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1.
Gastrointest Endosc ; 99(4): 577-586.e1, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37989466

RESUMO

BACKGROUND AND AIMS: Post-ERCP pneumobilia is not uncommon; however, studies focusing on the long-term prognosis of patients with post-ERCP pneumobilia are limited. This study aimed to explore long-term prognosis and risk factors associated with post-ERCP pneumobilia in patients with common bile duct stones (CBDSs). METHODS: We conducted a retrospective analysis of 1380 patients who underwent ERCP for CBDSs at our hospital from January 2010 to December 2017. Patients were selected based on inclusion and exclusion criteria and divided into pneumobilia and nonpneumobilia groups, followed by propensity score matching. The matched groups were then compared in terms of incidence rates of both single and multiple recurrences of CBDSs, acute cholangitis, and acute cholecystitis. Multivariate logistic regression analysis was used to explore risk factors associated with pneumobilia. RESULTS: After propensity matching, there was no significant difference in the rate of single recurrence of CBDSs (22.5% vs 30%; P = .446) between the pneumobilia and nonpneumobilia groups. However, the incidences of multiple recurrences of CBDSs (32.5% vs 12.5%; P = .032) and acute cholangitis without stone recurrence (32.5% vs 2.5%; P = <.001) were significantly higher in the pneumobilia group. Based on multivariate logistic regression analysis, in addition to a dilated CBD (diameter of >1 cm) (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.03-3.76; P = .043), endoscopic sphincterotomy with moderate incision (OR, 5.38; 95% CI, 1.14-25.47; P = .034) and with large incision (OR, 8.7; 95% CI, 1.83-41.46; P = .007) were identified as independent risk factors for pneumobilia after initial ERCP. CONCLUSIONS: Patients with post-ERCP pneumobilia have increased risk of multiple recurrences of CBDSs and acute cholangitis without stone recurrence. Independent risk factors for pneumobilia include peripapillary diverticulum, a dilated CBD (>1 cm), and endoscopic sphincterotomy with moderate and large incisions. A normal-sized CBD appears to serve as a secondary barrier against enterobiliary reflux, necessitating further research for confirmation.


Assuntos
Colangite , Cálculos Biliares , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Estudos Retrospectivos , Cálculos Biliares/epidemiologia , Cálculos Biliares/cirurgia , Esfinterotomia Endoscópica/efeitos adversos , Prognóstico , Fatores de Risco , Colangite/epidemiologia , Colangite/etiologia , Colangite/cirurgia , Ducto Colédoco/cirurgia
2.
Endoscopy ; 2024 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-39142349

RESUMO

BACKGROUND: This study aimed to assess the feasibility and safety of performing cholangiopancreatoscopy-assisted endoscopic mucosal resection (CA-EMR) for biliopancreatic intraductal lesions. METHODS: Special electrocautery snares and injection needles that can pass through the working channel of a single-operator cholangiopancreatoscope were developed. Between November 2023 and April 2024, we performed CA-EMR for two patients with gallbladder polyps, one patient with a neoplastic lesion in the common bile duct (CBD), and one patient with a neoplastic lesion in the main pancreatic duct. The technical success rate and adverse events were recorded. RESULTS: All four CA-EMR procedures were performed successfully. Postoperative pathology revealed inflammatory gallbladder polyps in two patients, low grade intraepithelial neoplasia of the CBD in one patient, and intraductal papillary mucinous neoplasm (IPMN) in one patient. The patient with IPMN experienced mild postoperative pancreatitis and recovered after conservative treatment. No adverse events were encountered in the other three CA-EMR procedures. CONCLUSION: This study preliminarily confirmed the feasibility and safety of CA-EMR for treating biliopancreatic intraductal lesions.

