Publications by authors named "Peiwen Li"

56 Publications

An integrated biomimetic array chip for establishment of collagen-based 3D primary human hepatocyte model for prediction of clinical drug-induced liver injury.

Biotechnol Bioeng 2021 Sep 3. Epub 2021 Sep 3.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.

Drug-induced liver injury (DILI) is a leading cause of therapy failure in the clinic and also contributes much to acute liver failure cases. Investigations of predictive sensitivity in animal models have limitations due to interspecies differences. Previously reported in vitro models of liver injury based on primary human hepatocytes (PHHs) cannot meet the requirements of high physiological fidelity, low cost, simple operation, and high throughput with improved sensitivity. Herein, we developed an integrated biomimetic array chip (iBAC) for establishing extracellular matrix (ECM)-based models. A collagen-based 3D PHH model was constructed on the iBAC as a case for the prediction of clinical DILI at throughput. The iBAC has a three-layer structure with a core component of 3D implanting holes. At an initial cell seeding numbers of 5000-10,000, the collagen-based 3D PHH model was optimized with improved and stabilized liver functionality, including cell viability, albumin, and urea production. Moreover, basal activities of most metabolic enzymes on the iBAC were maintained for at least 12 days. Next, a small-scale hepatotoxicity screening indicated that the 3D PHH model on the iBAC was more sensitive for predicting hepatotoxicity than the 2D PHH model on the plate. Finally, a large-scale screening of liver toxicity using 122 clinical drugs further demonstrated that the collagen-based 3D PHH model on the iBAC had superior predictive sensitivity compared to all previously reported in vitro models. These results indicated the importance of 3D collagen for liver physiological functionality and hepatotoxicity prediction. We anticipant it being a promising tool for risk assessment of drug-induced hepatotoxicity with a widespread acceptance in drug industry.
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http://dx.doi.org/10.1002/bit.27931DOI Listing
September 2021

Auditory Attention Detection via Cross-Modal Attention.

Front Neurosci 2021 21;15:652058. Epub 2021 Jul 21.

Shien-Ming Wu School of Intelligent Engineering, South China University of Technology, Guangzhou, China.

Humans show a remarkable perceptual ability to select the speech stream of interest among multiple competing speakers. Previous studies demonstrated that auditory attention detection (AAD) can infer which speaker is attended by analyzing a listener's electroencephalography (EEG) activities. However, previous AAD approaches perform poorly on short signal segments, more advanced decoding strategies are needed to realize robust real-time AAD. In this study, we propose a novel approach, i.e., cross-modal attention-based AAD (CMAA), to exploit the discriminative features and the correlation between audio and EEG signals. With this mechanism, we hope to dynamically adapt the interactions and fuse cross-modal information by directly attending to audio and EEG features, thereby detecting the auditory attention activities manifested in brain signals. We also validate the CMAA model through data visualization and comprehensive experiments on a publicly available database. Experiments show that the CMAA achieves accuracy values of 82.8, 86.4, and 87.6% for 1-, 2-, and 5-s decision windows under anechoic conditions, respectively; for a 2-s decision window, it achieves an average of 84.1% under real-world reverberant conditions. The proposed CMAA network not only achieves better performance than the conventional linear model, but also outperforms the state-of-the-art non-linear approaches. These results and data visualization suggest that the CMAA model can dynamically adapt the interactions and fuse cross-modal information by directly attending to audio and EEG features in order to improve the AAD performance.
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http://dx.doi.org/10.3389/fnins.2021.652058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333999PMC
July 2021

Hepatic differentiation of human embryonic stem cells by coupling substrate stiffness and microtopography.

Biomater Sci 2021 May;9(10):3776-3790

Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China. and School of Engineering Science, University of Chinese Academy of Sciences, Beijing 100049, China.

Mechanical or physical cues are associated with the growth and differentiation of embryonic stem cells (ESCs). While the substrate stiffness or topography independently affects the differentiation of ESCs, their cooperative regulation on lineage-specific differentiation remains largely unknown. Here, four topographical configurations on stiff or soft polyacrylamide hydrogel were combined to direct hepatic differentiation of human H1 cells via a four-stage protocol, and the coupled impacts of stiffness and topography were quantified at distinct stages. Data indicated that the substrate stiffness is dominant in stemness maintenance on stiff gel and hepatic differentiation on soft gel while substrate topography assists the differentiation of hepatocyte-like cells in positive correlation with the circularity of H1 clones initially formed on the substrate. The differentiated cells exhibited liver-specific functions such as maintaining the capacities of CYP450 metabolism, glycogen synthesis, ICG engulfment, and repairing liver injury in CCl4-treated mice. These results implied that the coupling of substrate stiffness and topography, combined with the biochemical signals, is favorable to improve the efficiency and functionality of hepatic differentiation of human ESCs.
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http://dx.doi.org/10.1039/d1bm00174dDOI Listing
May 2021

Underwater versus conventional endoscopic mucosal resection for colorectal polyps.

Gastrointest Endosc 2021 05;93(5):1192

Department of Thoracic Surgery, First Hospital of China Medical University, Shenyang, China.

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http://dx.doi.org/10.1016/j.gie.2020.11.008DOI Listing
May 2021

Self-assembled microcage fabrication for manipulating and selectively capturing microparticles and cells.

