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1.
Theor Appl Genet ; 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35570221

RESUMO

KEY MESSAGE: Thirty-four SNPs corresponding with 22 QTLs for lint percentage, including 13 novel QTLs, was detected via GWAS. Two candidate genes underlying this trait were also identified. Cotton (Gossypium spp.) is an important natural textile fiber and oilseed crop cultivated worldwide. Lint percentage (LP, %) is one of the important yield components, and increasing LP is a core goal of cotton breeding improvement. However, the genetic and molecular mechanisms underlying LP in upland cotton remain unclear. Here, we performed a genome-wide association study (GWAS) for LP based on 254 upland cotton accessions in four environments as well as the best linear unbiased predictors using the high-density CottonSNP80K array. In total, 41,413 high-quality single-nucleotide polymorphisms (SNPs) were screened, and 34 SNPs within 22 quantitative trait loci (QTLs) were significantly associated with LP. In total, 175 candidate genes were identified from two major genomic loci (GR1 and GR2), and 50 hub genes were identified through GO enrichment and weighted gene co-expression network analysis. Two candidate genes (Gh_D01G0162 and Gh_D07G0463), which may participate in early fiber development to affect the number of fiber protrusions and LP, were also identified. Their genetic variation and expression were verified by linkage disequilibrium blocks, haplotypes, and quantitative real-time polymerase chain reaction, respectively. The weighted gene interaction network analysis showed that the expression of Gh_D07G0463 was significantly correlated with that of Gh_D01G0162. These identified SNPs, QTLs and candidate genes provide important insights into the genetic and molecular mechanisms underlying variations in LP and serve as a foundation for LP improvement via marker-assisted breeding.

2.
Transl Lung Cancer Res ; 11(4): 656-669, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35529783

RESUMO

Background: The data about efficacy of immunotherapy for non-small cell lung cancer with brain metastases (BMs) from real-word settings are controversial. This real-word study is aimed to evaluate the clinical outcome of immune checkpoint inhibitor (ICI)-based treatment in lung adenocarcinoma patients with brain metastases (BMs) and explore potential risk factors, with a focus on the spatial distribution of BMs as previous studies suggested spatial heterogeneity on the brain immune microenvironment. Methods: Advanced lung adenocarcinoma patients with non-oncogene-addicted, who received ICI monotherapy or plus chemotherapy, were enrolled. Efficacy was assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Intergroup comparisons were performed using Pearson's χ2 or Fisher's exact tests for categorical variables. The progression-free survival (PFS) was estimated using Kaplan-Meier method and compared using log-rank test. Cox proportional hazards model was used for multivariate analyses. Peripheral blood was collected from 15 patients with BMs. Tumor-derived exosomes in plasma were isolated by size exclusion chromatography and the cDNA library preparations for miRNA were sequenced on an Illumina Hiseq platform. Differentially expressed genes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed. Results: A total of 198 patients were enrolled and brain metastasis occurred in 20.7% patients (N=41). Compared with patients without BMs, those with BMs had a comparable objective response rate (ORR; 29.3% vs. 43.9%; P=0.089), a lower disease control rate (DCR; 58.5% vs. 78.3%; P=0.01), and a shorter PFS (3.6 vs. 8.6 months; P=0.069). For patients with BMs, factors, including the presence of neurological symptoms, the treatment of intracranial radiotherapy, and the combination of ICI with chemotherapy, had no impact on PFS, whereas cerebellum metastasis was significantly associated with shorter PFS (2.8 vs. 13.8 months, P=0.007). Six upregulated miRNAs were identified in patients with cerebellum metastases (N=8) compared with those without (N=7). The enrichment of differentially expression genes in the KEGG pathways indicated upregulated sulfur metabolism pathway in patients with cerebellum metastases. Conclusions: For lung adenocarcinoma patients, those with BMs have inferior response to ICI-based treatment, but not significantly, and cerebellum metastasis is an independent risk factor with poor outcome for such patients, might attributing to the upregulated sulfur metabolism.

