RESUMO
INTRODUCTION: Although the 9-minute mean withdrawal time (m-WT) is often reported to be associated with the optimal adenoma detection rate (ADR), no randomized trials of screening colonoscopy have confirmed the impact of a 9-minute m-WT on adenoma miss rate (AMR) and ADR. METHODS: A multicenter tandem trial was conducted in 11 centers. Seven hundred thirty-three asymptomatic participants were randomized to receive segmental tandem screening colonoscopy with a 9-minute withdrawal, followed by a 6-minute withdrawal (9-minute-first group, 9MF, n = 366) or vice versa (6-minute-first group, 6MF, n = 367). The primary outcome was the lesion-level AMR. RESULTS: The intention-to-treat analysis revealed that 9MF significantly reduced the lesion-level (14.5% vs 36.6%, P < 0.001) and participant-level AMR (10.9% vs 25.9%, P < 0.001), advanced adenoma miss rate (AAMR, 5.3% vs 46.9%, P = 0.002), multiple adenomas miss rate (20.7% vs 56.5%, P = 0.01), and high-risk adenomas miss rate (14.6% vs 39.5%, P = 0.01) of 6MF without compromising detection efficiency ( P = 0.79). In addition, a lower false-negative rate for adenomas ( P = 0.002) and high-risk adenomas ( P < 0.05), and a lower rate of shortening surveillance schedule ( P < 0.001) were also found in 9MF, accompanying with an improved ADR in the 9-minute vs 6-minute m-WT (42.3% vs 33.5%, P = 0.02). The independent inverse association between m-WT and AMR remained significant even after adjusting ADR, and meanwhile, 9-minute m-WT was identified as an independent protector for AMR and AAMR. DISCUSSION: In addition to increasing ADR, 9-minute m-WT also significantly reduces the AMR and AAMR of screening colonoscopy without compromising detection efficiency.
Assuntos
Adenoma , Colonoscopia , Humanos , Adenoma/diagnósticoRESUMO
BACKGROUND: Endometrial dysfunction is closely correlated with the development of multiple severe gynecological disorders including intrauterine adhesion. Accumulating evidence supports that some long non-coding RNAs (lncRNAs) have peptide-coding potential. In this text, the peptide-coding ability of lncRNA SNHG6 was examined. Also, the effects of an SNHG6-encoded peptide on the viability and migration of human endometrial stromal cells (hESCs) and human endometrial epithelial cells (hEECs) and related molecular mechanisms were explored. METHODS: The peptide-encoding potential of SNHG6 was predicted by FuncPEP and getorf databases and validated by western blot assay. Cell viability was tested by cell counting kit-8 assay. Cell migratory ability was examined by wound healing and transwell migration assays. Protein levels of genes were measured by western blot assay. RESULTS: Prediction analysis suggested that SNHG6 had the potential peptide-coding ability and multiple open-reading frames (ORFs). Western blot validated that SNHG6 ORF#1 and ORF#2 could translate into short peptides. SNHG6 ORF#2 overexpression facilitated cell migration and epithelial-mesenchymal transition (EMT) in hESCs and hEECs, while these effects were abrogated by transforming growth factor-beta (TGF-ß)/SMAD signaling inhibitor GW788388. Moreover, GW788388 inhibited the increase of p-SMAD2 and p-SMAD3 levels induced by SNHG6 ORF#2 in hESCs. SNHG6 ORF#2-encoded peptide did not influence endometrial stromal and epithelial cell viability. CONCLUSIONS: LncRNA SNHG6 ORF#1 and ORF#2 could translate into small peptides and SNHG6 ORF#2 overexpression promoted cell migration and EMT by activating the TGF-ß/SMAD pathway in hESCs and hEECs, suggesting the potential roles of SNHG6-encoded peptides in the development of endometrial stromal and epithelial cells and related gynecological diseases.