Opt Express 2021 Mar;29(7):11144-11157

Single-cell-scale selective manipulation and targeted capture play a vital role in cell behavior analysis. However, selective microcapture has primarily been performed in specific circumstances to maintain the trapping state, making the subsequent in situ characterization and analysis of specific particles or cells difficult and imprecise. Herein, we propose a novel method that combines femtosecond laser two-photon polymerization (TPP) micromachining technology with the operation of optical tweezers (OTs) to achieve selective and targeted capture of single particles and cells. Diverse ordered microcages with different shapes and dimensions were self-assembled by micropillars fabricated via TPP. The micropillars with high aspect ratios were processed by single exposure, and the parameters of the micropillar arrays were investigated to optimize the capillary-force-driven self-assembly process of the anisotropic microcages. Finally, single microparticles and cells were selectively transported to the desired microcages by manipulating the flexibly of the OTs in a few minutes. The captured microparticles and cells were kept trapped without additional forces.
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http://dx.doi.org/10.1364/OE.420033DOI Listing
March 2021

Identification of Arctic Food Fish Species for Anthropogenic Contaminant Testing Using Geography and Genetics.

Foods 2020 Dec 8;9(12). Epub 2020 Dec 8.

Department of Biology, Queen's University, Kingston, ON K7L 3N6, Canada.

The identification of food fish bearing anthropogenic contaminants is one of many priorities for Indigenous peoples living in the Arctic. Mercury (Hg), arsenic (As), and persistent organic pollutants including polychlorinated biphenyls (PCBs) are of concern, and these are reported, in some cases for the first time, for fish sampled in and around King William Island, located in Nunavut, Canada. More than 500 salmonids, comprising Arctic char, lake trout, lake whitefish, and ciscoes, were assayed for contaminants. The studied species are anadromous, migrating to the ocean to feed in the summers and returning to freshwater before sea ice formation in the autumn. Assessments of muscle Hg levels in salmonids from fishing sites on King William Island showed generally higher levels than from mainland sites, with mean concentrations generally below guidelines, except for lake trout. In contrast, mainland fish showed higher means for As, including non-toxic arsenobetaine, than island fish. Lake trout were highest in As and PCB levels, with salmonid PCB congener analysis showing signatures consistent with the legacy of cold-war distant early warning stations. After DNA-profiling, only 4-32 Arctic char single nucleotide polymorphisms were needed for successful population assignment. These results support our objective to demonstrate that genomic tools could facilitate efficient and cost-effective cluster assignment for contaminant analysis during ocean residency. We further suggest that routine pollutant testing during the current period of dramatic climate change would be helpful to safeguard the wellbeing of Inuit who depend on these fish as a staple input to their diet. Moreover, this strategy should be applicable elsewhere.
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http://dx.doi.org/10.3390/foods9121824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764770PMC
December 2020

Matrix stiffness and shear stresses modulate hepatocyte functions in a fibrotic liver sinusoidal model.

Am J Physiol Gastrointest Liver Physiol 2020 Dec 9. Epub 2020 Dec 9.

Institute of Mechanics, Chinese Academy of Sciences, China.

Extracellular matrix rigidity has important effects on cell behaviors and is increased sharply during liver fibrosis and cirrhosis. Hepatic blood flow is essential in maintaining hepatocytes (HC) functions. However, it is still unclear how matrix stiffness and shear stresses orchestrate HC phenotype in concert. A fibrotic 3D liver sinusoidal model is constructed using a porous membrane sandwiched between two PDMS layers with respective flow channels. The HC are cultured in collagen gels of various stiffness in the lower channel, while the upper channel is pre-seeded with liver sinusoidal endothelial cells (LSEC) and accessible to shear flow. The results reveal that HC cultured within stiffer matrices exhibit less albumin production and cytochrome P450 (CYP450) reductase expression. Low shear stresses enhance synthetic and metabolic functions of HC, while high shear stresses lead to the loss of HC phenotype. Furthermore, both two mechanical factors regulate HC functions in a cooperative way by complementing with each other. These observations are likely attributed to mechanically-induced mass transport or key signaling molecule of hepatocyte nuclear factor 4 alpha (HNF4α). Present results provide an insight in understanding the mechanisms of HC dysfunction in liver fibrosis and cirrhosis especially from viewpoint of matrix stiffness and blood flow.
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http://dx.doi.org/10.1152/ajpgi.00379.2019DOI Listing
December 2020

What is the clinical significance of the multivariate prediction model for GI stromal tumors with high malignant potential before endoscopic resection?

Gastrointest Endosc 2020 10;92(4):977-978

Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, People's Republic of China.

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http://dx.doi.org/10.1016/j.gie.2020.05.003DOI Listing
October 2020

What is the true effect of gastric peroral endoscopic pyloromyotomy for refractory gastroparesis?

Gastrointest Endosc 2020 10;92(4):974

Department of Thoracic Surgery, First Hospital of China Medical University, Shenyang, China.

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http://dx.doi.org/10.1016/j.gie.2020.04.035DOI Listing
October 2020

Pneumothorax in 2019 novel coronavirus pneumonia needs to be recognized.

Infection 2021 04 2;49(2):367-368. Epub 2020 Sep 2.

Department of Surgical Oncology, The First Hospital of China Medical University, No. 155 Nanjing North Road, Shenyang, 110001, Liaoning, China.

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http://dx.doi.org/10.1007/s15010-020-01518-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463101PMC
April 2021

TME-Responsive Polyprodrug Micelles for Multistage Delivery of Doxorubicin with Improved Cancer Therapeutic Efficacy in Rodents.

Adv Healthc Mater 2020 09 20;9(18):e2000387. Epub 2020 Aug 20.

Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110001, P. R. China.

