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PURPOSE: We aimed to assess whether the aberrant methylation of GNAQ gene, which may involve in the clopidogrel resistance (CR), was associated with a higher risk of recurrent ischemic events in clopidogrel-treated acute ischemic stroke or transient ischemic attack (TIA) patients. METHODS: This is a nested case-control study, 152 clopidogrel-treated acute ischemic stroke or TIA patients that were propensity-matched were included in the final analysis, including 36 patients with vascular recurrence set as cases. Methylation levels of GNAQ gene were identified with MassARRAY EpiTYPER assays. Univariate and multivariate logistic regression analyses were conducted to explore the predictive value of CpG units for recurrent ischemic events within 1 year.Mediation analysis was performed to assess the role of CR in describing the effect of GNAQ methylation on recurrent ischemic events. RESULTS: A total of 16 differentially methylated CpG units were identified. Multivariate logistic analysis indicated that the average methylation of CpG 32-39 of GNAQ was associated with a significantly higher risk of ischemic events (p < 0.001). When transformed into dichotomous variables with the receiver operating characteristic curve, hypomethylation (<0.31) of CpG 32-39 of GNAQ significantly increased the risk of vascular recurrence (odds ratio 73.82, 95% confidence interval 20.33-268.01). The mediation effect of CR for recurrent ischemic events was not identified. CONCLUSIONS: Hypomethylation of CpG 32-39 of GANQ gene was associated with a higher risk of ischemic events for clopidogrel-treated acute ischemic stroke or TIA patients. Further studies were warranted to explain the possible mechanism.
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Clopidogrel , Metilação de DNA , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP , Ataque Isquêmico Transitório , AVC Isquêmico , Inibidores da Agregação Plaquetária , Humanos , Estudos de Casos e Controles , Clopidogrel/uso terapêutico , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/tratamento farmacológico , Ataque Isquêmico Transitório/genética , AVC Isquêmico/diagnóstico , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/genética , Inibidores da Agregação Plaquetária/uso terapêutico , Recidiva , Fatores de Risco , Resistência a Medicamentos/genéticaRESUMO
OBJECTIVE: Acute pancreatitis in pregnancy (APIP) is a rare and serious complication during pregnancy. It has acute onset and is difficult to diagnose and treat. The aim of the present study was to describe the etiology, clinical manifestations, and maternofetal outcomes of APIP. METHODS: We retrospectively reviewed 32 pregnant women who were treated at three tertiary care hospitals in Beijing, China. The correlation between the causes of APIP, severity, laboratory indices, and outcomes was analyzed. RESULTS: The most common causes of APIP were hypertriglyceridemia (56.2%,18/32) and gallstones (28.1%, 9/32). Hypertriglyceridemia-induced APIP was associated with a higher rate of severe acute pancreatitis (P = 0.025). Serum level of triglycerides showed a positive correlation with the severity of APIP (P = 0.039). The most frequent presentation of APIP was abdominal pain (93.7%, 30/32). There were no maternal or fetal deaths in our study. Apgar scores at 1 min, 5 min, and 10 min of the premature neonates was correlated with the severity of APIP of the mother (P = 0.022; 0.002; 0.002). CONCLUSION: High level of triglycerides may serve as a useful marker of the severity of APIP. The severity of APIP was associated with higher risk of neonate asphyxia. Appropriate timing of termination of pregnancy is a key imperative for APIP patients.
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Hipertrigliceridemia , Pancreatite , Complicações na Gravidez , Doença Aguda , Feminino , Humanos , Hipertrigliceridemia/complicações , Recém-Nascido , Pancreatite/complicações , Pancreatite/etiologia , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/etiologia , Estudos Retrospectivos , TriglicerídeosRESUMO
Newton's ring pattern is very common in interferometry. By analyzing it, the physical parameters can be estimated, such as the curvature radius and the rings' center. However, parameter estimation from large images using fractional Fourier transform (FRFT) consumes considerable time. A concise FRFT based on a non-uniform order searching method is proposed to reduce the computational time without decreasing the accuracy. Experimental results show that the time of the proposed method is about 2.7 s, which is about 1/600 of that of the traditional FRFT-based method and 1/5 of that of the Fast FRFT-based method when processing 960×960 pixel images.
