Publications by authors named "Biao Li"

411 Publications

Abnormal interhemispheric functional connectivity in patients with strabismic amblyopia: a resting-state fMRI study using voxel-mirrored homotopic connectivity.

BMC Ophthalmol 2021 Jun 9;21(1):255. Epub 2021 Jun 9.

Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

Background: Previous studies have demonstrated that strabismus amblyopia can result in markedly brain function alterations. However, the differences in spontaneous brain activities of strabismus amblyopia (SA) patients still remain unclear. Therefore, the current study intended to employthe voxel-mirrored homotopic connectivity (VMHC) method to investigate the intrinsic brain activity changes in SA patients.

Purpose: To investigate the changes in cerebral hemispheric functional connections in patients with SA and their relationship with clinical manifestations using the VMHC method.

Material And Methods: In the present study, a total of 17 patients with SA (eight males and nine females) and 17 age- and weight-matched healthy control (HC) groups were enrolled. Based on the VMHC method, all subjects were examined by functional magnetic resonance imaging. The functional interaction between cerebral hemispheres was directly evaluated. The Pearson's correlation test was used to analyze the clinical features of patients with SA. In addition, their mean VMHC signal values and the receiver operating characteristic curve were used to distinguish patients with SA and HC groups.

Results: Compared with HC group, patients with SA had higher VMHC values in bilateral cingulum ant, caudate, hippocampus, and cerebellum crus 1. Moreover, the VMHC values of some regions were positively correlated with some clinical manifestations. In addition, receiver operating characteristic curves presented higher diagnostic value in these areas.

Conclusion: SA subjects showed abnormal brain interhemispheric functional connectivity in visual pathways, which might give some instructive information for understanding the neurological mechanisms of SA patients.
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http://dx.doi.org/10.1186/s12886-021-02015-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188699PMC
June 2021

Differentiating TP53 Mutation Status in Pancreatic Ductal Adenocarcinoma Using Multiparametric MRI-Derived Radiomics.

Front Oncol 2021 17;11:632130. Epub 2021 May 17.

Department of Nuclear Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objectives: This study assessed the preoperative prediction of TP53 status based on multiparametric magnetic resonance imaging (mpMRI) radiomics extracted from two-dimensional (2D) and 3D images.

Methods: 57 patients with pancreatic cancer who underwent preoperative MRI were included. The diagnosis and TP53 gene test were based on resections. Of the 57 patients included 37 mutated TP53 genes and the remaining 20 had wild-type TP53 genes. Two radiologists performed manual tumour segmentation on seven different MRI image acquisition sequences per patient, including multi-phase [pre-contrast, late arterial phase (ap), portal venous phase, and delayed phase] dynamic contrast enhanced (DCE) T1-weighted imaging, T2-weighted imaging (T2WI), Diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC). PyRadiomics-package was used to generate 558 two-dimensional (2D) and 994 three-dimensional (3D) image features. Models were constructed by support vector machine (SVM) for differentiating TP53 status and DX score method were used for feature selection. The evaluation of the model performance included area under the curve (AUC), accuracy, calibration curves, and decision curve analysis.

Results: The 3D ADC-ap-DWI-T2WI model with 11 selected features yielded the best performance for differentiating TP53 status, with accuracy = 0.91 and AUC = 0.96. The model showed the good calibration. The decision curve analysis indicated that the radiomics model had clinical utility.

Conclusions: A non-invasive and quantitative mpMRI-based radiomics model can accurately predict TP53 mutation status in pancreatic cancer patients and contribute to the precision treatment.
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http://dx.doi.org/10.3389/fonc.2021.632130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165316PMC
May 2021

Synthesis of Transition Metal Complexes and Their Effects on Combustion Properties of Semi-Rigid Polyvinyl Chloride.

Materials (Basel) 2021 May 18;14(10). Epub 2021 May 18.

School of Materials and Chemical Engineering, Hubei University of Technology, Wuhan 430068, China.

Using introduction of MoO and Fe, Cu, or Zn into amphiphilic polymers (DN) via an ion-exchange reaction, different transition metal complexes, as retardants and smoke suppressants, including (DN)Mo, Fe(DN)Mo, Cu(DN)Mo, and Zn(DN)Mo were synthesized. Combined with the results of X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR), it could be determined that ionic bonding of these ions with DN occurred. Subsequently, the influence of flame-retardant, smoke-suppression, and mechanical properties of (DN)Mo, Fe(DN)Mo, Cu(DN)Mo, and Zn(DN)Mo on polyvinyl Chloride (PVC) were tested. It was demonstrated that transition metal complexes of three metal elements, Fe(DN)Mo, Cu(DN)Mo, and Zn(DN)Mo, showed better flame retardancy, smoke suppression, and thermal stability as confirmed by microcalorimetry, limiting oxygen index (LOI), smoke density, and thermogravimetric analysis (TGA) tests, in which Cu(DN)Mo worked best due to the Lewis acid mechanism and reductive coupling mechanism. Scanning electron microscopy (SEM) showed that the addition of (DN)Mo, Fe(DN)Mo, Cu(DN)Mo, and Zn(DN)Mo promoted the formation of a dense carbon layer on the PVC surface during combustion, which could protect the interior PVC. The addition of these transition metal complexes hardly impaired the mechanical properties of PVC.
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http://dx.doi.org/10.3390/ma14102634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157559PMC
May 2021

Characterization of the whole transcriptome of spleens from Chinese indigenous breed Ningxiang pig reveals diverse coding and non-coding RNAs for immunity regulation.

Genomics 2021 May 29;113(4):2468-2482. Epub 2021 May 29.

College of Animal Sciences, Hunan Agricultural University, Changsha, Hunan, China.

The spatio-temporal expression patterns of RNA and comparisons between different developmental stages have been one of the useful techniques for studying animal physiology and functional gene regulations. A Chinese indigenous breed Ningxiang pig is known for its quality meat production, disease resistance and slow growth performances in pig industry. To gain a better understanding of pig immunity and disease resistance, we comprehensively analyzed the whole transcriptome of the spleens from three important developmental nodes of Ningxiang pig at 30, 90 and 210 days of age. By three ways of comparisons (30vs 90 days, 30 vs 210 days and 90 vs 210 days), a total of 364to 865 differentially expressed mRNAs, 37 to 98 differentially expressed miRNAs,220 to 278 lncRNAs, and 96 to 113 circRNAs were identified. Further analysis of expression patterns, potential function and interactions with miRNAs identified the potential non-coding RNAs related to immunomodulation such as ssc-miRNA-150, ssc-miRNA-497, MSTRG24160, MSTRG18646. The results revealed that miRNAs and circRNAs may have evolved to regulate a large set of biological processes of spleen function in Ningxiang pigs, and circRNAs play a role of miRNA sponges. The results from study is the first report of whole transcriptome analysis of Ningxiang pig spleen and provide new insights into the expression changes of RNAs during the spleen development, which contribute to the phenotypic formation of immunity and disease resistancesin Chinese indigenous pig breeds.
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http://dx.doi.org/10.1016/j.ygeno.2021.05.025DOI Listing
May 2021

Effects of the Endophytic Fungus MF23 on Lindl. in an Artificial Primary Environment.

