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1.
Plant Methods ; 18(1): 81, 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35690826

RESUMO

BACKGROUND: Variety genuineness and purity are essential indices of maize seed quality that affect yield. However, detection methods for variety genuineness are time-consuming, expensive, require extensive training, or destroy the seeds in the process. Here, we present an accurate, high-throughput, cost-effective, and non-destructive method for screening variety genuineness that uses seed phenotype data with machine learning to distinguish between genetically and phenotypically similar seed varieties. Specifically, we obtained image data of seed morphology and hyperspectral reflectance for Jingke 968 and nine other closely-related varieties (non-Jingke 968). We then compared the robustness of three common machine learning algorithms in distinguishing these varieties based on the phenotypic imaging data. RESULTS: Our results showed that hyperspectral imaging (HSI) combined with a multilayer perceptron (MLP) or support vector machine (SVM) model could distinguish Jingke 968 from varieties that differed by as few as two loci, with a 99% or higher accuracy, while machine vision imaging provided ~ 90% accuracy. Through model validation and updating with varieties not included in the training data, we developed a genuineness detection model for Jingke 968 that effectively discriminated between genetically similar and distant varieties. CONCLUSIONS: This strategy has potential for wide adoption in large-scale variety genuineness detection operations for internal quality control or governmental regulatory agencies, or for accelerating the breeding of new varieties. Besides, it could easily be extended to other target varieties and other crops.

2.
Transl Lung Cancer Res ; 11(5): 776-785, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35693290

RESUMO

Background: Anlotinib demonstrated improved overall survival (OS) and progression-free survival (PFS) compared with placebo as a third-line or subsequent therapy in patients with non-small cell lung cancer (NSCLC) in the ALTER0303 trial. The status of epidermal growth factor receptor (EGFR) mutation, different previous treatment may affect the efficacy of subsequent therapy, and we did this subgroup analysis to characterize the efficacy of anlotinib in patients with and without EGFR mutation. Methods: The ALTER0303 trial was a randomized, double-blind, phase 3 study of anlotinib in patients with NSCLC who failed at least 2 lines of treatment. In the study, 138 of 437 randomized patients were EGFR mutation positive. A Cox model was used to examine the influence of previous treatment on the efficacy of anlotinib according to EGFR mutation status. Results: For patients with EGFR mutation, the OS was 10.7 and 6.3 months (HR 0.59; 95% CI: 0.38-0.94, P=0.025) in the anlotinib and placebo group, respectively. The PFS was 5.6 and 0.8 months (HR 0.21; 95% CI: 0.13-0.32, P<0.0001) in the anlotinib and placebo group, respectively. For patients without EGFR mutation, the OS was 8.9 months for anlotinib and 6.5 months for placebo (HR 0.73; 95% CI: 0.55-0.97, P=0.029), and the PFS was 5.4 months for anlotinib and 1.6 months for placebo (HR 0.29; 95% CI: 0.22-0.39, P<0.0001). In the anlotinib group, the OS and PFS for patients with and without EGFR mutation was 10.7 and 8.9 months (HR 0.69; 95% CI: 0.50-0.95, P=0.021), 5.6 and 5.4 months (HR 1.00; 95% CI: 0.75-1.34, P=1.000), respectively. The incidence of adverse events was similar in subgroups. Conclusions: This analysis demonstrated that the benefit of anlotinib as a third-line therapy for patients with NSCLC was independent of EGFR mutation status.

3.
J Nanobiotechnology ; 20(1): 256, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35658867

RESUMO

BACKGROUND: Ischemic stroke is one of the main causes of death and disability in the world. The treatment for ischemic stroke is to restore blood perfusion as soon as possible. However, when ischemic brain tissue is re-perfused by blood, the mitochondrial permeability transition pore (mPTP) in neuron and microglia is excessively opened, resulting in the apoptosis of neuron and nerve inflammation. This aggravates nerve injury. Cyclosporine A (CsA) inhibits the over-opening of mPTP, subsequently reducing the release of ROS and the apoptosis of cerebral ischemia/reperfusion injured neuron and microglia. However, CsA is insoluble in water and present in high concentrations in lymphatic tissue. Herein, cerebral infarction tissue targeted nanoparticle (CsA@HFn) was developed to treat cerebral ischemia/reperfusion injury. RESULTS: CsA@HFn efficiently penetrated the blood-brain barrier (BBB) and selectively accumulated in ischemic area, inhibiting the opening of mPTP and ROS production in neuron. This subsequently reduced the apoptosis of neuron and the damage of BBB. Consequently, CsA@HFn significantly reduced the infarct area. Moreover, CsA@HFn inhibited the recruitment of astrocytes and microglia in ischemic region and polarized microglia into M2 type microglia, which subsequently alleviated the nerve inflammation. CONCLUSIONS: CsA@HFn showed a significant therapeutic effect on cerebral ischemia/reperfusion injury by alleviating the apoptosis of neuron, nerve inflammation and the damage of BBB in ischemic area. CsA@HFn has great potential in the treatment of ischemic stroke.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Nanopartículas , Traumatismo por Reperfusão , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/uso terapêutico , Animais , Encéfalo , Isquemia Encefálica/tratamento farmacológico , Ciclosporina/farmacologia , Inflamação/tratamento farmacológico , Isquemia/tratamento farmacológico , Camundongos , Poro de Transição de Permeabilidade Mitocondrial , Espécies Reativas de Oxigênio , Traumatismo por Reperfusão/tratamento farmacológico
4.
BMC Public Health ; 22(1): 1115, 2022 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-35658937

