Publications by authors named "Zhao Lu"

581 Publications

Anatomic study of carpal tunnel in adults using monoenergetic reconstruction of dual-energy computed tomography.

J Pak Med Assoc 2021 Feb;71(2(B)):663-671

Department of Radiology, Shengjing Hospital of China Medical University, Heping, Shenyang, China.

Objective: To seek optimal keV settings for imaging carpal tunnel in adults by dual-energy computed tomography (DECT) monoenergetic technique; to describe anatomic characteristics of carpal tunnel and to observe correlation between carpal bony and soft tissue structures.

Methods: DECT images of 20 wrists (11 left and 9 right wrists; 14 men, mean age 26.93±1.38 years, range 23 to 28, and 6 women, mean age 24.17 ± 0.98 years, range 23 to 26) were evaluated. Monoenergetic images were reconstructed at 42, 62, 82, 102, 122, and 142 keV. Image quality was assessed along a 5-point Likert scale, and the highest-quality images were chosen for quantitative analysis. Two musculoskeletal radiologists performed both analyses independently.

Results: The optimal energy spectrum with the best contrast-to-noise ratio (CNR) for monoenergetic images were at 62 keV (19 wrists, 95%) and 61 keV (1 wrist, 5%). There was substantial interobserver agreement between the readers in the 5-point Likert scale analysis of image quality (k= 0.793). Bland-Altman plots also indicated good agreement between observers in quantitative analysis. Intra-category 1 and 2 correlation was mostly discovered at hamate hook level and middle level of pisiform (P < 0.05), while bony and soft tissue structures partly reached correlation (P < 0.05).

Conclusions: The optimal energy spectrum for monoenergetic DECT imaging of carpal tunnel structures was 62 keV. DECT monoenergetic imaging could predict changes in soft tissue structures and demonstrate carpal tunnel anatomic structures.
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http://dx.doi.org/10.47391/JPMA.1203DOI Listing
February 2021

Biocompatible BSA-MnO nanoparticles for timely permeability imaging of blood-brain barrier and prediction of hemorrhage transformation in acute ischemic stroke.

Nanoscale 2021 Apr 28. Epub 2021 Apr 28.

Department of Radiology, Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China.

Hemorrhage transformation (HT) is a frequent but maybe fatal complication following acute ischemic stroke due to severe damage of the blood-brain barrier (BBB). Quantitative BBB permeability imaging is a promising method to predict HT in stroke patients for a favorable prognosis. However, clinical gadolinium chelate-based magnetic resonance (MR) imaging of the stroke suffers from a relatively low sensitivity and potential side effects of nephrogenic systemic fibrosis and intracranial gadolinium deposition. Herein, BSA-MnO2 nanoparticles (BM NPs) fabricated by a facile disinfection-mimic method were employed for the permeability imaging of BBB in the stroke for the first time. The BM NPs showed a high T1 relaxivity (r1 = 5.9 mM-1 s-1), remarkable MR imaging ability, and good biocompatibility, allowing the noninvasive timely visualization of BBB permeability in the model rats of middle cerebral artery occlusion (MCAO). Furthermore, increased peak intensity, extended imaging duration, and expanded imaging region indicated by BM NPs in MR imaging showed a good prediction for the onset of HT in MCAO rats. Therefore, BM NPs hold an attractive potential to be an alternative biocompatible MR contrast agent for the noninvasive BBB permeability imaging in vivo, benefiting the fundamental research of diverse neurological disorders and the clinical treatment for stroke patients.
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http://dx.doi.org/10.1039/d1nr02015cDOI Listing
April 2021

ML-DTI: Mutual Learning Mechanism for Interpretable Drug-Target Interaction Prediction.

J Phys Chem Lett 2021 May 27;12(17):4247-4261. Epub 2021 Apr 27.

Artificial Intelligence Medical Center, School of Intelligent Systems Engineering, Sun Yat-sen University, Shenzhen 510275, China.

Deep learning (DL) provides opportunities for the identification of drug-target interactions (DTIs). The challenges of applying DL lie primarily with the lack of interpretability. Also, most of the existing DL-based methods formulate the drug and target encoder as two independent modules without considering the relationship between them. In this study, we propose a mutual learning mechanism to bridge the gap between the two encoders. We formulated the DTI problem from a global perspective by inserting mutual learning layers between the two encoders. The mutual learning layer was achieved by multihead attention and position-aware attention. The neural attention mechanism also provides effective visualization, which makes it easier to analyze a model. We evaluated our approach using three benchmark kinase data sets under different experimental settings and compared the proposed method to three baseline models. We found that the four methods yielded similar results in the random split setting (training and test sets share common drugs and targets), while the proposed method increases the predictive performance significantly in the orphan-target and orphan-drug split setting (training and test sets share only targets or drugs). The experimental results demonstrated that the proposed method improved the generalization and interpretation capability of DTI modeling.
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http://dx.doi.org/10.1021/acs.jpclett.1c00867DOI Listing
May 2021

Oestrogen receptor alpha in papillary thyroid carcinoma: association with clinical features and BRAFV600E mutation.

Jpn J Clin Oncol 2021 Apr 24. Epub 2021 Apr 24.

Department of Thyroid and Breast Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.

Background: Papillary thyroid cancer cells can express oestrogen receptor alpha, which is encoded by the ESR1 gene and may bind to oestrogen to induce the occurrence and development of papillary thyroid cancer. The BRAFV600E mutation is also an important biomarker for the occurrence and progression of papillary thyroid cancer. However, the association between the BRAFV600E mutation and oestrogen receptor alpha expression has not been identified. This study aims to investigate the association between ESR1 expression and the BRAFV600E mutation and its clinical significance.

Methods: Oestrogen receptor alpha and BRAFV600E proteins were detected by immunohistochemical staining of formalin-fixed paraffin-embedded thyroid tissues from 1105 patients with papillary thyroid cancer at our institution. Messenger RNA expression counts of ESR1 and clinicopathologic information were obtained from The Cancer Genome Atlas database.

Results: Oestrogen receptor alpha protein expression was significantly associated with BRAFV600E protein. The positive rate of oestrogen receptor alpha protein in papillary thyroid cancer patients was significantly higher in males, younger patients and patients with the multifocal type. In papillary thyroid cancer patients with positive BRAFV600E protein, oestrogen receptor alpha expression was significantly correlated with central lymph node metastasis. Data from the The Cancer Genome Atlas database also suggested that the ESR1 messenger RNA level was associated with the BRAFV600E mutation. Furthermore, classification analysis performed according to a tree-based classification method demonstrated that higher ESR1 messenger RNA expression indicated poorer overall survival in papillary thyroid cancer patients with the BRAFV600E mutation.