3.
Sleep Med ; 95: 112-119, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35569328

RESUMO

BACKGROUND: Circadian system plays an important role in cardiovascular health. Experimental studies have also identified sex differences in circadian system. We aim to explore the impact of sex on the association between symptom-onset pattern of STEMI and in-hospital adverse outcomes in Chinese population. METHODS: Data were used from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project. 18271 STEMI patients undergoing primary percutaneous coronary intervention entered the study, including 14785 (80.9%) men and 3486 (19.1%) women. The outcomes included all-cause mortality and a composite of major adverse cardiovascular and cerebrovascular events (MACCE) during hospitalization. RESULTS: Most participants experienced STEMI onset during 06:00 h to noon, and there was no difference in onset pattern between men and women (p = 0.582). Logistic regression showed that, after adjustment for cardiovascular risk factors, symptom onset time was significantly associated with in-hospital mortality in men, but not in women or the total population. The odds ratios (ORs) for male patients were 1.86 (95% CI 1.05 to 3.27) for midnight to 06:00 h, 1.58 (95% CI 0.95 to 2.64) for 06:00 h to noon, and 0.80 (95% CI 0.49 to 1.73) for 18:00 h to midnight as compared with STEMI presenting during noon to 18:00 h. But symptom onset time was not associated with MACCE in both sexes or the entire cohort. CONCLUSIONS: These findings show that STEMI onset time was independently associated with in-hospital mortality in male Chinese patients, indicating that sex should be taken into account in studying impact of circadian system on myocardial infarction.

4.
Artigo em Inglês | MEDLINE | ID: mdl-35578031

RESUMO

PURPOSE: Circulating tumor DNA is more and more accessible for patients who cannot undergo biopsy. No consistent conclusion has been reached on whether frequency and proportion of mutations defined by ctDNA profiling can predict therapeutic outcomes. METHODS: One hundred patients with non-small cell lung cancer harboring activating EGFR mutations (exon 19 deletion, L858R and T790M mutation) were collected in West China hospital from December 18, 2017 to December 31, 2019. We retrospectively analyzed the frequency and proportion distribution of ctDNA mutations and its relationship with tyrosine kinase inhibitors therapeutic outcomes. RESULTS: Patients with lower frequency of sensitizing EGFR mutations (< 3%) had a longer progression-free survival (PFS) time than those with higher frequency (15 months vs. 10 months, p = 0.028). Moreover, patients with the lower ratio of T790M mutation frequency and the maximum-somatic-allele-frequency (T790M/MSAF < 30%) had a less prolonged PFS than those with higher T790M/MSAF (7 months vs. 15 months, p = 0.013). CONCLUSION: The frequency and proportion of ctDNA mutations are worth clinical attention in the prediction of therapeutic outcomes.

5.
Int J Cancer ; 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35579989

RESUMO

Global phase 3 trials have demonstrated the priority of several next-generation anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs). However, clinical studies are conducted with specific populations that differ from the real world. The study aimed to evaluate the clinical outcomes of alectinib in real-world settings. Patients with advanced non-small-cell lung cancer (NSCLC) and EML4-ALK fusion were enrolled from two medical centers between June 2018 and June 2020. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) to alectinib. The secondary endpoint was response of brain metastases. The risk factors for disease progression were also investigated. In total, 127 patients with advanced NSCLC were enrolled into this study. Of them, 54.3% received first-line alectinib. The 1- and 2-year PFS rates were 77.4% and 68.3%, respectively. ORR and disease control rate (DCR) were 53.5% and 91.3%, respectively. Among patients with brain metastases, intracranial ORR and DCR were 63.6% and 88.6%, respectively. In addition, we found that "crizotinib pretreatment", "liver metastasis", and "TP53 co-mutation" were individually associated with shorter PFS in alectinib treatment. In conclusion, this study confirms the salient clinical outcomes of alectinib for ALK-fusion-driven NSCLC patients with or without brain metastases, adding real-world evidence to the priority of alectinib in clinical practice. This article is protected by copyright. All rights reserved.

6.
Anal Chem ; 94(16): 6261-6270, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35404585

RESUMO

DNA methylation analysis holds great promise in the whole process management of cancer early screening, diagnosis, and prognosis monitoring. Nevertheless, accurate detection of target methylated DNA, especially its methylation ratio in the genome, remains challenging. Herein, we report for the first time an integrated strategy of target-induced nanoparticle-coupling and site-specific base oxidation damage for DNA methylation analysis with the assistance of well-designed nanosensors. The ultrahigh sensitivity for detecting target methylated DNA as low as 32 × 10-17 M and high specificity for distinguishing 0.001% methylation ratio are achieved by this proposed strategy without amplification operations. Notably, the precise quantification of target DNA methylation ratio has been achieved for the first time. Through quantitative detection of target methylated DNA and methylation ratio, this proposed strategy could reliably diagnose and monitor cancer progression and treatment responses for colorectal cancer, which is superior to the clinical Septin 9 kit. It is anticipated that the proposed strategy has attractive application prospects in early diagnosis and monitoring for colorectal cancer and other various diseases.


