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1.
BMC Womens Health ; 22(1): 364, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056344

RESUMO

BACKGROUND: The infertility treatment process is associated with various psychological, physical, social, moral, and financial challenges, especially for women. The women are likely to report low marital satisfaction and emotional distress due to fertility treatment demands. This study explored how infertile women described their treatment experience and how they coped with treatment demands as they underwent treatment at three gynecology outpatient clinics in Kenya. METHODS: A qualitative phenomenological research design was used to analyze and describe women's fertility treatment experiences. The data were collected through semi-structured in-depth interviews with 33 infertile women selected purposively. Trustworthiness of the findings was ensured using Guba and Lincoln's criteria. The recorded interviews were transcribed verbatim and then analyzed using reflective thematic analysis, developed by Braun and Clarkes. RESULTS: Three themes and 13 sub-themes related to women's fertility treatment experiences and coping strategies were identified. The theme challenges encountered during fertility treatment have three sub-themes: emotional distressing, physical pain, and financial constraining. Theme impacts of fertility treatment on relationships have three sub-themes: relationship with their husband, relationship with their family, and relationship with their friends. Finally, coping with fertility treatment has six sub-themes: religious practices and personal faith, giving in to feelings, shifting focus, taking a break, staying with their relative's children, and receiving support from others. CONCLUSION: The experiences of women undergoing treatment are multi-dimensional. Therefore, incorporating psychosocial interventions or counseling into the fertility treatment routine with National Health Insurance Fund cards may reduce the treatment burden, improving women's psychological well-being and relationships with their husbands, family, and friends.


Assuntos
Infertilidade Feminina , Adaptação Psicológica , Criança , Feminino , Fertilidade , Humanos , Infertilidade Feminina/psicologia , Infertilidade Feminina/terapia , Quênia , Pesquisa Qualitativa
2.
Front Chem ; 10: 974607, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092664

RESUMO

An accurate diagnosis of acute kidney injury (AKI) at the early stage is critical to not only allow preventative treatments in time but also forecast probable medication toxicity for preventing AKI from starting and progressing to severe kidney damage and death. Therefore, supramolecular fluorescent biomaterials based on Q [8] and PEG-APTS have been prepared herein. This study has found that the unique properties of outer surface methine and the positive density of Q [8] can form a stable assembly with PEG-APTS, and has provided the possibility for the faster crossing of the glomerular filtration barrier to enter into the resident cells of the kidney. In addition to the excellent fluorescence properties, the as-synthesized biomaterial Q [8]@PEG-APTS has possessed significantly low biological toxicity. Most importantly, the accumulation of Q [8]@PEG-APTS in large amounts in cytoplasm and nucleus of HK2 and HMCs cells, respectively, within 24 h enabled distinguishing kidney cells when diagnosing and providing some foundation for early AKI.

3.
Lab Chip ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36106408

RESUMO

Antimicrobial resistance (AMR) by bacteria is a serious global threat, and a rapid, high-throughput, and easy-to-use phenotypic antimicrobial susceptibility testing (AST) method is essential for making timely treatment decisions and controlling the spread of antibiotic resistant micro-organisms. Traditional culture-based methods are time-consuming, and their capability to screen against a large number of different conditions is limited; meanwhile genotypic based methods, including sequencing and PCR based methods, are constrained by rarely identified resistance genes and complicated resistance mechanisms. Here, a combinatorial-screening SlipChip (cs-SlipChip) containing 192 nanoliter-sized compartments is developed which can perform high-throughput phenotypic AST within three hours by monitoring the bacterial growth within nanoliter-sized droplets with bright-field imaging and analyzing the changes in bacterial number and morphology. The minimum inhibitory concentration (MIC) of Escherichia coli ATCC 25922 against four antibiotics (ampicillin, ciprofloxacin, ceftazidime, and nitrofurantoin) can be measured in one chip within 3 hours. Furthermore, five antibiotic-resistant E. coli strains were isolated from patients diagnosed with urinary tract infections (UTIs), and an individual isolate was tested using four antibiotics and eleven antibiotic combinations simultaneously with three different concentrations of each. The results from the cs-SlipChip agree with those of a VITEK 2 automated system. This cs-SlipChip provides a practical high-throughput and rapid phenotypic method for AST and can also be used to screen different chemicals and antibiotic combinations for the treatment of multiple antibiotic-resistant bacteria.