3.
Genet Sel Evol ; 56(1): 6, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216889

RESUMO

BACKGROUND: Low-pass whole-genome sequencing and imputation offer significant cost savings, enabling substantial increases in sample size and statistical power. This approach is particularly promising in livestock breeding, providing an affordable means of screening individuals for deleterious alleles or calculating genomic breeding values. Consequently, it may also be of value in companion animal genomics to support pedigree breeding. We sought to evaluate in dogs the impact of low coverage sequencing and reference-guided imputation on genotype concordance and association analyses. RESULTS: DNA isolated from saliva of 30 Labrador retrievers was sequenced at low (0.9X and 3.8X) and high (43.5X) coverage, and down-sampled from 43.5X to 9.6X and 17.4X. Genotype imputation was performed using a diverse reference panel (1021 dogs), and two subsets of the former panel (256 dogs each) where one had an excess of Labrador retrievers relative to other breeds. We observed little difference in imputed genotype concordance between reference panels. Association analyses for a locus acting as a disease proxy were performed using single-marker (GEMMA) and haplotype-based (XP-EHH) tests. GEMMA results were highly correlated (r ≥ 0.97) between 43.5X and ≥ 3.8X depths of coverage, while for 0.9X the correlation was lower (r ≤ 0.8). XP-EHH results were less well correlated, with r ranging from 0.58 (0.9X) to 0.88 (17.4X). Across a random sample of 10,000 genomic regions averaging 17 kb in size, we observed a median of three haplotypes per dog across the sequencing depths, with 5% of the regions returning more than eight haplotypes. Inspection of one such region revealed genotype and phasing inconsistencies across sequencing depths. CONCLUSIONS: We demonstrate that saliva-derived canine DNA is suitable for whole-genome sequencing, highlighting the feasibility of client-based sampling. Low-pass sequencing and imputation require caution as incorrect allele assignments result when the subject possesses alleles that are absent in the reference panel. Larger panels have the capacity for greater allelic diversity, which should reduce the potential for imputation error. Although low-pass sequencing can accurately impute allele dosage, we highlight issues with phasing accuracy that impact haplotype-based analyses. Consequently, if accurately phased genotypes are required for analyses, we advocate sequencing at high depth (> 20X).


Assuntos
DNA , Polimorfismo de Nucleotídeo Único , Humanos , Animais , Cães , Haplótipos , Genótipo , Alelos
4.
Surg Endosc ; 38(3): 1289-1295, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38102397

RESUMO

BACKGROUND AND STUDY AIM: To assess the efficacy and safety of a fibrin sealant for the prevention of leak resulting from mucosal penetration at the esophagus or cardia during a STER procedure to remove gastrointestinal submucosal tumors (SMTs). PATIENTS AND METHODS: Between April 2014 and October 2022, a total of 290 patients with oesophageal or cardiac SMTs underwent STER at our centre. We retrospectively identified patients with oesophageal or cardia SMTs who underwent STER and experienced mucosal penetration of the cardia or oesophagus during the procedure. A total of 31 mucosal penetrations in 30 procedures were included. Of the 31 mucosal penetrations, 12 occurred in the cardia, and the other 19 occurred in the oesophagus. All 31 sites received the fibrin sealant to close the mucosal penetration. Clinical characteristics, procedure-related parameters, detailed data of the mucosal penetrations, and treatment outcomes using the fibrin sealant were reviewed for all 30 patients to assess the efficacy and safety of the fibrin sealant for closure of mucosal penetration at the cardia or oesophagus. RESULTS: For the 31 mucosal penetrations, the mean size was 0.08 ± 0.06 cm2 (range 0.01-0.25 cm2). Mucosal closure using the fibrin sealant was performed successfully in all 31 mucosal penetrations. Of the 31 mucosal penetrations, clips were used in 13 cases. All 30 patients were discharged after a median of 7 days (range 4-20 day) postoperatively. During a mean 62 months (range 6-107 months) follow-up, all 31 mucosal penetrations successfully healed without the occurrence of infection, ulcer, oesophagitis, chest infection or abdominal infection. CONCLUSION: For the closure of mucosal penetration during STER at the cardia or oesophagus, a fibrin sealant is both safe and efficacious. It is necessary to conduct more research on the viability, effectiveness, and safety of using a fibrin sealant to close wider mucosal penetrations.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Neoplasias Gastrointestinais , Neoplasias Gástricas , Humanos , Cárdia/cirurgia , Cárdia/patologia , Adesivo Tecidual de Fibrina/uso terapêutico , Ressecção Endoscópica de Mucosa/métodos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Estudos Retrospectivos , Esôfago/patologia , Neoplasias Gastrointestinais/patologia , Resultado do Tratamento , Mucosa Gástrica/cirurgia , Mucosa Gástrica/patologia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia
5.
Cell Mol Life Sci ; 81(1): 5, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38085330

