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1.
BMC Med Genomics ; 14(1): 172, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193132

RESUMO

BACKGROUND: Primary adrenal insufficiency (PAI) is life-threatening, and a definitive aetiological diagnosis is essential for management and prognostication. We conducted this study to investigate the genetic aetiologies of PAI in South China and explore their clinical features. METHODS: Seventy children were enrolled in this cross-sectional study. Clinical information was collected, and combined genetic tests were performed according to the children's manifestations. Statistical analysis was performed among the different groups. In silico or in vitro experiments were applied to determine the pathogenicity of novel variants. RESULTS: Among the 70 children, 84.3% (59/70) were diagnosed with congenital adrenal hyperplasia (CAH), and 21-hydroxylase deficiency (21-OHD) was genetically confirmed in 91.5% of these cases. Salt wasting (SW), simple virilization (SV), and non-classic (NC) CAH accounted for 66.1% (39/59), 30.5% (18/59), and 3.4% (2/59) of the cases, respectively. The 17-hydroxyprogesterone (17-OHP) and testosterone (TES) levels were significantly higher in children with SW than with SV. The 17-OHP and cortisol levels in female SW patients were significantly higher than those in males. The 17-OHP, cortisol, dehydroepiandrosterone (DHEAS) and TES levels in female SW patients were significantly higher than those in female SV patients. Additionally, 72.7% (8/11) of uncharacterized PAI patients had positive genetic findings. Among all the patients, two novel variants in the CYP21A2 gene (c.833dupT and c.651 + 2T > G) were found. A microdeletion (Xp21.2-21.3) and five novel variants, including 2 in the NR0B1 gene (c.323-324CG > GA and c.1231_1234delCTCA), 2 in the AAAS gene (c.399 + 1G > A and c.250delT) and 1 in the NNT gene (c.2274delT), were detected. The novel variant c.399 + 1G > A in the AAAS gene was further confirmed to lead to exon 4 skipping during mRNA transcription and produce a truncated ALADIN protein. CONCLUSIONS: We found ethnicity-based differences in the CYP21A2 gene variant spectrum among different study populations. Female 21-OHD patients tended to have higher 17-OHP and TES levels, which warrants caution in relation to the effects of virilization. Novel gene variants detected in the CYP21A2, NR0B1, AAAS and NNT genes expanded the genetic spectrum of PAI, however, further improvement of genetic testing tools beyond our protocol are still needed to uncover the complete aetiology of PAI in children.

2.
Anal Chem ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34212722

RESUMO

Single-atom catalysis efficiently exposes the catalytic sites to reactant molecules while rendering opportunity to investigate the catalysis mechanisms at atomic levels for scientific insights. Here, for the first time, atomically dispersed Co atoms are synthesized as biomimetic "enzymes" to monitor superoxide anions (O2•-), delivering ultraordinary high sensitivity (710.03 µA·µM-1·cm-2), low detection limit (1.5 nM), and rapid response time (1.2 s), ranking the best among all the reported either bioenzymatic or biomimetic O2•- biosensors. The sensor is further successfully employed to real-time monitor O2•- released from living cells. Moreover, theoretical calculation and analysis associated with experimental results discover that a mode of end adsorption of the negatively charged O2•- on the Co3+ atom rather than a bridge or/and side adsorption of the two atoms of O2•- on two Co3+ atoms, respectively, plays an important role in the single-atomic catalysis toward O2•- oxidation, which not only facilitates faster electron transfer but also offers better selectivity. This work holds great promise for an inexpensive and sensitive atomic biomimetic O2•- sensor for bioresearch and clinic diagnosis, while revealing that the adsorption mode plays a critical role in single-atom catalysis for a fundamental insight.

