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2.
J Formos Med Assoc ; 120(1 Pt 1): 189-195, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32402521

RESUMO

BACKGROUND: Sorafenib has been shown to prolong the progression free survival (PFS) of advanced radioiodine (RAI) refractory differentiated thyroid cancer (DTC) and has been approved by the FDA as the result of the phase III DECISION trial. Sorafenib has been reimbursed for the treatment of RAI refractory DTC in Taiwan since Jan 2017. High percentage of adverse events (AE) was noted in DECISION trial. We conducted a study to show the real-world experience of sorafenib in Taiwan. METHODS: We retrospectively collected the clinical data, including dose, AE, and PFS of sorafenib, of the DTC patients who received sorafenib treatment in National Cheng Kung University Hospital and China Medical University Hospital by chart review from 2012 to 2018. RESULTS: Thirty-six advanced DTC patients with progression were included in this study. The starting dose of sorafenib in most patients was 200 mg twice daily and the mean daily maintenance dose was 433 mg. Five patients had partial response (13.9%) and 28 patients had stable disease (77.8%). The median PFS was 17.3 months (95% confidence interval: 11.9-33.6 months). Daily maintenance dose ≥ 600 mg was associated with better PFS (median PFS, not reached). The most common toxicity of sorafenib was hand foot skin reaction (69%), followed by diarrhea (42%), and skin rash (33%). Most of the toxicities were grade I/II. CONCLUSION: Higher maintenance dose of sorafenib is associated with longer PFS while starting from half dose is feasible to minimize the incidence of high grade toxicities in the real-world use of sorafenib.

3.
J Affect Disord ; 278: 320-326, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979563

RESUMO

BACKGROUND: The hypothalamic-pituitary-adrenocortical (HPA) axis had been proved to calibrate to early-life adversity and puberty may reverse the calibration. This study examines the consequences of prolonged parent-child separation on HPA axis reactivity and the pubertal recalibration hypothesis. METHODS: Totally of 144 participants aged 8.75 to 15.25 (mean age 12.50 years, SD: 1.32) were enrolled from rural areas of Chizhou city, Anhui Province of China in 2019. Data on parent-child separation was collected from parents. Self-reported Peterson Pubertal Development Scale was used to assess pubertal maturation and HPA axis stress reactivity was measured using the Trier Social Stress Test for Children. RESULTS: For children at early stage of puberty, childhood parent-child separation experiences were associated with blunted HPA axis reactivity (B = -1.888, p = 0.034); while for those at later stage of puberty, HPA axis reactivity was similar between children experienced early childhood separation and those without separation (AUCi: B = -0.426, p = 0.878). In contrast, for children experienced persistent parent-child separation, blunted HPA axis reactivity was observed (all p < 0.05). LIMITATIONS: Due to the cross-sectional nature of this study, conclusions about causality remain speculative. CONCLUSIONS: The effect of parent-child separation on dysregulation of HPA axis acts in a time-dependent manner. This finding provides support for the pubertal recalibration hypothesis suggesting that a focus of improving environment in adolescence would help those individuals reared initially in non-supportive conditions.