RESUMO

BACKGROUND: Health information avoidance is common in real life, but because it is not always conducive to health promotion and maintenance, people often actively switch to health information acquisition. Understanding this process of active change can facilitate intervention in unreasonable avoidance behaviors. However, studies so far have mostly focused on why and how avoidance takes place, little is known about the process of active change from avoidance to acquisition. We thus use a grounded theory approach (GT) to explore how the active change takes place, and to generate a grounded theoretical framework capable of illustrating stages and influencing factors involved in the active change process. METHODS: Straussian grounded theory (Corbin & Strauss, 2015) was used to analyze data collected through semi-structured interviews with 30 adults (14 in good health, 11 with disease, 5 in other health status) who had experienced health information behavior change from avoidance to acquisition. These interviews focused on how the change occurred and what effected the change. RESULTS: The core category of Health Information Avoidance Change and 12 categories were identified and integrated to form a theoretical framework termed the Health Information Avoidance Change Model (HIACM). This model describes the process using five non-linear stage variables (initiation, preparation, action, maintenance, and abandonment) and seven moderating factor variables (cognitive change, social stimulus, beliefs and attitudes, intrapsychic literacy, social resources, information source, time and material resources). CONCLUSIONS: HIACM can be used to explain the process of active change from health information avoidance to health information acquisition. HIAC is a non-linear and holistic process, and it is necessary to dynamically analyze the impact of relevant factors and take targeted intervention measures in stages. HIAC is usually not only an individual behavior, but also a socialized behavior requiring the collaboration of individuals, families, health information providers, healthcare providers, and governments.


Assuntos
Pessoal de Saúde , Adulto , Teoria Fundamentada , Pessoal de Saúde/psicologia , Humanos
5.
J Nanobiotechnology ; 20(1): 251, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35659239

RESUMO

BACKGROUND: At present, patients with myocardial infarction remain an increased risk for myocardial ischemia/reperfusion injury (MI/RI). There lacks effectively method to treat MI/RI in clinic. For the treatment of MI/RI, it is still a bottleneck to effectively deliver drug to ischemic myocardium. In this paper, a regulatory T cells (Tregs) biomimetic nanoparticle (CsA@PPTK) was prepared by camouflaging nanoparticle with platelet membrane. RESULTS: CsA@PPTK actively accumulated in ischemic myocardium of MI/RI mice. CsA@PPTK significantly scavenged reactive oxygen species (ROS) and increased the generation of Tregs and the ratio of M2 type macrophage to M1 type macrophage in ischemic myocardium. Moreover, CsA@PPTK significantly attenuated apoptosis of cardiomyocytes and reduced the infarct size and fibrosis area in ischemic myocardium. CsA@PPTK markedly decreased the protein expression of MMP-9 and increased the protein expression of CX43 in ischemic myocardium tissue. Subsequently, the remodeling of the left ventricle was significant alleviated, and heart function of MI/RI mice was markedly improved. CONCLUSION: CsA@PPTK showed significant therapeutic effect on MI/RI, and it has great potential application in the treatment of MI/RI.