Conclusions: The percentage of BRAFV600E mutations is increased in patients with higher ESR1 messenger RNA levels, and the BRAFV600E protein might be co-expressed with oestrogen receptor alpha, which could be an indicator of cervical lymph node metastasis and poor overall survival in patients with papillary thyroid cancer.
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http://dx.doi.org/10.1093/jjco/hyab058DOI Listing
April 2021

Rationale and design of a Phase 3b, Prospective, Randomized, Open Label, Blinded-endpoint, Multicenter Trial of the Efficacy and Safety of Urokinase Thrombolysis Comparing With Antiplatelet Agents for Patients With Minor Stroke.

Int J Stroke 2021 Apr 20:17474930211014344. Epub 2021 Apr 20.

First Affiliated Hospital of Zhengzhou University, Neurology, 1 Jian-she east road, Zhengzhou, henan, China.

Rationale: Minor ischemic stroke attack has taken a significant part of cerebrovascular disease burden. Benefits of thrombolysis in minor stroke is under debates and the use of urokinase in developing countries needs to be further explored.

Aim: TRUST (ThRombolysis of Urokinase for minor STroke) trial was designed to evaluate the efficacy and safety of intravenous urokinase for the treatment of acute minor ischemic stroke.Sample size estimates: To reach a double-sided type I error rate of 0.05 to test our hypothesis, with β=0.80, sample size of 1002 subjects were determined after further adjustment to account for up to 5% nonadherence.

Methods And Design: TRUST trial was developed with PROBE design, as a multicenter, randomized, open label, single-blind clinical trial with the stage of phase 3b.

Study Outcomes: The proportion of patients retaining full ability of independent living, which is defined as patients scoring 0-1 on modified Rankin Scale score at 90 days.

Discussion: TRUST trial may potentially provide promising and affordable thrombolysis for acute minor ischemic stroke in the developing parts of the world.
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http://dx.doi.org/10.1177/17474930211014344DOI Listing
April 2021

Dysiscalarones A-E, scalarane sesterterpenoids with nitric oxide production inhibitory activity from marine sponge Dysidea granulosa.

Bioorg Chem 2021 Mar 5;111:104791. Epub 2021 Mar 5.

Research Center for Marine Drugs, State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China. Electronic address:

Dysiscalarones A-E (1-5), five new scalarane-type bishomoscalarane sesterterpenoids, were isolated from marine sponge Dysidea granulosa collected from the South China Sea, together with two known ones, honulactone A (6) and phyllofolactone I (7). The new structures were determined by extensive spectroscopic analysis including HR-ESI-MS and 1D and 2D NMR data, and their absolute configurations were assigned by single crystal X-ray diffraction analyses. The inhibitory activity of all the seven isolates on the production of nitric oxide (NO) stimulated by lipopolysaccharide (LPS) in mouse RAW 264.7 macrophages was evaluated. Of these metabolites, dysiscalarones A-B (1-2), honulactone A (6), and phyllofolactone I (7) showed inhibitory activities with respective IC values of 16.4, 18.5, 2.6, and 3.7 μM, which suggested that the γ-methylated α,β-unsaturated γ-lactone might be the functional group. In addition, all the seven metabolites showed no significant cytotoxicity against lung cancer PC9 cell line at the concentration of 20 μM.
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http://dx.doi.org/10.1016/j.bioorg.2021.104791DOI Listing
March 2021

Down-regulation of miR-340-5p promoted osteogenic differentiation through regulation of runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells.

Bioengineered 2021 Dec;12(1):1126-1137

Department of Endocrinology, The People's Hospital of China Medical University, The People's Hospital of Liaoning Province, Shenyang, Liaoning P.R. China.

Diabetic osteoporosis (DOP) is a chronic complication of diabetes in the skeletal system. High level of miR-340-5p may be harmful to the bone formation. In this study, the DOP model of rats was successfully established via streptozotocin (STZ) and ovariectomy (OVX) treatment. It was manifested by reduced body weight, insulin level, alkaline phosphatase (ALP) activity, and osteocalcin (OCN) and collagen-I expressions, as well as increased concentration of fasting blood glucose. Moreover, we found that miR-340-5p expression was increased while runt-related transcription factor-2 (RUNX2) was decreased in femurs. Furthermore, the effects of miR-340-5p on osteogenic differentiation (OD) in high glucose (HG)-treated MC3T3-E1 cells were explored. Exposure to OD and HG contributed to elevated miR-340-5p level. Inhibition of miR-340-5p enhanced ALP level, calcium deposition, and OCN, collagen-I and RUNX2 levels. On the contrary, miR-340-5p overexpression reversed these promotional effects. Luciferase assay indicated that RUNX2 may be a target gene of miR-340-5p. Moreover, RUNX2 deficiency decreased miR-340-5p inhibition-induced ALP activity, calcium accumulation and OCN, collagen-I, RUNX2 levels. In short, the above findings revealed that inhibition of miR-340-5p facilitated osteogenic differentiation through regulating RUNX2 in MC3TC-E1 cells, which provided targeted therapeutic strategies for the treatment of DOP.
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http://dx.doi.org/10.1080/21655979.2021.1905259DOI Listing
December 2021

Monitoring atmospheric Kr by atom counting.

J Environ Radioact 2021 Jul 1;233:106604. Epub 2021 Apr 1.

Hefei National Laboratory for Physical Sciences at the Microscale, CAS Center for Excellence in Quantum Information and Quantum Physics, University of Science and Technology of China, 96 Jinzhai Road, Hefei, 230026, China.

Radioactive Kr is a major gaseous fission product emitted into the air by the nuclear fuel reprocessing industry. Measuring atmospheric Kr has applications in environmental monitoring, atmospheric transport model validation and dating of environmental water samples, including groundwater, sea water and glacier ice. We present an ultra-sensitive method for fast analysis of atmospheric Kr at 10 parts per trillion level. This method is based on laser cooling and trapping and is capable of counting individual Kr atoms. Measurements at the 3% precision level can be made on krypton extracted from 1L STP of air with a turnaround time of 1.5 h. Moreover, we have realized a system for continuous air sampling over days to weeks. Based on this atom-counting technology and a portable air sample integrator we have realized atmospheric Kr baseline monitoring in Hefei, China, for over 20 months. The technological advances presented in this work lay the ground for a global atmospheric Kr monitoring network.
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http://dx.doi.org/10.1016/j.jenvrad.2021.106604DOI Listing
July 2021

A Novel Graph Neural Network Methodology to Investigate Dihydroorotate Dehydrogenase Inhibitors in Small Cell Lung Cancer.

Biomolecules 2021 Mar 23;11(3). Epub 2021 Mar 23.

Artificial Intelligence Medical Center, School of Intelligent Systems Engineering, Sun Yat-sen University, Shenzhen 510275, China.

