Publications by authors named "Jianrong Xu"

167 Publications

Morphological, Functional, and Tissue Characterization of Silent Myocardial Involvement in Patients With Primary Biliary Cholangitis.

Clin Gastroenterol Hepatol 2021 Aug 28. Epub 2021 Aug 28.

State Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute; Division of Gastroenterology and Hepatology, Division of Cardiology, Key Laboratory of Coronary Heart Disease, Shanghai Municipal Education Commission; Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Background & Aims: Cirrhotic cardiomyopathy is a major complication and cause of morbidity in end-stage primary biliary cholangitis (PBC). However, it is unclear whether there is clinically silent myocardial involvement at the early stage of PBC before cirrhosis and cardiac manifestations. This prospective, three-center, multi-modality cardiac imaging study on the early identification of myocardial impairment in PBC (EARLY-MYO-PBC) was designed to identify silent myocardial impairment in PBC patients without cardiac manifestations.

Methods: A total of 112 subjects (56 with PBC and 56 age- and sex-matched controls) undergoing cardiovascular magnetic resonance (CMR) were enrolled. Demographic, serologic, and cardiac imaging data were prospectively collected. All participants had no cardiac discomfort or previous heart disease and had normal electrocardiographic findings.

Results: Subclinical myocardial involvement, as evidenced by cardiac morphologic, functional, and tissue characterization changes on CMR, including hyperdynamic left ventricular (LV) ejection fraction (median, 75% in PBC patients vs 69% in controls, P = .029), subclinical myocardial edema by T2-short tau inversion recovery (21% vs 2% in controls, P = .001), elevated extracellular matrix indices (30% vs 26% in controls, P < .001), and impaired myocardial viability by positive late gadolinium enhancement (LGE) (36%), was detected in PBC patients. Importantly, a mid-wall "stripe" at the LV septum was identified as a PBC-specific LGE pattern that differs from other known cardiomyopathies. In multivariate analysis, gp210 positivity (odds ratio [OR] = 9.909, P = .010), lower hemoglobin (OR = 0.919, P = .004), and body mass index (OR = 0.638, P = .005) were independent predictors of cardiac abnormalities in PBC.

Conclusions: This study demonstrates clinically silent cardiac impairment with specific CMR patterns in PBC, allowing optimal screening for early myocardial impairment and potentially timely therapies. (Trial registration no.: NCT03545672).
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http://dx.doi.org/10.1016/j.cgh.2021.08.035DOI Listing
August 2021

sp. nov., an actinomycete isolated from human skin.

Int J Syst Evol Microbiol 2021 Aug;71(8)

Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu 610041, PR China.

A novel actinomycete, designated as strain WCH-YHL-001, was isolated from skin biopsy specimens of a patient at West China Hospital, Chengdu, Sichuan Province, PR China. The cells were Gram-positive, aerobic, heterotrophic and non-motile. They formed an extensive substrate with short aerial mycelia, whose branches fragmented into rod-shaped elements. Growth occurred at 10-40 °C, pH 5.0-12.0 and with NaCl concentrations of 0-4.0 % (w/v). The major cellular fatty acids of strain WCH-YHL-001 were C, C 9, C 10-methyl and summed feature 3. The predominant respiratory quinone was MK-8 (H4-cycl). The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol mannoside, unknown phospholipids and unidentified glycolipids. The diagnostic diamino acid of peptidoglycan was -diaminopimelic acid. The whole-cell sugar pattern consisted of arabinose and glucose. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain WCH-YHL-001 belonged to the genus . The average nucleotide identity (ANI) and DNA-DNA hybridization (DDH) values between strain WCH-YHL-001 and type strains of species were lower than the cut-offs (≥95-96 % for ANI and ≥70 % for DDH) required to define a bacterial species. The genomic DNA G+C content was 67.8 mol%. Phylogenetic, physiological and chemotaxonomic data suggested that strain WCH-YHL-001 represented a novel species of the genus , for which the name sp. nov. is proposed, with the type strain WCH-YHL-001 (=GDMCC 4.181=JCM 34475 =NBRC 114973).
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http://dx.doi.org/10.1099/ijsem.0.004970DOI Listing
August 2021

Intracranial Atherosclerotic Plaque Characteristics and Burden Associated With Recurrent Acute Stroke: A 3D Quantitative Vessel Wall MRI Study.

Front Aging Neurosci 2021 28;13:706544. Epub 2021 Jul 28.

Department of Radiology, University of Washington, Seattle, WA, United States.

Intracranial atherosclerotic disease (ICAD) tends to affect multiple arterial segments, and previous studies rarely performed a comprehensive plaque analysis of the entire circle of Willis for the evaluation of recurrent stroke risk. We aimed to investigate the features of circle of Willis ICAD on 3D magnetic resonance vessel wall imaging (MR-VWI) and their relationships with recurrent acute stroke. Patients with either acute ischemic stroke (within 4 weeks after stroke) or chronic ischemic stroke (after 3 months of stroke) due to intracranial atherosclerotic plaque underwent 3D contrast-enhanced MR-VWI covering major cerebral arteries. Participants were divided into three groups: first-time acute stroke, recurrent acute stroke, and chronic stroke. Culprit plaque (defined as the only lesion or the most stenotic lesion when multiple plaques were present within the same vascular territory of the stroke) and non-culprit plaque characteristics, including total plaque number, plaque thickness, plaque area, plaque burden (calculated as plaque area divided by outer wall area), enhancement ratio (ER), eccentricity, and stenosis, were measured and compared across the three groups. Associations between plaque characteristics and recurrent acute stroke were investigated by multivariate analysis. A total of 176 participants (aged 61 ± 10 years, 109 men) with 702 intracranial plaques were included in this study. There were 80 patients with first-time acute stroke, 42 patients with recurrent acute stroke, and 54 patients with chronic stroke. More intracranial plaques were found per patient in the recurrent acute stroke group than in the first-time acute stroke or chronic stroke group (5.19 ± 1.90 vs. 3.71 ± 1.96 and 3.46 ± 1.33, < 0.001). Patients in the recurrent acute stroke group had greater culprit plaque burden ( < 0.001) and higher culprit ER ( < 0.001) than the other two groups. After adjustment of clinical demographic factors, in multivariate analysis, coronary artery disease (CAD) (odds ratio, = 4.61; = 0.035), total plaque number ( = 1.54; = 0.003), culprit plaque ER ( = 2.50; = 0.036), and culprit plaque burden ( per 10% increment = 2.44; = 0.010) were all independently associated with recurrent acute stroke compared to the first-time acute stroke. Increased intracranial atherosclerotic plaque number, higher culprit plaque ER, greater culprit plaque burden, and CAD are independently associated with recurrent acute stroke.
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http://dx.doi.org/10.3389/fnagi.2021.706544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355600PMC
July 2021

A comprehensive comparative assessment of 3D molecular similarity tools in ligand-based virtual screening.

Brief Bioinform 2021 Jun 18. Epub 2021 Jun 18.

South China University of Technology, Guangzhou 510006, China.

