Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 113
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-36673652

RESUMO

Neuroticism is a personality trait that impacts daily life and raises the risk of mental problems and physical illnesses. To understand the emotion regulation mechanism of neurotic individuals, we developed two complementary studies to examine the effects of mindfulness and negative cognitive bias. In Study 1, four scales (EPQ-RSC, FFMQ, CERQ, NCPBQ) were used for assessment. Correlation analysis and structural comparison showed that: (1) the level of neuroticism was positively correlated with negative emotion regulation; (2) negative cognitive bias mediated the relationship between neuroticism and emotion regulation; (3) mindfulness and negative cognitive bias mediated the relationship in a chain. Study 1 showed that cognitive bias may play a key role in the emotion regulation mechanism. Study 2 further explored the cognitive bias of neurotic individuals using three behavioral experiments. A mixed-design ANOVA indicated that individuals with high neuroticism levels exhibited negative attention, memory, and interpretation biases. Our findings extend previous research on emotion regulation problems of neurotic individuals and broaden the field to personality-based emotion disorders. In particular, a theoretical rationale is provided for the application of cognitive behavioral therapy, such as mindfulness-based cognitive therapy (MBCT), to the emotion regulation of neurotic individuals.


Assuntos
Regulação Emocional , Atenção Plena , Humanos , Emoções/fisiologia , Viés , Cognição
2.
Artigo em Inglês | MEDLINE | ID: mdl-36707042

RESUMO

Aeromonas hydrophila can pose a great threat to fish survival. In this study, we investigated the differential immune and redox response in gut-liver axis of hybrid fish (WR) undergoing gut infection. WR anally intubated with A. hydrophila showed severe midgut injury with decreased length-to-width ratios of villi along with GC hyperplasia and enhanced antioxidant activities, but expression profiles of cytokines, chemokines, antibacterial molecules, redox sensors and tight junction proteins decreased dramatically. In contrast, immune-related gene expressions and antioxidant activities increased significantly in liver of WR following gut infection with A. hydrophila. These results highlighted the differential immune regulation and redox balance in gut-liver axis response to bacterial infection.

3.
Front Aging Neurosci ; 14: 1029533, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389078

RESUMO

Astrocytic Ca2+ transients are essential for astrocyte integration into neural circuits. These Ca2+ transients are primarily sequestered in subcellular domains, including primary branches, branchlets and leaflets, and endfeet. In previous studies, it suggests that aging causes functional defects in astrocytes. Until now, it was unclear whether and how aging affects astrocytic Ca2+ transients at subcellular domains. In this study, we combined a genetically encoded Ca2+ sensor (GCaMP6f) and in vivo two-photon Ca2+ imaging to determine changes in Ca2+ transients within astrocytic subcellular domains during brain aging. We showed that aging increased Ca2+ transients in astrocytic primary branches, higher-order branchlets, and terminal leaflets. However, Ca2+ transients decreased within astrocytic endfeet during brain aging, which could be caused by the decreased expressions of Aquaporin-4 (AQP4). In addition, aging-induced changes of Ca2+ transient types were heterogeneous within astrocytic subcellular domains. These results demonstrate that the astrocytic Ca2+ transients within subcellular domains are affected by aging differently. This finding contributes to a better understanding of the physiological role of astrocytes in aging-induced neural circuit degeneration.

