Publications by authors named "Yuan Ding"

401 Publications

Common markers of testicular Sertoli cells.

Expert Rev Mol Diagn 2021 May 4. Epub 2021 May 4.

College of Medicine, China Three Gorges University, Yichang 443002, China.

Introduction: Sertoli cells play central roles in the development of testis formation in fetuses and the initiation and maintenance of spermatogenesis in puberty and adulthood, and disorders of Sertoli cell proliferation and/or functional maturation can cause male reproductive disorders at various life stages. It's well documented that various genes are either overexpressed or absent in Sertoli cells during the conversion of an immature, proliferating Sertoli cell to a mature, non-proliferating Sertoli cell, which are considered as Sertoli cell stage-specific markers. Thus, it is paramount to choose an appropriate Sertoli cell marker that will be used not only to identify the developmental, proliferative, and maturation of Sertoli cell status in the testis during the fetal period, prepuberty, puberty, or in the adult, but also to diagnose the mechanisms underlying spermatogenic dysfunction.

Areas Covered: In this review, we principally enumerated 5 categories of testicular Sertoli cell markers-including immature Sertoli cell markers, mature Sertoli cell markers, immature/mature Sertoli cell markers, Sertoli cell functional markers, and others.

Expert Opinion: By delineating the characteristics and applications of more than 20 Sertoli cell markers, this review provided novel Sertoli cell markers for the more accurate diagnosis and mechanistic evaluation of male reproductive disorders.
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http://dx.doi.org/10.1080/14737159.2021.1924060DOI Listing
May 2021

Prostate cancer in young men represents a distinct clinical phenotype: gene expression signature to predict early metastases.

J Transl Genet Genom 2021 9;5:50-61. Epub 2021 Mar 9.

Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California, CA 91010, USA.

Aim: Several genomic signatures are available to predict Prostate Cancer (CaP) outcomes based on gene expression in prostate tissue. However, no signature was tailored to predict aggressive CaP in younger men. We attempted to develop a gene signature to predict the development of metastatic CaP in young men.

Methods: We measured genome-wide gene expression for 119 tumor and matched benign tissues from prostatectomies of men diagnosed at ≤ 50 years and > 70 years and identified age-related differentially expressed genes (DEGs) for tissue type and Gleason score. Age-related DEGs were selected using the improved Prediction Analysis of Microarray method (iPAM) to construct and validate a classifier to predict metastasis using gene expression data from 1,232 prostatectomies. Accuracy in predicting early metastasis was quantified by the area under the curve (AUC) of receiver operating characteristic (ROC), and abundance of immune cells in the tissue microenvironment was estimated using gene expression data.

Results: Thirty-six age-related DEGs were selected for the iPAM classifier. The AUC of five-year survival ROC for the iPAM classifier was 0.87 (95%CI: 0.78-0.94) in young (≤ 55 years), 0.82 (95%CI: 0.76-0.88) in middle-aged (56-70 years), and 0.69 (95%CI: 0.55-0.69) in old (> 70 years) patients. Metastasis-associated immune responses in the tumor microenvironment were more pronounced in young and middle-aged patients than in old ones, potentially explaining the difference in accuracy of prediction among the groups.

Conclusion: We developed a genomic classifier with high precision to predict early metastasis for younger CaP patients and identified age-related differences in immune response to metastasis development.
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http://dx.doi.org/10.20517/jtgg.2021.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081383PMC
March 2021

Effect of limb oversizing on the risk of type Ib endoleak in patients after endovascular aortic repair.

J Vasc Surg 2021 Apr 2. Epub 2021 Apr 2.

Department of Vascular Surgery, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Objective: We assessed the association between the degree of limb oversizing and the risk of type Ib endoleak (TIBEL) in different types of iliac landing zones after endovascular aortic aneurysm repair.

Methods: We performed a retrospective cohort study of patients who had undergone endovascular aortic aneurysm repair with bifurcated and limb endografts in an academic center. The main exposure was the degree of limb oversizing. The primary outcome was the occurrence of TIBELs. The secondary outcomes included limb occlusion, reintervention, and overall survival. Subgroup analyses stratified by ectatic and normal iliac landing zones were performed. Multivariate Cox regression analysis and sensitivity analyses using marginal structure model were conducted to adjust for potential confounders.

Results: A total of 750 patients with 1500 iliac limb endografts were included in our study (817 limbs with oversizing of ≤10% and 683 with oversizing >10%). The median 1-year freedom from TIBEL was 98.9% (interquartile range [IQR], 98.0%-99.8%) for limbs with oversizing of ≤10% and 99.6% (IQR, 99.0%-100%) for limbs with oversizing >10%. The median 3-year freedom from TIBEL was 95.6% (IQR, 93.1%-98.1%) and 98.2% (IQR, 96.5%-99.9%) for oversizing ≤10% and >10%, respectively. We found that limb oversizing >10% was associated with a significantly decreased risk of TIBEL (adjusted hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.19-0.76) in the overall population. After stratification by ectatic iliac landing zone, we found that limb oversizing >10% was associated with a significantly decreased risk of TIBEL in the ectatic iliac landing zones (adjusted HR, 0.38; 95% CI, 0.16-0.88). However, no significant difference was found in the limb endografts landing in normal iliac arteries (adjusted HR, 0.44; 95% CI, 0.13-1.45). In the subgroup of normal iliac arteries, we observed a significantly increased risk of limb occlusion in the limbs with distal oversizing >15% compared with the limbs with distal oversizing of ≤15% (adjusted HR, 4.66; 95% CI, 1.68-12.91).

Conclusions: Adequate limb oversizing >10% was associated with a significantly decreased risk of TIBEL in limbs with ectatic iliac landing zones. However, no additional benefit was observed for oversizing >10% in limb grafts landing in normal iliac arteries. Furthermore, excessive limb oversizing (>15%) in normal iliac landing zones can be associated with an increased risk of limb occlusion.
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http://dx.doi.org/10.1016/j.jvs.2021.03.020DOI Listing
April 2021

Influence of Distal Re-entry Tears on False Lumen Thrombosis After Thoracic Endovascular Aortic Repair in Type B Aortic Dissection Patients: A Computational Fluid Dynamics Simulation.

Cardiovasc Eng Technol 2021 Mar 25. Epub 2021 Mar 25.