ACS Omega 2021 Apr 7;6(15):10047-10053. Epub 2021 Apr 7.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, P. R. China.

The quality of Lindl. is related to its endophytic fungi. It has been reported that the mycorrhizal fungus MF23 helps to increase the content of dendrobine in , but few studies have explained the mechanism underlying this phenomenon. In a previous study, we verified the mechanism of symbiosis between MF23 and on agar medium. The research carried out in this study on bark medium, similar to the natural environment, is of great importance because of its benefits for wide application. We found a significant effect, especially in the later period of cultivation, in which the highest dendrobine content in the experimental group was 0.147%, which is equivalent to 2.88 times that of the control group, and suggesting that MF23 promoted in the natural environment, which verifies the application of the technique in field conditions. This result also implied that post-modification enzyme genes might play an important role in stimulating the biosynthesis of dendrobine.
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http://dx.doi.org/10.1021/acsomega.0c06325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153664PMC
April 2021

[Study on mechanism of Phytolaccae Radix and its split components based on network pharmacology].

Zhongguo Zhong Yao Za Zhi 2021 May;46(10):2434-2442

Technical Research Center for Standardized Processing of Chinese Herbal Medicine, College of Chinese Medicine, Guangdong Pharmaceutical University Guangzhou 510006, China.

This paper aimed to explore the mechanism of the split components of Phytolaccae Radix by means of network pharmaco-logy. Based on the theoretical hypothesis of the nature and taste of traditional Chinese medicine, the chemical components of the separated components of Phytolaccae Radix were selected by using Traditional Chinese Medicine Systems Pharmacology Database(TCMSP) and Traditional Chinese Medicines IntegratedDatabase(TCMID) databases in combination with related literatures. Relevant target analysis was carried out based on PubChem and SwissTargetPrediction databases. Targets corresponding to disease were excavated based on GeneCards for each split component, corresponding potential targets were obtained through mapping the target set of target compounds to disease targets. GO biological process analysis and KEGG pathway enrichment analysis were performed on the mapped targets with the help of DAVID database. Based on Cytoscape software and the corresponding efficacy, the network diagram of "medicinal material-split components-compound-target-pathway" was constructed to explore the mechanism of different efficacy of the separated components of Cytoscape. And the target purgation and diuretic mapping was used as the target of the traditional efficacy of smoothening secretion for the first time. The study explored esculentoside component, fatty oil component and phenolic acid component, a total of 30 target compounds and 301 corresponding targets, involving 44 potential targets for "anti-inflammatory", 50 potential targets for "immunoregulation", 52 potential targets for "smoothening secretion", 28 potential targets for "antibacterial activity", 28 potential targets for "antiviral effect", and 29 potential targets for "antitumor effect". Topological analysis revealed 14 key gene targets such as MAPK8, MAPK14, EGFR and PTGS2. A total of 684 GO entries and 235 KEGG pathways were obtained through bioinformatics enrichment analysis, mainly involving TNF signaling pathway, NF-kappaB signaling pathway and MAPK signaling pathway. This study revealed the multi-component, multi-target, and multi-channel action mechanism of the split components of Phytolaccae Radix, which provided certain basis for the next step to clarify the split components of Phytolaccae Radix through the method of system biology, and injected new content and significance into the study of properties and flavors theory.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210120.401DOI Listing
May 2021

High-efficiency CO separation using hybrid LDH-polymer membranes.

Nat Commun 2021 May 24;12(1):3069. Epub 2021 May 24.

Chemistry Research Laboratory, Department of Chemistry University of Oxford, Oxford, UK.

Membrane-based gas separation exhibits many advantages over other conventional techniques; however, the construction of membranes with simultaneous high selectivity and permeability remains a major challenge. Herein, (LDH/FAS)-PDMS hybrid membranes, containing two-dimensional sub-nanometre channels were fabricated via self-assembly of unilamellar layered double hydroxide (LDH) nanosheets and formamidine sulfinic acid (FAS), followed by spray-coating with a poly(dimethylsiloxane) (PDMS) layer. A CO transmission rate for (LDH/FAS)-PDMS of 7748 GPU together with CO selectivity factors (SF) for SF(CO/H), SF(CO/N) and SF(CO/CH) mixtures as high as 43, 86 and 62 respectively are observed. The CO permselectivity outperforms most reported systems and is higher than the Robeson or Freeman upper bound limits. These (LDH/FAS)-PDMS membranes are both thermally and mechanically robust maintaining their highly selective CO separation performance during long-term operational testing. We believe this highly-efficient CO separation performance is based on the synergy of enhanced solubility, diffusivity and chemical affinity for CO in the sub-nanometre channels.
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http://dx.doi.org/10.1038/s41467-021-23121-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144556PMC
May 2021

Identification of key gene modules and pathways of human platelet transcriptome in acute myocardial infarction patients through co-expression network.

Am J Transl Res 2021 15;13(4):3890-3905. Epub 2021 Apr 15.

Department of Cardiology/Cardiac Catheterization Lab, Second Xiangya Hospital, Central South University Changsha, China.

Acute myocardial infarction (AMI) seriously threatens human life. In this study we aimed to systemically analyze the function of key gene modules in human platelets in AMI. We used weighted gene co-expression network analysis (WGCNA) to construct a co-expression module, and analyzed the relationship between potential modules and clinical characteristics based on platelet RNA-seq RPKM count reads of 16 ST-segment elevation myocardial infarction (STEMI) patients and 16 non-STEMI (NSTEMI) patients provided by the GEO database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed with the DAVID tool. Hub genes were calculated by the Cytohubba package. A total of 3653 genes was selected to construct the co-expression modules. A significant correlation between BMI and the module with color of sky-blue in STEMI. In NSTEMI, there was a significant correlation between the sky blue module and CAD, the Salmon module and HT, and the Cyan module and HT. In STEMI, the Hub genes were mainly enriched in functions related to cell membrane signal transduction including and . In NSTEMI, the Hub genes are related mainly to energy metabolism in the sky-blue module including and ; they are mainly related to extracellular space and calcium binding in the Cyan module, including and . The hub genes in the Salmon module include and . Our results provide a framework for co-expression gene modules in STEMI and NSTEMI patients, and identify key targets as biomarkers for patients with different subtypes of AMI.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129354PMC
April 2021

Yeast-based nucleotide supplementation in mother sows modifies the intestinal barrier function and immune response of neonatal pigs.

Anim Nutr 2021 Mar 5;7(1):84-93. Epub 2021 Jan 5.

Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Changsha, Hunan 410125, China.