It is of great significance to develop multifunctional biomaterials to effectively deliver anticancer drug to tumor cells for cancer therapy. Here, inspired by the specific tumor microenvironment (TME) cues, a unique multistage pH/redox-responsive polyprodrug composed of amphiphilic pH-sensitive diblock copolymer poly(ethylene glycol) methyl ether-b-poly(β-amino esters) conjugated with doxorubicin (DOX) via redox-sensitive disulfide bonds (mPEG-b-PAE-ss-DOX) is designed and developed. This polyprodrug can self-assemble into micelles ([email protected]) at low concentration with high serum stability, indicating that [email protected] have prolonged circulation time. The dual pH/redox-responsiveness of the multistage platform is thoroughly evaluated. In vitro results demonstrate that [email protected] can highly accumulate at tumor site, followed by responding to the acidity for disassembly and effectively penetrating into the tumor cells. DOX is released from the platform due to the cleavage of disulfide bonds induced by high glutathione (GSH) concentration, thereby inducing the apoptosis of tumor cells. In vivo studies further reveal that multistage [email protected] can more efficiently inhibit the growth of tumors and improve the survival of tumor-bearing mice in comparison to the free drug and control. These results imply that multistage delivery system might be a potential and effective strategy for drug delivery and [email protected] could be a promising nanomedicine for cancer chemotherapy.
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http://dx.doi.org/10.1002/adhm.202000387DOI Listing
September 2020

Characterizing liver sinusoidal endothelial cell fenestrae on soft substrates upon AFM imaging and deep learning.

Biochim Biophys Acta Gen Subj 2020 12 16;1864(12):129702. Epub 2020 Aug 16.

Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China; School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Background: Liver sinusoidal endothelial cells (LSECs) display unique fenestrated morphology. Alterations in the size and number of fenestrae play a crucial role in the progression of various liver diseases. While their features have been visualized using atomic force microscopy (AFM), the in situ imaging methods and off-line analyses are further required for fenestra quantification.

Methods: Primary mouse LSECs were cultured on a collagen-I-coated culture dish, or a polydimethylsiloxane (PDMS) or polyacrylamide (PA) hydrogel substrate. An AFM contact mode was applied to visualize fenestrae on individual fixed LSECs. Collected images were analyzed using an in-house developed image recognition program based on fully convolutional networks (FCN).

Results: Key scanning parameters were first optimized for visualizing the fenestrae on LSECs on culture dish, which was also applicable for the LSECs cultured on various hydrogels. The intermediate-magnification morphology images of LSECs were used for developing the FCN-based, fenestra recognition program. This program enabled us to recognize the vast majority of fenestrae from AFM images after twice trainings at a typical accuracy of 81.6% on soft substrate and also quantify the statistics of porosity, number of fenestrae and distribution of fenestra diameter.

Conclusions: Combining AFM imaging with FCN training is able to quantify the morphological distributions of LSEC fenestrae on various substrates.

Significance: AFM images acquired and analyzed here provided the global information of surface ultramicroscopic structures over an entire cell, which is fundamental in understanding their regulatory mechanisms and pathophysiological relevance in fenestra-like evolution of individual cells on stiffness-varied substrates.
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http://dx.doi.org/10.1016/j.bbagen.2020.129702DOI Listing
December 2020

PRRX1 isoform PRRX1A regulates the stemness phenotype and epithelial-mesenchymal transition (EMT) of cancer stem-like cells (CSCs) derived from non-small cell lung cancer (NSCLC).

Transl Lung Cancer Res 2020 Jun;9(3):731-744

Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang 110001, China.

Backgrounds: The 2 isoforms of paired-related homeobox 1 (PRRX1), PRRX1A and PRRX1B, are critical in regulating several kinds of cancers, and figure prominently in the maintenance of stemness and progression of epithelial-mesenchymal transition (EMT). However their differential expression in non-small cell lung cancer (NSCLC) clinical samples and exact regulatory roles in cancer stem-like cells (CSCs) remain unknown.

Methods: and experiments were employed to investigate the molecular mechanism. Using CSCs, mouse models, and clinical tissues, we obtained a general picture of the relatively higher level of PRRX1A compared to PRRX1B, and PRRX1A thus promoting EMT and maintaining stemness of CSCs.

Results: PRRX1A but not PRRX1B was upregulated in lung cancer tissues and was positively correlated with TGF-β expression. In CSCs, overexpressed PRRX1A promoted malignant behaviors via transcriptional activation of TGF-β depending on TGF-β/TGF-βR signaling pathway. PRRX1A knockdown decreased self-renewal capacity accompanied by a decrease in stemness factor expression independent of the TGF-β/TGF-βR signaling pathway. Furthermore, PRRX1A was found to tightly bind to and stabilize SOX2. PRRX1A promoted sphere formation not only by enhancing stemness via stabilizing SOX2 but also by promoting cell proliferation.

Conclusions: PRRX1A, but not PRRX1B, was demonstrated to have important roles in the regulation of the stemness and metastatic potential of lung cancer, which suggests the potential application of PRRX1A in cancer treatment.
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http://dx.doi.org/10.21037/tlcr-20-633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354111PMC
June 2020

Underwater endoscopic mucosal resection for colorectal lesions: a meta-analysis.

Surg Endosc 2021 06 23;35(6):3003-3013. Epub 2020 Jun 23.

Department of Thoracic Surgery, The First Hospital of China Medical University, No.155 North Nanjing Street, Shenyang, 110001, People's Republic of China.

