Background
In pancreatic cancer, methods to predict early recurrence (ER) and identify patients at increased risk of relapse are urgently required.
Purpose
To develop a radiomic nomogram based on MR ...radiomics to stratify patients preoperatively and potentially improve clinical practice.
Study Type
Retrospective.
Population
We enrolled 303 patients from two medical centers. Patients with a disease‐free survival ≤12 months were assigned as the ER group (n = 130). Patients from the first medical center were divided into a training cohort (n = 123) and an internal validation cohort (n = 54). Patients from the second medical center were used as the external independent validation cohort (n = 126).
Field Strength/Sequence
3.0T axial T1‐weighted (T1‐w), T2‐weighted (T2‐w), contrast‐enhanced T1‐weighted (CET1‐w).
Assessment
ER was confirmed via imaging studies as MRI or CT. Risk factors, including clinical stage, CA19‐9, and radiomic‐related features of ER were assessed. In addition, to determine the intra‐ and interobserver reproducibility of radiomic features extraction, the intra‐ and interclass correlation coefficients (ICC) were calculated.
Statistical Tests
The area under the receiver‐operator characteristic (ROC) curve (AUC) was used to evaluate the predictive accuracy of the radiomic signature in both the training and test groups. The results of decision curve analysis (DCA) indicated that the radiomic nomogram achieved the most net benefit.
Results
The AUC values of ER evaluation for the radiomics signature were 0.80 (training cohort), 0.81 (internal validation cohort), and 0.78 (external validation cohort). Multivariate logistic analysis identified the radiomic signature, CA19‐9 level, and clinical stage as independent parameters of ER. A radiomic nomogram was then developed incorporating the CA19‐9 level and clinical stage. The AUC values for ER risk evaluation using the radiomic nomogram were 0.87 (training cohort), 0.88 (internal validation cohort), and 0.85 (external validation cohort).
Data Conclusion
The radiomic nomogram can effectively evaluate ER risks in patients with resectable pancreatic cancer preoperatively, which could potentially improve treatment strategies and facilitate personalized therapy in pancreatic cancer.
Level of Evidence: 4
Technical Efficacy: Stage 4
J. Magn. Reson. Imaging 2020;52:231–245.
Elevated liver enzyme levels are observed in patients with coronavirus disease 2019 (COVID-19); however, these features have not been characterized.
Hospitalized patients with COVID-19 in Zhejiang ...Province, China, from January 17 to February 12, 2020, were enrolled. Liver enzyme level elevation was defined as alanine aminotransferase level >35 U/L for men and 25 U/L for women at admission. Patients with normal alanine aminotransferase levels were included in the control group. Reverse transcription polymerase chain reaction was used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and patients symptomatic with SARS-CoV-2 infection were defined as patients with COVID-19. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected and compared.
Of 788 patients with COVID-19, 222 (28.2%) patients had elevated liver enzyme levels (median interquartile range {IQR} age, 47.0 35.0-55.0 years; 40.5% women). Being male, overweight, and smoking increased the risk of liver enzyme level elevation. The liver enzyme level elevation group had lesser pharyngalgia and more diarrhea than the control group. The median time from illness onset to admission was 3 days for liver enzyme level elevation groups (IQR, 2-6), whereas the median hospitalization time for 86 (38.7%) discharged patients was 13 days (IQR, 11-16). No differences in disease severity and clinical outcomes were noted between the groups.
We found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission, which could partially be related to SARS-CoV-2 infection. Male patients had a higher risk of liver enzyme level elevation. With early medical intervention, liver enzyme level elevation did not worsen the outcomes of patients with COVID-19.
A novel bifunctional squaramide-catalyzed one-pot electrophilic trifluoromethylthiolation–sulfur–Michael/aldol cascade reaction for the construction of CF3S-containing ...spiro-cyclopentanone–thiochromanes was developed. This convenient, one-pot cascade reaction serves as a powerful tool for the enantioselective construction of potential bioactive spiro-cyclopentanone–thiochromanes, which have one quaternary stereocenter containing a CF3S group and three contiguous stereocenters including one spiro all-carbon quaternary center, in moderate to good yields with excellent stereoselectivities (up to 15:1 dr, >99% ee). The synthetic transformations of the resulting products were also be achieved.
