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1.
Int J Ophthalmol ; 14(10): 1548-1552, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34667731

RESUMO

AIM: To investigate the safety and efficacy of phacoemulsification with capsular-tension-ring implantation and posterior chamber intraocular lens implantation combined with ophthalmic endoscope-controlled goniosynechialysis (Phaco-CTR-IOL-OE-GSL) for treating secondary angle-closure glaucoma induced by traumatic lens subluxation. METHODS: A retrospective and descriptive study was performed on patients with lens subluxation, angle closure, goniosynechia, and evaluated intraocular pressure (IOP) that cannot be controlled with medication, who underwent Phaco-CTR-IOL-OE-GSL. The postoperative best-corrected visual acuity (BCVA), IOP, range of goniosynechia and complications were retrospectively observed. RESULTS: Nine patients with secondary angle-closure glaucoma induced by traumatic lens subluxation were included. The follow-up period was 51.1±8.6mo. The preoperative range of zonule rupture was 158.2°±33.0°, and the range of goniosynechia was 220.0°±92.5°. The baseline BCVA was 0.9±1.0 logMAR, IOP was 30.7±17.3 mm Hg, and number of anti-glaucoma medication was 3.2±1.1. Mild intraoperative hyphaemia with 8 eyes (88.8%) in the anterior chamber, and was absorbed two days postoperatively. One eye (11.1%) had postoperative ciliary body detachment and was recovered after five days of topical drug treatment. BCVA was 0.2±0.2 logMAR at 3mo postoperatively. The average IOP at the last follow-up was 16.7±2.0 mm Hg, and no anti-glaucoma medications were used. The average range of recurrent goniosynechia was 54.9°±33° at the final postoperative gonioscopic examination. CONCLUSION: Phaco-CTR-IOL-OE-GSL is safe and effective in the treatment of secondary angle-closure glaucoma induced by traumatic lens subluxation. The use of an endoscope provides a more direct and clear examination for GSL, and 360° dissection is easily achieved.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34639570

RESUMO

There has long been a gender bias in medicine. This qualitative study aims to identify the experience of sexism among frontline female nurses and further explore their expectations and possible strategies to get rid of gender bias. This is a descriptive phenomenological study of 23 female nurses with 11 ± 3.98 years of experience who spent 36 ± 6.50 days at the frontline during the initial COVID-19 outbreak. We employed Colaizzi's phenomenological analysis method to understand the subjective experiences, revealing the following themes: (a) materialization of gender identity; (b) incoordinate relationships; (c) future voice of female nurses. The gender bias experienced by female frontline nurses further challenges their emotional identity and self-identity. Therefore, it is important to require extensive consciousness-raising and policy support to defend female nurses' rights.


Assuntos
COVID-19 , Recursos Humanos de Enfermagem no Hospital , China , Feminino , Identidade de Gênero , Humanos , Masculino , Pandemias , Pesquisa Qualitativa , SARS-CoV-2 , Sexismo
3.
CRISPR J ; 4(5): 710-727, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34661426

RESUMO

DNA base editors, comprising nucleotide deaminases and catalytically impaired Cas9 nickase, have been widely used in various organisms for the efficient creation of point mutations, providing researchers with powerful tools in precise genome editing. However, they have been limited by the scope of the editing. The discovery and engineering of various CRISPR-Cas systems, especially SpCas9 variants xCas9, Cas9-NG, and Cas9-SpRY, have diversified the range of targetable DNA sequences and expanded the targeting scope of genomic base editing. To understand the editing properties comprehensively, we conducted an analysis of the editing properties of adenine base editors and cytosine base editors with xCas9, Cas9-NG, and Cas9-SpRY at endogenous sites with NGN protospacer adjacent motifs (PAM). Then, human genetic disease-associated DNA point mutations were installed at a single site or at dual sites with NGH PAM using base editors with SpCas9-NG (ABEmax-NG and Anc-BE4max-NG [BEs-NG]) in cultured human cell lines. Finally, the editing properties of BEs-NG in discarded human tripronuclear embryos were characterized. This study investigated the editing properties of DNA base editors with a relaxed PAM requirement and demonstrated the potential of BEs-NG in human genetic disease-related research and treatment.

