Publications by authors named "Jing Gong"

341 Publications

Development of MRI-Based Radiomics Model to Predict the Risk of Recurrence in Patients With Advanced High-Grade Serous Ovarian Carcinoma.

AJR Am J Roentgenol 2021 Jul 14:1-12. Epub 2021 Jul 14.

Department of Radiology, Fudan University Shanghai Cancer Center, 270 Dongan Rd, Shanghai 200032, China.

The purpose of our study was to develop a radiomics model based on preoperative MRI and clinical information for predicting recurrence-free survival (RFS) in patients with advanced high-grade serous ovarian carcinoma (HGSOC). This retrospective study enrolled 117 patients with HGSOC, including 90 patients with recurrence and 27 without recurrence; 1046 radiomics features were extracted from T2-weighted images and contrast-enhanced T1-weighted images using a manual segmentation method. L1 regularization-based least absolute shrinkage and selection operator (LASSO) regression was performed to select features, and the synthetic minority oversampling technique (SMOTE) was used to balance our dataset. A support vector machine (SVM) classifier was used to build the classification model. To validate the performance of the proposed models, we applied a leave-one-out cross-validation method to train and test the classifier. Cox proportional hazards regression, Harrell concordance index (C-index), and Kaplan-Meier plots analysis were used to evaluate the associations between radiomics signatures and RFS. The fusion radiomics-based model yielded a significantly higher AUC value of 0.85 in evaluating RFS than the model using contrast-enhanced T1-weighted imaging features alone or T2-weighted imaging features alone (AUC = 0.79 and 0.74 and = .02 and .01, respectively). Kaplan-Meier survival curves showed significant differences between high and low recurrence risk in patients with HGSOC by different models. The fusion model combining radiomics features and clinical information showed higher performance than the clinical model (C-index = 0.62 and 0.60, respectively). The proposed MRI-based radiomics signatures may provide a potential way to develop a prediction model and can help identify patients with advanced HGSOC who have a high risk of recurrence.
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http://dx.doi.org/10.2214/AJR.20.23195DOI Listing
July 2021

Distribution of bacterial concentration and viability in atmospheric aerosols under various weather conditions in the coastal region of China.

Sci Total Environ 2021 Jun 25;795:148713. Epub 2021 Jun 25.

Key Laboratory of Marine Environment and Ecology, Ministry of Education, Ocean University of China, Qingdao 266100, China.

Airborne bacteria have an important role in atmospheric processes and human health. However, there is still little information on the transmission and distribution of bacteria via the airborne route. To characterize the impact of foggy, haze, haze-fog (HF) and dust days on the concentration and viability of bacteria in atmospheric aerosols, size-segregated bioaerosol samples were collected in the Qingdao coastal region from March 2018 to February 2019. The total airborne microbes and viable/non-viable bacteria in the bioaerosol samples were measured using an epifluorescence microscope after staining with DAPI (4', 6-diamidino-2-phenylindole) and a LIVE/DEAD® BacLight Bacterial Viability Kit. The average concentrations of total airborne microbes on haze and dust days were 6.75 × 10 and 1.03 × 10 cells/m, respectively, which increased by a factor of 1.3 and 2.5 (on average), respectively, relative to those on sunny days. The concentrations of non-viable bacteria on haze and dust days increased by a factor of 1.2 and 3.6 (on average), respectively, relative to those on sunny days. In contrast, the concentrations of viable bacteria on foggy and HF days were 7.13 × 10 and 5.74 × 10 cells/m, decreases of 38% and 50%, respectively, compared with those on sunny days. Foggy, haze, dust and HF days had a significant effect on the trend of the seasonal variation in the total airborne microbes and non-viable bacteria. Bacterial viability was 20.8% on sunny days and significantly higher than the 14.1% on foggy days, 11.2% on haze days, 8.6% during the HF phenomenon and 6.1% on dust days, indicating that special weather is harmful to some bacterial species. Correlation analysis showed that the factors that influenced the bacterial concentration and viability depended on different weather conditions. The main influential factors were temperature, NO and SO concentrations on haze days, and temperature, particulate matter (PM) and NO concentrations on foggy days. The median size of particles containing viable bacteria was 1.94 μm on sunny days and decreased to 1.88 μm and 1.74 μm on foggy and haze days, respectively, but increased to 2.18 μm and 2.37 μm on dust and HF days, respectively.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148713DOI Listing
June 2021

Deep Learning-Based Stage-Wise Risk Stratification for Early Lung Adenocarcinoma in CT Images: A Multi-Center Study.

Cancers (Basel) 2021 Jun 30;13(13). Epub 2021 Jun 30.

Department of Radiology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai 200032, China.

This study aims to develop a deep neural network (DNN)-based two-stage risk stratification model for early lung adenocarcinomas in CT images, and investigate the performance compared with practicing radiologists. A total of 2393 GGNs were retrospectively collected from 2105 patients in four centers. All the pathologic results of GGNs were obtained from surgically resected specimens. A two-stage deep neural network was developed based on the 3D residual network and atrous convolution module to diagnose benign and malignant GGNs (Task1) and classify between invasive adenocarcinoma (IA) and non-IA for these malignant GGNs (Task2). A multi-reader multi-case observer study with six board-certified radiologists' (average experience 11 years, range 2-28 years) participation was conducted to evaluate the model capability. DNN yielded area under the receiver operating characteristic curve (AUC) values of 0.76 ± 0.03 (95% confidence interval (CI): (0.69, 0.82)) and 0.96 ± 0.02 (95% CI: (0.92, 0.98)) for Task1 and Task2, which were equivalent to or higher than radiologists in the senior group with average AUC values of 0.76 and 0.95, respectively ( > 0.05). With the CT image slice thickness increasing from 1.15 mm ± 0.36 to 1.73 mm ± 0.64, DNN performance decreased 0.08 and 0.22 for the two tasks. The results demonstrated (1) a positive trend between the diagnostic performance and radiologist's experience, (2) the DNN yielded equivalent or even higher performance in comparison with senior radiologists, and (3) low image resolution decreased model performance in predicting the risks of GGNs. Once tested prospectively in clinical practice, the DNN could have the potential to assist doctors in precision diagnosis and treatment of early lung adenocarcinoma.
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http://dx.doi.org/10.3390/cancers13133300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269183PMC
June 2021

Trypsin-type serine protease p37k hydrolyzes CPAP3-type cuticle proteins in the molting fluid of the silkworm Bombyx mori.

Insect Biochem Mol Biol 2021 Jun 25:103610. Epub 2021 Jun 25.