4.
Front Oncol ; 12: 911160, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387112

RESUMO

This research found that the clinical outcomes (PFS, ORR, OS) of the non-platinum-based doublet regimen (docetaxel capecitabine combination) were similar to those of the platinum-based (oxaliplatin capecitabine combination) when used as first line therapy for MGC patients. Background: Docetaxel, platinum and fluorouracil are the three most important drugs in the treatment of MGC. This study was to compare clinical outcomes of the docetaxel capecitabine combination and the oxaliplatin capecitabine combination as first-line therapy in MGC patients. Methods: In this phase II trial, MGC patients were randomly assigned and treated with either TX (capecitabine 1000 mg/m2/twice daily/1-14 days and docetaxel 60/75 mg/m2 on the 1st day) (because of toxicity, the dose of docetaxel was reduced to 60 mg/m2) or XELOX (capecitabine the same dose with TX and oxaliplatin 130 mg/m2 on the 1st day) as first-line therapy. After progression, patients were crossover to the other group as second-line treatment. Results: Total 134 MGC patients were randomized (69 in TX, 65 in XELOX). There was no significant difference between the PFS of the two groups (TX vs XELOX, 4.6 months vs 5.1 months, p=0.359), and the SFS (9.3 months vs 7.5 months, p=0.705), OS (13.1 months vs 9.6 months, p=0.261), and ORR (46.4% vs 46.2%) were also similar. Among patients with ascites, the TX group had significantly longer PFS and OS than the XELOX group. A total of 85 patients (48 in TX, 37 in XELOX) received second-line treatment, with overall survival of second-line chemotherapy (OS2) of 8.0 m and 5.3 m (p=0.046), respectively. Grade 3 to 4 treatment-related adverse events of first line treatment occurred more in TX group than that in XELOX group(60.6% vs 55.4%). Conclusion: TX regimen is an alternative choice of first-line treatment for MGC patients. We still need to explore the large number of cohort to confirm this results.

5.
Child Adolesc Psychiatry Ment Health ; 16(1): 94, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36447259

RESUMO

BACKGROUND: This study explored mental health of pediatric patients with living donor liver transplantation. METHODS: A total of 741 children who successfully underwent living donor liver transplantation from 2009 to 2019 enrolled in this study. Participants were aged between 3 and 12 years (mean age = 5.28; SD = 2.01). The Strengths and Difficulties Questionnaire was used to evaluate emotional and behavioral problems. Parents completed the 5-item World Health Organization Well-Being Index and reported their child's height, weight, sleep duration, parent-child interactions, home environment, physical activities, and time spent on screen exposure. Propensity score matching method was used to generate a control group from 20,934 healthy children. Univariate analysis and multiple logistic regression analyses were used to identify the correlational factors in children's mental health following a liver transplantation. RESULTS: Compared to healthy children, patients after liver transplantation were prone to emotional problems, hyperactivity, and peer problems. Moreover, parental mental health, physical activity, and family environment were identified as factors associated with mental health of pediatric liver transplant patients. CONCLUSION: The findings highlight the need to focus on mental health of pediatric transplant patients, increase support for parents, and strengthen positive parent-child interactions.

7.
Molecules ; 27(11)2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35684454

RESUMO

The clinical pharmacodynamics of tacrolimus in renal transplant patients has significant interindividual variability. T lymphocytes were selected to study the pharmacodynamic response of tacrolimus, which was significantly correlated with renal function and the outcome of renal transplant patients. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectroscopy (UPLC/Q-TOF-MS) was performed to obtain the metabolic profiles of 109 renal transplant patients. A partial least squares (PLS) model was constructed to screen potential biomarkers that could predict the efficacy of tacrolimus. Multinomial logistic regression analysis established a bridge that could quantify the relationship between the efficacy of tacrolimus and biomarkers. The results showed a good correlation between endogenous molecules and the efficacy of tacrolimus. Metabolites such as serum creatinine, mesobilirubinogen, L-isoleucine, 5-methoxyindoleacetate, eicosapentaenoic acid, N2-succinoylarginine, tryptophyl-arginine, and butyric acid were indicated as candidate biomarkers. In addition, the key biomarkers could correctly predict the efficacy of tacrolimus with an accuracy of 82.5%. Finally, we explored the mechanism of individual variation by pathway analysis, which showed that amino acid metabolism was significantly related to the efficacy of tacrolimus. Moreover, orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there was no difference in key metabolites among different pharmacodynamic groups at 1 month and 3 months after dose adjustment, suggesting that pharmacometabonomics is a useful tool to predict individual differences in pharmacodynamics and thus to facilitate individualized drug therapy.


