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1.
Zhongguo Zhong Yao Za Zhi ; 47(6): 1666-1676, 2022 Mar.
Artigo em Zh | MEDLINE | ID: mdl-35347966

RESUMO

This study screened and analyzed the differentially expressed genes(DEGs) between colorectal cancer(CRC) tissues and normal tissues with bioinformatics techniques to predict biomarkers and Chinese medicinals for the diagnosis and treatment of CRC. The microarray data sets GSE21815, GSE106582, and GSE41657 were downloaded from the Gene Expression Omnibus(GEO), and the DEGs were screened by GEO2 R, followed by the Gene Ontology(GO) tern enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the DEGs based on DAVID. The protein-protein interaction network was constructed by STRING, and MCODE and Cytohubba plug-ins were used to screen the significant modules and hub genes in the network. UCSC, cBioPortal, and Oncomine were employed for hierarchical clustering, survival analysis, Oncomine analysis, and correlation analysis of clinical data. Coremine Medical was applied to predict the Chinese medicinals acting on hub genes. A total of 284 DEGs were screened out, with 146 up-regulated and 138 down-regulated. The up-regulated genes were mainly involved in cell cycle, NLRs pathway, and TNF signaling pathway, and the down-regulated genes were related to mineral absorption, nitrogen metabolism, and bicarbonate reabsorption in proximal tubules. The 15 hub genes were CDK1, CDC20, AURKA, MELK, TOP2 A, PTTG1, BUB1, CDCA5, CDC45, TPX2, NEK2, CEP55, CENPN, TRIP13, and GINS2, among which CDK1 and CDC20 were regarded as core genes. The high expression of CDK1 and CDC20 suggested poor prognosis, and they significantly expressed in many cancers, especially breast cancer, lung cancer, and CRC. The expression of CDK1 and CDC20 was correlated with gender, tumor type, TNM stage, and KRAS gene mutation. The potential effective medicinals against CRC were Scutellariae Radix, Scutellariae Barbatae Herba, Arnebiae Radix, etc. The significant expression of CDK1 and CDC20 can help distinguish tumor tissues from normal tissues, and is related to survival prognosis. Thus, the two can be used as biomarkers for the diagnosis and treatment of CRC. This study provides a reference for related drug development.


Assuntos
Neoplasias Colorretais , Biologia Computacional , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Biologia Computacional/métodos , Detecção Precoce de Câncer , Perfilação da Expressão Gênica/métodos , Humanos , Medicina Tradicional Chinesa
2.
Nano Lett ; 17(6): 3862-3869, 2017 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-28511013

RESUMO

Nanocrystal superlattices are typically fabricated by either solvent evaporation or destabilization methods that require long time periods to generate highly ordered structures. In this paper, we report for the first time the use of electric fields to reversibly drive nanocrystal assembly into superlattices without changing solvent volume or composition, and show that this method only takes 20 min to produce polyhedral colloidal crystals, which would otherwise need days or weeks. This method offers a way to control the lattice constants and degree of preferential orientation for superlattices and can suppress the uniaxial superlattice contraction associated with solvent evaporation. In situ small-angle X-ray scattering experiments indicated that nanocrystal superlattices were formed while solvated, not during drying.

3.
Nano Lett ; 17(9): 5580-5586, 2017 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-28762274

RESUMO

Auger recombination lifetimes, absorption cross sections, and the quantum yields of carrier multiplication (CM), or multiexciton generation (MEG), were determined for solvent-dispersed silicon (Si) nanorods using transient absorption spectroscopy (TAS). Nanorods with an average diameter of 7.5 nm and aspect ratios of 6.1, 19.3, and 33.2 were examined. Colloidal Si nanocrystals of similar diameters were also studied for comparison. The nanocrystals and nanorods were passivated with organic ligands by hydrosilylation to prevent surface oxidation and limit the effects of surface trapping of photoexcited carriers. All samples used in the study exhibited relatively efficient photoluminescence. The Auger lifetimes increased with nanorod length, and the nanorods exhibited higher CM quantum yield and efficiency than the nanocrystals with a similar band gap energy Eg. Beyond a critical length, the CM quantum yield decreases. Nanorods with the aspect ratio of 19.3 had the highest CM quantum yield of 1.6 ± 0.2 at 2.9Eg, which corresponded to a multiexciton yield that was twice as high as observed for the spherical nanocrystals.