Assuntos
RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transição Epitelial-Mesenquimal/genética , RNA Nucleolar Pequeno/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Fator de Crescimento Transformador beta/farmacologia , Transdução de Sinais , Movimento Celular/genética , Fatores de Crescimento Transformadores/genética , Fatores de Crescimento Transformadores/metabolismo , Fatores de Crescimento Transformadores/farmacologiaRESUMO
AIM: The functions and molecular mechanisms of SPI1-related protein (SPIB) were examined in cervical cancer (CC) cells. METHODS: Genes related to miscarriage and prognosis in CC were identified by Kaplan-Meier and differential expression analysis, respectively. Cell proliferation, apoptosis, migration, and invasion were examined by cell counting kit-8, flow cytometry, transwell migration, and transwell invasion assays, respectively. The potential functions and molecular mechanisms of SPIB in CC were speculated by gene set enrichment analysis (GSEA) analysis. The mRNA and protein levels of genes were examined by RT-qPCR and western blot assays, respectively. The effect of SPIB on macrophage cells was tested by macrophage recruitment assay and bioinformatics analysis. RESULTS: A total of 753 dysregulated genes were identified in 88 TCGA CC samples with a history of one or more miscarriages versus 208 CC samples with no miscarriage history. Also, 91 genes related to CC prognosis were identified. SPIB, a gene related to both miscarriage and CC prognosis, inhibited Hela cell proliferation, migration, and invasion, and facilitated Hela cell apoptosis. GSEA analysis disclosed that SPIB might play vital roles in immunity, chemokine signaling pathway, and macrophage chemotaxis/activation in CC. Moreover, SPIB inhibited C-X-C motif chemokine ligand 8 (CXCL8), C-C motif chemokine ligand 17 (CCL17), and C-C motif chemokine ligand 25 (CCL25) expression in Hela cells, and SPIB overexpression in Hela cells hampered THP-1 cell migration. Higher SPIB expression was associated with less M2 macrophage infiltration in CC. CONCLUSIONS: SPIB inhibited CC-cell progression and hindered macrophage cell migration in CC.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição/metabolismo , Neoplasias do Colo do Útero , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quimiocinas/genética , Quimiocinas/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Ligantes , Macrófagos/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismoRESUMO
A fluorometric clenbuterol immunoassay is described that uses S- and N-co-doped carbon quantum dots as the fluorescent probe. Strongly fluorescent S/N-doped carbon quantum dots (S/N-CDs) were synthesized by hydrothermal method using fructose as the carbon precursor and L-cysteine as S/N sources. The S/N-CDs were characterized by transmission electron microscopy, energy dispersive spectroscopy and Fourier transform infrared spectroscopy (FTIR). Under 350 nm photoexcitation, they display strong purple fluorescence with an emission peak at 405 nm. In pH 4.0 solution, the amino groups (confirmed by FTIR) on the carbon quantum dots were coupled to clenbuterol antibody (Ab) by amine-amine coupling reaction to quench the fluorescence. If clenbuterol (Clen) is added, it binds to the Ab to generate a stable Ab-Clen immunocomplex and free S/N-CD. This causes the fluorescence of nanoprobe to be restored. The fluorescence of the system increases linearly in the 0.07-1.7 ng·mL-1 Clen concentration range. The probe of type S/N4-CD displays the best sensitivity. The detection limit is 23 pg·mL-1. Graphical abstract Schematic presentation of clenbuterol fluorometric immunoassay using sulfur and nitrogen doped carbon quantum dots.
Assuntos
Carbono/química , Clembuterol/análise , Corantes Fluorescentes/química , Imunoensaio/métodos , Nitrogênio/química , Pontos Quânticos/química , Enxofre/química , Técnicas Biossensoriais/métodos , Limite de Detecção , Prata/química , Espectrometria de Fluorescência/métodosRESUMO
Novel ionic-liquid-functionalized Fe3 O4 magnetic nanoparticles were synthesized by the thiol-ene click reaction. The prepared functionalized Fe3 O4 nanoparticles possessed multiple interactions, such as electrostatic, hydrophobic, and π-π interactions. The functionalized Fe3 O4 nanoparticles were characterized by using Fourier transform infrared spectroscopy, X-ray diffraction, vibrating sample magnetometry, and transmission electron microscopy. Four kinds of linear alkylbenzene sulfonates, namely, sodium decylbenzenesulfonate, sodium undecylbenzene sulfonate, sodium dodecylbenzenesulfonate, and sodium tridecylbenzenesulfonate, were selected as model compounds to evaluate the applicability of adsorbents for extraction and subjected to high-performance liquid chromatography analysis. In addition, the effects of various parameters, such as sorbent amount, pH value, ionic strength, sample volume, extraction time, and elution conditions on extraction efficiency were studied in detail. Under the optimum conditions, good linearities were attained, with correlation coefficients between 0.9912 and 0.9968. The proposed method exhibited limits of detection ranging from 0.061 to 0.099 µg/L for all the target analytes. The spiked recoveries of the target analytes in real water samples ranged from 86.3 to 107.5%, with relative standard deviations lower than 7.96%. The enrichment factors of the analytes ranged from 364 to 391, indicating that the obtained functionalized Fe3 O4 nanoparticles can effectively extract trace target analytes from environmental water samples.