Assuntos
Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Nanopartículas , Animais , Apoptose , Biomimética , Humanos , Camundongos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Oxirredução
6.
BMC Med Educ ; 22(1): 410, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35644624

RESUMO

BACKGROUND: The life attitude of health care workers can deeply influence the quality of care. Examining the performance of the Short-Form Life Attitude Inventory (SF-LAI), this study analyzes the factorial structure, reliability, and invariance of the revised SF-LAI across genders and professions among the staff of a teaching medical center. METHODS: The SF-LAI was developed for university students in Taiwan. From January to February 2019, we administered a cross-sectional survey of life attitudes by distributing the SF-LAI to all staff members of a medical center in Taiwan. The construct validity was evaluated using a confirmatory factor analysis (CFA). Model fit was assessed in terms of the comparative fit index (CFI), Tucker-Lewis index (TFI), standardized root mean square residual (SRMR), and root mean square of error of approximation (RMSEA). Internal consistency was calculated using Cronbach's alpha and McDonald's omega. We also performed the CFA invariance analysis for the SF-LAI-R across genders and professions (physician, nurse and other hospital staff). RESULTS: Of 884 (24.62%) responses, 835 were valid. The participants had a mean age of 47.8 years, and 20.12% were male. In a comparison of multiple CFAs, a second-order model with six factors outperformed other models. The goodness of fit indices revealed the CFI was 0.955, TFI was 0.952, RMSEA was 0.071, and SRMR was 0.038. The Cronbach's alphas, McDonald's omega coefficients for internal consistency were all greater than 0.8. The first and second-order model had metric and scalar invariance across genders and professions. CONCLUSIONS: As health care demands evolve, humanities are becoming more important in medical education. Life attitude of hospital care worker is a crucial indicator of whether one embodies the ideals of a humanistic education. The revised SF-LAI has acceptable structural validity, internal consistency, and invariance across genders and professions among staff members of a teaching medical center.


Assuntos
Recursos Humanos em Hospital , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
7.
Stem Cell Res Ther ; 13(1): 271, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35729656

RESUMO

BACKGROUND: Severe ionizing radiation (IR)-induced intestinal injury associates with high mortality, which is a worldwide problem requiring urgent attention. In recent years, studies have found that the PHD-HIF signaling pathway may play key roles in IR-induced intestinal injury, and we found that FG-4592, the PHD inhibitor, has significant radioprotective effects on IR-induced intestinal injury. METHODS: In the presence or absence of FG-4592 treatment, the survival time, pathology, cell viability, cell apoptosis, and organoids of mice after irradiation were compared, and the mechanism was verified after transcriptome sequencing. The data were analyzed using SPSS ver. 19 software. RESULTS: Our results show that FG-4592 had significant radioprotective effects on the intestine. FG-4592 improved the survival of irradiated mice, inhibited the radiation damage of intestinal tissue, promoted the regeneration of intestinal crypts after IR and reduced the apoptosis of intestinal crypt cells. Through organoid experiments, it is found that FG-4592 promoted the proliferation and differentiation of intestinal stem cells (ISCs). Moreover, the results of RNA sequencing and Western blot showed that FG-4592 significantly upregulated the TLR4 signaling pathway, and FG-4592 had no radioprotection on TLR4 KO mice, suggesting that FG-4592 may play protective role against IR by targeting TLR4. CONCLUSION: Our work proves that FG-4592 may promote the proliferation and regeneration of ISCs through the targeted regulation of the TLR4 signaling pathway and ultimately play radioprotective roles in IR-induced injury. These results enrich the molecular mechanism of FG-4592 in protecting cells from IR-induced injury and provide new methods for the radioprotection of intestine.

8.
J Thorac Oncol ; 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35724798

RESUMO

INTRODUCTION: Befotertinib (D-0316) is a novel, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). This study evaluated befotertinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy. METHODS: This was a single-arm, open-label, phase 2 study at 49 hospitals across mainland China. Patients with locally advanced or metastatic NSCLC harboring EGFR T790M mutations with disease progression following prior first- or second- generation EGFR TKI therapy received oral befotertinib of 50 mg (cohort A) or 75-100 mg (cohort B) once daily. The primary endpoint was objective response rate (ORR) assessed by an independent review committee (IRC) in intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT03861156. RESULTS: A total of 176 patients and 290 patients were included in cohorts A (50 mg) and B (75-100 mg), respectively. At data-cutoff (August 15, 2021), IRC-assessed ORR was 67.6% (95% confidence interval [CI]: 61.9%-72.9%) in cohort B. The investigator-assessed ORR was 54.0% (95% CI: 46.3%-61.5%) in cohort A and 65.9% (95% CI: 60.1%-71.3%) in cohort B. Investigator-assessed disease control rate was 93.2% (95% CI: 88.4%-96.4%) in cohort A and 94.8% (95% CI: 91.6%-97.1%) in cohort B. Investigator-assessed intracranial ORR was 26.7% (95% CI: 7.8%-55.1%) in cohort A and 57.1% (95% CI: 34.0%-78.2%) in cohort B. The median investigator-assessed progression-free survival (PFS) was 11.0 (95% CI: 9.6-12.5) months in cohort A and 12.5 (95% CI: 11.1-13.8) months in cohort B. The median investigator-assessed intracranial PFS was 16.5 (95% CI: 8.6-not evaluable [NE]) months in cohort A and NE (95% CI: 13.8-NE) in cohort B. The overall survival was immature. Grade 3 or higher treatment-related adverse events and treatment-related serious adverse events occurred in 20.5% and 11.4% of patients in cohort A, and in 29.3% and 10.0% of patients in cohort B, respectively. CONCLUSION: Befotertinib of 75-100 mg has satisfying efficacy and manageable toxicity in patients with locally advanced or metastatic NSCLC harboring T790M mutation with resistance to first- or second- generation EGFR TKIs. A phase 3 randomized trial is underway (NCT04206072).

