Publications by authors named "Wen Jiang"

1,134 Publications

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Reduced kinase D‑interacting substrate of 220 kDa (Kidins220) in pancreatic cancer promotes EGFR/ERK signalling and disease progression.

Int J Oncol 2021 Jun 6;58(6). Epub 2021 May 6.

Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.

Kidins220 is a transmembrane scaffold protein involved in several types of cancer. The aim of the present study was to examine the role of Kidins220 in tumorigenesis and disease progression of pancreatic cancer. The relevant signalling pathways including EGFR, EMT, and MMP were also investigated. The expression of Kidins220 was examined at the transcript and protein level. The Kidins220 knockdown cell model was established and its influence on cellular functions was determined. Involvement of Kidins220 in tumorigenesis and metastasis was examined in CD1 mice, respectively. The results showed that, reduced Kidin220 expression was associated with tumorigenesis, metastasis, and overall survival of pancreatic cancer. Knockdown of Kidins220 promoted proliferation, colony formation and tumorigenic capacity of pancreatic cancer cells and , respectively. Kidins220 regulated pancreatic cancer cell migration through the EGFR/AKT/ERK signalling pathway. Furthermore, enhanced EMT was observed in the pancreatic cancer cell lines with the knockdown of Kidins220, underlying EGFR regulation. Kidins220 also affected cell invasion via MMP1. A reduced expression of Kidins220 was observed in pancreatic cancer, which is associated with disease progression, distant metastasis and poor prognosis. The loss of Kidins220 in pancreatic cancer may contribute to disease progression through the upregulation of EGFR and downstream signalling.
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http://dx.doi.org/10.3892/ijo.2021.5214DOI Listing
June 2021

Corrigendum: Identification of Two New Isolates of From Different Regions in China: Molecular Diversity, Phylogenetic and Recombination Analysis.

Front Microbiol 2021 19;12:670393. Epub 2021 Apr 19.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Biotechnology in Plant Protection of Ministry of Agriculture and Zhejiang Province, Institute of Plant Virology, Ningbo University, Ningbo, China.

[This corrects the article DOI: 10.3389/fmicb.2020.616171.].
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http://dx.doi.org/10.3389/fmicb.2021.670393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089474PMC
April 2021

Expression of Death Associated Proteins DAP1 and DAP3 in Human Pancreatic Cancer.

Anticancer Res 2021 May;41(5):2357-2362

Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, U.K.;

Background: Death associated proteins (DAPs) are involved in the apoptosis of various cell types in response to interferon gamma, including cancer cells. The present study assessed both DAP1 and DAP3 in human pancreatic cancer.

Materials And Methods: DAP1 and DAP3 transcripts were quantitatively analysed in pancreatic tumour tissues and paired adjacent normal tissues using real time PCR followed by statistical analyses for their clinical implications.

Results: Levels of DAP3 transcripts in pancreatic cancer were markedly higher than in normal tissues, whereas DAP1 had lower levels in cancer versus normal tissues. Adenocarcinomas showed higher levels of DAP3 than other histological types. Patients with high levels of DAP3 had a significantly shorter overall survival than those with low levels (p=0.012). The status of DAP3 and lymph node involvement identified patients with poor survival (p<0.00001).

Conclusion: DAP3 was highly expressed in pancreatic tumour tissues and was significantly associated with shorter survival.
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http://dx.doi.org/10.21873/anticanres.15010DOI Listing
May 2021

Dual effects of targeting S100A11 on suppressing cellular metastatic properties and sensitizing drug response in gastric cancer.

Cancer Cell Int 2021 Apr 30;21(1):243. Epub 2021 Apr 30.

Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.

Background: S100A11 is a member of the S100 family of proteins containing two EF-hand calcium-binding motifs. The dysregulated expression of the S100A11 gene has been implicated in tumour metastasis. However, the role of S100A11 protein in tumour cell response to chemotherapeutic drugs has not been characterised.

Methods: Transcript levels of S100A11 in gastric cancer were evaluated using an in-house patient cohort. Protein expression of S100A11 in gastric cancer was estimated by immunohistochemistry of a tissue microarray. The stable gastric cancer cell lines were established using lentiviral shRNA vectors. The knockdown of S100A11 was validated by qRT-PCR, PCR, and Western blot. The cellular function of S100A11 was estimated by assays of cell adhesion, migration, and invasion. The cell cytotoxic assay was performed to investigate the response to chemotherapeutic drugs. An unsupervised hierarchical clustering and principal component analysis (HCPC) was applied to unveil the dimensional role of S100A11 among all S100 family members in gastric cancer.

Results: High expression of S100A11 is associated with poor survival of gastric cancer patients (p < 0.001, HR = 1.85) and is an independent prognostic factor of gastric cancer. We demonstrate that S100A11 plays its role as a tumour promoter through regulating the MMP activity and the epithelial-mesenchymal transition (EMT) process. The stable knockdown of S100A11 suppresses the metastatic properties of gastric cancer cells, which include enhancing cell adhesion, but decelerating cell migration and invasion. Furthermore, the knockdown of S100A11 gene expression dramatically induces the cellular response of gastric cancer cells to the first-line chemotherapeutic drugs fluoropyrimidine 5-fluorouracil (5-FU) and cisplatin.

Conclusion: The present study identifies S100A11 as a tumour promoter in gastric cancer. More importantly, the S100A11-specific targeting potentially presents dual therapeutic benefits by not only controlling tumour progression but also sensitising chemotherapeutic cytotoxic response.
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http://dx.doi.org/10.1186/s12935-021-01949-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086328PMC
April 2021

Prostate Cancer Cell Extracellular Vesicles Increase Mineralisation of Bone Osteoblast Precursor Cells in an In Vitro Model.

Biology (Basel) 2021 Apr 10;10(4). Epub 2021 Apr 10.

Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff CF14 4YS, UK.