4.
Drug Deliv ; 28(1): 2127-2136, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34617835

RESUMO

The aim of this study was to develop and evaluate a triptolide phospholipid complex (TPCX) for the treatment of rheumatoid arthritis (RA) by transdermal delivery. TPCX was prepared and characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR) analysis, transmission electron microscope (TEM), and scanning electron microscope (SEM). The solubility of TPCX was determined. Then, a TPCX cream was prepared to evaluate its percutaneous permeability and the antiarthritis effect. The transdermal permeability was determined using the Franz method, and a microdialysis system was used for skin pharmacokinetic study. A rat model of RA was prepared to evaluate the pharmacological effects. TPCX increased the solubility of triptolide in water, and the percutaneous permeability of TPCX cream was greatly enhanced compared with triptolide cream. The skin pharmacokinetic study indicated that TPCX cream has a longer biological half-life (t1/2) and mean residence time (MRT), but it has a shorter Tmax than that of triptolide cream in vivo. The area under the curve (AUC0-t)/AUC0-∞) and the peak concentration (Cmax) of TPCX cream were obviously higher than those of triptolide cream. The TPCX-loaded cream alleviated paw swelling and slowed down the progression of arthritis by inhibiting the inflammatory response by down regulating the TNF-α, IL-1ß, and IL-6 levels, thus exhibiting excellent antiarthritic effects. In summary, the prepared TPCX effectively increases the hydrophilicity of triptolide, which is good for its percutaneous absorption and enhances its effect on RA rats. TPCX can be a good candidate for the transdermal delivery to treat RA.

5.
Nurs Open ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34546665

RESUMO

AIM: This study aims to develop a reliable and validate Chinese version of Oldenburg Burnout Inventory (OLBI). DESIGN: A cross-sectional validation design was adopted in this study. METHODS: After obtaining the copyright by contacting with the author, the original English OLBI was developed to Chinese by forward translation, back-translation, cultural adaptation and a pre-test (20 nurses). The Chinese OLBI and Maslach Burnout Inventory (MBI) were administered to 641 clinical nurses during July and August, 2020. Internal consistency (Cronbach's α coefficient), split reliability (split half coefficient), construct validity (confirmatory factor analysis) and criterion validity (comparison with MBI, using Pearson correlation analysis) were assessed. RESULTS: The Chinese OLBI included 16 items. Exploratory factor analysis extracted two factors with a cumulative contribution of 62.245%. Two-dimensional structure (exhaustion and disengagement) was confirmed. It has good internal consistency (Cronbach's α coefficient values of 0.905, 0.933 and 0.876 for the total questionnaire, exhaustion dimension and disengagement dimension, respectively), split half reliability (split half coefficient = 0.883, p < .01) and criterion validity (r = 0.873, p < .01). Pearson coefficients between 16 items and the scale varied from 0.479-0.765. An acceptable model fit (χ2 /df = 2.49, RMSEA = 0.068, TLI = 0.906, CFI = 0.922, SRMR = 0.061) was achieved.

6.
Eur J Investig Health Psychol Educ ; 11(3): 999-1010, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34563087

RESUMO

Previous findings have shown essential connections between linguistic and gustatory stimuli for people with autism or lexical gustatory synesthesia. We examined the associative learning of novel linguistic forms in Japanese as a native language and tastes (candies and chocolates) for healthy people. Healthy subjects performed four phases: (a) evaluation phase of gustatory features; (b) learning phases of novel linguistic form and gustatory stimulus pairs (G) or novel word forms (W); (c) recognition memory phases linked with G and W; and (d) free recall phase for G and W. In the recognition memory phases, the performance scores of W were higher than those of G, while there was no significant difference between response times of G and W. Additionally, no difference between recall performances in G and W was also shown. A subjective evaluation of gustatory features (sweetness) negatively correlated with the recall score for linguistic forms connected to the gustatory feature, whereas the accuracy rates of the recognition memory phase in G positively correlated with those of the free recall phase in G. Although learning of novel linguistic forms is more efficient than learning of the relationships between novel linguistic forms and tastes, gustatory features influence the free recall performances of linguistic forms linked with the tastes. These results may contribute to future applications to word learning not just for patients, but also healthy people.

