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1.
Front Med (Lausanne) ; 8: 730441, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604267

RESUMO

Objective: A considerable part of COVID-19 patients were found to be re-positive in the SARS-CoV-2 RT-PCR test after discharge. Early prediction of re-positive COVID-19 cases is of critical importance in determining the isolation period and developing clinical protocols. Materials and Methods: Ninety-one patients discharged from Wanzhou Three Gorges Central Hospital, Chongqing, China, from February 10, 2020 to March 3, 2020 were administered nasopharyngeal swab SARS-CoV-2 tests within 12-14 days, and 50 eligible patients (32 male and 18 female) with completed data were enrolled. Average age was 48 ± 11.5 years. All patients underwent non-enhanced chest CT on admission. A total of 568 radiomics features were extracted from the CT images, and 17 clinical factors were collected based on the medical record. Student's t-test and support vector machine-based recursive feature elimination (SVM-RFE) method were used to determine an optimal subset of features for the discriminative model development. Results: After Student's t-test, 62 radiomics features showed significant inter-group differences (p < 0.05) between the re-positive and negative cases, and none of the clinical features showed significant differences. These significant features were further selected by SVM-RFE algorithm, and a more compact feature subset containing only two radiomics features was finally determined, achieving the best predictive performance with the accuracy and area under the curve of 72.6% and 0.773 for the identification of the re-positive case. Conclusion: The proposed radiomics method has preliminarily shown potential in identifying the re-positive cases among the recovered COVID-19 patients after discharge. More strategies are to be integrated into the current pipeline to improve its precision, and a larger database with multi-clinical enrollment is required to extensively verify its performance.

2.
Respiration ; : 1-8, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34706367

RESUMO

BACKGROUND: Transbronchial cryobiopsy (TBCB), a novel way of obtaining a specimen of lung tissue using a flexible cryoprobe, can obtain large lung biopsies without crush artifacts. The freezing time of TBCB was empirically selected from 3 to 7 s in the previous studies. However, no consensus has yet been reached regarding the optimal freezing time used in TBCB. OBJECTIVES: The primary endpoint was biopsy size in different freezing times. The secondary endpoints included sample histological quality, diagnostic confidence, and complications in different freezing times. METHODS: Patients who were suspected of DPLD requiring histopathological examination for further evaluation were enrolled in this study. Distinct biopsies were obtained by using different freezing times increased from 3 to 6 s sequentially. Samples were reviewed by 2 external expert pathologists. RESULTS: A total of 33 patients were enrolled, and 143 transbronchial cryobiopsies were taken in this trial. An average of 4.33 samples were taken from each patient. The mean biopsy size of different freezing times from 3 to 6 s was 9.10 ± 4.37, 13.23 ± 5.83, 16.26 ± 5.67, and 18.83 ± 7.50 mm2, respectively. A strong correlation between freezing time and biopsy size was observed (r = 0.99, p < 0.01). Statistically significant difference of biopsy size was detected in the freezing time of 3 s versus 4 s (p < 0.01) and 4 s versus 5 s (p = 0.02), but not in the freezing time of 5 s versus 6 s (p = 0.10). Overall bleeding in different freezing times from 3 to 6 s was 53.33%, 67.50%, 89.47%, and 77.14%, respectively. A significantly higher overall bleeding was observed when the freezing time exceeded 4 s (RR = 1.67, p < 0.01). Pneumothorax occurred in 4 cases (12.12%). One lethal case (3.03%) was noted 25 days after TBCB. Lung parenchyma was preserved well in all cryobiopsy samples. Thirty-one (93.94%) patients' histopathological findings were identified as sufficient to establish a CRP diagnosis. There was no statistical difference in diagnostic confidence between different freezing times. CONCLUSION: A longer freezing time was associated with a larger size of the biopsy sample but a higher risk of bleeding. The optimal transbronchial cryobiopsy freezing time is 3-4 s, which is easily achievable and provides an adequate biopsy size whilst creating a safety threshold from complications.

