Publications by authors named "Yiran Zhou"

47 Publications

No significant long-term complications from inadvertent exposure to gonadotropin-releasing hormone agonist during early pregnancy in mothers and offspring: a retrospective analysis.

Reprod Biol Endocrinol 2021 Mar 20;19(1):46. Epub 2021 Mar 20.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, China.

Background: Administration of gonadotropin-releasing hormone agonist (GnRH-a) in the luteal phase is commonly used for pituitary suppression during in vitro fertilisation (IVF). There is an ineluctable risk of inadvertent exposure of spontaneous pregnancy to GnRH-a. However, little is known about the pregnancy complications and repregnancy outcomes of the affected women and the neurodevelopmental outcomes of the GnRH-a-exposed children.

Methods: Retrospective analysis was used to determine obstetric and repregnancy outcomes after natural conception in 114 women who naturally conceived while receiving GnRH-a during their early pregnancy over the past 17 years. The GnRH-a-exposed children were evaluated to determine their neonatal characteristics and long-term neurodevelopmental outcomes. The outcomes were compared to those of relevant age-matched control groups.

Results: Sixty-five women had 66 live births. The neonatal health outcomes and the incidence of maternal complications were similar in the GnRH-a-exposed and control groups. Thirty-one GnRH-a-exposed children, aged 2-8 years, were available for investigation of neurodevelopment. Except for one case of autism spectrum disorder, the full-scale intelligence quotient score was within the normal range and similar to that of the control group. Most mothers with successful pregnancies and about one-third of the women who had spontaneous abortions were subsequently able to conceive naturally again. IVF is recommended for repregnancy in women who have experienced ectopic pregnancies.

Conclusions: Accidental exposure to GnRH-a in early pregnancy might be safe. Reproductive treatment suggestions for repregnancy should be made with consideration of the outcomes of the previously GnRH-a-exposed spontaneous pregnancy.
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http://dx.doi.org/10.1186/s12958-021-00732-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980339PMC
March 2021

A novel nomogram for predicting the risk of major complications after pancreaticoduodenectomy in patients with obstructive jaundice.

Clin Chim Acta 2021 Mar 9;517:162-170. Epub 2021 Mar 9.

Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Research Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Background: The aim of this study was to construct and internally validate a nomogram for predicting major complications in obstructive jaundice patients planned to undergo pancreaticoduodenectomy (PD).

Methods: The clinical data of 835 obstructive jaundice patients who underwent PD in a high-volume center were collected and retrospectively analyzed during an 8-year period. Factors affecting the major complication rate were optimized by least absolute shrinkage and selection operator (LASSO) regression analysis and were incorporated in logistic regression analysis. The performance of this nomogram was evaluated by discrimination, calibration, internal validation and clinical utility.

Results: Predictors included in the model were sex, American Society of Anesthesiologists (ASA) score, preoperative biliary drainage (PBD), neutrophil-to-lymphocyte ratio (NLR), hemoglobin, prealbumin, total bilirubin, transfusion, and pathology category. The model had good discrimination and calibration with a C-index of 0.700. Internal validation generated an acceptable C-index of 0.701. Decision curve analysis indicated this nomogram was clinically useful for predicting the possibility of major complications at a threshold between 1% and 59%.

Conclusion: This novel nomogram could be conveniently used and assist in decisions for PBD in clinical practice.
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http://dx.doi.org/10.1016/j.cca.2021.02.018DOI Listing
March 2021

Long-term microstructure and cerebral blood flow changes in patients recovered from COVID-19 without neurological manifestations.

J Clin Invest 2021 04;131(8)

Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

BACKGROUNDThe coronavirus disease 2019 (COVID-19) rapidly progressed to a global pandemic. Although some patients totally recover from COVID-19 pneumonia, the disease's long-term effects on the brain still need to be explored.METHODSWe recruited 51 patients with 2 subtypes of COVID-19 (19 mild and 32 severe) with no specific neurological manifestations at the acute stage and no obvious lesions on the conventional MRI 3 months after discharge. Changes in gray matter morphometry, cerebral blood flow (CBF), and white matter (WM) microstructure were investigated using MRI. The relationship between brain imaging measurements and inflammation markers was further analyzed.RESULTSCompared with healthy controls, the decrease in cortical thickness/CBF and the changes in WM microstructure were more severe in patients with severe disease than in those with mild disease, especially in the frontal and limbic systems. Furthermore, changes in brain microstructure, CBF, and tract parameters were significantly correlated (P < 0.05) with the inflammatory markers C-reactive protein, procalcitonin, and interleukin 6.CONCLUSIONIndirect injury related to inflammatory storm may damage the brain, altering cerebral volume, CBF, and WM tracts. COVID-19-related hypoxemia and dysfunction of vascular endothelium may also contribute to neurological changes. The abnormalities in these brain areas need to be monitored during recovery, which could help clinicians understand the potential neurological sequelae of COVID-19.FUNDINGNatural Science Foundation of China.
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http://dx.doi.org/10.1172/JCI147329DOI Listing
April 2021

Formation of Phases and Microstructures in Al-8Si Alloys with Different Mg Content.

Materials (Basel) 2021 Feb 6;14(4). Epub 2021 Feb 6.

Key Laboratory for Anisotropy and Texture of Materials (Ministry of Education), Northeastern University, No. 3-11, Wenhua Road, Heping District, Shenyang 110819, China.