RESUMO

SHP2 phosphatase promotes full activation of the RTK-dependent Ras/MAPK pathway. Its mutations can drive cancer and RASopathies, a group of neurodevelopmental disorders (NDDs). Here we ask how same residue mutations in SHP2 can lead to both cancer and NDD phenotypes, and whether we can predict what the outcome will be. We collected and analyzed mutation data from the literature and cancer databases and performed molecular dynamics simulations of SHP2 mutants. We show that both cancer and Noonan syndrome (NS, a RASopathy) mutations favor catalysis-prone conformations. As to cancer versus RASopathies, we demonstrate that cancer mutations are more likely to accelerate SHP2 activation than the NS mutations at the same genomic loci, in line with NMR data for K-Ras4B more aggressive mutations. The compiled experimental data and dynamic features of SHP2 mutants lead us to propose that different from strong oncogenic mutations, SHP2 activation by NS mutations is less likely to induce a transition of the ensemble from the SHP2 inactive state to the active state. Strong signaling promotes cell proliferation, a hallmark of cancer. Weak, or moderate signals are associated with differentiation. In embryonic neural cells, dysregulated differentiation is connected to NDDs. Our innovative work offers structural guidelines for identifying and correlating mutations with clinical outcomes, and an explanation for why bearers of RASopathy mutations may have a higher probability of cancer. Finally, we propose a drug strategy against SHP2 variants-promoting cancer and RASopathies.


Assuntos
Neoplasias , Síndrome de Noonan , Humanos , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Síndrome de Noonan/genética , Mutação/genética , Neoplasias/genética , Domínios de Homologia de src/genética , Fenótipo
6.
JAMA ; 331(3): 201-211, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38227033

RESUMO

Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.


Assuntos
Anticorpos Monoclonais Humanizados , Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Compostos de Platina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Resposta Patológica Completa , Antineoplásicos/uso terapêutico , Terapia Combinada , Compostos de Platina/administração & dosagem , Compostos de Platina/uso terapêutico , Idoso
7.
Molecules ; 29(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38611788

RESUMO

Chenopodium quinoa Willd. is rich in phenolic compounds and exhibits diverse biological activities. Few studies have focused on the effect of colored quinoa's phenolic profile on potential biological activity. This study used a UPLC-MS/MS-based metabolomic approach to examine the quinoa phenolics and their association with in vitro antioxidant and hypoglycemic properties. In total, 430 polyphenols, mainly phenolic acids, flavonoids, and flavonols, were identified. Additionally, 121, 116, and 148 differential polyphenols were found between the white and black, white and red, and black and red comparison groups, respectively; 67 polyphenols were screened as shared key differential metabolites. Phenylalanine, tyrosine, and the biosynthesis of plant secondary metabolites were the main differently regulated pathways. Black quinoa had better total phenolic contents (643.68 mg/100 g DW) and antioxidant capacity, while white quinoa had better total flavonoid contents (90.95 mg/100 g DW) and in vitro α-amylase (IC50 value of 3.97 mg/mL) and α-glucosidase (IC50 value of 1.08 mg/mL) inhibition activities. Thirty-six polyphenols, including epicatechin and linarin, etc., were highly correlated with in vitro antioxidant activity, while six polyphenols, including tiliroside and chrysoeriol, etc., were highly correlated with in vitro hypoglycemic activity. This study may provide important information for colored quinoa resources to develop their healthy food applications.