Assuntos
Transplante de Rim , Metabolômica , Biomarcadores , Cromatografia Líquida de Alta Pressão , Humanos , Espectrometria de Massas/métodos , Metabolômica/métodos , Tacrolimo
8.
Stem Cell Res Ther ; 13(1): 285, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35765112

RESUMO

Aging causes astrocyte morphological degeneration and functional deficiency, which impairs neuronal functions. Until now, whether age-induced neuronal deficiency could be alleviated by engraftment of glial progenitor cell (GPC) derived astrocytes remained unknown. In the current study, GPCs were generated from embryonic cortical neural stem cells in vitro and transplanted into the brains of aged mice. Their integration and intervention effects in the aged brain were examined 12 months after transplantation. Results indicated that these in-vitro-generated GPC-derived astrocytes possessed normal functional properties. After transplantation they could migrate, differentiate, achieve long-term integration, and maintain much younger morphology in the aged brain. Additionally, these GPC-derived astrocytes established endfeet expressing aquaporin-4 (AQP4) and ameliorate AQP4 polarization in the aged neocortex. More importantly, age-dependent sensory response degeneration was reversed by GPC transplantation. This work demonstrates that rejuvenation of the astrocyte niche is a promising treatment to prevent age-induced degradation of neuronal and behavioral functions.


Assuntos
Células-Tronco Neurais , Neuroglia , Animais , Astrócitos/metabolismo , Camundongos , Neurônios , Transplante de Células-Tronco
9.
Int J Nurs Sci ; 9(2): 187-195, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35509700

RESUMO

Objective: To standardize the distress management of gastric cancer patients receiving chemotherapy, the adapted Cancer-related Distress Management Guidelines were implemented in nursing practice among gastric cancer patients receiving chemotherapy based on A Guideline Adaptation and Implementation Planning Resource (CAN-IMPLEMENT). Methods: Based on the theoretical framework of CAN-IMPLEMENT, A multidisciplinary team was established, barriers and facilitators obstacles of guidelines implementation in medical oncology units were assessed, corresponding solutions were formulated, the guidelines implementation process was monitored, and implementation results were evaluated. Results: The multidisciplinary team developed review criteria, standardized work paths, assessment tools, training manuals for healthcare professionals, education manuals for patients and their caregivers. After guidelines implementation, the completion rate of the distress management record came up to 97.9% (189/193). From September 2017 to December 2018, the compliance of medical staff on most items in the audit checklist was improved, ranging from 57.1% (100/175) to 100.0% (193/193). The positive distress rate of gastric cancer patients receiving chemotherapy was decreased from 22.7% (32/141) to 9.3% (18/193) (P < 0.05), and the Median (range) of the distress score declined from 2 (0-9) to 0 (0-7) (P < 0.001). Conclusions: The implementation of guidelines based on CAN-IMPLEMENT promotes the establishment of a distress management system in the medical oncology units. The review standards, standardized work paths, and evaluation tools for distress in cancer patients formulated by the multidisciplinary team had clinical applicability and effectiveness. Quality control in the practice of distress management was effective. The compliance of healthcare professionals with distress management was improved. The distress of gastric cancer patients receiving chemotherapy was alleviated effectively.

10.
Signal Transduct Target Ther ; 7(1): 132, 2022 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-35461307

RESUMO

Understanding the decay and maintenance of long-term SARS-CoV-2 neutralizing antibodies in infected or vaccinated people and how vaccines protect against other SARS-CoV-2 variants is critical for assessing public vaccination plans. Here, we measured different plasm antibody levels 2 and 12 months after disease onset, including anti-RBD, anti-N, total neutralizing antibodies, and two neutralizing-antibody clusters. We found that total neutralizing antibodies declined more slowly than total anti-RBD and anti-N IgG, and the two neutralizing-antibody clusters decayed even more slowly than total neutralizing antibodies. Interestingly, the level of neutralizing antibodies at 12 months after disease onset was significantly lower than that at 2 months but more broadly neutralized SARS-CoV-2 variants, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Lambda (C.37). Significant immune escape by the Omicron variant (B.1.1.529) was also observed 2 months post-recovery. Furthermore, we revealed that a high percentage of virus-specific CD4+ T cells and cTfh1 were associated with a slower decline in humoral immunity, accompanied by higher levels of CXCR3 ligands such as CXCL9 and CXCL10, higher frequency of cTfh1, and lower levels of cTfh2 and cTfh17. Our data highlight the importance of coordinating T-cell and humoral immunity to achieve long-term protective immunity.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes/genética , Anticorpos Antivirais/genética , Linfócitos T CD4-Positivos , Humanos , Linfócitos T
11.
Front Microbiol ; 13: 834311, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35356524