Skeletal metastases are the most common form of secondary tumour associated with prostate cancer (PCa). The aberrant function of bone cells neighbouring these tumours leads to the devel-opment of osteoblastic lesions. Communication between PCa cells and bone cells in bone envi-ronments governs both the formation/development of the associated lesion, and growth of the secondary tumour. Using osteoblasts as a model system, we observed that PCa cells and their conditioned medium could stimulate and increase mineralisation and osteoblasts' differentiation. Secreted factors within PCa-conditioned medium responsible for osteoblastic changes included small extracellular vesicles (sEVs), which were sufficient to drive osteoblastogenesis. Using MiR-seq, we profiled the miRNA content of PCa sEVs, showing that miR-16-5p was highly ex-pressed. MiR-16 was subsequently higher in EV-treated 7F2 cells and a miR-16 mimic could also stimulate mineralisation. Next, using RNA-seq of extracellular vesicle (EV)-treated 7F2 cells, we observed a large degree of gene downregulation and an increased mineralisation. Ingenuity® Pathway Analysis (IPA) revealed that miR-16-5p (and other miRs) was a likely upstream effec-tor. MiR-16-5p targets in 7F2 cells, possibly involved in osteoblastogenesis, were included for val-idation, namely AXIN2, PLSCR4, ADRB2 and DLL1. We then confirmed the targeting and dow-regulation of these genes by sEV miR-16-5p using luciferase UTR (untranslated region) reporters. Conversely, the overexpression of PLSCR4, ADRB2 and DLL1 lead to decreased osteoblastogene-sis. These results indicate that miR-16 is an inducer of osteoblastogenesis and is transmitted through prostate cancer-derived sEVs. The mechanism is a likely contributor towards the for-mation of osteoblastic lesions in metastatic PCa.
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http://dx.doi.org/10.3390/biology10040318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069461PMC
April 2021

EPLIN Expression in Gastric Cancer and Impact on Prognosis and Chemoresistance.

Biomolecules 2021 Apr 8;11(4). Epub 2021 Apr 8.

Cardiff China Medical Research Collaborative (CCMRC), Division of Cancer and Genetics (DCG), Cardiff University School of Medicine, Cardiff CF14 4XN, UK.

Epithelial protein lost in neoplasm (EPLIN) has been implicated as a suppressor of cancer progression. The current study explored EPLIN expression in clinical gastric cancer and its association with chemotherapy resistance. EPLIN transcript expression, in conjunction with patient clinicopathological information and responsiveness to neoadjuvant chemotherapy (NAC), was explored in two gastric cancer cohorts collected from the Beijing Cancer Hospital. Kaplan-Meier survival analysis was undertaken to explore EPLIN association with patient survival. Reduced EPLIN expression was associated with significant or near significant reductions of overall, disease-free, first progression or post-progression survival in the larger host cohort and Kaplan Meier plotter datasets. In the larger cohort EPLIN expression was significantly higher in the combined T1 + T2 gastric cancer group compared to the T3 + T4 group and identified to be an independent prognostic factor of disease-free survival and overall survival by multivariate analysis. In the smaller, NAC cohort, EPLIN expression was found to be significantly lower in tumour tissues than in paratumour tissues. EPLIN expression was significantly associated with responsiveness to chemotherapy which contributes to overall survival. Together, EPLIN appears to be a prognostic factor and may be associated with patient sensitivity to NAC.
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http://dx.doi.org/10.3390/biom11040547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068319PMC
April 2021

Affinity Capture of p97 with Small-Molecule Ligand Bait Reveals a 3.6 Å Double-Hexamer Cryoelectron Microscopy Structure.

ACS Nano 2021 Apr 26. Epub 2021 Apr 26.

Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United States.

Recent progress in the development of affinity grids for cryoelectron microscopy (cryo-EM) typically employs genetic engineering of the protein sample such as histidine or Spy tagging, immobilized antibody capture, or nonselective immobilization via electrostatic interactions or Schiff base formation. We report a powerful and flexible method for the affinity capture of target proteins for cryo-EM analysis that utilizes small-molecule ligands as bait for concentrating human target proteins directly onto the grid surface for single-particle reconstruction. This approach is demonstrated for human p97, captured using two different small-molecule high-affinity ligands of this AAA+ ATPase. Four electron density maps are revealed, each representing a p97 conformational state captured from solution, including a double-hexamer structure resolved to 3.6 Å. These results demonstrate that the noncovalent capture of protein targets on EM grids modified with high-affinity ligands can enable the structure elucidation of multiple configurational states of the target and potentially inform structure-based drug design campaigns.
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http://dx.doi.org/10.1021/acsnano.0c10185DOI Listing
April 2021

Platelet-Mimicking Therapeutic System for Noninvasive Mitigation of the Progression of Atherosclerotic Plaques.

Adv Sci (Weinh) 2021 04 18;8(8):2004128. Epub 2021 Feb 18.

State Key Laboratory of Natural Medicines School of Engineering China Pharmaceutical University Nanjing 211198 China.

Atherosclerotic plaque is the primary cause of cardiovascular disorders and remains a therapeutic hurdle for the early intervention of atherosclerosis. Traditional clinical strategies are often limited by surgery-related complications or unsatisfactory effects of long-term drug administration. Inspired by the plaque-binding ability of platelets, a biomimic photodynamic therapeutic system is designed to mitigate the progression of atherosclerotic plaques. This system is composed of photosensitizer-loaded upconversion nanoparticle cores entrapped in the platelet membrane. The platelet membrane coating facilitates specific targeting of the therapeutic system to macrophage-derived foam cells, the hallmark, and main component of early stage atherosclerotic plaques, which is firmly confirmed by in vivo fluorescent and single-photon emission computed tomography/computed tomography (SPECT/CT) radionuclide imaging. Importantly, in vivo phototherapy guided by SPECT/CT imaging alleviates plaque progression. Further immunofluorescence analysis reveals foam cell apoptosis and ameliorated inflammation. This biomimic system, which combines plaque-binding with radionuclide imaging guidance, is a novel, noninvasive, and potent strategy to mitigate the progression of atherosclerotic plaque.
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http://dx.doi.org/10.1002/advs.202004128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061396PMC
April 2021

High-fidelity diffusion tensor imaging of the cervical spinal cord using point-spread-function encoded EPI.