Assuntos
Neoplasias Colorretais , Nanopartículas , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , DNA , Metilação de DNA , Humanos , Estresse Oxidativo
7.
J Vis Exp ; (182)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35467666

RESUMO

Intravital imaging of leukocyte-endothelial interactions offers valuable insights into immune-mediated disease in live animals. The study of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and other respiratory pathologies in vivo is difficult due to the limited accessibility and inherent motion artifacts of the lungs. Nonetheless, various approaches have been developed to overcome these challenges. This protocol describes a method for intravital fluorescence microscopy to study real-time leukocyte-endothelial interactions in the pulmonary microcirculation in an experimental model of ALI. An in vivo lung imaging system and 3-D printed intravital microscopy platform are used to secure the anesthetized mouse and stabilize the lung while minimizing confounding lung injury. Following preparation, widefield fluorescence microscopy is used to study leukocyte adhesion, leukocyte rolling, and capillary function. While the protocol presented here focuses on imaging in an acute model of inflammatory lung disease, it may also be adapted to study other pathological and physiological processes in the lung.


Assuntos
Lesão Pulmonar Aguda , Síndrome do Desconforto Respiratório , Lesão Pulmonar Aguda/patologia , Animais , Pulmão/patologia , Camundongos , Microcirculação/fisiologia , Microscopia de Fluorescência , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Vácuo
8.
J Theor Biol ; 543: 111121, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35381225

RESUMO

Alzheimer's disease (AD) is one of the most common dementia, and its pathogenesis has not been clarified. The failure of amyloid targeted therapy has led us to rethink the pathogenesis of AD. There is growing evidence that complex diseases usually involve the impairment of multiple biological functions, rather than focus on several single genes. Protein-protein interaction network (PPIN) has been recognized as an important tool for identifying and predicting disease biomarkers. It is a great challenge to design network-based classification method for identifying effective, stable and interpretable biomarkers to distinguish the disease phenotype based on gene expression profile data. In this study, we used graph Laplacian regularization method to introduce topology information of PPIN, which can reveal the damaged networks involved in disease from heterogeneous gene expression profile data and identify disease-related biomarkers. The results in three AD datasets showed that the biomarkers identified by our method can not only distinguish the sample categories more accurately, but also help researchers understand the biological meaning behind complex diseases.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Biomarcadores/metabolismo , Humanos , Análise em Microsséries , Mapas de Interação de Proteínas , Projetos de Pesquisa
9.
Front Nutr ; 9: 846659, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433793

RESUMO

Background and Aims: Malnutrition is a well known risk factor for adverse outcomes in patients with cancer, cardiovascular disease (CVD) and chronic kidney disease, but epidemiological evidence on its relationship with the long-term risk of all-cause mortality and cardiovascular death is limited. Methods: A total of 20,116 adults from the United States National Health and Nutrition Examination Survey 2007-2014 were enrolled. The Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), Controlling Nutritional Status (CONUT) score, and Triglycerides (TG) × Total Cholesterol (TC) × Body Weight (BW) Index (TCBI) were calculated at baseline. Cox regression and the Kaplan-Meier analysis were conducted when participants were divided into three groups according to the tertiles of objective nutritional scores. Restricted cubic spline was performed to further explore the shape of the relationship between all-cause mortality, cardiovascular death, and nutritional scores. In addition, the area under the curve (AUC), continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were conducted to assess which nutritional scores have the greatest predictive value for all-cause death and cardiovascular death in the general population. Results: The cumulative incidence of all-cause death and cardiovascular death was significantly higher in participants with a higher CONUT score, lower GNRI, and lower PNI. TCBI showed the worst performance on grading and risk assessment. After adjusting confounding factors, the lowest PNI and GNRI tertile and highest COUNT score were independently and significantly associated with increased risk of all-cause death (all P < 0.01) and cardiovascular death (all P < 0.05) analyzed by a multivariate Cox regression model. An L-shaped association between the HR (hazard ratio) of all-cause mortality and nutritional scores (GNRI, PNI and TCBI) was observed in the overall populations. In addition, the PNI had the highest predictive value for all-cause mortality [AUC: 0.684, 95% confidence interval (CI): 0.667-0.701] and cardiovascular death (AUC: 0.710, 95% CI: 0.672-0.749) in the general population compared with other nutritional scores. Conclusion: The poorer the nutritional status of the general population, the higher the all-cause mortality and cardiovascular mortality. The PNI score may provide more useful predictive values than other nutritional scores.