7.
Int J Nanomedicine ; 16: 6129-6140, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511910

RESUMO

Purpose: With the development of nanomedicine, microwave ablation enhanced by multifunctional nanoplatforms has been widely studied for synergistic cancer therapy. Though scientists have got a lot of significant achievements in this field, the detailed molecular mechanisms and potential targets of microwave ablation enhanced by multifunctional nanoplatforms still need further exploration. In this study, we found that a kind of magnetite Fe3O4 nanoparticles (Fe3O4 NPs) could induce severe endoplasmic reticulum stress and activate cancer apoptosis under the irradiation of mild microwave. Methods: In this study, plenty of studies including cell immunofluorescence, mitochondrial membrane potential, electron microscopy, atomic force microscopy and microwave ablation in vivo were conducted to explore the molecular mechanisms and potential targets of microwave ablation enhanced by the Fe3O4 NPs. Results: The IRE1-ASK1-JNK pathway was strongly activated in A375 cells treated with both Fe3O4 NPs and mild microwave. The endoplasmic reticulum of the A375 cells was significantly dilated and exhibited ballooning degeneration. By investigating the mitochondrial membrane potential (ΔΨm), we found that the mitochondria of cancer cells had been significantly damaged under microwave treatment coupled with Fe3O4 NPs. In addition, melanoma of B16F10-bearing mice had also been effectively inhibited after being treated with Fe3O4 NPs and microwave. Conclusion: In this study, we found that a kind of magnetite Fe3O4 nanoparticles could induce severe ER stress and activate cancer apoptosis under mild microwave irradiation. Apparent apoptosis had been observed in the A375 cells under a scanning electron microscope and transmission electron microscope. Moreover, melanoma had also been inhibited effectively in vivo. As a result, the endoplasmic reticulum stress is a promising target with clinical potential in nanomedicine and cancer therapy.

8.
Cell Mol Immunol ; 18(10): 2344-2357, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34480146

RESUMO

Colitis is a common disease of the colon that is very difficult to treat. Probiotic bacteria could be an effective treatment. The probiotic Escherichia coli Nissle 1917 (EcN) was engineered to synthesize the ketone body (R)-3-hydroxybutyrate (3HB) for sustainable production in the gut lumen of mice suffering from colitis. Components of heterologous 3HB synthesis routes were constructed, expressed, optimized, and inserted into the EcN genome, combined with deletions in competitive branch pathways. The genome-engineered EcN produced the highest 3HB level of 0.6 g/L under microaerobic conditions. The live therapeutic was found to colonize the mouse gastrointestinal tract over 14 days, elevating gut 3HB and short-chain-length fatty acid (SCFA) levels 8.7- and 3.1-fold compared to those of wild-type EcN, respectively. The sustainable presence of 3HB in mouse guts promoted the growth of probiotic bacteria, especially Akkermansia spp., to over 31% from the initial 2% of all the microbiome. As a result, the engineered EcN termed EcNL4 ameliorated colitis induced via dextran sulfate sodium (DSS) in mice. Compared to wild-type EcN or oral administration of 3HB, oral EcNL4 uptake demonstrated better effects on mouse weights, colon lengths, occult blood levels, gut tissue myeloperoxidase activity and proinflammatory cytokine concentrations. Thus, a promising live bacterium was developed to improve colonic microenvironments and further treat colitis. This proof-of-concept design can be employed to treat other diseases of the colon.

9.
J Clin Psychiatry ; 82(6)2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34551222

RESUMO

Objective: Dyslipidemia is a controversial risk for Alzheimer's disease (AD) with unknown mechanisms. This study aimed to investigate polygenic effects of the lipid metabolic pathway on cerebrospinal fluid (CSF) core biomarkers, cognition, and default mode network (DMN).Methods: Cross-sectional data on serum lipids, CSF core biomarkers, and functional MRI findings for 113 participants (25 cognitively normal, 20 with subjective cognitive decline, 24 early amnestic, 23 with late mild cognitive impairment, and 21 with AD) from the Alzheimer's Disease Neuroimaging Initiative were included. Different cognitive stages were categorized based on neuropsychological assessments. Multivariable linear regression analyses were conducted to investigate the polygenic and interactive effects on the DMN. The correlations of lipid-related polygenes and serum lipids with cognitive performance were also studied via regression analyses.Results: The polygenic scores were significantly correlated with CSF levels of core biomarkers (P < .05) but not with cognition. Several serum lipids were associated with total tau. CSF core biomarkers and 6 serum lipids both could impact cognition in a nonlinear manner. Polygenic effects exhibited diverse trajectories on the DMN subsystems across the AD spectrum. Extensive genetic and interactive effects were mainly concentrated in the cortical frontal-parietal network and subcortical regions. Brain regions of lipid metabolites linking to DMN involved sensorimotor network and occipital lobe.Conclusions: Polygenic effects of the lipid metabolic pathway could accelerate pathological changes and disrupted DMN subsystem trajectory across the AD spectrum. These results deepen the understanding of the mechanism of lipid metabolism affecting the neural system and provide several lipid indicators that enable the impairments of lipid metabolism on the brain to be monitored.