Small cell lung cancer (SCLC) is a particularly aggressive tumor subtype, and dihydroorotate dehydrogenase (DHODH) has been demonstrated to be a therapeutic target for SCLC. Network pharmacology analysis and virtual screening were utilized to find out related proteins and investigate candidates with high docking capacity to multiple targets. Graph neural networks (GNNs) and machine learning were used to build reliable predicted models. We proposed a novel concept of multi-GNNs, and then built three multi-GNN models called GIAN, GIAT, and SGCA, which achieved satisfactory results in our dataset containing 532 molecules with all R values greater than 0.92 on the training set and higher than 0.8 on the test set. Compared with machine learning algorithms, random forest (RF), and support vector regression (SVR), multi-GNNs had a better modeling effect and higher precision. Furthermore, the long-time 300 ns molecular dynamics simulation verified the stability of the protein-ligand complexes. The result showed that ZINC8577218, ZINC95618747, and ZINC4261765 might be the potentially potent inhibitors for DHODH. Multi-GNNs show great performance in practice, making them a promising field for future research. We therefore suggest that this novel concept of multi-GNNs is a promising protocol for drug discovery.
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http://dx.doi.org/10.3390/biom11030477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005042PMC
March 2021

Antiviral activity of portulaca oleracea L. extracts against porcine epidemic diarrhea virus by partial suppression on myd88/NF-κb activation in vitro.

Microb Pathog 2021 Mar 26;154:104832. Epub 2021 Mar 26.

Institute of Poultry Science, Shandong Academy of Agricultural Science, Shandong Provincial Key Laboratory of Poultry Diseases Diagnosis and Immunology, Poultry Breeding Engineering Technology Center of Shandong Province, Jinan, 250023, Shandong, PR China; Shandong Key Laboratory of Animal Disease Control and Breeding, Jinan, 250100, Shandong, PR China. Electronic address:

Porcine epidemic diarrhea virus (PEDV), especially variants, causes a highly contagious enteric disease which could give rise to huge economic losses in the swine industry worldwide. Portulaca oleracea L. has been reported to regulate intestine disease and involved in viral infections. However, the underlying mechanisms of Portulaca oleracea L. extracts against PEDV have not been fully elucidated. In this study, the antiviral effects and potential mechanisms of Portulaca oleracea L. extracts against PEDV were investigated in vitro. We first examined the inhibitory effects of different Portulaca oleracea L. extracts on the PEDV(JX-16 strain) in vitro and found that the water extract of Portulaca oleracea L.(PO)could significantly inhibit PEDV replication by 92.73% on VH cells and 63.07% on Vero cells. Furthermore, time-course analysis showed PO inhibited PEDV replication during the adsorption period of infectious cycle. Western blot and indirect immunofluorescence assay indicated that PO down-regulated the S protein expression in a dose-dependent manner. In addition, our results demonstrated the ability of PO to inhibit PEDV replication in VH cells by down-regulating the cytokine levels (TNF-α,IL-22 and IFN-α) and inhibiting the NF-κB signaling pathway activated by PEDV. Thus, Portulaca oleracea L extracts have potential utility in the preventive and therapeutic strategies for PEDV infection.
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http://dx.doi.org/10.1016/j.micpath.2021.104832DOI Listing
March 2021

Catalpol Protects Against High Glucose-Induced Bone Loss by Regulating Osteoblast Function.

Front Pharmacol 2021 10;12:626621. Epub 2021 Mar 10.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.

The overall objective of this study was to investigate the effects of catalpol on bone remodeling of diabetic osteoporosis by regulating osteoblast differentiation and migration. Using a murine model of diabetic osteoporosis, to detect the protective effects of catalpol on bone loss, architectural deterioration of trabecular bone and bone metabolism biomarkers were tested. A model of MC3T3-E1 cells was established by treatment with high glucose; the regulatory role of catalpol in the differentiation and migration was tested by Western blot, ALP staining, and Alizarin Red staining. Catalpol treatment markedly ameliorated trabecular bone deterioration by reducing degenerative changes of the trabecular structure by improving the bone formation marker levels of ALP, osteopontin, type I collagen, and osteocalcin, as well as the level of OPG/RANKL. Catalpol enhanced cell motility and scattering following gap formation of MC3T3-E1 cells. The results indicated that catalpol exhibits a protective effect against diabetic osteoporosis by regulating the differentiation and migration of osteoblast.
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http://dx.doi.org/10.3389/fphar.2021.626621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987667PMC
March 2021

Does Additional Laparoscopic-Assisted Surgery after Endoscopic Submucosal Dissection Affect Short Outcomes in Patients with Stage T1 Colorectal Cancer? A Propensity Score-Based Analysis.

Dig Surg 2021 Mar 26:1-7. Epub 2021 Mar 26.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Background: Additional surgery is necessary in cases with non-curative endoscopic submucosal dissection. It is still unknown whether preceding endoscopic submucosal dissection (ESD) for T1 colorectal carcinoma affects the short outcomes of patients who underwent additional surgery or not as compared with surgery alone without ESD.

Methods: Patients (101 pairs) with T1 colorectal cancer who underwent additional laparoscopic-assisted surgery after endoscopic submucosal dissection (additional surgery group, n = 101) or laparoscopic-assisted surgery alone (surgery alone group, n = 101) were matched (1:1). Short-term morbidity, operation outcomes, and lymph node metastasis of the resected specimen were compared.

Results: There were no significant differences between the additional laparoscopic-assisted surgery and laparoscopic-assisted surgery alone groups in lymph node metastasis (9.9 vs. 5.9%, respectively, p = 0.297), operative time (147.76 ± 52.00 min vs. 156.50 ± 54.28 min, p = 0.205), first flatus time (3.56 ± 1.10 days vs. 3.63 ± 1.05 days, p = 0.282), first stool time (4.30 ± 1.04 days vs. 4.39 ± 1.22 days, p = 0.293), time to intake (5.00 ± 1.18 days vs. 5.25 ± 1.39 days, p = 0.079), blood loss (44.75 ± 45.40 mL vs. 60.40 ± 78.98 mL, p = 0.603), harvest lymph nodes (18.74 ± 7.22 vs. 20.32 ± 9.69, p = 0.438), postoperative surgical complications (p = 0.733), and postoperative length of hospital stay (8.68 ± 4.00 days vs. 8.39 ± 1.94 days, p = 0.401).

Conclusion: ESD did not increase the difficulty of additional laparoscopic-assisted surgery, hospital stay, or the incidence of postoperative complications. Additional laparoscopic-assisted surgery is safe and recommended for patients with T1 cancer at high risk of lymph node metastasis and residual cancer after non-curative ESD.
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http://dx.doi.org/10.1159/000509170DOI Listing
March 2021

Evaluation of pathology and environmental variables contributing to hepatopancreatic necrosis syndrome of Chinese mitten crab, Eriocheir sinensis.

Ecotoxicol Environ Saf 2021 Jun 25;215:112157. Epub 2021 Mar 25.