10.
ACS Appl Mater Interfaces ; 14(17): 19907-19917, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35441508

RESUMO

Modification of inorganic nanoparticles with human serum albumin (HSA) that load with chemotherapeutic agents has been reported to conduct chemo-photothermal synergistic therapy of tumors. However, loading some highly insoluble drugs would cause the conformation disorder of HSA, which is unable to give full play to tumor targeting and biological compatibility. Besides, inorganic nanoparticles with too large of a size would appear with unsatisfactory metabolism and lead to biological toxicity. Herein, the recombinant protein integrating histidine (His), HSA, enzyme responsive site, and arginine-glycine-aspartic acid (RGD) by genetic engineering technology was developed to co-load docetaxel (DTX) and gold nanoparticles (Au NPs) to construct RHMH18@AuD NPs. In which, DTX was encapsulated in the micelle part that self-assembled by histidine, while ultrasmall Au NPs were clustered in the HSA part through biomimetic mineralization. RHMH18@AuD NPs could maintain a consistent conformation with HSA and a uniform dispersion in saline. In vitro experiments verified that RHMH18@AuD NPs could target cancer cells followed by being structurally separated into RGD-HSA@Au and His@DTX under the restriction of MMP-2 enzymes. In vivo results verified the favorable biocompatibility and positive chemo-photothermal synergetic therapy efficiency of RHMH18@AuD NPs on a human ovarian tumor.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Neoplasias Ovarianas , Linhagem Celular Tumoral , Docetaxel/farmacologia , Feminino , Ouro , Histidina , Humanos , Nanopartículas/uso terapêutico , Oligopeptídeos , Neoplasias Ovarianas/tratamento farmacológico , Proteínas Recombinantes , Albumina Sérica Humana
11.
Gynecol Oncol ; 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35490033

RESUMO

OBJECTIVE: To evaluate the value of local treatment in stage IVB cervical cancer (CC). METHODS: Patients diagnosed with stage IVB CC between 2010 and 2015 were included using the data from the Surveillance, Epidemiology, and End Results program. Propensity score matching (PSM) was used to balance the clinicopathological variables of patients. Multivariate Cox regression analyses were performed to analyze the risk factors associated with cause-specific survival (CSS). RESULTS: We identified 960 patients in this study, all patients had received chemotherapy. Of these patients, 818 patients were treated with local treatment (85.2%), including 724 (88.5%) and 94 (11.5%) patients receiving radiotherapy (RT) alone and surgery ± RT, respectively. Local treatment was the independent prognostic factor associated with better CSS. Before PSM, patients who received RT (hazard ratio [HR] 0.633, 95% confidence interval [CI] 0.517-0.775, P < 0.001) or surgery (HR 0.391, 95% CI 0.277-0.552, P < 0.001) were independently associated with a better CSS compared to those with no local treatment. The 3-years CSS rate was 14.4%, 32.4%, and 54.8% in no local treatment, RT alone, and surgery groups, respectively (P < 0.001). Similar results were found after PSM. Patients receiving RT (HR 0.643, 95% CI 0.436-0.947, P = 0.025) and surgery (HR 0.146, 95% CI 0.052-0.410, P < 0.001) had better CSS compared to patients with no local treatment after PSM. While similar CSS was shown between RT alone cohort and the surgery cohort (HR 0.756, 95% CI 0.454-1.260, P = 0.284). CONCLUSIONS: The addition of local surgery or RT to chemotherapy appears to confer improved survival outcomes in patients with stage IVB CC.

12.
HLA ; 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35478384

RESUMO

HLA-DRB1*12:96 differs from HLA-DRB1*12:01:01:01 by 10 nucleotide substitutions within exon 2.