Neuroimage 2021 Apr 20;236:118043. Epub 2021 Apr 20.

Center for Biomedical Imaging Research, Department of Biomedical Engineering, Tsinghua University, Beijing, China. Electronic address:

Diffusion tensor imaging (DTI) of the spinal cord is technically challenging due to the size of its structure and susceptibility-induced field inhomogeneity, which impedes clinical applications. This study aimed to achieve high-fidelity spinal cord DTI with reasonable SNR and practical acquisition efficiency. Particularly, a distortion-free multi-shot EPI technique, namely point-spread-function encoded EPI (PSF-EPI), was adopted for diffusion imaging of the cervical spinal cord (CSC). The shot number can be reduced to six for sagittal scans through titled-CAIPI acceleration and partial Fourier undersampling, consequently rendering this technique beneficial in clinics. Fifteen healthy volunteers and seven patients with metallic implants underwent sagittal scans using tilted-CAIPI PSF-EPI at 3T. Unsuppressed fat signals were further removed by retrospective water/fat separation using the intrinsic chemical-shift encoded signals. Compared with multi-shot interleaved EPI method, highly accelerated PSF-EPI method provided evidently improved distortion reduction and higher consistency with anatomical references even with metallic implants. Additionally, axial DTI scans using PSF-EPI were also evaluated quantitatively, and the measured DTI metrics are similar to those obtained from the zonal oblique multi-slice EPI (ZOOM-EPI) method and reported values. The high anatomical consistency, practical scan time and quantitative reliability indicate PSF-EPI's clinical potential for CSC diffusion imaging.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118043DOI Listing
April 2021

Correlation of Seizure Increase and COVID-19 Outbreak in Adult Patients with Epilepsy: Findings and Suggestions from a Nationwide Multi-centre Survey in China.

Seizure 2021 Mar 31;88:102-108. Epub 2021 Mar 31.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, China. Electronic address:

Objectives: To investigate the impact of the COVID-19 outbreak on the behaviours, mental health and seizure control of adult patients with epilepsy (PWE) and to identify the correlation of seizure increase and the COVID-19 outbreak to guide the medical care of individuals with epilepsy during a public health crisis.

Methods: This study was conducted at 28 centres from February 2020 to April 2020. Participants filled out a 62-item online survey including sociodemographic, COVID-19-related, epilepsy-related and psychological variables and were divided into two groups based on whether their seizure frequency increased during the COVID-19 pandemic. Chi-square tests and t-tests were used to test differences in significant characteristics. Multiple logistic regression analyses were used to identify risk factors for seizure worsening.

Results: A total of 1,237 adult PWE were enrolled for analysis. Of this sample, 31 (8.33%) patients experienced an increase in seizures during the pandemic. Multivariate logistic regression suggested that feeling nervous about the pandemic (P < 0.05), poor quality of life (P = 0.001), drug reduction/withdrawal (P = 0.032), moderate anxiety during the COVID-19 outbreak (P = 0.046) and non-seizure free before the COVID-19 outbreak (P < 0.05) were independently related to seizure increase during the pandemic.

Conclusions: During the COVID-19 pandemic, PWE with poor quality of life and mental status, as well as AED reduction/withdrawal, were more likely to experience seizure increase. This observation highlights the importance of early identification of the population at high risk of seizure worsening and implementation of preventive strategies during the pandemic.
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http://dx.doi.org/10.1016/j.seizure.2021.03.029DOI Listing
March 2021

[Effect analysis of benign paroxysmal positional vertigo secondary to sudden sensorineural hearing loss].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 Mar;35(3):234-237

Department of Otolaryngology,Qingdao Municipal Hospital,Qingdao,266071,China.

To compare the effectiveness of canalith repositioning procedure between BPPV secondary to sudden sensorineural hearing loss(SSNHL) group and idiopathic BPPV(i-BPPV) group. A retrospective study of patients with evidence of idiopathic BPPV or SSNHL with BPPV. All participants were identified and categorized by using the Dix-Hallpike test and roll test, and then followed by canalith repositioning procedures (CRPs). The assessment of outcome was conducted at one-week post-CRPs. Sixty-four BPPV patients secondary to sudden sensorineural hearing loss and 328 patients with idiopathic BPPV were included. The posterior canal is the most affected in both group. At one-week post-treatment, the effectiveness of CRPs in the BPPV with SSNHL group was significantly lower than that of the i-BPPV group (<0.001). The clinical characteristics of BPPV secondary to SSNHL were like those of i-BPPV, while BPPV secondary to SSNHL was associated with poorer outcomes than i-BPPV when treated by CRPs.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2021.03.009DOI Listing
March 2021

Endocannabinoid system in the neurodevelopment of GABAergic interneurons: implications for neurological and psychiatric disorders.

Rev Neurosci 2021 Mar 30. Epub 2021 Mar 30.

Department of Neurobiology and Institute of Neurosciences, Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, 169 Chang Le Xi Road, Xi'an710032, Shaanxi, China.

In mature mammalian brains, the endocannabinoid system (ECS) plays an important role in the regulation of synaptic plasticity and the functioning of neural networks. Besides, the ECS also contributes to the neurodevelopment of the central nervous system. Due to the increase in the medical and recreational use of cannabis, it is inevitable and essential to elaborate the roles of the ECS on neurodevelopment. GABAergic interneurons represent a group of inhibitory neurons that are vital in controlling neural network activity. However, the role of the ECS in the neurodevelopment of GABAergic interneurons remains to be fully elucidated. In this review, we provide a brief introduction of the ECS and interneuron diversity. We focus on the process of interneuron development and the role of ECS in the modulation of interneuron development, from the expansion of the neural stem/progenitor cells to the migration, specification and maturation of interneurons. We further discuss the potential implications of the ECS and interneurons in the pathogenesis of neurological and psychiatric disorders, including epilepsy, schizophrenia, major depressive disorder and autism spectrum disorder.
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http://dx.doi.org/10.1515/revneuro-2020-0134DOI Listing
March 2021

Oridonin ameliorates noise-induced hearing loss by blocking NLRP3 - NEK7 mediated inflammasome activation.