3.
Clin Exp Med ; 21(3): 361-367, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33543353

RESUMO

BACKGROUND: The recurrence of positive SARS-CoV-2 RT-PCR is frequently found in discharged COVID-19 patients but its clinical significance remains unclear. The potential cause, clinical characteristics and infectiousness of the recurrent positive RT-PCR patients need to be answered. METHODS: A single-centered, retrospective study of 51 discharged COVID-19 patients was carried out at a designated hospital for COVID-19. The demographic data, clinical records and laboratory findings of 25 patients with recurrent positive RT-PCR from hospitalization to follow-up were collected and compared to 26 patients with negative RT-PCR discharged regularly during the same period. Discharged patients' family members and close contacts were also interviewed by telephone to evaluate patients' potential infectiousness. RESULTS: The titer of both IgG and IgM antibodies was significantly lower (p = 0.027, p = 0.011) in patients with recurrent positive RT-PCR. Median duration of viral shedding significantly prolonged in patients with recurrent positive RT-PCR (36.0 days vs 9.0 days, p = 0.000). There was no significant difference in demographic features, clinical features, lymphocyte subsets count and inflammatory cytokines levels between the two groups of patients. No fatal case was noted in two groups. As of the last day of follow-up, none of the discharged patients' family members or close contact developed any symptoms of COVID-19. CONCLUSIONS: Patients with low levels of IgG and IgM are more likely to have recurrent positive SARS-CoV-2 RT-PCR results and lead to a prolonged viral shedding. The recurrent positive of SARS-CoV-2 RT-PCR may not indicate the recurrence or aggravation of COVID-19. The detection of SARS-CoV-2 by RT-PCR in the patients recovered from COVID-19 is not necessarily correlated with the ability of transmission.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/diagnóstico , RNA Viral/genética , Reinfecção/virologia , SARS-CoV-2/isolamento & purificação , Adulto , COVID-19/sangue , COVID-19/imunologia , Estudos de Casos e Controles , China , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , Fatores de Tempo , Eliminação de Partículas Virais
4.
Cell Prolif ; 53(11): e12924, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33078469

RESUMO

OBJECTIVES: Chemoresistance induced by cisplatin has become the major impediment to lung cancer chemotherapy. This study explored the potential chemoresistant genes and underlying mechanisms of chemoresistance in NSCLC. MATERIALS AND METHODS: Gene expression profile was integrated with DNA methylation profile to screen the candidate chemoresistant genes. Bioinformatic analysis and immunohistochemistry were used to analyse the association of a candidate gene with the characteristics of NSCLC patients. Recombinant lentivirus vectors were utilized to overexpress or silence candidate gene. Microarrays and immunoblotting were applied to explore the downstream targets of candidate gene. Xenograft models were established to validate the findings in vitro. RESULTS: An increased ZNF300 expression was detected in three chemoresistant cell lines of NSCLC, and the higher expression of ZNF300 was associated with poor OS of NSCLC patients. Cells with upregulated ZNF300 presented chemoresistance and enhanced aggressive growth compared to cells with downregulated ZNF300. ZNF300 inhibited MAPK/ERK pathways and activated CDK1 through inhibiting WEE1 and MYT1 and modulating MYC/AURKA/BORA/PLK1 axis. ICA and ATRA improved the anti-tumour effect of cisplatin on chemoresistant cells by inducing differentiation. CONCLUSIONS: ZNF300 promotes chemoresistance and aggressive behaviour of NSCLC through regulation of proliferation and differentiation by downregulating MAPK/ERK pathways and regulation of slow-cycling phenotype via activating CDK1 by inhibiting WEE1/MYT1 and modulating MYC/AURKA/BORA/PLK1 axis. Cisplatin, combined with ATRA and ICA, might be beneficial in chemoresistant cases of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/genética , Proteínas Repressoras/genética , Transcriptoma , Animais , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Metilação de DNA/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Proteínas Repressoras/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos
5.
Biomed Pharmacother ; 87: 539-547, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28081464