Assuntos
Antioxidantes , Chenopodium quinoa , Antioxidantes/farmacologia , Cromatografia Líquida , Espectrometria de Massas em Tandem , Fenóis , Polifenóis
8.
BMC Pulm Med ; 23(1): 482, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38031067

RESUMO

BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients harboring neurotrophin receptor kinase (NTRK) family mutations remains obscure. METHODS: The Zehir cohort from cBioPortal was used to analyze the mutations (MT) frequency of NTRK family in patients with NSCLC, and their correlation with clinical characteristics and patient survival. The influence of NTRK MT on ICIs efficacy was evaluated in ICIs-treated patients from Samstein cohort and further validated by use of data from OAK/POPLAR cohort. RESULTS: In the Zehir cohort, a significant difference was observed in median overall survival (mOS) between patients with NTRK MT and wild-type (WT) (mOS: 18.97 vs. 21.27 months, HR = 1.34, 95%CI 1.00-1.78; log-rank P = 0.047). In Samstein cohort, the mOS of NTRK mutant patients receiving ICIs has improved compared to WT patients (mOS: 21.00 vs. 11.00 months, log-rank P = 0.103). Notably, in subgroup analysis, ICIs significantly prolonged mOS in patients with NTRK3 MT than in WT patients (mOS: not available vs. 11.00 months, HR = 0.36, 95%CI 0.16-0.81; log-rank P = 0.009). Identical mOS between NTRK MT and WT patients receiving ICIs treatment (mOS: 13.24 vs. 13.50 months, log-rank P = 0.775) was observed in OAK/POPLAR cohort. Moreover, a similar programmed death ligand 1 (PD-L1) expression, but higher tumor mutational burden (TMB), blood TMB (bTMB) and enriched anti-tumor immunity were observed in NTRK MT compared to WT (P < 0.05). CONCLUSION: Taking high TMB or bTMB into consideration, patients with NTRK mutant NSCLC could benefit from ICIs treatment.


Assuntos
Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Mutação , Biomarcadores Tumorais/genética
9.
Molecules ; 28(9)2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37175091

RESUMO

The aim of this study was to investigate the effect of ultrasonic stress germination (USG) on total phenolic contents (TPC), total flavonoid contents (TFC), the phenolic compositions, and antioxidant activities of black highland barley (BHB). The USG processing parameters, polyphenol profile, phenolic compositions, and antioxidant activities were explored after USG. Results showed that the optimal USG parameters were as follows: 350 W ultrasonic pretreatment power, 30 °C ultrasonication temperature, 25 min ultrasonication time, and 64 h germination time. Under these conditions, the total phenolic content (688.84 ± 5.30 mg/100 g) and total flavonoid content (59.23 ± 0.45 mg/100 g) of BHB were increased by 28.55% and 10.15%, respectively, compared to the untreated samples. In addition, the USG treatment could more effectively enrich bound phenolic acids and free flavonoids, among which the content of catechin was significantly increased by USG and was the main characteristic substance. Moreover, the USG treatment could improve the antioxidant activity and had a higher antioxidant potency composite index (APC index) (97.91%) of BHB. These results indicate that USG might be an effective method to enrich polyphenols and improve antioxidant activity in BHB.


Assuntos
Hordeum , Polifenóis , Polifenóis/farmacologia , Polifenóis/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Hordeum/metabolismo , Fenóis/metabolismo , Flavonoides/farmacologia , Flavonoides/metabolismo
10.
Molecules ; 28(4)2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36838651

RESUMO

Five different solvent extracts of highland barley bran were analyzed and compared for their polyphenol profile, antioxidant activity, and α-glucosidase and α-amylase inhibitory activities. The highland barley bran acetone extract had the highest total phenolic content, total flavonoid content, and antioxidant capacity. It was followed by the methanol and ethanol extracts, while n-butanol and ethyl acetate extracts exhibited lower measured values. Diosmetin, luteolin, protocatechuic acid, vanillic acid, ferulic acid, phlorogucinol, diosmin, isoquercitrin, catechin, and isovitexin were among the most abundant phenolic compounds identified in different solvent extracts, and their concentrations varied according to the solvent used. The highest α-glucosidase and α-amylase inhibitory activity were observed in the ethyl acetate extract of highland barley bran, followed by the acetone and methanol extracts. In contrast, n-butanol and ethanol extracts exhibited lower measured values. The different solvent extracts were effective inhibitors for α-glucosidase and α-amylase with activity reaching to 34.45-94.32% and 22.08-35.92% of that of positive control acarbose, respectively. There were obvious correlations between the phenolic content and composition of different solvent extracts and their in vitro antioxidant activity, α-glucosidase inhibition activity and α-amylase inhibition activity. Black barley bran is an excellent natural raw material for developing polyphenol-rich functional foods and shows good antioxidant and hypoglycemic potential to benefit human health.