4.
Front Immunol ; 13: 941547, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059464

RESUMO

Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma comorbidity (ACRSwNP) present severe symptoms and are more likely to relapse. However, the pathogenesis of ACRSwNP is not fully understood. The aim of this study was to explore the underlying pathogenesis of ACRSwNP using bioinformatics approaches. ACRSwNP-related differentially expressed genes (DEGs) were identified by the analysis of the GSE23552 dataset. The clusterProfiler R package was used to carry out functional and pathway enrichment analysis. A protein-protein interaction (PPI) network was built using the STRING database to explore key genes in the pathogenesis of ACRSwNP. The bioinformatics analysis results were verified through qRT-PCR. The Connectivity Map (CMap) database was used to predict potential drugs for the treatment of ACRSwNP. A total of 36 DEGs were identified, which were mainly enriched in terms of regulation of immune response and detection sensory perception of taste. Thirteen hub genes including AZGP1, AQP9, GAPT, PIP, and PRR4 were identified as potential hub genes in ACRSwNP from the PPI network. Analysis of the GSE41861 dataset showed that upregulation of CST1 in nasal mucosa was associated with asthma. qRT-PCR detection confirmed the bioinformatics analysis results. Tacrolimus and spaglumic acid were identified as potential drugs for the treatment of ACRSwNP from the CMap database. The findings of this study provide insights into the pathogenesis of ACRSwNP and may provide a basis for the discovery of effective therapeutic modalities for ACRSwNP.


Assuntos
Asma , Pólipos Nasais , Sinusite , Asma/epidemiologia , Asma/genética , Comorbidade , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Humanos , Pólipos Nasais/genética , Pólipos Nasais/patologia , Sinusite/genética
5.
J Oncol ; 2022: 8943643, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059798

RESUMO

Background: Clear cell renal cell carcinoma (ccRCC) is, by far, the most prevalent and fatal kind of kidney cancer. Ferrochelatase (FECH) is an enzyme that performs a significant function in the onset and progression of many distinct kinds of malignant tumors. Nevertheless, its predictive usefulness in renal clear cell carcinoma (RCC) has not yet been fully investigated. Methods: FECH expression in ccRCC and healthy adjoining tissues was primarily screened utilizing data sourced from The Cancer Genome Atlas (TCGA) and subsequently validated using data from an independent cohort derived from the Gene Expression Omnibus (GEO) and the Human Protein Atlas HPA databases. The relationship among FECH expression, clinicopathological parameters, and overall survival (OS) was assessed utilizing multivariate analysis and Kaplan-Meier survival curves. Additionally, the protein networks with FECH interaction were constructed with the aid of the online Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Gene ontology (GO) analysis, and gene set enrichment analysis (GSEA) were conducted based on TCGA data, and a single-sample GSEA was utilized to explore the link between FECH expression and the infiltration status of immune cells in the tumor. The Gene Expression Profiling Interactive Analysis (GEPIA) and TIMER databases were utilized to investigate the relationships of FECH expression with the infiltrating immune cells and the matching gene marker sets. Results: FECH expression was shown to be substantially lowered in ccRCC tumors as opposed to that observed in normal tissues (p < 0.05). Lower levels of FECH expression were shown to have a strong association with higher grades of cancer and more advanced TNM stages. The findings of multivariate and univariate analyses illustrated that the OS in patients with ccRCC with low FECH expression is shorter in contrast with that in the high FECH expression group (p < 0.05). It was discovered that CPOX and frataxin are key proteins that interact with FECH. ccRCC with FECH deficiency was linked to the lack of infiltrating immune cells and their respective marker sets, which included CD4+ T cells. Conclusion: In ccRCC, decreased FECH expression was linked to disease progression, unfavorable prognosis, and impaired immune cell infiltration.

6.
Adv Mater ; : e2201856, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36121344

RESUMO

Two-dimensional (2D) monolayers supporting a wide variety of highly confined plasmons, phonon polaritons, and exciton polaritons can be vertically stacked in vdWHs with controlled constituent layers, stacking sequence, and even twist angles. Van der Waals heterostructures (vdWHs) combine advantages of 2D material polaritons, rich optical structure design and atomic scale integration, which have greatly extended the performance and functions of polaritons, such as wide frequency range, long lifetime, ultrafast all-optical modulation, and photonic crystals for nanoscale light. Here, we review the state of the art of 2D material polaritons in vdWHs from the perspective of design principles and potential applications. We start by discussing some fundamental properties of polaritons in vdWHs, and then cover recent discoveries of plasmons, phonon polaritons, exciton polaritons and their hybrid modes in vdWHs, respectively. We conclude with a perspective discussion on potential applications of these polaritons such as nanophotonic integrated circuits, which will benefit from the intersection between nanophotonics and materials science. This article is protected by copyright. All rights reserved.

