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1.
Quant Imaging Med Surg ; 13(9): 5759-5769, 2023 Sep 01.
Article En | MEDLINE | ID: mdl-37711834

Background: To evaluate the diagnostic value of computed tomography (CT) attenuation in mediastinal lymph node metastases of malignant tumors. Methods: A retrospective review was conducted of a Chinese institutional database of consecutive patients with a history of malignant tumors. Those who had enlarged, necrotic, or hypermetabolic lymph nodes detected in the mediastinum during routine CT examination or positron emission tomography (PET)/CT imaging from January 2019 to December 2021 were collected for investigation. All patients underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and were followed up for at least 6 months to diagnose lymph node metastases. One-to-one correlation was attempted between the CT images of the lymph nodes and EBUS-TBNA area of the same lymph node groups and similar size. Radiologists measured size, as well as plain CT and contrast-enhanced CT (CECT) attenuation values of mediastinal lymph nodes, and evaluated the effectiveness of these variables in diagnosing lymph node metastasis. Results: A total of 135 lymph nodes of 114 patients were included in the study. In the univariate analysis, the long-axis diameter, short-axis diameter, short-axis/long-axis ratio, and plain CT attenuation values of lymph nodes were found to be statistically significantly different between the metastatic and non-metastatic lymph nodes. The areas under receiver operator characteristic (ROC) curves (AUCs) of long-axis diameter, short-axis diameter, short-axis/long-axis ratio, and plain CT attenuation value for diagnosing metastases were 0.711, 0.788, 0.671, and 0.827, respectively. The best value of the AUC for diagnosing lymph node metastases was 0.827 [95% confidence interval (CI): 0.749-0.890] using plain CT attenuation value ≤45 Hounsfield units (HU). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 92.8%, 69.2%, 86.5%, and 81.8%, respectively. Similar results were obtained from the 68 cases of lung cancer. Plain CT attenuation values reached the best AUC (0.860) for diagnosing lymph node metastases. Conclusions: Plain CT attenuation of lymph nodes is an effective method for diagnosing enlarged mediastinal lymph nodes with a history of multiple malignancies or lung cancer. Plain CT could be used as an additional test where there is no PET/CT available in cases of diagnostic dilemma.

2.
EClinicalMedicine ; 63: 102202, 2023 Sep.
Article En | MEDLINE | ID: mdl-37680944

Background: MRI is the routine examination to surveil the recurrence of nasopharyngeal carcinoma, but it has relatively lower sensitivity than PET/CT. We aimed to find if artificial intelligence (AI) could be competent pre-inspector for MRI radiologists and whether AI-aided MRI could perform better or even equal to PET/CT. Methods: This multicenter study enrolled 6916 patients from five hospitals between September 2009 and October 2020. A 2.5D convolutional neural network diagnostic model and a nnU-Net contouring model were developed in the training and test cohorts and used to independently predict and visualize the recurrence of patients in the internal and external validation cohorts. We evaluated the area under the ROC curve (AUC) of AI and compared AI with MRI and PET/CT in sensitivity and specificity using the McNemar test. The prospective cohort was randomized into the AI and non-AI groups, and their sensitivity and specificity were compared using the Chi-square test. Findings: The AI model achieved AUCs of 0.92 and 0.88 in the internal and external validation cohorts, corresponding to the sensitivity of 79.5% and 74.3% and specificity of 91.0% and 92.8%. It had comparable sensitivity to MRI (e.g., 74.3% vs. 74.7%, P = 0.89) but lower sensitivity than PET/CT (77.9% vs. 92.0%, P < 0.0001) at the same individual-specificities. The AI model achieved moderate precision with a median dice similarity coefficient of 0.67. AI-aided MRI improved specificity (92.5% vs. 85.0%, P = 0.034), equaled PET/CT in the internal validation subcohort, and increased sensitivity (81.9% vs. 70.8%, P = 0.021) in the external validation subcohort. In the prospective cohort of 1248 patients, the AI group had higher sensitivity than the non-AI group (78.6% vs. 67.3%, P = 0.23), albeit nonsignificant. In future randomized controlled trials, a sample size of 3943 patients in each arm would be required to demonstrate the statistically significant difference. Interpretation: The AI model equaled MRI by expert radiologists, and AI-aided MRI by expert radiologists equaled PET/CT. A larger randomized controlled trial is warranted to demonstrate the AI's benefit sufficiently. Funding: The Sun Yat-sen University Clinical Research 5010 Program (2015020), Guangdong Basic and Applied Basic Research Foundation (2022A1515110356), and Guangzhou Science and Technology Program (2023A04J1788).

