6110 of Mycobacterium tuberculosis (MTB) was detected by fluorescence PCR. Identification of Mycobacteria was by melting curve method. Fifty cases of pulmonary tuberculosis were selected in the same period as control. Results: The NTM lung cases included 18 cases (40.0%, 18/45) of M. intracellulare, eight cases (17.8%, 8/45) of M. xenopi, six cases (13.3%, 6/45) of M. avium, six cases (13.3%, 6/45) of M. kansasii, six cases (13.3%, 6/45) of M. chelonae and one case (2.2%, 1/45) of M. simiae. Histopathologically, there were necrotizing granulomas in 34 cases (75.6%, 34/45), non-necrotizing granuloma in one case (2.2%, 1/45) and non-granulomatous lesions in 10 cases (22.2%, 10/45). The necrosis was pink necrosis, basophilic necrosis rich in nuclear fragments and suppurative necrosis. Pulmonary TB showed more pink necrosis and basophilic necrosis, the difference was statistically significant (χ(2)=10.270, P=0.001; χ(2)=7.449, P=0.006). Seventeen cases (37.8%, 17/45) of NTM lung disease showed giant multinucleated giant cells, which were significantly different from those in pulmonary tuberculosis group (χ(2)=13.446, P<0.01). The number and morphology of AFB were also different. More AFB were found in M. intracellular cases and significant AFB were easily seen in M. kansasii infection. Conclusions: M. tuberculosis and NTM cannot be reliably differentiated by histologic features or by AFB morphology. Molecular assays are important to distinguish tuberculosis from NTM lung disease.


Assuntos
Pneumopatias , Humanos , Infecções por Mycobacterium não Tuberculosas , Micobactérias não Tuberculosas , Estudos Retrospectivos
15.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(3): 177-180, 2020 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-32164082

RESUMO

Respiratory support is a very important technique for saving severe 2019-nCoV pneumonia patients who suffering respiratory failure, which can improve oxygenation, reduce mortality. Therefore, how to reasonable using respiratory support technique is the key point that relating success or failure. In this paper, the authors introduce their experience on treating severe 2019-nCoV pneumonia, it is hopeful for current fighting against 2019-nCoV in China.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/tratamento farmacológico , Síndrome do Desconforto Respiratório/terapia , Insuficiência Respiratória/terapia , COVID-19 , China , Humanos , Pneumonia Viral/complicações , Pneumonia Viral/etiologia , Respiração Artificial , Síndrome do Desconforto Respiratório/virologia , Insuficiência Respiratória/virologia , SARS-CoV-2
16.
Zhonghua Nei Ke Za Zhi ; 59(4): 286-291, 2020 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-32209194

RESUMO

Objective: The aim of the study was to investigate the correlation between blood pressure response to cold pressor test (CPT) and follow-up blood pressure after 8 years in subjects, and to evaluate the predictive value of CPT for long-term blood pressure levels. Methods: A total of 365 individuals from eight natural villages were enrolled by stratified cluster sampling from Mei County, Shaanxi Province in 2004. Baseline characteristics of subjects were collected and CPTs were conducted. Subjects were followed up in 2009 and 2012, respectively. According to the maximal change of systolic response (SR), the area under the curve (AUC) of systolic blood pressure change (AUC-SBP), the maximal change of diastolic response (DR) and the AUC of diastolic blood pressure change (AUC-DBP) in CPT, the individuals were divided into four quartile groups by above parameters, respectively: group Ⅰ (P(25)), group Ⅱ (P(50)), group Ⅲ (P(75)) and group Ⅳ (P(100)). The correlation between blood pressure response to CPT and the follow-up blood pressure was analyzed. Results: (1) There were no significant differences in baseline blood pressure levels and prevalence of hypertension among four quartile groups no matter it was grouped on SR, DR, AUC-SBP or AUC-DBP. (2) The prevalence of hypertension in each group from lowest (P(25)) to highest (P(100)) in 2012 was 25.64%, 30.67%, 38.03%, 55.74% on SR grouping (P<0.01), and 27.5%, 29.17%, 38.46%, 57.35% on AUC-SBP grouping (P<0.05), respectively. (3) There were no significant differences in the prevalence of hypertension among four groups in 2012 (P>0.05) either on DR or on AUC-DBP grouping. (4) The random effects model analysis showed that the correlation coefficient between SR, AUC-SBP and long-term systolic blood pressure increase were 1.91 (P<0.05) and 1.44 (P<0.05), respectively, and the correlation coefficient between DR, AUC-DBP and long-term diastolic blood pressure increase were 0.82 (P<0.05) and 0.78 (P>0.05), respectively. Age, male, body mass index, and fasting blood glucose were independent risk factors for long-term blood pressure elevation, and age, body mass index and fasting blood glucose positively correlated with changes in long-term blood pressure (all P<0.05). Conclusion: Individual systolic blood pressure response to CPT can be used as a predictor of long-term hypertension.


Assuntos
Pressão Sanguínea/fisiologia , Temperatura Baixa , Hipertensão/fisiopatologia , Área Sob a Curva , Diástole , Humanos , Masculino , Valor Preditivo dos Testes , Fatores de Risco
17.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(3): E010, 2020 Feb 12.
Artigo em Chinês | MEDLINE | ID: mdl-32048501

RESUMO

Respiratory support is a very important technique for saving severe 2019-nCoV pneumonia patients who suffering respiratory failure, which can improve oxygenation, reduce mortality. Therefore, how to reasonable using respiratory support technique is the key point that relating success or failure. In this paper, the authors introduce their experience on treating severe 2019-nCoV pneumonia, it is hopeful for current fighting against 2019-nCoV in China.