Beijing Advanced Innovation Center of Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, China.

Purpose: Distal re-entry tears play a significant role in false lumen (FL) thrombosis, which will strongly affect the postoperative long-term survival of patients with type B aortic dissection (TBAD) after thoracic endovascular aortic repair (TEVAR). This study aimed to investigate the influence of a peculiar morphological parameter of the residual re-entry tears in TBAD patients after TEVAR on long-term FL thrombosis using the computational fluid dynamics.

Methods: Ideal population-based three-dimensional models of post-operative TBAD were established. Numerical simulation was performed to investigate the hemodynamic differences caused by different tear features, including the tear count, the maximum distance between tears, and the tear area.

Results: Although the low relative residence time (RRT) area did not change significantly when the tear distance was fixed, the area of oscillatory shear index (OSI) > 0.45 and endothelial cell activation potential (ECAP) > 1.5 decreased significantly with the tear count and area increased and a dramatic increase in blood flow into the FL was also observed. When tear count and total area were fixed, for each 10-mm increase in the maximum distance between tears, the area of low RRT in the FL increased significantly, while the average pressure difference increased by 10.85%.

Conclusion: The different morphology of the re-entry tears had different effects on the thrombosis-related hemodynamic parameters in FL following TEVAR. and the number of re-entry tears was most crucial to the potential thrombosis in the post-TEVAR FL of TBAD patients.
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http://dx.doi.org/10.1007/s13239-021-00532-zDOI Listing
March 2021

Endovascular Treatment of Aberrant Splenic Artery Aneurysm Presenting With Painless Progressive Jaundice: A Case Report and Literature Review.

Vasc Endovascular Surg 2021 Mar 24:15385744211005296. Epub 2021 Mar 24.

Department of Vascular Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Splenic artery (SA) originating from the superior mesenteric artery is a rare condition, and aneurysms in relation to this aberrant SA are even rarer. We reported the case of a 67-year-old female who presented with painless progressive jaundice for 2 months accompanied by thrombocytopenia and liver dysfunction. The computed tomographic angiography (CTA) showed an aberrant SAA located behind the pancreatic head along with the dilation of common bile duct. Stent-graft deployment in SMA and coil embolization of the aneurysm were performed. Her liver dysfunction and thrombocytopenia improved postoperatively. CTA at 2-year follow-up showed patency of stent-graft and SMA and the shrinkage of the excluded aneurysm sac. Considering the particular location of the aneurysm, painless progressive jaundice can be the initial symptom for the aberrant SAAs. This combined endovascular technique completely excluded the aneurysm and was beneficial for treating secondary liver dysfunction and thrombocytopenia.
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http://dx.doi.org/10.1177/15385744211005296DOI Listing
March 2021

A DM1-doped porous gold nanoshell system for NIR accelerated redox-responsive release and triple modal imaging guided photothermal synergistic chemotherapy.

J Nanobiotechnology 2021 Mar 19;19(1):77. Epub 2021 Mar 19.

Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China.

Background: Although many treatments for breast cancer are available, poor tumour targeting limits the effectiveness of most approaches. Consequently, it is difficult to achieve satisfactory results with monotherapies. The lack of accurate diagnostic and monitoring methods also limit the benefits of cancer treatment. The aim of this study was to design a nanocarrier comprising porous gold nanoshells (PGNSs) co-decorated with methoxy polyethylene glycol (mPEG) and trastuzumab (Herceptin®, HER), a therapeutic monoclonal antibody that binds specifically to human epidermal receptor-2 (HER2)-overexpressing breast cancer cells. Furthermore, a derivative of the microtubule-targeting drug maytansine (DM1) was incorporated in the PGNSs.

Methods: Prepared PGNSs were coated with mPEG, DM1 and HER via electrostatic interactions and Au-S bonds to yield DM1-mPEG/HER-PGNSs. SK-BR-3 (high HER2 expression) and MCF-7 (low HER2) breast cancer cells were treated with DM1-mPEG/HER-PGNSs, and cytotoxicity was evaluated in terms of cell viability and apoptosis. The selective uptake of the coated PGNSs by cancer cells and subsequent intracellular accumulation were studied in vitro and in vivo using inductively coupled plasma mass spectrometry and fluorescence imaging. The multimodal imaging feasibility and synergistic chemo-photothermal therapeutic efficacy of the DM1-mPEG/HER-PGNSs were investigated in breast cancer tumour-bearing mice. The molecular mechanisms associated with the anti-tumour therapeutic use of the nanoparticles were also elucidated.

Result: The prepared DM1-mPEG/HER-PGNSs had a size of 78.6 nm and displayed excellent colloidal stability, photothermal conversion ability and redox-sensitive drug release. These DM1-mPEG/HER-PGNSs were taken up selectively by cancer cells in vitro and accumulated at tumour sites in vivo. Moreover, the DM1-mPEG/HER-PGNSs enhanced the performance of multimodal computed tomography (CT), photoacoustic (PA) and photothermal (PT) imaging and enabled chemo-thermal combination therapy. The therapeutic mechanism involved the induction of tumour cell apoptosis via the activation of tubulin, caspase-3 and the heat shock protein 70 pathway. M2 macrophage suppression and anti-metastatic functions were also observed.

Conclusion: The prepared DM1-mPEG/HER-PGNSs enabled nanodart-like tumour targeting, visibility by CT, PA and PT imaging in vivo and powerful tumour inhibition mediated by chemo-thermal combination therapy in vivo. In summary, these unique gold nanocarriers appear to have good potential as theranostic nanoagents that can serve both as a probe for enhanced multimodal imaging and as a novel targeted anti-tumour drug delivery system to achieve precision nanomedicine for cancers.
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http://dx.doi.org/10.1186/s12951-021-00824-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976706PMC
March 2021

Endovascular treatment of an ilio-iliac arteriovenous fistula accompanied by venous thromboembolism presenting with multiple organ failure - A case report and literature review.

Vascular 2021 Mar 4:1708538121996576. Epub 2021 Mar 4.

Department of Vascular Surgery, West China Hospital, Sichuan University, Sichuan, P.R. China.

Objectives: Multiple organ failure is a rare manifestation of ilio-iliac arteriovenous fistula which can lead to a high rate of misdiagnosis and death.

