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1.
Biosens Bioelectron ; 171: 112729, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33113387

RESUMO

A novel chemiluminescence (CL) imaging platform was constructed for prostate specific antigen (PSA) detection in a multiple signal amplifying manner. To construct the platform, the primary antibody for PSA was firstly immobilized on a O-ring area of a glass slide for recognizing the PSA. The horseradish peroxidase (HRP) and the secondary antibody of PSA (Ab2) functionalized Au NPs (HRP-Au NPs-Ab2) were modified on the platform through immunoreaction between PSA and Ab2. The excellent catalytic effect of Au NPs and HRP on the HRP-Au NPs-Ab2 to the luminol-H2O2 CL system provided the dual-signal amplification for PSA detection. To further enhance the sensitivity, tyramine signal amplification (TSA) strategy was introduced: tyramine-HRP conjugates were added into the O-ring reservoir and thus tyramine-HRP repeats formed in the presence of H2O2, generating a multiple signal amplification because of the large amounts of HRP on the sensing interface. The excellent performance of HRP-Au NPs-Ab2 and TSA strategy endows the CL platform with high sensitivity. The PSA was detected with a photomultiplier tube (PMT) and visually analyzed by a charge coupled device (CCD), respectively. The linear ranges of PMT and CCD for PSA are 0.1-100.0 ng mL-1 with a detection limit of 0.05 pg mL-1 and 0.5 - 100.0 ng mL-1 with a detection limit of 0.1 pg mL-1, respectively. The levels of PSA in several human serum samples were determined and the recoveries are ranged from 82.5% - 117.0%. This CL immunosensing platform holds great potential for bioactive molecules detection visually and sensitively.

2.
Cancer Lett ; 496: 117-126, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32949678

RESUMO

Thyroid cancer is the most common endocrine malignant tumor, and its incidence has increased significantly in the past few years. A growing number of noncoding RNAs (ncRNAs) have shown abnormal expression patterns in human thyroid cancer in recent studies. Depending on size, ncRNAs are usually subdivided into two categories: short ncRNAs and long ncRNAs (longer than 200 nucleotides). Short ncRNAs include microRNAs (miRNAs), PIWI-interacting RNAs, small nucleolar RNAs, and endogenous small interfering RNAs, which have been extensively studied due to their roles in developmental and tumor biology. Compared to that of short ncRNAs, the involvement of lncRNAs in human cancers, especially in thyroid cancer, is not as well studied. Here, we reviewed the roles and clinical significance of miRNAs, lncRNAs, and circular RNA in thyroid development, tumorigenesis, and metastasis to offer a new approach to thyroid cancer treatment.

3.
Food Chem ; 335: 127647, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32739816

RESUMO

The inhibition mechanism of the texture deterioration of tilapia fillets after treatment with polyphenols during partial freezing for 49 days was studied. Carnosic acid (CA), procyanidin (PA), quercetin (QE), and resveratrol (RSV) treatments had significantly higher hardness values (over 230 g) than the control group (183 g) on day 49 (P < 0.05). Polyphenol treatments were effective in delaying the protein degradation, lipid oxidation and spoilage microbe growth. Moreover, the kinetic model showed that the predicted shelf life of tilapia fillets treated with PA (102 d) was extended by 25 d compared to the control group (77 d). It was the proposed possible mechanism that polyphenols comprehensively maintained the protein conformation (increased hydrogen bonds and decreased disulfide bonds) and retarded protein denaturation and degradation, protecting the texture of the fillets. Therefore, polyphenols can be used to maintain texture and extend the shelf life of tilapia fillets during partial freezing.