Assuntos
Antioxidantes , Hordeum , Humanos , Antioxidantes/farmacologia , Polifenóis , Solventes , Metanol , Acetona , alfa-Glucosidases , 1-Butanol , Extratos Vegetais/farmacologia , Fenóis/farmacologia , alfa-Amilases , Etanol
11.
J Phys Chem A ; 126(20): 3167-3173, 2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35533406

RESUMO

While plastic materials offer many benefits to society, the slow degradation and difficulty in recycling plastics raise important environmental and sustainability concerns. Traditional recycling efforts often lead to materials with inferior properties and correspondingly lower value, making them uneconomical to recycle. Recent efforts have shown promising chemical pathways for converting plastic materials into a wide range of value-added products, feedstocks or monomers. This is commonly referred to as "chemical recycling". Here, we use reactive molecular dynamics (MD) simulations to study the catalytic process of depolymerization of polyethylene (PE) using platinum (Pt) nanoparticles (NPs) in comparison to PE pyrolysis (thermal degradation). We apply a simple kinetic model to our MD results for the catalytic reaction rate as a function of temperature, from which we obtain the activation energy of the reaction, which shows the that the Pt NPs reduce the barrier for depolymerization. We further evaluate the molecular mass distribution of the reaction products to gain insight into the influence of the Pt NPs on reaction selectivity. Our results demonstrate the potential for the reactive MD method to help the design of recycling approaches for polymer materials.

12.
J Chem Phys ; 157(9): 094901, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36075703

RESUMO

The introduction of soft organic nanoparticles (NPs) into polymer melts has recently expanded the material design space for polymer nanocomposites, compared to traditional nanocomposites that utilize rigid NPs, such as silica, metallic NPs, and other inorganic NPs. Despite advances in the fabrication and characterization of this new class of materials, the effect of NP stiffness on the polymer structure and dynamics has not been systematically investigated. Here, we use molecular dynamics to investigate the segmental dynamics of the polymer interfacial region of isolated NPs of variable stiffness in a polymer matrix. When the NP-polymer interactions are stronger than the polymer-polymer interactions, we find that the slowing of segmental dynamics in the interfacial region is more pronounced for stiff NPs. In contrast, when the NP-polymer interaction strength is smaller than the matrix interaction, the NP stiffness has relatively little impact on the changes in the polymer interfacial dynamics. We also find that the segmental relaxation time τα of segments in the NP interfacial region changes from values lower than to higher than the bulk material when the NP-polymer interaction strength is increased beyond a "critical" strength, reminiscent of a binding-unbinding transition. Both the NP stiffness and the polymer-surface interaction strength can thus greatly influence the relative segmental relaxation and interfacial mobility in comparison to the bulk material.