10.
Org Biomol Chem ; 19(38): 8295-8300, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34519742

RESUMO

The electrochemical sulfonylation of enamides with sodium sulfinates was developed in an undivided cell in constant current mode, leading to the formation of ß-amidovinyl sulfones in moderate to good yields. The catalyst-, electrolyte- and oxidant-free protocol features good functional group tolerance and employs electric current as a green oxidant. Mechanistic insights into the reaction indicate that the reaction may proceed via a radical mechanism.

11.
Genome Biol ; 22(1): 230, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404453

RESUMO

BACKGROUND: Biomolecular condensates have been implicated in multiple cellular processes. However, the global role played by condensates in 3D chromatin organization remains unclear. At present, 1,6-hexanediol (1,6-HD) is the only available tool to globally disrupt condensates, yet the conditions of 1,6-HD vary considerably between studies and may even trigger apoptosis. RESULTS: In this study, we first analyzed the effects of different concentrations and treatment durations of 1,6-HD and found that short-term exposure to 1.5% 1,6-HD dissolved biomolecular condensates whereas long-term exposure caused aberrant aggregation without affecting cell viability. Based on this condition, we drew a time-resolved map of 3D chromatin organization and found that short-term treatment with 1.5% 1,6-HD resulted in reduced long-range interactions, strengthened compartmentalization, homogenized A-A interactions, B-to-A compartment switch and TAD reorganization, whereas longer exposure had the opposite effects. Furthermore, the long-range interactions between condensate-component-enriched regions were markedly weakened following 1,6-HD treatment. CONCLUSIONS: In conclusion, our study finds a proper 1,6-HD condition and provides a resource for exploring the role of biomolecular condensates in 3D chromatin organization.

12.
Ecotoxicol Environ Saf ; 223: 112582, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34365209

RESUMO

Heavy metal pollution in the environment is mostly manifested as a multi-elemental compound pollution. The effect of the long-term exposure to heavy metal pollution on the gut microbes of insects has remained unknown. For the current work, the population of Eucriotettix oculatus living in mining areas around the Diaojiang River with a history of hundreds of years of pollution, was selected along with the similar species living in non-mining areas to conduct a comparative study of their gut microbes. The microbial communities were analyzed using 16S rRNA amplicon sequencing. The results showed Proteobacteria to be dominant among gut microbes of E. oculatus, but the abundance of Proteobacteria was significantly increased when the insects were exposed to the environment with heavy metal pollution. The symbiotic bacteria belonging to genus Wolbachia were found to be dominant among the insect population from the non-mining area group, while the pathogenic bacteria belonging to Aeromonas were dominant among the insect population of the mining area group. The diversity analysis showed that the gut microbial community diversity of E. oculatus was reduced in the heavy metal pollution habitat. The analysis of the differences in the gut microbial population and metabolic pathways of the two groups showed that the heavy metal pollution caused the increase in pathogenic bacteria among the gut microbes of E. oculatus, which might have a negative impact on the health of the host. At the same time, probiotics and the beneficial metabolism pathways were also found to increase and enhance, helping the host to resist the damage caused by heavy metal stress. This might be one of the strategies used by E. oculatus to adapt to heavy metal pollution.


Assuntos
Gafanhotos , Metais Pesados , Microbiota , Poluentes do Solo , Animais , Metais Pesados/análise , Metais Pesados/toxicidade , RNA Ribossômico 16S/genética , Solo , Microbiologia do Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidade
13.
Artigo em Inglês | MEDLINE | ID: mdl-34444486

RESUMO

The outbreak of coronavirus disease in 2019 (COVID-19) in Wuhan has led Chinese health authorities to recruit healthcare providers from the least-affected areas to provide care to the infected patients in Wuhan. We took further steps to explain some plausible reasons for their experiences. We used interpretative phenomenological analysis (IPA) to understand the subjective experiences, as well as the reasons for these experiences among the healthcare providers who had traveled from the least-affected parts of China to render aid during Wuhan's COVID-19 outbreak. Using purposive and snowball sampling, healthcare professionals were recruited from three major hospitals in Jiangsu province. Semi-structured interviews were conducted from 1 September to 14 November 2020 in face-to-face contexts. Ten nurses and four doctors provided their informed consent for the study. The primary superordinate theme from the responses highlighted how social identity and individual needs were challenged by each individual's professional ethics. COVID-19 not only presents significant risks to the health of nurses and medical doctors; it further challenges their emotional and psychosocial wellbeing. Care should be taken in allocating support and help, with the careful deployment of professional values and beliefs, so that any human resource as precious as medical doctors and nurses can be protected.