RESUMO
The emergence and spread of bacteria carrying the bla(NDM-1) gene has become a worldwide concern. Here, we report eight cases of Klebsiella pneumoniae with bla(NDM-1) in the neonatal ward of a teaching hospital in mainland China. Multilocus sequence typing showed that seven isolates were clonally related and confirmed them as sequence type 17 (ST17). One isolate belonged to ST433. These findings suggest continuous spread of bla(NDM-1) in mainland China and emphasize the need for intensive surveillance and precautions.
Assuntos
Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , beta-Lactamases/genética , beta-Lactamases/metabolismo , Antibacterianos/uso terapêutico , China , DNA Bacteriano/genética , Enterocolite/microbiologia , Evolução Fatal , Feminino , Hospitais de Ensino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Infecções por Klebsiella/tratamento farmacológico , Masculino , Sepse/microbiologiaRESUMO
C2H2-type zinc finger proteins (ZFPs) have been shown to play important roles in the responses of plants to oxidative and abiotic stresses, and different members of this family might have different roles during stresses. Here a novel abscisic acid (ABA)- and hydrogen peroxide (H2O2)-responsive C2H2-type ZFP gene, ZFP36, is identified in rice. The analyses of ZFP36-overexpressing and silenced transgenic rice plants showed that ZFP36 is involved in ABA-induced up-regulation of the expression and the activities of superoxide dismutase (SOD) and ascorbate peroxidase (APX). Overexpression of ZFP36 in rice plants was found to elevate the activities of antioxidant enzymes and to enhance the tolerance of rice plants to water stress and oxidative stress. In contrast, an RNA interference (RNAi) mutant of ZFP36 had lower activities of antioxidant enzymes and was more sensitive to water stress and oxidative stress. ABA-induced H2O2 production and ABA-activated mitogen-activated protein kinases (MAPKs) were shown to regulate the expression of ZFP36 in ABA signalling. On the other hand, ZFP36 also regulated the expression of NADPH oxidase genes, the production of H2O2, and the expression of OsMPK genes in ABA signalling. These results indicate that ZFP36 is required for ABA-induced antioxidant defence, for the tolerance of rice plants to water stress and oxidative stress, and for the regulation of the cross-talk between NADPH oxidase, H2O2, and MAPK in ABA signalling.
Assuntos
Ácido Abscísico/metabolismo , Regulação da Expressão Gênica de Plantas , Oryza/genética , Proteínas de Plantas/genética , Transdução de Sinais , Antioxidantes/metabolismo , Ascorbato Peroxidases/metabolismo , Peróxido de Hidrogênio/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Oryza/enzimologia , Oryza/fisiologia , Estresse Oxidativo , Folhas de Planta/enzimologia , Folhas de Planta/genética , Folhas de Planta/fisiologia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Estresse Fisiológico , Superóxido Dismutase/metabolismo , Regulação para Cima , Dedos de ZincoRESUMO
HAuCl4 was reduced by sodium citrate to prepare 10 nm gold nanoparticles (AuNPs) that were modified by the bisphenol A aptamer (Apt) to obtain an aptamer-nanogold probe (Apt-AuNP) for bisphenol A (BPA). The probes were aggregated nonspecifically to form large clusters, which showed a strong resonance light scattering (RLS) peak at 520 nm, under preparation conditions (pH 7.6 Na2HPO4-NaH2PO4 buffer and ultrasonication). Upon addition of BPA, the probe reacted specifically to form dispersed BPA-Apt-AuNP conjugates that exhibited strong catalysis of the two particle reactions of glucose-Cu(II) and hydrazine hydrochloride-Cu(II) with a strong RLS peak at 360 nm and 510 nm respectively. When the BPA concentration increased, the RLS intensity at 360 nm and 510 nm increased respectively. Accordingly, two new and highly-sensitive RLS methods were established for the detection of BPA, using the Apt-AuNP catalytic amplification.
