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1.
BMJ Open ; 11(5): e047828, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33980532

RESUMO

OBJECTIVES: To assess the magnitude of mental health outcomes and associated factors among psychiatric professionals in mental health services during COVID-19 in China. DESIGN, SETTING AND PARTICIPANTS: This cross-sectional, survey-based, region-stratified study collected demographic data and mental health measurements from psychiatric professionals in 34 hospitals between 29 January and 7 February 2020, in China. Hospitals equipped with fever clinics or deployed on wards for patients with COVID-19 were eligible. PRIMARY OUTCOME AND MEASURES: The severity of symptoms of depression, anxiety, insomnia and distress were assessed by the Chinese versions of 9-item Patient Health Questionnaire, 7-item Generalised Anxiety Disorder, 7-item Insomnia Severity Index and 22-item Impact of Event Scale-Revised, respectively. Multivariable logistic regression and structural equation modelling was performed to identify factors associated with mental health outcomes. RESULTS: A total of 610 psychiatric professionals were included. 29.8% were employed in Wuhan, and 22.5% were frontline workers. A considerable proportion of participants reported symptoms of depression (461 (75.6%)), anxiety (282 (46.2%)), insomnia (336 (55.1%)) and mental stress (481 (78.9%)). Psychiatric symptoms were associated with worrying about infection (eg, OR 2.36 (95% CI 1.27 to 4.39) for anxiety), risks of exposure to COVID-19 (eg, having inadequate personal protection equipment, OR 2.43 (1.32 to 4.47) for depression) and self-perceived physical health (eg, OR 3.22 (2.24 to 4.64) for mental stress). Information sources of COVID-19 were also found to be both positively (eg, information from relatives, OR 2.16 (1.46 to 3.21) for mental stress) and negatively (eg, information from TV, OR 0.52 (0.35 to 0.77) for mental stress) associated with mental stress. There is preliminary evidence that mental health might benefit from greater availability of mental healthcare services. The structural equation model analysis indicated that worrying about infection may be the primary mediator via which risk of exposure to COVID-19 pandemic affects the mental health of psychiatric professionals. CONCLUSIONS: The current findings demonstrate several pathways via which the COVID-19 pandemic may have negatively affected the mental health of psychiatric professionals in China.

2.
Comput Biol Med ; 134: 104452, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33984751

RESUMO

BACKGROUND: Metabolic syndrome (MetS) is prevalent in patients receiving atypical antipsychotic drugs (AADs), but there are few effective interventions. The Traditional Chinese herbal decoction Liu-Yu-Tang (LYT) has achieved clinical improvement for AAD-induced MetS, but its pharmacological mechanism remains unclear. METHOD: A network pharmacology-based method was utilized in this study. First, the TCMSP and SwissTargetPrediction database were used to acquire plasma-absorbed components and putative targets of LYT, respectively. Second, an interaction network between shared targets of LYT and MetS was constructed using STRING online tool. Topological analyses were performed to extract hub gene targets. Finally, we did a pathway analysis of gene targets using the Kyoto Encyclopedia of Genes and Genomes (KEGG) to find biological pathways of LYT. RESULTS: We obtained 655 putative targets of LYT, 434 known targets of AADs, and 1577 MetS-related gene targets. There are 232 shared targets between LYT and MetS. Interaction network construction and topological analysis yielded 60 hub targets, of which 18 were major hub targets, among which IL-6, IL-8, TNF, PI3K, MAPK, and NF-κB (RELA) are the most important in LYT's treatment of AAD-induced MetS. Pathway enrichment analysis revealed a statistically high significance of the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis and the insulin resistance pathway. CONCLUSIONS: LYT may control activities of the pro-inflammatory cytokines IL-6, IL-8, TNF and the important signal transduction molecules PI3K, MAPKs, and NF-κB (RELA), regulating metabolic disturbance-related pathways like the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis, and the insulin resistance pathway, generating therapeutic effects for AAD-induced MetS.