Assuntos
COVID-19 , China/epidemiologia , Atenção à Saúde , Pessoal de Saúde , Humanos , Pesquisa Qualitativa , SARS-CoV-2
14.
Artigo em Inglês | MEDLINE | ID: mdl-34444362

RESUMO

The use of social network sites (SNSs) is inevitable in daily life. Everyone is likely to be addicted to SNSs, especially medical students. This study is aimed to assess the degree of SNS addiction and its relation to psychosocial factors such as depression, loneliness and unmet interpersonal needs among Chinese medical students. The cross-section survey was conducted from March to May in 2018 in Shanghai Jiao Tong University School of Medicine. Of the total 1067 participants, 33.18% had an SNS addiction, 87.7% of the participants used SNSs every day during last month and 53.42% of the participants used SNSs for at least an hour per day during the last week. SNS addiction is positively related with depression both directly and indirectly. The mediating roles of loneliness and unmet interpersonal needs on the relationship between SNS addiction and depression are significant. For the well-being of medical students, efforts should be taken to prevent them from becoming addicted to SNSs.


Assuntos
Mídias Sociais , Estudantes de Medicina , China/epidemiologia , Depressão/epidemiologia , Humanos , Solidão , Rede Social
15.
Sci Rep ; 11(1): 15764, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344976

RESUMO

The movements of ancient crop and animal domesticates across prehistoric Eurasia are well-documented in the archaeological record. What is less well understood are the precise mechanisms that farmers and herders employed to incorporate newly introduced domesticates into their long-standing husbandry and culinary traditions. This paper presents stable isotope values (δ13C, δ15N) of humans, animals, and a small number of plants from the Hexi Corridor, a key region that facilitated the movement of ancient crops between Central and East Asia. The data show that the role of animal products in human diets was more significant than previously thought. In addition, the diets of domestic herbivores (sheep/goat, and cattle) suggest that these two groups of domesticates were managed in distinct ways in the two main ecozones of the Hexi Corridor: the drier Northwestern region and the wetter Southeastern region. Whereas sheep and goat diets are consistent with consumption of naturally available vegetation, cattle exhibit a higher input of C4 plants in places where these plants contributed little to the natural vegetation. This suggests that cattle consumed diets that were more influenced by human provisioning, and may therefore have been reared closer to the human settlements, than sheep and goats.

16.
Nurs Ethics ; : 9697330211015284, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34254552

RESUMO

BACKGROUND: In 2019, an outbreak of COVID-19 broke out in Hubei, China. Medical workers from all over the country rushed to Hubei and participated in the treatment and care of COVID-19 patients. These nurses, dedicated to their professional practice, volunteered to provide compassion and expert clinical care during the pandemic. As with other acts of heroism, the ethical dilemmas associated with working on the front line must be considered for future practice. PURPOSE: To explore the ethical dilemmas of frontline nurses of Jiangsu Province in China during deployment to Wuhan to fight the novel coronavirus pneumonia, and to provide a basis for developing strategies to help nursing staff address personal and practice concerns in order to work more effectively during this pandemic and other disasters in the future. RESEARCH DESIGN AND METHOD: Using the phenomenological research method and the purpose sampling method, semi-structured interviews were conducted with 10 nurses, post-deployment to Wuhan, who had worked on the front line to fight the novel coronavirus. ETHICAL CONSIDERATIONS: The research proposal was approved by the Research Ethic Committee of Yangzhou University, China. FINDINGS: From the analysis of the interviews of the 10 participants, three main themes were identified: ethical dilemmas in clinical nursing, ethical dilemmas in interpersonal relationships, and ethical dilemmas in nursing management. CONCLUSION: During a quick response to public health emergencies, where nurses are deployed immediately as a call to action, the issues surrounding ethical dilemmas from several perspectives must be considered. This research suggests that a team approach to proactive planning and open communication during the emergency is an efficient and productive strategy to improve the nurses' experience and sense of well-being.

