Publications by authors named "Zheying Meng"

11 Publications

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Biodegradable cascade nanocatalysts enable tumor-microenvironment remodeling for controllable CO release and targeted/synergistic cancer nanotherapy.

Biomaterials 2021 Jul 6;276:121001. Epub 2021 Jul 6.

Department of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, PR China; State Key Laboratory of Oncogenes and Related Genes, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200233, PR China. Electronic address:

Gas therapy as an emerging therapeutic modality for cancer treatment is still facing critical challenges such as precise delivery and controllable release of therapeutic gas. Herein, we report a "tumor-microenvironment remodeling" strategy for in situ sustained release of CO gas and magnetic resonance imaging (MRI)-monitored targeted/synergistic cancer gas/starvation nanotherapy by engineering cascade biodegradable nanocatalyst. The nanocatalyst integrates the enzyme catalyst glucose oxidase (GOD) and HO-sensitive molecule manganese carbonyl (MnCO) entrapped biodegradable hollow mesoporous organosilica nanoparticles (HMONs). Especially, GOD is initially exploited as a gatekeeper, followed by surface engineering with arginine-glycine-aspartic acid (RGD) for specifically targeting αβ integrin-overexpressed cancer cells. The GOD is dissociated under reduced pH to release the loaded MnCO, and sequentially produce gluconic acid and HO to remodel the TME for facilitating the in situ generation of CO/Mn. As systematically demonstrated both at cellular level and in an animal tumor xenograft model, the engineered nanocatalyst achieves superior theranostics performance via combinatorial CO gas and starving-like nanotherapy. This work provides an effective strategy for augmenting CO-mediated antitumor efficacy by remodeling the tumor microenvironment.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121001DOI Listing
July 2021

Marriage of Virus-Mimic Surface Topology and Microbubble-Assisted Ultrasound for Enhanced Intratumor Accumulation and Improved Cancer Theranostics.

Adv Sci (Weinh) 2021 07 14;8(13):2004670. Epub 2021 May 14.

Department of Ultrasound in Medicine Shanghai Jiao Tong University Affiliated Sixth People's Hospital State Key Laboratory of Oncogenes and Related Genes Shanghai Jiao Tong University School of Medicine Shanghai 200032 P. R. China.

The low delivery efficiency of nanoparticles to solid tumors greatly reduces the therapeutic efficacy and safety which is closely related to low permeability and poor distribution at tumor sites. In this work, an "intrinsic plus extrinsic superiority" administration strategy is proposed to dramatically enhance the mean delivery efficiency of nanoparticles in prostate cancer to 6.84% of injected dose, compared to 1.42% as the maximum in prostate cancer in the previously reported study. Specifically, the intrinsic superiority refers to the virus-mimic surface topology of the nanoparticles for enhanced nano-bio interactions. Meanwhile, the extrinsic stimuli of microbubble-assisted low-frequency ultrasound is to enhance permeability of biological barriers and improve intratumor distribution. The enhanced intratumor enrichment can be verified by photoacoustic resonance imaging, fluorescence imaging, and magnetic resonance imaging in this multifunctional nanoplatform, which also facilitates excellent anticancer effect of photothermal treatment, photodynamic treatment, and sonodynamic treatment via combined laser and ultrasound irradiation. This study confirms the significant advance in nanoparticle accumulation in multiple tumor models, which provides an innovative delivery paradigm to improve intratumor accumulation of nanotherapeutics.
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http://dx.doi.org/10.1002/advs.202004670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261514PMC
July 2021

Ultrasound-assisted CF-filled PLGA nanobubbles for enhanced FGF21 delivery and improved prophylactic treatment of diabetic cardiomyopathy.

Acta Biomater 2021 Aug 12;130:395-408. Epub 2021 Jun 12.

Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, PR China.; Department of Ultrasound in Medicine, Shanghai Eighth People's Hospital, 8 Caobao Road, Shanghai 200235, PR China. Electronic address:

Diabetic cardiomyopathy (DCM) is a serious cardiac complication of diabetes that currently lacks specific treatment. Fibroblast growth factor 21 (FGF21) has been proved to have cardioprotective effect in DCM. However, the insufficient cardiac delivery effect of FGF21 limits its application in DCM. Therefore, to improve the therapeutic efficacy of FGF21 in DCM, an effective drug delivery system is urgently required. In this study, perfluoropropane (CF) and polyethylenimine (PEI)-doped poly (lactic-co-glycolic acid) (PLGA) nanobubbles (CPPNBs) were synthesized via double-emulsion evaporation and FGF21 was efficiently absorbed ([email protected]) via the electrostatic incorporation effect. [email protected] could effectively deliver FGF21 to the myocardial tissue through the cavitation effect under low-frequency ultrasound (LFUS). The as-prepared [email protected] could efficiently load FGF21 after doping with the cationic polymer PEI, and displayed uniform dispersion and favorable biosafety. After filling with CF, [email protected] could be used for distribution monitoring through ultrasound imaging. Moreover, [email protected] significantly downregulated the expression of ANP, CTGF, and caspase-3 mRNA via the action of LFUS owing to increased FGF21 release, therefore exhibiting enhanced inhibition of myocardial hypertrophy, apoptosis, and interstitial fibrosis in DCM mice. In conclusion, we established an effective protein delivery nanocarrier for the diagnosis and prophylactic treatment of DCM. STATEMENT OF SIGNIFICANCE: Diabetic cardiomyopathy (DCM) is a serious cardiac complication of diabetes that currently lacks effective clinical treatments. Fibroblast growth factor 21 (FGF21) can protect cardiomyocytes from diabetic damage, but insufficient cardiac drug delivery limits the application of FGF21 in DCM. In this study, perfluoropropane (C3F8) and polyethylenimine (PEI)-doped poly (lactic-co-glycolic acid) (PLGA) nanobubbles loaded with FGF21 ([email protected]) were developed for the prophylactic treatment of DCM. [email protected] could effectively deliver the FGF21 to the myocardial tissue through the cavitation effect of low-frequency ultrasound (LFUS). Our results indicated that [email protected] combined with LFUS could significantly down-regulate the expressions of ANP, CTGF, and caspase-3 mRNA, and as a result, it prevented the myocardial hypertrophy, apoptosis, and interstitial fibrosis of DCM mice. Overall, we established an effective protein delivery nanocarrier for the diagnosis and prophylactic treatment of DCM.
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http://dx.doi.org/10.1016/j.actbio.2021.06.015DOI Listing
August 2021

Monitoring radiofrequency therapy-induced tumor cell dissemination by in vivo flow cytometry.

Cytometry A 2021 Jun 2;99(6):593-600. Epub 2021 Mar 2.

Department of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.

Clinical and experimental findings have disclosed a high recurrence rate after radiofrequency ablation (RFA), which might be due to the dissemination of malignant cells into the vasculature during ablation. Here, we apply in vivo flow cytometry (IVFC) to monitor circulating tumor cells (CTCs) while performing ablation in a real-time and noninvasive way in an orthotopic model of prostate cancer. We report that CTCs are dramatically increased during RFA. The CTCs induced by ablation eventually translate into enhanced distant metastasis and reduced survival as compared to resection. Immunofluorescence analysis reveals that RFA significantly increases the infiltration of tumor-associated macrophages (TAMs) in the lung. Our study thus suggests that the ablative procedure of prostate tumors causes immediate tumor cell dissemination and increases distant metastasis.
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http://dx.doi.org/10.1002/cyto.a.24329DOI Listing
June 2021

Hollow Magnetic Nanocatalysts Drive Starvation-Chemodynamic-Hyperthermia Synergistic Therapy for Tumor.

ACS Nano 2020 08 30;14(8):9662-9674. Epub 2020 Jul 30.

Department of Ultrasound, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang 317000, P.R. China.