Three-dimensional (3D) molecular similarity, one major ligand-based virtual screening (VS) method, has been widely used in the drug discovery process. A variety of 3D molecular similarity tools have been developed in recent decades. In this study, we assessed a panel of 15 3D molecular similarity programs against the DUD-E and LIT-PCBA datasets, including commercial ROCS and Phase, in terms of screening power and scaffold-hopping power. The results revealed that (1) SHAFTS, LS-align, Phase Shape_Pharm and LIGSIFT showed the best VS capability in terms of screening power. Some 3D similarity tools available to academia can yield relatively better VS performance than commercial ROCS and Phase software. (2) Current 3D similarity VS tools exhibit a considerable ability to capture actives with new chemotypes in terms of scaffold hopping. (3) Multiple conformers relative to single conformations will generally improve VS performance for most 3D similarity tools, with marginal improvement observed in area under the receiving operator characteristic curve values, enrichment factor in the top 1% and hit rate in the top 1% values showed larger improvement. Moreover, redundancy and complementarity analyses of hit lists from different query seeds and different 3D similarity VS tools showed that the combination of different query seeds and/or different 3D similarity tools in VS campaigns retrieved more (and more diverse) active molecules. These findings provide useful information for guiding choices of the optimal 3D molecular similarity tools for VS practices and designing possible combination strategies to discover more diverse active compounds.
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http://dx.doi.org/10.1093/bib/bbab231DOI Listing
June 2021

Diffusion-weighted MRI for predicting pathologic response to neoadjuvant chemotherapy in breast cancer: evaluation with mono-, bi-, and stretched-exponential models.

J Transl Med 2021 06 2;19(1):236. Epub 2021 Jun 2.

Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160, Pujian Rd, Shanghai, 200127, China.

Background: To investigate the performance of diffusion-weighted (DW) MRI with mono-, bi- and stretched-exponential models in predicting pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) for breast cancer, and further outline a predictive model of pCR combining DW MRI parameters, contrast-enhanced (CE) MRI findings, and/or clinical-pathologic variables.

Methods: In this retrospective study, 144 women who underwent NACT and subsequently received surgery for invasive breast cancer were included. Breast MRI including multi-b-value DW imaging was performed before (pre-treatment), after two cycles (mid-treatment), and after all four cycles (post-treatment) of NACT. Quantitative DW imaging parameters were computed according to the mono-exponential (apparent diffusion coefficient [ADC]), bi-exponential (pseudodiffusion coefficient and perfusion fraction), and stretched-exponential (distributed diffusion coefficient and intravoxel heterogeneity index) models. Tumor size and relative enhancement ratio of the tumor were measured on contrast-enhanced MRI at each time point. Pre-treatment parameters and changes in parameters at mid- and post-treatment relative to baseline were compared between pCR and non-pCR groups. Receiver operating characteristic analysis and multivariate regression analysis were performed.

Results: Of the 144 patients, 54 (37.5%) achieved pCR after NACT. Overall, among all DW and CE MRI measures, flow-insensitive ADC change (ΔADC) at mid-treatment showed the highest diagnostic performance for predicting pCR, with an area under the receiver operating characteristic curve (AUC) of 0.831 (95% confidence interval [CI]: 0.747, 0.915; P < 0.001). The model combining pre-treatment estrogen receptor and human epidermal growth factor receptor 2 statuses and mid-treatment ΔADC improved the AUC to 0.905 (95% CI: 0.843, 0.966; P < 0.001).

Conclusion: Mono-exponential flow-insensitive ADC change at mid-treatment was a predictor of pCR after NACT in breast cancer.
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http://dx.doi.org/10.1186/s12967-021-02886-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173748PMC
June 2021

Post-transcriptional regulation of α7 nAChR expression by miR-98-5p modulates cognition and neuroinflammation in an animal model of Alzheimer's disease.

FASEB J 2021 06;35(6):e21658

Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Alzheimer's disease (AD) is a complicated neurodegenerative disease and therefore addressing multiple targets simultaneously has been believed as a promising therapeutic strategy against AD. α7 nicotinic acetylcholine receptor (nAChR), which plays an important role in improving cognitive function and alleviating neuroinflammation in central nervous system (CNS), has been regarded as a potential target in the treatment of AD. However, the regulation of α7 nAChR at post-transcriptional level in mammalian brain remains largely speculated. Herein, we uncovered a novel post-transcriptional regulatory mechanism of α7 nAChR expression in AD and further demonstrated that miR-98-5p suppressed α7 nAChR expression through directly binding to the 3'UTR of mRNA. Knockdown of miR-98-5p activated Ca signaling pathway and consequently reversed cognitive deficits and Aβ burden in APP/PS1 mice. Furthermore, miR-98-5p downregulation increased α7 nAChR expression, and ameliorated neuroinflammation via inhibiting NF-κB pathway and upregulating Nrf2 target genes. Our findings illustrate a prominent regulatory role of miR-98-5p in targeting inflammation and cognition, and provide an insight into the potential of miR-98-5p/α7 nAChR axis as a novel therapeutic strategy for AD.
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http://dx.doi.org/10.1096/fj.202100257RDOI Listing
June 2021

A graphene oxide coated tapered microfiber acting as a super-sensor for rapid detection of SARS-CoV-2.

Lab Chip 2021 06;21(12):2398-2406

Shanghai Key Laboratory of Modern Optical System, Engineering Research Center of Optical Instrument and System (Ministry of Education), School of Optical-Electrical and Computer Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.

COVID-19 is a new strain of highly contagious coronavirus, and at present, more than 221.4 million people have been infected with this virus, and the death toll exceeds 2793398. Early and fast detection of COVID-19 from infected individuals is critical to limit its spreading. Here, we report an innovative approach to detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein by combining DNA/RNA oligomers as aptamers and a graphene oxide (GO) coated optical microfiber as a sensor system. The DNA/RNA aptamers can effectively capture the SARS-CoV-2 N protein in vitro, with the GO coated optical microfiber aptasensor for real-time monitoring of the SARS-CoV-2 N protein. Due to the extremely high surface-to-volume ratio and excellent optical and biochemical properties of the GO surface layer, the fixing effect of the microfiber surface is significantly improved and the lowest limit of detection (LOD) is 6.25 × 10-19 M. Furthermore, in order to prove the feasibility of this sensing method in clinical applications, we use this sensor to detect the N protein mixed in fetal bovine serum (FBS) samples. The experimental results show that the biosensor can quickly and effectively detect the N protein (1 × 10-9 M) in a complex sample matrix within 3 minutes. These findings suggest that this approach can be utilized for quantitative monitoring of coronavirus particles due to its high sensitivity, which can help to quickly exclude patients who do not have the infection. Collectively, the optical microfiber sensor system could be expected to become an important platform for the diagnosis of coronavirus due to its simple detection scheme and easy miniaturization.
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http://dx.doi.org/10.1039/d0lc01231aDOI Listing
June 2021

Anti-inflammatory activity of psoralen in human periodontal ligament cells via estrogen receptor signaling pathway.

Sci Rep 2021 Apr 22;11(1):8754. Epub 2021 Apr 22.

Department of Periodontology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.