RESUMO

Fibromodulin (FMOD), an ECM small leucine-rich proteoglycan (SLRP), was reported to promote angiogenesis not only during wound healing, but also in optical and cutaneous angiogenesis-dependent diseases. However, whether it plays important roles in tumor angiogenesis remains unclear. To explore the role of FMOD in tumor angiogenesis of human small cell lung cancer (SCLC), initially the study analyzed the relationship of FMOD expression in cancer tissues of SCLC with clinical characteristics. The analysis revealed that the positive FMOD expression was significantly associated with extensive stage of SCLC and higher vascular density. In mouse models, xenograft tumors developed with FMOD-silenced H446 cells (H446-shFMOD) exhibited slowed growth rate, decreased microvessel density, and reduced blood perfusion related to that of controls (H446-shCON). Additionally, compared with that of controls, the decreased secretion of FMOD in conditioned medium (CM) from H446-shFMOD inhibited proliferation, migration, and invasion of human umbilical vessel endothelial cells (HUVECs). Moreover, the decreased secretion of FMOD downregulated the expression of VEGF, TGF-ß1, FGF-2, and PDGF-B in HUVECs. The findings strongly suggested that the autocrine FMOD of cancer cells may promote tumor angiogenesis of SCLC by upregulating the expression of angiogenic factors that act in concert to facilitate the angiogenic phenotype of endothelial cells as a proangiogenic factor. Therefore, silencing FMOD may be a potentially clinical therapy for repressing tumor angiogenesis.


Assuntos
Indutores da Angiogênese/metabolismo , Regulação para Baixo/fisiologia , Células Endoteliais/metabolismo , Fibromodulina/metabolismo , Neoplasias Pulmonares/metabolismo , Neovascularização Patológica/metabolismo , Carcinoma de Pequenas Células do Pulmão/metabolismo , Animais , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Feminino , Fator 2 de Crescimento de Fibroblastos/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Neovascularização Fisiológica/fisiologia , Fator de Crescimento Transformador beta1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
Oncotarget ; 7(37): 59742-59753, 2016 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-27486757

RESUMO

It has been well established that besides environmental factors, genetic factors are also associated with lung cancer risk. However, to date, the prior identified genetic variants and loci only explain a small fraction of the familial risk of lung cancer. Hence it is vital to investigate the remaining missing heritability to understand the development and process of lung cancer. In the study, to test our hypothesis that the previously identified breast cancer risk-associated genetic polymorphisms at the TOX3/LOC643714 locus might contribute to lung cancer risk, 16 SNPs at the TOX3/LOC643714 locus were evaluated in a Han Chinese population based on a case-control study. Pearson's chi-square test or Fisher's exact test revealed that rs9933638, rs12443621, and rs3104746 were significantly associated with lung cancer risk (P < 0.001, P < 0.001, and P = 0.005, respectively). Logistic regression analyses displayed that lung cancer risk of individuals with rs9933638(GG+GA) were 1.89 times higher than that of rs9933638AA carriers (OR = 1.893, 95% CI = 1.308-2.741, P = 0.001). Similar findings were manifested for rs12443621 (OR = 1.824, 95% CI = 1.272-2.616, P = 0.001, rs12443621(GG+GA) carriers vs. rs12443621AA carriers) and rs3104746 (OR = 1.665, 95% CI = 1.243-2.230, P = 0.001, rs3104746TT carriers vs. rs3104746(TA+AA) carriers). The study discovered for the first time that three SNPs (rs9933638, rs12443621, and rs3104746) at the TOX3/LOC643714 locus contributed to lung cancer risk, providing new evidences that lung cancer and breast cancer are linked at the molecular and genetic level to a certain extent.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Receptores de Progesterona/genética , Adulto , Idoso , Alelos , Proteínas Reguladoras de Apoptose , Neoplasias da Mama/etnologia , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Proteínas de Grupo de Alta Mobilidade , Humanos , Neoplasias Pulmonares/etnologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Transativadores
7.
Biomed Pharmacother ; 71: 172-84, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25960233