Methods: We reported a 61-year-old man presenting with multiple organ failure rapidly after right lower limb swelling. Computed tomography angiography showed an ilio-iliac arteriovenous fistula caused by right common iliac artery aneurysm, and venous thrombosis of bilateral common iliac veins. A bifurcated stent-graft with coil embolization of right internal iliac artery was used for repair.

Results: The patient recovered rapidly and was discharged without complications. Although arteriovenous fistula persisted due to type II endoleak, aneurysm sac and inferior vena cava significantly shrunk at six months follow-up.

Conclusions: This report demonstrated that multiple organ failure may appear when the distal outflow tracts of arteriovenous fistula are obstructed. Moreover, endovascular repair is effective for reversal of multiple organ failure caused by arteriovenous fistula, even if arteriovenous fistula persists due to type II endoleak.
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http://dx.doi.org/10.1177/1708538121996576DOI Listing
March 2021

Editor's Choice - Mid Term Outcomes of Crossed Limb vs. Standard Limb Configuration in Endovascular Abdominal Aortic Aneurysm Repair: A Propensity Score Analysis.

Eur J Vasc Endovasc Surg 2021 Apr 26;61(4):579-588. Epub 2021 Feb 26.

Department of Vascular Surgery, West China Hospital, Sichuan University, Chengdu, China.

Objective: The aim was to compare mid term outcomes between crossed limb (CL) and standard limb (SL) configuration in patients who underwent endovascular aortic aneurysm repair (EVAR).

Methods: This was a comparative cohort study. Eligible patients who underwent EVAR between September 2011 and March 2019 in a tertiary academic centre were included. Inverse probability of treatment weighting (IPTW) was used to balance the demographic, anatomical and operative baseline characteristics between the two groups. The primary outcome was adverse limb events including type IB endoleak (T1BEL), type III endoleak, and limb occlusion. Cox proportional hazards regression and marginal structural model were performed to compare time to event outcomes.

Results: The study included 729 patients (194 CL and 535 SL) with a median follow up of 34 months (interquartile range 16 - 62 months). The weighted analyses revealed no significant difference between CL and SL EVAR in terms of adverse limb events, type IA endoleak (T1AEL), type II endoleak (T2EL), re-intervention, and overall survival. In the subgroup analysis of large aneurysm sac, the CL configuration was associated with a significantly decreased risk of T1BEL (hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.12 - 0.78, p = .014). Similar results were also observed in the subgroup of tortuous iliac arteries (HR 0.30, 95% CI 0.11 - 0.81, p = .017). After stratification by severe neck angulation, no significant difference was found between CL and SL EVAR for T1AEL, but the CL configuration was associated with a significantly increased risk of re-intervention (HR 2.69, 95% CI 1.31 - 5.51, p = .007). In addition, a trend towards a higher risk of adverse limb events in the CL group with severely angulated proximal neck was observed.

Conclusion: CL configuration in EVAR is safe and may be associated with a lower risk of T1BEL in patients with a large aneurysm sac or tortuous iliac arteries. However, it should be applied cautiously to aneurysms with a severely angulated neck due to the potentially higher risk of re-intervention.
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http://dx.doi.org/10.1016/j.ejvs.2021.01.018DOI Listing
April 2021

Preoperative Portal Vein Embolization for Liver Resection: An updated meta-analysis.

J Cancer 2021 21;12(6):1770-1778. Epub 2021 Jan 21.

Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009.

Portal vein embolization (PVE) is performed before major liver resection to increase liver volume remnant, controversy remains on the adverse effect of PVE on liver tumor patients. The current study highlighted the effect of PVE on the degree of hypertrophy of future liver remnant (FLR) and summarized PVE-related complications, aiming to provide a guideline for surgeons. A search of current published studies on PVE was performed. Meta-analysis was conducted to assess the effect of PVE on hypertrophy of FLR and summarized PVE-related complications. 26 studies including 2335 patients were enrolled in the meta-analysis. All enrolled studies reported data regarding FLR hypertrophy rate, pooled effect size (ES) for FLR hypertrophy rate using a fixed-effect model was 0.105 (95%CI: 0.094-0.117, p=0.000), indicating PVE is favored in inducing FLR hypertrophy. Metatrim method indicated no obvious evidence of publication bias in the present meta-analysis. 247 (10.6%) patients exhibited PVE-related complications, receiving expectant treatment without affecting planned liver resection. Total 1782 patients (76%) underwent a subsequent liver resection after PVE, which is an encouraging result comparing with traditional resection rate in liver tumor patients. PVE is a safe and effective procedure with a low occurrence of related complications for inducing sufficient hypertrophy of FLR in liver tumor patients, which could elevate the resection rate of liver tumor patients. Careful patient cohort selection is crucial to avoid overuse of PVE in technically resectable patients. Further multiple central clinical trials are conducive to select optimal patient cohorts and provide a guideline for surgeons.
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http://dx.doi.org/10.7150/jca.50371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890316PMC
January 2021

p75NTR/proBDNF Modulates Basal Cell Carcinoma (BCC) Immune Microenvironment via Necroptosis Signaling Pathway.

J Immunol Res 2021 1;2021:6652846. Epub 2021 Feb 1.

Department of Dermatology and Venereology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830000, China.

Basal cell carcinoma (BCC) is the most common skin cancer. While most of the basal cell carcinomas were localized lesion and can be easily managed, the treatment options to the advanced basal cell carcinomas are still remarkably limited. In recent years, proBDNF and its receptor p75NTR have been reported to play important roles in various diseases, including cancers and psychotic disorders. However, the role of p75NTR/proBDNF signaling in basal cell carcinoma remains unclear. Here, we found that the expression level of p75NTR/proBDNF was decreased in basal cell carcinoma patient samples and cell lines. In vitro study showed overexpression of p75NTR/proBDNF could significantly facilitate tumor cell death, including inflammatory-silent apoptosis and lytic inflammatory activated necroptosis. In vivo study showed overexpression of p75NTR/proBDNF dramatically promotes tumor-associated macrophage (M1) and T cell recruitment in a syngeneic mouse model of BCC. These results show a crucial role for p75NTR/proBDNF signaling in basal cell carcinoma immune microenvironment.
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http://dx.doi.org/10.1155/2021/6652846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870300PMC
February 2021

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Nat Commun 2021 02 17;12(1):1078. Epub 2021 Feb 17.