State Key Laboratory of Silkworm Genome Biology, Southwest University, Beibei, Chongqing, 400715, China; Biological Science Research Center, Southwest University, Beibei, Chongqing, 400715, China; Chongqing Key Laboratory of Sericulture, Southwest University, Chongqing, 400716, China. Electronic address:

Cuticular proteins analogous to peritrophin 3 (CPAP3)-type cuticle proteins constitute a family of proteins with three chitin-binding domains (CBDs) that play an important role in cuticle formation by associating with chitin. In our previous study, we identified CPAP3-type cuticle proteins in the silkworm genome, of which we characterized CPAP3-A2 (BmCBP1), a protein highly expressed in the epidermis. In this study, to elucidate the digestion mechanism of CPAP3-type cuticle proteins, we incubated CPAP3-A2 with molting fluid in vitro and found that its hydrolysis, which was inhibited by serine and cysteine protease inhibitors, produced two major bands with a molecular weight of approximately 22 kD and 11 kD. A trypsin-type serine protease, p37k, was presumed to be responsible for hydrolyzing CPAP3-A2 based on liquid chromatography-tandem mass spectrometry analysis of naturally purified molting fluid. To verify this, p37k was subsequently expressed in Sf9 cells using the Bac-to-Bac baculovirus expression system. In its active form, the recombinant protease could successfully hydrolyze CPAP3-A2. Finally, we analyzed the CPAP3-A2 molting fluid digestion site. When arginine 169 of CPAP3-A2 was mutated to alanine, a weaker hydrolysis of mutant CPAP3-A2 was observed compared to that of normal CPAP3-A2. Collectively, we identified a trypsin-type serine protease that is involved in the degradation of CPAP3-type cuticle proteins, including CPAP3-A2, suggesting that this protease plays an important role during molting in Bombyx mori. These findings provide the basis for further elucidation of the mechanisms underlying insect molting and metamorphosis.
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http://dx.doi.org/10.1016/j.ibmb.2021.103610DOI Listing
June 2021

Relative clinical utility of simultaneous F-fluorodeoxyglucose PET/MRI and PET/CT for preoperative cervical cancer diagnosis.

J Int Med Res 2021 Jun;49(6):3000605211019190

Department of Obstetrics and Gynecology, The First Medical Center of Chinese PLA General Hospital, Beijing, China.

Objective: To investigate the utility of F-fluorodeoxyglucose (F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) for the preoperative diagnosis of cervical cancer.

Methods: We retrospectively analyzed 114 patients who were diagnosed with cervical cancer and underwent PET/MRI (n = 59) or PET/computed tomography (PET/CT) (n = 65) before surgery. The maximal standardized uptake value (SUV) and mean SUV (SUV) were determined for regions of interest in the resultant radiographic images.

Results: Relative to PET/CT, F-FDG PET/MRI exhibited higher specificity and sensitivity in defining the primary tumor bounds and higher sensitivity for detection of bladder involvement. The SUV and SUV of PET/MRI were remarkably higher than those of PET/CT as a means of detecting primary tumors, bladder involvement, and the lymph node status. However, no significant differences in these values were detected when comparing the two imaging approaches as a means of detecting vaginal involvement or para-aortic lymph node metastasis.

Conclusions: These outcomes may demonstrate the capability of F-FDG PET/MRI to clarify preoperative cervical cancer diagnoses in the context of unclear PET/CT findings. However, studies directly comparing SUVs in different lesion types from patients who have undergone both PET/MRI and PET/CT scans are essential to validate and expand upon these findings.
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http://dx.doi.org/10.1177/03000605211019190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236793PMC
June 2021

Scaffold-mediated CRISPR-Cas9 delivery system for acute myeloid leukemia therapy.

Sci Adv 2021 May 19;7(21). Epub 2021 May 19.

Department of Biomedical Engineering, Columbia University, New York, NY, USA.

Leukemia stem cells (LSCs) sustain the disease and contribute to relapse in acute myeloid leukemia (AML). Therapies that ablate LSCs may increase the chance of eliminating this cancer in patients. To this end, we used a bioreducible lipidoid-encapsulated Cas9/single guide RNA (sgRNA) ribonucleoprotein [lipidoid nanoparticle (LNP)-Cas9 RNP] to target the critical gene interleukin-1 receptor accessory protein () in human LSCs. To enhance LSC targeting, we loaded LNP-Cas9 RNP and the chemokine CXCL12α onto mesenchymal stem cell membrane-coated nanofibril (MSCM-NF) scaffolds mimicking the bone marrow microenvironment. In vitro, CXCL12α release induced migration of LSCs to the scaffolds, and LNP-Cas9 RNP induced efficient gene editing. knockout reduced LSC colony-forming capacity and leukemic burden. Scaffold-based delivery increased the retention time of LNP-Cas9 in the bone marrow cavity. Overall, sustained local delivery of Cas9/IL1RAP sgRNA via CXCL12α-loaded LNP/MSCM-NF scaffolds provides an effective strategy for attenuating LSC growth to improve AML therapy.
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http://dx.doi.org/10.1126/sciadv.abg3217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133753PMC
May 2021

Targeting glucose metabolism sensitizes pancreatic cancer to MEK inhibition.

Cancer Res 2021 Jun 11. Epub 2021 Jun 11.

Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center

Pancreatic ductal adenocarcinoma (PDAC) is almost universally lethal. A critical unmet need exists to explore essential susceptibilities in PDAC and identify druggable targets to improve PDAC treatment. KRAS mutations dominate the genetic landscape of PDAC and lead to activation of multiple downstream pathways and cellular processes. Here, we investigated the requirement of these pathways for tumor maintenance using an inducible KrasG12D-driven PDAC mouse model (iKras model), identifying that RAF-MEK-MAPK signaling is the major effector for oncogenic KRAS-mediated tumor maintenance. However, consistent with previous studies, MEK inhibition had minimal therapeutic effect as a single agent for PDAC in vitro and in vivo. Although MEK inhibition partially downregulated transcription of glycolysis genes, it failed to suppress glycolytic flux in PDAC cells, which is a major metabolic effector of oncogenic KRAS. Accordingly, an in vivo genetic screen identified multiple glycolysis genes as potential targets that may sensitize tumor cells to MEK inhibition. Inhibition of glucose metabolism with low dose 2-deoxyglucose in combination with a MEK inhibitor induced apoptosis in KrasG12D-driven PDAC cells in vitro. The combination also inhibited xenograft PDAC tumor growth and prolonged overall survival in a genetically engineered PDAC mouse model. Molecular and metabolic analyses indicated that co-targeting glycolysis and MAPK signaling results in apoptosis via induction of lethal ER stress. Together, our work suggests that combined inhibition of glycolysis and the MAPK pathway may serve as an effective approach to target KRAS-driven PDAC.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3792DOI Listing
June 2021

Effect of antifoaming agent on benign colorectal tumors in colonoscopy: A meta-analysis.