9.
J Pharm Biomed Anal ; 218: 114869, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-35688008

RESUMO

In present study, an integrating UPLC-QTOF-MS/MS chemical profiling and UPLC-TQ-MS/MS quantification strategy was developed for the holistic quality evaluation of Hibisci Mutabilis Folium (HMF), a traditional Chinese medicinal herb. Using UPLC-QTOF-MS/MS, a total of 58 components were characterized in HMF sample, of which 36 flavonoids, 3 coumarins, 7 organic acids and 4 triterpene acids were unambiguously identified by comparing the chromatographic behavior and mass spectrum with that of reference compounds, or tentatively assigned by comparing the fragmentation pathways and characteristic fragment ions with that of reference substances and/or published literatures together with mass defect filtering (MDF) screening. Meanwhile, 29 representative major components, including 16 flavonoids, 3 coumarins, 7 organic acids and 3 triterpene acids, were quantified by a newly established UPLC-TQ-MS/MS method that was validated in terms of linearity, sensitivity, precision, repeatability, accuracy and stability. The integrated strategy was applied to simultaneously qualifying and quantifying HMF commercial samples and self-prepared samples harvested in difference periods and dried with different methods. It was found that the contents of 29 major components were obviously different in commercial samples or self-prepared samples, suggesting that the holistic quality of HMF commercial samples was inconsistent, and harvesting period and drying method might be the main factors that affect the holistic quality consistency of commercial HMF samples. Standardized harvesting period and drying method should be established for ensuring the holistic quality consistency of HMF.


Assuntos
Medicamentos de Ervas Chinesas , Triterpenos , Cromatografia Líquida de Alta Pressão/métodos , Cumarínicos/análise , Medicamentos de Ervas Chinesas/química , Flavonoides/análise , Espectrometria de Massas em Tandem/métodos , Triterpenos/análise
10.
Int J Mol Sci ; 23(11)2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35682568

RESUMO

Lipoteichoic acid (LTA) is a key cell wall component and virulence factor of Gram-positive bacteria. LTA contributes a major role in infection and it mediates inflammatory responses in the host. Rutaecarpine, an indolopyridoquinazolinone alkaloid isolated from Evodia rutaecarpa, has shown a variety of fascinating biological properties such as anti-thrombotic, anticancer, anti-obesity and thermoregulatory, vasorelaxing activity. It has also potent effects on the cardiovascular and endocrine systems. Herein, we investigated rutaecarpine's (Rut) anti-inflammatory effects in LTA-stimulated RAW macrophage cells. The Western blot and spectrophotometric results revealed that Rut inhibited the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and interleukin (IL)-1ß in the LTA-induced macrophage cells. Successively, our mechanistic studies publicized that Rut inhibited LTA-induced phosphorylation of mitogen-activated protein kinase (MAPK) including the extracellular signal-regulated kinase (ERK), and p38, but not c-Jun NH2-terminal kinase (JNK). In addition, the respective Western blot and confocal image analyses exhibited that Rut reserved nuclear transcription factor kappa-B (NF-κB) by hindering inhibitor of nuclear factor κB-α (IκBα) and NF-κB p65 phosphorylation and p65 nuclear translocation. These results indicate that Rut exhibits its anti-inflammatory effects mainly through attenuating NF-κB and ERK/p38 signaling pathways. Overall, this result suggests that Rut could be a potential therapeutic agent for the treatment of Gram-positive bacteria induced inflammatory diseases.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular , NF-kappa B , Animais , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Alcaloides Indólicos/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Quinazolinas , Células RAW 264.7 , Ácidos Teicoicos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
11.
Tumori ; : 3008916221101426, 2022 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-35723064