Int Immunopharmacol 2021 Mar 23;95:107576. Epub 2021 Mar 23.

The Institute of Audiology and Balance Science of Xu zhou Medical University, Xuzhou 221004, China. Electronic address:

Inflammation is involved in noise-induced hearing loss (NIHL), but the mechanism is still unknown. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which triggers the inflammatory cascade, has been implicated in several inflammatory diseases in response to oxidative stress. However, whether the NLRP3 inflammasome is a key factor for permanent NIHL is still unknown. In this study, quantitative real-time polymerase chain reaction (qPCR), western blot, and enzyme-linked immunosorbent assays (ELISAs) demonstrated that the expression levels of activated caspase-1, interleukin (IL)-1β, IL-18, and NLRP3 were significantly increased in the cochleae of mice exposed to broadband noise (120 dB) for 4 h, compared with the control group. These results indicate that the activation of inflammasomes in the cochleae of mice during the pathological process of NIHL as well as NLRP3, a sensor protein of reactive oxygen species (ROS), may be key factors for inflammasome assembly and subsequent inflammation in cochleae. Moreover, many recent studies have revealed that NEK7 is an important component and regulator of NLRP3 inflammasomes by interacting with NLRP3 directly and that these interactions can be interrupted by oridonin. Here, we further determined that treatment with oridonin could indeed interrupt the interaction between NLRP3 and NEK7 as well as inhibit the downstream inflammasome activation in mouse cochleae after noise exposure. Furthermore, we tested anakinra, another inflammatory inhibitor, and it was shown to partially alleviate the degree of hearing impairment in some frequencies in an NIHL mouse model. These discoveries suggest that inhibiting NLRP3 inflammasomes and the downstream signaling pathway may provide a new strategy for the clinical treatment of NIHL.
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http://dx.doi.org/10.1016/j.intimp.2021.107576DOI Listing
March 2021

Self-Assembled pH-Sensitive Polymeric Nanoparticles for the Inflammation-Targeted Delivery of Cu/Zn-Superoxide Dismutase.

ACS Appl Mater Interfaces 2021 Apr 25;13(15):18152-18164. Epub 2021 Mar 25.

School of Life Sciences, Jilin University, No.2699, Qianjin Street, Changchun, Jilin 130012, China.

The use of superoxide dismutase (SOD) is currently limited by its short half-life, rapid plasma clearance rate, and instability. We synthesized a small library of biofriendly amphiphilic polymers that comprise methoxy poly(ethylene glycol)-poly(cyclohexane-1,4-diyl acetone dimethyleneketal) (mPEG-PCADK) and mPEG-poly((cyclohexane, 1,5-pentanediol)-1,4-diyl acetone dimethylene ketal) (PK3) for the targeted delivery of SOD. The novel polymers could self-assemble into micellar nanoparticles with favorable hydrolysis kinetics, biocompatibility, long circulation time, and inflammation-targeting effects. These materials generated a better pH-response curve and exhibited better hydrolytic kinetic behavior than PCADK and PK3. The polymers showed good biocompatibility with protein drugs and did not induce an acidic microenvironment during degradation in contrast to materials such as PEG--poly(lactic--glycolic acid) (PLGA) and PLGA. The SOD that contained reverse micelles based on mPEG2000-PCADK exhibited good circulation and inflammation-targeting properties. Pharmacodynamic results indicated exceptional antioxidant and anti-inflammatory activities in a rat adjuvant-induced arthritis model and a rat peritonitis model. These results suggest that these copolymers are ideal protein carriers for targeting inflammation treatment.
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http://dx.doi.org/10.1021/acsami.1c03589DOI Listing
April 2021

NUPR1 and its potential role in cancer and pathological conditions (Review).

Int J Oncol 2021 May 24;58(5). Epub 2021 Mar 24.

Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.

Nuclear protein‑1 (NUPR1) is also known as Com‑1 or p8. It is a protein primarily found in the nucleus of various cells, including cancer cells, and it has been found to play an important role in cell stress and stress‑related apoptosis. Over the past two decades, NUPR1 has been firmly indicated to play a role in the development and progression of numerous types of cancer, as well as in a number of other pathological conditions, including pancreatitis, diabetes, neurological and inflammatory conditions. The past decade has witnessed a rapid understanding of the biological and cellular mechanisms through which NUPR1 operates on cells and the identification of new variant of the protein. Most importantly, there have been comprehensive studies on the clinical and pathological aspects of NUPR1 and its variant in multiple malignancies and identification of therapeutic methods by targeting the protein. The present review aimed to summarise the current knowledge relating to NUPR1 in human malignancies and to discuss the associated controversies and potential future prospects of this molecule.
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http://dx.doi.org/10.3892/ijo.2021.5201DOI Listing
May 2021

Description of a new toad of Megophrys Kuhl amp; Van Hasselt, 1822 (Amphibia: Anura: Megophryidae) from western Yunnan Province, China.

Zootaxa 2021 Mar 15;4942(3):zootaxa.4942.3.3. Epub 2021 Mar 15.

CAS Key Laboratory of Mountain Ecological Restoration and Bioresource Utilization Ecological Restoration Biodiversity Conservation Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, Sichuan, China University of Chinese Academy of Sciences, Beijing 100049, China.

A new species of genus Megophrys from Gaoligong Mountains, Yunnan Province, China is described. Phylogenetic analyses based on mitochondrial DNA and nuclear DNA all clustered the new species as an independent clade nested into the subgenus Panophrys. The smallest genetic distance based on 16S rRNA gene between the new species and its congeners was 3.0%. The new species could be identified from its congeners by a combination of following characters: moderate body size (SVL 31.0-34.8 mm in males); vomerine ridge weak, vomerine teeth absent; dorsal skin relatively smooth; tongue slightly notched behind; tympanum rounded and relatively large, 0.54 times of eye length; a horn-like tubercle on edge of each upper eyelid small; tibio-tarsal articulation reaches middle eye when leg stretched forward; finger tips rounded, not expanded to small pad; toes with narrow fringes and rudimentary webbing; ventral hindlimbs semitransparent purplish with greyish white pigments; ventral body scattered with distinct dark patches in the middle.
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http://dx.doi.org/10.11646/zootaxa.4942.3.3DOI Listing
March 2021

Recombinant human epidermal growth factor combined with vacuum sealing drainage for wound healing in Bama pigs.