Psoralen is one of the most effective ingredients extracted from the Chinese herb, Psoralea corylifolia L. Studies have found that psoralen has anti-inflammatory and estrogen-like effects; however, little research has been conducted to elucidate the mechanisms underlying these effects. Through the molecule docking assay, psoralen was found to have a better combination with ERα than ERβ. In human periodontal ligament cells, psoralen was found to upregulate the estrogen target genes (e.g., CTSD, PGR, TFF1) and down-regulate the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8) stimulated by P. gingivalis LPS, as well as TLR4-IRAK4-NF-κb signaling pathway proteins. These effects were reversed by the ER antagonist ICI 182780. These results indicated that psoralen may exert anti-inflammatory effects as an agonist to ER, which could provide a theoretical basis for the use of psoralen for adjuvant therapy and prevention of periodontitis.
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http://dx.doi.org/10.1038/s41598-021-85145-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062431PMC
April 2021

Domain adaptive and fully automated carotid artery atherosclerotic lesion detection using an artificial intelligence approach (LATTE) on 3D MRI.

Magn Reson Med 2021 09 22;86(3):1662-1673. Epub 2021 Apr 22.

Department of Radiology, University of Washington, Seattle, Washington, USA.

Purpose: To develop and evaluate a domain adaptive and fully automated review workflow (lesion assessment through tracklet evaluation, LATTE) for assessment of atherosclerotic disease in 3D carotid MR vessel wall imaging (MR VWI).

Methods: VWI of 279 subjects with carotid atherosclerosis were used to develop LATTE, mainly convolutional neural network (CNN)-based domain adaptive lesion classification after image quality assessment and artery of interest localization. Heterogeneity in test sets from various sites usually causes inferior CNN performance. With our novel unsupervised domain adaptation (DA), LATTE was designed to accurately classify arteries into normal arteries and early and advanced lesions without additional annotations on new datasets. VWI of 271 subjects from four datasets (eight sites) with slightly different imaging parameters/signal patterns were collected to assess the effectiveness of DA of LATTE using the area under the receiver operating characteristic curve (AUC) on all lesions and advanced lesions before and after DA.

Results: LATTE had good performance with advanced/all lesion classification, with the AUC of >0.88/0.83, significant improvements from >0.82/0.80 if without DA.

Conclusions: LATTE can locate target arteries and distinguish carotid atherosclerotic lesions with consistently improved performance with DA on new datasets. It may be useful for carotid atherosclerosis detection and assessment on various clinical sites.
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http://dx.doi.org/10.1002/mrm.28794DOI Listing
September 2021

Three-dimensional breast tumor segmentation on DCE-MRI with a multilabel attention-guided joint-phase-learning network.

Comput Med Imaging Graph 2021 06 31;90:101909. Epub 2021 Mar 31.

Department of Electronic Engineering, Fudan University, Shanghai, 200433, China; Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention (MICCAI) of Shanghai, Shanghai, 200232, China. Electronic address:

Accurate breast and tumor segmentations from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is vital in breast disease diagnosis. Here, we propose a novel attention-guided joint-phase-learning network for multilabel segmentation including the breast and tumors simultaneously and automatically. Instead of common multichannel inputs, our novel network consists of five separated streams designed for extracting comprehensive features for each DCE-MRI phase to fully use the dynamic intensity of enhanced images. A new time-signal intensity map was designed based on the DCE-MRI pixel-by-pixel values and added as an additional stream to reflect breast tumor dynamic variations. The multiple streams were fused in a fully connected layer to integrate the comprehensive tumor information. Weighted-loss was applied to the multilabel strategy to highlight breast tumor segmentation. In addition, the net applies the self-attention module with grid-based attention coefficients based on a global feature vector to emphasize breast regions and suppress irrelevant non-breast tissue features. We trained our method on 144 DCE-MRI datasets acquired from Philips and achieved mean Dice coefficients of 0.92 and 0.86 for breast and tumor segmentations that were superior to common networks with multichannel structures. The model was extended to an independent test set with 59 cases from two different MRI machines and achieved a Dice coefficient of 0.83 for breast tumor segmentation, which illustrates the robustness of our framework. The automatically generated masks can improve the accuracy and time of diagnosis of malignant and benign breast tumors. Qualitative comparisons illustrate that the proposed method has high precision and generalizability.
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http://dx.doi.org/10.1016/j.compmedimag.2021.101909DOI Listing
June 2021

Change in mortality rates of respiratory disease during the COVID-19 pandemic.

Expert Rev Respir Med 2021 08 31;15(8):1083-1088. Epub 2021 Mar 31.

Department of Chronic Disease Prevention and Control, Suzhou Center for Disease Control and Prevention, Suzhou, Jiangsu, China.

Objective: This study explored the change in mortality rates of respiratory disease during the corona virus disease 2019 (COVID-19) pandemic.

Methods: Death data of registered residents of Suzhou from 2014 to 2020 were collected and the weekly mortality rates due to respiratory disease and all deaths were analyzed. The differences in mortality rates during the pandemic and the same period in previous years were compared.

Results: Before the pandemic, the crude mortality rate (CMR) and standardized mortality rate (SMR) of Suzhou residents including respiratory disease, were not much different from those in previous years. During the emergency period, the CMR of Suzhou residents was 180.2/100,000 and the SMR was 85.5/100,000, decreasing by 9.1% and 14.6%, respectively; the CMR of respiratory disease was 16.4/100,000 and the SMR was 6.8/100,000, down 41.4% and 44.9%, respectively. Regardless of the mortality rates of all deaths or respiratory disease, the rates were higher in males than in females, although males had aslightly greater decrease in all deaths during the emergency period compared with females, and the opposite was true for respiratory disease.

Conclusion: During the pandemic, the death rate of residents decreased, especially that due to respiratory disease.
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http://dx.doi.org/10.1080/17476348.2021.1908891DOI Listing
August 2021

Association of Type 2 Diabetes Mellitus and Glycemic Control With Intracranial Plaque Characteristics in Patients With Acute Ischemic Stroke.

J Magn Reson Imaging 2021 08 31;54(2):655-666. Epub 2021 Mar 31.

Department of Radiology, University of Washington, Seattle, Washington, USA.

Background: Type 2 diabetes mellitus (T2DM) has shown to be associated with carotid plaque vulnerability. However, the impact of T2DM on intracranial artery atherosclerosis is not well-understood.

Purpose: To evaluate the association of diabetes and glycemic control with intracranial atherosclerotic plaque characteristics identified by three-dimensional contrast enhanced MR vessel wall imaging in patients after acute ischemic stroke.

Study Type: Prospective.

Population: Two hundred and eighty-eight symptomatic patients with acute ischemic stroke due to intracranial atherosclerotic plaque.

Field Strength/sequence: T WI volume isotropic turbo spin-echo acquisition sequence at 3.0 T.

Assessment: Clinical profiles, blood biomarkers, the number of intracranial plaques, plaque enhanced score, and the features (location, luminal stenotic rate, intraplaque hemorrhage, length, burden, enhancement grade, and ratio) of culprit plaque (defined as the most stenotic lesion ipsilateral to the ischemic event) and nonculprit plaque were analyzed by three radiologists.

Statistical Tests: Analysis of variance (ANOVA), Shapiro-Wilk normality test, Levene's test, ANOVA with Bonferroni post-hoc test, Kruskal Wallis H test with subsequent pairwise comparisons, chi-square with Bonferroni post-hoc test, generalized linear regression, Pearson correlation test, Kendall's W and intra-class correlation coefficient.