Mg-containing high-silicon aluminum alloy is a heat-treatable aluminum alloy that is now widely used in the aerospace and automotive industries because of its high specific strength, high wear resistance and corrosion resistance, low thermal expansion coefficient, and low cost. More attention has been paid to optimizing the microstructure to increase the performance of this type of aluminum alloy. In the present work, the solidification processes of Mg-free and Mg-containing (0.33-1.32%) Al-8Si alloys were analyzed by the experimental results combined with the thermodynamic calculation. The results showed that α-Al, Si, and AlFeSi were in the Mg-free Al-8Si alloy ingots, while the AlFeSi phases in alloys with Mg additions were transformed into π phases (AlMgFeSi) by the reaction L+AlFeSi→α-Al+Si+AlMgFeSi. There was a binary eutectic reaction of L→α-Al+AlFeSi when the Mg content exceeded 0.51% and the Fe content was higher than 0.17%. With the increase of Mg content, the volume of MgSi was gradually increased while the divorced eutectic phenomenon of the quaternary eutectic structure (α-Al+Si+MgSi+AlMgFeSi) was weakened and the eutectic structure was significantly refined.
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http://dx.doi.org/10.3390/ma14040762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914800PMC
February 2021

Source, transportation, bioaccumulation, distribution and food risk assessment of perfluorinated alkyl substances in vegetables: A review.

Food Chem 2021 Jul 19;349:129137. Epub 2021 Jan 19.

College of Food Science and Engineering, Shandong Agricultural University, Tai'an 271018, China. Electronic address:

Contamination of perfluoroalkyl substances (PFASs) in agricultural products have attracted more and more attentions recently. In this review, relationship between PFASs and vegetables is summarized comprehensively. PFASs could transfer to cultivation soils by irrigation water, bio-amended soil, and atmospheric deposition mainly from industrial emissions. Carbon chain length of PFASs, species of vegetables and so on are key factors for PFASs migration and bioaccumulation in soils, plants and vegetables. Studies on food risk assessment of PFOA and PFOS show low consumption risk for most vegetables, however researches on other substances are lacking. In the future, we need to pay more attention on novel pollution pathway in cultivation, traceability research for considerable contamination, dietary exposure levels for different vegetables and more substances, as well as more exact and scientific food risk assessments. Additionally, effective means for PFASs adsorption in soil and removal from soil are also expected.
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http://dx.doi.org/10.1016/j.foodchem.2021.129137DOI Listing
July 2021

Room-temperature synthesis of magnetic covalent organic frameworks for analyzing trace benzoylurea insecticide residue in tea beverages.

Food Chem 2021 Jun 14;347:129075. Epub 2021 Jan 14.

College of Food Science and Engineering, Shandong Agricultural University, Taian 271018, China. Electronic address:

A novel magnetic covalent organic framework (NH-FeO@COF) was prepared using a simple room-temperature synthesis in this study. These magnetic particles exhibited high adsorption performance with short adsorption time (10 min) for six benzoylurea insecticides (BUs) as magnetic solid-phase extraction (MSPE) adsorbents. Quantum chemistry calculation demonstrated that adsorption mechanism was primarily attributed to strong halogen bonds between electronegative O atoms of COF and electropositive F atoms of BUs as well as potential hydrophobic effect. Wide linearities (10-1000 ng·L) and low limits of detection (0.06-1.65 ng·L) for six analytes were obtained via liquid chromatography-tandem mass spectrometry. Applicability of the proposed method was further evaluated by analyzing four kinds of original tea beverages. Recoveries of six BUs in spiked samples ranged from 80.1% to 108.4%.
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http://dx.doi.org/10.1016/j.foodchem.2021.129075DOI Listing
June 2021

Optimizing BIO feeding strategy promotes ex vivo expansion of human hematopoietic stem and progenitor cells.

J Biosci Bioeng 2021 Feb 27;131(2):190-197. Epub 2020 Oct 27.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China. Electronic address:

Ex vivo expansion is critical in facilitating the application of hematopoietic/progenitor stem cells (HSPCs) for regenerative therapies. Wnt signaling is implicated in the expansion and self-renewal maintenance of HSPCs. However, a reasonable method to regulate Wnt signaling in ex vivo cultures to achieve robust expansion of HSPCs has not yet been investigated. Here, cord blood-derived CD34 cells were cultured with the activator of Wnt signaling 6-bromoindirubin-3'-oxime (BIO) under the following conditions: vehicle control (group A); BIO was added to the culture on days 0, 4, and 7 (group B); and BIO was added to the culture on days 0 and 7 (group C). Initial BIO treatment promoted the expansion of CD34 cells on day 4. However, BIO supplementation on days 0 and 4 in group B attenuated HSPC expansion on day 7, while enhancing the multilineage commit potential and secondary expansion ability of expanded CD34 cells. Based on this finding, an optimized BIO feeding strategy (group C) was proposed to support substantial expansion of HSPCs. After 10 days of culture, the expansion fold of CD34 cells was 28.70 ± 0.46-folds, which was significantly higher than group A (16.20 ± 0.72-folds, p < 0.05). Moreover, the optimized BIO feeding strategy achieved increased primitive HSPC expansion without the loss of biological functions. Mechanistically, the optimized BIO feeding strategy avoided the excessive activation of Wnt observed in group B while maintaining a moderate level of intracellular β-catenin. These results provide an experimental and theoretical basis for Wnt regulation in ex vivo culture process and a potential strategy to expand HSPCs for transplantation.
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http://dx.doi.org/10.1016/j.jbiosc.2020.09.020DOI Listing
February 2021

Effects of childhood trauma experience and BDNF Val66Met polymorphism on brain plasticity relate to emotion regulation.