Sorafenib (SOR) resistance remains a major obstacle in the effective treatment of hepatocellular carcinoma (HCC). A number of long noncoding RNAs (lncRNAs) are responsible for this chemoresistance. ...This study aimed to reveal the essential function of a recently defined lncRNA, lncRNA‐POIR, in the epithelial–mesenchymal transition (EMT) and SOR sensitivity of HCC cells. SOR‐induced cytotoxicity was analyzed via cell counting kit‐8 and ethynyl‐2'‐deoxyuridine incorporation assays, whereas immunoblotting and confocal immunofluorescence were used to determine the expression levels of EMT markers. Furthermore, loss‐ or gain‐of‐function approaches were used to demonstrate the role of lncRNA‐POIR/miR‐182‐5p on EMT and SOR sensitivity in HCC. The direct interaction between lncRNA‐POIR and miR‐182‐5p was verified using a luciferase reporter assay. We found that knockdown of lncRNA‐POIR sensitized HCC cells to SOR and simultaneously reversed EMT. As expected, miR‐182‐5p was confirmed as the downstream target of lncRNA‐POIR. Moreover, miR‐182‐5p overexpression clearly reversed EMT and promoted SOR‐induced cytotoxicity in representative HCC cells, whereas miR‐182‐5p downregulation played a contrasting role; miR‐182‐5p knockdown abolished the modulatory effects of lncRNA‐POIR siRNA on EMT and SOR sensitivity. Together, these pieces of data suggest that lncRNA‐POIR promotes EMT progression and suppresses SOR sensitivity simultaneously by sponging miR‐182‐5p. Thus, we proposed a compelling rationale for the use of lncRNA‐POIR as a promising predictor of SOR response and as a potential therapeutic target for HCC treatment in the future.
In this study, we verified the biological functions of lncRNA‐POIR as an aberrantly expressed lncRNA in hepatocellular carcinoma (HCC) cells. lncRNA‐POIR modulated EMT and sorafenib sensitivity of HCC cells via functioning as a competing endogenous RNA (ceRNA) of miR‐182‐5p. Our findings provide a compelling rationale for the use of lncRNA‐POIR as a predictor of SOR response and a promising therapeutic target for future HCC treatment.
Squaramide‐Catalyzed Asymmetric Reactions Zhao, Bo‐Liang; Li, Jun‐Hua; Du, Da‐Ming
Chemical record,
October 2017, 2017-10-00, 20171001, Letnik:
17, Številka:
10
Journal Article
Recenzirano
Bifunctional squaramides have emerged as powerful hydrogen‐bonding catalysts for promoting a wide array of useful asymmetric reactions, which provides convenient methods for the construction of ...complex molecular structures and chiral biologically active compounds. This review highlights the recent advances of our research group in the chiral squaramide‐catalyzed asymmetric reactions, including Michael addition, Mannich reaction, aza‐Henry reaction, Strecker reaction as well as cascade or sequential reactions.
Bifunctional squaramides have emerged as powerful hydrogen‐bonding catalysts for promoting a wide array of useful asymmetric reactions, which provides convenient methods for the construction of complex molecular structures and chiral biologically active compounds. This review highlights the recent advances of our research group in the chiral squaramide‐catalyzed asymmetric reactions, including Michael addition, Mannich reaction, aza‐Henry reaction, Strecker reaction as well as cascade or sequential reactions.
Gene expression patterns can be used as prognostic biomarkers in various types of cancers. We aimed to identify a gene expression pattern for individual distant metastatic risk assessment in patients ...with locoregionally advanced nasopharyngeal carcinoma.
In this multicentre, retrospective, cohort analysis, we included 937 patients with locoregionally advanced nasopharyngeal carcinoma from three Chinese hospitals: the Sun Yat-sen University Cancer Center (Guangzhou, China), the Affiliated Hospital of Guilin Medical University (Guilin, China), and the First People's Hospital of Foshan (Foshan, China). Using microarray analysis, we profiled mRNA gene expression between 24 paired locoregionally advanced nasopharyngeal carcinoma tumours from patients at Sun Yat-sen University Cancer Center with or without distant metastasis after radical treatment. Differentially expressed genes were examined using digital expression profiling in a training cohort (Guangzhou training cohort; n=410) to build a gene classifier using a penalised regression model. We validated the prognostic accuracy of this gene classifier in an internal validation cohort (Guangzhou internal validation cohort, n=204) and two external independent cohorts (Guilin cohort, n=165; Foshan cohort, n=158). The primary endpoint was distant metastasis-free survival. Secondary endpoints were disease-free survival and overall survival.