In the present study, we aimed to evaluate the effects of maternal yeast-based nucleotide (YN) supplementation on the intestinal immune response and barrier function in neonatal pigs, as well as the diarrhoea rate and growth performance in suckling piglets. Sixty-four late-gestation sows were assigned to the following groups: the CON (fed a basal diet) and YN groups (fed a basal diet with 4 g YN/kg diet). The experiment started on d 85 of gestation and ended on d 20 of lactation. Diarrhoea rate and average daily gain of the piglets were recorded, and samples of blood and intestines from neonatal piglets were collected before they consumed colostrum during farrowing. Compared with the CON group, maternal YN supplementation increased the weaning weight of litter and decreased the diarrhoea rate ( < 0.01). In addition, maternal YN supplementation promoted the ileal villus development in the neonates compared with that in the CON group ( < 0.01). Maternal YN supplementation also increased the ileal secretory immunoglobulin A (sIgA) level compared with that in the CON group ( < 0.05). The real-time PCR results showed that maternal dietary YN supplementation increased the jejunal and ileal expression of interleukin (), , , and tumor necrosis factor ()- α in the neonates compared with that in the CON group ( < 0.05). Overall, maternal nucleotide supplementation improved the villus development and innate immunity of neonatal piglets during late pregnancy. This may be associated with the decrease in diarrhoea and the increase in weaning weight of the litter of suckling piglets.
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http://dx.doi.org/10.1016/j.aninu.2020.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110885PMC
March 2021

Metagenomic analysis reveals oropharyngeal microbiota alterations in patients with COVID-19.

Signal Transduct Target Ther 2021 05 13;6(1):191. Epub 2021 May 13.

School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.

COVID-19 remains a serious emerging global health problem, and little is known about the role of oropharynx commensal microbes in infection susceptibility and severity. Here, we present the oropharyngeal microbiota characteristics identified by shotgun metagenomic sequencing analyses of oropharynx swab specimens from 31 COVID-19 patients, 29 influenza B patients, and 28 healthy controls. Our results revealed a distinct oropharyngeal microbiota composition in the COVID-19 patients, characterized by enrichment of opportunistic pathogens such as Veillonella and Megasphaera and depletion of Pseudopropionibacterium, Rothia, and Streptococcus. Based on the relative abundance of the oropharyngeal microbiome, we built a microbial classifier to distinguish COVID-19 patients from flu patients and healthy controls with an AUC of 0.889, in which Veillonella was identified as the most prominent biomarker for COVID-19 group. Several members of the genus Veillonella, especially Veillonella parvula which was highly enriched in the oropharynx of our COVID-19 patients, were also overrepresented in the BALF of COVID-19 patients, indicating that the oral cavity acts as a natural reservoir for pathogens to induce co-infections in the lungs of COVID-19 patients. We also found the increased ratios of Klebsiella sp., Acinetobacter sp., and Serratia sp. were correlated with both disease severity and elevated systemic inflammation markers (neutrophil-lymphocyte ratio, NLR), suggesting that these oropharynx microbiota alterations may impact COVID-19 severity by influencing the inflammatory response. Moreover, the oropharyngeal microbiome of COVID-19 patients exhibited a significant enrichment in amino acid metabolism and xenobiotic biodegradation and metabolism. In addition, all 26 drug classes of antimicrobial resistance genes were detected in the COVID-19 group, and were significantly enriched in critical cases. In conclusion, we found that oropharyngeal microbiota alterations and functional differences were associated with COVID-19 severity.
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http://dx.doi.org/10.1038/s41392-021-00614-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116522PMC
May 2021

Efficacy and Safety of Adalimumab in Noninfectious Uveitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Front Pharmacol 2021 26;12:673984. Epub 2021 Apr 26.

Department of Ophthalmology, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Patients with noninfectious uveitis (NIU) are at risk of systemic side effects of long-term glucocorticoid therapy and uncontrolled inflammatory complications. In urgent need to identify more aggressive therapies, adalimumab (ADA) may be the right choice. To summarize the current evidence from randomized controlled trials (RCTs) regarding the efficacy and safety of ADA in the treatment of NIU. We searched Pubmed, Embase, Web of Science, Cochrane Library databases, and Clinical Trials Registry for qualifying articles from their inception to November 19, 2020, with no language restriction. Randomized controlled trials comparing ADA with conventional routine treatment in noninfectious uveitis patients of any age, gender, or ethnicity were included. The primary outcome was the time to treatment failure (TF). The secondary outcomes were the change in best-corrected visual acuity (BCVA), change in the anterior chamber (AC) cell grade, change in vitreous haze (VH) grade, and adverse events (AEs). The six studies comprised 605 participants in all, and the sample size of each study ranged from 16 to 225. The overall pooled results of the primary outcome (HR = 0.51; 95% CI, 0.41 to -0.63) showed that ADA nearly halved the risk of treatment failure compared to placebo for NIU patients. The pooled mean difference of change in BCVA was -0.05 (95% CI, -0.07 to -0.02). The pooled mean difference of change in AC cell grade and VH grade was -0.29 (95% CI, -0.62 to -0.05) and -0.21 (95% CI, -0.32 to -0.11), respectively. The incidence of AEs in the ADA group was numerically higher than that of AEs in the placebo group (2,237 events and 9.40 events per patient-year, equivalent to 1,257 events and 7.79 events per patient-year). This meta-analysis of six RCTs further confirmed that ADA considerably lowered the risk of treatment failure or visual loss, and moderately reduced AC cell grades and VH grades with slightly more AEs, as compared to placebo. ADA is both effective and safe in treating NIU. [https://clinicaltrials.gov], identifier [CRD42020217909].
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http://dx.doi.org/10.3389/fphar.2021.673984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109175PMC
April 2021

Regional brain changes in patients with diabetic optic neuropathy: a resting-state functional magnetic resonance imaging study.

Quant Imaging Med Surg 2021 May;11(5):2125-2137

Department of Ophthalmology, the First Affiliated Hospital of Nanchang University, Nanchang, China.

Background: To evaluate functional connection density (FCD) in patients with diabetic optic neuropathy (DON) using the resting functional connectivity (FC) method, and to determine the abnormal areas of brain activity.

Methods: Patients with DON (n=22; 10 male, 12 female) and healthy controls (HCs; n=22; 10 male, 12 female) were included in the study. The basic characteristics of the groups were matched. Functional magnetic resonance imaging (fMRI) was conducted with participants at rest, and long- and short-range FCD (long FCD and IFCD, respectively) were measured. Receiver operating characteristic (ROC) curve analysis was also conducted to determine whether DON and HC participants could be distinguished using fMRI indicators.

Results: Compared with HCs, the long FCD values of the left lingual gyrus, right lingual gyrus, right fusiform gyrus, and medial and lateral cingulate gyri were decreased in patients with DON. Further, the IFCD values of the left superior temporal gyrus, left inferior temporal gyrus, right inferior temporal gyrus, left cerebellar area 8, and right cerebellar Crus2 area were higher in patients with DON than in the HCs.