3.
Cancer Med ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34213079

RESUMO

BACKGROUND: Long non-coding RNA (lncRNA) HULC (highly upregulated in liver cancer) is considered as an oncogenic factor for various malignant tumors. This study aimed to reveal the role of lncRNA HULC in the malignant behavior of glioblastoma (GBM) by exploring its effects on the epithelial-mesenchymal transition (EMT) and vasculogenic mimicry (VM) of human GBM. MATERIALS AND METHODS: The contents of VM in 27 GBM samples were assessed by immunohistochemistry-histology and their association with progress-free survival (PFS) was analyzed. Human GBM SHG44 and U87 cells were manipulated to establish stable lncRNA HULC overexpressing and silencing cells by lentivirus-based technology. The effects of altered lncRNA HULC on vasculogenic tubular formation, invasion, and EMT process in GBM cells were tested in vitro and the growth of implanted GBM tumors and their EMT process were examined in vivo. RESULTS: The numbers of VM were positively associated with disease progression, but negatively with PFS periods of GBM patients. Compared with the control vec cells, lncRNA HULC overexpression significantly increased the tubular formation, invasion, and EMT process of both SHG44 and U87 cells, accompanied by promoting the growth of implanted GBM tumors and EMT process in mice. LncRNA HULC silencing had opposite effects on the tubular formation, invasion, and EMT process as well as tumor growth of GBM cells. CONCLUSION: LncRNA HULC stimulates the EMT process and VM in human GBM, and may be a therapeutic target for intervention of GBM.

4.
Lancet ; 398(10294): 53-63, 2021 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-34217401

RESUMO

BACKGROUND: In China, mean body-mass index (BMI) and obesity in adults have increased steadily since the early 1980s. However, to our knowledge, there has been no reliable assessment of recent trends, nationally, regionally, or in certain population subgroups. To address this evidence gap, we present detailed analyses of relevant data from six consecutive nationally representative health surveys done between 2004 and 2018. We aimed to examine the long-term and recent trends in mean BMI and prevalence of obesity among Chinese adults, with specific emphasis on changes before and after 2010 (when various national non-communicable disease prevention programmes were initiated), assess how these trends might vary by sex, age, urban-rural locality, and socioeconomic status, and estimate the number of people who were obese in 2018 compared with 2004. METHODS: We used data from the China Chronic Disease and Risk Factors Surveillance programme, which was established in 2004 with the aim to provide periodic nationwide data on the prevalence of major chronic diseases and the associated behavioural and metabolic risk factors in the general population. Between 2004 and 2018 six nationally representative surveys were done. 776 571 individuals were invited and 746 020 (96·1%) participated, including 33 051 in 2004, 51 050 in 2007, 98 174 in 2010, 189 115 in 2013, 189 754 in 2015, and 184 876 in 2018. After exclusions, 645 223 participants aged 18-69 years remained for the present analyses. The mean BMI and prevalence of obesity (BMI ≥30 kg/m2) were calculated and time trends compared by sex, age, urban-rural locality, geographical region, and socioeconomic status. FINDINGS: Standardised mean BMI levels rose from 22·7 kg/m2 (95% CI 22·5-22·9) in 2004 to 24·4 kg/m2 (24·3-24·6) in 2018 and obesity prevalence from 3·1% (2·5-3·7) to 8·1% (7·6-8·7). Between 2010 and 2018, mean BMI rose by 0·09 kg/m2 annually (0·06-0·11), which was half of that reported during 2004-10 (0·17 kg/m2, 95% CI 0·12-0·22). Similarly, the annual increase in obesity prevalence was somewhat smaller after 2010 than before 2010 (6·0% annual relative increase, 95% CI 4·4-7·6 vs 8·7% annual relative increase, 4·9-12·8; p=0·13). Since 2010, the rise in mean BMI and obesity prevalence has slowed down substantially in urban men and women, and moderately in rural men, but continued steadily in rural women. By 2018, mean BMI was higher in rural than urban women (24·3 kg/m2vs 23·9 kg/m2; p=0·0045), but remained lower in rural than urban men (24·5 kg/m2vs 25·1 kg/m2; p=0·0007). Across all six surveys, mean BMI was persistently lower in women with higher levels of education compared with women with lower levels of education, but the inverse was true among men. Overall, an estimated 85 million adults (95% CI 70 million-100 million; 48 million men [95% CI 39 million-57 million] and 37 million women [31 million-43 million]) aged 18-69 years in China were obese in 2018, which was three times as many as in 2004. INTERPRETATION: In China, the rise in mean BMI among the adult population appears to have slowed down over the past decade. However, we found divergent trends by sex, geographical area, and socioeconomic status, highlighting the need for a more targeted approach to prevent further increases in obesity in the Chinese general population. FUNDING: China National Key Research and Development Program, China National Key Project of Public Health Program, and Youth Scientific Research Foundation of the National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34201096