4.
Langmuir ; 33(45): 13068-13076, 2017 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-29058436

RESUMO

Colloidal dodecene-passivated silicon (Si) nanocrystals were dispersed in hexane or chloroform and deposited onto substrates as face-centered cubic superlattices by slowly evaporating the solvent. The uniformity of the nanocrystals enables extended order; however, the solvent and the evaporation protocol significantly influence the self-assembly process, determining the morphology of the films, the extent of order, and the superlattice orientation on the substrate. Chloroform yielded superlattices with step-flow growth morphologies and (111)SL, (100)SL, and (110)SL orientations. Hexane led to mostly island morphologies when evaporated at room temperature with exclusively (111)SL orientations. Higher evaporation temperatures led to more extensive step-flow deposition. A model for the surface diffusion of nanocrystals adsorbed on the superlattice surface is developed.

5.
Nano Lett ; 16(12): 7814-7821, 2016 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-27960489

RESUMO

Uniform silicon nanocrystals were synthesized with cuboctahedral shape and passivated with 1-dodecene capping ligands. Transmission electron microscopy, electron diffraction, and grazing incidence wide-angle and small-angle X-ray scattering show that these soft cuboctahedra assemble into face-centered cubic superlattices with orientational order. The preferred nanocrystal orientation was found to depend on the orientation of the superlattices on the substrate, indicating that the interactions with the substrate and assembly kinetics can influence the orientation of faceted nanocrystals in superlattices.

6.
Langmuir ; 31(23): 6532-7, 2015 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-26010097

RESUMO

Undecanoic acid facilitates attachment of styrene to hydride-terminated Si nanocrystals at room temperature, avoiding polymerization of styrene, yielding free-standing styrene-terminated Si nanocrystals. The nanocrystals have diamond cubic crystal structure, with photophysical properties similar to typical alkene-capped Si nanocrystals, such as bright photoluminescence with relatively long radiative lifetimes. We propose a reaction mechanism for room temperature styrene addition in which the resonance form of undecanoic acid coordinates to surface Si-H and facilitates H(-) attack at terminal C═C of styrene.

7.
Langmuir ; 31(24): 6886-93, 2015 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-26024323

RESUMO

Hydride-terminated silicon (Si) nanocrystals were capped with dodecanethiol by a thermally promoted thiolation reaction. Under an inert atmosphere, the thiol-capped nanocrystals exhibit photoluminescence (PL) properties similar to those of alkene-capped Si nanocrystals, including size-tunable emission wavelength, relatively high quantum yields (>10%), and long radiative lifetimes (26-280 µs). X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy confirmed that the ligands attach to the nanocrystal surface via covalent Si-S bonds. The thiol-capping layer, however, readily undergoes hydrolysis and severe degradation in the presence of moisture. Dodecanethiol could be exchanged with dodecene by hydrosilylation for enhanced stability.

8.
Langmuir ; 31(24): 6924-32, 2015 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-26013597

RESUMO

Dodecanethiol-capped gold (Au) nanocrystal superlattices can undergo a surprisingly diverse series of ordered structure transitions when heated (Goodfellow, B. W.; Rasch, M. R.; Hessel, C. M.; Patel, R. N.; Smilgies, D.-M.; Korgel, B. A. Nano Lett. 2013, 13, 5710-5714). These are the result of highly uniform changes in nanocrystal size, which subsequently force a spontaneous rearrangement of superlattice structure. Here, we show that halide-containing surfactants play an essential role in these transitions. In the absence of any halide-containing surfactant, superlattices of dodecanethiol-capped (1.9-nm-diameter) Au nanocrystals do not change size until reaching about 190-205 °C, at which point the gold cores coalesce. In the presence of halide-containing surfactant, such as tetraoctylphosphonium bromide (TOPB) or tetraoctylammounium bromide (TOAB), the nanocrystals ripen at much lower temperature and superlattices undergo various ordered structure transitions upon heating. Chloride- and iodide-containing surfactants induce similar behavior, destabilizing the Au-thiol bond and reducing the thermal stability of the nanocrystals.