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With the popularization of the concept of "metaverse", Augmented Reality (AR) technology is slowly being applied to people's daily life as its underlying technology support. In recent years, rapid 3D reconstruction of interior furniture to meet AR shopping needs has become a new method. In this paper, a virtual home environment system is designed and the related core technologies in the system are studied. Background removal and instance segmentation are performed for furniture images containing complex backgrounds, and a Bayesian Classifier and GrabCut (BCGC) algorithm is proposed to improve on the traditional foreground background separation technique. The reconstruction part takes the classical occupancy network reconstruction algorithm as the network basis and proposes a precise occupancy network (PONet) algorithm, which can reconstruct the structural details of furniture images, and the model accuracy is improved. Because the traditional 3D registration model is prone to the problems of model position shift and inaccurate matching with the scene, the AKAZE-based tracking registration algorithm is improved, and a Multiple Filtering-AKAZE (MF-AKAZE) based on AKAZE is proposed to remove the matching points. The matching accuracy is increased by improving the RANSAC filtering mis-matching algorithm based on further screening of the matching results. Finally, the system is verified to realize the function of the AR visualization furniture model, which can better complete the reconstruction as well as registration effect.
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Realidade Aumentada , Algoritmos , Teorema de Bayes , Ambiente Domiciliar , Humanos , Imageamento Tridimensional/métodos , Decoração de Interiores e MobiliárioRESUMO
BACKGROUND AND OBJECTIVE: To evaluate the cost-effectiveness of new anticoagulants and warfarin in the prevention of stroke in Chinese patients with atrial fibrillation (AF). METHODS: The Markov model was constructed to compare patients' quality-adjusted life-years (QALYs) using drug cost, the cost of the examination after taking a drug, and the incremental cost of other treatments. Both dabigatran (110 and 150 mg, twice a day) and rivaroxaban (20 mg, once a day) were compared with warfarin (3-6 mg, once a day). Willingness to pay, three times the 2018 China GDP per capita (9481.88 $), was the cost-effect threshold in our study. RESULTS: The total cost were was 5317.31$, 29673.33$, 23615.49$, and 34324.91$ for warfarin, rivaroxaban, dabigatran 110 mg bid, and dabigatran 150 mg bid, respectively. The QALYs for each of the four interventions were 11.07 years, 15.46 years, 12.4 years, and 15 years, respectively. The cost-effectiveness analysis of the three new oral anticoagulants and warfarin showed that the incremental cost-effectiveness ratio (ICER) was 5548.07$/QALY when rivaroxaban was compared with warfarin. Rivaroxaban was the most cost-effective choice and warfarin was the least. CONCLUSIONS: In Chinese patients with AF, although warfarin is cheaper, rivaroxaban has a better cost-effectiveness advantage from an economic point of view.