RESUMO

Objective: To evaluate the cost-effectiveness of dabrafenib plus trametinib combination therapy versus vemurafenib as first-line treatment in patients with BRAF V600 mutation-positive unresectable or metastatic melanoma from a healthcare system perspective in China. Methods: This study employed a partitioned survival model with three health states (progression-free survival, post-progression survival and dead) to parameterize the data derived from Combi-v trial and extrapolated to 30 years. Health states' utilities were measured by EQ-5D-3L, also sourced from the Combi-v trial. Costs including drug acquisition costs, disease management costs and adverse event costs were based on the Chinese Drug Bidding Database and physician survey in China. The primary outcomes of the model were lifetime costs, life-years (LYs), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses were conducted, respectively. Result: Dabrafenib plus trametinib is projected to increase a patient's life expectancy by 0.95 life-years over vemurafenib (3.03 vs. 2.08) and 1.09 QALY gains (2.48 vs. 1.39) with an incremental cost of $3833. The incremental cost-effectiveness ratio (ICER) was $3511 per QALY. In the probabilistic sensitivity analyses, at a threshold of $33,357 per QALY (three times the gross domestic product (GDP) per capita in China in 2020), the probability of dabrafenib plus trametinib being cost-effective was 90%. In the deterministic sensitivity analyses, the results were most sensitive to the dabrafenib plus trametinib drug costs, vemurafenib drug costs and discount rate of cost. Conclusion: Dabrafenib plus trametinib therapy yields more clinical benefits than vemurafenib. Using a threshold of $33,357 per QALY, dabrafenib plus trametinib is very cost-effective as compared with vemurafenib in China.


Assuntos
Melanoma , Proteínas Proto-Oncogênicas B-raf , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , China , Análise Custo-Benefício , Humanos , Imidazóis , Melanoma/tratamento farmacológico , Melanoma/genética , Mutação , Oximas , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/uso terapêutico , Piridonas/uso terapêutico , Pirimidinonas , Vemurafenib/uso terapêutico
6.
Artigo em Inglês | MEDLINE | ID: mdl-34299918