Behav Brain Res 2021 02 11;398:112949. Epub 2020 Oct 11.

Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address:

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism may modulate the link between childhood trauma experience and psychopathology by altering trophic signaling on neuroplasticity. However, few multimodal magnetic resonance imaging (MRI) researches have investigated this gene-environment interaction on both structural and functional plasticity, thereby advancing knowledge about the etiology, prevention, and customized therapeutic directions of mental disease in individuals with childhood trauma experience. We recruited a large non-clinical sample of young adults that completed Childhood Trauma Questionnaire (CTQ), behavioral scores, multimodal MRI scans, and genotyping. Morphometric similarity network (MSN) and independent component analysis were adopted to quantify brain structural and functional changes. Gene-environment-brain-behavior relationships were identified by multiple regression and mediation effect analysis. CTQ score was positively associated with depression and anxiety scores. We found interactions on MSN in sensorimotor, temporal, and orbitofrontal cortex. For intra-network connectivity, significant interaction was noted in clusters within sensorimotor network. For inter-network connectivity, connectivity between dorsal attention network and salience network showed an interactive effect. For mean connectivity strength of each network, we found a main effect of CTQ score on self-reference network that was an outstanding mediator supporting the relationship between CTQ score and anxiety. Our findings demonstrate that childhood trauma and the BDNF Val66Met polymorphism are associated with brain plasticity involving emotion regulation, structurally and functionally, which may contribute to understanding psychotic mechanisms and predicting differential susceptibility. Imaging genetics may be useful as biomarkers to provide early assessment and guide cognitive interventions to avoid or decrease the risk of developing psychopathology.
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http://dx.doi.org/10.1016/j.bbr.2020.112949DOI Listing
February 2021

tRFTar: Prediction of tRF-target gene interactions via systemic re-analysis of Argonaute CLIP-seq datasets.

Methods 2021 03 9;187:57-67. Epub 2020 Oct 9.

Department of Biomedical Informatics, Department of Physiology and Pathophysiology, Center for Noncoding RNA Medicine, MOE Key Lab of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University, Beijing 100191, China. Electronic address:

tRNA-derived fragments (tRFs), which by definition are cleaved from tRNAs, comprise a novel class of regulatory small non-coding RNAs. Recent evidence has revealed that tRFs can be loaded onto Argonaute (AGO) family proteins to perform post-transcriptional regulations via substantial tRF-target gene interactions (TGIs). However, there is no resource that systematically profiles potential AGO-mediated TGIs. To this end, we performed a systemic computational screening of potential AGO-mediated TGIs by a re-analysis of 146 crosslinking-immunoprecipitation and high-throughput sequencing (CLIP-seq) datasets in which 920,690 TGIs between 12,102 tRFs and 5,688 target genes were identified. The predicted TGIs have superior signal-to-noise ratio and good consistency with TGIs identified from an orthogonal technique. AGO-bound tRFs are not evenly distributed, where the 5'-tRF and 3'-tRF are enriched and some commonly expressed tRFs are also overrepresented. The tRFs tend to target conserved regions of transcripts and co-express with their target genes. Filtering TGIs with consistent co-expression with target genes results in a set of regulatory TGIs that contains 25,281 tRF-target pairs. Together, our results unveiled the extensive regulatory interactions between tRFs and target genes. Finally, the CLIP-derived TGIs were incorporated in a user-friendly online platform termed as tRFTar, where various functions like custom searching, co-expressed TGI filtering, genome browser and TGI-based tRF functional enrichment analysis are enabled to help users to investigate the functions of tRFs. The tRFTar is freely available at http://www.rnanut.net/tRFTar/.
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http://dx.doi.org/10.1016/j.ymeth.2020.10.006DOI Listing
March 2021

Does Pre-operative Biliary Drainage Influence Long-Term Survival in Patients With Obstructive Jaundice With Resectable Pancreatic Head Cancer?

Front Oncol 2020 16;10:575316. Epub 2020 Sep 16.

Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Whether pre-operative biliary drainage (PBD) affects long-term survival of patients with obstructive jaundice with pancreatic ductal adenocarcinoma (PDAC) who underwent pancreaticoduodenectomy is still controversial. Most of the previous research did not include the important total serum bilirubin (TB) level before intervention as well as before surgery. The aim of this study is to evaluate the impact of PBD on long-term survival after considering the TB level. Data were collected retrospectively from patients with obstructive jaundice who underwent resection of pancreatic head cancer in a high-volume center. X-Tile software and Kaplan-Meier survival analysis were applied to determine the optimal cut-off levels for TB and age based on the minimal probability ()-value and the largest χ2-value. Multivariate Cox regression analyses were performed after univariate analysis to assess independent prognostic factors for overall survival (OS) and disease-free survival (DFS). Of 426 patients with obstructive jaundice who underwent pancreaticoduodenectomy for resectable pancreatic head cancer during a 7 year period, 242 (56.8%) received PBD and 184 (43.2%) underwent surgery directly. The OS of patients who received PBD was significantly worse than that of patients who did not receive PBD by univariate analysis (median of 16.6 vs. 22.2 months, = 0.048). After including liver function parameters in the multivariate Cox regression, we found that the use of PBD was not associated with OS or DFS, while TB before intervention >150 μmol/L was an independent adverse prognostic factor for both OS [hazard ratio (HR), 1.42; 95% CI, 1.05-1.91] and DFS (HR, 1.38; 95% CI, 1.08-1.77). In patients with obstructive jaundice with resectable pancreatic head cancer, undergoing PBD before pancreaticoduodenectomy did not impair or benefit survival rates compared with surgery alone. However, TB before intervention >150 μmol/L predicted an unfavorable prognosis, irrespective of the PBD procedure.
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http://dx.doi.org/10.3389/fonc.2020.575316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525216PMC
September 2020

Effects of childhood trauma experience and COMT Val158Met polymorphism on brain connectivity in a multimodal MRI study.