3.
Dev Cell ; 58(21): 2376-2392.e6, 2023 11 06.
Article En | MEDLINE | ID: mdl-37643613

Embryo implantation requires temporospatial maternal-embryonic dialog. Using single-cell RNA sequencing for the uterus from 2.5 to 4.5 days post-coitum (DPC) and bulk sequencing for the corresponding embryos of 3.5 and 4.0 DPC pregnant mice, we found that estrogen-responsive luminal epithelial cells (EECs) functionally differentiated into adhesive epithelial cells (AECs) and supporting epithelial cells (SECs), promoted by progesterone. Along with maternal signals, embryonic Pdgfa and Efna3/4 signaling activated AECs and SECs, respectively, enhancing the attachment of embryos to the endometrium and furthering embryo development. This differentiation process was largely conserved between humans and mice. Notably, the developmental defects of SOX9-positive human endometrial epithelial cells (similar to mouse EEC) were related to thin endometrium, whereas functional defects of SEC-similar unciliated epithelial cells were related to recurrent implantation failure (RIF). Our findings provide insights into endometrial luminal epithelial cell development directed by maternal and embryonic signaling, which is crucial for endometrial receptivity.


Embryo Implantation , Epithelial Cells , Pregnancy , Female , Humans , Animals , Mice , Embryo Implantation/genetics , Embryonic Development , Endometrium/physiology , Cell Differentiation
4.
Lipids Health Dis ; 22(1): 108, 2023 Jul 29.
Article En | MEDLINE | ID: mdl-37516842

BACKGROUND: There is an urgent need to learn more about the epidemiological features of dyslipidemia in youth to address the high burden of cardiovascular disease. METHODS: This experiment was an observational, cross-sectional study. The samples were collected from 22,379 college students at Xinjiang Medical University. RESULT: The overall prevalence of dyslipidemia was 13.17%, which was significantly higher in men (23%) than in women (7.2%), p < 0.01. Similarly, the prevalence rate of obesity in men (11.4%) was significantly higher than that in women (3.4%). The composition of blood lipids, such as triglyceride (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C), began to increase gradually from the age of 22 and showed a sharp increase after the age of 30; however, a reverse trend was present in high density lipoprotein cholesterol (HDL-C). In terms of the proportion of dyslipidemia in both men and women, low HDL-C accounted for the largest proportion (74%), followed by elevated TGs (14.5%). The overall distribution of rates of dyslipidemia and excess weight showed a U-shaped trend with increasing age, with the lowest rates seen in the 20-24 age group. CONCLUSION: Our study sheds light on the epidemiological features of dyslipidemia in young adults and enriches the limited data available on dyslipidemia, providing a reference for the close monitoring and control of risk factors to reduce the occurrence and progression of atherosclerotic cardiovascular disease events.


Atherosclerosis , Cardiovascular Diseases , Dyslipidemias , Male , Adolescent , Humans , Female , Young Adult , Cross-Sectional Studies , Dyslipidemias/epidemiology , Cholesterol, HDL
5.
Cancer Med ; 12(6): 6811-6824, 2023 03.
Article En | MEDLINE | ID: mdl-36420689

BACKGROUND AND OBJECTIVE: In general, there are not many studies exploring the clinical value of adjuvant chemotherapy or maintenance chemotherapy (AC/MC) after induction chemotherapy and concurrent chemoradiotherapy (IC+CCRT+AC/MC). The purpose of this study was to establish a clinical nomogram for the use of AC/MC in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). MATERIAL AND METHODS: Two centers (Guangzhou Medical University Cancer Center [N = 1226] and Zhongshan People's Hospital [N = 150]) recruited 1376 patients with LA-NPC. All the patients underwent IC+CCRT; 560 patients received AC with cisplatin/nedaplatin plus docetaxel/paclitaxel (TP) or cisplatin/nedaplatin plus fluorouracil (PF), and 81 patients received MC with S-1. Multivariate Cox regression was used to confirm optimal predictors of progression-free survival (PFS), and a nomogram was established to identify patients into low-risk and high-risk cohorts. Additionally, bootstrap internal validation was performed to further verify our nomogram. RESULTS: After propensity score matching (PSM), the survival curves were not statistically different between IC+CCRT+AC/MC and IC+CCRT (all p > 0.05). Then, a nomogram was developed based on variables that were screened by univariate and multivariate Cox regression, including N stage, cumulative platinum dose during CCRT, body mass index (BMI), IC cycles, IC regimen and cervical lymph node (CLN) necrosis and infiltration of adjacent tissues. The results of the nomogram showed that the high-risk cohort had greatly worse 5-year DMFS, LRFS, PFS and OS compared to low-risk cohort (all p < 0.05), and subgroup analysis found that the 5-year DMFS, PFS and OS of patients treated with IC+CCRT+AC/MC were better than those treated with IC+CCRT in high-risk cohort (all p < 0.05). Notably, the incidence of adverse effects for IC+CCRT+AC cohort was higher than that for IC+CCRT+MC cohort, especially leukocytopenia and neutropenia. IC+CCRT and IC+CCRT+MC were associated with similar incidences of adverse effects. CONCLUSIONS: The addition of AC or MC to IC+CCRT could improve the DMFS of patients with high-risk NPC and prolong their survival. Additionally, our findings suggest a potential role of AC/MC following IC plus CCRT in the treatment of high-risk LA-NPC.