Department of Aquaculture, College of Animal Science & Technology, Sichuan Agricultural University, Wenjiang 611130, Sichuan, China. Electronic address:

Hepatopancreatic Necrosis Syndrome (HPNS) severely impacts the Chinese mitten crab (Eriocheir sinensis) industry. However, little knowledge of the aetiology and pathogenesis of the disease causes significant difficulties in its prevention and control. In this study, we conducted a pathological analysis of HPNS through time-integrated large-volume sampling, to clarify the disease characteristics and mechanism of HPNS-afflicted crabs; besides, animal models were constructed to verify the pathological diagnosis. The results showed that the hepatopancreas was the principal target organ of HPNS; multiple correspondence analysis revealed that the main histopathological characteristics included non-interstitial atrophic hepatopathy diseases such as hepatic tubule atrophy, dilated hepatic tubules, and hepatic tubule necrosis. Additionally, the muscles also showed signs of disease, including myofibre atrophy, necrosis, and inflammation. Ultrastructural studies showed prominent apoptosis and autophagy-like alterations in the hepatopancreas of HPNS-afflicted crabs. Further, the establishment of animal models revealed that the double variate stimulation of environmental variables such as abamectin/sewage with nutrition deficiency could result in HPNS-similar lesions. Based on these studies, we concluded that HPNS is a chronic hepatopancreas-initiated energy-consumed disease with a low likelihood of pathogen but a high probability of environment and nutrition.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112157DOI Listing
June 2021

HIF1α/HIF2α-Sox2/Klf4 promotes the malignant progression of glioblastoma via the EGFR-PI3K/AKT signalling pathway with positive feedback under hypoxia.

Cell Death Dis 2021 Mar 24;12(4):312. Epub 2021 Mar 24.

Department of Neurosurgery, Chongqing General Hospital, University of Chinese Academy of Sciences, 401147, Chongqing, China.

Previous studies have suggested that hypoxic responses are regulated by hypoxia-inducible factors (HIFs), which in turn promote the malignant progression of glioblastoma (GBM) by inhibiting apoptosis and increasing proliferation; these events lead to a poor prognosis of GBM patients. However, there are still no HIF-targeted therapies for the treatment of GBM. We have conducted series of experiments and discovered that GBM cells exhibit features indicative of malignant progression and are present in a hypoxic environment. Knocking out HIF1α or HIF2α alone resulted in no significant change in cell proliferation and cell cycle progression in response to acute hypoxia, but cells showed inhibition of stemness expression and chemosensitization to temozolomide (TMZ) treatment. However, simultaneously knocking out HIF1α and HIF2α inhibited cell cycle arrest and promoted proliferation with decreased stemness, making GBM cells more sensitive to chemotherapy, which could improve patient prognosis. Thus, HIF1α and HIF2α regulate each other with negative feedback. In addition, HIF1α and HIF2α are upstream regulators of epidermal growth factor (EGF), which controls the malignant development of GBM through the EGFR-PI3K/AKT-mTOR-HIF1α signalling pathway. In brief, the HIF1α/HIF2α-EGF/EGFR-PI3K/AKT-mTOR-HIF1α signalling axis contributes to the growth of GBM through a positive feedback mechanism. Finally, HIF1α and HIF2α regulate Sox2 and Klf4, contributing to stemness expression and inducing cell cycle arrest, thus increasing malignancy in GBM. In summary, HIF1α and HIF2α regulate glioblastoma malignant progression through the EGFR-PI3K/AKT pathway via a positive feedback mechanism under the effects of Sox2 and Klf4, which provides a new tumour development model and strategy for glioblastoma treatment.
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http://dx.doi.org/10.1038/s41419-021-03598-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990922PMC
March 2021

Tactile Perceptual Thresholds of Electrovibration in VR.

IEEE Trans Vis Comput Graph 2021 May 15;27(5):2618-2626. Epub 2021 Apr 15.

Haptic sensation plays an important role in providing physical information to users in both real environments and virtual environments. To produce high-fidelity haptic feedback, various haptic devices and tactile rendering methods have been explored in myriad scenarios, and perception deviation between a virtual environment and a real environment has been investigated. However, the tactile sensitivity for touch perception in a virtual environment has not been fully studied; thus, the necessary guidance to design haptic feedback quantitatively for virtual reality systems is lacking. This paper aims to investigate users' tactile sensitivity and explore the perceptual thresholds when users are immersed in a virtual environment by utilizing electrovibration tactile feedback and by generating tactile stimuli with different waveform, frequency and amplitude characteristics. Hence, two psychophysical experiments were designed, and the experimental results were analyzed. We believe that the significance and potential of our study on tactile perceptual thresholds can promote future research that focuses on creating a favorable haptic experience for VR applications.
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http://dx.doi.org/10.1109/TVCG.2021.3067778DOI Listing
May 2021

Lung Lesion Localization of COVID-19 from Chest CT Image: A Novel Weakly Supervised Learning Method.

IEEE J Biomed Health Inform 2021 Mar 19;PP. Epub 2021 Mar 19.

Chest computed tomography (CT) image data is necessary for early diagnosis, treatment, and prognosis of Coronavirus Disease 2019(COVID-19). Artificial intelligence has been tried to help clinicians in improving the diagnostic accuracy and working efficiency of CT. Whereas, existing supervised approaches on CT image of COVID-19 pneumonia require voxel-based annotations for training, which take a lot of time and effort. This paper proposed a weakly-supervised method for COVID-19 lesion localization based on generative adversarial network (GAN) with image-level labels only. We first introduced a GAN-based framework to generate normal-looking CT slices from CT slices with COVID-19 lesions. We then developed a novel feature match strategy to improve the reality of generated images by guiding the generator to capture the complex texture of chest CT images. Finally, the localization map of lesions can be easily obtained by subtracting the output image from its corresponding input image. By adding a classifier branch to the GAN-based framework to classify localization maps, we can further develop a diagnosis system with improved classification accuracy. Three CT datasets from hospitals of Sao Paulo, Italian Society of Medical and Interventional Radiology, and China Medical University about COVID-19 were collected in this article for evaluation. Our weakly supervised learning method obtained AUC of 0.883, dice coefficient of 0.575, accuracy of 0.884, sensitivity of 0.647, specificity of 0.929, and F1-score of 0.640, which exceeded other widely used weakly supervised object localization methods by a significant margin. We also compared the proposed method with fully supervised learning methods in COVID-19 lesion segmentation task, the proposed weakly supervised method still leads to a competitive result with dice coefficient of 0.575. Furthermore, we also analyzed the association between illness severity and visual score, we found that the common severity cohort had the largest sample size as well as the highest visual score which suggests our method can help rapid diagnosis of COVID-19 patients, especially in massive common severity cohort. In conclusion, we proposed this novel method can serve as an accurate and efficient tool to alleviate the bottleneck of expert annotation cost and advance the progress of computer-aided COVID-19 diagnosis.
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http://dx.doi.org/10.1109/JBHI.2021.3067465DOI Listing
March 2021

Antimicrobial Photodynamic Therapy Combined With Antibiotic in the Treatment of Rats With Third-Degree Burns.

Front Microbiol 2021 24;12:622410. Epub 2021 Feb 24.