Assuntos
Conservação de Alimentos/métodos , Conservantes de Alimentos/farmacologia , Carne/análise , Polifenóis/análise , Polifenóis/farmacologia , Animais , Biflavonoides/química , Catequina/química , Proteínas de Peixes/química , Conservação de Alimentos/instrumentação , Congelamento , Oxirredução/efeitos dos fármacos , Proantocianidinas/química , Desnaturação Proteica/efeitos dos fármacos , Tilápia
4.
J Clin Lab Anal ; : e23609, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33222271

RESUMO

BACKGROUND: For better understanding of the pathological changes of COVID-19, benefiting clinical management of the disease and the preparation for future waves of similar pandemics. METHODS: Hematology parameters from a total of 52 cases of COVID-19 admitted for treatment in a designated hospital were retrospectively analyzed. Data were analyzed by SPSS statistical software. RESULTS: Pre-treatment T-cell subsets, total lymphocytes, red blood cell distribution width (RDW), eosinophils, and basophils were significantly lower than that of post-treatment, while the inflammatory indexes neutrophils, neutrophil to lymphocyte ratio (NLR), and C-reactive protein (CRP) levels, as well as red blood cell (RBC) and hemoglobin, were significantly reduced after treatment. The T-cell subsets, total lymphocytes, and basophils in severely and critically ill patients were significantly lower than those in moderately ill patients. Neutrophils, NLR, eosinophils, procalcitonin (PCT), and CRP was significantly higher in severely and critically ill patients than in moderately ill patients. CD3+, CD8+, total lymphocytes, platelets, and basophils in patients older than 50 were lower than that of those younger than 50, while neutrophils, NLR, CRP, and RDW in patients older than 50 were higher than that of younger than 50. There was a positive correlation among prothrombin time (PT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in severely and critically ill patients. CONCLUSIONS: T-cell subsets, lymphocyte count, RDW, neutrophils, eosinophils, NLR, CRP, PT, ALT, and AST are important indicators in the management especially for severely and critically ill patients with COVID-19.

5.
Food Chem ; : 128422, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33143965

RESUMO

A simple and sensitive in situ antioxidation process assisted with a matrix solid-phase dispersion method for extracting chiral flavonoids in citrus fruit was established, and samples were further analyzed using ion mobility quadrupole time-of-flight high-resolution mass spectrometry. The collision cross-sections of the target compounds were studied using single-field and stepped-field methods. The optimal conditions were obtained using 30 mg of C18 as a dispersant, methanol as an elution solvent and 0.6 mM 1,1-diphenyl-2-picrylhydrazyl (DPPH) as a radical solution. Additionally, the method showed satisfactory limits of detection (3.70-6.52 ng/mL) and good recoveries (96.78-104.67%) for four flavonoids in citrus fruit. The IC50 values of DPPH radical-scavenging activities ranged from 817.8 to 981.55 µg/mL for tested samples. The method was a good alternative for the microextraction and determination of antioxidant capacity and chiral differentiation of narirutin, naringin, hesperidin and neohesperidin in citrus fruit.

6.
Org Lett ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33166154

RESUMO

A triethylamine-promoted domino reaction of three molecular 1,3-indanediones with various 3-methyleneoxindoles in refluxing ethanol has been developed. Series of novel polycyclic triindanone-fused spiro[bicyclo[2.2.2]octane-2,3'-indoline] derivatives were successfully synthesized in satisfactory yields with high diastereoselectivity. This domino reaction was accomplished with in situ generation of active cyclic dienes by base-promoted cyclotrimerization or cyclotetramerization of 1,3-indanediones and sequential Diels-Alder reaction of active cyclic dienes with dienophilic 3-methyleneoxindoles.

7.
Sci Total Environ ; : 143811, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33246717

RESUMO

In order to improve local air quality of Hong Kong, more than 99% taxies and public light buses were changed from diesel to liquefied petroleum gas (LPG) fuel type in the early 2000s. In addition to the catalytic converters wear and tear, it is necessary to control air pollutants emitted from LPG vehicles. Therefore, an LPG catalytic converter replacement programme (CCRP) was fulfilled from October 2013 to April 2014 by the Hong Kong government. Roadside volatile compounds (VOCs) were measured by on-line measurement techniques before and after the programme to evaluate the effectiveness of the LPG CCRP. The mixing ratios of total measured VOCs were found decreased from 69.3 ± 12.6 ppbv to 43.9 ± 6.5 ppbv after the LPG CCRP with the decreasing percentage of 36.7%. In addition, the total mixing ratio of LPG tracers, namely propane, i-butane, and n-butane, accounted for 49% of total measured VOCs before the LPG CCRP and the weighting percentage decreased to 34% after the programme. Moreover, the source apportionment of roadside VOCs also reflects the large decreasing trend of LPG vehicular emissions after the air pollution control measure. Due to the application of PTR-MS on measuring real-time VOCs and oxygenated volatile compounds (OVOCs) in this study, the emission ratios of individual OVOCs were investigated and being utilized to differentiate primary and secondary/biogenic sources of roadside OVOCs in Hong Kong. The findings demonstrate the effectiveness of the intervention programme, and are helpful to further implementation of air pollution control strategies in Hong Kong.