Cisplatin , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/pathology , Cisplatin/adverse effects , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/pathology , Induction Chemotherapy/methods , Maintenance Chemotherapy , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Chemotherapy, Adjuvant , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Docetaxel/therapeutic use
6.
World J Clin Cases ; 9(26): 7937-7943, 2021 Sep 16.
Article En | MEDLINE | ID: mdl-34621849

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and highly invasive endocrine malignant tumor with a poor prognosis. Although surgical resection is the main treatment for ACC, postoperative recurrence and metastasis have become the important factors of death. Transcatheter arterial chemoembolization (TACE) is an important option for the treatment of advanced ACC with liver metastasis. However, due to the small number of patients treated for ACC, the safety of the operation is not completely clear and needs to be further studied. CASE SUMMARY: A 47-year-old patient with ACC after surgery was admitted for reexamination by abdominal computerized tomography suggesting liver metastasis. Because the patient expressed reluctance to undergo surgery again, we treated her with TACE for the liver lesions. After treatment, symptoms of acute adrenal dysfunction such as decreased blood pressure, anorexia, and fatigue appeared, which were relieved after hydrocortisone treatment. To date, the patient's liver lesion is well controlled and no other metastases are observed. CONCLUSION: We report a rare case of acute adrenal hypofunction after TACE. Glucocorticoid supplementation can alleviate the symptoms.

7.
Ann Transl Med ; 9(3): 217, 2021 Feb.
Article En | MEDLINE | ID: mdl-33708844

BACKGROUND: Lateral pelvic lymph node (LPLN) is approximately 11-14% and always associated with poorer prognosis. This study investigated the efficacy and safety of simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) based on neoadjuvant chemoradiotherapy (NCRT) on locally advanced rectal cancer (LARC) patients with clinically suspected positive LPLNs. METHODS: We retrospectively screened distal LARC patients with NCRT in our center from May 2016 and June 2019. The diagnostic criteria of positive LPLN were nodes of over 7 mm in short axis and irregular border or mixed-signal intensity. All patients with clinically suspected positive LPLN received 56-60 Gy SIB-IMRT in the LPLN area. Concurrent chemotherapy regimens were capecitabine as monotherapy treatment or in combination with oxaliplatin. The toxicities, local-regional recurrence (LRR), and disease-free survival (DFS) were investigated. RESULTS: Fifty-two eligible patients with clinically suspected positive LPLN were screened and analyzed. The median distance from the distal tumor to the anal verge was 4 cm (range, 0-8 cm), while magnetic resonance imaging (MRI) analysis revealed the median short diameter of the pelvic LPLN to be 8 mm (range, 7-20 mm). There were 28 (53.8%) mesorectal fascia (MRF) positive and 22 (42.3%) extramural venous invasion (EMVI) positive patients. A radiotherapy dose of 41.8 Gy was administered to the pelvic area, while the LPLN received a median SIB dose of 60.0 Gy (range, 56-60 Gy) across 22 fractions. Synchronous capecitabine with or without oxaliplatin was administered during radiotherapy. In summary, 15 (28.8%) patients displayed grade 2-3 radiation-related toxicity, 8 (15.4%) patients underwent additional LPLN dissection, and positive nodes (26 nodes in total) were not observed. One patient suffered a LLR in the presacral region. The median follow-up duration was 21.2 months (range, 4.7-45.0 months), while the duration of 1- and 2-year DFS were 89.9% and 74.6%, respectively. Patients did not display LPLN recurrence. CONCLUSIONS: The safety and efficacy of SIB-IMRT on clinically suspected positive LPLN of LARC patients were deemed acceptable. Patients did not exhibit in-field LPLN recurrence after NCRT combined with single total mesorectal excision (TME).