RESUMO

OBJECTIVE: This study aimed to explore erb-b2 receptor tyrosine kinase 2 (ERBB2) gene mutations in patients with non-small cell lung cancers (NSCLC) in Northeast China, and to analyze ERBB2 mutation subtypes and clinicopathological characteristics related to the presence of ERBB2 mutations. METHODS: In this study, 1087 tissue samples, 368 whole blood samples, and 68 pleural effusion samples from 1349 NSCLC were collected. Next-generation sequencing (NGS) was used to perform genetic testing on the samples. The proportion of patients with ERBB2 mutations and related clinicopathological characteristics were analyzed. RESULTS: The mutation rate of ERBB2 in NSCLC was 5.58% (85/1523). Of the patients with ERBB2 mutations, 27.63% (21/76) were over 65 years old, 59.21% (45/76) were women, and 68.42% (52/76) were non-smokers. The majority of tumors were adenocarcinomas (92.1%, 70/76) and stage III and IV diseases accounted for 81.58% (62/76) of all cases. There were 14 subtypes of ERBB2 mutations; the most frequently seen were ERBB2 copy number alteration (41.76%, 38/91) and ERBB2 exon 20 in-frame insertion (36.26%, 33/91). Of the patients with ERBB2 mutations, 24 had concurrent epidermal growth factor receptor mutations, seven had mesenchymal epithelial transition factor amplifications, and three had anaplastic lymphoma kinase mutations. The agreement between tissue and paired blood samples in the presence of ERBB2 mutations was 64.3% (9/14). CONCLUSION: ERBB2 mutations in Northeast China NSCLC patients have a unique molecular spectrum. Our work can provide guidance for the clinical diagnosis and treatment of patients with ERBB2 mutations in Northeast China.

12.
Adv Mater ; : e2202026, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35661432

RESUMO

Multiplexing technology with increased information capacity plays a crucial role in the realm of acoustic communication. Different quantities of sound waves, including time, frequency, amplitude, phase, and orbital angular momentum (OAM), have been independently introduced as the physical multiplexing approach to allow for enhanced communication densities. An acoustic metasurface is decorated with carbon nanotube patches, which when electrically pumped and set to rotate, functions as a hybrid mode-frequency-division multiplexer with synthetic dimensions. Based on this spatiotemporal modulation, a superposition of vortex beams with orthogonal OAMs and symmetric harmonics are both numerically and experimentally demonstrated. Also, flexible combinations of OAM modes with diverse frequency shifts are obtained by transforming the azimuthal phase distributions, which inspires a mode-frequency-division multiplexing approach that significantly promotes the communication capacity.

13.
Lancet Respir Med ; 2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35662408

RESUMO

BACKGROUND: Furmonertinib (AST2818) is an irreversible, selective, third-generation EGFR tyrosine-kinase inhibitor. We aimed to investigate the efficacy and safety of furmonertinib versus the first-generation EGFR tyrosine-kinase inhibitor gefitinib as first-line treatment in patients with EGFR mutation-positive locally advanced or metastatic non-small-cell lung cancer (NSCLC). METHODS: The FURLONG study is a multicentre, double-blind, randomised, phase 3 study done in 55 hospitals across mainland China. We enrolled patients who were aged 18 years or older and had histologically confirmed, locally advanced or metastatic, stage IIIB, IIIC, or IV unresectable NSCLC with EGFR exon 19 deletions or exon 21 Leu858Arg mutation on tissue biopsy confirmed by a central laboratory. Eligible patients were stratified according to EGFR mutation (exon 19 deletions or exon 21 Leu858Arg) and CNS metastases (with or without) and randomly assigned (1:1) to receive either oral furmonertinib (80 mg/day) or oral gefitinib (250 mg/day) in 21-day cycles until disease progression, the occurrence of intolerable toxicities, withdrawal of consent, or other discontinuation reasons judged by the investigators. Investigators, clinicians, participants, independent review centre (IRC) members, the sponsor, and those analysing the data were all masked to treatment allocation. The primary endpoint was IRC-assessed progression-free survival and, along with safety, was analysed in the full analysis set, which comprised all randomly assigned patients who had received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03787992, and is ongoing for survival follow-up. FINDINGS: Between May 30, 2019, and Dec 5, 2019, 750 patients were screened, of whom 358 were randomly assigned to receive either furmonertinib and gefitinib-matching placebo (n=178) or gefitinib and furmonertinib-matching placebo (n=180). 178 patients randomly assigned to furmonertinib and 179 patients randomly assigned to gefitinib were treated and were included in the full analysis set. Median follow-up was 21·0 months (IQR 18·0-23·5) in the furmonertinib group and 21·0 months (18·0-23·5) in the gefitinib group. Median IRC-assessed progression-free survival was 20·8 months (95% CI 17·8-23·5) in the furmonertinib group and 11·1 months (9·7-12·5) in the gefitinib group (hazard ratio 0·44, 95% CI 0·34-0·58; p<0·0001). Treatment-related adverse events of a grade 3 or more occurred in 20 (11%) of 178 patients in the furmonertinib group and in 32 (18%) of 179 patients in the gefitinib group. Treatment-related serious adverse events were reported in ten (6%) patients in the furmonertinib group and in 11 (6%) patients in the gefitinib group. Ten (6%) patients in the furmonertinib group and three (2%) patients in the gefitinib group died due to adverse events, which were all judged to be possibly unrelated to study treatment by the investigators. INTERPRETATION: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in Chinese patients with EGFR mutation-positive NSCLC, along with an acceptable safety profile without new signals. Furmonertinib is a new potential treatment option for this population. FUNDING: Shanghai Allist Pharmaceuticals and the China National Major Project for New Drug Innovation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