RESUMO

Chenopodium ambrosioides L. (C. ambrosioides) has been used as dietary condiments and as traditional medicine in South America. The oil of Chenopodium ambrosioides L. (C. ambrosioides) can be used as a natural antioxidant in food processing. It also has analgesic, sedating, and deworming effects, and can be used along with the whole plant for its medical effects: decongestion, as an insecticide, and to offer menstruation pain relief. This study was conducted to investigate the cytotoxicity and apoptosis effects of an essential oil from C. ambrosioides in vitro. The cytotoxicity evaluation of the essential oil from C. ambrosioides on human normal liver cell line L02 was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. AO/EB dual fluorescent staining assay and Annexin V-FITC were used for apoptosis analysis. The changes in mitochondrial membrane potential (MMP) were analyzed with 5,5,6,6'-tetrachloro-1,1,3,3,-tetraethyl-imidacarbocyanine iodide (JC-1) dye under a fluorescence microscope. The level of apoptosis related protein expression was quantified by Western blot. The L02 cells were treated with the essential oil from C. ambrosioides at 24, 48, and 72 h, and the IC50 values were 65.45, 58.03, and 35.47 µg/mL, respectively. The AO/EB staining showed that viable apoptotic cells, non-viable apoptotic cells, and non-viable non-apoptotic cells appeared among the L02 cells under the fluorescence microscope. Cell cycle arrest at the S phase and cell apoptosis increased through flow cytometry in the L02 cells treated with the essential oil. MMP decreased in a concentration-dependent manner, as seen through JC-1 staining under the fluorescence microscope. In the L02 cells as shown by Western blot and qPCR, the amount of the apoptosis-related proteins and the mRNA expression levels of cytochrome C, Bax, Caspase-9, and Caspase-3 increased, Bcl-2 decreased, and Caspase-12, which is expressed in the endoplasmic reticulum, showed no obvious changes in protein amount or mRNA expression level. The essential oil form C. ambrosioides had a cytotoxic effect on L02 cells. It could inhibit L02 cell proliferation, arrest the cell cycle at the S phase, and induce L02 cell apoptosis through the endogenous mitochondrial pathway.

8.
Bioengineered ; 12(1): 4136-4149, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34288825

RESUMO

Inflammation and oxidative stress are crucial in ischemic stroke. Ephedrine (EPH) has been proven to have anti-inflammatory and anti-oxidative stress effects. The present study analyzes whether EPH possessed neuroprotective effects and explored the underlying mechanisms of EPH based on an experimental model of middle cerebral artery occlusion (MCAO). We found that intraperitoneal injection with EPH attenuated the neurological deficit, cerebral infarction, and cerebral edema induced by MCAO in rats. Besides, EPH treatment alleviated MCAO-induced brain tissue damage and morphological abnormality, as well as neuronal loss. Moreover, EPH treatment upregulated GPx and CAT activity and downregulated MDA and NO content. EPH also evidently decreased the levels of IL-6 and TNF-α but increased IL-4 and IL-10 levels. Of note, EPH treatment promoted the phosphorylation of PI3K and AKT proteins in MCAO rats. Furthermore, administration of PI3K/AKT pathway inhibitor LY294002 abolished the beneficial effects of EPH. These results confirmed that EPH alleviated brain injury induced by MCAO via activating PI3K/AKT signaling pathway.

9.
Brain Behav ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34291586

RESUMO

AIM: Drug-resistant epilepsy (DRE), most subsequently developing refractory epilepsy, causes a significant burden to the society. microRNAs have been demonstrated as key regulators and therapeutic targets in epilepsy. Accordingly, the aim of the present study was to test whether miR-485 could be a potential target for DRE. METHODS AND RESULTS: An in vivo DRE model was developed in Sprague-Dawley rats by lithium chloride-pilocarpine and screened by antiepileptic drugs. We found that miR-485-5p in hippocampus was significant downregulated at early stage and recovered to normal level at late stage of DRE. Overexpression of miR-485-5p in dentate gyrus (DG) of hippocampus in DRE rats could significantly decrease the frequency of seizures and the numbers of epileptiform spikes of hippocampal DG neuron, and could specifically decrease SV2A expression without affecting PSD-95 expression in DG. Furthermore, miR-485-5p overexpression could significantly downregulate the expression of efflux transporter related to multidrug resistance (ABCC1) in hippocampus at late stage of DRE. Finally, a specific expression pattern of neuronal signaling-transduction proteins (LRP4, MDM4, p53, and TMBIM1) for DRE was observed, and miR-485-5p overexpression could modulate these proteins' expression levels toward normal in hippocampus both at early and late stage of DRE. CONCLUSION: Collectively, these results suggest that miR-485 was a potential target for anti-DRE, and this effects might be partially via miR-485-5p/homeostatic-synaptic plasticity-molecule axis and/or targeting efflux transporter (ABCC1) and other neuronal signaling-transduction proteins (LRP4, MDM4, p53, and TMBIM1).