13.
Angew Chem Int Ed Engl ; : e202204012, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35475564

RESUMO

A nanochannel membrane has the prospect of large-scale separation. However, selectivity in enantioseparation is a challenge, due to the size difference between nanochannels and enantiomers. Here, we compartmented nanochannels by the in situ synthesis of a L-tyrosine functionalized covalent organic framework (L-Tyr-COF). The L-Tyr-COF decreased the pore size of channels to match with naproxen enantiomers (S/R-NPX) and improved the enantioselective gating. In contrast to the surface-functionalized nanochannels (L-Tyr channel), the L-Tyr-COF packed nanochannels (L-Tyr-COF channel) exhibited high enantioselectivity for S-NPX and realized the enantioseparation with the enantiomer excess value up to 94.2 %. The separation flux through the highly porous L-Tyr-COF channel was 1.33 mmol m-2 h-1 . This study provided a size-matching strategy and the chiral covalent organic framework packed nanochannel membrane to realize enantioseparation with high selectivity and flux.

14.
Int Immunopharmacol ; 108: 108760, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35398623

RESUMO

BACKGROUND: Circulating extracellular vesicles (EVs) are recognized as a promising source of cancer biomarkers. We previously reported that tumor cell-released autophagosomes, a new subgroup of EVs expressing the mature autophagosome-specific marker LC3B (LC3B+ EVs), are critical modulators of host anti-tumor immunity. This study aimed to assess the level of plasma LC3B+ EVs and the correlation with clinical outcomes in liver cancer patients. METHODS: The plasma and ascites samples were obtained from patients with liver cancer, non-malignant liver disease, and healthy controls. EVs were isolated by differential centrifugation and characterized using flow cytometry, nanoparticle tracking analysis, transmission electron microscopy, and western blotting. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of plasma LC3B+ EVs or HSP90α+LC3B+ EVs from liver cancer patients. The relationship between the expression levels of HSP90AA1 or MAP1LC3B and survival were analyzed using patient data from the TCGA database. The correlation between HSP90α in LC3B+ EVs and PD-1highCD8+ exhausted T cells from the ascites and peripheral blood of liver cancer patients was also evaluated. RESULTS: The EVs preparation from liver cancer patients contained LC3B+ EVs expressing epithelial tumor cell adhesion molecules (EpCAM), indicating that these LC3B+ EVs originated from epithelial tumor cells. The levels of plasma LC3B+ EVs and HSP90α+LC3B+ EVs in liver cancer patients were significantly higher than in non-malignant liver disease patients and healthy controls. The expression of HSP90α in plasma LC3B+ EVs (AUC 0.9595, sensitivity 86.00%, specificity 96.67%) accurately differentiated liver cancer patients from non-liver cancer controls. Additionally, a significant decrease in the levels of plasma LC3B+ EVs and HSP90α+LC3B+ EVs was found post-surgery in each patient, and high expression of HSP90AA1 or MAP1LC3B in the tumor tissue correlated with significantly worse survival compared to those with low expression. We also observed that the level of LC3B+ EVs and HSP90α+LC3B+ EVs positively correlated with the PD-1highCD8+ exhausted T cells in liver cancer patients. Human CD8+ T cells treated with purified LC3B+ EVs in vitro exhibited a dose-dependent increase in the percentage of PD-1+CD8+ T cells, whereas the production of IFN-γ was decreased. CONCLUSIONS: We demonstrated that isolation and detection of plasma LC3B+ EVs carrying bioactive molecules is an effective diagnostic marker of liver cancer, and may also be used as a potential marker for immune monitoring and predicting prognosis clinically.

15.
Dev Cogn Neurosci ; 55: 101107, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35413663

RESUMO

Early differences in reward behavior have been linked to executive functioning development. The nucleus accumbens (NAc) and orbitofrontal cortex (OFC) are activated by reward-related tasks and identified as key nodes of the brain circuit that underlie reward processing. We aimed to investigate the relation between NAc-OFC structural and functional connectivity in preschool children, as well as associations with future reward sensitivity and executive function. We showed that NAc-OFC structural and functional connectivity were not significantly associated in preschool children, but both independently predicted sensitivity to reward in males in a left-lateralized manner. Moreover, significant NAc-OFC structure-function coupling was only found in individuals who performed poorly on executive function tasks in later childhood, but not in the middle- and high-performing groups. As structure-function coupling is proposed to measure functional specialization, this finding suggests premature functional specialization within the reward network, which may impede dynamic communication with other regions, affects executive function development. Our study also highlights the utility of multimodal imaging data integration when studying the effects of reward network functional flexibility in the preschool age, a critical period in brain and executive function development.