RESUMO

Various amino acids are widely manufactured using engineered bacteria. It is crucial to keep the dissolved oxygen at a certain level during fermentation, but accompanied by many disadvantages, such as high energy consumption, reactive oxygen species, and risk of phage infections. Thus, anaerobic production of amino acids is worth attempting. Nitrate respiration systems use nitrate as an electron acceptor under anoxic conditions, which is different from the metabolism of fermentation and can produce energy efficiently. Herein, we engineered Corynebacterium crenatum to enhance L-arginine production under anaerobic conditions through strengthening nitrate respiration and reforming nitrogen flux. The construction of mutant strain produced up to 3.84 g/L L-arginine under oxygen limitation with nitrate, and this value was 131.33% higher than that produced by the control strain under limited concentrations of oxygen without nitrate. Results could provide fundamental information for improving L-arginine production by metabolic engineering of C. crenatum under oxygen limitation.

12.
Emerg Microbes Infect ; 11(1): 829-840, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35230230

RESUMO

Waned vaccine-induced immunity and emerging severe acute respiratory syndrome coronavirus 2 variants with potential for immune escape pose a major threat to the coronavirus disease (COVID-19) pandemic. Here, we showed that humoral immunity components, including anti-S + N, anti-RBD IgG, and neutralizing antibodies (NAbs), gradually waned and decreased the neutralizing capacity against emerging Omicron variants at 3 and 6 months after two inactivated COVID-19 vaccinations. We evaluated two boosting strategies with either a third dose of inactivated vaccine (homologous, I-I-I) or a recombinant subunit vaccine (heterologous, I-I-S). Both strategies induced the production of high levels of NAbs with a broad neutralizing capacity and longer retention. Interestingly, I-I-S induced 3.5-fold to 6.8-fold higher NAb titres than I-I-I, with a broader neutralizing capacity against six variants of concern, including Omicron. Further immunological analysis revealed that the two immunization strategies differ considerably, not only in the magnitude of total NAbs produced, but also in the composite pattern of NAbs and the population of virus-specific CD4+ T cells produced. Additionally, in some cases, heterologous boosted immunity induced the production of more effective epitopes than natural infection. The level of I-I-S-induced NAbs decreased to 48% and 18% at 1 and 3 months after booster vaccination, respectively. Overall, our data provide important evidence for vaccination strategies based on available vaccines and may help guide future global vaccination plans.


Assuntos
Anticorpos Neutralizantes , Vacinas contra COVID-19/imunologia , COVID-19 , Linfócitos T , Anticorpos Antivirais , COVID-19/prevenção & controle , Humanos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética , Linfócitos T/imunologia , Vacinação , Vacinas de Subunidades
13.
Front Oncol ; 12: 830816, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35280779

RESUMO

Background: Metastatic colorectal cancer (mCRC) is a heterogenous disease with limited precision medicine and targeted therapy options. Monoclonal antibodies against epidermal growth factor receptor (EGFR) have been a crucial treatment option for mCRC. However, proper biomarkers for predicting therapeutic response remain unknown. As a non-invasive test, circulating tumor DNA (ctDNA) is appropriately positioned to reveal tumor heterogeneity and evolution, as it can be used in real-time genomic profiling. To evaluate the significance of ctDNA in monitoring the dynamic therapeutic response and prognosis of mCRC, we detected the baseline and dynamic changes of ctDNA in mCRC patients receiving anti-EGFR therapies. Methods: A single-center study was conducted retrospectively. Plasma samples from mCRC patients who received anti-EGFR therapies were collected at baseline and continuous treatment points. The ctDNA was extracted and sequenced with a target panel of tumor-related genes via next-generation sequencing (NGS). Clinical information was also collected and analyzed. Results: We conducted dynamic sampling of 22 mCRC patients, analyzed 130 plasma samples, obtained a baseline genomic mutation profile of the patients. In total, 54 variations were detected in 22 plasma samples, with a positive rate of 77.3% (17/22). TP53 was the most mutated gene (59.1%, 13/22), followed by APC (18.2%, 4/22). There was a high concordance rate of genomic characteristics between the tumor tissue test by polymerase chain reaction and ctDNA test by NGS. The mutation discrepancy increased with an extended course of treatment. During remission TP53 and APC were the most frequently decreased clonal mutations and KRAS, NRAS, ERBB2 and PIK3CA were the most decreased subclonal mutations. Both mutation types were increased during progression. The ctDNA decreased earlier than did the responses of computed tomography and traditional tumor markers (carbohydrate antigen 19-9 and carcinoembryonic antigen [CEA]). Lactate dehydrogenase level (P = 0.041), CEA level (P = 0.038), and primary lesion site (P = 0.038) were independent risk factors that influenced overall survival. Moreover, patients with RAS mutations tended to have a worse prognosis (P = 0.072). Conclusions: This study demonstrates that ctDNA is a promising biomarker for monitoring the dynamic response to treatment and determining the prognosis of mCRC.