10.
Br J Nutr ; : 1-42, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34256876

RESUMO

The effect and the mechanism of high glucose on fish muscle cells are not fully understood. In the present study, muscle cells of olive flounder (Paralichthys olivaceus) were treated with high glucose (33 mM) in vitro. Cells were incubated in three kinds of medium containing 5 mM glucose, 5 mM glucose and 28 mM mannitol (as an isotonic contrast) or 33 mM glucose named the Control group, the Mannitol group and the HG (high glucose) group, respectively. Results showed that high glucose increased the ADP/ATP ratio and the reactive oxygen species (ROS) level, decreased mitochondrial membrane potential (MMP), induced the release of cytochrome C (CytC) and cell apoptosis. High glucose also led to cell glycogen accumulation by increasing the glucose uptake ability and affecting the mRNA expressions of glycogen synthase and glycogen phosphorylase. Meanwhile, it activated AMP-activated protein kinase (AMPK), inhibited the activity of mammalian target of rapamycin (mTOR) signaling pathway and the expressions of myogenic regulatory factors (MRFs). The expressions of myostatin-1 (mstn-1) and E3 ubiquitin ligases including muscle RING-finger protein 1 (murf-1) and muscle atrophy F-box protein (mafbx) were also increased by the high glucose treatment. No difference was found between the Mannitol group and the Control group. These results demonstrate that high glucose has the effects of inducing apoptosis, increasing glycogen accumulation and inhibiting protein synthesis on muscle cells of olive flounder. The mitochondria mediated apoptotic signaling pathway, AMPK and mTOR pathways participated in these biological effects.

11.
Trends Immunol ; 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34256989

RESUMO

Lymph nodes (LNs), where immune responses are initiated, are organized into distinctive compartments by fibroblastic reticular cells (FRCs). FRCs imprint immune responses by supporting LN architecture, recruiting immune cells, coordinating immune cell crosstalk, and presenting antigens. Recent high-resolution transcriptional and histological analyses have enriched our knowledge of LN FRC genetic and spatial heterogeneities. Here, we summarize updated anatomic, phenotypic, and functional identities of FRC subsets, delve into topological and transcriptional remodeling of FRCs in inflammation, and illustrate the crosstalk between FRCs and immune cells. Discussing FRC functions in immunity and tolerance, we highlight state-of-the-art FRC-based therapeutic approaches for maintaining physiological homeostasis, steering protective immunity, inducing transplantation tolerance, and treating diverse immune-related diseases.

12.
J Org Chem ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34251829

RESUMO

A new efficient synthesis of polysubstituted pyrazin-2(1H)-ones via the sequential Ugi/Staudinger/aza-Wittig/isomerization reaction has been developed. The four-component Ugi reactions of arylglyoxals 1, primary amines 2, α-azidovinyl acids 3, and isocyanides 4 produced the azides 5, which were treated with triphenylphosphine to give pyrazin-2(1H)-ones 6 in good yields through domino Staudinger/aza-Wittig/isomerization reactions.

13.
Antimicrob Agents Chemother ; : AAC0060021, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34252301

RESUMO

Ravidasvir (RDV) is a novel oral hepatitis C virus NS5A inhibitor. This study aimed to evaluate the pharmacokinetics and safety of RDV and the drug-drug interaction between RDV and ritonavir-boosted danoprevir (DNVr) in healthy adults. In 1st study, healthy volunteers were administered oral single doses of 100, 200 and 300 mg RDV and 200 mg once daily for 7 days. The 2nd study was randomized, double-blind and placebo-controlled sequential design (day 1 for 200 mg RDV alone, day 7 for 100 mg/100 mg DNVr, day 13 for 200 mg RDV plus 100mg/100mg DNVr, followed by RDV 200 mg once daily with DNVr 100mg/100mg twice daily for 10 days). The results showed that RDV exposure increased in a dose-proportional manner following a single dose with no evidence of accumulation with multiple doses. Co-administration with DNVr regimen (100 mg/100 mg, twice daily) resulted in a 2.92- and 1.99-fold increase in minimum plasma concentration at steady state (Cmin,ss) and area under the concentration-time curve at steady state (AUCτ) of RDV. With co-administration of RDV, maximum plasma concentration (Cmax) and area under the concentration curve from zero to 12 h (AUC0-12) of DNV increased 1.71-fold and 2.33-fold, respectively. We did not observe any significant changes in ritonavir exposure. Both single and multiple doses of RDV with or without DNVr were well tolerated. The favorable pharmacokinetic and safety results support ravidasvir's continued clinical development and treatment.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34199687