7.
BMC Surg ; 22(1): 335, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085058

RESUMO

BACKGROUND: Anastomotic leakage (AL) is one of most severe postoperative complications following low anterior resection (LAR) for rectal cancer, and has an adverse impact on postoperative recovery. The occurence of AL is associated with several factors, while few studies explored the role of intracorporeal barbed suture reinforcement in it. METHODS: Consecutive cases underwent laparoscopic LAR for rectal cancer from Mar. 2018 to Feb. 2021 in our center were retrospectively collected. Cases were classified into the intracorporeal barbed suture reinforcement group and the control group according to whether performing intracorporeal reinforcement with barbed suture, and AL incidences were compared between two groups. Propensity score matching (PSM) was then performed based on identified risk factors to reduce biases from covariates between two groups. AL incidences in the matched cohort were compared. RESULTS: A total of 292 cases entered into the study, and AL incidences were significantly lower in the intracorporeal barbed suture reinforcement group compared with the control group (10.00% vs 2.82%, P = 0.024). Sex, BMI, preoperative adjuvant chemoradiotherapy and anastomotic level were chose for PSM analyses based on previous studies. In the matched cohort, the AL incidences were still significantly lower in the intracorporeal barbed suture reinforcement group (10.57% vs 2.44%, SD = 0.334). CONCLUSIONS: Intracorporeal barbed suture reinforcement is associated with low AL incidences after laparoscopic LAR for rectal cancer, which is a potential procedure for reducing AL and worthy of application clinically.


Assuntos
Laparoscopia , Neoplasias Retais , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Humanos , Laparoscopia/efeitos adversos , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Suturas
8.
Arch Psychiatr Nurs ; 40: 167-173, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36064241

RESUMO

The mediating effects of three sources of perceived social support on frailty severity and depression were examined. Conducted in rural China, data on 570 frail older women were studied. Results showed that significant others' support (mainly daughters) (ß = 0.177 for frailty score = 3) mediated the relationship between frailty severity and depression, and the 95 % bias-corrected bootstrap confidence intervals did not straddle zero (0.013-0.419), while the mediating effects of family support (mainly sons) and friends support were not observed. Support from daughters contributes to frail mothers' mental health.


Assuntos
Fragilidade , Idoso , Depressão , Feminino , Fragilidade/psicologia , Humanos , Análise de Mediação , População Rural , Apoio Social
9.
Cancer Med ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127767

RESUMO

OBJECTIVE: This study evaluated the antitumor activity and safety of pemigatinib in previously treated Chinese patients with advanced cholangiocarcinoma and fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements. BACKGROUND: Pemigatinib provided clinical benefits for previously treated patients with cholangiocarcinoma carrying FGFR2 fusions or rearrangements and was approved for this indication in multiple countries. METHODS: In this ongoing, multicenter, single-arm, phase II study, adult patients with locally advanced or metastatic cholangiocarcinoma carrying centrally confirmed FGFR2 fusions or rearrangements who had progressed on ≥1 systemic therapy received 13.5 mg oral pemigatinib once daily (3-week cycle; 2 weeks on, 1 week off) until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was objective response rate (ORR) assessed by an independent radiology review committee. RESULTS: As of January 29, 2021, 31 patients were enrolled. The median follow-up was 5.1 months (range, 1.5-9.3). Among 30 patients with FGFR2 fusions or rearrangements evaluated for efficacy, 15 patients achieved partial response (ORR, 50.0%; 95% confidence interval [CI], 31.3-68.7); 15 achieved stable disease, contributing to a disease control rate of 100% (95% CI, 88.4-100). The median time to response was 1.4 months (95% CI, 1.3-1.4), the median duration of response was not reached, and the median progression-free survival was 6.3 months (95% CI, 4.9-not estimable [NE]). Eight (25.8%) of 31 patients had ≥grade 3 treatment-emergent adverse events. Hyperphosphatemia, hypophosphatasemia, nail toxicities, and ocular disorders were mostly