9.
Faraday Discuss ; 185: 481-95, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26399301

RESUMO

Silicon nanocrystals functionalized with tetraphenylporphyrin Zn(II) chromophores at the periphery perform as light harvesting antennae: excitation of the porphyrin units in the visible spectral region yields sensitized emission of the silicon nanocrystal core in the near infrared with a long lifetime (λ(max) = 905 nm, τ = 130 µs). This result demonstrates that this hybrid material has a potential application as a luminescent probe for bioimaging.

10.
Nano Lett ; 13(7): 3101-5, 2013 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-23731184

RESUMO

Silicon nanorods are grown by trisilane decomposition in hot squalane in the presence of tin (Sn) nanocrystals and dodecylamine. Sn induces solution-liquid-solid nanorod growth with dodecylamine serving as a stabilizing ligand. As-prepared nanorods do not luminesce, but etching with hydrofluoric acid to remove residual surface oxide followed by thermal hydrosilylation with 1-octadecene induces bright photoluminescence with quantum yields of 4-5%. X-ray photoelectron spectroscopy shows that the ligands prevent surface oxidation for months when stored in air.

11.
Sci Total Environ ; 912: 168713, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38007125

RESUMO

Pseudanabaena sp. and the odor compound it produces, 2-methylisoborneol (2-MIB), has been reportedly responsible for off-flavor pollution worldwide, leading to substandard drinking water sensory indicators and serious water supply crises. In this paper, the hydroxyl radical (•OH) produced by the synergistic effect of strong ionization discharge and hydrodynamic cavitation rapidly inactivated Pseudanabaena sp. and simultaneously mineralized 2-MIB to a concentration of 2.57 ng/L, which is below the odor threshold of 10 ng/L for a total reactive oxidants (TRO) concentration of 1.2 mg/L within 12 s. Crucially, the intracellular 2-MIB level was maintained in approximately 155.26- 162.29 ng/L range, indicating that 2-MIB was not released from the cells. Based on the scanning electron microscopy (SEM) results, the integrity of Pseudanabaena sp. cells was maintained with intact membranes and no intracellular organic matters (IOM) released during •OH inactivation. In contrast, ClO2 caused severe membrane rupture and massive IOM release. Based on the gas chromatograph/mass spectrometer (GC/MS) analyses and mass spectral database, the chromatogram fitted the baseline with a TRO concentration of 4 mg/L and no peaks corresponding to intermediates were detected. Moreover, •OH could mineralize 2-MIB by opening the ring structures of 1,2,3,3-tetramethyl-4-cyclopentenone, neomenthol, and 2-methylcyclohexene-1-aldehyde to produce small-molecule compounds, finally leading to CO2 and H2O formation via three reaction pathways. Therefore, the •OH not only maintained the cell integrity of Pseudanabaena sp. during inactivation but also mineralized 2-MIB simultaneously.


Assuntos
Canfanos , Cianobactérias , Radical Hidroxila , Odorantes , Cianobactérias/metabolismo , Abastecimento de Água , Oxidantes
12.
Langmuir ; 29(5): 1533-40, 2013 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-23312033

RESUMO

H-terminated Si nanocrystals undergo room temperature hydrosilylation with bifunctional alkenes with distal polar moieties-ethyl ester, methyl ester, or carboxylic acids-without the aid of light or added catalyst. The passivated Si nanocrystals exhibit bright photoluminescence (PL) and disperse in polar solvents, including water. We propose a reaction mechanism in which ester or carboxylic acid groups facilitate direct nucleophilic attack of the highly curved Si surface of the nanocrystals by the alkene.