World J Clin Cases 2021 May;9(15):3607-3622

Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, Hubei Province, China.

Background: Although several trials have shown that the addition of antifoaming agents to polyethylene glycol (PEG) can improve bowel preparation, whether PEG plus antifoaming agents have a beneficial role in the detection of benign tumors during colonoscopy has yet to be confirmed. Our aim was to clarify whether adding simethicone to PEG solution could improve the detection of benign colorectal tumors.

Aim: To clarify whether adding simethicone to PEG solution could improve the detection of benign colorectal tumors.

Methods: The PubMed, EMBASE, and Cochrane Library databases were searched for articles published prior to September 2019. The outcomes included the detection rates of colorectal adenomas and polyps.

Result: Twenty studies were eligible. Although there was no difference in the colorectal adenoma detection rate (ADR), a significant effect of simethicone for diminutive adenomas (< 10 mm) was revealed in the group taking simethicone. We also found that simethicone could significantly improve the ADR in the proximal colon but did not affect the colorectal polyp detection rate. Furthermore, the subgroup analyses revealed a beneficial effect of simethicone on the ADR among Asians ( = 0.005) and those with an ADR < 25% ( = 0.003). Moreover, it was a significant finding that the low dose simethicone was as effective as the high dose one with respect to the detection of benign colorectal tumors.

Conclusion: In summary, the addition of simethicone to PEG might improve the detection of diminutive adenomas in the right colon by colonoscopy in Asia. Low-dose simethicone was recommended for the detection of benign colorectal tumors. However, large clinical trials are necessary to validate our results and determine the ideal dose of simethicone.
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http://dx.doi.org/10.12998/wjcc.v9.i15.3607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130091PMC
May 2021

Prognostic significance of low TSH concentration in patients with COVID-19 presenting with non-thyroidal illness syndrome.

BMC Endocr Disord 2021 May 27;21(1):111. Epub 2021 May 27.

Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Low free triiodothyronine (FT3) levels are related to a poor prognosis deterioration in patients with COVID-19 presenting with non-thyroidal illness syndrome (NTI). This study was designed to explore whether free thyroxin (FT4) or thyroid stimulating hormone (TSH) levels affected the mortality of patients with COVID-19 presenting with NTI.

Methods: Patients with COVID-19 complicated with NTI who were treated at our hospital were included in this retrospective study. Patients were divided into low TSH and normal TSH groups, as well as low and normal-high FT4 group, according to the reference range of TSH or FT4 levels. The 90-day mortality and critical illness rates were compared among patients with low and normal TSH levels, as well as among patients with low FT4 levels and normal-high FT4 levels; in addition, differences in demographic and laboratory data were compared. A Kaplan-Meier analysis and Cox proportional hazards models were used to assess the associations of TSH and FT4 levels with mortality.

Results: One hundred fifty patients with low FT3 levels and without a history of thyroid disease were included, 68% of whom had normal FT4 and TSH levels. Critical illness rates (74.07% VS 37.40%, P = 0.001) and mortality rates (51.85% VS 22.76%, P = 0.002) were significantly higher in the low TSH group than in the normal TSH group. Although no significant difference in the critical illness rate was found (P = 0.296), the mortality rate was significantly higher in the low FT4 group (P = 0.038). Low TSH levels were independently related to 90-day mortality (hazard ratio = 2.78, 95% CI:1.42-5.552, P = 0.003).

Conclusions: Low FT4 and TSH concentrations were associated with mortality in patients with COVID-19 presenting with NTI; moreover, low TSH levels were an independent risk factor for mortality in these patients.
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http://dx.doi.org/10.1186/s12902-021-00766-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159017PMC
May 2021

Atomic Force Microscopy Study of Non-DLVO Interactions between Drops and Bubbles.

Langmuir 2021 Jun 27;37(22):6830-6837. Epub 2021 May 27.

Beijing Key Laboratory of Urban Oil and Gas Distribution Technology, State Key Laboratory of Natural Gas Hydrates, MOE Key Laboratory of Petroleum Engineering, China University of Petroleum, Beijing, No. 18 Fuxue Road, Changping District, 102249 Beijing, P. R. China.

The heterointeraction between liquid drops and air bubbles dispersed in another immiscible liquid is studied with the application of the atomic force microscopy (AFM) probe techniques. The tetradecane drops and air bubbles readily coalescence to form a lens-like structure in 100 mM sodium chloride aqueous solution, demonstrating strong hydrophobic (HB) attraction. The interaction range and strength of this hydrophobic attraction between oil drops and air bubbles is investigated by fine control of electrical double layer thicknesses related to specific electrolyte concentrations, and a midrange term in combination with a short-range term is found to present a proper characterization of this hydrophobic attraction. A further step is taken by introducing a triblock copolymer (Pluronic F68) into the aqueous solution, with results indicating that a relatively long-range steric hindrance (SH) furnished by a polymer "brush" surmounts the hydrophobic attraction. Finally, the interaction between a water drop and an air bubble in tetradecane is also measured as a comparison. The repelling action between a hydrophobic body (air bubble) and water drop indicates a strong repulsion. The present results show an interesting understanding of hydrophobic interactions between drops and bubbles, which is of potential application in controlling dispersion stability.
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http://dx.doi.org/10.1021/acs.langmuir.1c00937DOI Listing
June 2021

A systematic comparison of normalization methods for eQTL analysis.

Brief Bioinform 2021 May 20. Epub 2021 May 20.

Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, P. R. China.

Expression quantitative trait loci (eQTL) analysis has been widely used in interpreting disease-associated loci through correlating genetic variant loci with the expression of specific genes. RNA-sequencing (RNA-Seq), which can quantify gene expression at the genome-wide level, is often used in eQTL identification. Since different normalization methods of gene expression have substantial impacts on RNA-seq downstream analysis, it is of great necessity to systematically compare the effects of these methods on eQTL identification. Here, by using RNA-seq and genotype data of four different cancers in The Cancer Genome Atlas (TCGA) database, we comprehensively evaluated the effect of eight commonly used normalization methods on eQTL identification. Our results showed that the application of different methods could cause 20-30% differences in the final results of eQTL identification. Among these methods, COUNT, Median of Ratio (MED) and Trimmed Mean of M-values (TMM) generated similar results for identifying eQTLs, while Fragments Per Kilobase Million (FPKM) or RANK produced more differential results compared with other methods. Based on the accuracy and receiver operating characteristic (ROC) curve, the TMM method was found to be the optimal method for normalizing gene expression data in eQTLs analysis. In addition, we also evaluated the performance of different pairwise combinations of these methods. As a result, compared with single normalization methods, the combination of methods can not only identify more cis-eQTLs, but also improve the performance of the ROC curve. Overall, this study provides a comprehensive comparison of normalization methods for identifying eQTLs from RNA-seq data, and proposes some practical recommendations for diverse scenarios.
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http://dx.doi.org/10.1093/bib/bbab193DOI Listing
May 2021

Effects of dexmedetomidine on the elderly patients who received intracranial tumor surgeries.