Results: Two hundred and twenty-five participants (age 60 ± 10 years, 58.7% male) with 958 intracranial plaques were included. More intracranial plaques were found in the T2DM group than the non-T2DM group (4.80 ± 2.22 vs. 3.60 ± 1.78, P < 0.05). Patients with poorly-controlled T2DM exhibited higher culprit plaque enhancement ratio than patients with well-controlled T2DM and non-T2DM (2.32 ± 0.61 vs. 1.60 ± 0.62 and 1.39 ± 0.39; respectively, P < 0.05). After adjusting for other clinical variables, T2DM was independently associated with increased intracranial plaque number (β = 0.269, P < 0.05), and HbA1c level was independently associated with culprit plaque enhancement ratio (β = 0.641, P < 0.05) in multivariate analysis.

Data Conclusion: T2DM is associated with an increased intracranial plaque number. Higher HbA1c is associated with stronger plaque enhancement. 3D contrast enhanced MR vessel wall imaging may help better understand the association of T2DM and glycemic control with intracranial plaque.

Level Of Evidence: 1 TECHNICAL EFFICACY STAGE: 3.
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http://dx.doi.org/10.1002/jmri.27614DOI Listing
August 2021

Extract of inhibits lipid accumulation and ameliorates HFD-induced obesity in mice through regulating adipose differentiation by decreasing PPARγ and CEBP/α expression.

Food Nutr Res 2021 1;65. Epub 2021 Mar 1.

Tomas Lindahl Nobel Laureate Laboratory, Precision Medicine Research Centre, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.

Background: Obesity is a principal risk factor for the development of type 2 diabetes and cardiovascular diseases. Natural plants and/or foods play an important role in the management of obesity. (AAL) is a kind of potherb popular among Asian populations, and it is also consumed as a food ingredient and traditional herbal medicine.

Objective: We investigated the effects of water extract from AAL on high-fat-diet (HFD)-induced obese mice and 3T3-L1 adipocytes to develop a new functional food material.

Design: Nine-week-old male mice were randomly divided into control (chow diet, = 6) and HFD ( = 30) group. From 12-weeks onward, mice in the HFD group were further separated into model (saline, 6 mL/kg), simvastatin (0.11 mg/mL, 6 mL/kg), and AAL treatment (low, middle, and high dosage: 300, 600, and 900 mg/kg) group, with 6 animals per group, while mice in the control group were treated with saline (6 mL/kg). Food intake, body/fat weight, liver/kidney indexes, and lipid profiles were determined. Tissues were fixed with formalin for pathological examination. Western blotting and PCR were performed to evaluate the protein and mRNA expression in 3T3-L1 adipocytes. Oil Red O staining was used to determine lipid accumulation.

Results: AAL administration significantly suppressed body weight gain, and reduced fat pad weight and Lee's index in obese mice, but had no effect on liver/kidney index. AAL also reduced serum cholesterol, triglyceride, and LDL-C and increased HDL-C levels. Histological analysis revealed that AAL significantly ameliorated lipid accumulation in the liver and subcutaneous adipose tissue. , Oil Red O staining showed that AAL inhibited adipose differentiation by down-regulating the gene and protein expression of PPARγ and C/EBPα. AAL also reversed HFD-induced intestinal dysbacteriosis.

Conclusion: AAL water-soluble extract has a significant anti-adipogenic effect in the HFD-induced obese mice model.
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http://dx.doi.org/10.29219/fnr.v65.424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955518PMC
March 2021

A cascade-network framework for integrated registration of liver DCE-MR images.

Comput Med Imaging Graph 2021 04 24;89:101887. Epub 2021 Feb 24.

Shanghai United Imaging Intelligence Co., Ltd., China; Center for Advanced Medical Imaging Technology, Division of Life Sciences, Shanghai Advanced Research Institute, Chinese Academy of Sciences, China. Electronic address:

Registration of hepatic dynamic contrast-enhanced magnetic resonance images (DCE-MRIs) is an important task for evaluation of transarterial chemoembolization (TACE) or radiofrequency ablation by quantifying enhancing viable residue tumor against necrosis. However, intensity changes due to contrast agents combined with spatial deformations render technical challenges for accurate registration of DCE-MRI, and traditional deformable registration methods using mutual information are often computationally intensive in order to tolerate such intensity enhancement and shape deformation variability. To address this problem, we propose a cascade network framework composed of a de-enhancement network (DE-Net) and a registration network (Reg-Net) to first remove contrast enhancement effects and then register the liver images in different phases. In experiments, we used DCE-MRI series of 97 patients from Renji Hospital of Shanghai Jiaotong University and registered the arterial phase and the portal venous phase images onto the pre-contrast phases. The performance of the cascade network framework was compared with that of the traditional registration method SyN in the ANTs toolkit and Reg-Net without DE-Net. The results showed that the proposed method achieved comparable registration performance with SyN but significantly improved the efficiency.
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http://dx.doi.org/10.1016/j.compmedimag.2021.101887DOI Listing
April 2021

Response to letter to the editor: "Muscle blood flow, oxygen pressure, and hemoglobin/myoglobin saturation: The infernal triad".

Magn Reson Med 2021 07 8;86(1):15-16. Epub 2021 Mar 8.

Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

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http://dx.doi.org/10.1002/mrm.28735DOI Listing
July 2021

Loss of Integrity of Corpus Callosum White Matter Hyperintensity Penumbra Predicts Cognitive Decline in Patients With Subcortical Vascular Mild Cognitive Impairment.

Front Aging Neurosci 2021 18;13:605900. Epub 2021 Feb 18.

Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Loss of white matter (WM) integrity contributes to subcortical vascular mild cognitive impairment (svMCI). Diffusion tensor imaging (DTI) has revealed damage beyond the area of WM hyperintensity (WMH) including in normal-appearing WM (NAWM); however, the functional significance of this observation is unclear. To answer this question, in this study we investigated the relationship between microstructural changes in the WMH penumbra (WMH-P) and cognitive function in patients with svMCI by regional tract-based analysis. A total of 111 patients with svMCI and 72 patients with subcortical ischemic vascular disease (SIVD) without cognitive impairment (controls) underwent DTI and neuropsychological assessment. WMH burden was determined before computing mean values of fractional anisotropy (FA) and mean diffusivity (MD) within WMHs and WMH-Ps. Pearson's partial correlations were used to assess the relationship between measurements showing significant intergroup differences and composite -scores representing global cognitive function. Multiple linear regression analysis was carried out to determine the best model for predicting composite -scores. We found that WMH burden in the genu, body, and splenium of the corpus callosum (GCC, BCC, and SCC respectively); bilateral anterior, superior, and posterior corona radiata; left sagittal stratum was significantly higher in the svMCI group than in the control group ( < 0.05). The WMH burden of the GCC, BCC, SCC, and bilateral anterior corona radiata was negatively correlated with composite -scores. Among diffusion parameters showing significant differences across the 10 WM regions, mean FA values of WMH and WMH-P of the BCC were correlated with composite -scores in svMCI patients. The results of the multiple linear regression analysis showed that the FA of WMH-P of the BCC and WMH burden of the SCC and GCC were independent predictors of composite -score, with the FA of WMH-P of the BCC making the largest contribution. These findings indicate that disruption of the CC microstructure-especially the WMH-P of the BCC-may contribute to the cognitive deficits associated with SIVD.
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http://dx.doi.org/10.3389/fnagi.2021.605900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930322PMC
February 2021

Determining the invasiveness of ground-glass nodules using a 3D multi-task network.