13.
BMC Pulm Med ; 22(1): 483, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36539782

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been shown to significantly improve the survival of patients with advanced lung adenocarcinoma (LUAD). However, only limited proportion of patients could benefit from ICIs. Novel biomarkers with strong predictability are needed for clinicians to maximize the efficacy of ICIs. Our study aimed to identify potential biomarkers predicting ICIs efficacy in LUAD. METHODS: The Cancer Genome Atlas (TCGA) PanCancer Atlas studies in cBioportal were used to evaluate the mutation frequency of ANK2 across multiple cancers. Clinical and mutational data for LUAD from ICIs-treated cohorts (Hellmann et al. and Rizvi et al.) were collected to explore the correlation between ANK2 mutation and clinical outcomes. In addition, the relationship between ANK2 expression and clinical outcomes was analyzed using LUAD data from TCGA and Gene Expression Omnibus. Furthermore, the impact of ANK2 mutation and expression on the tumor immune microenvironment of LUAD was analyzed using TCGA and TISIDB databases. RESULTS: Patients with ANK2 mutation benefited more from ICIs. In ICIs-treated cohort, prolonged progression-free survival (PFS) (median PFS: NR (not reached) vs. 5.42 months, HR (hazard ratio) 0.31, 95% CI 0.18-0.54; P = 0.0037), improved complete response rate (17.65% vs. 1.85%, P = 0.0402), and improved objective response rate (64.71% vs. 24.07%, P = 0.0033) were observed in LUAD patients with ANK2 mutation compared to their wild-type counterparts. Regarding ANK2 expression, it was observed that ANK2 expression was decreased in LUAD (P < 0.05) and a higher level of ANK2 expression was associated with longer overall survival (HR 0.69, 95% CI 0.52-0.92; P = 0.012) in TCGA LUAD cohort. Moreover, ANK2 mutation or higher ANK2 expression correlated with enhanced antitumor immunity and "hot" tumor microenvironment in LUAD, which could be potential mechanisms that ANK2 mutation facilitated ICIs therapy and patients with higher ANK2 expression survived longer. CONCLUSION: Our findings suggest that ANK2 mutation or increased ANK2 expression may serve as a favorable biomarker for the efficacy of ICIs in patients with LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Biomarcadores , Bases de Dados Factuais , Mutação , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Biomarcadores Tumorais/genética , Microambiente Tumoral , Anquirinas/genética
14.
Molecules ; 27(11)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35684349

RESUMO

In this research, the composition of free phenols, bound phenols, and anthocyanins and their in vitro antioxidant activity and in vitro α-glucosidase inhibiting activity were observed in different barley colors. The outcomes revealed that the contents of total phenols (570.78 mg/100 gDW), total flavonoids (47.08 mg/100 gDW), and anthocyanins (48.07 mg/100 g) were the highest in purple barley. Furthermore, the structure, composition, and concentration of phenolics differed depending on the colors of barley. The types and contents of bound total phenolic acids and flavonoids were greater than those of free total phenolic acids and flavonoids. The main phenolic acids in blue barley were cinnamic acid polyphenols, whereas in black, yellow, and purple barley, benzoic acid polyphenols were the main phenolic acids, and the main types of flavonoids in black and blue barley were chalcones and flavanones, respectively, whereas flavonol was the main type of flavonoid in yellow and purple barley. Moreover, cornflower pigment-3-glucoside was the major anthocyanin in blue, yellow, and purple barley, whereas the main anthocyanin in black barley was delphinidin-3-glucoside. The dark color of barley indicated richness in the anthocyanins. In addition, the free polyphenol fractions had stronger DPPH and ABTS radical scavenging capacity as compared to the bound ones. In vitro α-glucosidase-inhibiting activity was greater in bound polyphenols than in free polyphenols, with differences between different varieties of barley. Purple barley phenolic fractions had the greatest ABTS radical scavenging and iron ion reduction capacities, as well as the highest α-glucosidase-inhibiting activity. The strongest DPPH radical scavenging capacity was found in yellow barley, while the strongest in vitro α-glucosidase-inhibiting activity was found in anthocyanins isolated from black barley. Furthermore, in different colors of barley, there was a strong association between the concentration of specific phenolic compounds and antioxidant and α-glucosidase-inhibiting activities. The outcomes of this study revealed that all colored barley seeds tested were high in phenolic compounds, and had a good antioxidant impact and α-glucosidase-inhibiting activity. As a result, colored barley can serve as an antioxidant and hypoglycemic food. Polyphenols extracted from purple barley and anthocyanins extracted from black barley stand out among them.


Assuntos
Antocianinas , Hordeum , Antocianinas/farmacologia , Antioxidantes/farmacologia , Cor , Flavonoides/farmacologia , Hordeum/química , Fenóis , Polifenóis/farmacologia , alfa-Glucosidases
15.
Phys Rev Lett ; 127(9): 090501, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34506190

RESUMO

Non-Hermitian topological phases exhibit a number of exotic features that have no Hermitian counterparts, including the skin effect and breakdown of the conventional bulk-boundary correspondence. Here, we implement the non-Hermitian Su-Schrieffer-Heeger Hamiltonian, which is a prototypical model for studying non-Hermitian topological phases, with a solid-state quantum simulator consisting of an electron spin and a ^{13}C nuclear spin in a nitrogen-vacancy center in a diamond. By employing a dilation method, we realize the desired nonunitary dynamics for the electron spin and map out its spin texture in the momentum space, from which the corresponding topological invariant can be obtained directly. From the measured spin textures with varying parameters, we observe both integer and fractional winding numbers. The non-Hermitian topological phase with fractional winding number cannot be continuously deformed to any Hermitian topological phase and is intrinsic to non-Hermitian systems. Our result paves the way for further exploiting and understanding the intriguing properties of non-Hermitian topological phases with solid-state spins or other quantum simulation platforms.