Mil Med Res 2021 03 9;8(1):18. Epub 2021 Mar 9.

Institute of Orthopaedics, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Chinese PLA General Hospital, Beijing, 100583, China.

Background: Vacuum sealing drainage (VSD) and epidermal growth factor (EGF) both play an important role in the treatment of wounds. This study aims to explore the effects of the combination of VSD and EGF on wound healing and the optimal concentration and time of EGF.

Methods: We tested the proliferation and migration capacity of HaCaT and L929 cells at different EGF concentrations (0, 1, 5, 10, and 100 ng/ml) and different EGF action times (2, 10, and 30 min). A full-thickness skin defect model was established using male, 30-week-old Bama pigs. The experiment included groups as follows: routine dressing change after covering with sterile auxiliary material (Control), continuous negative pressure drainage of the wound (VSD), continuous negative pressure drainage of the wound and injection of EGF 10 min followed by removal by continuous lavage (V + E 10 min), and continuous negative pressure drainage of the wound and injection of EGF 30 min followed by removal by continuous lavage (V + E 30 min). The wound healing rate, histological repair effect and collagen deposition were compared among the four groups.

Results: An EGF concentration of 10 ng/ml and an action time of 10 min had optimal effects on the proliferation and migration capacities of HaCaT and L929 cells. The drug dispersion effect was better than drug infusion after bolus injection effect, and the contact surface was wider. Compared with other groups, the V + E 10 min group promoted wound healing to the greatest extent and obtained the best histological score.

Conclusions: A recombinant human epidermal growth factor (rhEGF) concentration of 10 ng/ml can promote the proliferation and migration of epithelial cells and fibroblasts to the greatest extent in vitro. VSD combined with rhEGF kept in place for 10 min and then washed, can promote wound healing better than the other treatments in vivo.
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http://dx.doi.org/10.1186/s40779-021-00308-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941968PMC
March 2021

Tissue-Specific Hydrogels Ameliorate Hepatic Ischemia/Reperfusion Injury in Rats by Regulating Macrophage Polarization via TLR4/NF-κB Signaling.

ACS Biomater Sci Eng 2021 04 8;7(4):1552-1563. Epub 2021 Mar 8.

Laboratory of Basic Medicine, The General Hospital of Western Theater Command, Chengdu 610083, China.

Injectable acellular matrix hydrogels are proven to be potential translational materials to facilitate the repairment in various tissues. However, their potential to repair hepatic ischemia/reperfusion injury (IRI) has not been explored. In this work, we made hepatic acellular matrix (HAM) hydrogels based on the decellularized process and evaluated the biocompatibility and hepatoprotective effects in a rat IRI model. HAM hydrogels supported viability, proliferation, and attachment of hepatocytes . Treatment with HAM hydrogels significantly attenuated hepatic damage caused by IRI, as evidenced by hepatic biochemistry, histology, and inflammatory responses. Importantly, HAM hydrogels inhibited macrophage M1 (CD68/CCR7) differentiation but promoted M2 (CD68/CD206) differentiation. Additionally, TLR4/NF-κB signaling was found to be involved in the hepatoprotective effect of HAM hydrogels. Collectively, our study reveals that HAM hydrogels ameliorate hepatic IRI by facilitating M2 polarization via TLR4/NF-κB signaling.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01610DOI Listing
April 2021

Undifferentiated recurrent fevers in pediatrics are clinically distinct from PFAPA syndrome but retain an IL-1 signature.

Clin Immunol 2021 May 24;226:108697. Epub 2021 Feb 24.

Department of Pediatrics, Division of Allergy, Immunology and Rheumatology, University of California-San Diego, La Jolla, CA, United States of America; Rady Children's Foundation, Rady Children's Hospital, San Diego, CA, United States of America. Electronic address:

Autoinflammatory disorders of the innate immune system present with recurrent episodes of inflammation often beginning in early childhood. While there are now more than 30 genetically-defined hereditary fever disorders, many patients lack a clear diagnosis. Many pediatric patients are often grouped with patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome despite failing to meet diagnostic criteria. Here, we categorize these patients as syndrome of undifferentiated recurrent fever (SURF), and identify the unique features which distinguish them from the PFAPA syndrome. SURF patients were more likely to report gastrointestinal symptoms of nausea, vomiting and abdominal pain, and experienced inconsistent responses to on-demand steroid therapy compared to PFAPA patients. For this previously undefined cohort, an optimal course of therapy remains uncertain, with medical and surgical therapies largely driven by parental preference. A subset of patients with SURF underwent tonsillectomy with complete resolution. Flow cytometric evaluation demonstrates leukocytic populations distinct from PFAPA patients, with reduced CD3+ T cell numbers. SURF patient tonsils were predominantly characterized by an IL-1 signature compared to PFAPA, even during the afebrile period. Peripheral blood signatures were similar between groups suggesting that PFAPA and SURF patient tonsils have localized, persistent inflammation, without clinical symptoms. These data suggest that SURF is a heterogenous syndrome on the autoinflammatory disease spectrum.
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http://dx.doi.org/10.1016/j.clim.2021.108697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089050PMC
May 2021

Diagnostic utility of fine needle aspiration cytology in pediatric thyroid nodules based on Bethesda Classification.

J Pediatr Endocrinol Metab 2021 Apr 24;34(4):449-455. Epub 2021 Feb 24.

Division of Endocrinology, Department of Pediatrics, University of California San Diego, Rady Children's Hospital in San Diego, San Diego, CA, USA.

Objectives: The Bethesda system for reporting cytopathology (TBSRTC) has been widely adopted in the management of thyroid nodules. Based on the limited pediatric data available, the implied malignancy risk for each of the categories may be significantly different in pediatrics vs. adults, especially in the indeterminate categories (Bethesda Class III or IV). We report the diagnostic utility of fine needle aspiration (FNA) biopsy at our institution based on the Bethesda system and the risk of malignancy in each category.