8.
Abdom Radiol (NY) ; 46(7): 3011-3018, 2021 07.
Article En | MEDLINE | ID: mdl-33566165

OBJECTIVE: To explore which computed tomography (CT) features can predict pathological complete response (pCR) (ypT0N0) after neoadjuvant chemotherapy (NAC) in patients with gastric adenocarcinoma (GC). MATERIALS AND METHODS: This study reviewed an institutional database of patients who underwent resection of GC after NAC and identified patients with pCR from January 2010 to December 2013. The correlations between pre-chemotherapy and post-chemotherapy CT features and pCR were analyzed. RESULTS: Eleven of 199 patients with GC who achieved ypT0N0 status after NAC were classified as the pCR group in this study. After matching pCR (n = 11) and non-pCR patients (n = 44) in the ratio of 1:4, a total of 55 cases were analyzed. The binary logistic regression analysis showed that the post-chemotherapy short diameter of the largest lymph node and tumor thickness ratio reduction were independent predictors of pCR, with an area under the curve (AUC) of 0.94 on the receiver operating characteristic (ROC) curve analysis. CONCLUSION: Two CT features, including the short diameter of the largest lymph node post-chemotherapy and tumor thickness ratio reduction, are good predictors of pCR after NAC in patients with GC.


Neoadjuvant Therapy , Stomach Neoplasms , Area Under Curve , Humans , ROC Curve , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/drug therapy , Tomography, X-Ray Computed , Treatment Outcome
9.
Sci Rep ; 11(1): 2255, 2021 01 26.
Article En | MEDLINE | ID: mdl-33500428

Similar to sampling perfection with application-optimized contrast using different flip angle evolutions (SPACE), T2-weighted fast field echo (FFE) also has a black blood effect and a high imaging efficiency. The purpose of this study was to optimize 3D_T2_FFE and compare it with 3D_T2_SPACE for carotid imaging. The scanning parameter of 3D_T2_FFE was optimized for the imaging of the carotid wall. Twenty healthy volunteers and 10 patients with carotid plaque underwent cervical 3D_T2_FFE and 3D_T2_SPACE examinations. The signal-to-noise ratios of the carotid wall (SNRwall) and lumen (SNRlumen), and the contrast-to-noise ratios between the wall and lumen (CNRwall_lumen) were compared. The incidence of the residual flow signal at the carotid bifurcation and the grades of flow voids in the cerebellopontine angle region in the two sequences were also compared. The reproducibility of the two sequences was tested. No significant difference was observed between the two sequences in terms of the SNRwall of healthy individuals and patients (P = 0.132 and 0.102, respectively). The SNRlumen in the 3D_T2_FFE images was lower than that in the 3D_T2_SPACE images. No significant difference was observed between the two sequences in terms of the CNRwall-lumen. The incidence of the residual flow signal at the carotid bifurcation in 3D_T2_FFE was significantly lower than that in 3D_T2_SPACE. The grades of flow suppression in the cerebellopontine angle region in 3D_T2_SPACE was lower than that in 3D_T2_FFE. Both sequences showed excellent inter-and intra-observer reproducibility. Compared to 3D_T2_SPACE, 3D_T2_FFE showed stronger flow suppression while maintaining good imaging quality, which can be used as an alternative tool for carotid imaging.

10.
Abdom Radiol (NY) ; 46(4): 1478-1486, 2021 04.
Article En | MEDLINE | ID: mdl-33000287

OBJECTIVE: To analyze the diagnostic value of using the gastric window in computed tomography for differentiation of early gastric cancer (T1 stage) from muscularis involvement (T2 stage). MATERIALS AND METHODS: All patients with pathologically confirmed T1 stage and T2 stage gastric cancer and who underwent endoscopic resection or gastrectomy at our institution from January 2011 to November 2018 were examined. Each patient received an enhanced CT scan of the abdomen before the operation. T staging of tumors based on the CT scans was performed independently by two radiologists using the gastric window (width 150-200 HU, level 80-100 HU) and the abdominal window (width 350-400 HU, level 50 HU). RESULTS: Use of the gastric window to diagnose stage T1 EGC led to an accuracy of 88.9% for observer1 and 91.5% for observer2; use of the abdominal window led to an accuracy of 53.6% for observer1 and 51.6% (38/106) for observer2. Use of the gastric window to diagnose stage T2 led to an accuracy of 85.6% for observer1 and 82.4% for observer2; use of the abdominal window led to an accuracy of 52.3% for both observer1 and observer2. For observer1, use of the gastric window had a diagnostic accuracy of 69.2% for stage T1a and 62.5% for stage T1b; for observer2, the diagnostic accuracy was 65.1% for stage T1a and 67.0% for stage T1b. A Kappa test indicated moderate and substantial inter-observer agreement for T staging with gastric window (κ = 0.598, P < 0.001) and abdominal window (κ = 0.745, P < 0.001). CONCLUSION: Use of the gastric window in computed tomography provided more accurate staging for T1 and T2 stages of gastric cancer than the conventional abdominal window.