Copenhagen General Population Study, Herlev and Gentofte Hospital Copenhagen University Hospital, Herlev, Denmark.

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
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http://dx.doi.org/10.1038/s41467-020-20496-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890067PMC
February 2021

Repetitive syncope caused by a rare massive sporadic malignant peripheral nerve sheath tumor involving carotid arteries: A case report.

Medicine (Baltimore) 2021 Feb;100(5):e24386

Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.

Rationale: Malignant peripheral nerve sheath tumors (MPNSTs) are rare sarcomas arising from peripheral nerves. MPNSTs are uncommon in the head and neck, and various clinical manifestation often make the diagnosis challenging.

Patient Concerns: A 67-year-old female was referred for evaluation of repetitive syncope with a massive mass in the neck. Preoperative evaluation revealed potential neuroendocrine activity of the mass and enhanced computed tomography showed carotid artery was involved.

Diagnosis: According to the preoperative imaging, intraoperative finding and postoperative pathological examination, the diagnosis of left neck MPNST involving left carotid arteries was made.

Interventions: Volume expansion therapy with phenoxybenzamine started one week before surgery. Complete surgical resection of the mass was performed and pathological analysis suggested the diagnosis of MPNST. The postoperative radiotherapy was not given due to her poor nutrition.

Outcomes: This patient recovered well after surgery and no sign of recurrence was noted at 2-year follow-up.

Lessons: Though the involvement of carotid artery with neuroendocrine activity is rare in sporadic MPNST, preoperative scanning of blood and urine catecholamine is crucial for intraoperative hemodynamic stability, especially when carotid artery is involved.
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http://dx.doi.org/10.1097/MD.0000000000024386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870201PMC
February 2021

Meta-analysis of outcomes after intentional coverage of celiac artery in thoracic endovascular aortic repair.

J Vasc Surg 2021 Feb 13. Epub 2021 Feb 13.

Department of Vascular Surgery, West China Hospital, Chengdu, China.

Objective: The aim of the present study was to demonstrate the clinical outcomes of intentional coverage of the celiac artery (CA) during thoracic endovascular aneurysm repair (TEVAR).

Methods: The MEDLINE, EMBASE, and Cochrane Library databases were searched for studies reporting coverage of CA during TEVAR. The methodologic quality of the included studies was assessed using the Moga score and Newcastle-Ottawa scale. A random effects model was used to pool the estimates. A meta-analysis was performed with investigation of the following outcomes: visceral ischemia, spinal cord ischemia (SCI), stroke, endoleak, reintervention, 30-day mortality, and 1-year mortality.

Results: A total of 10 studies with 171 patients were included. The summary estimate rate of visceral ischemia events was 4.2% (95% confidence interval [CI], 0.9-8.9%; I = 4.1%). The incidence of stroke and SCI was 0.2% (95% CI, 0%-3.4%; I = 0%) and 3% (95% CI, 0.3%-7.4%; I = 6.1%). The rate of endoleak during the follow-up period was 24.1% (95% CI, 14.3%-35.1%; I = 20.0%). The reintervention rate was 13.6% (95% CI, 4.4%-25.7%; I = 66.0%). The 30-day and 1-year mortality were 2.9% (95% CI, 0.3%-7.2%; I = 6.2%) and 15.2% (95% CI, 7.8%-23.9%; I = 0%).

Conclusions: Among the patients with complex thoracic aortic pathologies deemed at high risk for open reconstruction, TEVAR with intentional coverage of the CA is a safe and feasible option to extend the distal sealing zone with acceptable rates of visceral ischemia, SCI, type II endoleak from the CA, and 30-day mortality.
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http://dx.doi.org/10.1016/j.jvs.2021.01.053DOI Listing
February 2021

Automatic Detection and Classification of Focal Liver Lesions Based on Deep Convolutional Neural Networks: A Preliminary Study.

Front Oncol 2020 29;10:581210. Epub 2021 Jan 29.

Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

With the increasing daily workload of physicians, computer-aided diagnosis (CAD) systems based on deep learning play an increasingly important role in pattern recognition of diagnostic medical images. In this paper, we propose a framework based on hierarchical convolutional neural networks (CNNs) for automatic detection and classification of focal liver lesions (FLLs) in multi-phasic computed tomography (CT). A total of 616 nodules, composed of three types of malignant lesions (hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and metastasis) and benign lesions (hemangioma, focal nodular hyperplasia, and cyst), were randomly divided into training and test sets at an approximate ratio of 3:1. To evaluate the performance of our model, other commonly adopted CNN models and two physicians were included for comparison. Our model achieved the best results to detect FLLs, with an average test precision of 82.8%, recall of 93.4%, and F1-score of 87.8%. Our model initially classified FLLs into malignant and benign and then classified them into more detailed classes. For the binary and six-class classification, our model achieved average accuracy results of 82.5 and73.4%, respectively, which were better than the other three classification neural networks. Interestingly, the classification performance of the model was placed between a junior physician and a senior physician. Overall, this preliminary study demonstrates that our proposed multi-modality and multi-scale CNN structure can locate and classify FLLs accurately in a limited dataset, and would help inexperienced physicians to reach a diagnosis in clinical practice.
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http://dx.doi.org/10.3389/fonc.2020.581210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878526PMC
January 2021

Influence of renal artery stenosis morphology on hemodynamics.

Comput Methods Biomech Biomed Engin 2021 Feb 10:1-19. Epub 2021 Feb 10.

Beijing Advanced Innovation Centre for Biomedical Engineering, Beihang University, Beijing.

Objective: Currently, the clinical classification of the severity of renal artery stenosis (RAS) solely depends on the degree of stenosis. In addition, when the stenosis degree is between 50% and 70%, the clinical strategy is decided based on whether the RAS is hemodynamically significant. In this study, the influence of RAS morphological parameters on hemodynamics was numerically analyzed to provide a theoretical basis for clinical treatment.

Methods: Idealized RAS models were established to investigate the hemodynamic effects of the stenosis length, asymmetric stenosis, and direction of the opening of the renal artery.