Assuntos
Alcenos/química , Nanopartículas/química , Silício/química , Temperatura , Ácidos Carboxílicos/química , Ésteres/química , Estrutura Molecular , Tamanho da Partícula , Propriedades de Superfície
13.
Chemosphere ; 321: 138160, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36796522

RESUMO

Efficient CH4/N2 separation from unconventional natural gas is vital for both energy recycling and climate change control. Figuring out the reason for the disparity between ligands in the framework and CH4 is the crucial problem for developing adsorbents in PSA progress. In this study, a series of eco-friendly Al-based MOFs, including Al-CDC, Al-BDC, CAU-10, and MIL-160, were synthesized to investigate the influence of ligands on CH4 separation through experimental and theoretical analyses. The hydrothermal stability and water affinity of synthetic MOFs were explored through experimental characterization. The active adsorption sites and adsorption mechanisms were investigated via quantum calculation. The results manifested that the interactions between CH4 and MOFs materials were affected by the synergetic effects of pore structure and ligand polarities, and the disparities of ligands within MOFs determined the separation efficiency of CH4. Especially, the CH4 separation performance of Al-CDC with high sorbent selection (68.56), moderate isosteric adsorption heat for CH4 (26.3 kJ/mol), and low water affinity (0.1 g/g at 40% RH) was superior to most porous adsorbents, which was attributed to its nanosheet structure, proper polarity, reduced local steric hindrance, and extra functional groups. The analysis of active adsorption sites indicated that hydrophilic carboxyl groups and hydrophobic aromatic ring were the dominant CH4 adsorption sites for liner ligands and bent ligands, respectively. The methylene groups with saturated C-H bonds enhanced the wdV interaction between ligands and CH4, resulting in the highest binding energy of CH4 for Al-CDC. The results provided valuable guidance for the design and optimization of high-performance adsorbents for CH4 separation from unconventional natural gas.


Assuntos
Estruturas Metalorgânicas , Ligantes , Gás Natural , Metano , Água
14.
Int Immunopharmacol ; 123: 110785, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37598630

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) with angiogenesis inhibitors have been used to treat advanced lung cancer. Their associated treatment-related adverse events (trAEs) are currently considered acceptable; however, no conclusion has been reached. We aimed to summarize the trAEs caused by ICIs combined with angiogenesis inhibitors in patients with advanced lung cancer. METHODS: Pulled studies met the following criteria: patients with advanced lung cancer who received treatment involving ICIs combined with angiogenesis inhibitors (with or without chemotherapy) in interventional or observational studies. Results included the type and number of trAEs or immune-related adverse events (irAEs), treatment-associated discontinuation and mortality, overall survival (OS), and progression-free survival (PFS). PROSPERO: CRD42022337656. RESULTS: The study enrolled 32 trials involving 2313 patients who had 7768 any-grade trAEs and 1078 grade ≥3 trAEs. The pooled incidences were 87.33% (95% confidence interval [CI]: 79.49-93.65; I2 = 94.04%) for any-grade trAEs, and 38.63% (95% CI: 28.28-49.50; I2 = 95.61%) for grade ≥3 trAEs. There were 132 kinds of any-grade trAEs involving 18 systems, and 99 kinds of grade ≥3 trAEs involving 16 systems. For all trAEs, we observed significant differences in the line of therapy, trial design, therapy combination, and types of angiogenesis inhibitors (all P < 0.05). The rate of trAEs increased with dosage and frequency of medication. Pooled incidences of discontinuation and mortality were 10.64% and 0.81%, respectively. Nearly 647 patients experienced irAEs, including 636 any-grade irAEs and 154 grade ≥3 irAEs. CONCLUSIONS: Overall, the incidence of trAEs caused by ICIs combined with angiogenesis inhibitors is generally acceptable. These trAEs have a wide spectrum nearly covering the full range of adverse events. Grade ≥3 trAEs are more closely associated with angiogenesis inhibitors than any grade. However, treatment-associated mortality remains concerning.