Background: Underwater endoscopic mucosal resection (UEMR) of colorectal lesions is emerging as an alternative method to conventional endoscopic mucosal resection (CEMR). This study aimed to evaluate the feasibility and safety of UEMR for colorectal lesions.

Methods: The PubMed, Embase, Cochrane and Web of Science databases were searched before May 10, 2020. The primary outcomes were en bloc resection rate (feasibility) and adverse event rate (safety). The secondary outcome was recurrence and residual adenoma rate. If there was a comparison between UEMR and CEMR, data about en bloc resection, delayed bleeding, and recurrence and residual adenoma were extracted and compared. The pooling of the effect size was conducted using random-effects models, and the Q-statistic, τ, and I were used to evaluate heterogeneity.

Results: Seventeen studies (759 patients, 893 lesions) were included. The pooled estimate for the en bloc resection rate was 59% (95% CI 43-75%) with significant heterogeneity (I = 97%). Due to the heterogeneity, it is not suitable to conduct pooled estimates analysis, so the en bloc resection rate was from 10 to 89%. The pooled estimate for delayed bleeding was 2% (95% CI, 1%-3%) and only two cases had perforation. The pooled rate of recurrence and residual adenoma was 5% (95% CI 2%-8%). Compared with CEMR, UEMR could achieve a higher en bloc resection rate (OR 1.61; 95% CI 1.02-2.53; p = 0.04) with a lower rate of recurrence and residual adenoma (OR 0.18; 95% CI 0.07-0.46; p < 0.01).

Conclusions: UEMR for colorectal lesions was capable of a high en bloc resection rate, low adverse event rate and low recurrence. UEMR may be considered an effective and safe alternative for treating colorectal lesions.
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http://dx.doi.org/10.1007/s00464-020-07745-8DOI Listing
June 2021

Gastric per-Oral Endoscopic Myotomy for Refractory Gastroparesis: A Meta-Analysis.

J Gastrointest Surg 2021 05 11;25(5):1108-1116. Epub 2020 May 11.

Department of Thoracic Surgery, The First Hospital of China Medical University, No.155 North Nanjing Street, Shenyang, 110001, People's Republic of China.

Background: The emerging gastric per-oral endoscopic myotomy (G-POEM) is becoming an alternative treatment method for gastroparesis. This study aimed to evaluate the feasibility and safety of G-POEM for gastroparesis.

Methods: Relevant publications were identified through searching PubMed, EMBASE, Cochrane Library, and Web of Science before April 1, 2019. Studies presenting the clinical data of G-POEM for the treatment of gastroparesis were included. Data about effectiveness and safety were extracted, pooled, and analyzed. Forest plots were graphed based on random effects models.

Results: A total of 272 patients representing 8 studies were eligible for analysis. The pooled rates of GCSI at preprocedure, 1-3 months, 6 months, and 12 months, were 3.25 (95% CI, 2.75-3.75), 1.80 (95% CI, 1.10-2.49), 1.56 (95% CI, 0.45-2.68), and 1.10 (95% CI, 0.75-1.45), respectively. The pooled results of 4-h GES pre- and post-G-POEM were 41.89% (95% CI, 32.75-51.03%) and 16.48% (95% CI, 9.83-23.14%), respectively. Furthermore, the pooled clinical response rate was 84% (95% CI, 77-89%). The GES improvement rate and GES normal rate were also analyzed, and the results were 84% (95% CI, 77-90%) and 53% (95% CI, 39-66%), respectively. Finally, the pooled adverse events rate was 12% (95% CI, 6-19%).

Conclusions: G-POEM was shown to be feasible and safe for the treatment of gastroparesis with various etiologies, which could be a potential first-line therapy for certain patients. Future studies are needed to investigate the appropriate patients for G-POEM to explore the "most beneficial" subgroup of patients.
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http://dx.doi.org/10.1007/s11605-020-04520-xDOI Listing
May 2021

Is endoscopic resection more effective than laparoscopic resection in gastric gastrointestinal stromal tumours?

Eur J Surg Oncol 2020 08 4;46(8):1561. Epub 2020 May 4.

Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.ejso.2020.04.053DOI Listing
August 2020

Effect of dynamic position changes during colonoscope withdrawal: a meta-analysis of randomized controlled trials.

Surg Endosc 2021 03 3;35(3):1171-1181. Epub 2020 Mar 3.

Department of Thoracic Surgery, The First Hospital of China Medical University, No.155 North Nanjing Street, Shenyang, 110001, People's Republic of China.

Background: Colonoscopies are considered to be the primary screening test and gold standard test for colorectal cancer. Position changes during colonoscope withdrawal are believed to be associated with an increased adenoma detection rate (ADR) and polyp detection rate (PDR). However, previous results conflicted, and this study aimed to elucidate the effectiveness of dynamic position changes during colonoscope withdrawal.

Methods: The relevant publications were identified by searching the medical databases. The primary outcomes were the ADR and PDR, which were pooled and analyzed. The secondary outcome was the withdrawal time. The studies that supplied the ADR and PDR for different segments of the colon were separated into subgroup analyses.

Results: Five randomized controlled trials were eligible for analysis. The total ADR was higher with dynamic position changes than with a static position (odds ratio, [OR] 1.34; 95% confidence interval [CI] 1.13-1.59; p < 0.001), with low evidence of between-study heterogeneity (I = 0%). Although the total PDR was slightly higher with dynamic position changes than with a static position (OR 1.23; 95% CI 0.88-1.73), there difference was not statistically significant (p = 0.22). The withdrawal time was only increased by 0.47 min (95% CI - 0.11 to 1.06) with dynamic position changes, without statistical significance (p = 0.11). The subgroup analysis showed that the ADR and PDR for the transverse colon were higher with dynamic position changes, with pooled estimates of ADR (OR 1.72; 95% CI 1.02-2.88; p = 0.04) and PDR (OR 1.79; 95% CI 1.08-2.96; p = 0.02).