Tianjin Key Laboratory of Biomedical Material, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

Cationic porphyrin conjugate, protoporphyrin IX-methyl ethylenediamine derivative (PPIX-MED) has a potent photosensitive antibacterial effect on clinically isolated bacteria, including methicillin-resistant , (MRSA), , and . This study investigated (i) the PPIX-MED-mediated antimicrobial photodynamic effect on these three species and (ii) the effect of antimicrobial photodynamic therapy (aPDT) combined with the use of an antibiotic on the healing of third-degree burns of rats with the wounds infected by these bacterial species. PPIX-MED exerted a potent inhibitory effect on the growth of the three bacterial species by producing reactive oxygen species when photoactivated. PPIX-MED-mediated antimicrobial photodynamic therapy (PPIX-MED-aPDT) had high bacterial photoinactivation ability , with a minimum inhibitory concentration of 15.6 μM PPIX-MED against each of the three types of bacteria and minimum bactericidal concentrations of 31.25 μM against MRSA and and 62.5 μM against In rats with third-degree burns infected by a mixture of these bacteria, the bactericidal efficiency of PPIX-MED-aPDT-combined-with-antibiotic treatment was higher than that of antibiotic or aPDT treatment alone. This was confirmed by analysis of viable bacterial counts in wound tissue and blood. Enzyme-linked immunosorbent assay revealed that aPDT-combined-with-antibiotic treatment resulted in an obvious reduction in tumor necrosis factor-alpha and interleukin-6 levels compared with the no-treatment control group and the other treatment groups. Immunohistochemistry revealed that the expression of basic fibroblast growth factor and CD31 (a marker of neovascularization), expressed in burn wound tissue was higher in the aPDT-combined-with-antibiotic treatment group than in the other groups. PPIX-MED-aPDT has a promising bactericidal effect both and , and PPIX-MED-aPDT-combined-with-antibiotic treatment enhanced the healing of infected third-degree burns in rats.
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http://dx.doi.org/10.3389/fmicb.2021.622410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943878PMC
February 2021

Dynamic Immune/Inflammation Precision Medicine: The Good and the Bad Inflammation in Infection and Cancer.

Front Immunol 2021 23;12:595722. Epub 2021 Feb 23.

New York University (NYU) Tandon School of Engineering, Six Metrotech Center, Brooklyn, NY, United States.

Normal or "good" inflammation process starts from a local cellular response against injury or any infectious agent, with the activation of neutrophils, macrophages, Langerhans cells, dendritic cells, and innate immune cells. Cytokines and chemokines are produced to amplify the local inflammatory process followed by the migration of immune cells to the regional lymph nodes where adaptive immune response is initiated. Systemic inflammation enhances the biological response to mobilize additional cells from central and peripheral immune/hematopoietic system. Local mechanisms to limit inflammation are initiated and lead to healing. During the normal inflammatory process, there is a balance between the production of inflammatory chemokines/cytokines such as Tumor Necrosis Factor (TNF)-α, interleukin (IL)-6 and IL-1 and the production of compounds that limit inflammation and have an immune suppressive effect, such as IL-10 and Transforming Factor (TGF) β. IL-6 and IL-6/soluble IL-6 Receptor (R) complex stimulate liver cells to produce inflammatory proteins, which represents the systemic inflammation response. The magnitude and the duration of the systemic inflammatory response are linked to the cause, under genetic and epigenetic control. Significant inflammation as seen in septic shock, in severe forms of infections or in certain active cancers, represents the "bad inflammation", correlated with a poor prognosis. In addition, the persistence of a chronic smoldering inflammation may lead to pathological situations which are observed in the majority of inflammatory, degenerative, dysmetabolic, or dysimmune diseases and cancer. Chronic smoldering inflammation is a cross between different pathological situations possibly linked. In addition, within the tumor microenvironment, inflammatory process results from different cellular mechanisms modulated by metabolic and vascular changes. On the contrary, a limited and balanced inflammation initiates the normal immune response, including the adaptive response which amplifies any immunotherapy, including vaccines. Immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cells are associated with cytokine release syndrome, a clinical risk leading to the use of anti-cytokine drugs. Nowadays, it is time to monitor the dynamic inflammatory process for a better immune precision medicine in both infections and cancer.
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http://dx.doi.org/10.3389/fimmu.2021.595722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940508PMC
February 2021

A novel artificial intelligence protocol to investigate potential leads for diabetes mellitus.

Mol Divers 2021 Mar 9. Epub 2021 Mar 9.

Artificial Intelligence Medical Center, School of Intelligent Systems Engineering, Sun Yat-Sen University, Shenzhen, 510275, China.

Dipeptidyl peptidase-4 (DPP4) is highly participated in regulating diabetes mellitus (DM), and inhibitors of DPP4 may act as potential DM drugs. Therefore, we performed a novel artificial intelligence (AI) protocol to screen and validate the potential inhibitors from Traditional Chinese Medicine Database. The potent top 10 compounds were selected as candidates by Dock Score. In order to further screen the candidates, we used numbers of machine learning regression models containing support vector machines, bagging, random forest and other regression algorithms, as well as deep neural network models to predict the activity of the candidates. In addition, as a traditional method, 2D QSAR (multiple linear regression) and 3D QSAR methods are also applied. The AI methods got a better performance than the traditional 2D QSAR method. Moreover, we also built a framework composed of deep neural networks and transformer to predict the binding affinity of candidates and DPP4. Artificial intelligence methods and QSAR models illustrated the compound, 2007_4105, was a potent inhibitor. The 2007_4105 compound was finally validated by molecular dynamics simulations. Combining all the models and algorithms constructed and the results, Hypecoum leptocarpum might be a potential and effective medicine herb for the treatment of DM.
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http://dx.doi.org/10.1007/s11030-021-10204-8DOI Listing
March 2021

Investigation and assessment of ecological water resources in the salt marsh area of a salt lake: A case study of West Taijinar Lake in the Qaidam Basin, China.

PLoS One 2021 23;16(2):e0245993. Epub 2021 Feb 23.

School of Chemical Engineering, Qinghai University, Xining, Qinghai, China.