Brain Behav 2020 12 30;10(12):e01858. Epub 2020 Sep 30.

Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Childhood adversity may act as a stressor to produce a cascade of neurobiological effects that irreversibly alter neural development, setting the stage for developing psychopathology in adulthood. The catechol-O-methyltransferase (COMT) Val158Met polymorphism has received much attention as a candidate gene associated with environmental adversity, modifying risk for psychopathology. In this study, we aim to see how gene × brain × environment models give a more integrative understanding of brain modifications that contribute to predicting psychopathology related to childhood adversity. A large nonclinical sample of young adults completed Childhood Trauma Questionnaire (CTQ), behavioral scores, multimodal magnetic resonance imaging (MRI) scans, and genotyping. We utilized graph-based connectivity analysis in morphometric similarity mapping and resting-state functional MRI to investigate brain alterations. Relationships among COMT genotypes, CTQ score, imaging phenotypes, and behavioral scores were identified by multiple regression and mediation effect analysis. Significant main effect of CTQ score was found in anatomic connectivity of orbitofrontal cortex that was an outstanding mediator supporting the relationship between CTQ score and anxiety/harm-avoiding personality. We also noted the main effect of childhood trauma on reorganization of functional connectivity within the language network. Additionally, we found genotype × CTQ score interactions on functional connectivity of the right frontoparietal network as well as anatomic connectivity of motor and limbic regions. Our data demonstrate childhood adversity and COMT genotypes are associated with abnormal brain connectivity, structurally and functionally. Early identification of individuals at risk, assessment of brain abnormality, and cognitive interventions may help to prevent or limit negative outcomes.
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http://dx.doi.org/10.1002/brb3.1858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749512PMC
December 2020

Inhibitory effects of canagliflozin on pancreatic cancer are mediated via the downregulation of glucose transporter‑1 and lactate dehydrogenase A.

Int J Oncol 2020 Nov 8;57(5):1223-1233. Epub 2020 Sep 8.

School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 211198, P.R. China.

Pancreatic cancer is one of the most lethal solid malignancies, with a poor prognosis and a high mortality rate. Pancreatic cancer cells exhibit enhanced glycolysis to maintain their rapid growth. Canagliflozin (CANA) is a sodium‑glucose co‑transporter 2 inhibitor used for the clinical treatment of diabetes. Recent studies have demonstrated the potential ability of CANA to suppress hepatocellular carcinoma, whereas its therapeutic effects on and mechanisms in pancreatic cancer have rarely been reported. In the present study, the antitumor effects of CANA on pancreatic cancer were investigated. The data obtained indicated that pancreatic cancer growth was effectively suppressed by CANA in a dose‑dependent manner, with peak inhibition rates of 54.3 and 57.6% in cultured Capan‑1 and PANC‑1 cells respectively. The tumor inhibitory rate reached 45.2% in nude mice with PANC‑1‑derived tumors, suggesting its effective antitumor activity against pancreatic cancer in vitro and/or in vivo. In addition, the combined treatment of Capan‑1 and PANC‑1 cells with gemcitabine and CANA exhibited a greater efficacy compared with that of treatment with gemcitabine alone. Moreover, glucose uptake and lactate production were decreased, and the mRNA levels of the glycolysis‑associated genes, including glucose transporter‑1 and lactate dehydrogenase A were decreased, indicating the inhibitory effects caused by the combination treatment on the metabolism of glucose in pancreatic cancer cells. Furthermore, CANA induced apoptosis, notably early apoptosis, and decreased the protein levels of PI3K, p‑AKT, p‑mTOR and HIF‑1α, which indicated that the PI3K/AKT/mTOR signaling pathway was involved in the glycolytic process. These results demonstrated that pancreatic cancer growth was effectively inhibited by CANA via the suppression of glycolysis. This was mediated primarily by the PI3K/AKT/mTOR signaling pathway, revealing the underlying role and potential of this pathway for the clinical treatment of pancreatic cancer. Novel applications for the existing drug CANA can be explored, which could reduce the cost and time required for drug development in the field of drug discovery.
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http://dx.doi.org/10.3892/ijo.2020.5120DOI Listing
November 2020

Novel proton exchange rate MRI presents unique contrast in brains of ischemic stroke patients.

J Neurosci Methods 2020 12 5;346:108926. Epub 2020 Sep 5.

Departments of Radiology, Department of Bioengineering, the Center for MR Research, University of Illinois at Chicago, Chicago, USA. Electronic address:

Background: To map and quantify the proton exchange rate (k) of brain tissues using improved omega plots in ischemic stroke patients and to investigate whether k can serve as a potential endogenous surrogate imaging biomarker for detecting the metabolic state and the pathologic changes due to ischemic stroke.