Conclusion: Dynamic position changes during colonoscope withdrawal increased the total ADR; however, no obvious increase was found in the total PDR. The withdrawal time was not significantly prolonged with dynamic position changes. Subgroup analysis showed that the ADR and PDR in the transverse colon were obviously improved with dynamic position changes.
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http://dx.doi.org/10.1007/s00464-020-07483-xDOI Listing
March 2021

A Meta-analysis-Based Assessment of Intense Pulsed Light for Treatment of Melasma.

Aesthetic Plast Surg 2020 06 13;44(3):947-952. Epub 2020 Feb 13.

Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, Tongzipo Road 138, Yuelu District, Changsha, 410013, China.

Background: A safe and effective treatment for melasma, an acquired refractory pigmented skin disease, remains a problem, although numerous clinical trials have explored the possibility of combined therapy involving intense pulsed light. To date, little is known regarding the efficacy of this treatment. The current study, therefore, sought to explore the effectiveness of intense pulsed light.

Methods: We used published studies from literature databases, based on established inclusion criteria, to calculate standardized mean differences (SMDs) and risk ratio (RRs), and evaluated the effectiveness of combined therapy with intense pulsed light in melasma patients. We performed data analysis using the Review Manager 5.3 software at 95% confidence interval.

Results: We obtained a total of 8 studies, involving 215 patients, from the databases and found a significant effect on efficacy following combined therapy with intense pulsed light. Specifically, the melasma area and severity index (MASI) score was significantly low (SMD = 0.61, CI [0.42, 0.80] P < 0.0001 for a fixed-effects model), while a four-point scoring scale self-assessment by patients was significantly high (RR = 1.44, CI [1.17, 1.76] P = 0.0004 for a fixed-effects model).

Conclusion: Our meta-analysis showed that IPL-based combination therapy for melasma can effectively reduce the MASI score and result in higher satisfaction among patients, indicating an effective method for treatment of the condition.

Level Of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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http://dx.doi.org/10.1007/s00266-020-01637-xDOI Listing
June 2020

Efficacy and safety of endoscopic full-thickness resection in the colon and rectum using an over-the-scope device: a meta-analysis.

Surg Endosc 2021 01 17;35(1):249-259. Epub 2020 Jan 17.

Department of Thoracic Surgery, The First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.

Objective: Relevant publications were identified by searching PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science before December 1, 2019. Studies in which ≥ 10 cases of colorectal lesions were resected with endoscopic full-thickness resection (EFTR) were included. Rates of efficacy (technical success (en bloc), full-thickness resection and R0 resection), rates of safety (bleeding, perforation and postpolypectomy syndrome) and rates of follow-up (residual/recurrent adenoma, fate of over-the-scope clip and surgery for any reason) were pooled and analyzed. Forest plots were graphed based on random effects models. Subgroup analyses and sensitivity analyses were also performed if significant heterogeneity existed.

Results: A total of 469 patients across 9 studies were eligible for analysis. The pooled rates of technical success, full-thickness resection and R0 resection were 94.0% (95% CI 89.8-97.3%), 89.5% (83.9-94.2%) and 84.9% (75.1-92.8%), respectively. The pooled estimates of bleeding, perforation and postpolypectomy syndrome were 2.2% (95% CI 0.4-4.9%), 0.19% (95% CI 0.00-1.25%) and 2.3% (95% CI 0.1-6.3%), respectively. Finally, the pooled rates of residual/recurrent adenoma, fate of OTSC and surgery for any reason were 8.5% (95% CI 4.1-14.0%), 80.3% (95% CI 67.5-90.8%) and 6.3% (2.4-11.7%), respectively.

Conclusions: EFTR for nonlifting, invasive lesions in the colon and rectum appears to be effective and safe. However, future studies are necessary to explore the role of EFTR in large colorectal lesions and specify its indications.
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http://dx.doi.org/10.1007/s00464-020-07387-wDOI Listing
January 2021

Segmentation and Re-encapsulation of Porous PtCu Nanoparticles by Generated Carbon Shell for Enhanced Ethylene Glycol Oxidation and Oxygen-Reduction Reaction.

ACS Appl Mater Interfaces 2020 Feb 22;12(5):6298-6308. Epub 2020 Jan 22.

School of Chemical Engineering , Nanjing University of Science and Technology , Nanjing 210094 , P. R. China.