Stomach Neoplasms , Early Detection of Cancer , Gastrectomy , Humans , Neoplasm Staging , Retrospective Studies , Stomach Neoplasms/pathology , Tomography, X-Ray Computed
11.
Mikrochim Acta ; 187(9): 533, 2020 09 01.
Article En | MEDLINE | ID: mdl-32870401

A series of haptens were rationally designed for producing monoclonal antibodies specific for EC and a simple fluorescence immunoassay platform was developed for the sensitive determination of EC based on alkaline phosphatase (ALP)-triggered Cu+ quenching of CdSe quantum dots (QDs). It was noted that Cd as a fluorescence substrate in CdSe QDs can be selectively substituted by Cu+ that resulted in a more significant fluorescence quenching in comparison with Cu2+. Meanwhile, because ALP catalyzed ascorbic acid phosphate and then assisted the transformation of Cu2+ to Cu+, the change in fluorescence intensity was found to be proportional to ALP concentration. After simple magnetic separation, the sensitivity and linear range of the established assay were improved approximately 53-fold and an order of magnitude, respectively, when compared with the conventional ELISA. The proposed platform was able to both amplify the signal and eliminate matrix interferences, making it a promising to determine EC as well as other contaminants in complex food matrix in a highly sensitive and simple manner. Graphical abstract.


Carcinogens/analysis , Fluorescent Dyes/chemistry , Immunoassay/methods , Quantum Dots/chemistry , Urethane/analysis , Alkaline Phosphatase/chemistry , Antibodies, Immobilized/immunology , Antibodies, Monoclonal/immunology , Ascorbic Acid/analogs & derivatives , Cadmium Compounds/chemistry , Copper/chemistry , Fluorescence , Food Contamination/analysis , Immunomagnetic Separation , Limit of Detection , Microscopy, Fluorescence , Selenium Compounds/chemistry , Urethane/immunology , Wine/analysis
12.
Front Oncol ; 10: 1524, 2020.
Article En | MEDLINE | ID: mdl-32984000

Objective: Determine the performance of a computed tomography (CT) -based radiomics model in predicting early response to immunotherapy in patients with metastatic melanoma. Methods: This retrospective study examined 50 patients with metastatic melanoma who received immunotherapy treatment in our hospital with an anti-programmed cell death-1 (PD-1) agent or an inhibitor of cytotoxic T lymphocyte antigen-4 (CTLA-4). Thirty-four patients who received an anti-PD-1 agent were in the training sample and 16 patients who received a CTLA-4 inhibitor were in the validation sample. Patients with true progressive disease (PD) were in the poor response group, and those with pseudoprogression, complete response (CR), partial response (PR), or stable disease (SD) were in the good response group. CT images were examined at baseline and after the first and second cycles of treatment, and the imaging data were extracted for radiomics modeling. Results: The radiomics model based on pre-treatment, post-treatment, and delta features provided the best results for predicting response to immunotherapy. Receiver operating characteristic (ROC) analysis for good response indicated an area under the curve (AUC) of 0.882 for the training group and an AUC of 0.857 for the validation group. The sensitivity, specificity, and accuracy of model were 85.70% (6/7), 66.70% (6/9), and 75% (12/16) for predicting a good response. Conclusion: A CT-based radiomics model for metastatic melanoma has the potential to predict early response to immunotherapy and to identify pseudoprogression.

13.
Cancer Biother Radiopharm ; 34(4): 224-230, 2019 May.
Article En | MEDLINE | ID: mdl-31070481

Purpose: This study is aimed to evaluate the iodine concentration in the lipid-poor portion of the renal mass as a potential tool for the differentiation between angiomyolipoma (AML) and renal cell carcinoma (RCC). Materials and Methods: There were eight cases of AML and eight cases of RCC. All patients received corticomedullary, nephrographic and excretory phase enhanced scanning. The regions of interest (ROI) were manually placed in the lipid-poor portion of the renal mass and in the abdominal aorta. Average iodine concentrations were obtained for the ROIs and abdominal aorta. Data were compared using repeated measures analysis with the Bonferroni correction for multiple comparisons. Results: At the unenhanced phase, the iodine concentration in the lipid-poor portion of the renal mass of RCC was not significantly different from that of AML (p = 0.298). At the three enhanced phases, the iodine concentrations in the renal mass of RCC were substantially elevated compared with those of AML. In addition, the CT values of the renal mass of RCC were significantly higher than those of AML at all the enhanced phases. Of note, there was a significant correlation between iodine concentrations and CT values (r = 0.919; p < 0.001) in the lipid-poor portion of the renal mass of RCC. Conclusions: Between RCC and AML there was significant difference in iodine concentrations in the lipid-poor portion of the renal masses. Iodine concentration holds promise as a diagnostic alternative to macroscopic fat for differentiation of AML from RCC.