Conclusions: DON is associated with abnormal spontaneous brain activity. Our findings contribute to elucidating the mechanisms underlying the neuropathology of DON, and provide direction for further clinical research.
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http://dx.doi.org/10.21037/qims-20-453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047353PMC
May 2021

Luteolin Ameliorates Experimental Pulmonary Arterial Hypertension via Suppressing Hippo-YAP/PI3K/AKT Signaling Pathway.

Front Pharmacol 2021 15;12:663551. Epub 2021 Apr 15.

Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Hunan, China.

Luteolin is a flavonoid compound with a variety of pharmacological effects. In this study, we explored the effects of luteolin on monocrotaline (MCT) induced rat pulmonary arterial hypertension (PAH) and underlying mechanisms. A rat PAH model was generated through MCT injection. In this model, luteolin improved pulmonary vascular remodeling and right ventricular hypertrophy, meanwhile, luteolin could inhibit the proliferation and migration of pulmonary artery smooth muscle cells induced by platelet-derived growth factor-BB (PDGF-BB) in a dose-dependent manner. Moreover, our results showed that luteolin could downregulate the expression of LATS1 and YAP, decrease YAP nuclear localization, reduce the expression of PI3K, and thereby restrain the phosphorylation of AKT induced by PDGF-BB. In conclusion, luteolin ameliorated experimental PAH, which was at least partly mediated through suppressing HIPPO-YAP/PI3K/AKT signaling pathway. Therefore, luteolin might become a promising candidate for treatment of PAH.
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http://dx.doi.org/10.3389/fphar.2021.663551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082250PMC
April 2021

Insight into Liver lncRNA and mRNA Profiling at Four Developmental Stages in Ningxiang Pig.

Biology (Basel) 2021 Apr 8;10(4). Epub 2021 Apr 8.

College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China.

Ningxiang pigs, a fat-type pig, are native to Ningxiang County in Hunan Province, with thousands of years of breeding history. This study aims to explore the expression profiles and functional networks on messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) in the liver. Liver tissue of Ningxiang piglets was collected at 30, 90, 150, and 210 days after birth (four development stages), and the mRNA and lncRNA expression was profiled. Compared to mRNA and lncRNA expression profiles, most differentially expressed mRNAs (DEmRNAs) were upregulated at 30 days; however, most DElncRNAs were downregulated at 210 days. Via Short Time-series Expression Miner (STEM) analysis and weighted gene co-expression network analysis (WGCNA), a complex interaction between mRNAs and lncRNAs was identified, indicating that lncRNAs may be a critical regulatory element for mRNAs. One module of genes in particular (module profile 4) was related to fibril organization, vasculogenesis, GTPase activator activity, and regulation of kinase activity. The mRNAs and lncRNAs in module profile 4 had a similar pattern of expression, indicating that they have functional and regulatory relationships. Only , , and in the particular mRNA profile 4 were the target genes of lncRNAs in that profile, which shows the possible regulatory relationship between lncRNAs and mRNAs. The expression of these genes and lncRNAs in profile 4 was the highest at 30 days, and it is believed that these RNAs may play a critical role during the suckling period in order to meet the dietary requirements of piglets. In the lncRNA-mRNA co-expression network, the identified gene hubs and associated lncRNAs were shown to be involved in saccharide, lipid, and glucose metabolism, which may play an important role in the development and health of the liver. This result will lead to further investigation of liver lncRNA functions at various stages of development in Ningxiang pigs.
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http://dx.doi.org/10.3390/biology10040310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068270PMC
April 2021

Biofriendly molecular and protein release substrate with integrated piezoelectric motivation and anti-oxidative stress capabilities.

Nanoscale 2021 May;13(18):8481-8489

Beijing Key Laboratory of Materials Utilization of Nonmetallic Minerals and Solid Wastes, National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences, Beijing, 100083, China.

Self-powered piezoelectrically active molecular or protein delivery devices have provoked great interest in recent years. However, electric fields used to promote delivery or healing may also induce the redox of water or oxygen to generate reactive oxygen species (ROS) and bring unintended oxidative pressure to the organism and harm biological functions. In addition, protein molecules are easily inactivated in the polymer reservoir matrix due to the pull of strong electrostatic effects. In this study, a multifunctional molecular delivery substrate was fabricated by integrating a piezoelectric-dielectric polymeric substrate, nanoscopic polyelectrolyte films and in-film deposited biomimetic porous CaP coating. The piezoelectric substrate promoted molecular release, and the mineralized coating effectively stored molecules or proteins and simultaneously eliminated ROS, reducing the oxidative stress response generated by oxidative pressure. The present work opens a new way for the development of multifunctional and biofriendly drug delivery devices.
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http://dx.doi.org/10.1039/d1nr01676hDOI Listing
May 2021

The kynurenine derivative 3-HAA sensitizes hepatocellular carcinoma to sorafenib by upregulating phosphatases.

Theranostics 2021 3;11(12):6006-6018. Epub 2021 Apr 3.

Basic Medical Institute; Hongqiao International Institute of Medicine, Tongren Hospital; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

: Sorafenib is the only FDA-approved first-line target drug for HCC patients. However, sorafenib merely confers 3-5 months of survival benefit with less than 30% of HCC patients sensitive to sorafenib therapy. Thus, it's necessary to develop a sensitizer for hepatocellular carcinoma (HCC) to sorafenib. : The principal component analysis, gene ontology, and KEGG analysis are utilized following RNA-sequencing. The mass spectrometry analysis following immunoprecipitation is performed to discover the phosphatase targets. Most importantly, both the cell line-derived xenograft (CDX) and the patient-derived xenograft (PDX) mouse model are used to determine the effect of 3-HAA on sorafenib-resistant HCC . : In nude mice carrying HCC xenograft, tumor growth is inhibited by sorafenib or 3-HAA alone. When used in combination, the treatment particularly prevents the xenograft from growing. Combined treatment also suppresses the growth of sorafenib-resistant (≥30mg/kg) PDXs. In a set of mechanistic experiments, we find enhanced AKT activation and decreased apoptotic cells in and acquired sorafenib-resistant HCC cells and tissues. 3-HAA decreases AKT phosphorylation and increases the apoptosis of HCC in both cultured cells and mouse xenografts by upregulation of phosphatases PPP1R15A/DUSP6. PPP1R15A/PPP1α directly reduces Akt phosphorylation while DUSP6 decreases Akt activity through inhibiting PDK1. The AKT activator abolishes 3-HAA inhibition of HCC growth and in mice. : This study demonstrates that 3-HAA sensitizes HCC cells to sorafenib by upregulation of phosphatases, suggesting it as a promising molecule for HCC therapy.
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http://dx.doi.org/10.7150/thno.59841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058709PMC
April 2021

Determination of crossing sequences between seal impression and laser-printed lines based on characteristics of the toner molten state.