14.
Luminescence ; 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35608368

RESUMO

In this work, carbon dots (CDs) was easily synthesized from aspartic acid through a pyrolysis method. Based on their favourable fluorescence properties, CDs were utilized to design a metal ion-mediated fluorescent probe for N-acetyl-l-cysteine (NAC) detection. The fluorescence intensity of CDs was firstly quenched by manganese ions (Mn2+ ) through static quenching effect and subsequently restored by NAC via the combination with Mn2+ due to the coordination effect. Therefore, the fluorescent turn-on sensing of NAC was actuated based on the fluorescence quenching stimulated by Mn2+ and recovery induced by coordination. The fluorescence recovery efficiencies showed a proportional range to the concentration of NAC in the range 0.04-5 mmol L-1 and the detection limit was 0.03 mmol L-1 . Furthermore, this metal ion-mediated fluorescent nanoprobe was applied to human urine sample detection and the standard recovery rates were located in the range 97.62-102.34%. This was the first time that Mn2+ was used to construct a fluorescent nanoprobe for NAC. Compared with other heavy metal ions, Mn2+ with good biosecurity prevented the risk of application, which made the nanoprobe green and biopractical. The facile synthesis of CDs and novel metal ion-mediated sensing mode made it a promising method for pharmaceutical analysis.

15.
EBioMedicine ; 80: 104026, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35576643

RESUMO

BACKGROUND: There have been mixed reports on the beneficial effects of meditation in cardiovascular disease (CVD), which is widely considered the leading cause of death worldwide. METHODS: To clarify the role of meditation in modulating the heart-brain axis, we implemented an extreme phenotype strategy, i.e., Tibetan monks (BMI > 30) who practised 19.20 ± 7.82 years of meditation on average and their strictly matched non-meditative Tibetan controls. Hypothesis-free advanced proteomics strategies (Data Independent Acquisition and Targeted Parallel Reaction Monitoring) were jointly applied to systematically investigate and target the plasma proteome underlying meditation. Total cholesterol, low-density lipoprotein cholesterol  (LDL-C), apolipoprotein B (Apo B) and lipoprotein (a) [Lp(a)] as the potential cardiovascular risk factors were evaluated. Heart rate variability (HRV) was assessed by electrocardiogram. FINDINGS: Obesity, hypertension, and reduced HRV is offset by long-term meditation. Notably, meditative monks have blood pressure and HRV comparable to their matched Tibetan controls. Meditative monks have a protective plasma proteome, related to decreased atherosclerosis, enhanced glycolysis, and oxygen release, that confers resilience to the development of CVD. In addition, clinical risk factors in plasma were significantly decreased in monks compared with controls, including total cholesterol, LDL-C, Apo B, and Lp(a). INTERPRETATION: To our knowledge, this work is the first well-controlled proteomics investigation of long-term meditation, which opens up a window for individuals characterized by a sedentary lifestyle to improve their cardiovascular health with an accessible method practised for more than two millennia. FUNDING: See the Acknowledgements section.


Assuntos
Doenças Cardiovasculares , Sistema Cardiovascular , Meditação , Monges , Apolipoproteínas B , Encéfalo , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol , Humanos , Proteoma , Proteômica , Tibet
16.
J Microbiol Methods ; 197: 106479, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35504367

RESUMO

Near-infrared (NIR) fluorophores are widely used as fluorescent probes for bioimaging because of their minimal photodamage to biological samples, deep penetration, and low interference from background autofluorescence. Here, we employed a NIR fluorescent cyanine dye Cy5.5 to label DNA probes for nucleic acid blot hybridization. The specificity and sensitivity of fluorescent DNA probes were proven by both Southern blot and Northern blot using cellulolytic bacterium Ruminiclostridium cellulolyticum as a model. Furthermore, employing the method, we successfully identified the gene disruption of ClosTron to rule out off-target, analyzed the differential transcription of genes under different conditions, and confirmed RNA cleavage. Compared to other nonradioactive probes, the preparation and detection of Cy5.5-labeled probes are more simple, more economical, and versatile, suggesting that the Cy5.5-labeled probes are suitable for nucleic acid blot hybridization in addition to bioimaging.