4.
J Ethnopharmacol ; 264: 113388, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32918990

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Kanglaite (KLT) is an active extract of the Coix lacryma-jobi seed, which can benefit Qi and nourish Yin, and disperse the accumulation of evils. It is used as a biphasic broad-spectrum anti-cancer drug, and shows synergistic effects with radiotherapy and chemotherapy. However, the mechanism of KLT combined with cisplatin (CDDP) against hepatocellular carcinoma (HCC) has not been elucidated. AIM OF THE STUDY: The aim of present study was to investigate the potential synergistic effects of KLT and CDDP on HepG2 cells, discussing the possible mechanisms from the perspective of CKLF1 and NF-κB mediated inflammatory response and chemoresistance, and the involvement of drug efflux transporters. MATERIALS AND METHODS: CDDP injured HepG2 cells were used to investigate the effects of KLT on chemotherapeutics treated HCC. Effects of KLT pretreatment on CDDP injured HepG2 cells were determined by MTT, wound healing assay, and transwell assay. Expression of chemokine-like factor 1 (CKLF1) and activation of nuclear factor κB (NF-κB) were examined by qPCR, western blot, and immunofluorescence staining. Furthermore, to study the role of CKLF1 in KLT mediated effects on this CDDP injured HCC cell model, HepG2 cells overexpressed with CKLF1 gene were used. Cell viability and NF-κB activation were investigated. Moreover, TNF-α and IL-1ß levels were measured by Elisa analysis and western blot to evaluate the inflammatory response. Additionally, ATP-binding cassette (ABC) drug efflux transporters, MDR1, MRP2, and BCRP were also determined in present study. RESULTS: KLT pretreatment followed by CDDP treatment was found to show synergistic effects, which showed by decreased cell viability, migration and invasion ability of HepG2 cells. Expression of CKLF1 enhanced significantly in CDDP treated HepG2 cells, and KLT decreased this elevation obviously. Furthermore, CDDP activated NF-κΒ and promoted translocation of NF-κB toward the nucleus. KLT inhibited the activation of NF-κΒ, which sensitized cancer cells. Overexpression of CKLF1 reversed the effects of KLT on CDDP injured HepG2 cells, which exhibited by increased cell viability and enhanced activation of NF-κΒ. CDDP induced NF-κΒ activation could also lead to excessive inflammatory response, and KLT can suppress the aggravating inflammation which may be beneficial for tumor progression. Furthermore, we found that ABC drug efflux transporters MDR1, MRP2, and BCRP in CDDP treated HepG2 cells were decreased when pretreated with KLT. CONCLUSIONS: KLT pretreatment may increase the effects of CDDP on HepG2 cells, by exhibiting cooperative effects on suppression of HepG2 cells. The mechanisms may partly by inhibiting CKLF1 mediated NF-κB pathway, which may contribute to inflammation of tumor microenvironment and chemoresistance of CDDP. Inhibition of transporter-mediated drug efflux is also involved in KLT mediated sensitization effects of CDDP.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33146858

RESUMO

PURPOSE: This study aimed to (1) explore the prevalence and relevant influencing factors of different mental disorders 5 years after the Lushan earthquake in Ya'an, China. METHODS: An epidemiological mental health survey was conducted to identify the prevalence of mental disorders in general population in Ya'an. A multi-stage, group-matching random sampling method was adopted. Face-to-face interviews were done with a two-stage design by trained interviewers and psychiatrists. The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) was used for the diagnosis. RESULTS: There were 8876 participants who were interviewed in this study. The total 12-month and lifetime prevalence of all mental disorders were 12.5% and 14.7%, respectively. There was a significant difference between males and females in the prevalence patterns of several mental disorders. Han ethnic group had higher prevalence of anxiety disorders (2.7%), and the Tibetan group had higher prevalence of alcohol-related disorders (5.0%). Logistic regression analysis showed that the areas severely affected by the earthquake had significantly higher prevalence of depressive disorders, and the extremely severe affected areas had significantly higher prevalence of trauma- and stressor-related disorders. CONCLUSION: Our findings show that the prevalence of a range of mental disorders 5 years after the earthquake in Ya'an are high, and the prevalence of depressive and trauma- and stressor-related disorders may be influenced differently by the various severity of earthquake impact. This study may be crucial for the health policy-making, cultural-specific mental health services and long-term mental recovery after the earthquake.

6.
Chembiochem ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146944

RESUMO

Chiral cyanohydrins are useful intermediates in pharmaceutical and agricultural industries. In nature, hydroxynitrile lyases (HNLs) represent a kind of elegant tool for enantioselective hydrocyanation of carbonyl compounds. Currently available methods for demonstration of hydrocyanation reaction still stalled at precise but low throughput GC or HPLC analyses. Herein we report a chromogenic high-throughput screening (HTS) method feasible for cyanohydrin synthesis reaction. This method was highly anti-interference and sensitive, and could be used to directly profile the substrate scope of HNLs neither in cell-free extract or fermentation clear broth. This HTS method was also validated by generating of new variants of Pc HNL5 which presented higher catalytic efficiency and stronger acidic tolerance in variant libraries.

8.
Neurosci Bull ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33180308

RESUMO

The paraventricular nucleus of the thalamus (PVT), which serves as a hub, receives dense projections from the medial prefrontal cortex (mPFC) and projects to the lateral division of central amygdala (CeL). The infralimbic (IL) cortex plays a crucial role in encoding and recalling fear extinction memory. Here, we found that neurons in the PVT and IL were strongly activated during fear extinction retrieval. Silencing PVT neurons inhibited extinction retrieval at recent time point (24 h after extinction), while activating them promoted extinction retrieval at remote time point (7 d after extinction), suggesting a critical role of the PVT in extinction retrieval. In the mPFC-PVT circuit, projections from IL rather than prelimbic cortex to the PVT were dominant, and disrupting the IL-PVT projection suppressed extinction retrieval. Moreover, the axons of PVT neurons preferentially projected to the CeL. Silencing the PVT-CeL circuit also suppressed extinction retrieval. Together, our findings reveal a new neural circuit for fear extinction retrieval outside the classical IL-amygdala circuit.