17.
J Exp Clin Cancer Res ; 40(1): 221, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34217349

RESUMO

Tumor immunity consists of various types of cells, which serve an important role in antitumor therapy. The gastrointestinal tract is colonized by trillions of microorganisms, which form the gut microbiota. In addition to pathogen defense and maintaining the intestinal ecosystem, gut microbiota also plays a pivotal role in various physiological processes. Recently, the association between these symbionts and cancer, ranging from oncogenesis and cancer progression to resistance or sensitivity to antitumor therapies, has attracted much attention. Metagenome analysis revealed a significant difference between the gut microbial composition of cancer patients and healthy individuals. Moreover, modulation of microbiome could improve therapeutic response to immune checkpoint inhibitors (ICIs). These findings suggest that microbiome is involved in cancer pathogenesis and progression through regulation of tumor immunosurveillance, although the exact mechanisms remain largely unknown. This review focuses on the interaction between the microbiome and tumor immunity, with in-depth discussion regarding the therapeutic potential of modulating gut microbiota in ICIs. Further investigations are warranted before gut microbiota can be introduced into clinical practice.

19.
Theranostics ; 11(14): 7092-7109, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093873

RESUMO

Background: Recent studies in non-small cell lung cancer (NSCLC) patients have demonstrated that first-line immunotherapy is associated with better therapeutic response than second-line treatment. So far, the mechanisms need to be explored. It prompted us to evaluate the association between first-line chemotherapy and subsequent immunotherapy in NSCLC as well as its underlying mechanisms at the genomic and transcriptomic level. Methods: We launched a prospective, observational clinical study, paired tumor biopsies before and after chemotherapy were collected from NSCLC patients without tyrosine kinase inhibitor (TKI)-related driver gene mutations. The analyses included genomic and transcriptional changes performed by next-generation sequencing (NGS)-based whole-exome sequencing (WES) and messager ribonucleic acid (mRNA) sequencing. Characteristic mutational alterations in 1574 genes were investigated based on mutational status, clinicopathological factors, and chemotherapy responses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, neoantigen prediction and intratumoral heterogeneity evaluation were also performed. Results: Samples and information from 32 NSCLC patients without TKI-related driver gene mutations were obtained. We found that the total number of single nucleotide variants (SNV)/insertion-deletion (INDEL) mutations did not change significantly after chemotherapy. The tumor mutation burden (TMB) decreased significantly after chemotherapy in smoking patients and the decreased TMB correlated with a better survival of smoking patients. The change in copy number variations (CNVs) exhibited a decreasing trend during chemotherapy. Subsequent analysis at mRNA level revealed a significant decrease in the expression levels of genes related to antigen processing and presentation as well as other factors relevant for response to immunotherapy. Pathway enrichment analysis confirmed that the immune-related signaling pathways or biological processes were decreased after first-line chemotherapy. Conclusions: Our study presents an explanation for the unsatisfactory results of immunotherapy when given after chemotherapy, and suggests that first-line chemotherapy is able to influence the tumor microenvironment and decrease the efficacy of subsequent immunotherapy. The study was registered at ClinicalTrials.gov, number NCT03764917, and has completed enrolment; patients are still in follow-up.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Biópsia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Inibidores Enzimáticos/metabolismo , Perfilação da Expressão Gênica , Ontologia Genética , Genômica , Humanos , Mutação INDEL , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Estudos Observacionais como Assunto , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Estudos Prospectivos , RNA-Seq , Fumantes , Microambiente Tumoral , Sequenciamento Completo do Exoma
20.
Adv Mater ; 33(30): e2004734, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34137090

RESUMO

When analyzing biological phenomena and processes, multiplexed biodetection has many advantages over single-factor biodetection and is highly relevant to both human health issues and advancements in the life sciences. However, many key problems with current multiplexed biodetection strategies remain unresolved. Herein, the main issues are analyzed and summarized: 1) generating sufficient signal to label targets, 2) improving the signal-to-noise ratio to ensure total detection sensitivity, and 3) simplifying the detection process to reduce the time and labor costs of multiple target detection. Then, available solutions made possible by designing and controlling the properties of micro- and nanomaterials are introduced. The aim is to emphasize the role that micro-/nanomaterials can play in the improvement of multiplexed biodetection strategies. Through analyzing existing problems, introducing state-of-the-art developments regarding relevant materials, and discussing future directions of the field, it is hopeful to help promote necessary developments in multiplexed biodetection and associated scientific research.

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