Minerva Med 2021 May 12. Epub 2021 May 12.

Department of Anesthesiology, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, China -

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http://dx.doi.org/10.23736/S0026-4806.21.07528-5DOI Listing
May 2021

Chickpea Extract Ameliorates Metabolic Syndrome Symptoms via Restoring Intestinal Ecology and Metabolic Profile in Type 2 Diabetic Rats.

Mol Nutr Food Res 2021 07 19;65(13):e2100007. Epub 2021 May 19.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.

Scope: Chickpeas have been recognized as a natural Uyghur medicine in Xinjiang (China) for 2500 years. Although the phenotypic effect on obesity or diabetes was authenticated, the mechanism was unclear. This work aims to study the effect of chickpea extract (CE) on metabolic syndrome induced by type 2 diabetes and to reveal its related mechanisms, focusing on intestinal flora and metabolomics.

Methods And Results: Diabetic rats are induced by a high-fat diet and intraperitoneal injection of streptozotocin. CE supplementation (3 g kg ) for 4 weeks improved the hyperglycemia, inflammatory state, and organ functions of diabetic rats. The metabolic profile trajectories of urine and faeces obtained by NMR have good separations among all groups, and CE significantly increases the contents of SCFAs in the cecum. Moreover, CE relieves intestinal dysbiosis by increasing the abundance of SCFAs-producing bacteria (e.g., Enterococcaceae) but reduces conditional pathogenic bacteria (e.g., Corynebacterium). PICRUSt predicts the functions of gut microbiome from the 16S rRNA gene sequences and metagenome, and finds that CE restored amino acids degradation, bile acids metabolism, and carbohydrate metabolism.

Conclusion: This study elucidates the role of CE from the perspective of metabolomics and the microbiota, which provides evidence for chickpea as a prebiotic to prevent diabetes.
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http://dx.doi.org/10.1002/mnfr.202100007DOI Listing
July 2021

Effects of Ultrasound-Guided Bilateral Cervical Plexus Block Combined with General Anesthesia in Patients Undergoing Total Parathyroidectomy and Partial Gland Autotransplantation Surgery.

Local Reg Anesth 2021 23;14:75-83. Epub 2021 Apr 23.

Department of Orthopaedics, The 960th Hospital of the People's Liberation Army Joint Logistical Support Force, Jinan, Shandong, People's Republic of China.

Background: The aim of this study is to evaluate the effect of ultrasound-guided bilateral cervical plexus block on general anesthesia, postoperative analgesia, and surgical outcomes in patients undergoing total parathyroidectomy with autotransplantation.

Patients And Methods: Forty-eight ASA III-IV patients with hyperparathyroidism secondary to renal failure were included: 24 patients received ultrasound-guided bilateral superficial and deep cervical plexus block combined with general anesthesia (group A), and 24 patients received general anesthesia alone (group B). Postoperative patient-controlled intravenous analgesia was provided with sufentanil 2 μg/kg. The primary outcome is the postoperative pain scores. Secondary outcomes include intraoperative remifentanil dosage, changes in hemodynamics, extubation time, and sufentanil consumption. Surgical outcomes regarding calcium, phosphorus and parathormone values were also noted.

Results: The patients in group A required less remifentanil than group B (2.56±0.92mg vs 3.38±0.84mg, =0.002) and lower VAS scores at 1, 3, 10, 24, and 48h postoperatively ( < 0.001). While the systolic blood pressure in group A patients was significantly greater than that in group B at T3 (immediately after extubation, [138.33±11.36 vs 129.08±17.06 mmHg; =0.032]), heart rates in group A were lower than in group B at 1 min before induction (T1 [89.46 ± 9.14 vs 96.71±14.19, =0.042]) and 1 min after intubation (T2 [70.08 ± 5.35 vs 79.25 ± 11.81, =0.002]). The extubation time in group A was shorter than that in group B ( < 0.001). There was no difference in calcium, phosphorus and parathormone values, nor in sufentanil consumption between the groups.

Conclusion: Ultrasound-guided bilateral superficial and deep cervical plexus block combined with general anesthesia for TPTA is an effective strategy to improve anesthesia management and achieve better postoperative analgesia, and has no impact on surgical outcomes.
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http://dx.doi.org/10.2147/LRA.S299312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079358PMC
April 2021

HLA-A2.1-restricted ECM1-derived epitope LA through DC cross-activation priming CD8 T and NK cells: a novel therapeutic tumour vaccine.

J Hematol Oncol 2021 Apr 28;14(1):71. Epub 2021 Apr 28.

Department of Pharmacology, School of Pharmacy, China Medical University, No. 13, Beihai Road, Dadong District, Shenyang, Liaoning Province, China.

Background: CD8 T cell-mediated adaptive cellular immunity and natural killer (NK) cell-mediated innate immunity both play important roles in tumour immunity. This study aimed to develop therapeutic tumour vaccines based on double-activation of CD8 T and NK cells.

Methods: The immune Epitope database, Molecular Operating Environment software, and enzyme-linked immunosorbent assay were used for epitope identification. Flow cytometry, confocal microscopy, UPLC-QTOF-MS, and RNA-seq were utilized for evaluating immunity of PBMC-derived DCs, CD8 T or NK cells and related pathways. HLA-A2.1 transgenic mice combined with immunologically reconstituted tumour-bearing mice were used to examine the antitumour effect and safety of epitope vaccines.

Results: We identified novel HLA-A2.1-restricted extracellular matrix protein 1(ECM1)-derived immunodominant epitopes in which LA induced a potent immune response. We also found that LA-loaded DCs upregulated the frequency of CD3/CD8 T cells, CD45RO/CD69 activated memory T cells, and CD3/CD16/CD56 NK cells. We demonstrated cytotoxic granule release of LA/DC-CTLs or LA/DC-NK cells and cytotoxicity against tumour cells and microtissue blocks via the predominant IFN-γ/perforin/granzyme B cell death pathway. Further investigating the mechanism of LA-mediated CD8 T activation, we found that LA could be internalized into DCs through phagocytosis and then formed a LA-MHC-I complex presented onto the DC surface for recognition of the T cell receptor to upregulate Zap70 phosphorylation levels to further activate CD8 T cells by DC-CTL interactions. In addition, LA-mediated DC-NK crosstalk through stimulation of the TLR4-p38 MAPK pathway increased MICA/B expression on DCs to interact with NKG2D for NK activation. Promisingly, LA could activate CD8 T cells and NK cells simultaneously via interacting with DCs to suppress tumours in vivo. Moreover, the safety of LA was confirmed.