J Forensic Sci 2021 Apr 22. Epub 2021 Apr 22.

Department of Document Examination, Criminal Investigation Police University of China, Shenyang, China.

Determining the sequence of intersection lines is a challenge in forensic document examination. To explore more advanced technology and meet the needs of practical applications, this study proposes a method based on the characteristics of the molten state to examine crossing-line sequences. This state can be considered as a melting state of solid laser toner through a dissolution process. Experimental results demonstrate that the molten state is always visible at intersections when a particular ink is stamped after laser printing; however, the presence of the molten state when the seal is stamped before laser printing largely depends on the time interval between printing and stamping. The degree of error obtained through blind tests indicates that this approach has its limitations; however, a high accuracy, which refers to the ability of an examiner, was achieved with respect to determining the sequence of strokes when using a fluorescence method in conjunction with this method. This further indicated the limitation of a single method and the importance of combining multiple methods for document examinations.
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http://dx.doi.org/10.1111/1556-4029.14715DOI Listing
April 2021

Increased free water in the substantia nigra in idiopathic REM sleep behaviour disorder.

Brain 2021 Jun;144(5):1488-1497

Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Imaging markers sensitive to neurodegeneration in the substantia nigra are critically needed for future disease-modifying trials. Previous studies have demonstrated the utility of posterior substantia nigra free water as a marker of progression in Parkinson's disease. In this study, we tested the hypothesis that free water is elevated in the posterior substantia nigra of idiopathic REM sleep behaviour disorder, which is considered a prodromal stage of synucleinopathy. We applied free-water imaging to 32 healthy control subjects, 34 patients with idiopathic REM sleep behaviour disorder and 38 patients with Parkinson's disease. Eighteen healthy control subjects and 22 patients with idiopathic REM sleep behaviour disorder were followed up and completed longitudinal free-water imaging. Free-water values in the substantia nigra were calculated for each individual and compared among groups. We tested the associations between posterior substantia nigra free water and uptake of striatal dopamine transporter in idiopathic REM sleep behaviour disorder. Free-water values in the posterior substantia nigra were significantly higher in the patients with idiopathic REM sleep behaviour disorder patients than in the healthy control subjects, but were significantly lower in patients with idiopathic REM sleep behaviour disorder than in patients with Parkinson's disease. In addition, we observed significantly negative associations between posterior substantia nigra free-water values and dopamine transporter striatal binding ratios in the idiopathic REM sleep behaviour disorder patients. Longitudinal free-water imaging analyses were conducted with a linear mixed-effects model, and showed a significant Group × Time interaction in posterior substantia nigra, identifying increased mean free-water values in posterior substantia nigra of idiopathic REM sleep behaviour disorder over time. These results demonstrate that free water in the posterior substantia nigra is a valid imaging marker of neurodegeneration in idiopathic REM sleep behaviour disorder, which has the potential to be used as an indicator in disease-modifying trials.
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http://dx.doi.org/10.1093/brain/awab039DOI Listing
June 2021

JRL-YOLO: A Novel Jump-Join Repetitious Learning Structure for Real-Time Dangerous Object Detection.

Comput Intell Neurosci 2021 1;2021:5536152. Epub 2021 Apr 1.

Department of Instrument Science and Technology, School of Automation and Electrical Engineering, University of Science and Technology Beijing, Beijing, China.

Campus security incidents occur from time to time, which seriously affect the public security. In recent years, the rapid development of artificial intelligence has brought technical support for campus intelligent security. In order to quickly recognize and locate dangerous targets on campus, an improved YOLOv3-Tiny model is proposed for dangerous target detection. Since the biggest advantage of this model is that it can achieve higher precision with very fewer parameters than YOLOv3-Tiny, it is one of the Tinier-YOLO models. In this paper, the dangerous targets include dangerous objects and dangerous actions. The main contributions of this work include the following: firstly, the detection of dangerous objects and dangerous actions is integrated into one model, and the model can achieve higher accuracy with fewer parameters. Secondly, to solve the problem of insufficient YOLOv3-Tiny target detection, a jump-join repetitious learning (JRL) structure is proposed, combined with the spatial pyramid pooling (SPP), which serves as the new backbone network of YOLOv3-Tiny and can accelerate the speed of feature extraction while integrating features of different scales. Finally, the soft-NMS and DIoU-NMS algorithm are combined to effectively reduce the missing detection when two targets are too close. Experimental tests on self-made datasets of dangerous targets show that the average MAP value of the JRL-YOLO algorithm is 85.03%, which increases by 3.22 percent compared with YOLOv3-Tiny. On the VOC2007 dataset, the proposed method has a 9.29 percent increase in detection accuracy compared to that using YOLOv3-Tiny and a 2.38 percent increase compared to that employing YOLOv4-Tiny, respectively. These results all evidence the great improvement in detection accuracy brought by the proposed method. Moreover, when testing the dataset of dangerous targets, the model size of JRL-YOLO is 5.84 M, which is about one-fifth of the size of YOLOv3-Tiny (33.1 M) and one-third of the size of YOLOv4-Tiny (22.4 M), separately.
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http://dx.doi.org/10.1155/2021/5536152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032535PMC
April 2021

Human growth hormone proteoform pattern changes in pituitary adenomas: Potential biomarkers for 3P medical approaches.

EPMA J 2021 Mar 3;12(1):67-89. Epub 2021 Mar 3.

Science and Technology Innovation Center, Shandong First Medical University, 6699 Qingdao Road, Jinan, Shandong 250117 People's Republic of China.

Relevance: Human growth hormone (hGH) is synthesized, stored, and secreted by somatotroph cells in the pituitary gland, and promotes human growth and metabolism. Compared to a normal pituitary, a GH-secreting pituitary adenoma can secrete excessive GH to cause pathological changes in body tissues. GH proteoform changes would be associated with GH-related disease pathogenesis.

Purpose: This study aimed to elucidate changes in GH proteoforms between GH-secreting pituitary adenomas and control pituitaries for the predictive diagnostics, targeted prevention, and personalization of medical services.

Methods: The isoelectric point (pI) and relative molecular mass (Mr) are two basic features of a proteoform that can be used to effectively array and detect proteoforms with two-dimensional gel electrophoresis (2DGE) and 2DGE-based western blot. GH proteoforms were characterized with liquid chromatography (LC) and mass spectrometry (MS). Phosphoproteomics, ubiquitinomics, acetylomics, and bioinformatics were used to analyze post-translational modifications (PTMs) of GH proteoforms in GH-secreting pituitary adenoma tissues and control pituitaries.