9.
AMB Express ; 10(1): 205, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175252

RESUMO

This paper studied the inhibitory effects of dithiocyano-methane (DM) on the glucose decomposition pathway in the respiratory metabolism of Escherichia coli. We investigated the effects of DM on the activities of key enzymes (ATPase and glucose-6-phosphate dehydrogenase, G6PDH), the levels of key product (nicotinamide adenosine denucleotide hydro-phosphoric acid, NADPH), and gene expression in the hexose monophosphate pathway (HMP). The results showed that the minimum inhibitory concentration (MIC) and the minimum bactericide concentration (MBC) of DM against the tested strains were 5.86 mg/L and 11.72 mg/L, respectively. Bacteria exposed to DM at MIC demonstrated an increase in bacterial ATPase and G6PDH activities, NADPH levels, and gene expression in the HMP pathway compared to bacteria in the control group, which could be interpreted as a behavioral response to stress introduced by DM. However, DM at a lethal concentration of 10 × MIC affected glucose decomposition by inhibiting mainly the HMP pathway in E. coli.

11.
Immunotherapy ; 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33238795

RESUMO

Despite the significant success of immune checkpoint blockade therapy in advanced non-small-cell lung cancer compared with chemotherapy, efficacy varies greatly across patients, and acquired resistance frequently occurs. In particular, during immunotherapy, the dynamic changes in molecular events have not been characterized. The authors report a case of squamous cell lung carcinoma with renal metastasis, treated with pembrolizumab, in which the primary tumor and rare renal metastases showed different responses. Using whole-exome sequencing, the authors found loss of heterogeneity in HLA genes in all tumors and high levels of intratumor heterogeneity in metastases. The increased levels of HLA loss led to therapy resistance during tumor evolution. In addition to tumor mutational burden and PD-L1, HLA loss of heterozygosity and intratumor heterogeneity should be taken into consideration during immunotherapy.

12.
BMC Cancer ; 20(1): 1144, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33238967

RESUMO

BACKGROUND: In order to obtain a high dose conformal index of tumor and steep dose fall-off in healthy tissues for brain metastasis stereotactic radiosurgery (SRS), the aim of this study was to investigate SRS planning optimization by comparing one multiple-lesions plan (MLP) with multiple single-lesion plans (SLPs) for patients with multiple brain metastases using the Cyberknife (CK) system. METHODS: Fifty non-small cell lung cancer (NSCLC) patients (28 males and 22 females) with 2-4 brain metastases, inter-tumour distances less than 3 cm, were retrospectively replanned with the original prescription dose (12-32 Gy) in the original fractions (1-3). Two different clinical CK SRS plans (SLPs and MLP) were generated for the same patients with the same collimator and prescription isodose line (62-68%) by the CK Multiplan System. Both SLPs and MLP were able to achieve > 95% PTV volume covered prescription dose and met the Timmerman 2011 organs at risk (brainstem, optic nerve and pituitary) constraints. RESULTS: Compared with those in the SLPs, the maximum dose (Dmax) and mean dose (Dmean) of brainstem in the MLP were reduced 0.22-3.13% (2.62%) and 2.71-12.56% (5.57%), respectively, all P < 0.05. Meanwhile, the volumes of the whole brain minus the tumors that received a single dose equivalent of 8-16 Gy (V8Gy-V16Gy) were effectively reduced in the MLP. The treatment time parameters, the total number of beams and monitor units, of the MLP were reduced by 3.31 and 1.47% (P < 0.05), respectively. Although there were a few differences in the conformity index (CI) and homogeneity index (HI) between the two treatment plans, the differences were not statistically significant (P = 2.94 and 1.08 > 0.05). CONCLUSION: One multiple-lesions plan for brain metastases could achieve higher precision in the target and lower doses in healthy tissue while shortening the treatment time and improving the treatment efficiency over multiple single-lesion plans.