New Method: Three sets of Z-spectra were acquired from seventeen ischemic stroke patients using a spin echo-echo planar imaging sequence with pre-saturation chemical exchange saturation transfer (CEST) pulse at B of 1.5, 2.5, and 3.5 μT, respectively. Pixel-wise k was calculated from improved omega plot of water direct saturation (DS)-removed Z-spectral signals.

Results: The derived k maps can differentiate infarcts from contralateral normal brain tissues with significantly increased signal (893 ± 52 svs. 739 ± 34 s, P < 0.001).

Comparison With Existing Method(s): The k maps were found to be different from conventional contrasts from diffusion-weighted imaging (DWI), CEST, and semi-solid magnetization transfer (MT) MRI. In brief, k MRI showed larger lesion areas than DWI with different degrees and different lesion contrast compared to CEST and MT.

Conclusions: In this preliminary translational research, the k MRI based on DS-removed omega plots has been demonstrated for in vivo imaging of clinical ischemic stroke patients. As a noninvasive and unique MRI contrast, k MRI at 3 T may serve as a potential surrogate imaging biomarker for the metabolic changes of stroke and help for monitoring the evolution and the treatment of stroke.
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http://dx.doi.org/10.1016/j.jneumeth.2020.108926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606776PMC
December 2020

Characterization of a polysaccharide from Eupolyphaga sinensis walker and its effective antitumor activity via lymphocyte activation.

Int J Biol Macromol 2020 Nov 15;162:31-42. Epub 2020 Jun 15.

School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Road, Nanjing, Jiangsu 211198, PR China. Electronic address:

A polysaccharide (ESPS) purified from Eupolyphaga sinensis Walker by ion exchange chromatography and gel chromatography was investigated, including its structure characterization and antitumor activity. The results showed that ESPS was composed of rhamnose, fucose, arabinose, xylose, glucose, and galactose in a molar ratio of 7.4: 3.1: 13.9: 9.3: 39.7: 26.5, with the mean weight (Mw) of 2.14 × 10Da; the main chain of ESPS was mainly composed of → 4) - α - D - Glcp - (1 → and → 3) - β - D - Galp - (1 →, and the side chains were connected to the main chain through the O-6 atom of glucose and O-4 and O-6 atom of galactose. In addition, ESPS promoted the lymphocyte proliferation and inhibited liver cancer cells growth through enhancing lymphocyte activity in vitro, mainly NK cells. Moreover, ESPS markedly stimulated immunity in H22-bearing mice by increasing the spleen and thymus indices and effectively inhibited H22 cell growth in vivo. These data indicated that ESPS was a polysaccharide component possessing high anti-hepatocellular carcinoma activity, representing a potential immunotherapy candidate for the treatment of liver cancer.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.06.120DOI Listing
November 2020

Transcriptomic landscape profiling of metformin-treated healthy mice: Implication for potential hypertension risk when prophylactically used.

J Cell Mol Med 2020 07 11;24(14):8138-8150. Epub 2020 Jun 11.

Department of Physiology and Pathophysiology, Department of Biomedical Informatics, Center for Non-coding RNA Medicine, MOE Key Lab of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University, Beijing, China.

Recently, the first-line anti-diabetic drug metformin shows versatile protective effects against several diseases and is potentially prescribed to healthy individual for prophylactic use against ageing or other pathophysiological processes. However, for healthy individuals, it remains unclear what effects metformin treatment will induce on their bodies. A systematic profiling of the molecular landscape of metformin treatment is expected to provide crucial implications for this issue. Here, we delineated the first transcriptomic landscape induced by metformin in 10 tissues (aorta, brown adipose, brain, eye, heart, liver, kidney, skeletal muscle, stomach and testis) of healthy mice by using RNA-sequencing technique. A comprehensive computational analysis was performed. The overrepresentation of cardiovascular disease-related gene sets, positive correlation with hypertension-related transcriptomic signatures and the associations of drugs with hypertensive side effect together indicate that although metformin does exert various beneficial effects, it would also increase the risk of hypertension in healthy mice. This prediction was experimentally validated by an independent animal experiments. Together, this study provided important resource necessary for investigating metformin's beneficial/deleterious effects on various healthy tissues, when it is potentially prescribed to healthy individual for prophylactic use.
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http://dx.doi.org/10.1111/jcmm.15472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348147PMC
July 2020

Age and anatomical location related hemodynamic changes assessed by 4D flow MRI in the carotid arteries of healthy adults.

Eur J Radiol 2020 Jul 4;128:109035. Epub 2020 May 4.

Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Purpose: To evaluate hemodynamic changes (volume, velocity, wall shear stress, pressure gradient, and energy loss) in the common carotid artery (CCA) and internal carotid artery (ICA) of healthy adults among different ages and anatomical locations using 4D flow MRI.

Methods: Sixty-two healthy volunteers aged 20-75 years were enrolled in this study. 4D flow MRI examinations were performed for each subject and were analyzed using the CVI42 platform to generate hemodynamic parameters. Hemodynamic parameters were compared among different age groups and anatomical locations (proximal CCA, distal CCA, proximal ICA and distal CCA) using one-way ANOVA. The paired t-test was used to estimate the differences between left and right vessels. The relationship between age and hemodynamic parameters was quantified by Pearson's correlation coefficient.