The water ecology of salt marshes plays a crucial role in climate regulation, industrial production, and flood control. Due to a poor understanding of water ecology and the extensive mining of salt resources, concerns are mounting about declining groundwater levels, shrinking salt marshes, and other problems associated with the simple yet extremely fragile water ecosystem of salt marshes in arid salt lake areas. This study assessed the ecological status of water resources in the downstream salt marsh area of West Taijinar Lake in the Qaidam Basin, China (2010-2018). Using data from a field investigation, the water ecosystem was divided into an ecological pressure subsystem, an environmental quality subsystem, and a socio-economic subsystem according to an analytic hierarchy process. Each subsystem was quantitatively assessed using the ecological footprint model, the single-factor index, and available data for the salt marsh area. The results showed that water resources were always in a surplus state during the study period, whose development and utilization had a safe status. Surface water had low plankton diversity with no evidence of eutrophication, but its Cl- and SO42- concentrations were too high for direct industrial water uses. Groundwater quality was classified into class V because of high salt concentrations, which could be considered for industrial use given the demand of industrial production. The socio-economic efficiency of water resources was high, as distinguished by decreased water consumption per 10,000 yuan GDP and excellent flood resistance. In conclusion, the ecological status of water resources was deemed good in the study area and this could help sustain regional development. However, since the water ecology in this area is mainly controlled by annual precipitation, it would be challenging to deal with the uneven distribution of precipitation and flood events and to make full use of them for groundwater recharge. This study provides insight into the impact of salt lake resource exploration on water ecology, and the results can be useful for the rational utilization of water resources in salt marshes in other arid areas.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245993PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901737PMC
February 2021

Plasma exosomes from depression ameliorate inflammation-induced depressive-like behaviors via sigma-1 receptor delivery.

Brain Behav Immun 2021 May 16;94:225-234. Epub 2021 Feb 16.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Jiangsu, China; Department of Pharmacy, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address:

A growing body of studies indicated that exosomes are one of vital players in pathological process of neuropsychiatric diseases, but their role in major depressive disorder (MDD) remains poorly understood. Here we purified plasma exosomes from depression including lipopolysaccharide (LPS)-challenged depression, chronic restraint stress (CRS)-induced depression, MDD subjects, and from control mice or volunteers. The therapeutic effect of these exogenous exosomes was assessed utilizing behavioral tests and biochemical approaches in the LPS-caused depression or microglial BV2 cells. The expression of exosomal sigma-1 receptor (Sig-1R) was evaluated by western blotting. The role of Sig-1R in the biological function of exosomes was determined using Sig-1R knockout mice and HEK 293 cells. Our results revealed that injection of exosomes from depression models or patients rather than normal controls significantly ameliorated depressive-like behaviors, deficiency of BDNF expression and neuro-inflammation in LPS-challenged mice. In addition, co-culture with exosomes from depression models or patients instead of from controls prevented LPS-induced inflammation responses in microglial BV2 cells. Moreover, Sig-1R was demonstrated for the first time to significantly be enriched in exosomes from depression models or patients compared with that from normal controls. However, Sig-1R null exosomes no longer emerged antidepressant-like action in LPS-challenged mice. Thus, we demonstrated that plasma exosomes from depression exerted antidepressant-like effects in a Sig-1R dependent manner in the LPS-induced depression. This work improves our understanding of the exosomes in depression, suggesting a novel exosomes-based approach for MDD treatment.
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http://dx.doi.org/10.1016/j.bbi.2021.02.004DOI Listing
May 2021

The storage stability of Bacillus subtilis spore displaying cysteine protease of Clonorchis sinensis and its effect on improving the gut microbiota of mice.

Appl Microbiol Biotechnol 2021 Mar 19;105(6):2513-2526. Epub 2021 Feb 19.

Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

Bacillus subtilis (B. subtilis) spore can serve as an ideal vehicle for expressing heterologous antigens, and elicit specific immune responses by oral administration. In previous studies, we successfully constructed the recombinant B. subtilis spores expressing cysteine protease of Clonorchis sinensis (C. sinensis, B.s-CsCP), and confirmed that oral administration of B.s-CsCP could elicit good protective immune responses in mice. In this study, Gram staining was used to observe the morphology of B.s-CsCP in different form, and the storage of liquid spores and lyophilized spores at different temperatures was compared. The mice were orally immunized with three different doses of spores (2×10, 1×10, and 5×10 CFU/day) for three times in total at biweekly interval. Then, antibody levels of mice were measured, the safety of spores was evaluated, and the changes of gut microbiota after oral gavage of spores (1×10 dose) were investigated. Results showed that B. subtilis was a typical Gram-positive bacterium, and its spore had good resistance to chemical dye. Liquid B. subtilis spores resuspended in sterile water could be stored for a long time at 4 °C or below, while lyophilized spores could be well stored even at RT and better at lower temperatures. Oral administration of B. subtilis spores to mice could stimulate both local mucosal and systemic immune responses in a dose-dependent manner without toxic side effects. Besides, beneficial bacteria producing butyrate such as Odoribacter were increased, while potential pathogens such as Escherichia-Shigella were decreased in mice intestine. Therefore, our work further confirmed that B. subtilis spores expressing CsCP could be a promising oral vaccine against C. sinensis with the advantages of stability, safety, easy storage, and promotion of intestinal health.Key Points• Recombinant CsCP B. subtilis spores could be easily preserved in either liquid or freeze-dried state.• Oral immunization of recombinant spores in mice could increase both local and system immune levels in a dose-dependent manner.• Oral administration of recombinant spores increased the number of beneficial bacteria and reduced the number of harmful bacteria in the intestinal tract of mice.
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http://dx.doi.org/10.1007/s00253-021-11126-zDOI Listing
March 2021

Multimodal Retinal Imaging for Detection of Ischemic Stroke.

Front Aging Neurosci 2021 2;13:615813. Epub 2021 Feb 2.

Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

: This study aims to evaluate ocular changes in patients with ischemic stroke using multimodal imaging and explore the predictive value of ocular abnormalities for ischemic stroke. : A total of 203 patients (ischemic stroke group, 62; control group, 141) were enrolled in this study. Basic data from patients, including age; gender; height; weight; history of hypertension, hyperlipidemia, diabetes, alcohol use, and coronary heart disease; and smoking status, were collected. Consequently, Doppler color ultrasound, color fundus photography, and optical coherence tomography (OCT) examinations were conducted. Differences in traditional risk factors and ocular parameters between the two groups were compared, and binary logistic regression was used for multivariate analysis. : The central retinal artery equivalent (CRAE) in the ischemic stroke group was 150.72 ± 20.15 μm and that in the control group was 159.68 ± 20.05 μm. The difference was statistically significant ( = 0.004). Moreover, the subfoveal choroidal thickness (SFChT) in the ischemic stroke group was 199.90 ± 69.27 μm and that in the control group was 227.40 ± 62.20 μm. The difference was statistically significant ( = 0.006). Logistic regression results showed that smoking [odds ratio (OR) = 2.823; 95% confidence interval (95% CI) = 1.477-5.395], CRAE (OR = 0.980; 95% CI = 0.965-0.996), and SFChT (OR = 0.994; 95% CI = 0.989-0.999) are associated with increased risk of ischemic stroke when ocular parameters were combined with traditional risk factors. The area under the receiver operating characteristic (ROC) curve was 0.726, which shows good diagnostic accuracy. : SFChT may be a diagnostic marker for early detection and monitoring of ischemic stroke. Combined with traditional risks, retinal artery diameter, and choroidal thickness, the prediction model can improve ischemic stroke prediction.
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http://dx.doi.org/10.3389/fnagi.2021.615813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884475PMC
February 2021

Randomized Trial of Different initial IVIG Regimens in Kawasaki Disease.