Conclusions: LA-induced immune antitumour activity through DC cross-activation with CD8 T and NK cells, which demonstrated proof-of-concept evidence for the capability and safety of a novel therapeutic tumour vaccine.
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http://dx.doi.org/10.1186/s13045-021-01081-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082934PMC
April 2021

Selinexor in combination with topotecan in patients with advanced or metastatic solid tumors: Results of an open-label, single-center, multi-arm phase Ib study.

Invest New Drugs 2021 Apr 28. Epub 2021 Apr 28.

Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.

Background Selinexor, a first-in-class, oral selective inhibitor of nuclear export (SINE) compound inhibits Exportin-1(XPO1), had demonstrated synergistic activity with many chemotherapies and conferred in vivo antitumor efficacy in hematologic as well as solid tumors. Methods This open-label, single-center, multi-arm phase 1b study used a standard 3 + 3 design and a "basket type" expansion. Selinexor with intravenous topotecan was given in one of the 13 parallel arms. Patients with advanced or metastatic relapsed/refractory solid tumors following prior systemic therapy, or in whom the addition of selinexor to standard chemotherapy deemed appropriate, were eligible. Results Fourteen patients with the median age of 61 years (range, 22-68years) were treated, and the most common cancer types were gynecological cancers; ovarian (n = 5), endometrial (n = 2), and 1 each with fallopian tube and vaginal cancers. Of the 14 patients treated, 12 (86 %) had at least one treatment-related adverse event (TRAE). The most common TRAEs were anemia (71 %), thrombocytopenia (57 %), hyponatremia (57 %), vomiting (57 %), fatigue (50 %), nausea (50 %), and neutropenia (36 %). Two patients had dose limiting toxicities. One patient dosed at selinexor 80 mg had grade 3 nausea and vomiting and one patient dosed at selinexor 60 mg experienced grade 4 neutropenia and thrombocytopenia. Of the 13 efficacy evaluable patients, one (8 %) with endometrial cancer achieved unconfirmed partial response (uPR) and the time-to-treatment failure (TTF) was 48 weeks, whereas 6 of the 13 (46 %) patients had stable disease (SD) contributing to the clinical benefit rate of 46 %. The median TTF for all patients was 9 weeks (range, 2-48weeks). Conclusions Once weekly selinexor in combination with topotecan was viable and showed some preliminary tumor efficacy. The recommend phase 2 dose of selinexor was 60 mg once weekly in combination with IV topotecan.Trial registration: NCT02419495. Registered 14 April 2015, https://clinicaltrials.gov/ct2/show/NCT02419495.
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http://dx.doi.org/10.1007/s10637-021-01119-0DOI Listing
April 2021

Impact of simethicone on bowel cleansing during colonoscopy in Chinese patients.

World J Clin Cases 2021 Apr;9(10):2238-2246

Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, Hubei Province, China.

Background: Four-liter polyethylene glycol (PEG) solutions are effective for bowel cleansing, but their large volume might hinder patient compliance. Due to the unique features of Asians, 4 L PEG might be a suboptimal bowel preparation in predominantly ethnically Asian countries. In view of this, a balance should be achieved between the volume and effectiveness. The ideal bowel cleansing regimen for a colonoscopy has yet to be determined in a Chinese population.

Aim: To compare the cleansing efficacy of 3 L PEG plus simethicone with 4 L PEG.

Methods: A total of 291 patients were randomly allocated to two groups: Group 1 ( = 145) received 4 L split-dose PEG (4-P); group 2 ( = 146) received 3 L split-dose PEG plus simethicone (3-PS). Bowel-cleansing efficacy was evaluated by endoscopists using the Boston bowel preparation scale (BBPS) and the bubbles score.

Results: Although there were no significant differences in the total BBPS score or the adequate rate of bowel preparation between the two groups, the BBPS score of the right-side colon was significantly higher in the 3-SP group (2.37 ± 0.54 2.21 ± 0.78; = 0.04). Moreover, the use of simethicone significantly reduced bubbles in all colon segments ( < 0.001). The mean withdrawal time was significantly shorter in the 3-PS group (8.8 ± 3.4 9.6 ± 2.3; = 0.02). Furthermore, significantly more proximal adenomas were detected in the 3-PS group (53.6% 45.7%; = 0.03). In addition, the proportions of patients with nausea and bloating were significantly lower in the 3-SP group ( < 0.01 for both). More patients in the 3-PS group expressed willingness to repeat the bowel preparation (87.7% 76.6%, = 0.01).

Conclusion: Three-liter PEG shows satisfactory bowel cleansing despite the decrease in dosage, and addition of simethicone with better bubble elimination and enhanced patient acceptance offers excellent potential impact on the detection of proximal adenomas in Chinese patients.
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http://dx.doi.org/10.12998/wjcc.v9.i10.2238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026841PMC
April 2021

Metanephric Adenoma Mimicking Renal Cell Carcinoma on 99mTc-MIBI SPECT/CT.

Clin Nucl Med 2021 Apr 5. Epub 2021 Apr 5.

From the Departments of Radiology Nuclear Medicine, Changhai Hospital, Navy Military Medical University, Shanghai, China.

Abstract: Metanephric adenoma is a rare benign renal tumor. A 49-year-old woman presented with a left renal pelvic mass detected by ultrasound. Enhanced CT of the kidney showed slight enhancement of the mass. For characterization of the mass, 99mTc-MIBI SPECT/CT was performed showing photopenia of the mass. Renal cell carcinoma was suspected. The mass was removed surgically. Metanephric adenoma was confirmed by histopathology. This case indicates that metanephric adenoma can appear cold on 99mTc-MIBI SPECT/CT, mimicking renal cell carcinoma.
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http://dx.doi.org/10.1097/RLU.0000000000003645DOI Listing
April 2021

A CT-Based Radiomics Approach to Predict Nivolumab Response in Advanced Non-Small-Cell Lung Cancer.

Front Oncol 2021 24;11:544339. Epub 2021 Feb 24.

Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Purpose: This study aims to develop a CT-based radiomics model to predict clinical outcomes of advanced non-small-cell lung cancer (NSCLC) patients treated with nivolumab.