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Fibrilação Atrial , Acidente Vascular Cerebral , Anticoagulantes , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , China/epidemiologia , Análise Custo-Benefício , Dabigatrana , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Rivaroxabana , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , VarfarinaRESUMO
PURPOSE: Sodium glucose cotransporter 2 (SGLT2) inhibitors are shown to cause small, but significant changes of lipid profiles, we aim to investigate whether such altered lipid profiles can be translated into clinically meaningful changes in dyslipidemia. METHODS: PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized controlled trials (RCTs) that compared SGLT2 inhibitors with placebo or other oral glucose-lowering drugs in patients with type 2 diabetes mellitus and reported the events of dyslipidemia. A random-effect meta-analysis was performed to calculate the pooled estimates with risk ratio (RR) for dyslipidemia risk and weighted mean difference for lipid profiles with their 95% confidential intervals (CIs). RESULTS: Of 2427 studies identified, 15 RCTs involving 7578 patients were included. This meta-analysis found no association between SGLT2 inhibitors and risk of dyslipidemia (RR: 1.13; 95% CI: 0.91-1.40). However, SGLT2 inhibitors were significantly associated with increases in total cholesterol by 0.15 mmol/L, low-density lipoprotein cholesterol by 0.12 mmol/L, and high-density lipoprotein cholesterol by 0.07 mmol/L while they can significantly decrease triglycerides by -0.12 mmol/L compared to controls. CONCLUSIONS: SGLT2 inhibitors were not associated with increased risk of dyslipidemia. Further trials with longitudinal assessment are needed to assess the effect of SGLT2 inhibitors on trajectories of changes of lipid metabolism.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Dislipidemias/epidemiologia , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Dislipidemias/induzido quimicamente , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de RiscoRESUMO
A C3-symmetric benzotrithiophene tricarbaldehyde (BTT) is synthesized for the first time with a facile method, which is used to construct BTT-based covalent organic frameworks (COFs) with different pore sizes. Meanwhile, the structure transformations of the COFs under high-temperature ionothermal condition are studied systematically, and the relationships between the regularly changed structures of the further-cross-linked COFs and their supercapacitor performances are investigated. It turns out that dealing with COFs of designated structures under ionothermal condition is a great method to build highly conductive structure-controllable materials for electrochemical applications.
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AIM: To evaluate the diagnostic value of dynamic contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) in the differential diagnosis of hepatic angiomyolipoma (HAML) and hepatocellular carcinoma (HCC) and to clarify the relationship between histopathological features and CT or MRI imaging performances in HAML. MATERIAL AND METHODS: Six HAML and 33 non-cirrhotic HCC patients confirmed by histopathology were retrospectively analyzed. The serum biomarkers, CT and MRI examinations were conventionally performed before the confirmatory histological diagnosis. The clinical data from their medical records was also analyzed. RESULTS: Six HAML patients were annotated as two types according to CT and MRI imaging characteristics, including hypovascular type (n = 1) and hypervascular type (n = 5). The imaging performances of the 33 HCC patients were hypervascular type. Moreover, all the 5 hypervascular type HAML patients were misdiagnosed as HCC by CT or MRI. We also found that the hypervascular type of HAML patients contained more vessels and less fatty tissues in histopathology than hypovascular type of HAML patients. However, the clinical features included HCC high risk factors (hepatitis B or C), non-specific symptoms, male and increased serum alpha fetoprotein (AFP) were more common in HCC patients than HAML patients (P < 0.05, respectively). CONCLUSIONS: The CT or MRI imaging performances of HAML patients containing more vessels and less fatty tissues in histopathology resemble the imaging performance of HCC patients. These clinical features may be of great help in the differential diagnosis in the current clinical practices.
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Angiomiolipoma/diagnóstico por imagem , Angiomiolipoma/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Adulto , Idoso , Angiomiolipoma/química , Biomarcadores Tumorais/análise , Biópsia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Meios de Contraste/administração & dosagem , Diagnóstico Diferencial , Erros de Diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/química , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de RiscoRESUMO
In our study, three series of hydroxamate, 2-aminobenzamide, and trifluoromethyl ketone analogues have been designed and synthesized. The synthesized compounds were investigated for their in vitro antiproliferative activities using the MTT-based assay against three human cancer cell lines including A549, NCI-H661, and U937. Most analogues exhibited higher antiproliferative activities against human acute myeloid leukemia cell U937 than the other two human lung cancer cell lines. Furthermore, the compounds were examined against HDAC1, 2, and 8 isoforms. Docking study of compounds 6h, 9b, and 10a suggested that they might bind tightly to the binding pocket of HDAC2 and/or HDAC8. The results suggest that these compounds might have potential as lead compounds for the development of anti-tumor drugs with HDACs inhibitory activities.