Methods: We retrospectively reviewed all patients who underwent a thyroid FNA at our tertiary pediatric hospital from 12/1/2002 to 11/30/2018. FNA results were classified according to TBSRTC. Patient demographics, cytology, histopathology, radiological and clinical follow-ups were examined.

Results: A total of 171 patients were included with 203 cytological samples. Average age at initial FNA was 14.7 years (range 6.9-18.6 years). The numbers of nodules reported for Bethesda categories I-VI were 29, 106, 22, 14, 6 and 26, respectively, and the rate of malignancy was: 13.8, 4.7, 22.7, 35.7, 83.3 and 100%, respectively. Use of ultrasound guidance reduced the non-diagnostic rate from 38.1 to 11.5%. Introduction of on-site adequacy testing further reduced the non-diagnostic rate to 6.5% since 2014.

Conclusions: The risk of malignancy for thyroid nodules in this pediatric cohort is higher than reported in adults. However, rates described here are much closer to adult ranges than previously published pediatric cohorts. The addition of adequacy testing improved the non-diagnostic rate of FNA procedures performed with ultrasound guidance.
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http://dx.doi.org/10.1515/jpem-2020-0645DOI Listing
April 2021

Extracellular Vesicles: An Emerging Nanoplatform for Cancer Therapy.

Front Oncol 2020 8;10:606906. Epub 2021 Feb 8.

Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, United States.

Extracellular vesicles (EVs) are cell-derived membrane particles that represent an endogenous mechanism for cell-to-cell communication. Since discovering that EVs have multiple advantages over currently available delivery platforms, such as their ability to overcome natural barriers, intrinsic cell targeting properties, and circulation stability, the potential use of EVs as therapeutic nanoplatforms for cancer studies has attracted considerable interest. To fully elucidate EVs' therapeutic function for treating cancer, all current knowledge about cellular uptake and trafficking of EVs will be initially reviewed. In order to further improve EVs as anticancer therapeutics, engineering strategies for cancer therapy have been widely explored in the last decade, along with other cancer therapies. However, therapeutic applications of EVs as drug delivery systems have been limited because of immunological concerns, lack of methods to scale EV production, and efficient drug loading. We will review and discuss recent progress and remaining challenges in developing EVs as a delivery nanoplatform for cancer therapy.
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http://dx.doi.org/10.3389/fonc.2020.606906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897670PMC
February 2021

Comprehensive Analysis of Differentially Expressed lncRNA, circRNA and mRNA and Their ceRNA Networks in Mice With Severe Acute Pancreatitis.

Front Genet 2021 28;12:625846. Epub 2021 Jan 28.

Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command, Chengdu, China.

Severe acute pancreatitis (SAP) is an acute digestive system disease with high morbidity mortality and hospitalization rate worldwide, due to various causes and unknown pathogenesis. In recent years, a large number of studies have confirmed that non-coding RNAs (ncRNAs) play an important role in many cellular processes and disease occurrence. However, the underlying mechanisms based on the function of ncRNAs, including long noncoding RNA (lncRNA) and circular RNA (circRNA), in SAP remain unclear. In this study, we performed high-throughput sequencing on the pancreatic tissues of three normal mice and three SAP mice for the first time to describe and analyze the expression profiles of ncRNAs, including lncRNA and circRNA. Our results identified that 49 lncRNAs, 56 circRNAs and 1,194 mRNAs were differentially expressed in the SAP group, compared with the control group. Furthermore, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed lncRNAs and circRNAs, and found that the functions of the parental genes are enriched in the calcium-regulated signaling pathway, NF-κB signaling pathway, autophagy and protein digestion and absorption processes, which are closely related to the central events in pathogenesis of SAP. We also constructed lncRNA/circRNA-miRNA-mRNA networks to further explore their underlying mechanism and possible relationships in SAP. We found that in the competitive endogenous RNA (ceRNA) networks, differentially expressed lncRNAs and circRNAs are mainly involved in the apoptosis pathway and calcium signal transduction pathway. In conclusion, we found that lncRNAs and circRNAs play an important role in the pathogenesis of SAP, which may provide new insights in further exploring the pathogenesis of SAP and seek new targets for SAP.
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http://dx.doi.org/10.3389/fgene.2021.625846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876390PMC
January 2021

Effect of oral supplements on the nutritional status of nasopharyngeal carcinoma patients undergoing concurrent chemotherapy: A randomized controlled Phase II trial.

J Cancer Res Ther 2020 ;16(7):1678-1685

Radiotherapy Division, Department of Oral and Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.

Objectives: The objectives of this study were to prospectively compare individualized dietary counseling with or without oral nutritional supplements (ONSs) in nasopharyngeal carcinoma (NPC) patients undergoing concurrent chemoradiotherapy (CCRT) in a Phase II, randomized trial.

Materials And Methods: Between June 2014 and August 2016, Stage II-IVb NPC patients were randomly enrolled. The primary endpoint was change in body weight between during CCRT, and the secondary endpoints were change in body mass index (BMI) and fat-free mass index (FFMI).

Results: Fifty-two patients were randomized; 19 patients in the control group and 23 in the ONS group were eligible for analysis. Weight, BMI, and body composition parameters significantly decreased from baseline to week 6. FFMI was significantly better in patients with ONS intake >2/3 planed than the control group (P = 0.028). Weight and BMI maintenance was slightly better in patients with total intake >2/3 planed (P = 0.170 and P= 0.229, respectively). The mean Patient-Generated Subjective Global Assessment score was also better in the ONS group at the end of CCRT (P = 0.053).

Conclusions: ONSs with individualized dietary counseling may be beneficial in patients with enough intake, and further prospective studies with large groups of patients are warranted.
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http://dx.doi.org/10.4103/jcrt.JCRT_273_20DOI Listing
January 2020

Influence of anaesthetics on the production of cancer cell motogens, stromal cell-derived factor-1 and hepatocyte growth factor by fibroblasts.