RESUMO

Objectives: China is the country most afflicted by hepatocellular carcinoma in the world. However, little is known about the epidemiology of hepatocellular carcinoma in China. This study aimed to examine the trends of the prevalence, incidence, and mortality of hepatocellular carcinoma in China, and to investigate the effects of age, period, and birth cohort on the epidemiological trend. Methods: The data were obtained from the Urban Employee Basic Medical Insurance claims database (2003-2017) in Tianjin, China, which covers 5.95 million individuals. The average annual percentage change of the prevalence, incidence, and mortality were accessed using joinpoint regression. Age-period-cohort models were produced to quantify the effects of age, period, and cohort. Results: The hepatocellular carcinoma prevalence rate increased by 5.13% annually from 20.12/100,000 in 2008 to 30.49/100,000 in 2017, and the incidence rate was almost unchanged, from 13.91/100,000 in 2008 to 14.09/100,000 in 2017, but mortality decreased by 1.80% annually from 8.18/100,000 in 2008 to 7.34/100,000 in 2017. The age-period-cohort analysis revealed that the prevalence rate was remarkably increased from age 25, peaked in age 60, and decreased at age 70 and over. In the period index, the prevalence rate increased gradually from 2008 to 2016, and decreased a little in 2017. In the cohort index, the prevalence rate decreased approximately linearly from the 1925 cohort to the 1990 cohort. The result for the incidence was similar to the prevalence. The mortality rate increased approximately linearly from age 45 to 85, decreased from the 1925 cohort to the 1990 cohort, but it changed a little with the change of period. Conclusions: The findings of this study could inform the necessity of conducting earlier screening for high-risk individuals and improving the treatment of hepatocellular carcinoma, which may also help to predict future changes in hepatocellular carcinoma epidemiology.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/epidemiologia , China/epidemiologia , Efeito de Coortes , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Pessoa de Meia-Idade , Mortalidade , Prevalência
15.
Abdom Radiol (NY) ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34286371

RESUMO

PURPOSE: In this study, we developed radiomic models that utilize a combination of imaging features and clinical variables to distinguish endometrial cancer (EC) from normal endometrium on routine computed tomography (CT). METHODS: A total of 926 patients consisting of 416 endometrial cancer (EC) and 510 normal endometrium were included. The CT images of these patients were segmented manually, and divided into training, validation, testing and external testing sets. Non-texture and texture features of these images with endometrium or uterus as region of interest were extracted. The clinical feature "age" was also included in the feature set. Feature selection and machine learning classifier were applied to normalized feature set. This manual optimized combination was then compared with the best pipeline exported by Tree-Based Pipeline Optimization Tool (TPOT) on testing and external testing set. The performances of these machine learning pipelines were compared to that of radiologists. RESULTS: The manual expert optimized pipeline using the "reliefF" feature selection method and "Bagging" classifier on the external testing set achieved a test ROC AUC of 0.73, accuracy of 0.73 (95% CI 0.62-0.82), sensitivity of 0.64 (95% CI 0.45-0.79), and specificity of 0.78 (95% CI 0.65-0.87), while TPOT achieved a test ROC AUC of 0.79, accuracy of 0.80 (95% CI 0.70-0.87), sensitivity of 0.61 (95% CI 0.43-0.77), and specificity of 0.90 (95% CI 0.78-0.96). When compared to average radiologist performance, the TPOT achieved higher test accuracy (0.80 vs. 0.49, p < 0.001) and specificity (0.90 vs. 0.51, p < 0.001), with comparable sensitivity (0.61 vs. 0.46, p = 0.130). CONCLUSION: Our results demonstrate that automatic machine learning can distinguish EC from normal endometrium on routine CT imaging with higher accuracy and specificity than radiologists.