8.
Med Sci Monit ; 26: e927187, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33250509

RESUMO

BACKGROUND This retrospective single-center study conducted in China aimed to investigate the clinical outcomes of patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) treated with palbociclib plus endocrine therapy (ET) and subsequent therapy. MATERIAL AND METHODS Eligible patients were women with HR+ and HER2- MBC who initiated palbociclib plus ET between September 2016 and August 2019 at Fudan University Shanghai Cancer Center. Clinical characteristics and efficacy data were retrospectively recorded from the electronic medical record system. RESULTS In total, 130 patients were included in the study, of whom 87.0% of patients started palbociclib on 125 mg/day, 8.5% of patients had dose reduction, and 2.3% of patients discontinued the treatment because of toxicity. Overall, the disease control rate was 77.4% and clinical benefit rate was 63.4%. After a median follow-up period of 10.6 months, the median progression-free survival was 9.2 months. There was limited efficacy in patients who received palbociclib as no less than a fourth line of ET, except for patients who added palbociclib to the ET, which they had acquired resistance to. After disease progression on palbociclib, further treatment with chemotherapy and ET had similar efficacy (P=0.571). CONCLUSIONS The findings from this real-world single-center study in China showed that treatment with palbociclib plus ET exhibited favorable efficacy and good tolerance in patients with HR+ and HER2- MBC, even in patients who were initially resistant to endocrine therapy, and there was no difference in outcomes between subsequent treatment with chemotherapy and ET.

9.
Pain ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33230002

RESUMO

Pain experience can change the central processing of nociceptive inputs, resulting in persistent allodynia and hyperalgesia. However, the underlying circuit mechanisms remain underexplored. Here, we focus on pain-induced remodeling of the projection from the mediodorsal thalamus (MD) to anterior cingulate cortex (ACC), a projection that relays spinal nociceptive input for central processing. Using optogenetics combined with slice electrophysiology, we detected in male mice that 7 days of chronic constriction injury (CCI; achieved by loose ligation of the sciatic nerve) generated AMPA receptor (AMPAR)-silent glutamatergic synapses within the contralateral MD-to-ACC projection. AMPAR-silent synapses are typically GluN2B-enriched nascent glutamatergic synapses that mediate the initial formation of neural circuits during early development. During development, some silent synapses mature and become 'unsilenced' by recruiting and stabilizing AMPARs, consolidating and strengthening the newly formed circuits. Consistent with these synaptogenic features, pain-induced generation of silent synapses was accompanied by increased densities of immature dendritic spines in ACC neurons and increased synaptic weight of GluN2B-containing NMDA receptors (NMDARs) in the MD-to-ACC projection. After prolonged (∼30 days) CCI, injury-generated silent synapses declined to low levels, which likely resulted from a synaptic maturation process that strengthens AMPAR-mediated MD-to-ACC transmission. Consistent with this hypothesis, viral-mediated knockdown of GluN2B in ACC neurons, which prevented pain-induced generation of silent synapses and silent synapse-mediated strengthening of MD-to-ACC projection after prolonged CCI, prevented the development of allodynia. Taken together, our results depict a silent synapse-mediated mechanism through which key supraspinal neural circuits that regulate pain sensitivity are remodeled to induce allodynia and hyperalgesia.