RESUMO

Contactin-1 (CNTN-1), a glycosyl phosphatidylinositol anchor neural cell adhesion molecule (ACAM), is thought to function not only in nervous system development but also in the invasion and metastasis of several tumours. To investigate whether CNTN-1 is involved in multidrug resistance (MDR) in lung adenocarcinoma, CNTN-1 expression was compared between MDR human lung adenocarcinoma A549/cisplatin (A549/DDP) cells and its progenitor A549 cells. The comparison showed that CNTN-1 expression in A549/DDP cells was significantly higher than in A549 cells both at the mRNA level and the protein level. In order to confirm the physiological function of the abnormal expression, lentivirus-mediated short hairpin RNA (shRNA) was used to silence CNTN-1. Cell cytotoxicity assay and cell apoptosis assay revealed that silencing CNTN-1 both in A549 cells and in A549/DDP cells not only rendered cells more sensitive to cisplatin than the negative control, but also increased the cisplatin-induced apoptosis. Metastasis and invasion assays demonstrated that CNTN-1 knockdown reduced metastasis and invasion but did not affect A549 or A549/DDP cell proliferation. To investigate whether the abnormal expression of CNTN-1 is associated with characteristics of patients with non-small cell lung cancer (NSCLC), immunohistochemistry was used to detect CNTN-1 expression in 143 tissue samples from NSCLC patients and the results showed that the degree of CNTN-1 expression positively correlated with lymphatic invasion in patients with lung adenocarcinoma who received adjuvant cisplatin- or carboplatin-based treatment after surgery. Thus, we concluded that CNTN-1 is closely related with MDR of lung adenocarcinoma. Additionally, CNTN-1 is a novel marker to predict chemotherapeutic efficacy of patients with lung adenocarcinoma, especially with regard to cisplatin- or carboplatin-based regimens.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Cisplatino/farmacologia , Contactina 1/genética , Regulação para Baixo/efeitos dos fármacos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma de Pulmão , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , Contactina 1/metabolismo , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , RNA Interferente Pequeno/metabolismo
8.
Front Biosci (Landmark Ed) ; 17: 2691-7, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22652807

RESUMO

The serious global TB epidemic coupled with limited diagnostic and therapeutic technologies necessitate the study of the role phage in TB treatment. Mycobacterium phage have been used for TB diagnosis, but the accuracy of such methods needs to be improved. Phage have various advantages in treating many kinds of bacterial infection, and coupled with the abuse and misuse of antibiotics, and the increasing prevalence of drug-resistant bacteria, they have been studied as a novel therapy to support antibiotics. The study of phage in TB therapy has developed from the selection of appropriate phage to the simultaneous use of multiple phage and even the use of purified lyase proteins. Though phage have great potential in TB therapy, the technology is still in the in vitro and animal experiment stages, and needs further study.


Assuntos
Bacteriófagos/fisiologia , Mycobacterium/virologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/terapia , Antituberculosos/uso terapêutico , Bacteriófagos/genética , Genes Reporter , Humanos , Luciferases/genética , Liases/uso terapêutico , Testes de Sensibilidade Microbiana
9.
Langmuir ; 22(3): 1241-6, 2006 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-16430289

RESUMO

After determining the size dependent miscibility of binary polymer blend films using molecular dynamics simulation and thermodynamics, the size dependent glass transition temperatures Tg(w,D) of several polymer blend films in miscible ranges are determined by computer simulation and the Fox equation where w is the weight fraction of the second component and D denotes thickness of films. The Tg(w,D) function of a thin film can decrease or increase as D decreases depending on their surface or interface states. The computer simulation results are consistent with available experimental results and theoretical results for polymer blend films of PPO/PS [poly(2,6-dimethyl-1,4-phenylene oxide)/polystyrene] and stereoregular PMMA/PEO [poly(methyl methacrylate)/poly(ethylene oxide)]. The physical background of the above results is related to the root of mean square displacement of thin films in their different regions.

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