Magnetic hyperthermia therapy (MHT) has been considered as an excellent alternative for treatment of deep tumor tissue; however, up-regulation of heat shock proteins (HSPs) impairs its hyperthermal therapeutic effect. Reactive oxygen species (ROS) and competitive consumption of ATP are important targets that can block excessive HSP generation. We developed a magnetic nanocatalytic system comprised of glucose oxidase (GOD)-loaded hollow iron oxide nanocatalysts (HIONCs) to drive starvation-chemodynamic-hyperthermia synergistic therapy for tumor treatment. The Fe present in HIONCs contributed to ROS generation the Fenton reaction, relieving thermo-resistance and inducing cell apoptosis by chemodynamic action. The Fenton effect was enhanced through the conditions created by increased MHT-related temperature, GOD-mediated HO accumulation, and elevated tumor microenvironment acidity. The HIONCs catalase-like activity facilitated conversion of HO to oxygen, thereby replenishing the oxygen levels. We further demonstrated that locally injected HIONCs-GOD effectively inhibited tumor growth in PC3 tumor-bearing mice. This study presents a multifunctional nanocarrier system driving starvation-chemodynamic-magnetic-thermal synergistic therapy ROS and oxygen modulation for prostate tumor treatment.
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http://dx.doi.org/10.1021/acsnano.0c00910DOI Listing
August 2020

Real-Time Elastography in the diagnosis of prostate cancer: a systematic review.

Med Ultrason 2019 Aug;21(3):327-335

Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Shanghai Jiao Tong University Affliated Sixth People's Hospital, Shanghai, P.R.China.

Aim: To evaluate the diagnostic accuracy of real-time elastography as a method for detecting prostate cancer.

Material And Methods: Relevant studies applying real-time elastography as the diagnostic modality and biopsy as the reference standard, published by March 1, 2018 were retrieved from PubMed, EMBASE, Web of Science and Cochrane Library databases. Two independent reviewers inspected all these articles to confirm the matching of the inclusion criteria. One reviewer with methodological expertise extracted the data from the included studies. Sensitivity, specificity and diagnostic odds ratio (DOR) were used to obtain overall estimates. Randomized effect method, meta-regression and subgroup analysis were performed.

Results: Twenty-four studies out of 1156 identified articles met the inclusion criteria. Three groups were set: analysisby patient (Group 1), by core (Group 2), and by image (Group 3) and subgroups set in Group 1. The pooled estimate ofreal-time elastography sensitivity/ specificity/ DOR calculated with the identical P-value 0.00. Within subgroups "Asia" and"PSA>=10 ng/ml", the pooled sensitivity, specificity and DOR were 0.83, 0.65 (p=0.01, I2=73.40%; p=0.02, I2=69.5%), 0.80, 0.82 (p=0.66, I2=0.00%; p=0.58, I2=0.00%) and 20.2, 8.67 (p=0.09, I2=54.2%; p=0.20, I2=35.5%), respectively. In these three groups, the areas under the SROC curve were 0.7417, 0.9246, and 0.6213 independently.

Conclusions: Real-time elastography is a promising, reliable modality for the non-invasive diagnosis of patients with prostate cancer. The diagnostic accuracy of real-time elastography correlates tightly to the presence of higher PSA level and may help avoid unnecessary biopsy. It seems to be a useful tool in systemic biopsy.
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http://dx.doi.org/10.11152/mu-1965DOI Listing
August 2019

Whole transcriptome sequencing reveals biologically significant RNA markers and related regulating biological pathways in cardiomyocyte hypertrophy induced by high glucose.

J Cell Biochem 2019 01 22;120(1):1018-1027. Epub 2018 Sep 22.

Department of Ultrasound in Medicine, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Cardiomyocyte hypertrophy is a physiological adaptation used in an attempt to augment or preserve cardiac function for short periods. Long-term cardiomyocyte hypertrophy often progresses to heart failure. Previous studies have presented comprehensive mechanisms underlying cardiomyocyte hypertrophy, such as signaling pathways, marker genes, and marker miRNAs or lncRNAs. However, the mechanism in RNA level is still unclear. In this study, we used the whole transcriptome technology on cardiomyocety hypertrophy cells, which were cultured with a high concentration of d-glucose. Many differentially expressed markers, including genes, lncRNAs, miRNAs, and circRNAs were identified. Further quantitative real-time PCR verified the highly specific expressed genes, such as Eid1, Timm8b, Mrpl50, Dusp18, Abrc1, Klf13, and Igf1. Moreover, the functional pathways were also enriched with the differentially expressed lncRNA, miRNA, and circRNA. Our study gives new insights into cardiomyocyte hypertrophy and makes great progress in comprehending its mechanism.
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http://dx.doi.org/10.1002/jcb.27546DOI Listing
January 2019