Oncol Lett 2021 Feb 20;21(2):140. Epub 2020 Dec 20.

Cardiff China Medical Research Collaborative (CCMRC), Division of Cancer and Genetics (DCG), Cardiff University School of Medicine, Cardiff CF14 4XN, UK.

Anaesthetics have been implicated to influence cancer cells and progression. Similarly, crosstalk between cancer cells and stromal components within the microenvironment is also an important factor driving progression. Stromal cell-derived factor-1 (SDF-1) and hepatocyte growth factor (HGF) are key chemokines/cytokines produced by fibroblasts which have been established as influential factors in cancer progression. The present study explored the capacity of anaesthetics to influence the expression of these key molecules in fibroblasts. The anaesthetics rocuronium bromide (RB), vecuronium bromide (VB), suxamethonium chloride CRS (SCC), dexmedetomidine hydrochloride (DH) and lidocaine were used to treat MRC-5 fibroblasts over a range of concentrations. Following treatment, transcript expression of SDF-1 and HGF was quantified using quantitative PCR. Treatment of MRC-5 cells with RB brought about a reduction of SDF-1 expression which was found to be significant in the 45 µg/ml treatment group. Treatment with the other anaesthetics brought about some alterations in SDF-1 expression but these were not found to be statistically significant. Treatment with the tested anaesthetics did not have any significant effect on HGF transcript expression within MRC-5 cells, although again some alterations were observed. The results indicated that anaesthetics may have an impact on the fibroblast component of the tumour microenvironment, potentially influencing SDF-1 and HGF expression which in turn could influence tumour progression.
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http://dx.doi.org/10.3892/ol.2020.12401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798094PMC
February 2021

The efficacy and safety of Hirudin plus Aspirin versus Warfarin in the secondary prevention of Cardioembolic Stroke due to Nonvalvular Atrial Fibrillation: A multicenter prospective cohort study.

Int J Med Sci 2021 9;18(5):1167-1178. Epub 2021 Jan 9.

Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

To investigate the efficacy and safety of hirudin plus aspirin therapy compared with warfarin in the secondary prevention of cardioembolic stroke due to nonvalvular atrial fibrillation (NVAF). Patients with cardioembolic stroke due to NVAF were prospectively enrolled from 18 collaborating hospitals from Dec 2011 to June 2015. Fourteen days after stroke onset, eligible patients were assigned to the hirudin plus aspirin group (natural hirudin prescribed as the traditional Chinese medicine Maixuekang capsule, 0.75 g, three times daily, combined with aspirin 100 mg, once daily) or the warfarin group (dose-adjusted warfarin targeting international normalized ratio (INR) 2-3, with an initial daily dose of 1.25 mg). Patients were followed up at 1, 2, 3, 6, 9, and 12 months after stroke onset. Time in therapeutic range (TTR) was calculated according to Rosendaal methodology to evaluate the quality of INR management in the warfarin group. The primary efficacy endpoint was the recurrence of stroke within 12 months after stroke onset. Safety was assessed as the occurrence of the composite event "intracranial hemorrhage and other bleeding events, death, and other serious adverse events". The Cox proportional hazard model and Kaplan-Meier curve were used to analyze the efficacy and safety events. A total of 221 patients entered final analysis with 112 patients in the hirudin plus aspirin group and 109 in the warfarin group. Over the whole duration of our study, TTR for patients taking warfarin was 66.5 % ± 21.5%. A significant difference was not observed in the recurrence of stroke between the two groups (3.57% vs. 2.75%; = 0.728). The occurrence of safety events was significantly lower in the hirudin plus aspirin group (2.68% vs.10.09%; = 0.024). The risk for efficacy event was similar between the two groups (hazard ratio (HR), 1.30; 95% confidence interval (CI), 0.29-5.80). The safety risk was significantly lower in the hirudin plus aspirin group (HR, 0.27; 95% CI, 0.07-0.95). Kaplan-Meier analysis revealed significant difference in the temporal distribution in safety events ( = 0.023) but not in stroke recurrence ( = 0.726). Significant difference in efficacy was not detected between warfarin group and hirudin plus aspirin group. Compared with warfarin, hirudin plus aspirin therapy had lower safety risk in the secondary prevention of cardioembolic stroke due to NVAF.
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http://dx.doi.org/10.7150/ijms.52752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847633PMC
January 2021

A Novel INCNS Score for Prediction of Mortality and Functional Outcome of Comatose Patients.

Front Neurol 2020 15;11:585818. Epub 2021 Jan 15.

Department of Neurology, Xijing Hospital, The Forth Military Medical University, Xi'an, China.

The purpose of this study was to verify the veracity and reliability of the INCNS score for prediction of neurological ICU (NICU) mortality and 3-month functional outcome and mortality in comatose patients. In this prospective study, data of the patients admitted to NICU from January 2013 to January 2019 were collected for validation. The 3-month functional outcomes were evaluated using modified Rankin Scale (mRS). By using the receiver operating characteristics curve (ROC) analysis, we compared the INCNS score with Glasgow Coma Scale (GCS), Full Outline of Un-Responsiveness Score (FOUR) and Acute Physiology and Chronic Health Evaluation II (APACHE II) for assessment of the predictive performance of these scales for 3-month functional outcome and mortality and NICU mortality performed at 24- and 72-h after admission to the NICU. Totally 271 patients were used for evaluation; the INCNS score achieved an AUC (area under the receiver operating characteristic curve) of 0.766 (95% CI: 0.711-0.815) and 0.824 (95% CI: 0.774-0.868) for unfavorable functional outcomes, an AUC of 0.848 (95% CI: 0.800-0.889) and 0.892 (95% CI: 0.848-0.926) for NICU mortality, and an AUC of 0.811 (95% CI: 0.760-0.856) and 0.832 (95% CI: 0.782-0.874) for the 3-month mortality after discharge from the NICU at 24- and 72-h. The INCNS score exhibited a significantly better predictive performance of mortality and 3-month functional outcomes than FOUR and GCS. There was no significant difference in predicting NICU mortality and 3-month functional outcomes between INCNS and APACHE II, but INCNS had better predictive performance of 3-month mortality than APACHE II. The INCNS score could be used for predicting the functional outcomes and mortality rate of comatose patients.
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http://dx.doi.org/10.3389/fneur.2020.585818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843913PMC
January 2021

Association study of hypertension susceptibility genes , and with preeclampsia in Chinese Han population.