Assuntos
Aptâmeros de Nucleotídeos/química , Compostos Benzidrílicos/química , Ouro/química , Nanopartículas Metálicas/química , Fenóis/química , Análise Espectral/métodos , Catálise , Análise Espectral/instrumentaçãoRESUMO
Brucellosis is far more frequent in a pasturing area in the northern part of our country and it has many clinical manifestations. It may cause multiple organ damage and its features lack specificity. It is rare in the south, so it is extremely easy to be misdiagnosed or overlooked. The retrospective analysis of a case with Brucellosis misdiagnosed as osteoarthrosis provides a guide for clinical doctors to understand Brucellosis, so that early diagnosis would be accessible, and prognosis could be improved.
Assuntos
Brucelose/diagnóstico , Osteoartrite , Erros de Diagnóstico , Humanos , Estudos RetrospectivosRESUMO
Covalent organic frameworks (COFs) are porous crystals that have high designability and great potential in designing, encapsulating, and immobilizing nanozymes. COF nanozymes have also attracted extensive attention in analyte sensing and detection because of their abundant active sites, high enzyme-carrying capacity, and significantly improved stability. In this paper, we classify COF nanozymes into three types and review their characteristics and advantages. Then, the synthesis methods of these COF nanozymes are introduced, and their performances are compared in a list. Finally, the applications of COF nanozymes in environmental analysis, food analysis, medicine analysis, disease diagnosis, and treatment are reviewed. Furthermore, we also discuss the application prospects of COF nanozymes and the challenges they face.
Assuntos
Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Técnicas Biossensoriais , Nanoestruturas , Química Analítica , Análise de Alimentos , Técnicas de Química Analítica/métodosRESUMO
In this paper, a titanium dioxide/covalent organic framework (TiO2/COF) composite was prepared and its photocatalytic removal of dye was investigated. Using tetrabutyl titanate as a titanium source, TiO2 nanomaterial was prepared by sol-gel method. In the presence of TiO2, TiO2/COF core-shell composite was prepared by solvothermal synthesis using melamine and 1,4-phthalaldehyde as ligands. The prepared materials are characterized by SEM, TEM, XPS, XRD, TG, FTIR, BET, EPR, PL, and UV-Vis-DRS techniques. Using malachite green as a model of dye wastewater, the photocatalytic degradation performance of TiO2/COF composites was investigated under the irradiation of ultraviolet light. The results show that the modification of COF significantly improves the photocatalytic efficiency of TiO2, the degradation rate increases from 69.77 % to 93.64 %, and the reaction rate constant of the first-order kinetic equation is increased from 0.0078â min-1 to 0.0192â min-1. Based on the free radical capture experiment, the photocatalytic degradation mechanism of TiO2/COF was discussed, and the feasibility of its photocatalytic degradation of malachite green was theoretically clarified. Accordingly, a simple and practical method for photocatalytic degradation of malachite green was constructed, which has potential application value in the degradation of dye wastewater.
RESUMO
OBJECTIVES: The study aimed to investigate the knowledge, attitude and practice (KAP) of contraceptive methods among women with an unplanned pregnancy, aiming to improve their reproductive health and increase their understanding of contraceptive methods. DESIGN: This is a cross-sectional study. SETTING: The study was conducted at the Maternity and Child Healthcare Hospital of Hubei between 20 November 2022 and 20 January 2023. PARTICIPANTS: Women with an unplanned pregnancy were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The questionnaire was in the Chinese language and included demographic data, KAP assessments. Multivariate linear regression was performed to explore the factors associated with knowledge or practice scores. RESULTS: During the study period, 510 participants with valid questionnaires were included. The KAP scores were 7.30±2.91, 32.61±3.13 and 28.58±3.59, respectively. Place of residence (urban vs non-urban; B=0.66, 95% CI 0.02 to 1.29, p=0.043) and educational level (master's degree or above vs post secondary or below; B=1.07, 95% CI 0.17 to 1.96, p=0.020) were positively associated with knowledge. Knowledge (B=0.25, 95% CI 0.17 to 0.32, p<0.001) and attitude (B=0.26, 95% CI 0.19 to 0.32, p<0.001) were positively associated with practice. CONCLUSIONS: This study indicates a low level of KAP regarding contraceptive methods among women facing unplanned pregnancies. Place of residence and educational level were positively associated with knowledge scores. These findings may help improve future sex education policies and programmes.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Gravidez não Planejada , Gravidez , Criança , Feminino , Humanos , Estudos Transversais , Anticoncepção , EscolaridadeRESUMO