Hierarchical porous carbon-encapsulated ultrasmall PtCu ([email protected]) nanoparticles (NPs) were constructed based on segmentation and re-encapsulation of porous PtCu NPs by using glucose as a green biomass carbon source. The synergistic electronic effect from the bimetallic elements can enhance the catalytic activity by adjusting the surface electronic structure of Pt. Most importantly, the generated porous carbon shell provided a large contact surface area, excellent electrical conductivity, and structural stability, and the ultrasmall PtCu NPs exhibited an increased electrochemical performance compared with their PtCu matrix because of the exposure of more catalytically active centers. This synergistic relationship between the components resulted in enhanced catalytic activity and better stability of the obtained [email protected] for ethylene glycol oxidation reaction and the oxygen-reduction reaction in alkaline electrolyte, which was higher than the PtCu NPs and commercial Pt/C (20 wt % Pt on Vulcan XC-72). The electrochemically active surface areas of the [email protected], PtCu NPs, and commercial Pt/C were calculated to be approximately 230.2, 32.8, and 64.0 m/g, respectively; the mass activity of the [email protected] for the ethylene glycol oxidation reaction was 8.5 A/mg, which was 14.2 and 8.5 times that of PtCu NPs and commercial Pt/C, respectively. The specific activity of [email protected] was 3.7 mA/cm, which was 2.1 and 2.3 times that of PtCu NPs and commercial Pt/C, respectively. The onset potential () of [email protected] for the oxygen-reduction reaction was 0.96 V (vs reversible hydrogen electrode, RHE), which was 110 and 60 mV higher than PtCu and commercial Pt/C, respectively. The half-wave potentials () of [email protected], PtCu, and Pt/C were 0.88, 0.56, and 0.82 V (vs RHE), respectively, which indicated that the [email protected] catalyst had an excellent bifunctional electrocatalytic activity.
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http://dx.doi.org/10.1021/acsami.9b20504DOI Listing
February 2020

RUFY3 Predicts Poor Prognosis and Promotes Metastasis through Epithelial-mesenchymal Transition in Lung Adenocarcinoma.

J Cancer 2019 17;10(25):6278-6285. Epub 2019 Oct 17.

Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

: RUFY3 (RUN and FYVE domain-containing protein 3) has been shown to participate in cell migration, membrane transportation, and cellular signaling and is dysregulated in several cancer processes. However, the role of RUFY3 in lung cancer remains unclear. In the present study, we aimed to study the expression of RUFY3 and assess its clinical significance in lung adenocarcinoma. : We used immunohistochemistry to detect RUFY3 protein expression in human lung adenocarcinoma and adjacent normal lung tissue from 125 patients who underwent surgical resection of the lung cancer. RUFY3 expression was assessed in association with clinicopathological characteristics and clinical prognosis of lung adenocarcinoma patients. The expression of RUFY3 in three different lung adenocarcinoma cell lines and one normal lung epithelial cell (BEAS-2B) was detected by western blot. RNAi technique was used to silence RUFY3. We assessed cell migration by Trans-well assay and wound healing assay. : In lung adenocarcinoma tissues, RUFY3 protein was significantly upregulated compared to paired normal lung tissues. High cytoplasmic RUFY3 levels were associated with lymph node metastasis, TNM staging, and survival status. Patients with the highest expression level of RUFY3 had a shorter survival time than patients with the lowest expression. Inhibition of RUFY3 by siRNA inhibited cell migration. Furthermore, silence of RUFY3 lead to up-regulation of E-cadherin, but down-regulation of N-cadherin, Vimentin and Slug. : Our study is first to demonstrated that abnormal expression of RUFY3 indicates poor prognosis in lung adenocarcinoma and also indicates that RUFY3 may be related to EMT process. This highlights the potential of RUFY3 as a novel prognostic biomarker for lung adenocarcinoma.
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http://dx.doi.org/10.7150/jca.35072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856751PMC
October 2019

RFC3 induces epithelial‑mesenchymal transition in lung adenocarcinoma cells through the Wnt/β‑catenin pathway and possesses prognostic value in lung adenocarcinoma.

Int J Mol Med 2019 Dec 29;44(6):2276-2288. Epub 2019 Oct 29.

Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

Lung cancer is a malignant tumor responsible for the highest mortality rate in humans. The identification of novel functional genes is of great importance in the treatment of lung cancer. The reported roles of replication factor C subunit 3 (RFC3) in tumorigenesis are contradictory. The present study aimed to explore the role and mechanism of RFC3 in lung cancer cells. An immunohistochemical study of 165 lung cancer and adjacent tissues was conducted (123 lung adenocarcinoma tissues and 42 lung squamous cell carcinoma tissues). Kaplan‑Meier analysis and Cox multivariate analysis were employed to explore the relationship between RFC3 and patient prognosis. In addition, the proliferation, cell cycle distribution and apoptosis of A549 and H1299 cells were determined by MTT assay and flow cytometry, respectively, following cell transfection to induce overexpression and knockdown of RFC3. A Boyden chamber assay and wound‑healing assay were conducted to determine the invasive and migratory abilities of A549 and H1299 cells. Western blotting was used to analyze the effects of RFC3 overexpression and RFC3 small interfering RNA‑induced knockdown, and to explore the potential mechanism and pathway underlying the effects of RFC3. Positive expression of RFC3 was detected in lung adenocarcinoma, and overexpression of RFC3 shortened the survival time of patients with lung adenocarcinoma. Furthermore, overexpression of RFC3 increased the invasion and migration of A549 cells, whereas knockdown of RFC3 significantly reduced the invasion and migration of H1299 cells. Ectopic expression of RFC3 induced epithelial‑mesenchymal transition (EMT), as determined by downregulation of E‑cadherin, and upregulation of N‑cadherin, vimentin and Wnt signaling target genes, including c‑MYC, Wnt1 and β‑catenin, and the ratio of phosphorylated‑glycogen synthase kinase 3 (GSK3)‑β (Ser9)/GSK3‑β. In conclusion, RFC3 may be considered a coactivator that promotes the Wnt/β‑catenin signaling pathway, and induces EMT and metastasis in lung adenocarcinoma.
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http://dx.doi.org/10.3892/ijmm.2019.4386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844605PMC
December 2019

What is the true effect of endoscopic full-thickness resection on early colorectal cancer?

Gastrointest Endosc 2019 09;90(3):539-540

Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, People's Republic of China.