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Antineoplásicos/síntese química , Histona Desacetilase 1/antagonistas & inibidores , Histona Desacetilase 2/antagonistas & inibidores , Inibidores de Histona Desacetilases/síntese química , Ácidos Hidroxâmicos/química , Oxidiazóis/síntese química , Proteínas Repressoras/antagonistas & inibidores , Antineoplásicos/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Descoberta de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Histona Desacetilase 1/metabolismo , Histona Desacetilase 2/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Humanos , Ácidos Hidroxâmicos/farmacologia , Concentração Inibidora 50 , Cetonas/química , Simulação de Acoplamento Molecular , Oxidiazóis/farmacologia , Ligação Proteica , Proteínas Repressoras/metabolismo , Relação Estrutura-Atividade , Vorinostat , ortoaminobenzoatos/químicaRESUMO
The tandem Michael addition/decarboxylation of (thio)coumarin-3-carboxylic acids with indoles has been developed and the biologically important indole-3-substituted dihydrocoumarins were obtained in good to excellent yields under catalyst-free conditions.
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Cumarínicos/síntese química , Indóis/química , Indóis/síntese química , Compostos de Sulfidrila/química , Catálise , Cumarínicos/química , Descarboxilação , Estrutura MolecularRESUMO
OBJECTIVE: Previous studies have shown that immune checkpoint inhibitors can improve the survival of patients with advanced non-small cell lung cancer with KRAS mutations; however, there is a lack of comparisons between treatment regimens associated with immune checkpoint inhibitors, and our study aims to compare several treatment parties to find a more effective treatment regimen. METHOD: A comprehensive literature search was conducted across multiple databases, namely PubMed, Web of Science, Embase, and Cochrane Library, to identify relevant studies. The screened studies were thoroughly examined, and data were collected to establish a Bayesian framework. The study focused on two primary endpoints: overall survival (OS) and progression-free survival (PFS). Data analysis and graphical plotting using R software and Revman (version 5.3). It is worth mentioning that the study protocol was registered with the International Prospective Registry for Systematic Reviews, ensuring transparency and adherence to predetermined protocols (CRD42022379595). RESULT: In total, our analysis included six RCTs involving 469 patients with KRAS mutations. Among these patients, 224 received chemotherapy, while 245 were treated with immune checkpoint inhibitors. Meta-analysis results showed that the addition of ICIs could significantly improve OS and PFS (0.69, 95% CI 0.55, 0.86; 0.57, 95% CI 0.42, 0.77). The results of the network meta-analysis showed that Pembrolizumab could improve OS (HR 0.42, 95% CI 0.22-0.80) and Pembrolizumab emerged as the most effective treatment option for enhancing OS in patients (SUCRA 65.03%). Additionally, pembrolizumab in combination with chemotherapy showed improvement in PFS (HR 0.47, 95% CI 0.29-0.76). CONCLUSION: Our analysis found that among advanced NSCLC patients with KRAS gene mutations, first-line treatment with pembrolizumab alone demonstrated greater efficacy. Similarly, second-line treatment with nivolumab alone was found to be more effective in this patient population. However, the sample size of this study was limited, Therefore, additional clinical data is necessary to validate this finding in subsequent research.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/genética , Metanálise em Rede , Teorema de Bayes , Revisões Sistemáticas como Assunto , MutaçãoRESUMO
In this study, we employed the principle of Relative Mode Transfer Method (RMTM) to establish a model for a single pendulum subjected to sudden changes in its length. An experimental platform for image processing was constructed to accurately track the position of a moving ball, enabling experimental verification of the pendulum's motion under specific operating conditions. The experimental data demonstrated excellent agreement with simulated numerical results, validating the effectiveness of the proposed methodology. Furthermore, we performed simulations of a double obstacle pendulum system, investigating the effects of different parameters, including obstacle pin positions, quantities, and initial release angles, on the pendulum's motion through numerical simulations. This research provides novel insights into addressing the challenges associated with abrupt and continuous changes in pendulum length.