10.
J Texture Stud ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33230818

RESUMO

In order to improve the gel performance and edible quality of surimi for sustainable manufacture, the present study explored the feasibility of four kinds of starchs (potato, corn, sweet potato and wheat) and fresh water fish tilapia as additives for golden pompano based surimi production. Sweet potato starch stood out as the most appropriate additive for golden pompano surimi due to the highest gel strength, lowest expressible moisture content and more compact microstructure. When the tilapia flesh substitution ratio reached 30%, best gel property of tilapia-golden pompano compound surimi with best texture property and whiteness value was achieved. Moreover, addition of 5% sweet potato starch to the golden pompano-tilapia (7:3) compound surimi comparatively obtained the optimal effect. Namely, it was observed that the texture parameters with hardness (3.62 N), gumminess (2.74 N), chewiness (17.35 mJ), cohesiveness (4.918) and springiness (0.872) being biggest values. On the other hand, the gel strength and expressible moisture content were 2137.31 g. mm and 3.52%, respectively, which were overwhelming than other levels. Simultaneously, the whiteness of 5% addition group was 74.75, which was also a little higher than other groups. In summary, partial substitution of tilapia and proper addition of sweet potato starch effectively improved the gel performance and quality of golden pompano based surimi products, which has potential applications in the industry of surimi. This article is protected by copyright. All rights reserved.

11.
Mol Ther ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33221435

RESUMO

Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive tumors all over the world, has a generally poor prognosis, and its progression is positively correlated with the density of blood vessels. Recently, the tumor-associated macrophages (TAM) were proved to be beneficial for angiogenesis, but their action mechanism remains unclear. Our study indicated that M2 macrophages were positively correlated with the microvessel density (MVD) of PDAC tissues, and M2 macrophage-derived exosomes (MDE) could promote the angiogenesis of mouse aortic endothelial cells (MAEC) in vitro. At the same time, the M2 MDE could also promote the growth of subcutaneous tumors and increase the vascular density of mice. Moreover, we also found that mir-155-5p and mir-221-5p levels in the M2 MDE were higher than those in M0 MDE, and they could be transferred into MAEC as demonstrated by RNA-seq and qPCR analysis. Our data confirmed the interaction between TAM and the angiogenesis of PDAC by exosomes. And targeting the exosomal miRNAs derived from TAM might provide potentially diagnostic and therapeutic strategies for PDAC.

12.
J Cell Physiol ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33200401

RESUMO

Tumor-associated macrophages (TAMs) in solid tumors exert protumor activities by releasing cytokines or growth factors into the tumor microenvironment. Increasing studies have also shown that TAMs play a key role in tumor progression, such as tumor angiogenesis, immunosuppression, cell proliferation, migration, invasion, and metastasis. A large body of evidence shows that the abundance of TAMs in solid tumors is correlated with poor disease prognosis and resistance to therapies. Therefore, targeting TAMs in solid tumors is considered to be a promising immunotherapeutic strategy. At present, the therapeutic strategies of targeting macrophages mainly include limiting monocyte recruitment, depletion strategies, promoting macrophage phagocytic activity, and induction of macrophage reprogramming. Additionally, targeting TAMs in combination with conventional therapies has been demonstrated to be a promising therapeutic strategy in solid tumors. In the present review, we summarized various TAMs-targeting therapeutic strategies for treating solid tumors. This review also discusses the challenges for targeting TAMs as tumor treatments, the obstacles in clinical trials, and the perspective for the future development of TAMs-targeting therapies for various cancers.