10.
ACS Appl Mater Interfaces ; 14(32): 37068-37075, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35926157

RESUMO

Potassium ferricyanide in an aqueous solution is easily decomposed into highly toxic substances (potassium cyanide and hydrogen cyanide) by light or alkaline action, which poses a major hazard to environmental and human health. Here, a reticulated aggregation-induced emission (AIE) supramolecular polymer material (TPAP-Mb@tQ[14]) was prepared by the supramolecular self-assembly of twisted cucurbit[14]uril (tQ[14]) and a triphenylamine derivative (TPAP-Mb). TPAP-Mb@tQ[14] not only recognizes Fe(CN)63- with sensitive specificity with a limit of detection (LOD) of 1.64 × 10-7 M but can also effectively remove and adsorb Fe(CN)63- from an aqueous solution with a removal rate as high as 97.38%. Meanwhile, an important component of the supramolecular polymer material (tQ[14]) can be reused. Thus, the tQ[14]-based supramolecular assembly has the potential to be used for applications addressing toxic anionic contaminants present in aqueous environments.

11.
Front Microbiol ; 13: 956489, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992719

RESUMO

A total of 14 Festuca sinensis seed lots were collected from different geographical locations on the Qinghai-Tibet Plateau to study the seed microbiota and determine the abiotic (temperature, precipitation, and elevation) and biotic (Epichloë sinensis infection rate) factors likely to shape the seed microbiome. The 14 seed lots had different bacterial and fungal structures and significantly different diversities (p < 0.05). The α-diversity indices of the bacteria were significantly correlated with precipitation (p < 0.05), whereas those of the fungi were significantly correlated with temperature (p < 0.05). Microbiota analysis showed that Proteobacteria, Cyanobacteria, and Bacteroidetes were the most abundant bacteria at the phylum level in the seeds, and Ascomycota and Basidiomycota were the most abundant fungi. ß-diversity analysis suggested large differences in the microbial communities of each sample. Redundancy analysis showed that temperature and precipitation were the main environmental factors that drive variations in the microbial community, at the medium-high elevation (3,000-4,500 m), the impact of temperature and precipitation on microbial community is different, and the other elevations that effect on microbial community were basically identical. Spearman's correlation analysis showed that the relative abundances of the most abundant bacterial phyla were significantly correlated with temperature (p < 0.05), whereas those of the most abundant fungal phyla were significantly correlated with precipitation (p < 0.05). E. sinensis infection rates were significantly correlated with elevation and temperature (p < 0.05). These results suggest that temperature and precipitation are the key factors driving the microbial community, that temperature and elevation also had a great influence on the E. sinensis infection rate, and that environmental factors (temperature and elevation) may further affect the microbial community by regulating the E. sinensis infection rate.

12.
Biomater Adv ; 137: 212831, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35929264

RESUMO

Adjuvant systemic chemotherapy with gemcitabine (GEM) is recognized as the standard of care to improve the prognosis of patients with resected pancreatic cancer (PC); however, it is greatly limited by poor absorption of chemotherapy agents. Moreover, surgical site infection and Gammaproteobacteria-induced GEM resistance further decrease the chemotherapy efficacy and increase the risk of recurrence and even mortality. Here, we develop an implantable anti-bacterial and anti-cancer fibrous membrane (AAFM) to inhibit PC recurrence in a well-coordinated manner. Our AAFM can be readily prepared via simple co-electrospinning of GEM and poly-L-lactic acid (PLLA) and subsequent tannic acid (TA)-mediated in-situ generation of silver nanoparticles (AgNPs). The resultant membrane presents highly porous fibrous morphology and appropriate mechanical performance. Most importantly, we find the surface-deposited TA/AgNP complexes can exert multiple therapeutic effects: (1) they can act as a fence to extend GEM diffusion route, achieving a sustained drug release; (2) they can fight the pathogenic microorganisms in the local microenvironment and prevent infectious complications and alleviate Gammaproteobacteria-induced chemotherapy resistance; (3) they can combat residual cancer cells to synchronously strengthen the effectiveness of GEM-based chemotherapy. Altogether, our AAFM provides a proof-of-concept demonstration of the integrated anti-cancer and anti-bacterial strategy for enhanced therapeutic efficacy and will inspire the design of other high-performance implants for prevention of tumor relapse.