Assuntos
Inibidores da Angiogênese , Neoplasias Pulmonares , Humanos , Inibidores da Angiogênese/efeitos adversos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Intervalo Livre de Progressão
15.
J Oncol ; 2023: 2525903, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36647390

RESUMO

Background: Immune checkpoint inhibitors (ICIs) have changed the situation of tumor therapy in recent years. However, for security reasons, those special populations are often excluded from clinical trials, such as infected hepatitis B or hepatitis C patients. ICIs are systematically reviewed and meta-analyzed for the first time in patients infected with hepatitis B or C in this paper. Methods: The relevant studies were searched in PubMed, EMBASE, Cochrane Library, and Web of Science until October 2022. Trials and observational studies meeting the inclusion criteria were included. The outcomes included the effectiveness of ICIs in patients with HBC/HCV (ORR, DCR, mOS, and mPFS), the incidence of adverse reactions, high-grade adverse reactions, and abnormal liver enzymes. At the same time, these indexes were compared with those of uninfected patients. Results: A total of 2,625 patients were enrolled, involving 1,179 patients with hepatitis (HBV or HCV). We found that ICIs showed higher ORR (25.80% vs. 18.10%) and DCR (66.22% vs. 58.74%) in patients with hepatitis B/C than those without infection. In terms of survival time, patients with hepatitis virus infection showed longer mOS (15.44 m vs. 13.30 m) but shorter mPFS (4.94 m vs. 5.01 m) than uninfected patients. As for safety data, patients with hepatitis showed a lower incidence of all-grade irAEs (68.02% vs. 70.43%) than uninfected patients, while that of 3-4 irAEs (21.27% vs. 21.79%) was similar in the two groups. However, hepatic dysfunction was more common and serious in hepatitis patients. Four HBVr and no HCVr were observed. Conclusion: According to this meta-analysis, ICIs are effective and safe for patients with hepatitis B or C, but basic liver enzymes have to be evaluated before treatment to avoid liver adverse events.

16.
Eur J Dermatol ; 33(2): 147-156, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37431117

RESUMO

BACKGROUND: Psoriasis is a chronic immune-mediated skin disease. However, the pathogenesis is not yet well established. OBJECTIVES: This study aimed to screen psoriasis biomarker genes and analyse their significance in immune cell infiltration. MATERIALS & METHODS: GSE13355 and GSE14905 datasets were downloaded from Gene Expression Omnibus (GEO) as training groups to establish the model. GSE30999 obtained from GEO was used to validate the model. Differential expression and multiple enrichment analyses were performed on 91 psoriasis samples and 171 control samples from the training group. The "LASSO" regression model and support vector machine model were used to screen and verify genes implicated in psoriasis. Genes with an area under the ROC curve >0.9 were selected as candidate biomarkers and verified in the validation group. Differential analysis of immune cell infiltration was performed on psoriasis and control samples using the "CIBERSORT" algorithm. Correlation analyses between the screened psoriasis biomarkers and 22 types of immune cell infiltration were performed. RESULTS: In total, 101 differentially expressed genes were identified, which were mainly shown to be involved in regulating cell proliferation and immune functions. Three psoriasis biomarkers, BTC, IGFL1, and SERPINB3, were identified using two machine learning algorithms. These genes showed high diagnostic value in training and validation groups. The proportion of immune cells during immune infiltration differed between psoriasis and control samples, which was associated with the three biomarkers. CONCLUSION: BTC, IGFL1, and SERPINB3 are associated with the infiltration of multiple immune cells, and may therefore be used as biomarkers for psoriasis.