13.
J Affect Disord ; 280(Pt A): 72-76, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33202340

RESUMO

BACKGROUND: Suicidal behavior is a major concern for patients who suffer from major depressive disorder (MDD), especially among adolescents and young adults. Machine learning models with the capability of suicide risk identification at an individual level could improve suicide prevention among high-risk patient population. METHODS: A cross-sectional assessment was conducted on a sample of 66 adolescents/young adults diagnosed with MDD. The structural T1-weighted MRI scan of each subject was processed using the FreeSurfer software. The classification model was conducted using the Support Vector Machine - Recursive Feature Elimination (SVM-RFE) algorithm to distinguish suicide attempters and patients with suicidal ideation but without attempts. RESULTS: The SVM model was able to correctly identify suicide attempters and patients with suicidal ideation but without attempts with a cross-validated prediction balanced accuracy of 78.59%, the sensitivity was 73.17% and the specificity was 84.0%. The positive predictive value of suicide attempt was 88.24%, and the negative predictive value was 65.63%. Right lateral orbitofrontal thickness, left caudal anterior cingulate thickness, left fusiform thickness, left temporal pole volume, right rostral anterior cingulate volume, left lateral orbitofrontal thickness, left posterior cingulate thickness, right pars orbitalis thickness, right posterior cingulate thickness, and left medial orbitofrontal thickness were the 10 top-ranked classifiers for suicide attempt. CONCLUSIONS: The findings indicated that structural MRI data can be useful for the classification of suicide risk. The algorithm developed in current study may lead to identify suicide attempt risk among MDD patients.

14.
Oncologist ; 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33191524

RESUMO

BACKGROUND: This study investigated the incidence, radiographic patterns and relevance to clinical outcome of everolimus-related pneumonitis (ERP) in metastatic breast cancer (MBC) patients. MATERIALS AND METHODS: Data of MBC patients treated with everolimus who had baseline and at least one follow-up chest CT were obtained from medical electronic database system. An independent review of the CT scans of these patients were conducted by two radiologists (NCT03730428). Log-rank and Cox proportional hazard regression analysis were used for time-to-event analyses. RESULTS: ERP was radiographically detected in 45 of 86 patients (52.3%). More than 80% patients with ERP occurred during the first 4 months of everolimus treatment. Only 14 of the 45 patients with ERP were symptomatic (31.1%). Symptoms included cough, fever and shortness of breath. Bilateral and lower distribution of the pneumonitis was most common. In most of the cases, ground-glass opacities and reticular opacities were noticed. Elderly patients were more likely to develop ERP. Patients with ERP had significantly longer progression-free survival (PFS, 6.8 vs 4.1 months, P = 0.024) and overall survival (OS, 42.8 vs 21.3 months, P = 0.016). ERP was a predictor of OS improvement confirmed by multivariate Cox analysis (HR 0.49, 95%CI 0.25-0.97, P =0.040). CONCLUSIONS: ERP was noted in half of the MBC patients treated with everolimus. Our data suggested that ERP was associated with improved prognosis and may be used as a biomarker for the efficacy of everolimus in MBC. Close monitoring, prompt diagnosis and proper treatment for ERP are essential to maintain the quality of life of patients and achieve maximum treatment benefits. IMPLICATIONS FOR PRACTICE: Everolimus-related pneumonitis (ERP) is one of the most worrying drug adverse events, especially in Asian patients. However, little has been known about the clinical and radiographic details of ERP in patients with metastatic breast cancers (MBC) treated with everolimus. The present study investigated the clinical characteristics, radiographic patterns, and its correlation with treatment outcome in MBC patients. ERP was identified in more than half of the MBC patients during everolimus therapy and was associated with improved outcome.Close monitoring and prompt diagnosis and appropriate treatment for ERP are critical for the preservation of patients' quality of life and achievement of maximal treatment benefits.

15.
Electrophoresis ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33215711

RESUMO

Natural product analysis has gained wide attention in recent years, especially for herbal medicines, which contain complex ingredients and play a significant clinical role in the therapy of numerous diseases. The constituents of natural products are usually found at low concentrations, and the matrices are complex. Thus, the extraction of target compounds from natural products before analysis by analytical instruments is very significant for human health and its wide application. The commonly used traditional extraction methods are time-consuming, using large amounts of sample and organic solvents, as well as expensive and inefficient. Recently, microextraction techniques have been used for natural product extraction to overcome the disadvantages of conventional extraction methods. In this paper, the successful applications of and recent developments in microextraction techniques including solvent-based and sorbent-based microextraction methods, in natural product analysis in recent years, especially in the last five years, are reviewed for the first time. Their features, advantages, disadvantages and future development trends are also discussed. This article is protected by copyright. All rights reserved.

