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Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from 13C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.
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Objective:To systematically evaluate the quality of continuing care services carried out by nursing staff in China, comprehensively integrate the influencing factors of continuing care services, and provide guidance for promoting the development of continuing care in China.Methods:PubMed, EMbase, Web of Science, the Cochrane Library, CMB, SinoMed, CINAHL, CNKI, Wanfang Data and VIP related qualitative studies were searched from the database establishment to March 2022. The NoteExpress software was used to screen and analyze the literature, the 2017 Australian JBI Evidence-based Health Care Center quality research quality evaluation standard was used to conduct qualitative evaluation of the literature, and the Meta-integration method was adopted to carry out pooled integration. The ConQual approach was used to evaluate the quality of the integrated results.Results:A total of 39 results were extracted from 11 studies. Eleven new categories were summarized and four integrated results were obtained, which were: nurses lack relevant cognitive, motivational and behavioral skills; patients have poor compliance and low trust in medical prescriptions; lack of team management, method guidance and system standards; lack of connection sharing, input supply and upper protection. The total evidential quality of the integration results was intermediate.Conclusions:At present, nurses should strengthen their own ability, pay attention to patient education, enhance the sense of trust between doctors and patients. Managers should pay attention to team building, standardize the service standards and systems. The state should increase input, improve social policy support and legal protection; for the orderly development of continuity of care services escort.
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Background@#and Purpose Intracranial vertebrobasilar atherosclerotic stenosis (IVBAS) is a major cause of posterior circulation stroke. Some patients suffer from stroke recurrence despite receiving medical treatment. This study aimed to determine the prognostic value of a new score for the posterior communicating artery and the P1 segment of the posterior cerebral artery (PCoA-P1) for predicting stroke recurrence in IVBAS. @*Methods@#We retrospectively enrolled patients with severe IVBAS (70%–99%). According to the number of stroke recurrences, patients were divided into no-recurrence, single-recurrence, and multiple-recurrences groups. We developed a new 5-point grading scale, with the PCoA-P1 score ranging from 0 to 4 based on magnetic resonance angiography, in which primary collaterals were dichotomized into good (2–4 points) and poor (0 or 1 point). Stroke recurrences after the index stroke were recorded. Patients who did not experience stroke recurrence were compared with those who experienced single or multiple stroke recurrences. @*Results@#From January 2012 to December 2019, 176 patients were enrolled, of which 116 (65.9%) had no stroke recurrence, 35 (19.9%) had a single stroke recurrence, and 25 (14.2%) had multiple stroke recurrences. Patients with single stroke recurrence (odds ratio [OR]= 4.134, 95% confidence interval [CI]=1.822–9.380, p=0.001) and multiple stroke recurrences (OR=6.894, 95% CI=2.489–19.092, p<0.001) were more likely to have poor primary collaterals than those with no stroke recurrence. @*Conclusions@#The new PCoA-P1 score appears to provide improve predictions of stroke recurrence in patients with IVBAS.
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Fibroblast growth factor receptors (FGFRs) have emerged as promising targets for anticancer therapy. In this study, we synthesized and evaluated the biological activity of 66 pyrazolo[3,4-
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Objective To explore the relationship between the features of thyroid carcinoma and its metas tasis to cervical lymph nodes(MCLN) with conventional and contrast-enhanced ultrasound imaging.Methods Totally 89 thyroid carcinoma nodules were used in this study.The pathology of those samples was confirmed by surgical pathology at the First Affiliated Hospital of Shanxi Medical University from Sep 1,2014 to Oct 30,2015.The samples were divided into two groups based on the surgical pathology report:the group with MCLN (49) and the group without MCLN (40).Using the pathology report as gold standard,we analyzed the conventional ultra sound features,contrast-enhanced ultrasound enhancement pattern as well as the quantitative parameters.Results ① There was statistically significant difference in tumor size,contact of the tumor with capsule or not,microcalcification of the tumor,as well as echo texture of the thyroid carcinoma nodules between the groups (P＜0.05).②) There was statistically significant difference in peak intensity (PI) between the two groups (P＜0.05).Conclusion There is a positive correlation between cervical lymph nodes metastasis and tumor size,with or without contact with fibrous capsule,with or without microcalcification,the internal echo as well as PI.