BACKGROUND: Cervical intraepithelial neoplasia (CIN) is an important precursor of cervical cancer. Early detection and treatment can reduce the incidence of cervical cancer. AIM: To investigate the detection rate of human papillomavirus (HPV) E6/E7 mRNA in cervical tissue of patients with different types of epithelial cell neoplasia (CIN) and its relationship with CIN progression and diagnosis. METHODS: One hundred women with HPV infection detected by cervical exfoliation cytology between January 2022 and January 2023 were retrospectively selected. These patients were graded CIN based on colposcopy and cervical pathology. The positive expression rates of HPV E6/E7 mRNA and HPV [polymerase chain reaction (PCR)-reverse dot crossing] were compared among all groups. Patients with HPV E6/E7 mRNA expression in the grade 1 CIN group were followed up for 1 yr. The relationship between atypical squamous epithelium and high malignant epithelial neoplasia was investigated by univariate and multivariate analysis. RESULTS: The diagnostic sensitivity, specificity, and sensitivity of PCR-reverse point hybridization technology for secondary CIN were 70.41%, 70.66%, and 0.714, respectively. Sensitivity and specificity for secondary CIN were 752% and 7853%, respectively, the area under the curve value was 0.789. Logistic Multifactorial model analysis revealed that the HPV positive rates and the HPV E6/E7 mRNA positive rates were independent risk factors of CIN grade I (P < 0.05). In CIN grade I patients with positive for HPV E6/E7 mRNA, in its orientation to grade CIN patients, in its orientation to grade CIN patients, at 69.2%, compared with patients negative for HPV E6/E7 mRNA (30.8%), significant difference (P < 0.05). CONCLUSION: HPV E6/E7 mRNA and HPV (PCR-reverse dot hybrid) positive expression have a close relationship with CIN-grade disease progression and is an independent risk factor for high-grade CIN lesions.
RESUMO
OBJECTIVE: To establish and validate a risk prediction model for cervical high-grade squamous intraepithelial lesions (HSIL). METHODS: This retrospective study included patients who underwent cervical biopsies at the Cervical Disease Centre of Maternal and Child Hospital of Hubei Province between January 2021 and December 2021. RESULTS: A total of 1630 patients were divided into the HSIL + cervical lesion group (n = 186) and the ≤ LSIL cervical lesions group (n = 1444). LSIL, ASC-H, HSIL and SCC, high-risk HPV, HPV16, HPV18/45, multiple HPV strains, acetowhite epithelium, atypical vessels, and mosaicity were independently associated with HSIL + lesions. These factors were used to establish a risk prediction model with a demonstrated area under the curve (AUC) of 0.851 and a C-index of 0.829. Calibration curve analysis showed that the model performed well, with a mean absolute error (MAE) of 0.005. The decision curve showed that the model created by combining the risk factors was more specific and sensitive than each predictive variable. CONCLUSION: The model for predicting HSIL demonstrated promising predictive capability and might help identify patients requiring biopsy and treatment.
Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Criança , Humanos , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal , Estudos Retrospectivos , PapillomaviridaeRESUMO
Graphite/epoxy resin (G/EP) composites are extensively utilized in bipolar plates for fuel cells owing to their outstanding electrical and mechanical properties. However, the mechanical strength of these composites declines notably due to the inadequate bonding interface between graphite and epoxy resin. To address this issue, we used molecular dynamics (MD) simulations to study the influence of graphite surface functionalization on the interfacial structures of composites. The results of this study revealed that the functionalization of the graphite surface led to an increase in the interface thickness of the composite. This phenomenon can be attributed to the interdiffusion and hydrogen bond formation between functionalized graphite and epoxy molecular chains. And all four types of functional groups demonstrated a promoting effect on the adsorption process. Additionally, the adsorption and contact angle results provided further evidence that the adsorption rate of graphite to the epoxy resin significantly improved after functionalization. These findings contribute to a more comprehensive understanding of the microscopic process of forming interfaces in G/EP composites. In addition, these insights provide valuable guidance for improving the interface bonding of composite bipolar plates, which can ultimately increase their mechanical strength.