Assuntos
DNA , Corantes Fluorescentes , Sondas de DNA/genética , Hibridização de Ácido Nucleico/métodos
17.
Ecotoxicol Environ Saf ; 239: 113643, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35588614

RESUMO

Humans maybe simultaneously exposed to multiple-metals and indoor air pollution in daily life. However, limited prospective studies have assessed the interaction between multiple metals exposure and biomass fuels use on hypertension in China. The prospective cohort study in rural areas along the Yangtze River included 2625 adults in 2014-2015, and they were followed up till 2019. Among 1248 rural residents who were without hypertension at baseline, 377 hypertension events (30.21%) were observed after 4.5 years of average follow-up time. First-morning urine samples of residents were collected at baseline, the association between urinary metals level and hypertension were assessed using quantile g-computation. Additionally, we also examined the effect of biomass fuels use, fuels switching, and cookstove ventilation on the association of metals exposure with hypertension. Quantile g-computation analyses showed a positive joint effect of 17 metals on hypertension, with the odds ratio (OR) of 1.68 (95% CI: 0.89, 3.14) when increasing all seventeen metals by one quartile, and cadmium, lithium, copper contributed the largest positive weights. Biomass fuels use can interact with cadmium exposure on hypertension with OR for interaction of 1.28 (95%CI: 1.00, 1.73), and increase the association between copper, manganese and zinc exposure and systolic blood pressure, lithium exposure and diastolic blood pressure at the follow-up visit. Moreover, switching from biomass fuels to clean fuels during follow up, cookstove ventilation can alleviate the risk of higher blood pressure from metals exposure. In rural areas along the Yangtze River, China, biomass fuels use for cooking can interact with multiple-metals exposure on hypertension. Residents who switched from biomass fuels to clean fuels and who used ventilation had a lower risk of hypertension. Further cohort studies are needed to clarify the mechanism of combined effects of metals exposure and biomass fuels use on the human health.

18.
Lancet Oncol ; 23(6): 739-747, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35576956

RESUMO

BACKGROUND: Extensive-stage small-cell lung cancer (ES-SCLC) is associated with poor prognosis and treatment options are scarce. Immunotherapy has shown robust clinical activity in ES-SCLC in previous phase 3 trials. We aimed to assess the efficacy and safety of adebrelimab (SHR-1316), a novel anti-PD-L1 antibody, with standard chemotherapy as a first-line treatment for ES-SCLC. METHODS: The CAPSTONE-1 study was a randomised, double-blind, placebo-controlled, phase 3 trial, done in 47 tertiary hospitals in China. Key inclusion criteria were patients aged 18-75 years, with previously untreated histologically or cytologically confirmed ES-SCLC and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Eligible patients were randomly assigned (1:1) to receive four to six cycles of carboplatin (area under the curve of 5 mg/mL per min, day 1 of each cycle) and etoposide (100 mg/m2 of body-surface area, on days 1-3 of each cycle) with either adebrelimab (20 mg/kg, day 1 of each cycle) or matching placebo, followed by maintenance therapy with adebrelimab or placebo. All treatments were given intravenously in 21-day cycles. Randomisation was done using a centralised interactive web response system with a block size of four, stratified by liver metastases, brain metastases, and lactate dehydrogenase concentration. The primary endpoint was overall survival in patients who received at least one dose of study medication. Safety was analysed in the as-treated population. This study is complete and registered with ClinicalTrials.gov, NCT03711305. FINDINGS: Between Dec 26, 2018, and Sept 4, 2020, 462 eligible patients were enrolled and randomly assigned: 230 (50%) patients received adebrelimab plus chemotherapy (adebrelimab group) and 232 (50%) patients received placebo plus chemotherapy (placebo group). At data cutoff (Oct 8, 2021), median follow-up was 13·5 months (IQR 8·9-20·1). Median overall survival was significantly improved in the adebrelimab group (median 15·3 months [95% CI 13·2-17·5]) compared with the placebo group (12·8 months [11·3-13·7]; hazard ratio 0·72 [95% CI 0·58-0·90]; one-sided p=0·0017). The most common treatment-related grade 3 or 4 adverse events were decreased neutrophil count (174 [76%] patients in the adebrelimab group and 175 [75%] patients in the placebo group), decreased white blood cell count (106 [46%] and 88 [38%]), decreased platelet count (88 [38%] and 78 [34%]), and anaemia (64 [28%] and 66 [28%]). Treatment-related serious adverse events occurred in 89 (39%) patients in the adebrelimab group and 66 (28%) patients in the placebo group. Four treatment-related deaths were reported: two each in the adebrelimab group (respiratory failure and interstitial lung disease and pneumonia) and placebo group (multiple organ dysfunction and unknown cause of death). INTERPRETATION: Adding adebrelimab to chemotherapy significantly improved overall survival with an acceptable safety profile in patients with ES-SCLC, supporting this combination as a new first-line treatment option for this population. FUNDING: Jiangsu Hengrui Pharmaceuticals.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina , Método Duplo-Cego , Etoposídeo , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico
19.
Toxicol Ind Health ; 38(7): 377-388, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35548910