3.
Front Immunol ; 12: 654749, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936081

RESUMO

Background: Less than 20% of melanoma patients respond to programmed cell death-1 (PD-1) blockade immunotherapies. Thus, it is crucial to understand the dynamic changes in the tumor microenvironment (TME) after PD-1 blockade, for developing immunotherapy efficacy. Methods: A genomic analysis was conducted by The Cancer Genome Atlas (TCGA) datasets and web platform TIMER2.0 datasets. Pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Peripheral blood mononuclear cells (PBMCs), regulatory T (Treg) cells, and B16-F10 melanoma mice were used as models. The cellular and molecular characteristics and mechanisms of Treg cells in melanoma were assessed by performing gene expression studies, immunohistochemistry, RNA sequencing, and flow cytometry. Results: Here, we evaluate the countenance of T cell immunoglobulin and mucin-domain containing-3 (Tim-3), and various immunosuppressive factors within tumor-infiltrated Treg cells after treatment with anti-PD-1 or the indicator transduction and activator of transcription 3 (STAT3) inhibitors. Increased expression of Tim-3 is markedly observed within the tissues of the PD-1 blockade resistance of melanoma patients. Targeting STAT3 significantly boosts the response of resistant-PD-1 therapy within the melanoma mouse model. Mechanistically, the manifestation of STAT3 decreases the expression of Tim-3 and various cytokines in the purified Treg cells from individual PBMCs and the murine melanoma model, limiting the immunosuppression of Treg cells. Conclusions: Our findings indicate that Tim-3 expression on Treg cells within the TME is STAT3-dependent, providing support to STAT3 as a target and enhancing the immunotherapy for patients suffering from melanoma.

4.
HLA ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33886168

RESUMO

HLA-DQB1*04:74 differs from HLA-DQB1*04:01:01:01 by one nucleotide substitution in codon 54 in exon 2. This article is protected by copyright. All rights reserved.

5.
Front Public Health ; 9: 615817, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33816416

RESUMO

Background: More than 300 million smokers make China the largest cigarette consumer globally, which is a huge economic burden. Smoking cessation (SC) clinics can offer counseling and follow-up services. The operational experience of SC clinics in China needs to be summarized and improved based on research evidence. Purpose: The objectives of this study were to describe quit rates among attendees of SC clinics in Hunan and assess predictors of successful SC. Methods: The participants in this study were smokers who visited the SC clinic of Hunan Cancer Hospital from February 1, 2015 to September 30, 2018. Individuals who received individual counseling and assessment from the SC clinic staff and were willing to quit smoking were eligible for inclusion. Those with critical illness or cancer were excluded. Application of smoking cessation clinic registration form (unified by Chinese Center for Disease Control and Prevention) was used to assess participants at the consultation. Follow-ups and counseling were performed over telephone at 1 week, 1 month, and 3 months after the initial cessation consultation or in times of need. Successful SC was checked for at 3 months after the start of SC. Results: A total of 328 smokers (mean age 45.67 ± 12.38 years) had participated. The abstinence rate at 3 months was 28.4%. Binary regression analysis revealed significant independent predictors to be the total numbers of SC follow up sessions, previous SC attempts, and participants' decision on when to quit smoking (The relative to quit immediately group, quit within 30 days, quit after 30 days, and undecided quit were less likely to succeed in quitting. while quit within seven days had no statistical significance. Conclusion: SC clinics can achieve a desirably high quit rate. Participant's previous attempts at quitting, three or more follow-ups, and the decision to quit immediately or within seven days were factors helpful in predicting the success of SC.