Results: There were no differences between the left and right carotid arteries for any of the hemodynamic parameters (all p values > 0.05), so we set each vessel as an independent sample. The proximal ICA had significantly lower volume, velocity, wall shear stress, and pressure gradient values than the values determined for other locations (p < 0.05), and energy loss was similar among different locations. Wall shear stress (except in the distal ICA), velocity, pressure gradient, and energy loss decreased with age (p < 0.05).

Conclusions: The multiparameter analysis of 4D flow MRI can identify age and anatomical location changes in hemodynamic parameters in the carotid arteries of healthy adults. The lower velocity, wall shear stress, and pressure gradient in the proximal ICA and the reduced trend with age may be associated with disease occurrence.
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http://dx.doi.org/10.1016/j.ejrad.2020.109035DOI Listing
July 2020

Disordered Gut Microbiota in Children Who Have Chronic Pancreatitis and Different Functional Gene Mutations.

Clin Transl Gastroenterol 2020 03;11(3):e00150

Department of General Surgery and Research Institute of Pancreatic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objectives: Chronic pancreatitis (CP) is a serious condition whose pathogenic mechanism is unclear. Interactions of host genetic factors with gut microbiota have a role, but little is known, especially in children with CP (CCP), in which the external factors are less important. Our objective was to identify the main gut microbiota genera in CCP and to characterize the functional mutations of these patients.

Methods: We used 16S rRNA sequencing to compare the gut microbiota of healthy controls with patients who had CCP and different functional gene mutations.

Results: CCP is characterized by gut microbiota with remarkably reduced alpha diversity. Receiver operating characteristic curve analyses indicated that the abundances of 6 genera-Faecalibacterium, Subdoligranulum, Phascolarctobacterium, Bifidobacterium, Eubacerium, and Collinsella-were significantly decreased in CCP, with an area under curve (AUC) of 0.92 when considering all 6 genera together. Functional analysis of gut microbiota in CCP indicated reduced ribosomal activity, porphyrin and chlorophyll metabolism, starch and sucrose metabolism, and aminoacyl-tRNA biosynthesis, but an enrichment of phosphotransferase system pathways. The abundance of Butyricicoccus was significantly decreased in CCP in the presence of CFTR mutations when combined with mutations in CASR, CTSB, SPINK1, and/or PRSS1. The abundance of Ruminococcaceae was significantly increased in CCP when there were mutations in CASR, CTSB, SPINK1, and/or PRSS1. Patients with CCP but no gene mutations had greater abundances of Veillonella and reduced abundances of Phascolarctobacterium.

Discussion: CCP is associated with a depletion of probiotic gut microbiota, and CCP patients with different functional gene mutations have different gut microbiota.
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http://dx.doi.org/10.14309/ctg.0000000000000150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145041PMC
March 2020

Preoperative biliary drainage of severely obstructive jaundiced patients decreases overall postoperative complications after pancreaticoduodenectomy: A retrospective and propensity score-matched analysis.

Pancreatology 2020 Apr 5;20(3):529-536. Epub 2020 Feb 5.

Pancreatic Disease Center, Ruijin Hospital Shanghai Jiaotong University School of Medicine, Shanghai, China; Research Institute of Pancreatic Disease, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address:

Objectives: The influence of preoperative biliary drainage (PBD) for obstructive jaundiced patients before pancreaticoduodenectomy is debated in the past decades. The aim of this study is to assess the impact of preoperative biliary drainage on intraoperative and postoperative outcomes in patients with severely obstructive jaundice.

Methods: Data were collected retrospectively from severely obstructive jaundiced patients with serum total bilirubin level exceeding 250 μmol/L and undergoing pancreaticoduodenectomy from January 2012 to December 2017. The univariate and multivariate analyses were performed to assess independent risk factors for overall postoperative complications. A propensity score-matched (PSM) analysis was performed to adjust baseline characteristics between PBD and direct surgery (DS) groups. After PSM, intraoperative data and postoperative complications were compared between the two groups.

Results: A total of 200 patients were included. The rate of overall postoperative complication occurred in 119 (59.5%) patients, with prealbumin <150 mg/L (OR = 3.03; 95%CI = [1.63-5.62]; p < 0.001), ASA (American Society of Anesthesiology score) classification II-III (OR = 2.27; 95%CI = [1.21-4.27]; p = 0.011), and direct surgery (OR = 3.88; 95%CI = [1.67-8.99]; p = 0.002) identified as independent risk factors in multivariate analysis. After PSM, there was similar operative time and intraoperative transfusion between PBD and DS group. However, DS group had a higher incidence of overall postoperative complication (p = 0.005), grades B and C of post-pancreatectomy hemorrhage (PPH) (p = 0.032), and grades B and C of postoperative pancreatic fistula (POPF) (p = 0.045) compared to PBD group.

Conclusions: In this retrospective study, in order to reduce overall postoperative complications, PBD should be performed routinely for those patients with serum total bilirubin level exceeding 250 μmol/L and undergoing pancreaticoduodenectomy.
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http://dx.doi.org/10.1016/j.pan.2020.02.002DOI Listing
April 2020

NmSEER V2.0: a prediction tool for 2'-O-methylation sites based on random forest and multi-encoding combination.

BMC Bioinformatics 2019 Dec 24;20(Suppl 25):690. Epub 2019 Dec 24.

Department of Biomedical Informatics, Department of Physiology and Pathophysiology, Center for Noncoding RNA Medicine, MOE Key Lab of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University, 38 Xueyuan Rd, Beijing, 100191, China.