16.
Medicine (Baltimore) ; 99(43): e22903, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120842

RESUMO

Laparoscopic cholecystectomy is the routine method to treat gallbladder polyps. Nowadays, endoscopic ultrasound (EUS)-guided cholecystostomy as a bridge for per-oral transmural endoscopic resection of gallbladder polyps is introduced because preservation of gallbladder is increasingly getting attention. The aim of our study was to evaluate the approach in the treatment of patients with gallbladder polyps and symptomatic gallstones.EUS-guided cholecystostomy with the placement of a lumen-apposing metal stent (LAMS) was performed for those patients with accompanying gallbladder polyps and symptomatic gallstones. Several days after the cholecystostomy with LAMS, a gastroscope was introduced into the gallbladder to remove gallbladder polyps.All patients were successfully performed with the procedures of EUS-guided cholecystoduodenostomy (n = 3) or cholecystogastrostomy (n = 1) and endoscopic resection of gallbladder polyps. One patient experienced severe peritonitis. During the follow-up at 3 months, 1 patient was performed with laparoscopic cholecystectomy because ultrasonography examination showed the reappeared gallstones. No stone recurrence was found in other patients. During the follow-up of 3 to 15 months, no polyp recurrence was found in all the patients.The approach is novel for performing EUS-guided gallbladder fistulization, which can subsequently allow procedures of per-oral transmural endoscopic resection of gallbladder polyps to avoid cholecystectomy in the patients with gallbladder polyps and gallstones. However, further studies are needed before clinical recommendation because of the complications and stone recurrence.


Assuntos
Colecistostomia/métodos , Endossonografia/métodos , Vesícula Biliar/diagnóstico por imagem , Pólipos/cirurgia , Adulto , Anastomose Cirúrgica/métodos , Duodenostomia/métodos , Feminino , Seguimentos , Vesícula Biliar/patologia , Cálculos Biliares/cirurgia , Gastrostomia/métodos , Humanos , Masculino , Metais , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents , Resultado do Tratamento , Ultrassonografia de Intervenção/instrumentação
17.
Artigo em Inglês | MEDLINE | ID: mdl-33121683

RESUMO

Anti-tuberculosis drug-induced liver injury (ATB-DILI) is a common adverse reaction of anti-tuberculosis drug treatment. Studies have shown that isoniazid (INH) and rifampicin (RFP) are mainly metabolized in the liver and a large amount of intracellular glutathione is used up during the metabolism of these drugs, resulting in lipid peroxidation and hepatocyte death. Ferroptosis is a novel form of programmed cell death caused by iron-ion-dependent lipid peroxidation. In this study, we explored lipid peroxidation and ferroptosis during ATB-DILI. Morphology of ferroptosis was discovered in ATB-DILI mouse livers by transmission electron microscopy. Flow cytometry was used to assess the molecular markers of lipid peroxidation and ferroptosis including reactive oxygen species, lipid peroxidation, and cellular iron content. Glutathione peroxidase 4 (GPX4) was depleted, while acyl-CoA synthetase long chain family member 4 (ACSL4) was overexpressed in the ATB-DILI tissues. And glutathione supplementation significantly reduced the level of lipid peroxidation and the risk of liver damage. Retrospective study of tuberculosis patients who underwent INH and RFP treatment also revealed an association between the intake of glutathione and a negative ATB-DILI rate. In addition, iron supplementation enhanced the degree of lipid peroxidation and liver injury induced by INH and RFP in vivo and clinical retrospective study. Taken together, these results indicate that lipid peroxidation and evidence suggestive of ferroptosis occurs during ATB-DILI, and glutathione replenishment prevents this process while iron supplementation augmenting this effect.