6.
World J Surg ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33821350

RESUMO

AIM: Laparoscopic total mesorectal excision (LaTME) following preoperative chemoradiotherapy (PCRT) in locally advanced rectal cancer (LARC) is technically demanding. The present study is intended to evaluate predictive factors of surgical difficulty of LaTME following PCRT by using pelvimetric and nutritional factors. METHOD: Consecutive LARC patients receiving LaTME after PCRT were included. Surgical difficulty was classified based upon intraoperative (operation time, blood loss, and conversion) and postoperative outcomes (postoperative hospital stay and morbidities). Pelvimetry was performed using preoperative T2-weighted MRI. Nutritional factors such as albumin-to-globulin ratio (AGR) and prognostic nutritional index (PNI) were calculated. Multivariable logistic analysis was used to identify predictors of high surgical difficulty. A predictive nomogram was developed and validated internally. RESULTS: Among 294 patients included, 36 (12.4%) patients were graded as high surgical difficulty. Logistic regression analysis demonstrated that previous abdominal surgery (OR = 6.080, P = 0.001), tumor diameter (OR = 1.732, P = 0.003), intersphincteric resection (vs. low anterior resection, OR = 13.241, P < 0.001), interspinous distance (OR = 0.505, P = 0.009), and preoperative AGR (OR = 0.041, P = 0.024) were independently predictive of high surgical difficulty of LaTME after PCRT. Then, a predictive nomogram was built (C-index = 0.867). CONCLUSION: Besides previous abdominal surgery, type of surgery (intersphincteric resection), tumor diameter, and interspinous distance, we found that preoperative AGR could be useful for the prediction of surgical difficulty of LaTME after PCRT. A predictive nomogram for surgical difficulty may aid in planning an appropriate approach for rectal cancer surgery after PCRT.

7.
BMC Health Serv Res ; 21(1): 262, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33743674

RESUMO

BACKGROUND: The association of workplace factors on mental health of healthcare workers (HCWs) during the COVID-19 pandemic needs to be urgently established. This will enable governments and policy-makers to make evidence-based decisions. This international study reports the association between workplace factors and the mental health of HCWs during the pandemic. METHODS: An international, cross-sectional study was conducted in 41 countries. The primary outcome was depressive symptoms, derived from the validated Patient Health Questionnaire-2 (PHQ-2). Multivariable logistic regression identified factors associated with mental health outcomes. Inter-country differences were also evaluated. RESULTS: A total of 2527 responses were received, from 41 countries, including China (n = 1213; 48.0%), UK (n = 891; 35.3%), and USA (n = 252; 10.0%). Of all participants, 1343 (57.1%) were aged 26 to 40 years, and 2021 (80.0%) were female; 874 (34.6%) were doctors, and 1367 (54.1%) were nurses. Factors associated with an increased likelihood of depressive symptoms were: working in the UK (OR = 3.63; CI = [2.90-4.54]; p < 0.001) and USA (OR = 4.10; CI = [3.03-5.54]), p < 0.001); being female (OR = 1.74; CI = [1.42-2.13]; p < 0.001); being a nurse (OR = 1.64; CI = [1.34-2.01]; p < 0.001); and caring for a COVID-19 positive patient who subsequently died (OR = 1.20; CI = [1.01-1.43]; p = 0.040). Workplace factors associated with depressive symptoms were: redeployment to Intensive Care Unit (ICU) (OR = 1.67; CI = [1.14-2.46]; p = 0.009); redeployment with perceived unsatisfactory training (OR = 1.67; CI = [1.32-2.11]; p < 0.001); not being issued with appropriate personal protective equipment (PPE) (OR = 2.49; CI = [2.03-3.04]; p < 0.001); perceived poor workplace support within area/specialty (OR = 2.49; CI = [2.03-3.04]; p < 0.001); and perceived poor mental health support (OR = 1.63; CI = [1.38-1.92]; p < 0.001). CONCLUSION: This is the first international study, demonstrating that workplace factors, including PPE availability, staff training pre-redeployment, and provision of mental health support, are significantly associated with mental health during COVID-19. Governments, policy-makers and other stakeholders need to ensure provision of these to safeguard HCWs' mental health, for future waves and other pandemics.


Assuntos
/psicologia , Pessoal de Saúde/psicologia , Saúde Mental , Pandemias/prevenção & controle , Local de Trabalho/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Equipamento de Proteção Individual
8.
Eur J Cancer ; 148: 1-13, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33691262