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Objective To investigate the impact of secreted frizzled-related protein 1 (SFRP 1) gene polymorphisms and gene-smoking interactions on the risk of large artery atherosclerotic (LAA) stroke.Methods Two hundred and sixty-four patients diagnosed with LAA stroke and 228 healthy controls were enrolled from the Department of Neurology,Affiliated Hospital of Qingdao University from August 2016 to June 2017.The methods of polymerase chain reaction-restriction fragment length polymorphism,combined with DNA sequencing,were used to detect the three single nucleotide polymorphisms (SNPs:rs7832767,rs1127379,rs3242) in the SFRP 1 gene.Logistic regression was applied to analyze associations between SNPs and LAA stroke.Cross analysis of additive model was used to evaluate gene-smoking interactions.Results The genotype TT/CT and allele T of rs7832767 in case group were in higher frequency than that in controls (54.9％ (145/264) vs 37.7％ (86/228),OR =2.123,95％ CI 1.482-3.041,P ＜0.01;33.9％ (179/528) vs 20.0％ (91/456),OR=2.057,95％ CI 1.536-2.755,P＜ 0.01).However,the frequencies of genotypes and alleles in other SNPs (rs1127379,rs3242) showed no significant differences between cases and controls.Multivariate Logistic regression analysis showed that TT/CT genotype was a risk factor for LAA stroke (OR =1.649,95％ CI 1.066-2.550.P =0.025).Moreover.SFRP 1 gene was not related to the distribution of cerebralvascular stenosis in LAA stroke patients.Additive model analysis showed significant interactions between rs7832767 and smoking (relative excess risk of interaction =2.442,95％ CI 0.281-4.603).Smokers with T allele of rs7832767 showed significantly increased risk of LAA stroke (OR =3.252,95％ CI 1.629-6.491,P =0.001).Whereas,no significant interaction was detected between rs3242 or rs1127379 and smoking.Conclusion The T allele of rs7832767 within SFRP 1 gene may be a risk factor of LAA stroke,and the interactions between rs7832767 and smoking can significantly increase the risk of LAA stroke.
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Objective To investigate the influence of size and depth of thyroid carcinoma for diagnostic accuracy of ultrasound-guided fine-needle aspiration (US-FNA).Methods A retrospective review of clinical and preoperative US-FNA data of 87 malignant thyroid nodules confirmed by surgical pathology from 87 patients was performed.According to the the Bethesda System for Reporting Thyroid Cytopathology (BSTC),the grade that higher than grade Ⅳ was the cytologic criteria for diagnosis of thyroid carcinoma.According to the cytopathological data of thyroid carcinoma confirmed by surgical pathology,the patients were divided into group A (cytopathological data was same as the surgical pathology result) and group B (cytopathological data was not same as the surgical pathology result).The longest diameter of malignant thyroid nodules and the distance from the shallow of thyroid nodules to superficial capsule of thyroid gland were analyzed.The ROC analysis was performed to find the optimal cut-off value of the longest diameter of thyroid carcinoma and the distance from the shallow of thyroid carcinoma to superficial capsule of thyroid gland.Results The consistent rate between US-FNA and surgical pathologic results was 79.31 ％ (69/87).The longest diameter of thyroid carcinoma of group A and group B was (1.63±0.58)cm and (1.01±0.42)cm respectively,which was statistically different (P＜0.01).The distance from the shallow of thyroid carcinoma to superficial capsule of thyroid gland of group A and group B was (4.15±1.83) mm and (7.86±2.08)mm respectively,which was statistically different (P＜0.01).According to the ROC analysis results,the optimal cut-off value of the longest diameter of thyroid carcinoma and the distance from the shallow of thyroid carcinoma to superficial capsule of thyroid gland was 1.05 cm and 6.1 mm respectively.Conclusion Diagnosis accuracy of US-FNA could be influenced by size and depth of thyroid carcinoma.
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Objective To investigate the accuracy of functional magnetic resonance imaging(fMRI) and contrast-enhanced ultrasound on evaluation of the breast cancer patients after neoadjuvant chemotherapy.Methods Forty-eight patients with breast cancer who were confirmed by biopsy,undergoing 4 cycles weekly dose-concentrated programs (wPC) neoadjuvant chemotherapy,evaluated the efficacy by fMRI and contrastenhanced ultrasound.Results In pathology,complete remission was 12 cases (25.0％,12/48),non remission was 13 cases (27.1％,13/48).In contrast-enhanced ultrasound,complete remission was 20 cases (41.7％,20/48),non remission was 10 cases (20.8％,10/48).In fMRI,complete remission was 17 cases (35.4％,17/48),non remission was 11 cases (22.9％,11/48).The P values more than 0.05 showed no statistically significant among three methods,the Kappa test showed that fMRI were superior to contrastenhanced ultrasound on evaluating the efficacy of neoadjuvant chemotherapy.Conclusions fMRI and contrast-enhanced ultrasound can be used in evaluating the efficacy of neoadjuvant chemotherapy,however,the data shows fMRI is superior to contrast-enhanced ultrasound.Contrast-enhanced ultrasound must be as the supplementary method.
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Objective To investigate cyclic mechanical stimulation on expression of connective tissue growth factor (CTGF) in osteoblast-like cells (MG63) and to explore the rote of MAPK involved in the process.Methods Expressions of CTGF protein and mRNA in MG63 cells were detected by Western blot and RT-PCR,respectively. Phosphorylation levels of p38, ERK, JNK were examined by Western blot. Results Cyclic mechanical stimulation upregulated expressions of CTGF protein and mRNA. The levels reached a maximal response of 2-3 fold after 3-6 h. ERK and JNK signal pathways were activated by cyclic mechanical stimulation, the phosphorylated proteins increased within 10 min of stretch, phosphorylated ERK reached maximal levels by 60 min of stretch, phosphorylated JNK reached maximal levels by 15-30 min of stretch, but not for p38 signal pathway.Only the inhibitior of JNK signal pathway (SP600125) markedly suppressed stretch-induced CTGF expression,meanwhile the inhibitors of ERK (PD98059) and p38 (SB203580) did not show such effect. Conclusion Cyclic mechanical stimulation upregulates CTGF expression via JNK-dependent pathway in MG63 cells.