13.
Epidemiol Psychiatr Sci ; 29: e179, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33153509

RESUMO

AIMS: Compared to their heterosexual peers, youth who identify as lesbian, gay or bisexual (LGB) tend to suffer higher rates of peer victimisation from bullying. However, studies of LGB adolescents' participation as bullies are scarce. We aimed to examine the possible association of sexual minority identity and the heightened risk of not only being bullied but bullying others as well. We also explored the effect of one's sexual identity on their involvement in bullying through the mediation of coping strategies and mood states. METHODS: A total of 12 218 students were recruited from 18 secondary schools in China. The demographic information, positive and negative coping strategies, mood state (anxiety, depression and hypomania) and information related to bullying and being bullied were collected. Multinomial regression was used to assess the heightened risk of sexual minority groups in comparison to their heterosexual adolescents' counterparts. A structural equation model (SEM) was used to test the mediating role of coping strategy and mood state between one's sex, sexual identity and bullying experience. RESULTS: Two trends could be observed: (1) LGB groups reported heightened risks of being bullied and bullying others at school than heterosexual peers. However, being a sexual-undeveloped girl seemed to have a protective effect on bullying-related problems. (2) Birth-assigned males were more likely to be bullied as well as bullying others at school when compared to birth-assigned females. SEM analysis revealed that being a sexual minority was directly associated with a higher frequency of being bullied (B = 0.16, 95% CI [0.10, 0.22], p < 0.001) but not bullying others (B = 0.02, 95% CI [-0.02, 0.06], p = 0.398) when compared to the heterosexual group. Negative coping, hypomania, anxiety and depression were associated with a higher frequency of being bullied, while positive coping was associated with a lower frequency of being bullied. Moreover, negative coping, hypomania and depression were associated with a higher frequency of bullying others, while positive coping was associated with a reduced likelihood of bullying others. In addition, being bullied and bullying others were significantly correlated in the SEM model. CONCLUSIONS: This novel research investigated the dynamic nature of the interaction between victim and bullying of LGB school adolescents in China, with a specific exploration of the psychological mechanism behind the pattern of being bullied and bullying others. School-level interventions aimed at teaching positive coping strategies to lower psychological distress are recommended to support sexual minority students.

14.
J Agric Food Chem ; 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33249835

RESUMO

Isoleucine dioxygenase (IDO)-catalyzed hydroxylation of isoleucine is a promising method for the synthesis of the diabetic drug (2S,3R,4S)-4-hydroxyisoleucine [(2S,3R,4S)-4-HIL]. However, the low activity of IDO significantly limits its practical application. In this work, a high-throughput screening method was developed and directed evolution was performed on the IDO from Bacillus subtilis, resulting in a double mutant with improvements in specific activity, protein expression level, and fermentation titer of 3.2-, 2.8-, and 9.4-fold, respectively. l-Isoleucine (228 mM) was completely converted to (2S,3R,4S)-4-HIL by the best variant with a space-time yield of up to 80.8 g L-1 d-1, which is the highest record reported so far. With a further increase of the substrate loading to 1 M, a high conversion of 91% could also be achieved. At last, enzymatic synthesis of (2S,3R,4S)-4-HIL was successfully carried out on a 3 L scale, indicating tremendous potential of the IDO variant I162T/T182N for green and efficient production of (2S,3R,4S)-4-HIL.

15.
Psychosom Med ; 82(9): 823-829, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33156262

RESUMO

OBJECTIVE: This study aimed to examine the developmental pattern of diurnal cortisol rhythm during pubertal transition and its prospective association with psychopathological symptoms. METHODS: A cohort of 1158 children consisting of 608 boys and 550 girls aged 7 to 9 years (mean [standard deviation] age = 8.04 [0.61] years) were recruited in the Anhui Province of China in 2015 (wave 1). A single awakening sample was collected at baseline, and three additional samples were collected at one weekday in wave 2 to wave 4. Four indices of cortisol activity were evaluated and calculated across the day: awakening cortisol level, cortisol awakening response, the area under the curve with respect to ground (AUC), and the diurnal cortisol slope. In each wave, pubertal development was assessed by testicular size in boys and Tanner scales in girls. Psychopathological symptoms were ascertained in waves 2 to 4. RESULTS: Multilevel mixed models revealed no significant pubertal changes in diurnal cortisol activity in girls. In boys, awakening cortisol (ß = -0.005, p = .004) and total cortisol output (lnAUC, ß = -0.005, p = .040) significantly decreased across pubertal transition. Higher awakening cortisol and total cortisol output (lnAUC) were associated with higher scores on internalizing symptoms in girls (ß = 0.82, p < .001; ß = 0.62, p = .012) and externalizing symptoms in boys (ß = 0.73, p = .001; ß = 0.55, p = .019) during the 3-year follow-up. In contrast, no associations were found between cortisol awakening response and diurnal cortisol slope with psychopathological symptom scores in boys or girls. CONCLUSIONS: Development of diurnal cortisol activity during pubertal transition occurs in a sex-specific manner. Awakening cortisol level and daily total cortisol output may serve as markers for psychopathology during pubertal transition.