Angiomyolipoma/diagnostic imaging , Carcinoma, Renal Cell/diagnostic imaging , Image Processing, Computer-Assisted/methods , Iodine/analysis , Kidney Neoplasms/diagnostic imaging , Adult , Aged , Angiomyolipoma/pathology , Carcinoma, Renal Cell/pathology , Contrast Media/administration & dosage , Contrast Media/chemistry , Diagnosis, Differential , Female , Humans , Iohexol/administration & dosage , Iohexol/chemistry , Kidney/diagnostic imaging , Kidney/pathology , Kidney Neoplasms/pathology , Lipids , Male , Middle Aged , Sensitivity and Specificity , Tomography, X-Ray Computed/methods
14.
Korean J Radiol ; 20(3): 422-428, 2019 03.
Article En | MEDLINE | ID: mdl-30799573

OBJECTIVE: To analyze the detection rate of the inferior pyloric artery (IPA) in patients with gastric cancer by computed tomography arteriography (CTA). MATERIALS AND METHODS: Fifty-four patients (48 males and 6 females; mean age, 59.0 ± 1.5 years) who had undergone radical gastrectomy for gastric cancer from September 2016 to July 2017 at our institution were recruited prospectively. Patients underwent abdominal contrast-enhanced CT scans and CTA imaging reconstruction before the operation. The origin of the IPA in all cases was determined by a radiologist based on CTA images and verified by the surgeon. The accuracy of CTA in diagnosing the origin of the IPA was calculated. Dominant vessels of the origin were analyzed. RESULTS: IPAs were detected by CTA in 51 patients (94.4%). Among these, IPAs originated from the right gastroepiploic artery (RGEA) (24 cases), the gastroduodenal artery (GDA) (4 cases), and the anterior superior pancreaticoduodenal artery (ASPDA) (20 cases). In the remaining 3 cases, the IPAs contained two branches originating from the RGEA and ASPDA, respectively. During surgery, in 2 (3.7%) of the 54 cases of gastric cancer, IPAs could not be detected; the IPAs originated from the RGEA (22 cases), GDA (5 cases), and ASPDA (24 cases). One case had an IPA originating from both the RGEA and the GDA. Finally, the accuracy of CTA in diagnosing the origin artery of the IPA was 85.2% (46/54). CONCLUSION: CTA can detect the origin of the IPA accurately, which can aid surgeons while performing pylorus-preserving operations.


Angiography , Gastroepiploic Artery/diagnostic imaging , Stomach Neoplasms/diagnosis , Angiography/methods , Female , Gastrectomy , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Prospective Studies , Stomach Neoplasms/surgery , Tomography, X-Ray Computed
15.
Medchemcomm ; 10(12): 2131-2139, 2019 Dec 01.
Article En | MEDLINE | ID: mdl-32904145

Previously we identified a series of amidoalkylindoles as potent and selective CB2 partial agonists. In the present study, we report our continuous effort to improve the aqueous solubility by introducing N atoms to the amidoalkylindole framework. Synthesis, characterization, and pharmacology evaluations were described. Bioisosteric replacements of the indole nucleus with an indazole, azaindole and benzimidazole were explored. Benzimidazole 43 (EC50,CB1 = NA, EC50,CB2 = 0.067 µM) and azaindole 24 (EC50,CB1 = NA, EC50,CB2 = 0.048 µM) were found to be potent and selective CB2 receptor partial agonists, both with improved aqueous solubility.