18.
Cancer Med ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33022852

RESUMO

Fulvestrant 500 mg is standard of care for endocrine therapy-naive or pretreated women with hormone receptor-positive (HR+) metastatic breast cancer (MBC). This study was conducted to explore the potential factors and duration of last endocrine therapy as predictors for the efficacy of fulvestrant 500 mg on Chinese patients in real-world practice. Two hundred and fifty-two MBC patients who were treated with fulvestrant 500 mg consecutively between January 2011 and December 2015 in our institute were included in this study. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), and clinical benefit rate (CBR). The optimal cut-off value for duration of last endocrine therapy was determined by survival ROC analysis. Adverse events were graded according to NCI-CTC AE 4.0. Fulvestrant 500 mg demonstrated a median PFS of 5.8 months (95%CI 4.6-6.9), and a median OS of 35.9 months (95%CI 30.2-41.4). CBR was 41.3% (95%CI 35-47). Liver metastasis, bone alone metastasis, lines of endocrine therapy for MBC, and sensitivity to last endocrine therapy were statistically significant in the Cox multivariate analysis (P values of 0.022, 0.02, 0.03, and 0.038, respectively). The optimal cut-off values for duration of last endocrine therapy to predict the efficacy of fulvestrant 500 mg were 25.08 months for adjuvant endocrine therapy and 5.17 months for first-line endocrine therapy, which showed no difference in prediction power with ABC clinical definition. Patients with prior adjuvant endocrine therapy ≥25.08 months or first-line therapy≥5.17 months reached a longer PFS of fulvestrant (p = 0.04). Six patients discontinued the treatment due to intolerable adverse events. Patients with the duration of prior endocrine therapy longer than optimal cut-off points indicate better PFS of fulvestrant. Liver metastasis, bone alone metastasis, line of fulvestrant, and sensitivity to last endocrine therapy were also predictors for response of fulvestrant. ClinicalTrials.gov Identifier: NCT03708432.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33038193

RESUMO

STUDY DESIGN: Questionnaire translation and validation. OBJECTIVE: The aim of this study was to translate the Early-Onset Scoliosis 24-Item Questionnaire (EOSQ-24) into simplified Chinese and to evaluate the reliability and validity of this questionnaire in children with early-onset scoliosis (EOS) in mainland China. SUMMARY OF BACKGROUND DATA: The EOSQ-24 is a validated quality of life questionnaire in children with EOS and has been translated into multiple languages and used worldwide. However, there is currently no simplified Chinese version available for use in mainland China. METHODS: The English version of the EOSQ-24 questionnaire was translated into simplified Chinese based on the recommendations of the International Quality of Life Assessment (IQoLA) group. The reliability of the scale was evaluated using test-retest reliability and internal consistency, and construct validity was examined through factor analysis. Hundred childrenwith EOS were enrolled in the study. To assess the test-retest reliability of the scale, the parents or caregivers of 38 of participants repeated the questionnaire after 2 weeks. RESULTS: Test-retest reliability was excellent overall (intraclass correlation coefficient [ICC] = 0.935) and ranged from moderate to excellent for each domain (ICC = 0.681-0.945). The overall internal consistency was excellent (Cronbach α = 0.893) and had a variable range for each domain (Cronbach α = 0.560-0.889). Factor analysis was performed, and seven principal components were extracted that accounted for 70.1% of the variance. CONCLUSION: The simplified Chinese version of the EOSQ-24 scale has acceptable reliability and construct validity, and it can be used for the assessment of health-related quality of life (HRQL), caretaker burden, and satisfaction for children with EOS in mainland China. LEVEL OF EVIDENCE: 3.

20.
Molecules ; 25(20)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066298

RESUMO

Protein-tyrosine phosphatase 1B (PTP1B) has been considered as a promising target for treating insulin resistance. In searching for naturally occurring PTB1B antagonists, two new pimarane diterpenoids, named 2α-hydroxy-7-oxo-pimara-8(9),15-diene (1) and 19-hydroxy-2α-acetoxy-7-oxo-pimara-8(9),15-diene (2), were isolated from the seeds of Caesalpinia minax. Their structures were determined by extensive analysis of NMR and HR-ESIMS data, and their absolute configurations were determined by electronic circular dichroism (ECD) spectra. Compound 1 was disclosed as a competitive inhibitor of PTP1B with an IC50 (the half-maximal inhibitory concentration) value of 19.44 ± 2.39 µM and a Ki (inhibition constant) value of 13.69 ± 2.72 µM. Moreover, compound 1 dose-dependently promoted insulin-stimulated glucose uptake in C2C12 myotubes through activating insulin signaling pathway. Compound 1 might be further developed as an insulin sensitizer.

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