Background: 2'-O-methylation (2'-O-me or Nm) is a post-transcriptional RNA methylation modified at 2'-hydroxy, which is common in mRNAs and various non-coding RNAs. Previous studies revealed the significance of Nm in multiple biological processes. With Nm getting more and more attention, a revolutionary technique termed Nm-seq, was developed to profile Nm sites mainly in mRNA with single nucleotide resolution and high sensitivity. In a recent work, supported by the Nm-seq data, we have reported a method in silico for predicting Nm sites, which relies on nucleotide sequence information, and established an online server named NmSEER. More recently, a more confident dataset produced by refined Nm-seq was available. Therefore, in this work, we redesigned the prediction model to achieve a more robust performance on the new data.

Results: We redesigned the prediction model from two perspectives, including machine learning algorithm and multi-encoding scheme combination. With optimization by 5-fold cross-validation tests and evaluation by independent test respectively, random forest was selected as the most robust algorithm. Meanwhile, one-hot encoding, together with position-specific dinucleotide sequence profile and K-nucleotide frequency encoding were collectively applied to build the final predictor.

Conclusions: The predictor of updated version, named NmSEER V2.0, achieves an accurate prediction performance (AUROC = 0.862) and has been settled into a brand-new server, which is available at http://www.rnanut.net/nmseer-v2/ for free.
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http://dx.doi.org/10.1186/s12859-019-3265-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929462PMC
December 2019

Polysaccharide enhanced NK cell cytotoxicity against pancreatic cancer via TLR4/MAPKs/NF-κB pathway in vitro/vivo.

Carbohydr Polym 2019 Dec 20;225:115223. Epub 2019 Aug 20.

School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, Jiangsu, 210009, PR China. Electronic address:

A polysaccharide isolated from Strongylocentrotus nudus eggs (SEP) reportedly displays immune activity in vivo. Here, its effect and underlying mechanism in the treatment of pancreatic cancer were investigated. SEP obviously inhibited pancreatic cancer growth by activating NK cells in vitro/vivo via TLR4/MAPKs/NF-κB signaling pathway, The tumor inhibitory rate achieved to 44.5% and 50.8% at a dose of 40 mg/kg in Bxpc-3 and SW1990 nude mice, respectively. Moreover, SEP obviously augmented the Gemcitabine (GEM) antitumor effect by upregulating NKG2D, which improved the sensitivity of NK cells targeting to its ligand MICA; meanwhile, the antitumor inhibitory rate was 68.6% in BxPC-3 tumor-bearing mice. Moreover, SEP reversed GEM-induced apoptosis and atrophy in both spleen and bone marrow via suppressing ROS secretion in vivo. These results suggested that pancreatic cancer was effectively inhibited by SEP-enhanced NK cytotoxicity mediated primarily through TLR4/MAPKs/NF-κB signaling pathway, representing a potential immunotherapy candidate for the treatment of pancreatic cancer.
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http://dx.doi.org/10.1016/j.carbpol.2019.115223DOI Listing
December 2019

Biomaterials and controlled release strategy for epithelial wound healing.

Biomater Sci 2019 Nov 22;7(11):4444-4471. Epub 2019 Aug 22.

Department of Biomedical Materials Engineering, Kangwon National University, Chuncheon, 24341, Republic of Korea. and Institute of Bioscience and Biotechnology, Kangwon National University, Republic of Korea.

The skin and cornea are tissues that provide protective functions. Trauma and other environmental threats often cause injuries, infections and damage to these tissues, where the degree of injury is directly correlated to the recovery time. For example, a superficial skin or corneal wound may recover within days; however, more severe injuries can last up to several months and may leave scarring. Thus, therapeutic strategies have been introduced to enhance the wound healing efficiency and quality. Although the skin and cornea share similar anatomic structures and wound healing process, therapeutic agents and formulations for skin and cornea wound healing differ in accordance with the tissue and wound type. In this review, we describe the anatomy and epithelial wound healing processes of the skin and cornea, and summarize the therapeutic molecules that are beneficial to the respective regeneration process. In addition, biomaterial scaffolds that inherently possess bioactive properties or modified with therapeutic molecules for topical controlled release and enhanced wound healing efficiency are also discussed.
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http://dx.doi.org/10.1039/c9bm00456dDOI Listing
November 2019

PACES: prediction of N4-acetylcytidine (ac4C) modification sites in mRNA.

Sci Rep 2019 07 31;9(1):11112. Epub 2019 Jul 31.

Department of Biomedical Informatics, Department of Physiology and Pathophysiology, Center for Noncoding RNA Medicine, MOE Key Lab of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University, 38 Xueyuan Rd, Beijing, 100191, China.

N4-acetylcytidine (ac4C) is a highly conserved RNA modification and is the first acetylation event described in mRNA. ac4C in mRNA has been demonstrated to be involved in the regulation of mRNA stability, processing and translation, but the exact means by which ac4C works remain unclear. In addition, ac4C is widely distributed within the human transcriptome at physiologically relevant levels and so far only a small fraction of modified sequences have been detected by experiments. In this study, we developed a predictor of ac4C sites in human mRNA named PACES to help mining possible modified motifs. PACES combines two random forest classifiers, position-specific dinucleotide sequence profile and K-nucleotide frequencies. With genomic sequences as input, PACES gives possible modified sequences based on the training model. PACES is freely available at http://www.rnanut.net/paces/.
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http://dx.doi.org/10.1038/s41598-019-47594-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668381PMC
July 2019

Novel alanyl-tRNA synthetase 2 (AARS2) homozygous mutation in a consanguineous Chinese family with premature ovarian insufficiency.