Results: Sixty-six 2D gel spots were found to contain hGH, including 46 spots (46 GH proteoforms) in GH-secreting pituitary adenomas and 35 spots (35 GH proteoforms) in control pituitaries. Further, 35 GH proteoforms in control pituitary tissues were matched with 35 of 46 GH proteoforms in GH-secreting pituitary adenoma tissues; and 11 GH proteoforms were presented in only GH-secreting pituitary adenoma tissues but not in control pituitary tissues. The matched 35 GH proteoforms showed quantitative changes in GH-secreting pituitary adenomas compared to the controls. The quantitative levels of those 46 GH proteoforms in GH-secreting pituitary adenomas were significantly different from those 35 GH proteoforms in control pituitaries. Meanwhile, different types of PTMs were identified among those GH proteoforms. Phosphoproteomics identified phosphorylation at residues Ser77, Ser132, Ser134, Thr174, and Ser176 in hGH. Ubiquitinomics identified ubiquitination at residue Lys96 in hGH. Acetylomics identified acetylation at reside Lys171 in hGH. Deamination was identified at residue Asn178 in hGH.

Conclusion: These findings provide the first hGH proteoform pattern changes in GH-secreting pituitary adenoma tissues compared to control pituitary tissues, and the status of partial PTMs in hGH proteoforms. Those data provide in-depth insights into biological roles of hGH in GH-related diseases, and identify hGH proteoform pattern biomarkers for treatment of a GH-secreting pituitary adenoma in the context of 3P medicine -predictive diagnostics, targeted prevention, and personalization of medical services.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-021-00232-7.
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http://dx.doi.org/10.1007/s13167-021-00232-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954920PMC
March 2021

Total metabolic lesion volume of lymph nodes measured by F-FDG PET/CT: a new predictor of macrophage activation syndrome in adult-onset Still's disease.

Arthritis Res Ther 2021 03 30;23(1):97. Epub 2021 Mar 30.

Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China.

Background: To investigate the potential utility of quantitative parameters obtained by F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) in the assessment of disease severity and the occurrence of macrophage activation syndrome (MAS) in adult-onset Still's disease (AOSD).

Methods: Fifty-seven patients with AOSD who underwent pre-treatment F-FDG PET/CT were recruited in this study and compared with 60 age- and sex-matched healthy controls. Clinical features and laboratory data were recorded. The systemic score was assessed to determine the disease severity. The maximal standardized uptake value (SUV), metabolic lesion volume (MLV), and total lesion glycolysis (TLG) were used to evaluate the involved organs and tissues that abnormally accumulated F-FDG. Multivariate analysis was performed to identify the PET/CT-derived risk factors contributing to the AOSD-related MAS, and their diagnostic efficiency was evaluated.

Results: High F-FDG accumulation was observed in the bone marrow (SUV median, 5.10), spleen (SUV median, 3.70), and lymph nodes (LNs, SUV median, 5.55). The SUV of the bone marrow (rho = 0.376, p = 0.004), SUV of the spleen (rho = 0.450, p < 0.001), TLG of LNs (rho = 0.386, p = 0.017), and MLV of LNs (rho = 0.391, p = 0.015) were correlated with the systemic score. The SUV of the spleen (p = 0.017), TLG of LNs (p = 0.045), and MLV of LNs (p = 0.012) were higher in patients with MAS than in those without MAS. A MLV of LNs > 62.2 (OR 27.375, p = 0.042) was an independent predictive factor for MAS with a sensitivity of 80.0% and a specificity of 93.9%.

Conclusions: The glucose metabolic level of the spleen could be an effective and easy-to-use imaging indicator of disease severity, and MLV of LNs > 62.2 was a strong predictor of MAS occurrence in patients with AOSD.
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http://dx.doi.org/10.1186/s13075-021-02482-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008587PMC
March 2021

Deauville score evaluation of interim PET/CT in primary mediastinal large B-cell lymphoma.

Eur J Nucl Med Mol Imaging 2021 Mar 23. Epub 2021 Mar 23.

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China.

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http://dx.doi.org/10.1007/s00259-021-05310-6DOI Listing
March 2021

Altered spontaneous brain activity in patients with diabetic optic neuropathy: A resting-state functional magnetic resonance imaging study using regional homogeneity.

World J Diabetes 2021 Mar;12(3):278-291

Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.

Background: Diabetes is a common chronic disease. Given the increasing incidence of diabetes, more individuals are affected by diabetic optic neuropathy (DON), which results in decreased vision. Whether DON leads to abnormalities of other visual systems, including the eye, the visual cortex, and other brain regions, remains unknown.

Aim: To investigate the local characteristics of spontaneous brain activity using regional homogeneity (ReHo) in patients with DON.

Methods: We matched 22 patients with DON with 22 healthy controls (HCs). All subjects underwent resting-state functional magnetic resonance imaging. The ReHo technique was used to record spontaneous changes in brain activity. Receiver operating characteristic (ROC) curves were applied to differentiate between ReHo values for patients with DON and HCs. We also assessed the correlation between Hospital Anxiety and Depression Scale scores and ReHo values in DON patients using Pearson correlation analysis.

Results: ReHo values of the right middle frontal gyrus (RMFG), left anterior cingulate (LAC), and superior frontal gyrus (SFG)/left frontal superior orbital gyrus (LFSO) were significantly lower in DON patients compared to HCs. Among these, the greatest difference was observed in the RMFG. The result of the ROC curves suggest that ReHo values in altered brain regions may help diagnose DON, and the RMFG and LAC ReHo values are more clinically relevant than SFG/LFSO. We also found that anxiety and depression scores of the DON group were extremely negatively correlated with the LAC ReHo values ( = -0.9336, < 0.0001 and = -0.8453, < 0.0001, respectively).

Conclusion: Three different brain regions show ReHo changes in DON patients, and these changes could serve as diagnostic and/or prognostic biomarkers to further guide the prevention and treatment of DON patients.
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http://dx.doi.org/10.4239/wjd.v12.i3.278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958477PMC
March 2021

Diffuse large B-cell lymphoma segmentation in PET-CT images via hybrid learning for feature fusion.

Med Phys 2021 Mar 18. Epub 2021 Mar 18.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200040, China.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of lymphoma with high mortality and poor prognosis that especially has a high incidence in Asia. Accurate segmentation of DLBCL lesions is crucial for clinical radiation therapy. However, manual delineation of DLBCL lesions is tedious and time-consuming. Automatic segmentation provides an alternative solution but is difficult for diffuse lesions without the sufficient utilization of multimodality information. Our work is the first study focusing on positron emission tomography and computed tomography (PET-CT) feature fusion for the DLBCL segmentation issue. We aim to improve the fusion performance of complementary information contained in PET-CT imaging with a hybrid learning module in the supervised convolutional neural network.

Methods: First, two encoder branches extract single-modality features, respectively. Next, the hybrid learning component utilizes them to generate spatial fusion maps which can quantify the contribution of complementary information. Such feature fusion maps are then concatenated with specific-modality (i.e., PET and CT) feature maps to obtain a representation of the final fused feature maps in different scales. Finally, the reconstruction part of our network creates a prediction map of DLBCL lesions by integrating and up-sampling the final fused feature maps from encoder blocks in different scales.