16.
Surg Endosc ; 35(12): 6524-6531, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33179181

RESUMO

BACKGROUND AND AIM: With the worldwide spread of coronavirus disease 2019 (COVID-19), it has devastated the economy and taken a toll on people' life in every aspects. In this study, we aimed to evaluate the influence of the COVID-19 epidemic on the GI endoscopy practice in China. METHODS: The nationwide survey conducted from 13 to 19 April, 2020. A predesigned standard structured questionnaire was sent to all members of the Chinese Society of Digestive Endoscopy (CSDE) in mainland China by email. Number of various GI endoscopic procedures and participants getting endoscopic training from January 1 to April 10, 2020 (the COVID-19 period) and the same period of 2019 were collected and analyzed. RESULTS: A total of 468 hospitals responded to this survey, and most of them (85.4%) were tertiary referral hospitals. The sum number of GI endoscopic procedures deceased significantly from 3,203,594 in 2019 to 1,512,619 in 2020, including 2,996,779 to 1,401,665 of diagnostic procedures and 206,815 to 110,954 of therapeutic procedures. More than half of centers (57.1%) reduced about 1,000-5,000 endoscopic activities. Of 271 hospitals (57.9%) providing endoscopic training, the total number of participants decreased from 2,977 in 2019 to 1,131 in 2020. Most of hospitals (93.8%) adhered to the recommendation of endoscopy practice issued by CSDE during the outbreak of COVID-19, and there was no cases of infection in endoscopic departments of all surveyed hospitals. CONCLUSION: With the influence of the COVID-19 epidemic, there has been significant decease of GI endoscopy practice in mainland China.


Assuntos
COVID-19 , Epidemias , China/epidemiologia , Endoscopia Gastrointestinal , Humanos , SARS-CoV-2
17.
Surg Endosc ; 35(11): 6132-6138, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33104918

RESUMO

BACKGROUND AND AIMS: Gastric schwannoma (GS) is not well clinically recognized and surgical resection (SR) remains the mainstay of treatment. Recently, endoscopic resection (ER) appears to be a safe and effective alternative. However, its comparative outcomes with SR is lacking. Our aim was to first compare clinical outcomes and costs between ER and SR in the management of GSs. METHODS: A total of 46 consecutive patients with GSs who underwent ER (n = 16) or SR (n = 30) in our large tertiary center between July 2007 and Oct 2018 were included. Clinicopathologic features, clinical outcomes, medical costs and follow-up were retrospectively reviewed and compared between two groups. RESULTS: Baseline characteristics are comparable except for a smaller tumor size in ER group (22.9 vs 41.0 mm, p = 0.002). Complete resection was achieved in 87.5% of patients with ER and 100% of patients with SR (p = 0.116). The ER group had a significant shorter operative time (91.6 vs 128.2 min), less blood loss (16.9 vs 62.7 mL) and lower operation cost (21,054.4 vs 30,843.4 RMB) than SR group (all p < 0.05). There was no significant difference in adverse events (12.5% vs 10%, p = 0.812) and length of postoperative hospital stay (8.3 vs 8.2 days, p = 0.945). During a long-term follow-up of mean 37.4 months (range 6-140 months), no residue, recurrence or metastasis was observed in both groups. CONCLUSIONS: Compared with SR, ER has the similar safety and efficacy in the management of GSs, but contributes to a shorter operation time and lower medical costs. ER may be considered as the first-line treatment, especially for patients with GSs smaller than 30 mm.