16.
Med Phys ; 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34287939

RESUMO

PURPOSE: The net uptake rate constant (Ki ) derived from dynamic imaging is considered the gold standard quantification index for FDG PET. In this study, we investigated the feasibility and assessed the clinical usefulness of generating Ki images for FDG PET using only two 5-min scans with population-based input function (PBIF). METHODS: Using a Siemens Biograph mCT, 10 subjects with solid lung nodules underwent a single-bed dynamic FDG PET scan and 13 subjects (5 healthy and 8 cancer patients) underwent a whole-body dynamic FDG PET scan in continuous-bed-motion mode. For each subject, a standard Ki image was generated using the complete 0-90 min dynamic data with Patlak analysis (t* = 20 min) and individual patient's input function, while a dual-time-point Ki image was generated from two 5-min scans based on the Patlak equations at early and late scans with the PBIF. Different start times for the early (ranging from 20 min to 55 min with an increment of 5 min) and late (ranging from 50 min to 85 min with an increment of 5 min) scans were investigated with the interval between scans being at least 30 min (36 protocols in total). The optimal dual-time-point protocols were then identified. Regions of interest (ROI) were drawn on nodules for the lung nodule subjects, and on tumors, cerebellum, and bone marrow for the whole-body-imaging subjects. Quantification accuracy was compared using the mean value of each ROI between standard Ki (gold standard) and dual-time-point Ki , as well as between standard Ki and relative SUV change that is currently used in clinical practice. Correlation coefficients and least squares fits were calculated for each dual-time-point protocol and for each ROI. Then, the predefined criteria for identifying a reliable dual-time-point Ki estimation for each ROI were empirically determined as: (1) the squared correlation coefficient (R2 ) between standard Ki and dual-time-point Ki is larger than 0.9; (2) the absolute difference between the slope of the equality line (1.0) and that of the fitted line when plotting standard Ki versus dual-time-point Ki is smaller than 0.1; (3) the absolute value of the intercept of the fitted line when plotting standard Ki versus dual-time-point Ki normalized by the mean of the standard Ki across all subjects for each ROI is smaller than 10%. Using Williams' one-tailed t test, the correlation coefficient (R) between standard Ki and dual-time-point Ki was further compared with that between standard Ki and relative SUV change, for each dual-time-point protocol and for each ROI. RESULTS: Reliable dual-time-point Ki images were obtained for all the subjects using our proposed method. The percentage error introduced by the PBIF on the dual-time-point Ki estimation was smaller than 1% for all 36 protocols. Using the predefined criteria, reliable dual-time-point Ki estimation could be obtained in 25 of 36 protocols for nodules and in 34 of 36 protocols for tumors. A longer time interval between scans provided a more accurate Ki estimation in general. Using the protocol of 20-25 min plus 80-85 or 85-90 min, very high correlations were obtained between standard Ki and dual-time-point Ki (R2 = 0.994, 0.980, 0.971 and 0.925 for nodule, tumor, cerebellum and bone marrow), with all the slope values with differences ≤ 0.033 from 1 and all the intercept values with differences ≤ 0.0006 mL/min/cm3 from 0. The corresponding correlations were much lower between standard Ki and relative SUV change (R2 = 0.673, 0.684, 0.065, 0.246). Dual-time-point Ki showed a significantly higher quantification accuracy with respect to standard Ki than relative SUV change for all the 36 protocols (p < 0.05 using Williams' one-tailed t test). CONCLUSIONS: Our proposed approach can obtain reliable Ki images and accurate Ki quantification from dual-time-point scans (5-min per scan), and provide significantly higher quantification accuracy than relative SUV change that is currently used in clinical practice.