18.
Artigo em Chinês | MEDLINE | ID: mdl-31495108

RESUMO

Objective: To investigate the protective effect of oligomeric proanthocyanidins (OPCs) in paraquat-exposed mice. Methods: An acute lung injury model was established by a single intraperitoneal injection of paraquat (PQ) in BALB/c mice. The mice were randomized into control group, paraquat-exposed group (PQ group) , oligomeric proanthocyanidins group (OPCs group) , and paraquat and oligomeric proanthocyanidins-exposed group (PQ+OPCs group) , with 10 mice in each group. Only normal saline was intraperitoneally injected into the mice in the control group. The mice in the PQ group were divided into 8 subgroups according to the dose of poison administered, i.e., 0, 25, 50, 75, 100, 150, 200, and 300 mg/kg; the mice in each subgroup were given a single intraperitoneal injection of PQ and were observed and recorded for death at 3, 6, 12, 24, 36, 48, 60, 84, and 96 hours after PQ injection. Origin 8.0 was used to calculate the median lethal dose (LD(50)) of the mice at 24, 36, 48, and 60 hours after PQ injection, and the PQ dose (100 mg/kg, ip) was chosen based on the accumulated mortality rate. An OPCs-treated experimental model was established by an intraperitoneal injection of OPCs followed by a single PQ injection (100 mg/kg, ip) 1 hour later to observe the effects of OPCs on the apparent poisoning effect and fatality rate in PQ-induced mice. Immunohistochemistry was used to determine the effect of OPCs on PQ-induced lung tissue lesions. The peripheral blood samples of the mice were collected to determine the effects of OPCs on PQ-induced inflammatory factors such as tumor necrosis factor-α (TNF-α) , interleukine-1ß (IL-1ß) , and transforming growth factor-ß1 (TGF-ß1) using enzyme-linked immunosorbent assay. Results: The mortality rate was significantly correlated with the dose and exposure time in PQ-exposed mice; the mortality rate gradually increased with increasing dose and exposure time of the poison (P<0.05) . The LD(50) values for the mice were 216.67, 124.11, and 71.24 mg/kg at 24, 48, and 72 hours after PQ exposure, respectively. PQ could induce animal death at 12 hours after injection, and the mortality rate of the animals was 40% (4/10) at 48 hours after PQ exposure. The PQ-induced mortality rate of the mice in the PQ+OPCs group was reduced, and the mortality rate of the animals was 10% (1/10) at 48 hours after PQ exposure. Compared with treatment in the control group, OPCs exposure alone had no significant effect on the expression of TNF-α and TGF-ß1 in the peripheral blood (P>0.05) , but it significantly inhibited the expression of IL-1ß (P<0.05) . After 48 hours, the expression of TNF-α, TGF-ß1, and IL-1ß in peripheral blood significantly increased by 39%, 45%, and 38%, respectively, in the PQ group (P<0.05) , but they significantly decreased by 31%, 13%, and 22%, respectively, in the OPCs+PQ group as compared with the PQ group (P<0.05) . Conclusion: OPCs pretreatment can significantly alleviate PQ-induced poisoning effect.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Paraquat/toxicidade , Proantocianidinas/farmacologia , Substâncias Protetoras/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Interleucina-1beta/sangue , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Fator de Crescimento Transformador beta1/sangue , Fator de Necrose Tumoral alfa/sangue
19.
Zhonghua Nei Ke Za Zhi ; 58(9): 668-672, 2019 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-31461818

RESUMO

Objective: To retrospectively analyze the efficacy and safety of modified cell infusion method in reducing the incidence of febrile non-hemolytic transfusion reaction (FNHTR). Methods: A total of 69 patients were enrolled in the clinical trial of CD(19) chimeric antigen receptor T (CAR-T) cell treatment from February 2017 to October 2018. Study group received the modified cell infusion method, that 1×10(6) CAR-T cells were re-suspended in 2 mg human serum albumin with total volume of 20 ml and injected intravenously. The control group was intravenously administrated with CAR-T cell in 100 ml normal saline. The incidence of FNHTR, cytokine releasing syndrome (CRS) grade, cytokine level and efficacy were compared. Results: (1)The incidence of FNHTR in the study group was 21.1%, significantly lower than that in the control group (71%)(P=0.000). (2)There was no statistical difference in cell proliferation between the study group and the control group on day 4, 7, 14 and 21 after CAR-T cell infusion (P=10.223, 3.254, 5.551, 7.605). (3)There was no statistical difference in CRS grading between the study group and the control group (P=0.767). There was no statistical difference in the levels of interleukin 2 receptor (IL-2R), IL-6, tumor necrosis factor (TNF)-α between the two groups. (4)The C-reaction protein (CRP) level of the study group was lower than that of the control group on day 4 and 7 (P=0.026, 0.007). (5)There was no statistical difference of response rates in acute lymphocytic leukemia (ALL) and non-Hodgkin lymphoma (NHL) patients between the two groups (P(ALL)=0.842; P(NHL)=0.866). Conclusion: The modified cell infusion method in CD(19) CAR-T cell treatment reduces the incidence of treatment-related FNHTR. It does not affect the proliferation of CAR-T cells in vivo, the grading of CRS and the response rates.


Assuntos
Antígenos CD19/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos de Linfócitos T/uso terapêutico , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T , Reação Transfusional/prevenção & controle , Humanos , Receptores de Antígenos Quiméricos/uso terapêutico , Estudos Retrospectivos
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