RESUMO

To explore the epigenetic mechanism of deoxyribonucleic acid (DNA) damage induced by vinyl chloride (VC), we studied the micronuclei of peripheral blood lymphocytes in 193 subjects (92 in a VC exposure group employed in a chlorine-alkali plant; 101 in a control group employed in a power plant) and selected three pairs from the subjects (exposed and control) for whole-genome bisulfite sequencing (WGBS). The results showed that the rate of micronucleus formation in the VC exposure group was higher than that of control group (6.05 ± 3.28‰ vs. 2.01 ± 1.79‰). A total of 9534 differentially methylated regions (DMRs) were identified by WGBS, of which 4816 were hypomethylated and 4718 were hypermethylated. The Kyoto encyclopedia of genes and genomes (KEGG) pathway and gene ontology (GO) analyses showed the top three KEGG pathways were cancer , neuroactive ligand-receptor interaction, and axon guidance, and the top three GO-BP pathways enriched were multicellular organismal process, developmental process, and anatomical structure development. In the most enriched DMR pathway (pathways in cancer), we found that BCL2, TJP2, TAOK1, PFKFB3, LIPI, and LIPH were hypermethylated, and the methylation levels of BNIP1 and GRPEL2 were decreased. The methylation of differentially methylated genes (DMGs) mentioned above were verified by methylation-specific PCR (MSP) and agarose gel electrophoresis (AGE) in 50 pairs of subjects, where the coincidence rate was 60-100%. In conclusion, the epigenetic perturbations of specific DMGs (BCL2, TJP2, TAOK1, PFKFB3, LIPI, LIPH, BNIP1, and GRPEL2) may be associated with DNA damage from vinyl chloride exposure.


Assuntos
Neoplasias , Cloreto de Vinil , DNA , Metilação de DNA , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Cloreto de Vinil/toxicidade
20.
Oncol Rep ; 48(1)2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35583004

RESUMO

Relapse and drug resistance are the main causes of mortality in patients with small­cell lung cancer (SCLC). Intratumoral heterogeneity (ITH) is a key biological mechanism that leads to relapse and drug resistance. Phenotypic plasticity is an important factor that leads to ITH in SCLC, although its mechanisms and key regulatory factors remain to be elucidated. In the present study, cell proliferation and cell switch assay were measured using trypan blue. Alamar Blue was used to test drug sensitivity. Differential genes were screened by RNA sequencing. Reverse transcription­quantitative PCR and western blotting were performed to assess the expressions of CSF2/p­STAT3/MYC pathway related molecules, neuroendocrine (NE)/non­neuroendocrine (non­NE), transcription factors and drug­related targets. The present study found that SCLC cell line NCI­H69 exhibited adherent (H69A) and suspensive (H69S) phenotypes, which could switch back and forth. The two phenotypic cells had significant differences in cellular NE and non­NE characteristics, drug sensitivity and expression of drug­related targets. RNA sequencing showed that granulocyte­macrophage colony­stimulating factor [i.e., colony­stimulating factor 2 (CSF2)] was the main differentially expressed gene between the two phenotypes and that H69A cells highly expressed CSF2. The inhibition of CSF2 promoted the transformation from H69A to H69S, increased drug sensitivity and NE marker expression and decreased the non­NE marker expression in H69A. The STRING, Pathway Commons and Reactome databases showed a potential regulatory relationship between CSF2 and phosphorylated signal transducer and activator of transcription 3 (p­STAT3)/MYC. p­STAT3 and MYC expression was higher in H69A cells than in H69S cells and CSF2 silencing inhibited their expression. Taken together, these results indicated that CSF2 may regulate the phenotypic plasticity of SCLC through the phosphorylated STAT3/MYC pathway, thereby limiting the transformation between cell clones with different phenotypes and changing the sensitivity of specific cell clones to targeted drugs. Targeting CSF2 may be a potential therapeutic strategy to overcome drug resistance in SCLC treatment by influencing ITH.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Adaptação Fisiológica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/metabolismo
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