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http://dx.doi.org/10.1016/j.gie.2019.04.202DOI Listing
September 2019

Underwater EMR for colorectal lesions.

Gastrointest Endosc 2019 09;90(3):536

Department of Thoracic Surgery, First Hospital of China Medical University, Shenyang, People's Republic of China.

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http://dx.doi.org/10.1016/j.gie.2019.03.006DOI Listing
September 2019

Efficacy and safety of endoscopic sleeve gastroplasty for obesity patients: a meta-analysis.

Surg Endosc 2020 03 24;34(3):1253-1260. Epub 2019 Jun 24.

Department of Thoracic Surgery, The First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.

Background: Endoscopic sleeve gastroplasty (ESG) is a minimally invasive, effective, and safe technique for weight loss intervention. Since a relatively small number of cases were present in previous studies, this study aimed to elucidate the efficacy and safety of ESG.

Methods: Relevant publications were identified through searching PubMed, EMBASE, Cochrane, and Web of Science before March 1, 2019. The percentage of total body weight loss (%TBWL), percentage of excess weight loss (%EWL), and the adverse event rate in each follow-up session were extracted, pooled, and analyzed. Forest plots were graphed based on random effects models.

Results: A total of 1542 patients from nine studies were eligible for analysis. The pooled results of %TBWL at 1, 3, 6, and 12 months were 8.78% (p = 0.000), 11.85% (p = 0.000), 14.47% (p = 0.024), and 16.09% (p = 0.063), respectively. The pooled results of %EWL at 1, 3, 6, and 12 months were 31.16% (p = 0.000), 43.61% (p = 0.000), 53.14% (p = 0.000), and 59.08% (p = 0.015), respectively. Finally, the pooled rate of mild adverse events was 72% (p < 0.01), and the pooled estimate of severe adverse events was only 1% (p = 0.08).

Conclusion: Although the conventional surgical sleeve gastrectomy is the gold standard for bariatric surgery, ESG could be a promising minimally invasive alternative for treating obesity with satisfactory efficacy and low risk.
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http://dx.doi.org/10.1007/s00464-019-06889-6DOI Listing
March 2020

Endoscopic submucosal tunnel dissection for superficial esophageal neoplastic lesions: a meta-analysis.

Surg Endosc 2020 03 3;34(3):1214-1223. Epub 2019 Jun 3.

Department of Thoracic Surgery, The First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.

Background And Aims: The emerging endoscopic submucosal tunnel dissection (ESTD) is becoming an alternative method for superficial esophageal neoplastic lesions. This study aimed to evaluate the effectiveness and feasibility of ESTD for superficial esophageal neoplastic lesions.

Methods: A comprehensive literature review was conducted to search relevant studies through PubMed, EMBASE, Cochrane Library, and Web of Science before 1 December 2018. Studies relating to ESTD for superficial esophageal neoplastic lesions were included. Rates of effectiveness (en bloc resection rate, R0 resection rate, and curative resection rate), rates of feasibility (muscular damage rate, perforation rate, postprocedural bleeding rate, and emphysema rate), and rates of follow-up (recurrence rate and stricture rate) were pooled and analyzed. Forest plots were constructed based on the random-effects model. Sensitivity analyses were also performed if significant heterogeneity existed.

Results: Six studies including 414 patients and 436 superficial esophageal neoplastic lesions that underwent ESTD were available for analysis. The pooled estimates of en bloc resection rate, R0 resection rate, and curative resection rate were 98% (95% CI 95.8-99.0%), 87.0% (95% CI 78.2-92.5%), and 87.6% (95% CI 67.4-96.0%), respectively. The pooled outcomes of muscular damage rate, perforation rate, postprocedural bleeding rate and emphysema rate were 19.1% (95% CI 9.8-33.8%), 2.2% (95% CI 1.1-4.1%), 1.6% (95% CI 0.7-3.5%), and 12.2% (95% CI 4.3-29.9%), respectively. Finally, the pooled results of recurrence and stricture were 4.7% (0.9-20.5%) and 20.9% (11.3-35.2%), respectively.

Conclusions: ESTD appears to be an effective and feasible approach for treating superficial esophageal neoplastic lesions. However, future research is needed for new and comprehensive methods to decrease the stricture rate after ESTD.
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http://dx.doi.org/10.1007/s00464-019-06875-yDOI Listing
March 2020

Screening Therapeutic Agents Specific to Breast Cancer Stem Cells Using a Microfluidic Single-Cell Clone-Forming Inhibition Assay.

Small 2020 03 18;16(9):e1901001. Epub 2019 Apr 18.

Department of Laboratory Medicine, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China.

Screens of cancer stem cells (CSCs)-specific agents present significant challenges to conventional cell assays due to the difficulty in preparing CSCs ready for drug testing. To overcome this limitation, developed is a microfluidic single-cell assay for screening breast cancer stem cell-specific agents. This assay takes advantage of the single-cell clone-forming capability of CSCs, which can be specifically inhibited by CSC-targeting agents. The single-cell assay is performed on a microfluidic chip with an array of 3840 cell-capturing units; the single-cell arrays are easily formed by flowing a cell suspension into the microchip. Achieved is a single cell-capture rate of ≈60% thus allowing more than 2000 single cells to be analyzed in a single test. Over long-term suspension culture, only a minority of cells survive and form tumorspheres. The clone-formation rate of MCF-7, MDA-MB-231, and T47D cells is 1.67%, 5.78%, and 5.24%, respectively. The clone-forming inhibition assay is conducted by exposing the single-cell arrays to a set of anticancer agents. The CSC-targeting agents show complete inhibition of single-cell clone formation while the nontargeting ones show incomplete inhibition effects. The resulting microfluidic single-cell assay with the potential to screen CSC-specific agents with high efficiency provides new tools for individualized tumor therapy.
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http://dx.doi.org/10.1002/smll.201901001DOI Listing
March 2020

Primary hyperparathyroidism due to ectopic parathyroid adenoma in an adolescent: a case report and review of the literature.