Results: The longer the stenosis length, the greater is the ratio of the low time-averaged wall shear stress (WSS) and high oscillatory shear index (OSI) area distal stenosis (when the stenosis area is the same). In addition, asymmetric stenosis leads to a significant increase in the ratio of the renal artery peak systolic velocity (R-PSV) and the abdominal aorta peak systolic velocity (A-PSV) when the stenosis area is 60-70%. Furthermore, the fraction flow reserve (FFR) of the RAS model with 12 mm stenosis length, upward eccentricity and upward direction of renal artery opening was approximately equal to the cumulative value of the influence of different stenosis morphologies on FFR.

Conclusion: An assessment of the severity of RAS should consider the stenosis area and other morphological parameters, including the length and asymmetry of RAS as well as the direction of the opening of renal artery, particularly when the stenosis degree of RAS is between 50% and 70%.
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http://dx.doi.org/10.1080/10255842.2021.1883592DOI Listing
February 2021

Icariin improves brain function decline in aging rats by enhancing neuronal autophagy through the AMPK/mTOR/ULK1 pathway.

Pharm Biol 2021 Dec;59(1):183-191

Medical College of China Three Gorges University, Yichang, P. R. Chinas.

Context: Icariin (ICA) is the main active ingredient of Maxim (Berberidaceae), which is used in the immune, reproductive, neuroendocrine systems, and anti-aging.

Objective: To evaluate the effect of ICA on natural aging rat.

Materials And Methods: 16-month-old Sprague-Dawley (SD) rats were randomly divided into aging, low and high-dose ICA groups ( = 8); 6-month-old rats were taken as the adult control ( = 8). Rats were fed regular feed (aging and adult control) or feed containing ICA (ICA 2 and 6 mg/kg group) for 4 months. HE and Nissl staining were used to assess pathological changes. Western blot was used to test the expression of autophagy (LC3B, p62, Atg5, Beclin1) and p-AMPK, p-mTOR and p-ULK1 (ser 757). Immunofluorescence was used to detect the co-localization of LC3 and neurons.

Results: ICA improved neuronal degeneration associated with aging and increased the staining of Nissl bodies. Western blot showed that ICA up-regulated autophagy-related proteins LC3B (595%), Beclin1 (73.5%), p-AMPK (464%) protein ( < 0.05 vs. 20 M) in the cortex and hippocampus of aging rats, down-regulated the expression of p62 (56.9%), p-mTOR (53%) and p-ULK1 (ser 757) (65.4%) protein ( < 0.05 vs. 20 M). Immunofluorescence showed that the fluorescence intensity of LC3 decreased in the aging rat brain, but increased and mainly co-localized with neurons after ICA intervention.

Conclusions: Further research needs to verify the expression changes of AMPK/mTOR/ULK1 and the improvement effect of ICA in elderly. These results will further accelerate the applications of ICA and the treatment for senescence.
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http://dx.doi.org/10.1080/13880209.2021.1878238DOI Listing
December 2021

Frailty as a predictor of major adverse cardiac and cerebrovascular events after endovascular aortic aneurysm repair.

J Vasc Surg 2021 Feb 4. Epub 2021 Feb 4.

Department of Vascular Surgery, West China Hospital, Sichuan University, Sichuan, China. Electronic address:

Objective: To evaluate the effect of frailty assessed by the modified Frailty Index (mFI) on major adverse cardiac and cerebrovascular events (MACCE) in the elderly patients after endovascular aortic aneurysm repair (EVAR).

Methods: This was a retrospective cohort study of elderly patients who underwent EVAR in a tertiary hospital. The main exposure was frailty status assessed by the mFI. The primary outcomes were 30-day and long-term MACCE. The predictive ability of the mFI was compared with the Revised Cardiac Risk Index (RCRI) using net reclassification improvement (NRI) and integrated discrimination improvement (IDI) statistics.

Results: Of 749 participants, 134 (17.89%) were identified as frail and 185 (24.70%) as prefrail. Thirteen patients (1.74%) were lost in follow-up after surgery, and the median length of follow-up was 32.00 months (range, 15.00-59.25 months). Frailty was associated with a significantly increased risk of 30-day MACCE (adjusted odds ratio OR, 14.53; 95% confidence interval [CI], 4.59-46.04; P < .0001) and longer intensive care unit stay (adjusted odds ratio, 2.43; 95% CI, 1.17-5.07; P = .0176). As for long-term outcomes, both frailty and prefrailty were associated significantly increased risks of MACCE after EVAR (prefrail: adjusted hazard ratio [HR] 1.71; 95% CI, 1.12-2.61; frail: adjusted HR, 3.37; 95% CI, 1.86-6.10). When considering death as a competing risk, we also observed a significant association between frailty and cardiac and cerebrovascular events (adjusted HR, 2.95; 95% CI, 1.06-8.15). In addition, frailty was associated with a significantly increased risk of all-cause mortality (adjusted HR, 1.93; 95% CI, 1.28-2.90). Compared with the RCRI, the mFI had better discrimination in predicting 30-day MACCE (IDI: 0.225; 95% CI, 0.018-0.431; P = .033; NRI: 0.225; 95% CI, 0.023-0.427; P = .029) and long-term MACCE (IDI: 0.056; 95% CI, 0.018-0.128; P = .013; NRI: 0.237; 95% CI, 0.136-0.359; P < .001).

Conclusions: Frailty assessed by the mFI may serve as a useful predictor of both short-term and long-term MACCE in elderly patients after EVAR, with improved discrimination and reclassification abilities compared with the RCRI.
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http://dx.doi.org/10.1016/j.jvs.2021.01.025DOI Listing
February 2021

Grain refining of Ti-6Al-4V alloy fabricated by laser and wire additive manufacturing assisted with ultrasonic vibration.

Ultrason Sonochem 2021 May 21;73:105472. Epub 2021 Jan 21.

Key Laboratory of Superlight Materials & Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001, China.