16.
ChemMedChem ; 13(22): 2455-2463, 2018 11 20.
Article En | MEDLINE | ID: mdl-30246417

Herein we describe the design and synthesis of a new series of heteroarylpyrimidine/heteroaryltriazine derivatives on the basis of quinazoline-2,4(1H,3H)-diones as CB2 R-selective ligands using a bioisosterism strategy. An acetamide group was explored to displace the enamine linker of the lead compound for the purpose of stereoisomerism elimination and hydrophilicity increase. As a result, some of the synthesized compounds showed high bioactivity and selectivity for CB2 R in calcium mobilization assays, and four displayed CB2 R agonist activity, with EC50 values below 30 nm. The compound exhibiting the highest agonist activity toward CB2 R (EC50 =7.53±3.15 nm) had a selectivity over CB1 R of more than 1328-fold. Moreover, structure-activity relationship (SAR) studies indicated that the substituents on the nucleus play key roles in the functionality of a ligand, with one such example demonstrating CB2 R antagonist activity. Additionally, molecular docking simulations were conducted with the aim of better understanding of these new derivatives in relation to the structural requirements for agonists/antagonists binding to CB2 R.


Cannabinoid Receptor Agonists/pharmacology , Pyrimidines/pharmacology , Receptor, Cannabinoid, CB2/agonists , Triazines/pharmacology , Animals , Binding Sites , CHO Cells , Cannabinoid Receptor Agonists/chemical synthesis , Cannabinoid Receptor Agonists/chemistry , Cricetulus , Drug Design , Ligands , Molecular Docking Simulation , Molecular Structure , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Receptor, Cannabinoid, CB1/agonists , Receptor, Cannabinoid, CB2/chemistry , Structure-Activity Relationship , Triazines/chemical synthesis , Triazines/chemistry
17.
Int J Oncol ; 53(3): 1374-1384, 2018 Sep.
Article En | MEDLINE | ID: mdl-30015836

Long non-coding RNAs (lncRNAs) play important roles in biological processes and provide a novel approach with which to understand the molecular mechanisms responsible for glioma. Previous studies have demonstrated that lncRNA small nucleolar RNA host gene 12 (SNHG12) is involved in cell growth and migration. However, the accurate expression pattern of SNHG12 in glioma and the possible associations between this pattern and the clinicopathological characteristics of glioma cohorts are not yet known. The present study investigated the role of lncRNA SNHG12 in the development and progression of glioma, as well as the potential diagnostic value of SNHG12 in patients with glioma. The levels of SNHG12 were detected in resected specimens from patients and in glioma cell lines using reverse transcription-quantitative polymerase chain reaction. The potential effects of SNHG12 on the viability, mobility and apoptosis of glioma cells were evaluated using in vitro assays. The association between SNHG12 and Hu antigen R (HuR) was also determined using RNA immunoprecipitation (RIP) and RNA pull-down assays. The results revealed that SNHG12 was significantly upregulated in glioma tissues and cell lines. High levels of SNHG12 were associated with the deterioration of patients with glioma. Patients with high levels of SNHG12 exhibited a reduced 5-year overall survival rate (compared to those with lower levels), particularly in cohorts with high-grade carcinoma (III-IV). The silencing of SNHG12 expression by RNA interference led to a reduced viability and mobility, and in an increased apoptosis of human glioma cells. Furthermore, RIP and RNA pull-down assays demonstrated that SNHG12 was associated with and was stabilized by HuR. The findings of the present study thus identify a novel therapeutic target in glioma.


Brain Neoplasms/genetics , ELAV-Like Protein 1/metabolism , Gene Expression Regulation, Neoplastic , Glioma/genetics , RNA, Long Noncoding/metabolism , Apoptosis/genetics , Brain/pathology , Brain/surgery , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Brain Neoplasms/surgery , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease Progression , Female , Glioma/mortality , Glioma/pathology , Glioma/surgery , Humans , Male , Middle Aged , Neoplasm Grading , RNA Interference , RNA, Long Noncoding/genetics , RNA, Small Interfering/metabolism , Survival Analysis , Up-Regulation
18.
Bioorg Med Chem ; 26(12): 3559-3572, 2018 07 23.
Article En | MEDLINE | ID: mdl-29805075

The chemokine CC receptor subtype 2 (CCR2) has attracted intensive interest for drug development in diverse therapeutic areas, including chronic inflammatory diseases, diabetes, neuropathic pain, atherogenesis and cancer. By employing a cut-and-sew scaffold hopping strategy, we identified an active scaffold of 3,4-dihydro-2,6-naphthyridin-1(2H)-one as the central pharmacophore to derive novel CCR2 antagonists. Systematic structure-activity relationship study with respect to the ring size and the substitution on the naphthyridinone ring gave birth to 1-arylamino-6-alkylheterocycle-6,7,8,9-tetrahydro-5H-pyrido[4,3-c]azepin-5-ones as a brand new chemotype of CCR2 antagonists with nanomolar inhibitory activity. The best antagonism activity in this series was exemplified by compound 13a, which combined the optimal substitutions of 3,4-dichlorophenylamino at C-1 and 3-(4-(N-methylmethylsulfonamido)piperidin-1-yl)propyl at N-6 position, leading to an IC50 value of 61 nM and 10-fold selectivity for CCR2 over CCR5. Efficient and general synthesis was established to construct the innovative core structure and derive the compound collections. This is the first report on our designed 6,7,8,9-tetrahydro-5H-pyrido[4,3-c]azepin-5-one as novel CCR2 antagonist scaffold and its synthesis.