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Processamento de Imagem Assistida por Computador , Modalidades de Fisioterapia , Movimento (Física)RESUMO
A novel impregnation-deposition method was applied to prepare presulfided MoS2/Al2O3 catalysts with large surface areas for the application of hydrodesulfurization (HDS). The synthesized catalysts were characterized systematically, and their catalytic performances were evaluated by the HDS of dibenzothiophene (DBT). It is found that the impregnation-deposition method improves the surface area of the synthesized catalysts by eliminating the micropores of the alumina support and adding mesostructured MoS2 particles within the support. Moreover, this method enhances the reducibility of the sulfided Mo species, as characterized by temperature-programed reduction (TPR) and X-ray photoelectron spectroscopy. Compared to the impregnation method, the impregnation-deposition method leads to the formation of more active sites as proved by TPR and CO-Fourier-transform infrared analyses. Hence, the reaction conversion rates and the hydrogenation/direct-desulfurization ratios of the DBT on the catalysts synthesized by the impregnation-deposition method are 1.3 times and 1.5 times as high as those of the catalysts made by the conventional impregnation method, respectively.
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Polyetheretherketone (PEEK) is a high-performance thermoplastic polymer with an elastic modulus close to that of the jawbone. PEEK has the potential to become a new dental implant material for special patients due to its radiolucency, chemical stability, color similarity to teeth, and low allergy rate. However, the aromatic main chain and lack of surface charge and chemical functional groups make PEEK hydrophobic and biologically inert, which hinders subsequent protein adsorption and osteoblast adhesion and differentiation. This will be detrimental to the deposition and mineralization of apatite on the surface of PEEK and limit its clinical application. Researchers have explored different modification methods to effectively improve the biomechanical, antibacterial, immunomodulatory, angiogenic, antioxidative, osteogenic and anti-osteoclastogenic, and soft tissue adhesion properties. This review comprehensively summarizes the latest research progress in material property advantages, three-dimensional printing synthesis, and functional modification of PEEK in the fields of implant dentistry and provides solutions for existing difficulties. We confirm the broad prospects of PEEK as a dental implant material to promote the clinical conversion of PEEK-based dental implants.
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BACKGROUND: Emerging studies indicate the critical involvement of microorganisms, such as Epstein-Barr virus (EBV), in the pathogenesis of inflammatory bowel disease (IBD). Immunosuppressive therapies for IBD can reactivate latent EBV, complicating the clinical course of IBD. Moreover, the clinical significance of EBV expression in B lymphocytes derived from IBD patients' intestinal tissues has not been explored in detail. AIM: To explore the clinical significance of latent EBV infection in IBD patients. METHODS: Latent EBV infection was determined by double staining for EBV encoded RNA and CD20 in colon specimens of 43 IBD patients who underwent bowel resection. Based on the staining results, the patients were divided into two groups, according to their latent EBV infection states - negative (n = 33) and positive (n = 10). Illness severity of IBD were assigned according to Crohn's disease activity index (ulcerative colitis) and Mayo staging system (Crohn's disease). The clinic-pathological data were analyzed between the two different latent EBV groups and also between the mild-to-moderate and severe disease groups. RESULTS: Systolic pressure (P = 0.005), variety of disease (P = 0.005), the severity of illness (P = 0.002), and pre-op corticosteroids (P = 0.025) were significantly different between the EBV-negative and EBV-positive groups. Systolic pressure (P = 0.001), variety of disease (P = 0.000), pre-op corticosteroids (P = 0.011) and EBV infection (P = 0.003) were significantly different between the mild-to-moderate and severe disease groups. CONCLUSION: IBD patients with latent EBV infection may manifest more severe illnesses. It is suggested that the role of EBV in IBD development should be further investigated, latent EBV infection in patients with serious IBD should be closely monitored, and therapeutic course should be optimized.