14.
Front Oncol ; 12: 747124, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35174078

RESUMO

BACKGROUND: It is still controversial whether primary tumor resection (PTR) improves survival in colorectal cancer (CRC) patients with unresectable metastases. METHODS: Colon cancer patients were enrolled and randomly allocated to with or without PTR after induction chemotherapy with XELOX or mFOLFOX6, and those with chemotherapy failure were excluded. The primary endpoint was TTF (time to strategy failure) on an intent-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02291744. RESULTS: Between April 2015 and July 2020, 140 patients were enrolled, and 54 patients were excluded due to colon obstruction (16), perforation (1), disease progression (22), death (1), radical resection (3), or other reasons (11). After induction chemotherapy, 86 patients were randomized into group A (the resection group, n = 42) or group B (chemotherapy-alone group, n = 44). The median TTF was 143 days (95% CI: 104.9-181.1) in group A and 196 days (95% CI: 96.5-295.5) in group B (HR: 0.930 95% CI: 0.589-1.468, p = 0.755), and there was no significant difference in PFS, OS, and incidence of chemotherapy-related adverse events between two groups. The primary lesion-related events after PTR in group A were significantly fewer than those in group B. Patients with a tumor regression grade (TRG) score of 2 had longer TTF and PFS than those with score of 3. CONCLUSION: PTR after induction chemotherapy could not bring survival benefits for colon cancer patients with unresectable metastases, and it is not recommended routinely. However, it also requires individualized treatment as colon obstruction or perforation occurred in some patients and PTR could reduce primary tumor-related events, and the TRG score might help for selection of beneficial patients.

15.
Cancer Commun (Lond) ; 42(4): 314-326, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35212487

RESUMO

BACKGROUND: There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer (AGC). We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine (XELOX) and epirubicin, oxaliplatin, plus capecitabine (EOX) regimens in treating AGC. METHODS: This phase III trial enrolled previously untreated patients with AGC who were randomly assigned to receive the XELOX or EOX regimen. The primary endpoint was non-inferiority in progression-free survival (PFS) for XELOX as compared with EOX on an intention-to-treat basis. RESULTS: Between April 10, 2015 and August 20, 2020, 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). The median PFS (mPFS) was 5.0 months (95% confidence interval [CI] = 4.5-6.0 months) in the XELOX arm and 5.5 months (95% CI = 5.0-6.0 months) in the EOX arm (hazard ratio [HR] = 0.989, 95% CI = 0.812-1.203; Pnon-inferiority = 0.003). There was no significant difference in median overall survival (mOS) (12.0 vs. 12.0 months, P = 0.384) or objective response rate (37.4% vs. 45.1%, P = 0.291) between the two groups. In patients with poorly differentiated adenocarcinoma and liver metastasis, the EOX arm had a significantly longer mOS (P = 0.021) and a trend of longer mPFS (P = 0.073) than the XELOX arm. The rate of grade 3/4 adverse events (AEs) was 42.2% (90/213) in the XELOX arm and 72.5% (156/215) in the EOX arm (P = 0.001). The global health-related quality of life (QoL) score was significantly higher in the XELOX arm than in the EOX arm during chemotherapy. CONCLUSIONS: This non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC patients. However, the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.