The formation of the coarse columnar crystal structure of Ti-6Al-4V alloy in the process of additive manufacturing greatly reduces the mechanical performance of the additive manufactured parts, which hinders the applications of additive manufacturing techniques in the engineering fields. In order to refine the microstructure of the materials using the high intensity ultrasonic via the acoustic cavitation and acoustic flow effect in the process of metal solidification, an ultrasonic vibration technique was developed to a synchronous couple in the process of Laser and Wire Additive Manufacturing (LWAM) in this work. It is found that the introduction of high-intensity ultrasound effectively interrupts the epitaxial growth tendency of prior-β crystal and weakens the texture strength of prior-β crystal. The microstructure of Ti-6Al-4V alloy converts to fine columnar crystals from typical coarse columnar crystals. The simulation results confirm that the acoustic cavitation effect applied to the molten pool created by the high-intensity ultrasound is the key factor that affects the crystal characteristics.
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http://dx.doi.org/10.1016/j.ultsonch.2021.105472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848607PMC
May 2021

The glucagon-like peptide-1 (GLP-1) analog exenatide ameliorates intrauterine adhesions in mice.

Peptides 2021 Mar 12;137:170481. Epub 2021 Jan 12.

The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou, China; Gansu Key Laboratory of Reproductive Medicine and Embryo, Gansu International Scientific and Technological Cooperation Base of Reproductive Medicine Transformation Application, Lanzhou, China. Electronic address:

Objective: The purpose of the experiments in this study was to explore the effect of exenatide on intrauterine adhesions (IUAs) and to elucidate its mechanism to provide new ideas for the clinical treatment of IUAs.

Methods: In this study, an animal model of IUAs was established by double stimulation using mechanical curettage and inflammation. After modeling, the treatment group was injected subcutaneously with three doses of exenatide for two weeks. The model group was injected with sterile ultrapure water, and the sham operation group was treated the same as the normal group, except for the observation of abdominal wound changes. Two weeks later, all mice were sacrificed by cervical dysfunction. The obtained mouse uterine tissue was used for subsequent experimental detection, using HE and Masson staining for histomorphological and pathological analysis; qRT-PCR for the detection of TGF-β1, α-SMA, and MMP-9 gene expression in uterine tissue; and western blotting analysis of TGF-β1, α-SMA, and collagen 1 protein expression to verify whether exenatide has a therapeutic effect on IUAs in mice.

Results: In the high-dose exenatide treatment group, the endometrial glands significantly increased in size, and the deposition area of collagen fibers in the endometrial tissue was significantly reduced. We observed that the mRNA expression of TGF-β1 and α-SMA in the endometrial tissue of IUAs mice in this group was significantly reduced, while the expression of MMP-9 was significantly increased. In addition, we found that the protein expression of TGF-β1, α-SMA, and collagen 1 remarkably decreased after treatment with exenatide.

Conclusion: Exenatide may reduce the deposition of collagen fibers in the uterus of IUAs mice and promote the proliferation of endometrial glands in mice.
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http://dx.doi.org/10.1016/j.peptides.2020.170481DOI Listing
March 2021

A novel simple risk model to predict the prognosis of patients with paraquat poisoning.

Sci Rep 2021 Jan 8;11(1):237. Epub 2021 Jan 8.

Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

To identify risk factors and develop a simple model to predict early prognosis of acute paraquat (PQ) poisoning patients, we performed a retrospective cohort study of acute PQ poisoning patients (n = 1199). Patients (n = 913) with PQ poisoning from 2011 to 2018 were randomly divided into training (n = 609) and test (n = 304) samples. Another two independent cohorts were used as validation samples for a different time (n = 207) and site (n = 79). Risk factors were identified using a logistic model with Markov Chain Monte Carlo (MCMC) simulation and further evaluated using a latent class analysis. The prediction score was developed based on the training sample and was evaluated using the testing and validation samples. Eight factors, including age, ingestion volume, creatine kinase-MB [CK-MB], platelet [PLT], white blood cell [WBC], neutrophil counts [N], gamma-glutamyl transferase [GGT], and serum creatinine [Cr] were identified as independent risk indicators of in-hospital death events. The risk model had C statistics of 0.895 (95% CI 0.855-0.928), 0.891 (95% CI 0.848-0.932), and 0.829 (95% CI 0.455-1.000), and predictive ranges of 4.6-98.2%, 2.3-94.9%, and 0-12.5% for the test, validation_time, and validation_site samples, respectively. In the training sample, the risk model classified 18.4%, 59.9%, and 21.7% of patients into the high-, average-, and low-risk groups, with corresponding probabilities of 0.985, 0.365, and 0.03 for in-hospital death events. We developed and evaluated a simple risk model to predict the prognosis of patients with acute PQ poisoning. This risk scoring system could be helpful for identifying high-risk patients and reducing mortality due to PQ poisoning.
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http://dx.doi.org/10.1038/s41598-020-80371-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794476PMC
January 2021

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Nat Genet 2021 01 4;53(1):65-75. Epub 2021 Jan 4.

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
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http://dx.doi.org/10.1038/s41588-020-00748-0DOI Listing
January 2021

Successful endovascular treatment with long-term antibiotic therapy for infectious pseudoaneurysm due to : A case report.

World J Clin Cases 2020 Dec;8(24):6529-6536

Department of Vascular Surgery, West China Hospital, Sichuan University, Chengdu 610000, Sichuan Province, China.

Background: Infectious common femoral artery pseudoaneurysm caused by pulmonary infection is a relatively infrequent entity but is potentially life and limb threatening. The management of infectious pseudoaneurysm remains controversial.

Case Summary: We reported a 79-year-old man with previous pulmonary infection and multiple comorbidities who presented with a progressive pulsate mass at the right groin and with right lower limb pain. Computed tomography angiography showed a 6 cm × 6 cm × 9 cm pseudoaneurysm of the right common femoral artery accompanied by occlusion of the right superficial femoral artery and deep femoral artery. He underwent endovascular treatment (EVT) with stent-graft, and etiology of infectious pseudoaneurysm was confirmed. Then, 3-mo antibiotic therapy was given. One-year follow-up showed the stent-graft was patent and complete removal of surrounding hematoma.

Conclusion: The femoral artery pseudoaneurysm can be caused by deriving from the pulmonary infection. Moreover, this unusual case highlights the use of EVT and prolonged antibiotic therapy for infectious pseudoaneurysm.
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http://dx.doi.org/10.12998/wjcc.v8.i24.6529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760425PMC
December 2020

Influence of Anesthetic Techniques on Perioperative Outcomes after Endovascular Aneurysm Repair.

Ann Vasc Surg 2020 Dec 29. Epub 2020 Dec 29.