Pediatr Int 2021 Feb 18. Epub 2021 Feb 18.

Pediatric Heart Center, Children's Hospital of Fudan University, Shanghai, China.

Background: We aimed to assess the efficacy of different initial intravenous immunoglobulin (IVIG) regimens in Kawasaki disease (KD) patients to find more cost-effective therapy options.

Methods: A multicentre, open-label, blind-endpoint randomized controlled trial was conducted from January 2014 to December 2015. KD Patients within 10 days of illness were randomly assigned to receive different IVIG regimens (Group A, 2 g/kg once; Group B, 1 g/kg for 2 consecutive days; Group C, 1 g/kg once) and aspirin 30mg/kg/d. Primary outcomes included hours to defervescence and development of coronary artery lesions (CAL) during the study period. Major secondary outcomes included total fever days, total dose of IVIG, changes of laboratory data, length of stay, and hospitalization expenses. (ClinicalTrials.gov: NCT02439996).

Results: A total of 404 patients underwent randomization. No difference was found in the outcomes of defervescence among three groups at 6, 12, 24, and 36 hours after completion of initial IVIG infusion. There were no differences in the incidence of CAL during the study period (at week 2, month 1, month 3, and month 6 of illness), changes of laboratory data, total fever days and length of stay. Group C patients had the lowest total dose of IVIG (mean: 1.2 vs 2.2 vs 2.1 g/kg; P<0.001) and hospitalization expenses (mean: 8443.8 vs 10798.4 vs 11011.4 RMB; P<0.001) than other two groups.

Conclusions: A single dose of 1g/kg IVIG is a low-cost treatment with the same efficacy as 2 g/kg IVIG and can be an option for the initial therapy of KD patients.
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http://dx.doi.org/10.1111/ped.14656DOI Listing
February 2021

Pathogenesis and Immune Response of Ebinur Lake Virus: A Newly Identified That Exhibited Strong Virulence in Mice.

Front Microbiol 2020 1;11:625661. Epub 2021 Feb 1.

Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.

are a group of viruses with significant public and veterinary health importance. These viruses are mainly transmitted through mosquito-, midge-, and tick-vectors, and are endemic to various regions of the world. Ebinur Lake virus (EBIV), a newly identified member of , was isolated from mosquitoes in Northwest China. In the present study, we aimed to characterize the pathogenesis and host immune responses of EBIV in BALB/c mice, as an animal model. Herein, we determined that BALB/c mice are highly susceptible to EBIV infection. The infected mice exhibited evident clinical signs including weight loss, mild encephalitis, and death. High mortality of mice was observed even with inoculation of one plaque-forming unit (PFU) of EBIV, and the infected mice succumbed to death within 5-9 days. After EBIV challenge, rapid viremic dissemination was detected in the peripheral tissues and the central nervous system, with prominent histopathologic changes observed in liver, spleen, thymus, and brain. Blood constituents' analysis of EBIV infected mice exhibited leukopenia, thrombocytopenia, and significantly elevated ALT, LDH-L, and CK. Further, EBIV infection induced obvious cytokines changes in serum, spleen, and brain in mice. Collectively, our data describe the first study that systematically examines the pathogenesis of EBIV and induced immune response in an immunocompetent standard mouse model, expanding our knowledge of this virus, which may pose a threat to One Health.
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http://dx.doi.org/10.3389/fmicb.2020.625661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882632PMC
February 2021

Using the Compressed Sensing Technique for Lumbar Vertebrae Imaging: Comparison with Conventional Parallel Imaging.

Curr Med Imaging 2021 Jan 26. Epub 2021 Jan 26.

Department of Radiology, Shengjing Hospital of China Medical University. China.

Objective: To compare conventional sensitivity encoding turbo spin-echo (SENSE-TSE) with compressed sensing plus SENSE turbo spin-echo (CS-TSE) in lumbar vertebrae magnetic resonance imaging (MRI).

Methods: This retrospective study of lumbar vertebrae MRI included 600 patients; 300 patients received SENSE-TSE and 300 patients received CS-TSE. The SENSE acceleration factor was 1.4 for T1WI, 1.7 for T2WI, and 1.7 for PDWI. The CS total acceleration factor was 2.4, 3.6, 4.0, and 4.0 for T1WI, T2WI, PDWI sagittal, and T2WI transverse, respectively. The image quality of each MRI sequence was evaluated objectively by the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) and subjectively on a five-point scale. Two radiologists independently reviewed the MRI sequences of the 300 patients receiving CS-TSE, and their diagnostic consistency was evaluated. The degree of intervertebral foraminal stenosis and nerve root compression was assessed using the T1WI sagittal and T2WI transverse images.

Results: The scan time was reduced from 7 min 28 s to 4 min 26 s with CSTSE. The median score of nerve root image quality was 5 (p > 0.05). The diagnostic consistency using CS-TSE images between the two radiologists was high for diagnosing lumbar diseases (κ > 0.75) and for evaluating the degree of lumbar foraminal stenosis and nerve root compression (κ = 0.882). No differences between SENSE-TSE and CS-TSE were observed for sensitivity, specificity, positive predictive value, or negative predictive value.

Conclusion: CS-TSE has potential for diagnosing lumbar vertebrae and disc disorders.
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http://dx.doi.org/10.2174/1573405617666210126155814DOI Listing
January 2021

Risk and Prognosis of Secondary Bladder Cancer After Radiation Therapy for Rectal Cancer: A Large Population-Based Cohort Study.

Front Oncol 2020 25;10:586401. Epub 2021 Jan 25.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Although radiation therapy (RT) improves local control for rectal cancer (RC), the long-term risks from RT, including development of a secondary malignancy, are controversial. The risk and prognosis of secondary bladder cancer (SBC) in RC patients undergoing RT have not been adequately studied. Our goal is to investigate the impact of RT on the risk of developing SBC and assess their survival outcomes.

Methods: This large population-based study included RC patients as their initial primary cancer from nine registries of the Surveillance, Epidemiology and End Results (SEER) database between 1973 and 2015. The cumulative incidence of SBC was assessed by using Fine and Gray's competing risk regression. The standardized incidence ratio (SIR) was used to compare the incidence of SBC in RC survivors to the US general population. The Kaplan-Meier method was used to evaluate the 10-year overall survival (OS) and 10-year cancer specific survival (CSS) for patients with SBC.

Results: Of 74,646 RC patients, 24,522 patients were treated with surgery and RT and 50,124 patients were treated with surgery alone. The incidence of SBC was 1.85% among patients who received RT and 1.24% among patients who did not. The incidence of SBC in RC patients who received RT was higher than the US general population (SIR, 1.35; 95% CI, 1.19-1.53, P<0.05), and decreased with increasing age at diagnosis, and increased with time since diagnosis. In competing risk regression analysis, undergoing RT was associated with a higher risk of SBC (hazard ratio [HR], 1.443, 95% confidence interval [CI], 1.209-1.720; P<0.001). The results of the dynamic SIR for SBC revealed that a slightly increased risk of SBC was observed after RT in the early latency, and was significantly related to the variations of age at RC diagnosis and decreased with time progress. The 10-year OS and CSS among SBC patients after RT were comparable to SBC patients after NRT.