RESUMO

BACKGROUND: GLS-010, a novel engineered fully human immunoglobin G4 monoclonal antibody, can specially block the PD-1/PD-L1/2 axis and reactivate the antitumor immunity. AIM: This phase Ia/Ib study was carried out to evaluate the safety, recommended phase II dose (R2PD), and primary antitumor effects of GLS-010 in patients with advanced, refractory lymphoma and solid tumors. METHODS: In phase Ia study, patients with refractory solid tumors and lymphoma enrolled and received GLS-010 at a dose of 1, 4, or 10 mg/kg Q2W; 240 mg Q3W or Q2W. The primary objective was to assess the dose-limiting toxicity (DLT). In phase Ib study, doses were expanded in 9 specific tumors to ensure the R2PD and explore the efficacy. Tumor mutation burden level and PD-L1 expression were also assessed with whole-exome sequencing and immunohistochemistry (SP263), respectively. RESULTS: Up to April 18, 2020, a total of 289 patients (n = 24, phase Ia; n = 265, phase Ib) were enrolled. DLT was not observed in phase Ia part. The T1/2, CLss, and Vd were similar among all dose groups and different tumors. The most common treatment-emergent adverse events (TEAEs) were anemia, leukopenia, elevated alanine aminotransaminase/asparate aminotransferase (ALT/AST), and elevated bilirubin. And hypothyroidism was the most common immune-related adverse event (irAE). The incidence of grade ≥3 TEAE was 39.8%, while grade ≥3 irAE was only 4.5%. Based on safety studies, pharmacokinetics/pharmacodynamics, and preclinical data, 240-mg Q2W was recommended as the expansion dose. The overall objective response rate was 23.6%, with 10 patients achieving complete response. Patients with a high PD-L1 expression level (31.3% Versus. 13.7%, p = 0.012) or t-issue tumor mutation burden level (31.3% Versus. 5.6%, p = 0.009) showed a significantly better response. CONCLUSION: GLS-010 showed acceptable safety profile and favorable clinical response. The dose of 240 mg Q2W was an optimal recommended dose as monotherapy.

9.
Ultrasonics ; 114: 106419, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33740499

RESUMO

Grading red blood cell (RBC) aggregation is important for the early diagnosis and prevention of related diseases such as ischemic cardio-cerebrovascular disease, type II diabetes, deep vein thrombosis, and sickle cell disease. In this study, a machine learning technique based on an adaptive analysis of ultrasonic radiofrequency (RF) echo signals in blood is proposed, and its feasibility for classifying RBC aggregation is explored. Using an adaptive empirical wavelet transform (EWT) analysis, the ultrasonic RF signals are decomposed into a series of empirical mode functions (EMFs); then, dominant empirical mode functions (DEMFs) are selected from the series. Six statistical characteristics, including the mean, variance, median, kurtosis, root mean square (RMS), and skewness are calculated for the locally normalized DEMFs, aiming to form primary feature vectors. Random forest (RDF) and support vector machine (SVM) classifiers are trained with the given feature vectors to obtain prediction models for RBC classification. Ultrasonic RF echo signals are acquired from five groups of six types of porcine blood samples with average numbers of aggregated RBCs of 1.04, 1.20, 1.83, 2.31, 2.72, and 4.28, respectively, to test the classification performance of the proposed method. The best subset with regard to the variance, kurtosis, and RMS is determined according to the maximum accuracy based on the RDF and SVM classifiers. The classification accuracies are 84.03 ±â€¯3.13% for the RDF classifier, and 85.88 ±â€¯2.99% for the SVM classifier. The mean classification accuracy of the SVM classifier is 1.85% better than that of the RDF classifier. In conclusion, the machine learning method is useful for the discrimination of varying degrees of RBC aggregation, and has potential for use in characterizing and monitoring the RBC aggregation in vessels.


Assuntos
Agregação Eritrocítica , Aprendizado de Máquina , Ondas de Rádio , Ultrassom , Análise de Ondaletas , Animais , Máquina de Vetores de Suporte , Suínos
10.
Huan Jing Ke Xue ; 42(4): 1642-1648, 2021 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742799

