Two new polyprenylated acylphloroglucinols, (1S,32R,5S,6R,7R)-6-((R)-3,4-di-hydroxy-4-methylpentyl)-2-(2-hydroxypropan-2-yl)-7-isobutyryl-6-methyl-5,9-bis(3-methylbut-2-en-1-yl)-4,5,6,7-tetrahydro-2H-32,7-methanocycloocta[b]furan-8,10(3H)-dione (1) and (4R,5R,7R)-4-((R)-3,4-dihydroxy-4-methylpentyl)-2,2,4-trimethyl-5,7-bis(3-methyl-but-2-en-1-yl)-7-(5-methylhex-4-enoyl)-4,5,6,7-tetrahydrobenzofuran-3(2H)-one (2) were isolated from Hypericum scabrum. The structures were elucidated by means of spectroscopic methods, including MS, IR, NMR, OR, and CD. 相似文献
PURPOSEWe aimed to explore the diagnostic efficiency of shear-wave elastography (SWE) ultrasomics in the preoperative prediction of lymph node (LN) metastasis in rectal cancer.METHODSThis study included 87 patients with pathologically confirmed rectal cancer, with data gathered from August 2017 to August 2018. A total of 1044 ultrasomics features of rectal tumor were collected with AK software from the SWE examinations. The least absolute shrinkage and selection operator (LASSO) regression model was used for feature selection and building a SWE ultrasomics signature. The diagnostic performance was evaluated with an area under the receiver operating characteristic curve (AUC) analysis. Then, the diagnostic performance of the SWE ultrasomics signature was compared with magnetic resonance imaging (MRI).RESULTSOf the 87 patients, 40 (46.0%) had LN metastasis. Thirteen ultrasomics features of rectal tumor were selected as the most significant features. The SWE ultrasomics signature correlated with LN metastasis (p < 0.001). Patients with LN metastasis had higher signature than patients without LN metastasis. In terms of diagnostic performance, SWE ultrasomics signature was significantly superior to MRI (AUC, 0.883 vs. 0.760, p = 0.034). The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of SWE ultrasomics signature were 82.8%, 87.5%, 78.8%, 77.8%, and 88.1%, respectively, while those of MRI were 75.9%, 77.5%, 74.5%, 72.1%, and 79.6%, respectively.CONCLUSIONSWE ultrasomics is a more accurate predictive method for identifying LN metastasis preoperatively than MRI. Thus, SWE ultrasomics might be used to better guide preoperative individual therapies for patients with rectal cancer.Colorectal cancer is the third most common cancer and the fourth frequent cause of cancer death worldwide; approximately one-third of these tumors is rectal cancer (1). Accurate identification of lymph node (LN) involvement is important in determining whether rectal cancer patients require preoperative neoadjuvant therapy (2, 3). Therefore, accurate prediction of LN metastasis can provide valuable information and is crucial for treatment decisions and prognosis (4).According to ESGAR guidelines (European Society of Gastrointestinal and Abdominal Radiology) 2016 recommendations, magnetic resonance imaging (MRI) is considered the gold standard for rectal cancer staging (3, 5–7). However, MRI is not perfect for determination of LNs status, and the criteria used to indicate LN metastasis may vary in different institutions (8). A meta-analysis found MRI to be 77% sensitive (95% CI, 69%–84%) and 71% specific (95% CI, 59%–81%) for detection of LN involvement (9). In addition, endoscopic ultrasonography (EUS) is also a widely used method for patients with rectal cancer, but the accuracy of EUS to identify LN involvement is inferior to that of both computed tomography (CT) and MRI because of a lack of visualization of the entire mesorectum and the difficulty in accurately distinguishing benign from malignant nodes based only on the shape, echo feature and size criterion (10–13). Given these limitations, neither MRI nor EUS is an ideal method for diagnosing LN status in rectal cancer.Radiomics, extracted from CT, MRI, or positron emission tomography images, uses a set of quantitative features to describe the geometrical structure, intensity distribution and texture of a region of interest (ROI). These features include shape, edge, and texture metrics, which can provide important insights into the tumor phenotype and the interaction of the tumor with its microenvironment (14, 15). Similarly, we have applied the concept to computing quantitative ultrasound imaging, a term defined as “ultrasomics” (16). Shear-wave elastography (SWE), an ultrasound elastography technique that provides a real-time two-dimensional (2D) quantifiable image of tissue stiffness (17), has emerged as an efficient tool in detection of malignancies. The report of Wang et al. (18) confirmed that the deep learning of elastography showed a better prediction of liver fibrosis staging compared with transient elastography, 2D-SWE, and serological examinations. Therefore, SWE-based ultrasomics has a promising future in staging and prediction.To our knowledge, there has been no study that combines SWE and ultrasomics to predict the LN metastasis. In order to build a robust model, we hypothesized that SWE ultrasomics could be a better option in LN status prediction of colorectal cancer patients. Therefore, the purpose of this study was to evaluate the accuracy of LN metastasis identification before surgical resection using SWE ultrasomics of primary tumor and compare it with MRI. 相似文献
Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic-target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high-throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPs that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. 相似文献