Assuntos
Nanopartículas Metálicas , Neoplasias Pancreáticas , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Prata/farmacologia , Microambiente Tumoral
13.
Clin Breast Cancer ; 2022 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-35961861

RESUMO

BACKGROUND: Few studies have concerned the prognosis of metaplastic breast cancer (MpBC), a rare and diverse malignancy. A prognostic index estimating the MpBC survival would be attractive in clinical practice. PATIENTS AND METHODS: We retrospectively analyzed MpBC patients from the Surveillance, Epidemiology, and End Results (SEER) database. Prognostic factors were identified and the final nomogram was developed to predict the 1-, 3-, or 5-year overall survival (OS). Calibration curves were provided to internally validate the performance of the nomogram and discriminative ability was appraised by concordance index (C-index). RESULTS: A total of 1017 MpBC patients diagnosed between 2010 and 2015 were assigned into 3:1 as training set (n = 763) and SEER validation set (n = 254). An external validation was performed by an individual set of 94 MpBC patients from National Cancer Center in China from 2010 to 2018. The nomogram finally consisted of 7 independent prognostic factors and presented a good accuracy for predicting the OS with the C-index of 0.77 (95% CI: 0.751-0.786). Interestingly, the nomogram based on the western (including 92.5% non-Asian) SEER validation population (C-index of nomogram: 0.76, 95% CI: 0.737-0.796) also has an optimal discrimination in Asian population (C-index of nomogram: 0.70). The calibration plots of the nomogram predictions were also accurate and corresponded closely with the actual survival rates. CONCLUSION: This novel nomogram was accurate enough to predict the OS by using readily available clinicopathologic factors in MpBC general population, which could provide individualized recommendations for patients and clinical decisions for physicians.

14.
Mater Today Bio ; 16: 100379, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36042850

RESUMO

Recognizing multidrug-resistant (MDR) bacteria with high accuracy and precision from clinical samples has long been a difficulty. For reliable detection of MDR bacteria, we investigated a programmable molecular circuit called the Background-free isothermal circuital kit (BRICK). The BRICK method provides a near-zero background signal by integrating four inherent modules equivalent to the conversion, amplification, separation, and reading modules. Interference elimination is largely owing to a molybdenum disulfide nanosheets-based fluorescence nanoswitch and non-specific suppression mediated by molecular inhibitors. In less than 70 â€‹min, an accurate distinction of various MDR bacteria was achieved without bacterial lysis. The BRICK technique detected 6.73 â€‹CFU/mL of methicillin-resistant Staphylococcus aureus in clinical samples in a proof-of-concept trial. By simply reprogramming the sequence panel, such a high signal-to-noise characteristic has been proven in the four other superbugs. The proposed BRICK method can provide a universal platform for infection surveillance and environmental management thanks to its superior programmability.

15.
Front Genet ; 13: 945414, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003333

RESUMO

Background: Ulcerative colitis (UC) is a well-known risk factor for developing colitis-associated colorectal cancer (CAC). However, the molecular mechanism of the pathogenesis of CAC remains unclear. This study aimed to explore candidate genes involved in the tumorigenesis of CAC. Methods: GSE75214 and the Cancer Genome Atlas Program (TCGA) dataset were used to analyze the differentially expressed genes (DEGs) in UC and colorectal cancer (CRC), respectively. Survival-hub genes were identified from these DEGs by sequentially constructing a protein-protein interaction network, selecting hub genes, and conducting survival analysis. Regulatory signatures were also predicted on these genes through the online database. Apc min/+ and UC mice models were used to validate the expression of the above-predicted molecules. Gene set enrichment analysis and CIBERSORT were performed to explore the enriched molecular pathways and associated tissue-infiltrating immune cells of genes. Results: Here, 376 common DEGs were identified from the GSE75214 and TCGA datasets. Through survival-hub gene selection and in vivo experiments, we confirmed that CXCL10 and CXCL11 were significantly upregulated in UC and CRC. We also proved that miR-34a-5p and miR-203a-5p were potential regulators of CXCL10 and CXCL11. Meanwhile, CXCL10 and CXCL11 may activate the JAK-STAT signaling pathway via the interaction with cytokine receptors in UC. Furthermore, CXCL10 and CXCL11 were positively associated with the tissue infiltration of proinflammatory M1 macrophages in UC and CRC. Conclusion: CXCL10 and CXCL11 may act as the candidate genes involved in the tumorigenesis of CAC and potential therapeutic targets to prevent the development of CAC from UC.