RESUMO

The particle size multiplier is a valuable parameter for depicting the particle size distribution characteristics of road dust and calculating road dust emissions. In order to realize the localization of the particle size multiplier, the AP-42 and TRAKER methods were used for sampling on typical and different types of roads in Baoding in March 2019. Then, the particle size multiplier of road dust PM2.5 (K2.5) was calculated using the correction formula, and the characteristics were analyzed. The results indicated:① The K2.5 obtained separately by AP-42 and TRAKER were 0.21 g·VKT-1 and 0.23 g·VKT-1 on average, which correlated well, with a high correlation coefficient of 0.6. The PM2.5 emission factors calculated using the K2.5 of the different methods were almost at the same value, indicating that TRAKER method based on a laser sensor could measure and calculate the K2.5 and could be directly used to obtain the particle size multiplier or be converted using the fitting equation. ② The characteristics of the K2.5 in Baoding were ranked as:Expressway

11.
Artigo em Inglês | MEDLINE | ID: mdl-33772467

RESUMO

The Belt and Road Initiative (BRI) has promoted the deployment of renewable energy to achieve sustainability. It is essential to reveal the influence of renewable energy on low-carbon economic development. The share of renewable energy consumption (SREC) is taken as the core explanatory variable in this paper, and its impacts on carbon emission intensity (CEI) and economic growth are investigated from the spatial-temporal perspective. First, the panel Granger causality test is applied for revealing the causal links among SREC, CEI, and economic growth during 1999-2017. Then, this paper investigates the impacts of SREC on economic growth and CEI through rigorous econometric techniques. Based on the regression results, Shapley value decomposition is utilized to account for the cross-country inequalities of economic growth and CEI. The main findings are as follows: (1) There exist bidirectional Granger causalities between SREC, economic growth, and CEI, which shows there is a systematic link between the three variables. (2) All models demonstrate SREC negatively influences economic growth, indicating renewable energy deployment costs are urgent to be decreased with SREG increasing. Besides, capital investment and openness positively affect economic growth, but energy intensity has an opposite impact. (3) From the spatial heterogeneity perspective, the cross-country inequality in economic growth is primarily due to the regional inequality of capital investment, followed by energy intensity and SREC. By contrast, the impacts of labor and openness are negligible. (4) SREC has a negative effect on CEI. In addition, an inverted U-shaped nexus between economic growth and CEI is observed. Energy intensity positively affects CEI, while the impacts of urbanization and openness are insignificant. (5) From the spatial heterogeneity perspective, the cross-country CEI inequality is mostly caused by the inequality of energy intensity, followed by SREC, urbanization, and economic growth, while the contribution of the openness gap is little. This article provides important implications for low-carbon development in the BRI countries.

12.
Adv Mater ; 33(14): e2007041, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33655643

RESUMO

Organic polymer electrochemical transistors (OECTs) are of great interest for flexible electronics and bioelectronics applications owing to their high transconductance and low operating voltage. However, efficient OECT operation must delicately balance the seemingly incompatible materials optimizations of redox chemistry, active layer electronic transport, and ion penetration/transport. The latter characteristics are particularly challenging since most high-mobility semiconducting polymers are hydrophobic, which hinders efficient ion penetration, hence limiting OECT performance. Here, the properties and OECT response of a series of dense and porous semiconducting polymer films are compared, the latter fabricated via a facile breath figure approach. This methodology enables fast ion doping, high transconductance (up to 364 S cm-1 ), and a low subthreshold swing for the hydrophobic polymers DPPDTT and P3HT, rivalling or exceeding the metrics of the relatively hydrophilic polymer, Pg2T-T. Furthermore, the porous morphology also enhances the transconductance of hydrophilic polymers, offering a general strategy for fabricating high-performance electrochemical transistors.