Results: The ability of our method was evaluated to detect foreground and segment lesions in three independent body regions (nasopharynx, chest, and abdomen) of a set of 45 PET-CT scans. Extensive ablation experiments compared our method to four baseline techniques for multimodality fusion (input-level (IL) fusion, multichannel (MC) strategy, multibranch (MB) strategy, and quantitative weighting (QW) fusion). The results showed that our method achieved a high detection accuracy (99.63% in the nasopharynx, 99.51% in the chest, and 99.21% in the abdomen) and had the superiority in segmentation performance with the mean dice similarity coefficient (DSC) of 73.03% and the modified Hausdorff distance (MHD) of 4.39 mm, when compared with the baselines (DSC: IL: 53.08%, MC: 63.59%, MB: 69.98%, and QW: 72.19%; MHD: IL: 12.16 mm, MC: 6.46 mm, MB: 4.83 mm, and QW: 4.89 mm).

Conclusions: A promising segmentation method has been proposed for the challenging DLBCL lesions in PET-CT images, which improves the understanding of complementary information by feature fusion and may guide clinical radiotherapy. The statistically significant analysis based on P-value calculation has indicated a degree of significant difference between our proposed method and other baselines (almost metrics: P < 0.05). This is a preliminary research using a small sample size, and we will collect data continually to achieve the larger verification study.
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http://dx.doi.org/10.1002/mp.14847DOI Listing
March 2021

Improved prediction of chemoresistance in patients with diffuse large B-cell lymphoma through a new interim positron emission tomography-computed tomography evaluation model.

Acta Oncol 2021 Mar 15:1-9. Epub 2021 Mar 15.

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objectives: The positron emission tomography (PET) could predict the prognosis of DLBCL patients, but the exact procedure on interim PET (iPET) to determine chemoresistant patients remains elusive.

Methods: We retrospectively analyzed 593 newly diagnosed DLBCL patients uniformly treated with R-CHOP regimen. Among them, 352 patients diagnosed from August 2010 to December 2016 were included in the test cohort and 241 patients diagnosed from January 2017 to December 2019 were included in the validation cohort. The iPET was evaluated with Deauville criteria and ΔSUVmax method. The reduction of maximal SUV between baseline and after 4 cycles of chemotherapy were defined as ΔSUVmax. The survival functions were depicted using the Kaplan-Meier method and compared with the log-rank test.

Results: Patients with iPET Deauville 4 had heterogeneous outcome and end of treatment complete response rates (eCRR). Combined Deauville with ΔSUVmax method, we proposed a modified-Deauville model: patients with Deauville 4 and ΔSUVmax > 70%, as well as those with Deauville 1-3, were reclassified into the modified-Deauville negative group, while patients with Deauville 4 and ΔSUVmax ≤ 70%, as well as those with Deauville 5, into the modified-Deauville positive group. In the test cohort, 3-year PFS, OS and eCRR of modified-Deauville negative group were 80.2%, 89.9% and 91.8%, significantly higher than those of positive group (12.5%, 27.3% and 29.2%,  ≤ .001). Similar results were found in the validation cohort, that 3-year PFS, OS and eCRR were 87.8%, 95.4%, 96.3% in modified-Deauville negative group, and 27.4%, 32.5%, 13.5% in positive group. Through modified-Deauville model, patients in iPET positive group had very low eCRR and were resistant to conventional chemotherapy.

Conclusions: The modified-Deauville model could better distinguish DLBCL patients with poor response to chemotherapy. Accordingly, these patients could be recognized early and provided with alternative therapeutic agents, which might improve the clinical outcome of refractory DLBCL patients.
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http://dx.doi.org/10.1080/0284186X.2021.1894477DOI Listing
March 2021

Bone marrow mesenchymal stem cell-mediated ultrasmall gold nanoclusters and hNIS gene synergize radiotherapy for breast cancer.

J Mater Chem B 2021 03 15;9(12):2866-2876. Epub 2021 Mar 15.

Department of Nuclear Medicine, Ruijin Hospital, School of Medicine, Shanghai JiaoTong University, P. R. China.

The human sodium iodide symporter (hNIS) can be linked to the downstream of radiation-sensitive early growth response protein1 (Egr1) promoter, and activated by the Egr1 following I treatment. However, the rapid outflow of I restricted the radiotherapy effect. To overcome this barrier, ultrasmall gold nanoclusters (usAuNCs) were used to enhance the radiotherapy efficacy of Egr1-hNIS for its radiation sensitization. In this work, we prepared "cell bomb" BMSCs carrying both [email protected] and Egr1-hNIS. We found that the "cell bomb" can target TNBC tumor and reach a maximum I concentration 9 h following I injection. Colony formation assay revealed that I, I combined with [email protected] could independently inhibit 39.5% and 66.4% of cell growth, respectively. Moreover, in vivoI therapy further demonstrated that the growth of triple negative breast cancer (TNBC) was controlled by BMSC-Egr1-hNIS + AuNCs group, with relative volume inhibition percentages of 56.16% (compared with the control group) and 36.20% (compared with the BMSC-Egr1-hNIS group), respectively. To summarize, we successfully prepared BMSC-Egr1-hNIS carrying [email protected] to target TNBC which could synergistically improve the efficacy of hNIS gene therapy.
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http://dx.doi.org/10.1039/d1tb00186hDOI Listing
March 2021

Clinical Utility of F-PSMA-1007 Positron Emission Tomography/Magnetic Resonance Imaging in Prostate Cancer: A Single-Center Experience.

Front Oncol 2020 11;10:612701. Epub 2021 Feb 11.

Department of Urinary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Purpose: This study aimed to evaluate the clinical utility of F-PSMA-1007 positron emission tomography (PSMA PET)/magnetic resonance imaging (MRI) imaging in patients with suspected or defined prostate cancer.

Methods: In the pilot study, we retrospectively investigated 62 patients who underwent PSMA-PET/MRI for suspected or defined PCa between June 2019 and June 2020. Patients were grouped into three subgroups: (1) suspected PCa without histological evidence, (2) primary PCa, (3) biochemical recurrent prostate cancer (BRPCa). Two nuclear physicians independently interpreted the results of PSMA-PET/MRI. Management strategies before PSMA-PET/MRI were retrospectively reported, and the management strategy was re-evaluated for each patient considering the PSMA-PET/MRI result. The changes in strategies were recorded. Besides, the correlation between prostate specific antigen (PSA) level and management changes was also accessed by Fisher exact test, and two-side p < 0.05 was assumed as statistical significance.