16.
Zhongguo Zhong Yao Za Zhi ; 45(17): 4120-4128, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33164396

RESUMO

As a prescription for promoting blood circulation and removing blood stasis, Taohong Siwu Decoction(THSWD) has certain effects in delaying the progression of renal fibrosis. However, as a traditional Chinese medicine compound containing many monomer components, it has been a research hotspot in the field of exploring the research methods and targets for the complex pathological process. The method of activating blood circulation and removing blood stasis has certain clinical effect in retarding the process of IgA nephropathy(IgAN) fibrosis, but the mechanism of action is still unclear. In this study, the network pharmacology method was used to investigate the active ingredients, targets and molecular mechanisms of THSWD in the intervention of IgAN fibrosis. On this basis, in vitro experiments were conducted to verify the effect of THSWD on the expression of ERK factor in BALB/c 3 T3 cells. The active ingredients and targets in THSWD were collected through the TCMSP. Sixty-one active ingredients and 240 targets including luteolin and quercetin were screened, and 185 targets were obtained by intersecting with CTD database to search IgAN related targets. Cytoscape software and STRING database were used to construct "THSWD-active ingredients-targets" network and protein-protein interaction network, and 69 core targets were screened. In DAVID's GO enrichment analysis and KEGG pathway analysis of the core targets and cell experiments, the results showed that ERK was an important factor for THSWD to interfere with IgAN fibrosis, and THSWD intervention could significantly decrease cell activity, ERK1/2 mRNA expression, and p-ERK1/2 protein expression. This study preliminarily revealed that THSWD may delay the growth of fibroblasts by affecting ERK factor and its phosphorylation level.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Fibroblastos , Mapas de Interação de Proteínas
17.
Int Immunopharmacol ; 88: 106963, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33182028

RESUMO

Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by progressive cognitive dysfunction and memory impairment. Dopamine is an important catecholaminergic neurotransmitter that controls movement, reward, motivation, and cognition. Recently, dopamine receptors were reported to regulate immune system in both periphery and central nervous system. However, whether dopamine D1 receptor (DRD1) activation could improve neuroinflammation in AD conditions remains unknown. The present study aimed to investigate the therapeutic effects and underlying mechanisms of a potent and selective DRD1 agonist A-68930 on Aß1-42-induced mice. Here we showed that intraperitoneal injection of A-68930 significantly ameliorated Aß1-42-induced cognitive dysfunction in mice. Moreover, both in vivo and in vitro data showed that A-68930-induced DRD1 activation significantly inhibited NLRP3 inflammasome-dependent neuroinflammation induced by Aß1-42, and this effect may be mediated by the activation of AMPK/autophagy signaling pathway, which enhanced NLRP3 inflammasome degradation and thus decreased the secretion of IL-1ß and IL-18. The present study suggests that A-68930-induced DRD1 signaling efficiently alleviates Aß1-42-induced cognitive impairment and neuroinflammation in mice and BV2 cells, and DRD1 may become a promising therapeutic target for AD.

18.
Cell Mol Immunol ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33184450

RESUMO

Activation of the TAK1 signalosome is crucial for mediating the innate immune response to pathogen invasion and is regulated by multiple layers of posttranslational modifications, including ubiquitination, SUMOylation, and phosphorylation; however, the underlying molecular mechanism is not fully understood. In this study, TRIM60 negatively regulated the formation and activation of the TAK1 signalosome. Deficiency of TRIM60 in macrophages led to enhanced MAPK and NF-κB activation, accompanied by elevated levels of proinflammatory cytokines but not IFN-I. Immunoprecipitation-mass spectrometry assays identified TAB2 as the target of TRIM60 for SUMOylation rather than ubiquitination, resulting in impaired formation of the TRAF6/TAB2/TAK1 complex and downstream MAPK and NF-κB pathways. The SUMOylation sites of TAB2 mediated by TRIM60 were identified as K329 and K562; substitution of these lysines with arginines abolished the SUMOylation of TAB2. In vivo experiments showed that TRIM60-deficient mice showed an elevated immune response to LPS-induced septic shock and L. monocytogenes infection. Our data reveal that SUMOylation of TAB2 mediated by TRIM60 is a novel mechanism for regulating the innate immune response, potentially paving the way for a new strategy to control antibacterial immune responses.