Endocrine 2019 04 25;64(1):38-42. Epub 2019 Feb 25.

Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.

Purpose: Primary hyperparathyroidism (PHPT) is a common endocrine disorder and is usually diagnosed in adults. PHPT due to ectopic parathyroid adenoma in adolescents is rare.

Methods: We describe the case of a 15-year-old boy with PHPT due to ectopic parathyroid adenoma. A review of the literature of PHPT in adolescents was performed, focusing on etiology, clinical presentation, preoperative localization methods, pathology, and treatment.

Results: The patient was successfully treated with surgery and was followed up for 5 years with no signs or symptoms of hyperparathyroidism. By reviewing the literature, only seven cases of PHPT associated with ectopic parathyroid lesions in adolescents have been reported. Parathyroidectomy is the only known curative treatment. Accurate preoperative localization of the target lesion is critical.

Conclusions: This study should raise awareness of the diagnosis and treatment of PHPT due to ectopic parathyroid adenoma/carcinoma in adolescents.
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http://dx.doi.org/10.1007/s12020-019-01875-3DOI Listing
April 2019

Insights into aggregation and transport of graphene oxide in aqueous and saturated porous media: Complex effects of cations with different molecular weight fractionated natural organic matter.

Sci Total Environ 2019 Mar 30;656:843-851. Epub 2018 Nov 30.

School of Chemical & Environmental Engineering, China University of Mining & Technology-, Beijing, Beijing 100083, China.

The stability of nanomaterials in aquatic environment is a critical factor that governs their fate and ecotoxicity. Meanwhile, the interaction between nanomaterials and ubiquitous natural organic matter (NOM) is a vital process that influences the transport and biological effects of nanomaterials in the environment. However, impacts of NOM on the aggregation and transport of two-dimensional nanomaterials, especially for the increasingly used graphene oxide (GO), are not well understood. Particularly, there is lack of exploration on potential impacts of the heterogeneous properties of NOM on GO behaviour, especially that induced by the wide molecular weight (MW) span of NOM. In this study, effects of several kinds of well-characterized MW fractionated Suwannee River NOM (M-SRNOMs) on the aggregation and transport of GO in aqueous media and saturated porous media were investigated. Our results suggest that the stability and migration capacity of GO under most investigated electrolyte conditions are promoted by all Mf-SRNOMs, and efficiencies of different Mf-SRNOMs are generally positively correlated with their MW. Primarily, mechanisms including MW-dependent steric hindrance and sorption of Mf-SRNOMs onto GO are critical in stabilizing GO, and thus facilitating its transport. However, the stronger sorption of higher Mf-SRNOMs onto the GO basal plane through π-π interaction further facilitated the cation bridging between both ends of Mf-SRNOM and GO, and resulted in heteroaggregation of NOM-GO. Moreover, the weight analysis indicated that despite the fact that high Mf-SRNOMs only occupied a small percentage of pristine-SRNOM, they showed a stronger contribution towards pristine-SRNOM's capacity in stabilizing GO, when compared with that of lower MW counterpart. These findings pointed out that complex effects of the heterogeneities of NOM and cations should be highly relevant when the aggregation and transport behaviour of two-dimensional nanomaterials is investigated, and NOM fractions that are highly aromatic and of a higher MW should receive greater attention.
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http://dx.doi.org/10.1016/j.scitotenv.2018.11.387DOI Listing
March 2019

Long noncoding RNA H19 participates in metformin-mediated inhibition of gastric cancer cell invasion.

J Cell Physiol 2019 04 7;234(4):4515-4527. Epub 2018 Sep 7.

Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, China.

Recent research suggests that the first-line oral antidiabetes drug metformin may prevent gastric cancer progression and improve prognosis. Many studies have also shown that long noncoding RNAs (lncRNAs) play important roles in many biological processes. Therefore, we aimed to explore whether lncRNAs participate in the mechanisms by which metformin affects gastric cancer cells. In the current study, we found that metformin significantly inhibited the cellular functions of gastric cancer cells through Cell Counting Kit-8 and invasion assays. We found that lncRNA H19 was greatly downregulated in gastric cancer cells treated with metformin using lncRNA microassays. Based on bioinformatics analyses of the Oncomine and The Cancer Genome Atlas databases, H19 is shown to be overexpressed in gastric cancer tissues, with increased expression of H19 relating to advanced pathological tumor stage and pathological tumor node metastasis stage, indicating that H19 may be associated with the invasive ability of gastric cancer. We knocked down H19 in AGS and SGC7901 cell lines and found that knocked-down H19 could decrease gastric cancer cell invasion and that metformin could not further decrease invasion after the knock down. Moreover, H19 depletion increased AMPK activation and decreased MMP9 expression, and metformin could not further activate AMPK or decrease MMP9 in H19 knocked-down gastric cancer cells. In summary, metformin has a profound antitumor effect on gastric cancer cells, and H19 is a key component in the process of metformin suppressing gastric cancer cell invasion.
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http://dx.doi.org/10.1002/jcp.27269DOI Listing
April 2019
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