RESUMO
Crohn's disease (CD) is a complex autoimmune disorder presumed to be driven by complex interactions of genetic, immune, microbial and even environmental factors. Intrinsic molecular mechanisms in CD, however, remain poorly understood. The identification of novel biomarkers in CD cases based on larger samples through machine learning approaches may inform the diagnosis and treatment of diseases. A comprehensive analysis was conducted on all CD datasets of Gene Expression Omnibus (GEO); our team then used the robust rank aggregation (RRA) method to identify differentially expressed genes (DEGs) between controls and CD patients. PPI (proteinâprotein interaction) network and functional enrichment analyses were performed to investigate the potential functions of the DEGs, with molecular complex detection (MCODE) identifying some important functional modules from the PPI network. Three machine learning algorithms, support vector machine-recursive feature elimination (SVM-RFE), random forest (RF), and least absolute shrinkage and selection operator (LASSO), were applied to determine characteristic genes, which were verified by ROC curve analysis and immunohistochemistry (IHC) using clinical samples. Univariable and multivariable logistic regression were used to establish a machine learning score for diagnosis. Single-sample GSEA (ssGSEA) was performed to examine the correlation between immune infiltration and biomarkers. In total, 5 datasets met the inclusion criteria: GSE75214, GSE95095, GSE126124, GSE179285, and GSE186582. Based on RRA integrated analysis, 203 significant DEGs were identified (120 upregulated genes and 83 downregulated genes), and MCODE revealed some important functional modules in the PPI network. Machine learning identified LCN2, REG1A, AQP9, CCL2, GIP, PROK2, DEFA5, CXCL9, and NAMPT; AQP9, PROK2, LCN2, and NAMPT were further verified by ROC curves and IHC in the external cohort. The final machine learning score was defined as [Expression level of AQP9 × (2.644)] + [Expression level of LCN2 × (0.958)] + [Expression level of NAMPT × (1.115)]. ssGSEA showed markedly elevated levels of dendritic cells and innate immune cells, such as macrophages and NK cells, in CD, consistent with the gene enrichment results that the DEGs are mainly involved in the IL-17 signaling pathway and humoral immune response. The selected biomarkers analyzed by the RRA method and machine learning are highly reliable. These findings improve our understanding of the molecular mechanisms of CD pathogenesis.
Assuntos
Doença de Crohn , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/genética , Genes Reguladores , Pesquisa , Algoritmos , BiomarcadoresRESUMO
BACKGROUND: The CREST study showed that the addition of thoracic radiotherapy (TRT) could improve the survival rate in patients with extensive stage small cell lung cancer (ES-SCLC), but whether TRT can bring survival benefit in the era of immunotherapy remains controversial. This study aimed to explore the efficacy and safety of adding TRT to the combination of PD-L1 inhibitors and chemotherapy. METHODS: The patients who received durvalumab or atezolizumab combined with chemotherapy as the first-line treatment of ES-SCLC from January 2019 to December 2021 were enrolled. They were divided into two groups, based on whether they received TRT or not. Propensity score matching (PSM) with a 1:1 ratio was performed. The primary endpoints were progression-free survival (PFS), overall survival (OS) and safety. RESULTS: A total of 211 patients with ES-SCLC were enrolled, of whom 70 (33.2%) patients received standard therapy plus TRT as first-line treatment, and 141 (66.8%) patients in the control group received PD-L1 inhibitors plus chemotherapy. After PSM, a total of 57 pairs of patients were enrolled in the analysis. In all patients, the median PFS (mPFS) in the TRT and non-TRT group was 9.5 and 7.2 months, respectively, with HR = 0.59 (95%CI 0.39-0.88, p = 0.009). The median OS (mOS) in the TRT group was also significantly longer than that in the non-TRT group (24.1 months vs. 18.5 months, HR = 0.53, 95%CI 0.31-0.89, p = 0.016). Multivariable analysis showed that baseline liver metastasis and the number of metastases ≥ 3 were independent prognostic factors for OS. Addition of TRT increased the incidence of treatment-related pneumonia (p = 0.018), most of which were grade 1-2. CONCLUSIONS: Addition of TRT to durvalumab or atezolizumab plus chemotherapy significantly improves survival in ES-SCLC. Although it may leads to increased incidence of treatment-related pneumonia, a majority of the cases can be relieved after symptomatic treatment.
Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Inibidores de Checkpoint Imunológico/uso terapêuticoRESUMO
OBJECTIVE: Using an adenoviral vector, the wild-type PTEN gene was transduced into activated hepatic stellate cell (HSC) cultured in vitro and cell cycle markers and were detect. Thereby, the potential mechanisms of inhibitory effect of the wild-type PTEN overexpression on the proliferation in activated HSC was investigated. METHODS: The wild type PTEN gene was transduced into activated HSC (HSC-T6 ) cultured in vitro mediated by adenoviral vector. PTEN expression in HSC was measured by Western blot and Real-time fluorescent quantitation PCR. Flow cytometry (FCM) was then used to detect cell cycle phase of activated HSC. And the expressions of cyclinD1 and cyclin dependent kinase 4 (CDK4) in HSC were determined by Western blot. RESULTS: The data showed that exogenous wild type PTEN gene was successfully transduced and expressed in activated HSC cultured in vitro. The over-expression of wild type PTEN resulted in the increased number of HSC at G0/G1 phase ( P less than 0.01), and the number of HSC at S phase and G2/M phase were decreased significantly, P less than 0.01. Furthermore, there were decreased cyclinD1 and CDK4 expression in HSC infected with Ad-PTEN, P less than 0.01. CONCLUSION: The over-expression of wild type PTEN inhibit transition of activated HSC in vitro from G1 to S phase and arrest cell cycle of them at G0/G1 phase via the down-regulated expressions of cyclinD1 and CDK4, and then inhibit HSC proliferation.
Assuntos
Proliferação de Células/efeitos dos fármacos , Quinase 4 Dependente de Ciclina/metabolismo , Células Estreladas do Fígado/metabolismo , PTEN Fosfo-Hidrolase/farmacologia , Adenoviridae/genética , Animais , Ciclo Celular , Linhagem Celular , Ciclina D1/metabolismo , Vetores Genéticos , Ratos , TransfecçãoRESUMO
In this paper, covalent organic frameworks (COFs) are prepared by solvothermal synthesis using 1,3,5-benzenetricarboxaldehyde and benzidine as ligands. Then, using COFs as a template, AgCOFs with high catalytic activity is prepared by in situ loading silver nanoparticles (AgNC) on the surface of COFs by sodium borohydride reduction method. AgCOFs are characterized by TEM, SEM, FTIR and XRD. At the same time, the catalytic ability of AgCOFs for trisodium citrate-AgNO3 nanosilver reaction is studied. The results show that AgCOFs can catalyze the reaction of trisodium citrate-AgNO3 to generate silver nanoparticles (AgNPs). The solution color of the system gradually changes from colorless to yellow, and the absorbance value increases. Based on the catalytic reaction of AgCOFs and the regulation effect of nucleic acid aptamer reaction on AgCOFs, a new "on-off-on" colorimetric analysis platform is constructed and applied to the detection of trace Pb2+ in water samples. This analytical platform is simple, sensitive and selective. Finally, the catalytic mechanism of the system is discussed to verify the feasibility of constructing a colorimetric analysis platform.
RESUMO
Circular RNAs (circRNAs) have been identified as critical regulators in human cancers, including cervical cancer (CC). However, the precise action of circ_0084904 in cervical carcinogenesis remains to be elucidated. The levels of circ_0084904, microRNA (miR)-802, and Mal, T cell differentiation protein 2 (MAL2) were checked by quantitative real-time PCR (qRT-PCR) or western blot. Ribonuclease R (RNase R) and subcellular localization assays were used to detect the stability and localization of circ_0084904, respectively. Cell colony formation ability was assessed by colony formation assay. Cell cycle and apoptosis were detected by flow cytometry. Cell migration and invasion abilities were gauged by transwell assay. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were applied to determine the direct relationship between miR-802 and circ_0084904 or MAL2. The xenograft experiments were performed to evaluate the role of circ_0084904 in tumor growth in vivo. Circ_0084904 was markedly up-regulated in CC tissues and cell lines. Silencing endogenous circ_0084904 impeded cell colony formation, cell cycle progression, migration, invasion, epithelial-mesenchymal transition (EMT), and promoted apoptosis in vitro, as well as diminished tumor growth in vivo. Mechanistically, circ_0084904 targeted miR-802, and the effects of circ_0084904 silencing were mediated by miR-802. MAL2 was directly targeted and inhibited by miR-802, and MAL2 was a functional target of miR-802. Moreover, circ_0084904 modulated MAL2 expression via miR-802. Our study identified circ_0084904 as a novel oncogenic driver in CC depending on the modulation of the miR-802/MAL2 axis, establishing the notion that silencing of circ_0084904 might represent a promising targeted therapy for CC.