17.
Zhongguo Zhong Yao Za Zhi ; 46(11): 2766-2772, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34296574

RESUMO

Tumor metastasis is an important cause of tumor treatment failure. Its molecular mechanism is closely related to tumor cells remodeling immune cells and immunosuppressive microenvironment, so as to create a suitable soil for tumor cell invasion and growth. "Huoxue Huayu" is one of the important therapeutic principles in cancer treatment, but the influence of Huoxue drugs on tumor metastasis has been controversial in clinical application. In this paper, we systematically summarized the comparative study of Huoxue drugs and Yiqi Huoxue drugs in tumor metastasis in recent years, and discussed the differences of molecular mechanisms of Huoxue drugs and Yiqi Huoxue drugs in anti-tumor metastasis from the perspective of immune remodeling, so as to provide scientific basis for clinical rational application of Huoxue drugs and Yiqi Huoxue drugs.

18.
Clin Immunol ; 229: 108800, 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34289424

RESUMO

The study aimed to investigate the soluble programmed death-1 (sPD-1) and its ligand (sPD-L1) levels in systemic juvenile idiopathic arthritis (sJIA) patients and elucidate its underlying immunomodulatory mechanisms. Plasma levels of sPD-1, sPD-L1 and related cytokines and proteins were detected using an enzyme-linked immunosorbent assay (ELISA) and Luminex. The effects of PD-1/PD-L1 signal on mDC (myeloid dendritic cell) and IL-6 secretion were measured using flow cytometry. The results revealed decreased levels of sPD-1 in sJIA patients negatively correlated with JADAS-27, PGA, PtGA and CRP. sJIA patients had lower CD86 and MHC-II expression on mDC. When blocking PD-1/PD-L1 signal, IL-6 secretion of DC were increased. Our finding displayed downregulated sPD-1 was related with clinical indicators and could be a new biomarker for sJIA diagnosis. The reduced membrane and soluble forms of PD-1/PD-L1 might take part in sJIA pathogenesis by enhancing mDC proliferation and IL-6 secretion.

19.
Neuro Oncol ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244788
20.
J Clin Lab Anal ; : e23920, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34318534

RESUMO

BACKGROUND: Molecular testing for oncogenic mutations in fine-needle aspiration has showed high predictive value in identifying malignant lesions from thyroid nodules with indeterminate cytology. METHODS: To figure out an efficient and economical gene panel for most medical institutions in China, we designed a five-gene panel including BRAF/NRAS/KRAS/HRAS/TERT genes and conducted a retrospective study to evaluate the role of this five-gene diagnostic panel in differential diagnosis of thyroid nodules. RESULTS: A total of 665 patients with 695 thyroid nodules were investigated in the current study. The fine-needle aspiration biopsy and surgically separated thyroid tissue specimens were harvested to test BRAF, TERT, NRAS, KRAS, and HRAS mutations. We identified 261 mutations in 665 patients, including 177 V600E mutations in BRAF. Three hundred and sixty-nine patients who underwent thyroid surgery after completion of the initial clinical and cytological evaluation were enrolled in the final analysis. The diagnostic sensitivity, specificity, and accuracy of the combination of FNAB cytology and five-gene detection were 74.7%, 93.8%, and 84.8%, respectively. BRAF V600E and five-gene panel could recognize 46.4% and 53.6% of papillary thyroid carcinoma in the patients with cytologically indeterminate nodules. CONCLUSION: The five-gene panel can effectively improve the sensitivity, negative predictive value, and accuracy of fine-needle aspiration biopsy cytology, especially in the patients with cytologically indeterminate nodules.

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