Fibroblast growth factor 21 inhibition aggravates cardiac dysfunction in diabetic cardiomyopathy by improving lipid accumulation.

Exp Ther Med 2018 Jan 25;15(1):75-84. Epub 2017 Oct 25.

Department of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.

Diabetic cardiomyopathy (DCM) is one of the major causes of morbidity and mortality in diabetic patients. Recent studies have demonstrated an increased level of fibroblast growth factor 21 (FGF21) in the plasma of DCM patients, and FGF21 has been proven to be a cardiovascular protector of the heart. The present study aimed to further investigate the pathogenic role of FGF21 in DCM, hypothesizing that a lack of FGF21 may promote the progression of DCM by regulating the lipid metabolism, cardiac hypertrophy and cardiac fibrosis, thus deteriorating the cardiac dysfunction. A total of 44 mice were randomly assigned into the normal (n=6), DCM (n=6), normal + scrambled siRNA (n=6), DCM + scrambled siRNA (n=6), normal + FGF21 siRNA (n=10) and DCM + FGF21 siRNA (n=10) groups. Type 1 diabetes mellitus was induced to mice in the DCM groups by streptozotocin injection, while FGF21 expression was inhibited by FGF21 siRNA. Normal and DCM mice administrated with scrambled siRNA were respectively regarded as the controls for the normal + FGF21 siRNA and DCM + FGF21 siRNA groups. In the DCM group, FGF21 inhibition promoted cardiac hypertrophy and fibrosis, and the expression levels of their indicators, including atrial natriuretic factor, α-skeletal actin, collagen type I and III, and transforming growth factor-β, increased, leading to further decreased cardiac function. In addition, FGF21 inhibition in DCM mice elevated the quantity of lipid droplets and the concentration of heart triglycerides, plasma triglycerides and cholesterol levels, accompanied by downregulation of peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) and upregulation of cluster of differentiation (CD)36. Thus, the results indicated that FGF21 inhibition exacerbates the cardiac dysfunction by aggravating the lipid accumulation through regulating the expression levels of PGC-1α and CD36. In conclusion, it is suggested that FGF21 may be a potentially useful agent in the treatment of DCM.
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http://dx.doi.org/10.3892/etm.2017.5375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763648PMC
January 2018

[MicroRNA-182 modulates high glucose-induced cardiomyocyte hypertrophy via targeting Rac1].

Zhonghua Xin Xue Guan Bing Za Zhi 2015 Jul;43(7):619-24

Department of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Institute of Ultrasound in Medicine, Shanghai 200233, China; Email:

Objective: To investigate the role and signalling of microRNA(miR)-182 on regulating high glucose-induced cardiomyocyte hypertrophy.

Methods: The candidates of miR which might potentially be involved on targeting Rac1 were predicted by applying bioinformatics analysis. The expression of all related candidates miRs was verified by real-time reverse transcription-PCR (RT-PCR) in cardiac tissues of db/db mice and db/m mice. Then the relationship between candidates miR and Rac1 was investigated with Pearson relevant analysis. Neonatal mice cardiomyocytes were cultured and divided into 2 groups: normal glucose group and high glucose group. The level of selected miR and Rac1 in two groups was detected by RT-PCR. Neonatal mice cardiomyocytes were then randomly divided into 4 groups: normal glucose group, selected microRNA mimics control group, high glucose group, high glucose plus selected miR mimics control group. The morphology of cardiomyocyte in each group was detected under light microscope. Furthermore, Rac1, β-MHC and α-SMA expressions were detected in cultured cardiomyocyte treated by high glucose for 48 h after transfecting selected miR mimics by RT-PCR and Western blot.