Azepines/chemistry , Receptors, CCR2/antagonists & inhibitors , Animals , Azepines/chemical synthesis , CHO Cells , Calcium/metabolism , Cricetinae , Cricetulus , Drug Evaluation, Preclinical , Humans , Inhibitory Concentration 50 , Receptors, CCR2/metabolism , Structure-Activity Relationship
19.
J Med Chem ; 61(11): 5020-5033, 2018 06 14.
Article En | MEDLINE | ID: mdl-29767965

To address the urgent need for new agents to reduce the global occurrence and spread of AIDS, we investigated the underlying hypothesis that antagonists of the HIV-1 envelope (Env) gp120 protein and the host-cell coreceptor (CoR) protein can be covalently joined into bifunctional synergistic combinations with improved antiviral capabilities. A synthetic protocol was established to covalently combine a CCR5 small-molecule antagonist and a gp120 peptide triazole antagonist to form the bifunctional chimera. Importantly, the chimeric inhibitor preserved the specific targeting properties of the two separate chimera components and, at the same time, exhibited low to subnanomolar potencies in inhibiting cell infection by different pseudoviruses, which were substantially greater than those of a noncovalent mixture of the individual components. The results demonstrate that targeting the virus-cell interface with a single molecule can result in improved potencies and also the introduction of new phenotypes to the chimeric inhibitor, such as the irreversible inactivation of HIV-1.


Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , HIV Envelope Protein gp120/metabolism , HIV-1/drug effects , HIV-1/metabolism , Receptors, CCR5/metabolism , Anti-HIV Agents/metabolism , Drug Design , HIV Envelope Protein gp120/chemistry , Models, Molecular , Molecular Targeted Therapy , Protein Conformation , Small Molecule Libraries/chemistry , Triazoles/chemistry
20.
Eur Radiol ; 28(9): 3770-3778, 2018 Sep.
Article En | MEDLINE | ID: mdl-29651765

OBJECTIVE: This study evaluated the imaging characteristics and accuracy of T2-weighted (T2W) balanced steady-state free procession (b-SSFP) magnetic resonance imaging, relative to b-SSFP or single-shot fast spin echo (SSFSE), for the diagnosis of placental adhesion disorder (PAD). METHODS: Fifty-one pregnant patients suspected of PAD were examined with T2W b-SSFP, b-SSFP and SSFSE. The image types were independently analysed for signs of PAD: abnormal placental bulge (APB), dark intraplacental bands (DIB), placental heterogeneity (PH) and placental protrusion into adjacent structures (PPAS). The sequences were compared for muscle-to-placenta signal ratio, signs of PAD and area under the receiver operating characteristic curve (AUC) for diagnostic accuracy of PAD. RESULTS: PAD was confirmed in 34 women. The muscle-to-placenta signal ratio was highest in the T2W b-SSFP. The diagnostic rates of APB in T2W b-SSFP were comparable to that of b-SSFP, but were significantly higher than that of SSFSE. The rates of PH in SSFE were comparable to that of b-SSFP, but both were significantly lower than that of T2W b-SSFP. The rates of DIB were significantly higher in T2W b-SSFP images compared with SSFSE. Rates of PPAS were comparable among three sequences. The AUCs of the T2W b-SSFP, b-SSFP and SSFSE were 0.966, 0.890 and 0.823, respectively. CONCLUSION: T2W b-SSFP has high diagnostic accuracy for PAD relative to SSFSE or b-SSFP, which may be due to its high SNR, T2-weighting and lack of blur. KEY POINTS: • Signal myometrium-to-placenta ratio was highest in the T2W b-SSFP images. • Diagnostic rate of APB in T2W b-SSFP was highest. • Diagnostic rate of DIB was higher in T2W b-SSFP than in SSFSE. • Diagnostic rate of PH in T2W b-SSFP was highest. • Maximum AUC for diagnostic accuracy of PAD was in T2W b-SSFP.


Magnetic Resonance Imaging/methods , Placenta Diseases/diagnostic imaging , Adult , Female , Humans , Placenta/diagnostic imaging , Pregnancy , Pregnancy Trimester, Third , Prospective Studies , ROC Curve , Reproducibility of Results
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