Methods: Forty-six stage IIIB/IV NSCLC patients without EGFR mutation or ALK rearrangement who received nivolumab were enrolled. After segmenting primary tumors depicting on the pre-anti-PD1 treatment CT images, 1,106 radiomics features were computed and extracted to decode the imaging phenotypes of these tumors. A L1-based feature selection method was applied to remove the redundant features and build an optimal feature pool. To predict the risk of progression-free survival (PFS) and overall survival (OS), the selected image features were used to train and test three machine-learning classifiers namely, support vector machine classifier, logistic regression classifier, and Gaussian Naïve Bayes classifier. Finally, the overall patients were stratified into high and low risk subgroups by using prediction scores obtained from three classifiers, and Kaplan-Meier survival analysis was conduct to evaluate the prognostic values of these patients.

Results: To predict the risk of PFS and OS, the average area under a receiver operating characteristic curve (AUC) value of three classifiers were 0.73 ± 0.07 and 0.61 ± 0.08, respectively; the corresponding average Harrell's concordance indexes for three classifiers were 0.92 and 0.79. The average hazard ratios (HR) of three models for predicting PFS and OS were 6.22 and 3.54, which suggested the significant difference of the two subgroup's PFS and OS (p<0.05).

Conclusion: The pre-treatment CT-based radiomics model provided a promising way to predict clinical outcomes for advanced NSCLC patients treated with nivolumab.
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http://dx.doi.org/10.3389/fonc.2021.544339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943844PMC
February 2021

Associations between the gut microbiome and fatigue in cancer patients.

Sci Rep 2021 Mar 12;11(1):5847. Epub 2021 Mar 12.

Department of Investigational Cancer Therapeutics, Unit 0455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.

Fatigue is the most prevalent symptom of cancer and its treatments. Changes in the intestinal microbiome have been identified in chronic fatigue syndrome and other neuropsychiatric disorders, and cancer patients. However, the association between intestinal microbiome and fatigue in patients with advanced cancers has not been evaluated. Understanding the connection between intestinal microbiome and fatigue will provide interventional and therapeutic opportunities to manipulate the microbiome to improve fatigue and other patients' reported outcomes. In this project, we aimed to identify associations between microbiome composition and fatigue in advanced cancer patients. In this cross-sectional observational study at a tertiary cancer care center, we included 88 patients with advanced, metastatic, unresectable cancers who were in a washout period from chemotherapy. We measured fatigue using the MD Anderson Symptom Inventory-Immunotherapy fatigue score, and used 16srRNA to analyze intestinal microbiome. Using correlation analysis we found that Eubacterium hallii was negatively associated with fatigue severity scores (r = - 0.30, p = 0.005), whereas Cosenzaea was positively associated with fatigue scores (r = 0.33, p = 0.0002). We identified microbial species that exhibit distinct composition between high-fatigued and low-fatigued cancer patients. Further studies are warranted to investigate whether modulating the microbiome reduces cancer patients' fatigue severity and improves their quality of life.
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http://dx.doi.org/10.1038/s41598-021-84783-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954807PMC
March 2021

Berberine Ameliorates Glucose Metabolism in Diabetic Rats through the alpha7 Nicotinic Acetylcholine Receptor-Related Cholinergic Anti-Inflammatory Pathway.

Planta Med 2021 Mar 5. Epub 2021 Mar 5.

Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Berberine is an isoquinoline derivative alkaloid extracted from Chinese herbs. Recent studies have demonstrated the therapeutic effect of berberine on glucose metabolic disorders. However, its specific mechanism is still unclear. Our study aimed to research the glucose-lowering effect of berberine in diabetic rats and to reveal the possible role of the cholinergic anti-inflammatory pathway. Diabetic rats induced by administration of a high-calorie diet and streptozocin tail vein injection were assessed by the oral glucose tolerance test. Then, the diabetic rats were divided into two groups, those with or without the alpha7 nicotinic acetylcholine receptor gene downregulated, respectively, followed by treatment including berberine for 6 weeks. Results of this study show that the administration of berberine downregulated levels of fasting blood glucose and fasting insulin, and ameliorated insulin resistance in diabetic rats. Treatment with berberine inhibited acetylcholinesterase activity, and upregulated acetylcholine levels in the serum and alpha7 nicotinic acetylcholine receptor gene expression in the liver tissue. Meanwhile, berberine reversed elevated expression of cytokines interleukin-1 and TNF- in the serum and downregulated nuclear factor B expression. However, berberine administration showed no glucose-lowering or anti-inflammatory effect in diabetic rats in which alpha7 nicotinic acetylcholine receptor gene expression was downregulated, and acetylcholinesterase activity was also significantly inhibited. In conclusion, berberine may ameliorate glucose metabolism by activating the alpha7 nicotinic acetylcholine receptor-mediated cholinergic anti-inflammatory pathway.
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http://dx.doi.org/10.1055/a-1385-8015DOI Listing
March 2021

Effect of Surface Tension, Foaming Stabilizer, and Graphene Oxide on the Properties of Foamed Paste.

J Nanosci Nanotechnol 2021 05;21(5):3123-3133

Department of Civil & Environmental Engineering, Washington State University, Pullman, WA 99164-2910, USA.

Foamed paste has attracted much attention because of its excellent thermal insulation performance and diverse applications in infrastructure projects. However, there are still some shortcomings hindering the further application of foamed paste, such as the low mechanical strength and the lack of effective methods to evaluate the properties of foaming bubbles. In this study, surface tension was used as the key parameter to characterize the properties of bubbles. A novel nanomaterial, graphene oxide was employed to enhance the mechanical strength of foamed paste, which was also effective in decreasing the surface tension of aqueous solution. A central composite design scheme was employed to evaluate the influence of three selected factors, surface tension, Sodium Phosphate/foaming reagents mass ratio, and graphene oxide/binder mass ratio, on the engineering properties of foamed paste. Additionally, mercury intrusion porosimetry and scanning electron microscope were employed to elucidate the structure of pores, X-ray diffraction and thermogravimetric analysis were employed to further analyze the hydration products at the microscopic scale. This study reveals that surface tension holds great potential in predicting the engineering properties or performances of foamed paste, and a new mechanism may be developed for explaining the influence of graphene oxide on the pore structure of cementitious materials by evaluating the surface tension of pore solution.
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http://dx.doi.org/10.1166/jnn.2021.19282DOI Listing
May 2021

Computer-aided diagnosis of ground glass pulmonary nodule by fusing deep learning and radiomics features.

Phys Med Biol 2021 03 4;66(6):065015. Epub 2021 Mar 4.

Department of Radiology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, 200032, People's Republic of China.

Objectives: This study aims to develop a computer-aided diagnosis (CADx) scheme to classify between benign and malignant ground glass nodules (GGNs), and fuse deep leaning and radiomics imaging features to improve the classification performance.