J Matern Fetal Neonatal Med 2021 Jan 24:1-9. Epub 2021 Jan 24.

Department of Obstetrics, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, P.R. China.

Objective: Preeclampsia (PE) is a disorder that occurs during the pregnancy and could affect the maternal and perinatal mortality as well as morbidity. The aim of our study is to investigate the associations between the hypertension susceptibility genes , and with PE in Chinese Han population.

Methods: A case-control study including 178 PE patients and 202 healthy controls was conducted to assess the associations between three loci ( rs155524, rs2932538 and rs4373814) and PE. The TaqMan probe assay was applied for genotyping in our study. Quantitative real-time PCR was performed to detect the mRNA expression levels of ITGA9, MOV10 and CACNB2. ELISA was carried out to detect the concentration of serum sFlt-1 or PLGF.

Results: Our study detected no significant differences in allelic frequencies of three SNPs between PE patients and healthy controls. In the genetic model, the results showed that the patients with rs155524 GA or AA genotypes had a higher risk of PE development compared to those with GG genotype in codominant model. And PE patients had a higher frequency of GA + AA genotypes based on the dominant model. Subgroup analysis showed rs155524 was associated with early-onset PE but not with late-onset PE. No association was observed between and with PE in any genetic model and subgroup analysis. Quantitative real-time PCR results showed that ITGA9 mRNA expression level was apparently increased in the placental tissues of PE patients. In addition, ITGA9 expression levels of GA + AA subjects were apparently higher than that in the genotype GG of placental tissues. sFlt-1/PLGF ratio was higher in GA + AA subjects than that in GG subjects. Regression analysis revealed that ratio of sFlt-1/PLGF was positively correlated with ITGA9 mRNA expression level.

Conclusion: This study has identified is a promising candidate susceptibility gene for early-onset PE. Our findings demonstrated that the high expression of ITGA9 might be associated with an increased risk of PE.
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http://dx.doi.org/10.1080/14767058.2021.1876022DOI Listing
January 2021

Role-play in Endodontic Teaching: a Case Study.

Chin J Dent Res 2020 ;23(4):281-288

Objective: To investigate the role of the application of role-play in endodontic study in improving the communication skills of Chinese dental undergraduates prior to their direct interactions with patients at the Fourth Military Medical University’s School of Stomatology, China. Methods: Students were recruited from the 5-year bachelor’s programme (n = 36) and randomly divided into six groups, and from the 8-year DDS programme (n = 10) and randomly divided into two groups to participate in the role-play training. Cases selected randomly from the case pool were distributed to the groups. The teacher gave an outline of the roles in the simulation. Each member of each group randomly selected their own role for the role-play. Four types of surveys were distributed to students and faculty members at different points after the role-plays had taken place, to evaluate their attitude towards the use of role-plays in endodontic study. Frequency analysis and a one sample t test were used to describe and analyse students’ acceptance of role-play as a teaching technique. The level of statistical significance was set at P < 0.05. Results: Students’ performance and satisfaction as well as the supporting faculty responses were very favourable towards role-playing. In total, 93.5% of students responded favourably to the role-play, answering ‘strongly agree’ or ‘agree’ to the positive statements about their role-play performance. A total of 95.1% of students stated that they had benefited psychologically and technically from the role-play (‘strongly agree’ or ‘agree’) after their 1-year rotating internship. Conclusion: The application of role-play in endodontic study is an effective way of educating Chinese dental undergraduates and can be beneficial for their transition from students to dentists.
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http://dx.doi.org/10.3290/j.cjdr.b867891DOI Listing
January 2021

Erratum: Tongxinluo inhibits neointimal formation by regulating the expression and post-translational modification of KLF5 in macrophages.

Am J Transl Res 2020 15;12(12):8256-8258. Epub 2020 Dec 15.

Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University Shijiazhuang 050017, PR China.

[This corrects the article on p. 4778 in vol. 8, PMID: 27904679.].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791492PMC
December 2020

Lead DEAD/H box helicase biomarkers with the therapeutic potential identified by integrated bioinformatic approaches in lung cancer.

Comput Struct Biotechnol J 2021 28;19:261-278. Epub 2020 Dec 28.

Cardiff China Research Collaborative, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.

DEAD/H box helicases are implicated in lung cancer but have not been systematically investigated for their clinical significance and function. In this study, we aimed to evaluate the potential of DEAD/H box helicases as prognostic biomarkers and therapeutic targets in lung cancer by integrated bioinformatic analysis of multivariate large-scale databases. Survival and differential expression analysis of these helicases enabled us to identify four biomarkers with the most significant alterations. These were found to be the negative prognostic factors DDX11, DDX55 and DDX56, and positive prognostic factor DDX5. Pathway enrichment analysis indicates that MYC signalling is negatively associated with expression levels of the DDX5 gene while positively associated with that of DDX11, DDX55 and DDX56. High expression levels of the DDX5 gene is associated with low mutation levels of TP53 and MUC16, the two most frequently mutated genes in lung cancer. In contrast, high expression levels of DDX11, DDX55 and DDX56 genes are associated with high levels of TP53 and MUC16 mutation. The tumour-infiltrated CD8 + T and B cells positively correlate with levels of DDX5 gene expression, while negatively correlate with that of the other three DEAD box helicases, respectively. Moreover, the DDX5-associated miRNA profile is distinguished from the miRNA profiles of DDX11, DDX55 and DDX56, although each DDX has a different miRNA signature. The identification of these four DDX helicases as biomarkers will be valuable for prognostic prediction and targeted therapeutic development in lung cancer.
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http://dx.doi.org/10.1016/j.csbj.2020.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779375PMC
December 2020