Department of Vascular Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China. Electronic address:

Background: The purpose of the study was to explore the influence of anesthetic techniques on perioperative outcomes after endovascular aneurysm repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA) in a Chinese population.

Methods: A retrospective review was performed in patients after elective EVAR for infrarenal AAA at our single center. Patients were classified into general anesthesia (GA), regional anesthesia (RA), and local anesthesia (LA) groups. The primary outcomes (30-day mortality and morbidity) and secondary outcomes [procedure time, mean arterial pressure (MAP), and length of hospital stay (LOS)] were collected and analyzed.

Results: From January 2006 to December 2015, 486 consecutive patients underwent elective EVAR at our center. GA was used in 155 patients (31.9%), RA in 56 (11.5%), and LA in 275 (56.6%). The GA patients had fewer respiratory comorbidities, shorter and more angulated proximal necks, and more concomitant iliac aneurysms. LA during EVAR was significantly associated with a shorter procedure time (GA, P < 0.001; RA, P < 0.001) and shorter LOS (GA, P = 0.002; RA, P = 0.001), but a higher MAP (GA, P < 0.001; RA, P < 0.001) compared with GA and RA. LA was associated with a significantly lower risk of cardiac (odds ratio (OR) 4.27, 95% confidence interval (CI) 1.21-15.04), pulmonary (OR 5.37, 95% CI 1.58-18.23), and systemic complications (OR 4.15, 95% CI 1.85-9.33) compared with GA. RA was also associated with a decreased risk of systemic complications (OR 4.74, 95% CI 1.19-18.92) compared with GA. There was no difference in the 30-day mortality, neurologic complications, renal complications, and intraoperative extra procedures among the 3 groups.

Conclusions: Anesthetic techniques for EVAR have no influence on the 30-day mortality. LA for EVAR appears to be beneficial concerning the procedure time, LOS, and 30-day systemic complications for patients after elective EVAR for infrarenal AAA in the Chinese population.
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http://dx.doi.org/10.1016/j.avsg.2020.11.034DOI Listing
December 2020

Comparison of Clinical Outcomes Following One versus Two Stage Hybrid Repair of Thoraco-Abdominal Aortic Aneurysms: A Comprehensive Meta-Analysis.

Eur J Vasc Endovasc Surg 2021 03 6;61(3):396-406. Epub 2021 Jan 6.

Department of Vascular Surgery, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Objective: For thoraco-abdominal aortic aneurysms (TAAA), it is unclear whether it is better to perform hybrid repair in one (single) or two stages (staged). This study aimed to compare the clinical outcomes of single vs. staged hybrid repair of TAAA.

Methods: The Medline, Embase, and Cochrane Databases (1 January 1994 to 11 May 2020) were searched for studies on hybrid repair of TAAA. Cohort studies and case series reporting outcomes of single and staged hybrid repair of TAAA were eligible for inclusion. The Newcastle-Ottawa scale and an 18 item tool were used to assess the risk of bias. The primary outcome was 30 day mortality, and the secondary outcomes included post-operative complications, overall survival, and other mid term events. A random effects model was used to calculate pooled estimates.

Results: A total of 37 studies was included in the meta-analysis. The quality assessment of the included studies suggested low or moderate risk of bias. The pooled estimates for aneurysm rupture and death during stage interval were 2% (95% CI 0%-4%, I = 0%) and 4% (95% CI 2%-7%, I = 0%), respectively. Single repair was associated with a significantly higher 30 day risk of death when compared with patients who completed staged procedures successfully (OR 2.64, 95% CI 1.36-5.12, I = 0%). Staged repair also had lower incidence of major adverse cardiac events (MACE) (single: 10%, 95% CI 5%-16%; staged: 2%, 95% CI 0%-5%) and intestinal complications (single: 15%, 95% CI 8%-25%; staged: 3%, 95% CI 1%-6%). For mid term outcomes, single and staged repair had comparable 12 month overall survival, aneurysm related mortality, rate of re-intervention, and graft patency.

Conclusion: Two stage hybrid repair may represent a better choice for patients with controlled risk of aneurysm rupture, because it can provide lower 30 day mortality risks, MACE, and intestinal complications, as well as comparable mid term outcomes. Randomised controlled trials are needed to ascertain the effect of repair staging in patients for elective TAAA.
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http://dx.doi.org/10.1016/j.ejvs.2020.11.033DOI Listing
March 2021

Reversibility of hAT-MSCs phenotypic and metabolic changes after exposure to and withdrawal from HCC-conditioned medium through regulation of the ROS/MAPK/HIF-1α signaling pathway.

Stem Cell Res Ther 2020 11 27;11(1):506. Epub 2020 Nov 27.

Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.

Background: Mesenchymal stem cells (MSCs) play an important role in tumor progression; concomitantly, MSCs also undergo profound changes in the tumor microenvironment (TME). These changes can directly impact the application and efficacy of MSC-based anti-tumor therapy. However, few studies have focused on the regulation of MSC fate in TME, which will limit the progress of MSC-based anti-tumor therapy. Herein, we investigated the effects of conditioned medium from human hepatocellular carcinoma cells (HCC-CM) on the phenotype and glucose metabolism of human adipose tissue-derived MSCs (hAT-MSCs).

Methods: The passage 2 (P2) to passage 3 (P3) hAT-MSCs were exposed to conditioned medium from Hep3B, Huh7 and HCCLM3 cells for 4-8 weeks in vitro. Then, immunofluorescent, CCK-8 assay, EdU assay, Transwell assay, and flow cytometry were used to assess the alterations in cell phenotype in terms of cell morphology, secretory profiles, proliferation, migration, invasion, cell cycle, and apoptosis. In addition, glucose metabolism was evaluated by related kits. Next, the treated hAT-MSCs were subjected to withdrawal from HCC-CM for 2-4 weeks, and alterations in phenotype and glucose metabolism were reevaluated. Finally, the molecular mechanism was clarified by Western blotting.