13.
Theranostics ; 11(7): 3229-3243, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33537084

RESUMO

The notion of personalized medicine demands proper prognostic biomarkers to guide the optimal therapy for an invasive breast cancer patient. However, various risk prediction models based on conventional clinicopathological factors and emergent molecular assays have been frequently limited by either a low strength of prognosis or restricted applicability to specific types of patients. Therefore, there is a critical need to develop a strong and general prognosticator. Methods: We observed five large-scale tumor-associated collagen signatures (TACS4-8) obtained by multiphoton microscopy at the invasion front of the breast primary tumor, which contrasted with the three tumor-associated collagen signatures (TACS1-3) discovered by Keely and coworkers at a smaller scale. Highly concordant TACS1-8 classifications were obtained by three independent observers. Using the ridge regression analysis, we obtained a TACS-score for each patient based on the combined TACS1-8 and established a risk prediction model based on the TACS-score. In a blind fashion, consistent retrospective prognosis was obtained from 995 breast cancer patients in both a training cohort (n= 431) and an internal validation cohort (n = 300) collected from one clinical center, and in an external validation cohort (n = 264) collected from a different clinical center. Results: TACS1-8 model alone competed favorably with all reported models in predicting disease-free survival (AUC: 0.838, [0.800-0.872]; 0.827, [0.779-0.868]; 0.807, [0.754-0.853] in the three cohorts) and stratifying low- and high-risk patients (HR 7.032, [4.869-10.158]; 6.846, [4.370-10.726], 4.423, [2.917-6.708]). The combination of these factors with the TACS-score into a nomogram model further improved the prognosis (AUC: 0.865, [0.829-0.896]; 0.861, [0.816-0.898]; 0.854, [0.805-0.894]; HR 7.882, [5.487-11.323]; 9.176, [5.683-14.816], and 5.548, [3.705-8.307]). The nomogram identified 72 of 357 (~20%) patients with unsuccessful 5-year disease-free survival that might have been undertreated postoperatively. Conclusions: The risk prediction model based on TACS1-8 considerably outperforms the contextual clinical model and may thus convince pathologists to pursue a TACS-based breast cancer prognosis. Our methodology identifies a significant portion of patients susceptible to undertreatment (high-risk patients), in contrast to the multigene assays that often strive to mitigate overtreatment. The compatibility of our methodology with standard histology using traditional (non-tissue-microarray) formalin-fixed paraffin-embedded (FFPE) tissue sections could simplify subsequent clinical translation.

14.
J Alzheimers Dis ; 80(1): 407-419, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33554907

RESUMO

BACKGROUND: The choroid is involved directly or indirectly in many pathological conditions such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). OBJECTIVE: The objective of this study was to investigate the association between retinal choroidal properties and the pathology of AD by determining choroidal thickness, hippocampus volume, cognitive functions, and plasma BACE1 activity. METHODS: In this cross-sectional study, 37 patients with AD and 34 age-matched controls were included. Retinal choroidal thickness was measured via enhanced depth imaging optical coherence tomography. Hippocampal volume was measured via 3.0T MRI. Cognitive functions were evaluated using the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog). Plasma BACE1 activity was analyzed using a fluorescence substrate-based plasma assay, and regression model were to analyze the data. RESULTS: Retinal choroidal thickness was significantly thinner in the AD group than in the control group [(114.81±81.30) µm versus (233.79±38.29) µm, p < 0.05]. Multivariable regression analysis indicated that the ADAS-cog scores (ß=-0.772, p = 0.000) and age (ß=-0.176, p = 0.015) were independently associated with choroidal thickness. The logistic regression model revealed that the subfoveal choroidal thickness was a significant predictor for AD (OR = 0.984, 95% CI: 0.972-0.997). CONCLUSION: There was a general tendency of choroid thinning as the cognitive function declined. Although choroidal thickness was not a potential indicator for early stage AD, it was valuable in monitoring AD progression.

15.
Cancer Med ; 10(6): 2063-2074, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33624385

RESUMO

AIMS: To investigate novel biomarker for diagnosis of cervical cancer, we analyzed the datasets in Gene Expression Omnibus (GEO) and confirmed the candidate biomarker in patient sample. MATERIALS AND METHODS: We collected major datasets of cervical cancer in GEO, and analyzed the differential expression of normal and cancer samples online with GEO2R and tested the differences, then focus on the GSE63514 to screen the target genes in different histological grades by using the R-Bioconductor package and R-heatmap. Then human specimens from the cervix in different histological grades were used to confirm the top 8 genes expression by immunohistochemical staining using Ki67 as a standard control. RESULTS: We identified genes differentially expressed in normal and cervical cancer, 274 upregulated genes and 206 downregulated genes. After intersection with GSE63514, we found the obvious tendency in different histological grades. Then we screened the top 24 genes, and confirmed the top 8 genes in human cervix tissues. Immunohistochemical (IHC) results confirmed that keratin 17 (KRT17) was not expressed in normal cervical tissues and was over-expressed in cervical cancer. Cysteine-rich secretory protein-2 (CRISP2) was less expressed in high-grade squamous intraepithelial lesions (HSILs) than in other histological grades. CONCLUSION: For the good repeatability and consistency of KRT17 and CRISP2, they may be good candidate biomarkers. Combined analysis of KRT17, CRISP2 expression at both genetic and protein levels can determine different histological grades of cervical squamous cell carcinoma. Such combined analysis is capable of improving diagnostic accuracy of cervical cancer.