Eur Radiol 2021 Sep 4;31(9):7162-7171. Epub 2021 Mar 4.

Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.

Objectives: The aim of this study was to determine the invasiveness of ground-glass nodules (GGNs) using a 3D multi-task deep learning network.

Methods: We propose a novel architecture based on 3D multi-task learning to determine the invasiveness of GGNs. In total, 770 patients with 909 GGNs who underwent lung CT scans were enrolled. The patients were divided into the training (n = 626) and test sets (n = 144). In the test set, invasiveness was classified using deep learning into three categories: atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive pulmonary adenocarcinoma (IA). Furthermore, binary classifications (AAH/AIS/MIA vs. IA) were made by two thoracic radiologists and compared with the deep learning results.

Results: In the three-category classification task, the sensitivity, specificity, and accuracy were 65.41%, 82.21%, and 64.9%, respectively. In the binary classification task, the sensitivity, specificity, accuracy, and area under the ROC curve (AUC) values were 69.57%, 95.24%, 87.42%, and 0.89, respectively. In the visual assessment of GGN invasiveness of binary classification by the two thoracic radiologists, the sensitivity, specificity, and accuracy of the senior and junior radiologists were 58.93%, 90.51%, and 81.35% and 76.79%, 55.47%, and 61.66%, respectively.

Conclusions: The proposed multi-task deep learning model achieved good classification results in determining the invasiveness of GGNs. This model may help to select patients with invasive lesions who need surgery and the proper surgical methods.

Key Points: • The proposed multi-task model has achieved good classification results for the invasiveness of GGNs. • The proposed network includes a classification and segmentation branch to learn global and regional features, respectively. • The multi-task model could assist doctors in selecting patients with invasive lesions who need surgery and choosing appropriate surgical methods.
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http://dx.doi.org/10.1007/s00330-021-07794-0DOI Listing
September 2021

Texture Analysis of Native T1 Images as a Novel Method for Noninvasive Assessment of Uremic Cardiomyopathy.

J Magn Reson Imaging 2021 07 18;54(1):290-300. Epub 2021 Feb 18.

Department of Nephrology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Noncontrast cardiac T times are increased in dialysis patients which might indicate fibrotic alterations in uremic cardiomyopathy.

Purpose: To explore the application of the texture analysis (TA) of T images in the assessment of myocardial alterations in dialysis patients.

Study Type: Case-control study.

Population: A total of 117 subjects, including 22 on hemodialysis, 44 on peritoneal dialysis, and 51 healthy controls.

Field Strength: A 3 T, steady-state free precession (SSFP) sequence, modified Look-Locker imaging (MOLLI).

Assessment: Two independent, blinded researchers manually delineated endocardial and epicardial borders of the left ventricle (LV) on midventricular T maps for TA.

Statistical Tests: Texture feature selection was performed, incorporating reproducibility verification, machine learning, and collinearity analysis. Multivariate linear regressions were performed to examine the independent associations between the selected texture features and left ventricular function in dialysis patients. Texture features' performance in discrimination was evaluated by sensitivity and specificity. Reproducibility was estimated by the intraclass correlation coefficient (ICC).

Results: Dialysis patients had greater T values than normal (P < 0.05). Five texture features were filtered out through feature selection, and four showed a statistically significant difference between dialysis patients and healthy controls. Among the four features, vertical run-length nonuniformity (VRLN) had the most remarkable difference among the control and dialysis groups (144 ± 40 vs. 257 ± 74, P < 0.05), which overlap was much smaller than Global T times (1268 ± 38 vs. 1308 ± 46 msec, P < 0.05). The VRLN values were notably elevated (cutoff = 170) in dialysis patients, with a specificity of 97% and a sensitivity of 88%, compared with T times (specificity = 76%, sensitivity = 60%). In dialysis patients, VRLN was significantly and independently associated with left ventricular ejection fraction (P < 0.05), global longitudinal strain (P < 0.05), radial strain (P < 0.05), and circumferential strain (P < 0.05); however, T was not.

Data Conclusion: The texture features obtained by TA of T images and VRLN may be a better parameter for assessing myocardial alterations than T times.

Level Of Evidence: 4 TECHNICAL EFFICACY: Stage 3.
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http://dx.doi.org/10.1002/jmri.27529DOI Listing
July 2021

Qualitative and Quantitative MRI Analysis in IDH1 Genotype Prediction of Lower-Grade Gliomas: A Machine Learning Approach.

Biomed Res Int 2021 22;2021:1235314. Epub 2021 Jan 22.

Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

Purpose: Preoperative prediction of isocitrate dehydrogenase 1 (IDH1) mutation in lower-grade gliomas (LGGs) is crucial for clinical decision-making. This study aimed to examine the predictive value of a machine learning approach using qualitative and quantitative MRI features to identify the IDH1 mutation in LGGs.

Materials And Methods: A total of 102 LGG patients were allocated to training ( = 67) and validation ( = 35) cohorts and were subject to Visually Accessible Rembrandt Images (VASARI) feature extraction (23 features) from conventional multimodal MRI and radiomics feature extraction (56 features) from apparent diffusion coefficient maps. Feature selection was conducted using the maximum Relevance Minimum Redundancy method and 0.632+ bootstrap method. A machine learning model to predict IDH1 mutation was then established using a random forest classifier. The predictive performance was evaluated using receiver operating characteristic (ROC) curves.

Results: After feature selection, the top 5 VASARI features were enhancement quality, deep white matter invasion, tumor location, proportion of necrosis, and T1/FLAIR ratio, and the top 10 radiomics features included 3 histogram features, 3 gray-level run-length matrix features, and 3 gray-level size zone matrix features and one shape feature. Using the optimal VASARI or radiomics feature sets for IDH1 prediction, the trained model achieved an area under the ROC curve (AUC) of 0.779 ± 0.001 or 0.849 ± 0.008 on the validation cohort, respectively. The fusion model that integrated outputs of both optimal VASARI and radiomics models improved the AUC to 0.879.

Conclusion: The proposed machine learning approach using VASARI and radiomics features can predict IDH1 mutation in LGGs.
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http://dx.doi.org/10.1155/2021/1235314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847347PMC
May 2021

Low-Dose vs Standard-Dose Alteplase in Acute Lacunar Ischemic Stroke: The ENCHANTED Trial.

Neurology 2021 03 3;96(11):e1512-e1526. Epub 2021 Feb 3.