Results: A total of 6 miR candidates potentially targeting Rac1 were screened by bioinformatics, which were miR-182, miR-142-3p, miR-140, miR-101a, miR-429 and miR-200b. Among these candidates, miR-182 and miR-142-3p expression was significantly downregulated in cardiac tissues of db/db mice compared with db/m controls (P < 0.05). MiR-182 was negatively correlated with Rac1 by person analysis (r = -0.891 02). Downregulation of miR-182 and upregulation of Rac1, β-MHC, α-SMA were found in high glucose-induced cardiomyocyte. After transfection of miR-182 mimics, hypertrophic changes were significantly reduced and Rac1 as well β-MHC expression was significantly downregulated in cardiomyocyte incubated with high glucose.

Conclusion: MiR-182 might be involved in the regulation of high glucose-induced myocardial hypertrophy process via targeting Rac1.
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July 2015

Effects of Vaccinium Berries on Serum Lipids: A Meta-Analysis of Randomized Controlled Trials.

Evid Based Complement Alternat Med 2015 9;2015:790329. Epub 2015 Aug 9.

Department of Geriatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai 200233, China.

The beneficial effects of anthocyanins consumption on cardiovascular risk are supported by mechanistic and epidemiologic evidence. In order to explore the effects of Vaccinium berries rich in anthocyanins on serum lipids, we conducted a meta-analysis of relevant randomized controlled trials (RCTs). Sixteen studies with 1109 subjects were included in this meta-analysis. Significant heterogeneity confirmed differential effects between Vaccinium subclasses. The whortleberry group is significantly superior to placebo in lipids improvement. Besides, bilberry groups show significant differences in reducing LDL-C and increasing HDL-C in comparison with other treatments. For many of the other subgroups and comparison arms, there was insufficient evidence to draw conclusions about efficacy.
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http://dx.doi.org/10.1155/2015/790329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546752PMC
September 2015

Diagnostic performance of the automated breast volume scanner: a systematic review of inter-rater reliability/agreement and meta-analysis of diagnostic accuracy for differentiating benign and malignant breast lesions.

Eur Radiol 2015 Dec 28;25(12):3638-47. Epub 2015 Apr 28.

Department of Ultrasound in Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111 Xianxia Road, Shanghai, 200336, China.

Objectives: To investigate the inter-rater reliability and agreement of the automated breast volume scanner (ABVS) and the diagnostic accuracy for differentiating malignant and benign lesions. The overall aim was to find out if the ABVS is applicable to daily clinical practice.

Methods: Qualifying studies were retrieved from Pubmed, EMBASE, Cochrane Library, Biosis Preview, CBM disc and by manual search and reference lists up to 30 September 2014. Pooled sensitivity and specificity of ABVS were calculated and summary receiver operating characteristic curves were drawn.

Results: Thirteen studies were included in the meta-analysis of diagnostic accuracy and seven studies were included in the systematic review of inter-rater reliability/agreement of ABVS. For 'diagnostic accuracy', the pooled values of sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were 92 % (95 % CI 89.9-93.8), 84.9 % (82.4-87.0), 6.172 (4.364-8.730), 0.101 (0.075-0.136), and 72.226 (39.637-131.61), respectively. For the studies of inter-rater reliability/agreement, the quality was heterogeneous and no evidenced result can be pooled.

Conclusions: Sensitivity and specificity of ABVS for differentiating malignant and benign breast lesions were high. More sound studies focusing on inter-rater reliability/agreement of ABVS, which deeply affect the clinical utilization and generalization of ABVS, are urgently needed.

Key Points: • ABVS has high sensitivity and specificity in differentiating malignant and benign breast lesions. • The quality of published inter-rater reliability studies is heterogeneous. • Empirical evidence concerning the inter-rater reliability/agreement for the ABVS is rare. • Comparison studies on ABVS and other medical imaging examinations are warranted.
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http://dx.doi.org/10.1007/s00330-015-3759-3DOI Listing
December 2015
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