Methods: We first retrospectively collected 513 surgery histopathology confirmed GGNs from two centers. Among these GGNs, 100 were benign and 413 were malignant. All malignant tumors were stage I lung adenocarcinoma. To segment GGNs, we applied a deep convolutional neural network and residual architecture to train and build a 3D U-Net. Then, based on the pre-trained U-Net, we used a transfer learning approach to build a deep neural network (DNN) to classify between benign and malignant GGNs. With the GGN segmentation results generated by 3D U-Net, we also developed a CT radiomics model by adopting a series of image processing techniques, i.e. radiomics feature extraction, feature selection, synthetic minority over-sampling technique, and support vector machine classifier training/testing, etc. Finally, we applied an information fusion method to fuse the prediction scores generated by DNN based CADx model and CT-radiomics based model. To evaluate the proposed model performance, we conducted a comparison experiment by testing on an independent testing dataset.

Results: Comparing with DNN model and radiomics model, our fusion model yielded a significant higher area under a receiver operating characteristic curve (AUC) value of 0.73 ± 0.06 (P < 0.01). The fusion model generated an accuracy of 75.6%, F1 score of 84.6%, weighted average F1 score of 70.3%, and Matthews correlation coefficient of 43.6%, which were higher than the DNN model and radiomics model individually.

Conclusions: Our experimental results demonstrated that (1) applying a CADx scheme was feasible to diagnosis of early-stage lung adenocarcinoma, (2) deep image features and radiomics features provided complementary information in classifying benign and malignant GGNs, and (3) it was an effective way to build DNN model with limited dataset by using transfer learning. Thus, to build a robust image analysis based CADx model, one can combine different types of image features to decode the imaging phenotypes of GGN.
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http://dx.doi.org/10.1088/1361-6560/abe735DOI Listing
March 2021

Characteristics of Viral Shedding in Respiratory Samples and Specific Antibodies Production in 564 COVID-19 Patients.

Curr Med Sci 2021 Feb 13;41(1):46-50. Epub 2021 Feb 13.

Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Positive nucleic acid (NA) results have been found in recovered and discharged COVID-19 patients, but the proportion is unclear. This study was designed to analyze the recurrent positive rate of NA results after consecutively negative results, and the relationship between the specific antibody production and positive NA rate. According to Strengthening the Reporting of Observational Studies in Epidemiology guidelines, data of inpatients in Sino-French New City Branch of Tongji Hospital between Jan. 28 and Mar. 6, 2020 were collected. A total of 564 COVID-19 patients over 14 years old who received the examinations of NA and antibodies against SARS-CoV-2 were included. Days of viral shedding and specific antibodies were recorded and assessed. Among NA tests in respiratory samples (throat swabs, nasopharyngeal swabs, sputum and flushing fluid in alveoli), the patients with all-negative NA results accounted for 17.20%, those with single-positive results for 46.63%, and those with multiple-positive results for 36.17% respectively. Besides, the recurrent positive NA results after consecutively negative results appeared in 66 patients (11.70%). For multiple-positive patients, median viral shedding duration was 20 days (range: 1 to 57 days). Of the 205 patients who received 2 or more antibody tests, 141 (68.78%) had decreased IgG and IgM concentrations. IgM decreased to normal range in 24 patients, with a median of 44 days from symptom onset. Viral shedding duration was not significantly correlated with gender, age, disease severity, changes in pulmonary imaging, and antibody concentration. It is concluded that antibody level and antibody change had no significant correlation with the positive rate of NA tests and the conversion rate after continuous negative NA tests. In order to reduce the recurrent positive proportion after discharge, 3 or more consecutive negative NA test results with test interval more than 24 h every time are suggested for the discharge or release from quarantine.
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http://dx.doi.org/10.1007/s11596-021-2316-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881913PMC
February 2021

Pembrolizumab in vaginal and vulvar squamous cell carcinoma: a case series from a phase II basket trial.

Sci Rep 2021 02 11;11(1):3667. Epub 2021 Feb 11.

Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1400 Holcombe Blvd, FC8.2026, Houston, TX, 77030, USA.

Vaginal and vulvar squamous cell carcinoma (SCC) are rare tumors that can be challenging to treat in the recurrent or metastatic setting. We present a case series of patients with vaginal or vulvar SCC who were treated with single-agent pembrolizumab as part of a phase II basket clinical trial to evaluate efficacy and safety. Two cases of recurrent and metastatic vaginal SCC, with multiple prior lines of systemic chemotherapy and radiation, received pembrolizumab. One patient had significant reduction (81%) in target tumor lesions prior to treatment discontinuation at cycle 10 following confirmed progression of disease with new metastatic lesions (stable disease by irRECIST criteria). In contrast, the other patient with vaginal SCC discontinued treatment after cycle 3 due to disease progression. Both patients had PD-L1 positive vaginal tumors and tolerated treatment well. One case of recurrent vulvar SCC with multiple surgical resections and prior progression on systemic carboplatin had a 30% reduction in her target tumor lesions following pembrolizumab treatment with a PD-L1 positive tumor. Treatment was discontinued for grade 3 mucositis after cycle 5. Pembrolizumab may provide some clinical benefit to some patients with vaginal or vulvar SCC and is overall safe to utilize in this population. Future studies are needed to evaluate the efficacy of pembrolizumab in these rare tumor types and to identify predictive biomarkers of response.
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http://dx.doi.org/10.1038/s41598-021-83317-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878854PMC
February 2021

The Effect of in the Treatment of Diabetes Mellitus: A Review.

Evid Based Complement Alternat Med 2021 16;2021:3796265. Epub 2021 Jan 16.

Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

In recent years, many studies of (MC) in the treatment of diabetes mellitus (DM) and its complications have been reported. This article reviewed the effect and mechanism of MC against diabetes, including the results from in vitro and in vivo experiments and clinical trials. The common side effects of MC were also summarized. We hope that it might open up new ideas for further mechanism exploration and clinical application as well as provide a scientific theoretical basis for the development of drugs or foods derived from MC.
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http://dx.doi.org/10.1155/2021/3796265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826218PMC
January 2021

Three-dimensional in vitro tissue culture models of brain organoids.