From The George Institute for Global Health, Faculty of Medicine (Z.Z., C.D., C.X., S. Yoshimura, C.C., T.T.-Y., A.M., X.C., M.L.H., M.W., J.C., C.S.A.), and South Western Clinical School (M.W.P.), University of New South Wales Sydney, Australia; Department of Radiology (Z.Z., J.X.), Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China; Department of Neurology (C.D., C.C., C.S.A.), Royal Prince Alfred Hospital, Sydney Health Partners; Sydney Medical School (C.D., C.C.), University of Sydney, Australia; Department of Neurosurgery (C.X.), West China Hospital, Sichuan University, Chengdu, China; Department of Cerebrovascular Medicine (S. Yoshimura, T.T.-Y.), National Cerebral and Cardiovascular Center, Osaka; Department of Neurology and Neuroscience (T.T.-Y.), Nagoya City University Graduate School of Medical Science, Japan; Department of Neurology (S. You), the Second Affiliated Hospital of Soochow University, Suzhou, China; The George Institute for Global Health, School of Public Health (M.W.), Imperial College, London; Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Center (T.G.R.), University of Leicester, UK; Melbourne Brain Centre, Royal Melbourne Hospital University Department of Medicine (M.W.P.), University of Melbourne, Australia; Departments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, Cumming School of Medicine (A.M.D.), University of Calgary, Canada; Westmead Applied Research Centre (R.I.L.), University of Sydney, Australia; Division of Neuroimaging Sciences, Edinburgh Imaging and Centre for Clinical Brain Sciences (G.M., J.M.W.), and UK Dementia Research Institute (J.M.W.), University of Edinburgh; and The George Institute China at Peking University Health Science Center (C.S.A.), Beijing, China.

Objective: To determine any differential efficacy and safety of low- vs standard-dose IV alteplase for lacunar vs nonlacunar acute ischemic stroke (AIS), we performed post hoc analyzes from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) alteplase dose arm.

Methods: In a cohort of 3,297 ENCHANTED participants, we identified those with lacunar or nonlacunar AIS with different levels of confidence (definite/according to prespecified definitions based on clinical and adjudicated imaging findings. Logistic regression models were used to determine associations of lacunar AIS with 90-day outcomes (primary, modified Rankin Scale [mRS] scores 2-6; secondary, other mRS scores, intracerebral hemorrhage [ICH], and early neurologic deterioration or death) and treatment effects of low- vs standard-dose alteplase across lacunar and nonlacunar AIS with adjustment for baseline covariables.

Results: Of 2,588 participants with available imaging and clinical data, we classified cases as definite/probable lacunar (n = 490) or nonlacunar AIS (n = 2,098) for primary analyses. Regardless of alteplase dose received, lacunar AIS participants had favorable functional (mRS 2-6, adjusted odds ratio [95% confidence interval] 0.60 [0.47-0.77]) and other clinical or safety outcomes compared to participants with nonlacunar AIS. Low-dose alteplase (versus standard) had no differential effect on functional outcomes (mRS 2-6, 1.04 [0.87-1.24]) but reduced the risk of symptomatic ICH in all included participants. There were no differential treatment effects of low- vs standard-dose alteplase on all outcomes across lacunar and nonlacunar AIS (all ≥0.07).

Conclusions: We found no evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard dose for definite/probable lacunar AIS.

Classification Of Evidence: This study provides Class II evidence that for patients with lacunar AIS, low-dose alteplase had no additional benefit or safety over standard-dose alteplase.

Clinical Trial Registration: Clinicaltrials.gov identifier NCT01422616.
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http://dx.doi.org/10.1212/WNL.0000000000011598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032382PMC
March 2021

Irregular pulsation of intracranial unruptured aneurysm detected by four-dimensional CT angiography is associated with increased estimated rupture risk and conventional risk factors.

J Neurointerv Surg 2021 Sep 20;13(9):854-859. Epub 2021 Jan 20.

Department of Radiology, University of Washington, Seattle, Washington, USA.

Background: Intracranial aneurysms (IAs) are common in the population and current imaging-based rupture risk assessment needs to be refined. We aimed to use four-dimensional CT angiography (4D-CTA) to investigate the associations of irregular pulsation of IAs with conventional risk factors and the estimated rupture risk.

Methods: One hundred and five patients with 117 asymptomatic IAs underwent 4D-CTA. Geometric and morphologic parameters were measured and the presence of irregular pulsation (defined as a temporary focal protuberance ≥1 mm on more than three successive frames) was identified on 4D-CTA movies. One- and 5 year aneurysm rupture risk were estimated using UCAS and PHASES calculators. Univariate and multivariate analyses were performed to investigate the conventional risk factors associated with irregular pulsation.

Results: Irregular pulsation was observed in 41.0% (48/117) of IAs. Aneurysm size (OR=1.380, 95% CI 1.165 to 1.634), irregular shape (OR=3.737, 95% CI 1.108 to 12.608), and internal carotid artery location (OR=0.151, 95% CI 0.056 to 0.403) were independently associated with irregular pulsation (P<0.05). Aneurysms with irregular pulsation had more than a 6-fold higher estimated rupture risk (1- and 5-year risk [95% CI], 1.56% [0.42%-3.91%], and 2.40% [1.30%-4.30%], respectively) than aneurysms without irregular pulsation (0.23% [0.14%-0.78%] and 0.40% [0.40%-1.30%], respectively) (P<0.001).

Conclusions: IAs with irregular pulsation are associated with larger size, irregular-shape, and non-ICA origin, and have more than a 6-fold higher estimated 1- and 5-year rupture risk than aneurysms without irregular pulsation. Irregular pulsation should be validated in future longitudinal studies to determine its predictive value for aneurysm growth and rupture.
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http://dx.doi.org/10.1136/neurintsurg-2020-016811DOI Listing
September 2021

Combination Therapy Using Kartogenin-Based Chondrogenesis and Complex Polymer Scaffold for Cartilage Defect Regeneration.

ACS Biomater Sci Eng 2020 11 13;6(11):6276-6284. Epub 2020 Oct 13.

Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.

Articular cartilage has a highly organized structure, responsible for supporting tremendous mechanical loads. How to repair defected articular cartilage has become a great challenge as the avascular nature of cartilage limits its regenerative ability. Aiming to facilitate chondrogenic differentiation and cartilage regeneration, we recently explored a novel combination therapy using soluble poly-l-lysine/Kartogenin (L-K) nanoparticles and a poly(lactic--glycolic acid) PLGA/methacrylated hyaluronic acid (PLHA) complex scaffold. The potential use for joint cartilage reconstruction was investigated through L-K nanoparticles stimulating adipose-derived stem cells (ADSCs) on PLHA scaffolding, which ultimately differentiated into cartilage . In this study, on one hand, an effective method was established for obtaining uniform L-K nanoparticles by self-assembly. They were further proved to be biocompatible to ADSCs cytotoxicity assays and to accelerate ADSCs secreting type 2 collagen in a dose-dependent manner by immunofluorescence. On the other hand, the porous PLHA scaffold was manufactured by the combination of coprecipitation and ultraviolet (UV) cross-linking. Nanoindentation technology-verified PLHA had an appropriate stiffness close to actual cartilage tissue. Additional microscopic observation confirmed that the PLHA platform supported proliferation and chondrogenesis for ADSCs . In the presence of ADSCs, a 12-week osteochondral defect regeneration by the combination therapy showed that smooth and intact cartilage tissue successfully regenerated. Furthermore, the results of combination therapy were superior to those of phosphate-buffered saline (PBS) only, KGN, or KGN/PLHA treatment. The results of magnetic resonance imaging (MRI) and histological assessment indicated that the renascent tissue gradually regenerated while the PLHA scaffold degraded. In conclusion, we have developed a novel multidimensional combination therapy of cartilage defect repair that facilitated cartilage regeneration. This strategy has a great clinical translational potential for articular cartilage repair in the near future.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00724DOI Listing
November 2020

Optimal vacuum erectile device therapy regimen for penile rehabilitation in a bilateral cavernous nerve crush rat model.