16.
J Thorac Oncol ; 16(5): 827-839, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33588113

RESUMO

INTRODUCTION: By implementing dynamic circulating tumor DNA (ctDNA) analysis, we explored the impact of TP53 mutations on tumor evolution and resistance mechanisms to ensartinib in patients with ALK-positive NSCLC. METHODS: In a multicenter phase 2 trial, patients with ALK-positive NSCLC who progressed on crizotinib were treated with ensartinib. Blood samples for ctDNA analysis were collected at baseline, cycle 3 day 1, and progression disease (PD) and analyzed with a 212-gene panel. RESULTS: A total of 440 samples were collected from 168 patients. Baseline TP53 mutations (20.2%) significantly correlated with inferior progression-free survival (4.2 mo versus 11.7 mo, p < 0.0001). Patients with TP53 mutations had higher mutation load than those without TP53 mutations at baseline (13.79 ± 3.72 versus 4.67 ± 0.39, p < 0.001). Although there was no significant difference in mutation load between these groups at cycle 3 day 1 (5.89 ± 2.25 versus 3.72 ± 0.62, p = 0.425), patients with mutated TP53 developed more mutations at PD (7.07 ± 1.25 versus 3.20 ± 0.33, p = 0.003). Frequency and abundance of secondary ALK mutations G1269A, G1202R, and E1210K increased markedly at PD than baseline. In patients without secondary ALK mutations, we identified ALK-independent resistance mechanisms including bypass signaling activation, downstream effector protein reactivation, epithelial-mesenchymal transformation, and epigenetic dysregulation. CONCLUSIONS: Our study highlighted the advantage of ctDNA analysis for monitoring tumor evolution. TP53 mutations promoted genetic evolution and accelerated occurrence of resistance. We also unveiled ALK-dependent resistance mechanisms, mainly by G1269A, G1202R, and E1210K mutations, and ALK-independent resistance mechanisms to ensartinib.

17.
Acta Radiol ; : 284185120983971, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33412924

RESUMO

BACKGROUND: Multiple neurovascular contacts in patients with vascular compressive trigeminal neuralgia often challenge the diagnosis of responsible contacts. PURPOSE: To analyze the magnetic resonance imaging (MRI) features of responsible contacts and establish a predictive model to accurately pinpoint the responsible contacts. MATERIAL AND METHODS: Sixty-seven patients with unilateral trigeminal neuralgia were enrolled. A total of 153 definite contacts (45 responsible, 108 non-responsible) were analyzed for their MRI characteristics, including neurovascular compression (NVC) grading, distance from pons to contact (Dpons-contact), vascular origin of compressing vessels, diameter of vessel (Dvessel) and trigeminal nerve (Dtrigeminal nerve) at contact. The MRI characteristics of the responsible and non-responsible contacts were compared, and their diagnostic efficiencies were further evaluated using a receiver operating characteristic (ROC) curve. The significant MRI features were incorporated into the logistics regression analysis to build a predictive model for responsible contacts. RESULTS: Compared with non-responsible contacts, NVC grading and arterial compression ratio (84.44%) were significantly higher, Dpons-contact was significantly lower at responsible contacts (P < 0.001, 0.002, and 0.033, respectively). NVC grading had a highest diagnostic area under the ROC curve (AUC) of 0.742, with a sensitivity of 64.44% and specificity of 75.00%. The logistic regression model showed a higher diagnostic efficiency, with an AUC of 0.808, sensitivity of 88.89%, and specificity of 62.04%. CONCLUSION: Contact degree and position are important MRI features in identifying the responsible contacts of the trigeminal neuralgia. The logistic predictive model based on Dpons-contact, NVC grading, and vascular origin can qualitatively improve the prediction of responsible contacts for radiologists.