16.
Insects ; 13(4)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35447787

RESUMO

In this study, 50 species of the leafhopper subgenus Eurhadina (Singhardina) Mahmood from China are reviewed based on comparative morphological characteristics, including 14 new species: Eurhadina (Singhardina) amacularis, E. (S.) extensa, E. (S.) flaviscutella, E. (S.) foliiformis, E. (S.) galacta, E. (S.) gracilifurca, E. (S.) lata, E. (S.) parilintanonica, E. (S.) quadrimacularis, E. (S.) recta, E. (S.) scalesa, E. (S.) scamba, E. (S.) scandens and E. (S.) uprotrusa&nbsp;sp. nov. Four additional species E. (S.) fasciata, E. (S.) jarrayi, E. (S.) prima and E. (S.) zadyma are recorded from China for the first time. Two new synonymies are proposed. Eurhadina (Singhardina) flavescens Huang et Zhang, 1999 syn. nov. is synonymized with Eurhadina wuyiana Yang et Li, 1991 and Eurhadina rubromia Cai et Kuoh, 1993 syn. nov. is synonymized with Eurhadina (Singhardina) biavis Yang et Li, 1991. A key to all Chinese Singhardina species is also provided.

17.
Front Immunol ; 13: 848387, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35300325

RESUMO

Purpose: To investigate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib plus PD-1 inhibitor (TACE-L-P) versus TACE combined with lenvatinib (TACE-L) for patients with advanced hepatocellular carcinoma (HCC). Materials and Methods: Data of advanced HCC patients treated with TACE-L-P (TACE-L-P group) or TACE-L (TACE-L group) from January 2019 to December 2020 were prospectively collected and retrospectively analyzed. The differences in overall survival (OS), progression-free survival (PFS), tumor responses (based on modified Response Evaluation Criteria in Solid Tumors) and adverse events (AEs) were compared between the two groups. Potential factors affecting OS and PFS were determined. Results: A total of 81 patients were included in this study. Among them, 41 received TACE-L-P and 40 received TACE-L. The patients in TACE-L-P group had prolonged OS (median, 16.9 vs. 12.1 months, P=0.009), longer PFS (median, 7.3 vs. 4.0 months, P=0.002) and higher objective response rate (56.1% vs. 32.5%, P=0.033) and disease control rate (85.4% vs. 62.5%, P=0.019) than those in TACE-L group. Multivariate analyses revealed that the treatment option of TACE-L, main portal vein invasion and extrahepatic metastasis were the independent risk factors for OS, while TACE-L and extrahepatic metastasis were the independent risk factors for PFS. In subgroup analyses, a superior survival benefit was achieved with TACE-L-P in patients with extrahepatic metastasis or tumor number >3 but not in those with main portal vein invasion. The incidence and severity of AEs in TACE-L-P group were comparable to those in TACE-L group (any grade, 92.7% vs. 95.0%, P=1.000; grade 3, 36.6% vs. 32.5%, P=0.699). Conclusion: TACE-L-P significantly improved survival over TACE-L with an acceptable safety profile in advanced HCC patients, especially those with extrahepatic metastasis or tumor number >3 but without main portal vein invasion.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas/patologia , Compostos de Fenilureia , Quinolinas , Estudos Retrospectivos , Resultado do Tratamento
18.
Molecules ; 27(5)2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35268633

RESUMO

The Valsa canker caused by Valsa mali seriously harmed the production of East Asian apples and caused very significant economic losses. Considering the chemical residues and the improvement of people's awareness of environmental protection, there is a need for screening new green pesticides for the control of Valsa canker. Therefore, we conducted systematic evaluations on the antifungal activity of wood tar. In this research, the effective concentration (EC50) of six strains of V. mali to wood tar was determined, and the EC50 ranged from 69.54 to 92.81 µg/mL. After treatment with wood tar, the hyphae of V. mali broke, swelled, and deformed; the permeability of the cell membrane increased; and the activity of pectinase reduced. Moreover, the expression levels of five genes related to pectinase also decreased significantly. In addition, the activities of phenylalanine ammonia lyase (PAL) and peroxidase (POD) of apple leaves treated with wood tar also increased. On detached apple branches, wood tar also showed therapeutic and protective activities. In the 2016-2019 field experiments, wood tar also showed good efficacy against Valsa canker and promoted the formation of callus. (In the experiments from 2016 to 2019, it can be seen that the control effect of 50% wood tar and 100% wood tar in the field is above 75% and promoted the formation of callus.) This study is the first to report the bidirectional efficacy of wood tar against Valsa mali and for trunk wound healing. The above results evidenced that wood tar has great potential to be developed as a natural alternative to commercial fungicides for the management of apple Valsa canker.