Andrology 2021 05 26;9(3):894-905. Epub 2021 Jan 26.

Andrology Laboratory, West China Hospital, Sichuan University, Chengdu, China.

Background: Vacuum erectile device (VED) therapy has been widely used in penile rehabilitation after radical prostatectomy; however, there is no consensus on the best regimen.

Objectives: To explore an optimal VED therapy regimen in bilateral cavernous nerve crush (BCNC) rat model.

Materials And Methods: Adult male rats were used to measure the effects of different durations (1-30 min) of VED treatment on penile length, penile blood gas analysis, and adverse effects. Forty-eight adult male rats were randomly divided into Sham, BCNC, and VED treatment groups (2-3-2-3 min, 4-3-3 min, 5-5 min, and 10 min). Penile length, erectile function, and side effects were detected after VED treatment. Histopathological staining and Western blotting were performed to explore the cellular and molecular changes.

Results: Prolongation of the duration of VED treatment significantly decreased the penile oxygen saturation, partial oxygen pressure, and arterial blood ratio (P < 0.05). Compared with the BCNC group, all VED treatment regimens partially reversed BCNC-induced penile shortening and erectile dysfunction (P < 0.0001), with the 4-3-3-min and 5-5-min treatment groups exhibiting more significant improvement than the 10-min and 2-3-2-3-min treatment groups (P < 0.0001). The mechanism may be related to the up-regulation of the smooth muscle cell/collagen ratio, endothelial nitric oxide synthase, and α-smooth muscle actin (all P < 0.0001); and the down-regulation of hypoxia-inducible factor-1α, transforming growth factor-β1, and apoptosis (all P < 0.0001). The incidence of adverse effects in the 2-3-2-3-min treatment group was the highest.

Discussion: The commonly used VED therapy regimens maintained erectile function and penile length of BCNC rat by relieving hypoxia and fibrosis, and no further benefits were observed with increased treatment frequency or prolonged treatment duration.

Conclusion: Two consecutive 5-min treatments with a short interval is the optimal VED therapy regimen for penile rehabilitation in BCNC rat model.
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http://dx.doi.org/10.1111/andr.12968DOI Listing
May 2021

Comparison of mono-exponential, bi-exponential, kurtosis, and fractional-order calculus models of diffusion-weighted imaging in characterizing prostate lesions in transition zone.

Abdom Radiol (NY) 2021 06 3;46(6):2740-2750. Epub 2021 Jan 3.

Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China.

Purpose: To compare various models of diffusion-weighted imaging including mono-exponential, bi-exponential, diffusion kurtosis (DK) and fractional-order calculus (FROC) models in diagnosing prostate cancer (PCa) in transition zone (TZ) and distinguish the high-grade PCa [Gleason score (GS) ≥ 7] lesions from the total of low-grade PCa (GS ≤ 6) lesions and benign prostatic hyperplasia (BPH) in TZ.

Methods: 80 Patients with 103 lesions were included in this study. Nine metrics [including apparent diffusion coefficient (ADC) derived from mono-exponential model, slow diffusion coefficient (D), fast diffusion coefficient (D),, and f (the fraction of fast diffusion) from bi-exponential model; mean diffusivity (MD) and mean kurtosis (MK) from DK model; diffusion coefficient (D), fractional-order derivative in space (β), and spatial metric (μ) from FROC model] were calculated. Comparisons between BPH and PCa lesions as well as between clinically significant PCa (CsPCa) (GS ≥ 7, n = 31) and clinically insignificant lesions (Cins) (GS ≤ 6 and BPH, n = 72) of these metrics were conducted. Mann-Whitney U-test and receiver operating characteristic (ROC) analysis were used for statistical evaluations.

Results: The areas under the ROC curve (AUC) values of β derived from FROC model were 0.778 and 0.853 in differentiating PCa from BPH and in differentiating CS (GS ≥ 7) from Cins (GS ≤ 6 and BPH), both were the highest compared to other metrics. The AUC value of β was significantly higher than that of ADC (P = 0.009) in differentiating CS from Cins, while the differentiation between BPH and PCa did not reach the statistical significance when comparing with ADC (P = 0.089).

Conclusion: Although no significant difference was found in distinguishing PCa from BPH, the metric β derived from FROC model was superior to other diffusion metrics in differentiation between CS and Cins in TZ.
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http://dx.doi.org/10.1007/s00261-020-02903-xDOI Listing
June 2021

The optimization of a novel selective antagonist for human M muscarinic acetylcholine receptor.

Bioorg Med Chem Lett 2020 12 24;30(24):127632. Epub 2020 Oct 24.

Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pu Jian Road, Shanghai 200127, China. Electronic address:

Muscarinic acetylcholine receptors (mAChRs) comprise five distinct subtypes denoted M to M. The antagonism of M subtype could increase the release of acetylcholine from vesicles into the synaptic cleft and improve postsynaptic functions in the hippocampus via M receptor activation, displaying therapeutic potentials for Alzheimer's disease. However, drug development for M antagonists is still challenged among different receptor subtypes. In this study, by optimizing a scaffold from virtual screening, we synthesized two focused libraries and generated up to 50 derivatives. By measuring potency and binding selectivity, we discovered a novel M antagonist, ligand 47, featuring submicromolar IC, high M/M selectivity (~30-fold) and suitable lipophilicity (cLogP = 4.55). Further study with these compounds also illustrates the structure-activity relationship of this novel scaffold. Our study could not only provide novel lead structure, which was easy to synthesize, but also offer valuable information for further development of selective M ligands.
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http://dx.doi.org/10.1016/j.bmcl.2020.127632DOI Listing
December 2020

Blood oxygenation level-dependent cardiovascular magnetic resonance of the skeletal muscle in healthy adults: Different paradigms for provoking signal alterations.

Magn Reson Med 2021 03 16;85(3):1590-1601. Epub 2020 Sep 16.

Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Purpose: Stress blood oxygenation level-dependent (BOLD) cardiovascular magnetic resonance allows for quantitative evaluation of blood flow reserve in skeletal muscles. This study aimed to prospectively compare three commonly used skeletal BOLD cardiovascular magnetic resonance paradigms in healthy adults: gas inhalation, cuff compression-induced ischemia and postocclusive reactive hyperemia, and exercise.

Methods: Twelve young (22 ± 0.9 years) and 10 elderly (58 ± 5.0 years) healthy subjects underwent BOLD cardiovascular magnetic resonance under the three paradigms. signal intensity time curves were generated and quantitative parameters were calculated. Meanwhile, stress transcutaneous oxygen pressure measurements were obtained as comparison. Measurement reproducibility was assessed with intraclass correlation coefficients. Differences in the BOLD variation, the correlation with transcutaneous oxygen pressure, and the age-related change between paradigms were statistically analyzed.

Results: Minimum ischemic value and maximum hyperemic peak value showed the highest interobserver and interscan reproducibilities (intraclass correlation coefficient >0.90). The plantar dorsiflexion exercise paradigm elicited the largest BOLD variation (15.48% ± 10.56%), followed by ischemia (8.30% ± 6.33%). Negligible to weak changes were observed during gas inhalation. Correlations with transcutaneous oxygen pressure measurements were found in the ischemic phase (r = 0.966; P < .001) and in the postexercise phase (r = -0.936; P < .001). Minimum ischemic value, maximum hyperemic peak value, maximum postexercise value, and slope of postexercise signal decay showed significant differences between young and elderly subjects (P < .01).