Conclusion: Radiation was associated with an increased risk of developing SBC in RC patients, and special attention should be paid to the surveillance of these patients.
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http://dx.doi.org/10.3389/fonc.2020.586401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868538PMC
January 2021

A Longitudinal Study of T2 Mapping Combined With Diffusion Tensor Imaging to Quantitatively Evaluate Tissue Repair of Rat Skeletal Muscle After Frostbite.

Front Physiol 2020 25;11:597638. Epub 2021 Jan 25.

Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China.

: T2 mapping and diffusion tensor imaging (DTI) enable the detection of changes in the skeletal muscle microenvironment. We assessed T2 relaxation times, DTI metrics, performed histological characterization of frostbite-induced skeletal muscle injury and repair, and provided diagnostic imaging biomarkers. : Thirty-six Sprague Dawley rats (200 ± 10 g) were obtained. Thirty rats were used for establishing a skeletal muscle frostbite model, and six were untreated controls. Functional MR sequences were performed on rats on days 0, 3, 5, 10, and 14 ( = 6 per time point). Rats were then sacrificed to obtain the quadriceps muscles. Tensor eigenvalues (1, λ2, and λ3), mean diffusivity (MD), fractional anisotropy (FA), and T2 values were compared between the frostbite model and control rats. ImageJ was used to measure the extracellular area fraction (EAF), muscle fiber cross-sectional area (fCSA), and skeletal muscle tumor necrosis factor (TNF-), and Myod1 expression. The correlation between the histological and imaging parameters of the frostbitten skeletal muscle was evaluated. Kolmogorov-Smirnoff test, Leven's test, one-way ANOVA, and Spearman coefficient were used for analysis. T2 relaxation time of frostbitten skeletal muscle was higher at all time points ( < 0.01). T2 relaxation time correlated with EAF, and TNF- and Myod1 expression ( = 0.42, < 0.05; = 0.86, < 0.01; = 0.84, < 0.01). The average tensor metrics (MD, 1, λ2, and λ3) of skeletal muscle at 3 and 5 days of frostbite increased ( < 0.05), and fCSA correlated with 1, λ2, and λ3, and MD ( = 0.65, < 0.01; = 0.48, < 0.01; = 0.52, < 0.01; = 0.62, < 0.01). T2 mapping and DTI imaging detect frostbite-induced skeletal muscle injury early. This combined approach can quantitatively assess skeletal muscle repair and regeneration within 2 weeks of frostbite. Imaging biomarkers for the diagnosis of frostbite were suggested.
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http://dx.doi.org/10.3389/fphys.2020.597638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868413PMC
January 2021

Topical Steroids and Antibiotics for Adult Blepharokeratoconjunctivitis (BKC): A Meta-Analysis of Randomized Clinical Trials.

J Ophthalmol 2021 8;2021:3467620. Epub 2021 Jan 8.

Beijing Tongren Eye Center, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.

Purpose: A meta-analysis was conducted to evaluate the efficacy and safety of topical treatments (including steroids and antibiotics) for adults with blepharokeratoconjunctivitis (BKC).

Methods: The following databases were searched for relevant randomised controlled trials (RCTs): China National Knowledge Infrastructure (CNKI), Web of Science, MEDLINE, PubMed, Embase, and Cochrane Central Register of Controlled Trials database (CENTRAL). Two reviewers selected studies and analyzed the risk of bias independently. The treatments were loteprednol 0.5%/tobramycin 0.3% (LE/T) and dexamethasone 0.1%/tobramycin 0.3% (DM/T). The efficacy outcome measures were change from baseline (CFB) in composite scores of ocular symptoms and signs; the CFB in the signs composite scores for blepharitis, conjunctivitis, and keratitis at each visit; the total ocular adverse event incidence (AEs); and the incidence of intraocular pressure (IOP) increase after treatment. Prepost mean differences (MDs) were compared for continuous outcome variables, and incidences were analyzed for dichotomous data. The pooled effect sizes were analyzed using 95% confidence intervals (CIs) in a fixed-effect model. Heterogeneity was evaluated using the -test and statistic.

Results: The CFB to final visit in ocular symptoms and signs of BKC was not statistically different between the two treatments (95% CI, -0.33 to 1.50; MD = 0.58; =0.21). The CFB in signs composite scores for blepharitis (95% CI, -0.16 to 0.48; MD = 0.16; =0.32), conjunctivitis (95% CI, -0.55 to 1.76; MD = 0.61; =0.30), and keratitis (95% CI, 0.00-0.28; MD = 0.14; =0.05) was also similar with the two treatments. LE/T was a safer intervention than DM/T, with fewer overall adverse events (95% CI, 0.34-0.80; RR = 0.52; =0.003) and significantly less elevation of intraocular pressure (IOP) (95% CI, 0.32-0.70; RR = 0.47; =0.0002).

Conclusions: DM/T and LE/T are both effective treatments for BKC, but LE/T may be a safer intervention.
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http://dx.doi.org/10.1155/2021/3467620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817233PMC
January 2021

Synergistic Effects of Cryptotanshinone and Senkyunolide I in Guanxinning Tablet Against Endogenous Thrombus Formation in Zebrafish.

Front Pharmacol 2020 14;11:622787. Epub 2021 Jan 14.

Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

Thrombosis is a key pathological event in cardiovascular diseases, and is also the most important targeting process for their clinical management. New drug development in thrombosis treatment is still in great demand. According to the traditional Chinese medicine (TCM) theory, thrombosis belongs to the syndrome of blood stasis. Bunge and DC are two common TCM herbs with long-term documented function in promoting blood circulation and inhibiting thrombosis, especially when used together. Guanxinning Tablet, a modern Chinese drug which contains extracts of the two herbs, also showed strong therapeutic effects in coronary heart disease. However, the pharmacological mechanism is still lacking for the compatibility of the two herbs. Here, through zebrafish-based fluorescence screening, we demonstrated the synergistic effects between Bunge and DC. in regulating endogenous thrombosis. Moreover, combined with high-resolution mass spectrometry, the main compounds of the botanical drugs were analyzed and screened in our model system. Interestingly, cryptotanshinone and senkyunolide I, two representative compounds, respectively derived from the two herbs, also showed synergistic antithrombotic effects. Further analysis suggested that they may regulate thrombi formation at different levels multiple signaling pathways, including oxidative stress, platelet activation and coagulation cascade. Taken together, our findings provided solid biological supports toward the drug compatibility theory of TCM, and suggested cryptotanshinone and senkyunolide I as promising drug candidates in thrombosis management.
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http://dx.doi.org/10.3389/fphar.2020.622787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841298PMC
January 2021