Hormetic response is an adaptive mechanism for a cell or organism surviving in an unfavorable environment. It has been an intriguing subject of researches covering a broad range of biological and medical disciplines, in which the underlying significance and molecular mechanisms are under intensive investigation. In the present study, we demonstrated that topoisomerase I inhibitor camptothecin (CPT), a potent anticancer agent, induced an obvious hormetic response in rat pheochromocytoma PC12 cells. Camptothecin inhibited PC12 cell growth at relative high doses as generally acknowledged while stimulated the cell growth by as much as 39% at low doses. Moreover, low doses of CPT protected the cells from hydrogen peroxide (H2O2)-induced cell death. Phosphoinositide 3-kinase (PI3K)/Akt and nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathways were reported playing pivotal roles in protecting cells from oxidative stress. We observed that these 2 pathways were upregulated by low doses of CPT, as evidenced by increased levels of phosphorylated PI3K, phosphorylated Akt, phosphorylated mammalian target of rapamycin, Nrf2, and HO-1; and abolishment of the growth-promoting and neuroprotective effects of CPT by {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002, a PI3K inhibitor. These results suggest that the hormetic and neuroprotective effects of CPT at low doses on PC12 cells were attributable, at least partially, to upregulated PI3K/Akt and Nrf2/HO-1 pathways. 相似文献
Patients with schizophrenia have high rates of comorbid physical illness, but there has been less attention to dental diseases in these patients. This meta-analysis of case-control studies systematically examined the oral health in patients with schizophrenia. Case-control studies comparing the oral health in patients with schizophrenia and healthy controls were screened and identified. Standardized mean difference (SMD) with its 95% confidence interval (CI) was calculated using RevMan version 5.3. Three case-control studies comprising 306 patients with schizophrenia and 306 healthy controls were included in this meta-analysis. All studies were rated as “high quality”. Patients with schizophrenia had significantly higher scores of decayed, missing and filled teeth (SMD?=?0.83, 95%CI: 0.57, 1.09, p?<?0.001; I2 =?51%), missing teeth (SMD?=?0.79, 95%CI: 0.59, 0.98, p?<?0.001; I2 =?19%), and decayed teeth (SMD?=?0.89, 95%CI: 0.24, 1.54, p?=?0.008; I2 =?92%) when compared to healthy controls. Similarly, patients with schizophrenia had significantly lower filled teeth scores (SMD?=?-0.76, 95%CI: ?1.44, ?0.09, p?=?0.03; I2 =?93%) when compared to healthy controls. This meta-analysis found that patients with schizophrenia were likely to have worse oral health when compared to healthy controls.
AIM: To compare the safety and efficacy of conbercept intravitreal injection and half-dose photodynamic therapy (PDT) in treating chronic central serous chorioretinopathy (CSC).
METHODS: This study was retrospective. Thirty-seven patients (37 eyes) with chronic CSC received conbercept injections while 57 patients (57 eyes) were treated with half-dose PDT. All subjects were followed in 6mo. Outcome measures included change in best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and resolution of subretinal fluid (SRF).
RESULTS: There was no adverse event observed in either treatment group. At the 6-month follow-up, 26 eyes (70.3%) in the conbercept group and 54 eyes (94.7%) in the half-dose PDT group (P<0.05) reached full resolution of SRF. The mean logarithm of the minimum angle of resolution (logMAR) BCVA significantly improved (P<0.001) in both treatment groups with better outcome at early phase in the half-dose PDT group (2wk, 1, and 2mo, P<0.05). All subjects experienced significant CMT improvement (P<0.001) with no statistical difference between the two groups (P>0.05). The SFCT also improved in all subjects (P<0.001) with better outcome in the half-dose PDT group (P<0.05).
CONCLUSION: Both intravitreal conbercept and half-dose PDT are safe to use in treating chronic CSC. By 6mo, both treatment groups are efficacious in improving BCVA, reducing CMT and SFCT, and resolving SRF in eyes with chronic CSC. Half-dose PDT may show better outcome at initial phase of treatment in chronic CSC. Longer follow-up period is necessary to study for long-term effect and safety. 相似文献
To develop a machine learning–based ultrasound (US) radiomics model for predicting tumour deposits (TDs) preoperatively. From December 2015 to December 2017, 127 patients with rectal cancer were prospectively enrolled and divided into training and validation sets. Endorectal ultrasound (ERUS) and shear-wave elastography (SWE) examinations were conducted for each patient. A total of 4176 US radiomics features were extracted for each patient. After the reduction and selection of US radiomics features , a predictive model using an artificial neural network (ANN) was constructed in the training set. Furthermore, two models (one incorporating clinical information and one based on MRI radiomics) were developed. These models were validated by assessing their diagnostic performance and comparing the areas under the curve (AUCs) in the validation set. The training and validation sets included 29 (33.3%) and 11 (27.5%) patients with TDs, respectively. A US radiomics ANN model was constructed. The model for predicting TDs showed an accuracy of 75.0% in the validation cohort. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and AUC were 72.7%, 75.9%, 53.3%, 88.0% and 0.743, respectively. For the model incorporating clinical information, the AUC improved to 0.795. Although the AUC of the US radiomics model was improved compared with that of the MRI radiomics model (0.916 vs. 0.872) in the 90 patients with both ultrasound and MRI data (which included both the training and validation sets), the difference was nonsignificant (p = 0.384). US radiomics may be a potential model to accurately predict TDs before therapy. • We prospectively developed an artificial neural network model for predicting tumour deposits based on US radiomics that had an accuracy of 75.0%. • The area under the curve of the US radiomics model was improved than that of the MRI radiomics model (0.916 vs. 0.872), but the difference was not significant (p = 0.384). • The US radiomics–based model may potentially predict TDs accurately before therapy, but this model needs further validation with larger samples. 相似文献