16.
Bioinspir Biomim ; 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36044879

RESUMO

A three-dimensional pulsed-jet propulsion model consisting of a flexible body and a steerable bent nozzle in tethered mode is presented and studied numerically. By prescribing the body deformation and nozzle angle, we examine the flow evolution and propulsive/turning performance via thrust vectoring. Our results show that the vortex ring is no longer axis-symmetric when the jet is ejected at an angle with the incoming flow. A torque peak is observed during jetting, which is mainly sourced from the suction force (negative pressure) at the lower part of the internal nozzle surface when the flow is directed downward through an acute angle. After this crest, the torque is dominated by the positive pressure at the upper part of the internal nozzle surface, especially at a relatively low jet-based Reynolds number (О(102)). The torque production increases with a larger nozzle bent angle as expected. Meanwhile, the thrust production remains almost unchanged, showing little trade-off between thrust and torque production which demonstrates the advantage of thrust vectoring via a bent nozzle. By decoupling the thrust at the internal and outer surfaces considering special characteristics of force generation by pulsed-jet propulsion, we find that variations in Reynolds number mostly affect the viscous friction at the outer surfaces. The influence of the maximum stroke ratio is also studied. Results show that both the time-averaged thrust and the torque decrease at a larger stroke ratio.

17.
Chin Med J (Engl) ; 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-35984107

RESUMO

BACKGROUND: This study aimed to reveal the treatment patterns and clinical outcomes of diverse palbociclib-based regimens in Han patients with estrogen receptor-positive (ER+) metastatic breast cancer in routine clinical practice. METHODS: The clinical data of patients with ER+ metastatic breast cancer treated with palbociclib were collected from the National Cancer Center database. The efficacy profile of palbociclib in this Han population was evaluated, especially for various combination regimens. The efficacy of palbociclib-based therapy in patients with prior everolimus treatment was also assessed. RESULTS: A total of 186 patients from 89 cities in 18 provinces in China were enrolled. The median progression-free survival (PFS) was similar among different palbociclib-combined groups (P = 0.566): 10.0 months (95% confidence interval [CI] 3.8-16.1) in the +exemestane group, 9.7 months (95% CI 6.3-13.1) in the +letrozole group, 7.8 months (95% CI 5.5-10.2) in the +fulvestrant group, 7.2 months (95% CI 3.2-11.3) in the +toremifene group, and 6.1 months (95% CI 1.2-11.0) in the +anastrozole group. Thirty-four patients (18.3%) had received everolimus for their metastatic disease before the prescription of palbociclib. The disease control rate was significantly lower in patients who had received previous everolimus than in the everolimus-naïve group (50.0% vs. 82.2%, P < 0.001). Patients pre-treated with everolimus had significantly worse PFS than those in the everolimus-naïve group (3.4 months vs. 8.8 months, P  = 0.001). After propensity score matching, patients pre-treated with everolimus had similar PFS (4.4 months, 95% CI 0.5-8.2) compared with everolimus-naïve patients (6.1 months, 95% CI 4.7-7.5, P  = 0.439). CONCLUSIONS: Various palbociclib-based regimens have promising efficacy in ER+ metastatic breast cancer in real-world settings, even in patients who had been pre-treated with everolimus.

18.
Anal Chem ; 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-35980378

RESUMO

Cancer-derived small extracellular vesicles (csEVs) play critical roles in the genesis and development of various cancers. However, accurate detection of low-abundance csEVs remains particularly challenging due to the complex clinical sample composition. In the present study, we constructed a Programmable Isothermal Cascade Keen Enzyme-free Reporter (PICKER) for the reliable detection and acquisition of the relative abundance of csEVs in total sEVs (tsEVs) by integrating dual-aptamer recognition (cancer-specific protein EpCAM and tetraspanin protein CD63) with a catalytic hairpin assembly (CHA) amplification. By employing this strategy, we were able to achieve a detection limit of 420 particles/µL csEVs. Particularly, we proposed a novel particle ratio index of csEV against tsEV (PRcsEV/tsEV) to greatly eliminate errors from inconsistent centrifugation, which was calculated from the fluorescence ratio produced by csEVs and tsEVs. The PICKER showed a 1/10,000 discrimination capability by successfully picking out 1.0 × 103 csEV from 1.0 × 107 tsEV per microliter. We also found that the PRcsEV/tsEV value increased proportional to the stages of breast cancer by analyzing EVs from clinical patients' plasma. Taken together, we established a PICKER strategy capable of accurately discriminating csEVs, and the proposed PRcsEV/tsEV had been proven a potential indicator of breast cancer staging, paving the way toward facilitating cancer diagnosis and precision therapeutics.