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Mediastinal masses are uncommon and difficult to diagnose. Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is a minimally invasive technique for diagnosis of mediastinal lesions with few complications. Our report described a mediastinal bronchogenic cyst with soft tissue density infected by Streptococcus pyogenes (S. pyogenes) after EUS-FNA, accompanied by respiratory cardiac arrest and superior vena cava syndrome. The patient underwent cardiopulmonary resuscitation to gain the chance for emergency surgery and recovered. Clinicians should be aware that mediastinal mass with soft tissue density shown on imaging may be mediastinal cyst containing high density mucin, FNA should be avoided if cystic masses cannot be ruled out.
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OBJECTIVE: To evaluate whether the efficacy of Getong Tongluo Capsule (, GTC, consisted of total flavone of Radix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract of Ginkgo biloba (EGB) for patients with convalescent-phase ischemic stroke and primary hypertension. METHODS: This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed. RESULTS: The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P<0.05), and no statistical significance was found between the GTC and EGB groups (P>0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P<0.01). There were no statistically significant differences in the incidences of AEs, adverse drug reactions, or serious AEs among the 3 groups (P>0.05). CONCLUSION: GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667).
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Isquemia Encefálica , Medicamentos de Ervas Chinesas/uso terapêutico , Hipertensão , AVC Isquêmico , Isquemia Encefálica/tratamento farmacológico , Cápsulas , Método Duplo-Cego , Humanos , Hipertensão/tratamento farmacológico , Qualidade de Vida , Resultado do TratamentoRESUMO
Purpose: This study aimed to determine whether detecting elastic fibers in tumor stroma (EFTS) could be used as a new method for predicting the prognosis of gastric cancer (GC) patients. Materials and Methods: EFTS expression was determined by histochemistry in 160 GC patients who underwent gastrectomy. Based on the staining results, the patients were divided into three groups according to their EFTS expression level: low (n = 57), moderate (n = 50), and high (n = 53). The clinicopathological data and 6-year survival data were analyzed among different EFTS groups. Results: The expression of EFTS was closely related to lymphovascular invasion (P = 0.010), blood transfusion in operation (P < 0.001), recurrence rate (P < 0.001), and motility (P < 0.001). High expression of EFTS was also correlated with recurrence-free survival (RFS) and overall survival (OS) in GC patients by Kaplan-Meier curve (P < 0.001 for RFS and P < 0.001 for OS). Conclusions: Multivariate analysis showed that EFTS was an independent prognostic factor for RFS and OS. In conclusion, detecting EFTS to predict the prognosis of GC patients is effective and highly feasible.
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Quantitative structure-activity relationship (QSAR) studies have been carried out on 4-anilino-3-quinolinecarbonitriles, a set of novel Src kinase inhibitors, with the aim of dissecting the structural requirements for Src inhibitory activities. After outlier identification using robust principal component analysis (robust PCA), linear models based on forward selection combined with multiple linear regression, (FS-MLR), enhanced replacement method followed by multiple linear regression (ERM) and a nonlinear model using support vector regression (SVR) were constructed and compared. All models were rigorously validated using leave-one-out cross-validation (LOOCV), 5-fold cross-validations (5-CV) and shuffling external validation (SEVs). ERM seems to outperform both FS-MLR and SVR evidenced by better prediction performance (n = 35, R(2)(training) = 0.918, R(2)(pred) = 0.928). Robustness and predictive ability of ERM model were also evaluated. The generated QASR model revealed that the Src inhibitory activity of 4-anilino-3-quinolinecarbonitriles could be associated with the size of substituents in the C7 position and the steric hindrance effect. The results of the present study may be of great help in designing novel 4-anilino-3-quinolinecarbonitriles with more potent Src kinase inhibitory activity.