19.
Anal Bioanal Chem ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33184759

RESUMO

The toxic protein of ricin has drawn wide attention in recent years as a potential bioterrorism agent due to its high toxicity and wide availability. For the verification of the potential anti-terrorism activities, it is urgent for the quantification of ricin in food-related matrices. Here, a novel strategy of trypsin/Glu-C tandem digestion was introduced for quantitative detection of ricin marker peptides in several beverage matrices using isotope-labeled internal standard (IS)-mass spectrometry. The ricin in beverages was captured and enriched by biotinylated anti-ricin polyclonal antibodies conjugated to streptavidin magnetic beads. The purified ricin was cleaved using the developed trypsin/Glu-C tandem digestion method and then quantitatively detected by ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with isotope-labeled T7A and TG11B selected as IS. The use of trypsin/Glu-C digestion allows shorter peptides, which are more suitable for MS detection, to be obtained than the use of single trypsin digestion. Under the optimized tandem digestion condition, except for T7A in the A-chain, two resulting specific peptides of TG13A, TG28A from the A-chain and two of TG11B, TG33B from the B-chain were chosen as novel marker peptides with high MS response. The uniqueness of the selected marker peptides allows for unambiguous identification of ricin among its homologous proteins in a single run. The MS response of the four novel marker peptides is increased by more than 10 times compared with that of individual corresponding tryptic peptides. Both the marker peptides of A-chain T7A and B-chain TG11B were selected as quantitative peptides based on the highest MS response among the marker peptides from their individual chains. The limit of detection (LOD) of ricin is 0.1 ng/mL in PBS and 0.5 ng/mL in either milk or orange juice. The linear range of calibration curves for ricin were 0.5-300 ng/mL in PBS, 1.0-400 ng/mL in milk, and 1.0-250 ng/mL in orange juice. The method accuracy ranged between 82.6 and 101.8% for PBS, 88.9-105.2% for milk, and 95.3-118.7% for orange juice. The intra-day and inter-day precision had relative standard deviations (%RSD) of 0.3-9.4%, 0.7-8.9%, and 0.2-6.9% in the three matrices respectively. Furthermore, whether T7A or TG11B is used as a quantitative peptide, the quantitative results of ricin are consistent. This study provides not only a practical method for the absolute quantification of ricin in beverage matrices but also a new strategy for the investigation of illegal use of ricin in chemical weapon verification tasks such as OPCW biotoxin sample analysis exercises.

20.
Eur J Radiol ; 133: 109301, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-33157372

RESUMO

PURPOSE: To investigate the midterm efficacy and prognostic evaluation of patients with diffuse large B-cell lymphoma (DLBCL) by three image analysis methods: International Harmonization Project (IHP), Deauville 5-Point Scale (5-PS) and Δ SUVmax criteria in 18F-FDG PET/CT. METHODS: This was a retrospective analysis of 141 patients with DLBCL. All patients were given 3-4 cycles of chemotherapy and 18F-FDG PET/CT. According to three criteria, the patients were divided into negative and positive groups, respectively. Statistical methods were used to assess the midterm efficacy and prognosis factors. RESULTS: During the midterm follow-up, a total of 109 people achieved CR. Three methods showed statistically significant differences in OS and PFS for the interim PET/CT, and Δ SUVmax criterion was an independent risk factor for the prognosis of DLBCL patients. CONCLUSION: In our research, IHP, 5-PS and Δ SUVmax criteria all had a significant predictive value, while Δ SUVmax criterion had more advantages in evaluating the midterm efficacy and predicting prognosis for patients with DLBCL in interim PET/CT. But it should be noticed that Δ SUVmax criterion needs more strict guidelines in multicenter trials. The optimal cutoff value of Δ SUVmax% we recommended was 81.54%, which helped to judge the midterm efficacy.

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