Assuntos
Adenocarcinoma , Neoplasias Hepáticas , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Oxaliplatina , Oxaloacetatos , Estudos Prospectivos , Qualidade de Vida , Neoplasias Gástricas/patologia
16.
Int J Nurs Sci ; 9(1): 56-62, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35079605

RESUMO

OBJECTIVE: This study aimed to adapt relevant clinical practice guidelines for distress management in cancer patients based on A Guideline Adaptation and Implementation Planning Resource (CAN-IMPLEMENT), and develop Cancer-related Distress Management Guidelines in the context of the research site. METHODS: According to CAN-IMPLEMENT, the symptoms of cancer patients in Shanghai were investigated, and a work plan was formulated to adapt cancer-related distress management guidelines. The relevant clinical practice guidelines for distress management in cancer patients were searched, screened and assessed, the contents of the included clinical practice guidelines were screened, extracted and integrated, and the Cancer-related Distress Management Guidelines was developed. After peer review, the Cancer-related Distress Management Guidelines was finally formed. RESULTS: The physical symptom distress score was higher than the psychological symptom distress score among cancer patients in Shanghai. Two clinical practice guidelines related to distress management in cancer patients were included after searching, screening, assessment and selection systematically. The domain scores of the draft Cancer-related Distress Management Guidelines on Appraisal of Guidelines for Research and Evaluation II (AGREE II) were 73.75%-87.50%, respectively. The scores of most recommendations on feasibility, appropriateness, meaningfulness and effectiveness were at least 90%. The final guidelines included 13 recommendations. CONCLUSIONS: The quality of the draft Cancer-related Distress Management Guidelines based on two included guidelines was well-accepted. The final Cancer-related Distress Management Guidelines needs to be further verified in clinical practice for feasibility, suitability and effectiveness.

17.
Ther Adv Med Oncol ; 14: 17588359211068737, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35069808

RESUMO

BACKGROUND: FOLFIRI [irinotecan, folinic acid (CF), and fluorouracil] is considered a standard second-line chemotherapy regimen for patients with metastatic colorectal cancer (mCRC) who failed first-line XELOX/FOLFOX regimens. However, it remains unknown whether fluorouracil is still necessary in this case. This trial was designed to test the superiority of FOLFIRI over single-agent irinotecan as a second-line treatment for patients with mCRC. METHODS: This randomized clinical trial was conducted in five hospitals in China. From 4 November 2016 to 17 January 2020, patients aged 18 years or older with histologically confirmed unresectable mCRC and who had failed first-line XELOX/FOLFOX regimens were screened and enrolled. Patients were randomized to receive either FOLFIRI or irinotecan. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and toxicity. Data were analyzed on an intention-to-treat basis. RESULTS: A total of 172 patients with mCRC were randomly treated with FOLFIRI (n = 88) or irinotecan (n = 84). The median PFS was 104 and 112 days (3.5 and 3.7 months) in the FOLFIRI and irinotecan groups, respectively [hazard ratio (HR) = 1.084, 95% confidence interval (CI) = 0.7911-1.485; p = 0.6094], and there was also no significant difference in OS and ORR between the two groups. The incidence of the following adverse events (AEs) was significantly higher in the FOLFIRI group than in the irinotecan group: any grade AEs including leucopenia (73.9% versus 55.4%), neutropenia (72.7% versus 56.6%), thrombocytopenia (31.8% versus 18.1%), jaundice (18.2% versus 7.2%), mucositis (40.9% versus 14.5%), vomiting (37.5% versus 21.7%), and fever (19.3% versus 7.2%) and grade 3-4 neutropenia (47.7% versus 21.7%). CONCLUSION: This is the first head-to-head trial showing that single-agent irinotecan yielded PFS, OS, and ORR similar to FOLFIRI, with a more favorable toxicity profile; therefore, it might be a more favorable standard chemotherapy regimen for mCRC patients who failed first-line XELOX/FOLFOX regimens. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number NCT02935764, registered 17 October 2016, https://clinicaltrials.gov/ct2/show/NCT02935764.