We identified 137 differentially expressed genes between metastatic and non-metastatic locoregionally advanced nasopharyngeal carcinoma tissues. A distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) that consisted of 13 genes was generated to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter distant metastasis-free survival (hazard ratio HR 4·93, 95% CI 2·99–8·16; p<0·0001), disease-free survival (HR 3·51, 2·43–5·07; p<0·0001), and overall survival (HR 3·22, 2·18–4·76; p<0·0001) than patients with low-risk scores. The prognostic accuracy of DMGN was validated in the internal and external cohorts. Furthermore, among patients with low-risk scores in the combined training and internal cohorts, concurrent chemotherapy improved distant metastasis-free survival compared with those patients who did not receive concurrent chemotherapy (HR 0·40, 95% CI 0·19–0·83; p=0·011), whereas patients with high-risk scores did not benefit from concurrent chemotherapy (HR 1·03, 0·71–1·50; p=0·876). This was also validated in the two external cohorts combined. We developed a nomogram based on the DMGN and other variables that predicted an individual's risk of distant metastasis, which was strengthened by adding Epstein–Barr virus DNA status.
The DMGN is a reliable prognostic tool for distant metastasis in patients with locoregionally advanced nasopharyngeal carcinoma and might be able to predict which patients benefit from concurrent chemotherapy. It has the potential to guide treatment decisions for patients at different risk of distant metastasis.
The National Natural Science Foundation of China, the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period, the Natural Science Foundation of Guang Dong Province, the National Key Research and Development Program of China, the Innovation Team Development Plan of the Ministry of Education, the Health & Medical Collaborative Innovation Project of Guangzhou City, China, and the Program of Introducing Talents of Discipline to Universities.
More and more studies have demonstrated that proteasomal degradation occurs in the development of various diseases, including ventricular remodeling, which is a cardiac pathological change and ...seriously makes patient outcomes worse. Our preliminary results showed that Guanxin V, an effective and safe complementary and alternative medicine for ventricular remodeling, reverses ventricular hypertrophy by transforming growth factor-beta 1 (TGF-β1), but the specific mechanism needs to be explored. The left anterior descending coronary artery was ligated to build a ventricular remodeling model. Cardiac function and histopathology were measured. Fibrosis-related indicators were detected. Moreover, cardiomyocytes were exposed to hydrogen peroxide to construct an in vitro model of ventricular remodeling. The stability of the Vimentin protein was assessed with cycloheximide and MG132. Endogenous and exogenous TGF-β1-Vimentin interactions were detected by co-immunoprecipitation. Guanxin V significantly eased heart function and improved fibrosis in ventricular remodeling. Mechanistically, Guanxin V promoted TGF-β1-mediated proteasomal degradation of Vimentin and reduced the TGF-β1-Vimentin interaction. Here, we reported a completely new mechanism, Guanxin V alleviates ventricular remodeling by promoting and targeting TGF-β1-mediated proteasomal degradation of Vimentin, which provides a new target for the management of ventricular remodeling and lays the foundation for the further clinical promotion of Guanxin V.
Sterol regulatory element-binding proteins (SREBPs) are major transcription factors activating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. In this ...study, we identified a small molecule, betulin, that specifically inhibited the maturation of SREBP by inducing interaction of SREBP cleavage activating protein (SCAP) and Insig. Inhibition of SREBP by betulin decreased the biosynthesis of cholesterol and fatty acid. In vivo, betulin ameliorated diet-induced obesity, decreased the lipid contents in serum and tissues, and increased insulin sensitivity. Furthermore, betulin reduced the size and improved the stability of atherosclerotic plaques. Our study demonstrates that inhibition SREBP pathway can be employed as a therapeutic strategy to treat metabolic diseases including type II diabetes and atherosclerosis. Betulin, which is abundant in birch bark, could be a leading compound for development of drugs for hyperlipidemia.
► The small molecule betulin inhibits SREBP pathway ► Betulin decreases the biosynthesis of cholesterol and fatty acid ► Betulin improves insulin sensitivity ► Betulin reduces atherosclerotic plaques
The present paper reports a highly stereoselective synthesis of spirooxindole-fused spiropyrazolones through the asymmetric 3 + 2 cyclization reaction of 2-(1-methyl-2-oxoindolin-3-yl)malononitriles ...with unsaturated pyrazolones under mild conditions. With only a 1 mol % bifunctional squaramide catalyst, a series of chiral dispirocyclic pyrazolone derivatives were attained in high yields (85–97%) with excellent stereoselectivities (up to >99% ee and in all cases >20:1 dr). Moreover, gram-scale synthesis and further transformation of the products were also demonstrated.
PDF