Conclusion: Ischemia and reactive hyperemia have superior reproducibility, and exercise could induce the largest variation. Key parameters from the two paradigms show age-related differences.
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http://dx.doi.org/10.1002/mrm.28495DOI Listing
March 2021

Combating COVID-19 with integrated traditional Chinese and Western medicine in China.

Acta Pharm Sin B 2020 Jul 27;10(7):1149-1162. Epub 2020 Jun 27.

Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

COVID-19, an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout the world. China has achieved rapid containment of this highly infectious disease following the principles of early detection, early quarantine and early treatment with integrated traditional Chinese and Western medicine. The inclusion of traditional Chinese medicine (TCM) in the Chinese protocol is based on its successful historic experience in fighting against pestilence. Current findings have shown that the Chinese medicine can reduce the incidence of severe or critical events, improve clinical recovery and help alleviate symptoms such as cough or fever. To date there are over 133 ongoing registered clinical studies on TCM/integrated traditional Chinese and Western medicine. The three Chinese patent medicines (/ (Forsythiae and Honeysuckle Flower Pestilence-Clearing Granules/Capsules), (Honeysuckle Flower Cold-Relieving Granules) and (Stasis-Resolving & Toxin-Removing) were officially approved by the National Medical Products Administration to list COVID-19 as an additional indication. The pharmacological studies have suggested that Chinese medicine is effective for COVID-19 probably through its host-directed regulation and certain antiviral effects.
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http://dx.doi.org/10.1016/j.apsb.2020.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319939PMC
July 2020

Thrombolysis Outcomes in Acute Ischemic Stroke by Fluid-Attenuated Inversion Recovery Hyperintense Arteries.

Stroke 2020 07 17;51(7):2240-2243. Epub 2020 Jun 17.

The George Institute for Global Health, Faculty of Medicine, University of New South Wales Sydney, Australia (Z.Z., S.Y., C.D., A.M., T.T.-Y., C.C., X.W., X.C., J.C., C.S.A.).

Background And Purpose: To determine factors associated with fluid-attenuated inversion recovery (FLAIR) hyperintense arteries (FLAIR-HAs) on magnetic resonance imaging and their prognostic significance in thrombolysis-treated patients with acute ischemic stroke from the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) trial alteplase-dose arm.

Methods: Patients with acute ischemic stroke (N=293) with brain magnetic resonance imaging (FLAIR and diffusion-weighted imaging sequences) scanned <4.5 hours of symptom onset were assessed for location and extent (score) of FLAIR-HAs, infarct volume, large vessel occlusion (LVO), and other ischemic signs. Logistic regression models were used to determine predictors of FLAIR-HAs and the association of FLAIR-HAs with 90-day outcomes: favorable functional outcome (primary; modified Rankin Scale scores, 0-1), other modified Rankin Scale scores, and intracerebral hemorrhage.

Results: Prior atrial fibrillation, LVO, large infarct volume, and anterior circulation infarction were independently associated with FLAIR-HAs. The rate of modified Rankin Scale scores 0 to 1 was numerically lower in patients with FLAIR-HAs versus without (69/152 [45.4%] versus 75/131 [57.3%]), as was the subset of LVO (37/93 [39.8%] versus 9/16 [56.3%]), but not in those without LVO (25/36 [69.4%] versus 60/106 [56.6%]). After adjustment for covariables, FLAIR-HAs were independently associated with increased primary outcome (adjusted odds ratio [95% CI]: overall 4.14 [1.63-10.50]; with LVO 4.92 [0.87-27.86]; no LVO 6.16 [1.57-24.14]) despite an increased risk of hemorrhagic infarct (4.77 [1.12-20.26]).

Conclusions: FLAIR-HAs are more frequent in acute ischemic stroke with cardioembolic features and indicate potential for a favorable prognosis in thrombolysis-treated patients possibly mediated by LVO. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01422616.
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http://dx.doi.org/10.1161/STROKEAHA.119.028550DOI Listing
July 2020

Evaluation of chronic carotid artery occlusion by non-contrast 3D-MERGE MR vessel wall imaging: comparison with 3D-TOF-MRA, contrast-enhanced MRA, and DSA.

Eur Radiol 2020 Nov 11;30(11):5805-5814. Epub 2020 Jun 11.

Department of Radiology, University of Washington, Seattle, WA, USA.

Objectives: To analyze the accuracy of a non-contrast MR vessel wall imaging technique, three-dimensional motion-sensitized driven equilibrium prepared rapid gradient echo (3D-MERGE) for diagnosing chronic carotid artery occlusion (CCAO) characteristics compared with 3D time-of-flight (TOF) MRA, and contrast-enhanced MRA (CE-MRA), using digital subtraction angiography (DSA) as a reference standard.

Methods: Subjects diagnosed with possible CCAO by ultrasound were retrospectively analyzed. Patients underwent 3.0-T MR imaging with 3D-MERGE, 3D-TOF-MRA, and CE-MRA followed by DSA within 1 week. Diagnostic accuracy of occlusion, occlusion site, and proximal stump condition were assessed independently on 3 MRI sequences and DSA. Agreement of the above indicators was evaluated in reference to DSA.

Results: One hundred twenty-four patients with 129 suspected CCAO (5 with bilateral occlusions) met the inclusion criteria for our study. 3D-MERGE demonstrated a sensitivity, specificity, and accuracy of 97.0%, 86.7%, and 94.6%, respectively, with excellent agreement (Cohen's κ = 0.85; 95% CI, 0.71, 0.94) for diagnosing CCAO in reference to DSA. 3D-MERGE was superior in diagnosing CCAO compared with 3D-TOF-MRA (Cohen's κ = 0.61; 95% CI, 0.42, 0.77) and similar to CE-MRA (Cohen's κ = 0.93; 95% CI, 0.86, 1.00). 3D-MERGE also had excellent agreement compared with DSA for assessing occlusion sites (Cohen's κ = 0.85; 95% CI, 0.71, 0.97) and stump condition (Cohen's κ = 0.83; 95% CI, 0.71, 0.94). Moreover, 3D-MERGE provided additional information regarding the occluded segment, such as distal lumen collapse and vessel wall lesion components.

Conclusion: 3D-MERGE can reliably assess chronic carotid occlusive characteristics and has the ability to identify other vessel wall features of the occluded segment. This non-contrast MR vessel wall imaging technique is promising for assessment of CCAO.

Key Points: • Excellent agreement was found between 3D-MERGE and DSA for assessing chronic carotid artery occlusion, occlusion site, and proximal stump condition. • 3D-MERGE was shown to be a more accurate and efficient tool than 3D-TOF-MRA to detect the characteristics of the occluded segment. • 3D-MERGE provides not only luminal images for characterizing the proximal characteristics of occlusion but also vessel wall images for assessing the distal lumen and morphology of occlusion segment, which might help clinicians to optimize the treatment strategy for patients with chronic carotid artery occlusion.
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http://dx.doi.org/10.1007/s00330-020-06989-1DOI Listing
November 2020
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