Assuntos
Psoríase , Humanos , Psoríase/diagnóstico , Psoríase/genética , Proliferação de Células , Algoritmos , Biomarcadores , Aprendizado de Máquina
17.
Chin Med ; 18(1): 59, 2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-37210537

RESUMO

Immune checkpoint inhibitors (ICIs) have revolutionized cancer management and have been widely applied; however, they still have some limitations in terms of efficacy and toxicity. There are multiple treatment regimens in Traditional Chinese Medicine (TCM) that play active roles in combination with Western medicine in the field of oncology treatment. TCM with ICIs works by regulating the tumor microenvironment and modulating gut microbiota. Through multiple targets and multiple means, TCM enhances the efficacy of ICIs, reverses resistance, and effectively prevents and treats ICI-related adverse events based on basic and clinical studies. However, there have been few conclusions on this topic. This review summarizes the development of TCM in cancer treatment, the mechanisms underlying the combination of TCM and ICIs, existing studies, ongoing trials, and prospects for future development.

18.
Langmuir ; 28(43): 15160-7, 2012 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-23033891

RESUMO

Assemblies of saturated 1,2-diacylphosphatidylcholine lipid and hydrophobic dodecanethiol-capped 1.8 nm diameter gold nanocrystals were studied as a function of lipid chain length and the addition of the naturally occurring oil, squalene. The gold nanocrystals formed various lipid-stabilized agglomerates, sometimes fusing with lipid vesicle bilayers. The nanocrystal assembly structure depended on the hydrocarbon chain length of the lipid fatty acids. The lipid with the shortest fatty acid length studied, dilauroylphosphatidylcholine, created extended chains of gold nanocrystals. The lipid with slightly longer fatty acid chains created planar sheets of nanocrystals. Further increases of the fatty acid chain length led to spherical agglomerates. The inclusion of squalene led to lipid- and nanocrystal-coated oil droplets.


Assuntos
Ouro/química , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas Metálicas/química , Fosfatidilcolinas/química , Esqualeno/química , Bicamadas Lipídicas/química
19.
Langmuir ; 28(36): 12971-81, 2012 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-22897240

RESUMO

Vesicles of dioleoylphosphatidylcholine (DOPC) formed by extrusion (liposomes) with hydrophobic alkanethiol-capped Au nanocrystals were studied. Dodecanethiol-capped 1.8-nm-diameter Au nanocrystals accumulate in the lipid bilayer, but only when dried lipid-nanocrystal films were annealed with chloroform prior to hydration. Without chloroform annealing, the Au nanocrystals phase separate from DOPC and do not load into the liposomes. Au nanocrystals with slightly longer capping ligands of hexadecanethiol or with a larger diameter of 4.1 nm disrupted vesicle formation and created lipid assemblies with many internal lamellar attachments.


Assuntos
Clorofórmio/química , Ouro/química , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas Metálicas/química , Fosfatidilcolinas/química , Lipossomos , Tamanho da Partícula , Compostos de Sulfidrila/química , Propriedades de Superfície
20.
Medicine (Baltimore) ; 101(46): e31761, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401365

RESUMO

Immune checkpoint inhibitors (ICIs) have changed the status of tumor immunotherapy. ICIs-related adverse events (irAEs) have the high incidence and are difficult to predict and prevent. Researches have suggested that changes of cytokines were associated with irAEs. This study focused on the changes of interleukin-6 (IL-6) and interferon-γ in patients before and after irAEs and trying to find the biomarkers of irAEs. Collect basic data of patients who were treated with ICIs in China-Japan Friendship Hospital from January 2017 to August 2021 and had irAEs. Make statistics on IL-6 and INF-γ in the blood before and after irAEs. A total of 10 patients were enrolled, including 7 males and 3 females. According to statistical analysis, the IL-6 concentration level after irAEs was significantly higher than before, and the difference was statistically significant (P = .023); the interferon-γ concentration level was not changed significantly from before, the difference was not statistically significant (P = .853). The elevation of IL-6 was associated with the occurrence of adverse reactions in ICIs.


Assuntos
Inibidores de Checkpoint Imunológico , Interleucina-6 , Humanos , Masculino , Feminino , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Interferon gama , Imunoterapia/efeitos adversos
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