Results: The results revealed that after exposure to HCC-CM, hAT-MSCs developed a stellate-shaped morphology. In association with cytoskeleton remodeling, hAT-MSCs showed enhanced capacities for migration and invasion, while cell proliferation was inhibited by regulating the cell cycle by downregulating cyclins and cyclin-dependent kinases and activating the mitochondrial apoptosis pathway. In terms of glucose metabolism, our results showed mitochondrial dysfunction and elevated glycolysis of hAT-MSCs. However, interestingly, when the treated hAT-MSCs were subjected to withdrawal from HCC-CM, the alterations in phenotype and glucose metabolism could be reversed, but secretory phenotype and tumor-promoting properties appear to be permanent. Further studies showed that these changes in hAT-MSCs may be regulated by the ROS/MAPK/HIF-1α signaling pathway.

Conclusion: Taken together, the effects of long-term HCC-CM treatment on phenotype and glucose metabolism in hAT-MSCs are modest and largely reversible after withdrawal, but HCC-CM endow hAT-MSCs with permanent secretory phenotype and tumor-promoting properties. This is the first report on the reversal of phenotype and glucose metabolism in tumor-associated MSCs (TA-MSCs), it is anticipated that new insights into TA-MSCs will lead to the development of novel strategies for MSC-based anti-tumor therapy.
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http://dx.doi.org/10.1186/s13287-020-02010-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694319PMC
November 2020

Protective effects of saponins from Panax japonicus on neurons of the colon myenteric plexus in aging rats through reduction of α-synuclein through endoplasmic reticulum stress.

Geriatr Gerontol Int 2021 Jan 27;21(1):85-93. Epub 2020 Nov 27.

Medical College of China Three Gorges University, Yichang, China.

Aim: The enteric nervous system degenerates gradually with age, and α-synuclein (α-syn) is a suitable marker of enteric nervous system degeneration, which is intimately related with endoplasmic reticulum stress and unfolded protein response (UPR ). Saponins from Panax japonicus (SPJ) have obvious protective effects on neurons in several degenerative disease models. Here, the study was designed to investigate whether SPJ could reverse the neuron degeneration through regulating the UPR in the colon myenteric plexus of aging rats.

Methods: Aging rats had been treated with SPJ for 6 months since they were aged 18 months. Then, the colon samples were collected and neuron morphology in the myenteric plexus was observed. Immunohistochemistry staining was used to detect the expressions of NeuN, α-syn, GRP78 and three different UPR branches. Double immunofluorescence was used to determine the co-localization of α-syn and NeuN, GRP78 and NeuN.

Results: Neurons degenerated in the colon myenteric plexus of aging rats, but co-localization of α-syn and NeuN increased. In addition, both the expressions of GRP78 and three UPR branch signaling pathway proteins decreased in the colon myenteric plexus of aging rats. Treatment of SPJ almost alleviated the above effects in aging rats, except for ATF6.

Conclusions: SPJ could reverse the neuron loss caused by accumulation of α-syn in the myenteric plexus of colon in aging rats, which is potentially associated with increased GRP78 and most URP changes. Geriatr Gerontol Int 2021; 21: 85-93.
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http://dx.doi.org/10.1111/ggi.13882DOI Listing
January 2021

Characteristics of TGFBR1-EGFR-CTNNB1-CDH1 Signaling Axis in Wnt-Regulated Invasion and Migration in Lung Cancer.

Cell Transplant 2020 Jan-Dec;29:963689720969167

Department of Interventional and Vascular Surgery, 12476Tenth People's Hospital of Tongji University, Shanghai, China.

This study aimed to explore the characteristics of TGFBR1-epidermal growth factor receptor (EGFR)-CTNNB1-CDH1 axis in regulating the invasion and migration in lung cancer. Using the small interfering RNA technology, EGFR was silenced in H2170 and H1299 cells. Then, the colony formation, migration, and invasion abilities were detected using colony-forming assay and transwell assay. Moreover, the mRNA expression of smad2, smad3, CTNNB1, and CDH1, and the protein expression of TGFBR1, CDH1, and TCF were determined using the real-time polymerase chain reaction and western blotting. The results showed that silencing EGFR could significantly decrease the colony-forming ability in H2170 and H1299. Knocking down EGFR could significantly inhibit the invasion and migration ability of H2179 and H1299. Inhibiting the expression of EGFR could significantly decrease the expression of smad2, smad3, CDH1, and CTNNB1, with all -values <0.05. In addition, silencing EGFR could markedly decrease the expression of TGFBR1 and CDH1 in H1299 and H2170, with all values <0.05. In conclusion, silencing EGFR could significantly regulate the progression of lung cancer via TGFBR1-EGFR-CTNNB1-CDH1 axis in Wnt signaling pathway.
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http://dx.doi.org/10.1177/0963689720969167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784602PMC
November 2020

[D-galactose (D-gal) disrupts barrier function of murine TM4 sertoli cells via activation of p38MAPK signaling pathway].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2020 Nov;36(11):1002-1008

Third-Grade Pharmacological Laboratory on Traditional Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University, Yichang 443002, China. *Corresponding author, E-mail:

Objective To explore the effects of D-galactose (D-gal) on barrier function of murine TM4 sertoli cells and its mechanism. Methods TM4 cells were divided into control group and 25, 50, 100, 150, 200, 250 mmol/L D-gal stimulation group. The viability of TM4 cells was determined by MTT assay. The protein expression levels of tight junction-related proteins including zonula occluden-1 (ZO-1) and occludin, adheren junction-related proteins including neural cadherin (N-cadherin), epithelial cadherin (E-cadherin) and β-catenin, gap junction-related protein connexin43 (CX43) and cytoskeleton-related protein vimentin, and MAPK signaling pathway-related proteins ERK1/2, phosphorylated ERK1/2 (p-ERK1/2), JNK, phosphorylated JNK (p-JNK), p38MAPK and phosphorylated p38MAPK (p-p38MAPK) were detected by Western blot analysis. Results Compared with the control group, the viability of TM4 cells significantly decreased when the concentration of D-gal was more than 50 mmol/L. In addition, the protein expression levels of ZO-1, occludin, N-cadherin, E-cadherin and β-catenin were significantly down-regulated in D-gal-treated group, while the protein expression levels of p-p38MAPK were significantly up-regulated. However, there were no differences in the protein expression levels of CX43, vimentin, p-ERK, ERK1/2, p-JNK and JNK between the control group and D-gal-treated groups. Conclusion D-gal can disrupt tight junction and adheren junction of TM4 cells via the activation of p38MAPK signaling pathway.
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November 2020