Assuntos
Ressecção Endoscópica de Mucosa , Neurilemoma , Neoplasias Gástricas , Gastroscopia , Humanos , Recidiva Local de Neoplasia , Neurilemoma/cirurgia , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
18.
J Chem Phys ; 155(17): 174901, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34742183

RESUMO

We examine the mobility gradient in the interfacial region of substrate-supported polymer films using molecular dynamics simulations and interpret these gradients within the string model of glass-formation. No large gradients in the extent of collective motion exist in these simulated films, and an analysis of the mobility gradient on a layer-by-layer basis indicates that the string model provides a quantitative description of the relaxation time gradient. Consequently, the string model indicates that the interfacial mobility gradient derives mainly from a gradient in the high-temperature activation enthalpy ΔH0 and entropy ΔS0 as a function of depth z, an effect that exists even in the high-temperature Arrhenius relaxation regime far above the glass transition temperature. To gain insight into the interfacial mobility gradient, we examined various material properties suggested previously to influence ΔH0 in condensed materials, including density, potential and cohesive energy density, and a local measure of stiffness or u2(z)-3/2, where u2(z) is the average mean squared particle displacement at a caging time (on the order of a ps). We find that changes in local stiffness best correlate with changes in ΔH0(z) and that ΔS0(z) also contributes significantly to the interfacial mobility gradient, so it must not be neglected.

19.
Proc Natl Acad Sci U S A ; 115(22): 5641-5646, 2018 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-29760090

RESUMO

There is significant variation in the reported magnitude and even the sign of [Formula: see text] shifts in thin polymer films with nominally the same chemistry, film thickness, and supporting substrate. The implicit assumption is that methods used to estimate [Formula: see text] in bulk materials are relevant for inferring dynamic changes in thin films. To test the validity of this assumption, we perform molecular simulations of a coarse-grained polymer melt supported on an attractive substrate. As observed in many experiments, we find that [Formula: see text] based on thermodynamic criteria (temperature dependence of film height or enthalpy) decreases with decreasing film thickness, regardless of the polymer-substrate interaction strength ε. In contrast, we find that [Formula: see text] based on a dynamic criterion (relaxation of the dynamic structure factor) also decreases with decreasing thickness when ε is relatively weak, but [Formula: see text] increases when ε exceeds the polymer-polymer interaction strength. We show that these qualitatively different trends in [Formula: see text] reflect differing sensitivities to the mobility gradient across the film. Apparently, the slowly relaxing polymer segments in the substrate region make the largest contribution to the shift of [Formula: see text] in the dynamic measurement, but this part of the film contributes less to the thermodynamic estimate of [Formula: see text] Our results emphasize the limitations of using [Formula: see text] to infer changes in the dynamics of polymer thin films. However, we show that the thermodynamic and dynamic estimates of [Formula: see text] can be combined to predict local changes in [Formula: see text] near the substrate, providing a simple method to infer information about the mobility gradient.

20.
Mycorrhiza ; 31(2): 161-171, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33559745

RESUMO

Arbuscular mycorrhizal fungi (AMF) are suggested to be important for invasions by many exotic plants. However, it is not yet known how associations between AMF and invasive plant populations change in mountains ranges and how changed associations affect further expansion of different populations in new habitats. We conducted a field survey to detect AMF colonization rate of the invasive Galinsoga quadriradiata along an elevational gradient ranging from 223 to 1947 masl in the Qinling and Bashan Mountains, China. Additionally, a greenhouse experiment was conducted to compare plant growth performance among five elevational populations. In the field, total plant mass and seed production, as well as root AMF colonization rate, significantly decreased with elevation. When populations were grown in a novel soil environment in the greenhouse, the high-altitude populations achieved higher seed and total mass at lower AMF colonization rate than the low-altitude populations. Moreover, high AMF association was related to high intraspecific competition within low-altitude populations and limited seed production. Our results revealed that the associations between AMF and G. quadriradiata decrease with altitude in mountain ranges, and this may indicate that differentiation of association between AMF and elevational populations occurs during range expansion of G. quadriradiata. The results of the greenhouse experiment suggest that the high-altitude populations are more aggressive than the low-altitude populations in a non-stressful environment.


Assuntos
Micorrizas , Altitude , China , Raízes de Plantas , Plantas
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