Results: There were 28 patients in the suspected PCa group (group 1), 12 in the primary PCa group (group 2), and 22 in the BRPCa group (group 3). Overall, the intended decisions were changed in 26 (41.9%) of 62 patients after PSMA-PET/MRI, including 11/28 (39.3%) in suspected PCa group, 1/12 (8.4%) in primary PCa group, and 14/24 (63.6%) in BCR group. In group 1, the main impact on subsequent management included decreased active surveillance (from 20 to 9) and increased prostate biopsy (from 8 to 19). PSA levels were not significantly associated with management changes in suspected PCa patients (p = 0.865). In group 2, the main impact on subsequent management included decreased radical surgery (from 8 to 7), and multimodal therapy appearance (n = 1). Only in the category of PSA levels of ≥20 ng/ml, the management of primary PCa was changed. In group 3, the main impact on subsequent management included decreased salvage radiotherapy (from 5 to 2), increased systemic therapy (from 6 to 7), and increased multimodal therapy (from 11 to 13). The highest proportion of management changes occurred in BCR patients with 0.5≤PSA<1 ng/ml.

Conclusion: From our preliminary experience, PSMA-PET/MRI may be a valued tool for defining PCa lesions and changing management. The biggest impact of management intent was in patients with BRPCa, especially in patients with 0.5≤PSA<1 ng/ml. However, further studies are needed to confirm our pilot findings.
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http://dx.doi.org/10.3389/fonc.2020.612701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928386PMC
February 2021

Comprehensive Analysis of Tumor Microenvironment Identified Prognostic Immune-Related Gene Signature in Ovarian Cancer.

Front Genet 2021 10;12:616073. Epub 2021 Feb 10.

Science and Technology Innovation Center, Shandong First Medical University, Jinan, China.

Background: Accumulating evidence demonstrated that tumor microenvironmental cells played important roles in predicting clinical outcomes and therapeutic efficacy. We aimed to develop a reliable immune-related gene signature for predicting the prognosis of ovarian cancer (OC).

Methods: Single sample gene-set enrichment analysis (ssGSEA) of immune gene-sets was used to quantify the relative abundance of immune cell infiltration and develop high- and low-abundance immune subtypes of 308 OC samples. The presence of infiltrating stromal/immune cells in OC tissues was calculated as an estimate score. We estimated the correlation coefficients among the immune subtype, clinicopathological feature, immune score, distribution of immune cells, and tumor mutation burden (TMB). The differentially expressed immune-related genes between high- and low-abundance immune subtypes were further used to construct a gene signature of a prognostic model in OC with lasso regression analysis.

Results: The ssGSEA analysis divided OC samples into high- and low-abundance immune subtypes based on the abundance of immune cell infiltration, which was significantly related to the estimate score and clinical characteristics. The distribution of immune cells was also significantly different between high- and low-abundance immune subtypes. The correlation analysis showed the close relationship between TMB and the estimate score. The differentially expressed immune-related genes between high- and low-abundance immune subtypes were enriched in multiple immune-related pathways. Some immune checkpoints (PDL1, PD1, and CTLA-4) were overexpressed in the high-abundance immune subtype. Furthermore, the five-immune-related-gene-signature prognostic model (CCL18, CXCL13, HLA-DOB, HLA-DPB2, and TNFRSF17)-based high-risk and low-risk groups were significantly related to OC overall survival.

Conclusion: Immune-related genes were the promising predictors of prognosis and survival, and the comprehensive landscape of tumor microenvironmental cells of OC has potential for therapeutic schedule monitoring.
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http://dx.doi.org/10.3389/fgene.2021.616073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928403PMC
February 2021

Nicotinamide mononucleotide attenuates isoproterenol-induced cardiac fibrosis by regulating oxidative stress and Smad3 acetylation.

Life Sci 2021 Jun 3;274:119299. Epub 2021 Mar 3.

Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha City, Hunan Province, China. Electronic address:

Aims: Cardiac fibrosis is a pathological hallmark of progressive heart diseases currently lacking effective treatment. Nicotinamide mononucleotide (NMN), a member of the vitamin B family, is a defined biosynthetic precursor of nicotinamide adenine dinucleotide (NAD). Its beneficial effects on cardiac diseases are known, but its effects on cardiac fibrosis and the underlying mechanism remain unclear. We aimed to elucidate the protective effect of NMN against cardiac fibrosis and its underlying mechanisms of action.

Materials And Methods: Cardiac fibrosis was induced by isoproterenol (ISO) in mice. NMN was administered by intraperitoneal injection. In vitro, cardiac fibroblasts (CFs) were stimulated by transforming growth factor-beta (TGF-β) with or without NMN and sirtinol, a SIRT1 inhibitor. Levels of cardiac fibrosis, NAD/SIRT1 alteration, oxidative stress, and Smad3 acetylation were evaluated by real-time polymerase chain reaction, western blots, immunohistochemistry staining, immunoprecipitation, and assay kits.

Key Findings: ISO treatment induced cardiac dysfunction, fibrosis, and hypertrophy in vivo, whereas NMN alleviated these changes. Additionally, NMN suppressed CFs activation stimulated by TGF-β in vitro. Mechanistically, NMN restored the NAD/SIRT1 axis and inhibited the oxidative stress and Smad3 acetylation induced by ISO or TGF-β. However, the protective effects of NMN were partly antagonized by sirtinol in vitro.

Significance: NMN could attenuate cardiac fibrosis in vivo and fibroblast activation in vitro by suppressing oxidative stress and Smad3 acetylation in a NAD/SIRT1-dependent manner.
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http://dx.doi.org/10.1016/j.lfs.2021.119299DOI Listing
June 2021

Functional connectivity density alterations in middle-age retinal detachment patients.

Brain Behav 2021 Apr 1;11(4):e01783. Epub 2021 Mar 1.

Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Objective: Middle-age patients with retinal detachment (RD) exhibit a loss of visual information, and previous studies of functional magnetic resonance imaging (fMRI) have demonstrated abnormal spontaneous activity in the RD brain. Therefore, this study assessed changes in local functional connectivity density (lFCD) and long-range functional connectivity density (longFCD) in middle-age RD patients during resting-state FC.

Methods: In total, 32 middle-age patients with RD (18 men and 14 women), and 32 age-, sex-, and education-matched normal controls (NCs) (18 men and 14 women) were recruited and underwent functional magnetic resonance examination in the resting state. Two-sample t test was performed to compare lFCD and longFCD between groups. Receiver operating characteristic (ROC) curves were generated to distinguish middle-age RD patients from NCs.

Results: Compared with NCs, middle-age RD patients demonstrated increased lFCD values in the right inferior temporal gyrus, and increased longFCD values in the bilateral inferior frontal gyri, left superior and middle frontal gyrus, bilateral inferior temporal gyri, and left cerebellum posterior lobe. Middle-age RD patient exhibited decreased lFCD values in the left cuneus, right lingual gyrus, and left middle frontal gyrus. They also had lower longFCD values in the left lingual gyrus and left inferior occipital gyrus. ROC curve analysis showed excellent accuracy of the specific areas under the curve.

Conclusion: Our results reveal that middle-age RD patients exhibited variations of binarized lFCD and longFCD in specific brain areas, which provides insight into the pathological mechanism of RD patients with acute visual loss.
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http://dx.doi.org/10.1002/brb3.1783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035440PMC
April 2021