Assuntos
Ascomicetos , Fungicidas Industriais , Malus , Ascomicetos/genética , Fungicidas Industriais/farmacologia , Humanos , Malus/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Madeira
19.
Front Oncol ; 12: 852736, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35311094

RESUMO

Background: The non-invasive preoperative diagnosis of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is vital for precise surgical decision-making and patient prognosis. Herein, we aimed to develop an MVI prediction model with valid performance and clinical interpretability. Methods: A total of 2160 patients with HCC without macroscopic invasion who underwent hepatectomy for the first time in West China Hospital from January 2015 to June 2019 were retrospectively included, and randomly divided into training and a validation cohort at a ratio of 8:2. Preoperative demographic features, imaging characteristics, and laboratory indexes of the patients were collected. Five machine learning algorithms were used: logistic regression, random forest, support vector machine, extreme gradient boosting (XGBoost), and multilayer perception. Performance was evaluated using the area under the receiver operating characteristic curve (AUC). We also determined the Shapley Additive exPlanation value to explain the influence of each feature on the MVI prediction model. Results: The top six important preoperative factors associated with MVI were the maximum image diameter, protein induced by vitamin K absence or antagonist-II, α-fetoprotein level, satellite nodules, alanine aminotransferase (AST)/aspartate aminotransferase (ALT) ratio, and AST level, according to the XGBoost model. The XGBoost model for preoperative prediction of MVI exhibited a better AUC (0.8, 95% confidence interval: 0.74-0.83) than the other prediction models. Furthermore, to facilitate use of the model in clinical settings, we developed a user-friendly online calculator for MVI risk prediction based on the XGBoost model. Conclusions: The XGBoost model achieved outstanding performance for non-invasive preoperative prediction of MVI based on big data. Moreover, the MVI risk calculator would assist clinicians in conveniently determining the optimal therapeutic remedy and ameliorating the prognosis of patients with HCC.

20.
J Hepatocell Carcinoma ; 9: 157-170, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35300208

RESUMO

Purpose: To evaluate the safety and efficacy of regorafenib combined with anti-PD-1 antibody sintilimab (rego-sintilimab) as a second-line treatment for advanced hepatocellular carcinoma (HCC). Methods: This multicenter retrospective study evaluated consecutive patients with advanced HCC who received rego-sintilimab (rego-sintilimab group) or regorafenib alone (regorafenib group) as a second-line treatment from January 2019 to December 2020. Adverse events, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Uni- and multi-variable analyses of prognostic factors for OS and PFS were performed using Cox proportional hazard regression models. Results: In total, 113 patients were included in the study: 58 received rego-sintilimab and 55 received regorafenib. The rego-sintilimab group had higher ORR (36.2% vs 16.4%, P = 0.017), longer PFS (median 5.6 vs 4.0 months; P = 0.045), and better OS (median 13.4 vs 9.9 months; P = 0.023) than the regorafenib group. Regorafenib alone, Child-Pugh B, and neutrophil-to-lymphocyte ratio (NLR) > 3.6 were independent prognostic factors for poor OS. Regorafenib alone, α-fetoprotein level, and NLR > 3.6 were independent prognostic factors for poor PFS. Subgroup analyses showed a survival benefit of rego-sintilimab in patients with NLR ≤ 3.6 (hazard ratio 0.518 [95% CI, 0.257-0.955]) but not in those with NLR > 3.6 (0.852 [0.461-1.572]); P = 0.002 for interaction. The difference in incidence of grade 3/4 adverse events between the two groups was not statistically significant (39.7% vs 30.9%; P = 0.331). Conclusion: Rego-sintilimab was tolerated and led to better OS than regorafenib as a second-line treatment for advanced HCC patients, especially in those with NLR ≤ 3.6.

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