19.
Front Immunol ; 13: 932722, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967417

RESUMO

Cyprinid herpesvirus 2 (CyHV-2) causes herpesviral hematopoietic necrosis (HVHN) disease outbreaks in farmed Cyprinid fish, which leads to serious economic losses worldwide. Although oral vaccination is considered the most suitable strategy for preventing infectious diseases in farmed fish, so far there is no commercial oral vaccine available for controlling HVNN in gibel carp (C. auratus gibelio). In the present study, we developed for the first time an oral vaccine against CyHV-2 by using yeast cell surface display technology and then investigated the effect of this vaccine in gibel carp. Furthermore, the protective efficacy was evaluated by comparing the immune response of a single vaccination with that of a booster vaccination (booster-vaccinated once 2 weeks after the initial vaccination). Critically, the activities of immune-related enzymes and genes expression in vaccine group, especially in the booster vaccine group, were higher than those in the control group. Moreover, strong innate and adaptive immune responses could be elicited in both mucosal and systemic tissues after receipt of the oral yeast vaccine. To further understand the protective efficacy of this vaccine in gibel carp, we successfully developed the challenge model with CyHV-2. Our results showed the relative percent survival was 66.7% in the booster vaccine group, indicating this oral yeast vaccine is a promising vaccine for controlling CyHV-2 disease in gibel carp aquaculture.


Assuntos
Doenças dos Peixes , Infecções por Herpesviridae , Vacinas , Animais , Carpa Dourada , Herpesviridae , Infecções por Herpesviridae/prevenção & controle , Infecções por Herpesviridae/veterinária , Imunidade nas Mucosas , Saccharomyces cerevisiae
20.
mBio ; : e0214122, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35997285

RESUMO

Examining the neutralizing capacity of monoclonal antibodies (MAbs) used to treat COVID-19, as well as antibodies recovered from unvaccinated, previously vaccinated, and infected individuals, against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) remains critical to study. Here, we report on a SARS-CoV-2 nosocomial outbreak caused by the SARS-CoV-2 R.1 variant harboring the E484K mutation in a 281-bed psychiatric facility in New Jersey among unvaccinated inpatients and health care professionals (HCPs). A total of 81 inpatients and HCPs tested positive for SARS-Cov-2 by reverse transcription (RT)-PCR from 29 October 9 to 30 November 2020. The R.1 variant exhibits partial or complete resistance to two MAbs in clinical use, as well as 2 receptor binding domain MAbs and 4 N-terminal domain (NTD) MAbs. NTD MAbs against pseudovirus harboring single characteristic R.1 mutations highlight the role of S255F in loss of activity. Additionally, we note dampened neutralization capacity by plasma from individuals with previous SARS-CoV-2 infection or sera from vaccinated individuals. The relative resistance of the R.1 variant is likely lower than that of B.1.351 and closer to that of P.1 and B.1.526. The R.1 lineage has been reported in 47 states in the United States and 40 countries. Although high proportions exhibited symptoms (26% and 61% among patients and HCPs, respectively) and relative antibody resistance, we detected only 10 R.1 variants from over 2,900 samples (~0.34%) collected from January to October 2021. Among 3 vaccinated individuals previously infected with R.1, we observed robust neutralizing antibody responses against SARS-CoV-2 wild type and VOCs. IMPORTANCE The neutralizing capacities of monoclonal antibodies used to treat COVID-19 and of those recovered from previously infected and vaccinated individuals against SARS-CoV-2 variants of concern (VOCs) remain important questions. We report on a nosocomial outbreak caused by a SARS-CoV-2 R.1 variant harboring an E484K mutation among 81 unvaccinated inpatients and health care professionals. We note high attack rates with symptoms in nearly 50% of infected individuals, in sharp contrast to an unrelated institutional outbreak caused by the R.1 variant among a vaccinated population. We found little evidence of significant community spillover. This variant exhibits partial or complete resistance to two monoclonal antibodies in clinical use and dampened the neutralization capacity of convalescent-phase plasma from individuals with previous infection or sera from vaccinated individuals. Among three vaccinated individuals previously infected with R.1, we observed robust neutralizing antibody responses against SARS-CoV-2 wild type and VOCs. These findings underscore the importance of vaccination for prevention of symptomatic COVID-19 disease.

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