Exp Neurol 2021 May 23;339:113619. Epub 2021 Jan 23.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China. Electronic address:

Brain organoids are three-dimensional self-assembled structures that are derived from human induced pluripotent stem cells (hiPSCs). They can recapitulate the spatiotemporal organization and function of the brain, presenting a robust system for in vitro modeling of brain development, evolution, and diseases. Significant advances in biomaterials, microscale technologies, gene editing technologies, and stem cell biology have enabled the construction of human specific brain structures in vitro. However, the limitations of long-term culture, necrosis, and hypoxic cores in different culture models obstruct brain organoid growth and survival. The in vitro models should facilitate oxygen and nutrient absorption, which is essential to generate complex organoids and provides a biomimetic microenvironment for modeling human brain organogenesis and human diseases. This review aims to highlight the progress in the culture devices of brain organoids, including dish, bioreactor, and organ-on-a-chip models. With the modulation of bioactive molecules and biomaterials, the generated organoids recapitulate the key features of the human brain in a more reproducible and hyperoxic fashion. Furthermore, an outlook for future preclinical studies and the genetic modifications of brain organoids is presented.
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http://dx.doi.org/10.1016/j.expneurol.2021.113619DOI Listing
May 2021

Pembrolizumab in Patients with Advanced Metastatic Germ Cell Tumors.

Oncologist 2021 07 12;26(7):558-e1098. Epub 2021 Feb 12.

Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Lessons Learned: Advanced germ cell tumors are aggressive and associated with poor prognosis. Pembrolizumab was overall well tolerated in 12 heavily pretreated patients. Three patients had radiographic stable disease that lasted for 10.9 months, 5.5 months, and 4.5 months, respectively. Published data of immunotherapeutic agents in patients with advanced germ cell tumors are confirmed. The limited antitumor activity of immunotherapy in germ cell tumors is, at least partially, attributed to tumor biology (low tumor mutational burden; low PD-1 expression) and other poor-risk features. Tumor profiling to understand the mechanisms of resistance to pembrolizumab and innovative clinical trials that may include immunotherapy are warranted.

Background: Advanced germ cell tumors are associated with poor prognosis. We investigated the role of pembrolizumab in patients with advanced germ cell tumors.

Methods: We analyzed a prespecified cohort of an open-label, phase II clinical trial in which patients with advanced germ cell tumors were treated with pembrolizumab (200 mg) intravenously every 21 days. The endpoints of the study were the non-progression rate (NPR) at 27 weeks, safety, and tolerability. An NPR >20% was considered successful and worthy of further pursuit.

Results: From August 2016 to February 2018, 12 patients (10 men, 2 women) were treated (median age, 35 years [range, 22-63 years]; median number of prior systemic therapies, 3.5 [range, 2-7]; median number of metastatic sites, 3 [range, 2-8]). Overall, pembrolizumab was well tolerated. One patient experienced both grade 1 immune-related skin rash and grade 3 immune-related pneumonitis. No patient died from toxicity. Three patients had radiographic stable disease that lasted for 10.9 months, 5.5 months, and 4.5 months, respectively. No objective response was noted. The median progression-free survival was 2.4 months (95% confidence interval [CI], 1.5-4.5 months), and the median overall survival was 10.6 months (95% CI, 4.6-27.1 months). The 27-week NPR was 9.0% (95% CI, 0.23-41.2%).

Conclusion: Overall, pembrolizumab was safe and had limited antitumor activity in these patients. In the advanced, metastatic setting, tumor profiling to understand the mechanisms of resistance to immunotherapy and innovative clinical trials to identify efficacious combination regimens rather than off-label use of pembrolizumab are warranted.
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http://dx.doi.org/10.1002/onco.13682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265349PMC
July 2021

A combined radiomics and clinical variables model for prediction of malignancy in T2 hyperintense uterine mesenchymal tumors on MRI.

Eur Radiol 2021 Aug 23;31(8):6125-6135. Epub 2021 Jan 23.

Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Chongming Branch, No.25, Nanmen Road, Chongming District, 202150, Shanghai, China.

Objective: This study aims to develop a machine learning model for prediction of malignancy in T2 hyperintense mesenchymal uterine tumors based on T2-weighted image (T2WI) features and clinical information.

Methods: This retrospective study included 134 patients with T2 hyperintense uterine mesenchymal tumors (104 patients in training cohort and 30 in testing cohort). A total of 960 radiomics features were initially computed and extracted from each 3D segmented tumor depicting on T2WI. The support vector machine (SVM) classifier was applied to build computer-aided diagnosis (CAD) models by using selected clinical and radiomics features, respectively. Finally, an observer study was conducted by comparing with two radiologists to evaluate the diagnostic performance. The area under the receiver operating characteristic (ROC) curve (AUC) was computed to assess the performance of each model.

Results: Comparing with the T2WI-based radiomics model (AUC: 0.76 ± 0.09) and the clinical model (AUC: 0.79 ± 0.09), the combined model significantly improved the AUC value to 0.91 ± 0.05 (p < 0.05). The clinical-radiomics combined model yielded equivalent or higher performance than two radiologists (AUC: 0.78 vs. 0.91, p = 0.03; 0.90 vs.0.91, p = 0.13). There was a significant difference between the AUC values of two radiologists (p < 0.05).

Conclusions: It is feasible to predict malignancy risk of T2 hyperintense uterine mesenchymal tumors by combining clinical variables and T2WI-based radiomics features. Machine learning-based classification model may be useful to assist radiologists in decision-making.

Key Points: • Radiomics approach has the potential to distinguish between benign and malignant mesenchymal uterine tumors. • T2WI-based radiomics analysis combined with clinical variables performed well in predicting malignancy risk of T2 hyperintense uterine mesenchymal tumors. • Machine learning-based classification model may be useful to assist radiologists in characterization of a T2 hyperintense uterine mesenchymal tumor.
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http://dx.doi.org/10.1007/s00330-020-07678-9DOI Listing
August 2021

Effects of Curing Conditions on the MECHANICAL and Microstructural Properties of Ultra-High-Performance Concrete (UHPC) Incorporating Iron Tailing Powder.

Materials (Basel) 2021 Jan 4;14(1). Epub 2021 Jan 4.

Liaoning Provincial Transportation Planning and Design Institute Co., Ltd., Shenyang 110111, China.

It has been reported that iron tailing powder (ITP) has the potential to partially replace cement to prepare ultra-high-performance concrete (UHPC). However, the reactivity of ITP particles in concrete largely depends on the curing method. This study investigates the effects of curing conditions on the mechanical and microstructural properties of UHPC containing ITP. To achieve this objective, three research tasks are conducted, including (1) preparing seven concrete formulations by introducing ITP; (2) characterizing their mechanical performance under different curing regimes; and (3) analyzing their microstructure by XRD patterns, FTIR analysis, and SEM observation. The experimental results show that there is an optimum ITP dosage (15%) for their application. The concrete with 15% ITP under standard curing obtains 94.3 MPa at 7 days, their early-age strength could be even further increased by ~30% (warm-water curing) and ~35% (steamed curing). The steam curing regime stimulates the activity of ITP and refines the microstructure. This study demonstrates the potential of replacing Portland cement with ITP in UHPC production.
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http://dx.doi.org/10.3390/ma14010215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795680PMC
January 2021
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