18.
Surg Today ; 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33420827

RESUMO

PURPOSE: Laparoscopic total mesorectal excision (LaTME) is technically demanding in rectal cancer after neoadjuvant chemoradiotherapy (NCRT). This study aimed to predict the surgical difficulty of LaTME after NCRT based on pelvimetric parameters. METHODS: This study enrolled 147 patients who underwent LaTME after NCRT. The surgical difficulty was graded as high or low according to the operative time, estimated blood loss, conversion to open surgery, postoperative hospital stay, and postoperative complications. Pelvimetry parameters were collected based on preoperative MRI. A logistic regression analysis was performed to identify predictors of high surgical difficulty, and a nomogram was developed. RESULTS: Totally, 18 (12.2%) patients were graded as high surgical difficulty. High surgical difficulty was correlated with a shorter interspinous distance (P = 0.014), a small angle α and γ (P = 0.008, P = 0.008, respectively), and a larger mesorectal area and mesorectal fat area (P = 0.041, P = 0.046, respectively). Tumor distance from the anal verge (OR = 0.619, P = 0.024), tumor diameter (OR = 3.747, P = 0.004), interspinous distance (OR = 0.127, P = 0.007), and angle α (OR = 0.821, P = 0.039) were independent predictors of high surgical difficulty. A predictive nomogram was developed with a C-index of 0.867. CONCLUSION: A shorter tumor distance from the anal verge, larger tumor diameter, shorter interspinous distance, and smaller angle α could help to predict high surgical difficulty of LaTME in male LARC patients after NCRT.

19.
Neurol Sci ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462635

RESUMO

OBJECTIVES: Diagnosis of hyperkinetic movement disorders with an unknown cause is usually challenging. The objective of this study is to learn about video electroencephalogram (VEEG) combined with electromyography (EMG) in the diagnosis of hyperkinetic movement disorders with an unknown cause. METHODS: We performed an observational cohort study by recruiting consecutive patients with hyperkinetic movements as the main manifestation with an unknown cause for VEEG combined with EMG evaluations. RESULTS: A total of 77 consecutive patients were enrolled for VEEG-EMG examination. Among them, 57 patients changed their diagnosis after VEEG-EMG assessment, with a mean final diagnosis age of 35.4 ± 20.3 years (range, 4-74 years). The mean duration between initial and final diagnosis was 54.8 ± 71.3 months (range 0.5-300 months). The most common misdiagnosed hyperkinetic movement disorders were myoclonus (40.4%), followed by tremors (24.6%), dystonia (15.8%), psychogenic movement disorders (10.5%), and periodic leg movement syndrome (PLMS) (7.0%). Outcomes of therapy were significantly improved after VEEG-EMG examination (p = 0.000). CONCLUSIONS: Simultaneous VEEG and EMG are important in the diagnosis of hyperkinetic movement disorders with an unknown cause.

20.
Int J Biol Macromol ; 175: 30-39, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33513422

RESUMO

A high serum uric acid (SUA) concentration is associated with hyperuricemia (HUA) and gout. In order to obtain long-acting therapeutic effect, correction of purine metabolism at genetic level is advantageous. For this purpose, we expressed three "human-like" urate oxidases in human hepatocytes (HL-7702) by lentivirus-mediated transduction. Enzymatic assay revealed that the recombinant urate oxidases expressed in HL-7702 cells were functionally active. Electron microscopy study showed that the recombinant enzymes were localized to peroxisome and formed distinct crystalloid core structures as in other mammal cells. Although similar rate of uric acid degradation was observed for all recombinant urate oxidases, HL-7702-pLVX-UOX83 cells and HL-7702-pLVX-UOX214/217 cells retained more cell viability compared with HL-7702-pLVX-UOXPBC at high uric acid level. This study provides a new direction for the treatment of gout and hyperuricemia.

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