18.
J Hematol Oncol ; 15(1): 11, 2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-35073937

RESUMO

Limited previous studies focused on the death and progression risk stratification of colorectal cancer (CRC) lung metastasis patients. The aim of this study is to construct a nomogram model combing machine learning-pathomics, radiomics features, Immunoscore and clinical factors to predict the postoperative outcome of CRC patients with lung metastasis. In this study, a total of 103 CRC patients having metastases limited to lung and undergoing radical lung resection were identified. Patch-level convolutional neural network training in weakly supervised manner was used to perform whole slides histopathological images survival analysis. Synthetic minority oversampling technique and support vector machine classifier were used to identify radiomics features and build predictive signature. The Immunoscore for each patient was calculated from the density of CD3+ and CD8+ cells at the invasive margin and the center of metastatic tumor which were assessed on consecutive sections of automated digital pathology. Finally, pathomics and radiomics signatures were successfully developed to predict the overall survival (OS) and disease free survival (DFS) of patients. The predicted pathomics and radiomics scores are negatively correlated with Immunoscore and they are three independent prognostic factors for OS and DFS prediction. The combined nomogram showed outstanding performance in predicting OS (AUC = 0.860) and DFS (AUC = 0.875). The calibration curve and decision curve analysis demonstrated the considerable clinical usefulness of the combined nomogram. Taken together, the developed nomogram model consisting of machine learning-pathomics signature, radiomics signature, Immunoscore and clinical features could be reliable in predicting postoperative OS and DFS of colorectal lung metastasis patients.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Pulmonares/secundário , Complexo CD3/análise , Antígenos CD8/análise , Neoplasias Colorretais/diagnóstico , Aprendizado Profundo , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Nomogramas
19.
Nano Lett ; 21(24): 10333-10340, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34874740

RESUMO

Here, six phenanthrene (the smallest arm-chair graphene nanoribbon) derivatives with dithiomethyl substitutions at different positions as the anchoring groups were synthesized. Scanning tunneling microscopy break junction technique was used to measure their single molecule conductances between gold electrodes, which showed a difference as much as 20-fold in the range of ∼10-2.82 G0 to ∼10-4.09 G0 following the trend of G2,7 > G3,6 > G2,6 > G1,7 > G1,6 > G1,8. DFT calculations agree well with this measured trend and indicate that the single molecule conductances are a combination of energy alignment, electronic coupling, and quantum effects. This significant regio- and steric effect on the single molecule conductance of phenanthrene model molecules shows the complexity in the practice of graphene nanoribbons as building blocks for future carbon-based electronics in one hand but also provides good conductance tunability on the other hand.


Assuntos
Nanotubos de Carbono , Fenantrenos , Eletrônica , Microscopia de Tunelamento , Nanotecnologia
20.
Toxins (Basel) ; 13(11)2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34822566

RESUMO

Enzyme-linked immunosorbent assay (ELISA) is widely used in the routine screening of mycotoxin contamination in various agricultural and food products. Herein, a cascade-amplifying system was introduced to dramatically promote the sensitivity of an immunoassay for ochratoxin A (OTA) detection. Specifically, a biotinylated M13 bacteriophage was introduced as a biofunctional competing antigen, in which a seven-peptide OTA mimotope fused on the p3 protein of M13 was used to specifically recognize an anti-OTA monoclonal antibody, and the biotin molecules modified on capsid p8 proteins were used in loading numerous streptavidin-labeled polymeric horseradish peroxidases (HRPs). Owing to the abundance of biotinylated p8 proteins in M13 and the high molar ratio between HRP and streptavidin in streptavidin-polyHRP, the loading amount of HRP enzymes on the M13 bacteriophage were greatly boosted. Hence, the proposed method exhibited high sensitivity, with a limit of detection of 2.0 pg/mL for OTA detection, which was 250-fold lower than that of conventional ELISA. In addition, the proposed method showed a slight cross-reaction of 2.3% to OTB, a negligible cross-reaction for other common mycotoxins, and an acceptable accuracy for OTA quantitative detection in real corn samples. The practicability of the method was further confirmed with a traditional HRP-based ELISA method. In conclusion, the biotinylated bacteriophage and polyHRP structure showed potential as a cascade-amplifying enzyme loading system for ultra-trace OTA detemination, and its application can be extended to the detection of other analytes by altering specific mimic peptide sequences.


Assuntos
Imunoensaio/métodos , Ocratoxinas/análise , Venenos/análise , Bacteriófagos/química , Biotinilação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...