Fertil Steril 2019 09 4;112(3):569-576.e2. Epub 2019 Jul 4.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Biopreservation and Artificial Organs, Hefei, People's Republic of China; Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, People's Republic of China. Electronic address:

Objective: To explore the candidate pathogenic gene in a premature ovarian insufficiency (POI) proband from a consanguineous marriage and detect the potential effects of mutation on cellular energy metabolism.

Design: Genetic and functional studies.

Setting: Reproductive medicine center.

Patient(s): A patient with POI, from a consanguineous family, and her family members were recruited from the Reproductive Center of the First Affiliated Hospital of Anhui Medical University.

Intervention(s): Whole exome sequencing (WES) was performed for the proband. Variation revealed by WES sequencing was validated by Sanger sequencing in her family. Sequencing data were combined with those of other sporadic cases listed in public databases to identify the causative gene.

Main Outcome Measure(s): Rare homozygous nonsynonymous variants were identified and included in subsequent analysis. Metabolic analyzes were performed using Seahorse XFe96 analyzers to measure oxygen consumption and then obtain further results of ATP production and extracellular acidification rate. The differences in energy metabolism measurements between wild type and mutation were analyzed and compared.

Result(s): A novel alanyl-tRNA synthetase 2 (AARS2) homozygous mutation (NM_020745: exon2: c.337G>C: p. G113R) was identified in the aminoacylation region using WES. The mutation was highly conserved among species and predicted to be disease causing. AARS2 encodes mitochondrial alanyl-tRNA synthetase, which attaches alanine onto tRNA-ala. AARS2 mutations were previously reported in female leukodystrophy patients with POI. In mitochondrial stress tests, the ATP productions of the mutation group (3.58 ± 0.46 fmol/min/cell) was significantly lower than that of the wild type group (6.96 ± 1.56 fmol/min/cell).

Conclusion(s): This is the first report of a homozygous pathogenic AARS2 mutation in POI. This mutation may lead to incorrect aminoacylation of tRNA, affect mitochondrial translation, and cause oxidative phosphorylation defects, which may be responsible for POI.
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http://dx.doi.org/10.1016/j.fertnstert.2019.05.005DOI Listing
September 2019

Determination of 20 perfluoroalkyl substances in greenhouse vegetables with a modified one-step pretreatment approach coupled with ultra performance liquid chromatography tandem mass spectrometry(UPLC-MS-MS).

Chemosphere 2019 Jul 9;227:470-479. Epub 2019 Apr 9.

College of Food Science and Engineering, Shandong Agricultural University, Tai'an, 271001, PR China. Electronic address:

A new rapid modified one-step QuEChERS (quick, easy, cheap, effective, rugged, and safe) approach was developed for the simultaneous determination of 20 perfluoroalkyl substances (PFASs) from samples of cucumber, lettuce, eggplant, tomato, and leek. Several parameters were optimized. Similar pretreatment approaches were employed for comparison; the results verified the satisfactory performance of this new method. The detection limits of this method for the selected matrices ranged from 0.003 to 0.034 μg kg, and the method was verified to be satisfactory in terms of precision, accuracy, and matrix effects. 35 greenhouse vegetable samples were determined. PFASs were detected in 26 samples, with perfluorooctanoic acid (PFOA) being detected most frequently and much higher levels of PFBA and PFPeA being found in some samples. The total PFAS concentrations ranged from not detectable to 0.683 μg kg. This method could be applied for large scale determination of vegetables to research the migration and accumulation trends of PFASs from the environment to crops in the future.
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http://dx.doi.org/10.1016/j.chemosphere.2019.04.034DOI Listing
July 2019

LncRNA SNHG7 promotes pancreatic cancer proliferation through ID4 by sponging miR-342-3p.

Cell Biosci 2019 22;9:28. Epub 2019 Mar 22.

1Pancreatic Disease Center, Department of General Surgery, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No.197 Rui Jin Er Road, Shanghai, China.

Background: Small nucleolar RNA host gene 7 (SNHG7) is a novel identified oncogenic gene in tumorigenesis. However, the role that SNHG7 plays in pancreatic cancer (PC) remains unclear. In this study, we aimed to investigate the functional effects of SNHG7 on PC and the possible mechanism.

Methods: The expression levels of SNHG7 in tissues and cell lines were measured by RT-qPCR. Cell viability, apoptosis, migration and invasion were examined to explore the function of SNHG7 on PC. Bioinformatics methods were used to predict the target genes. The mechanism was further investigated by transfection with specific si-RNA, miRNA mimics or miRNA inhibitor. Tumor xenograft was carried out to verify the effects of SNHG7 in vivo.

Results: We found that SNHG7 was overexpressed in both PC tissues and cell lines. High expression level of SNHG7 was correlated with the poor prognosis. SNHG7 knockdown inhibited the proliferation, migration and invasion of PC cells. Moreover, SNHG7 was found to regulate the expression of ID4 via sponging miR-342-3p. Additionally, this finding was supported by in vivo experiments.

Conclusions: LncRNA SNHG7 was overexpressed in PC tissues, and knockdown of SNHG7 suppressed PC cell proliferation, migration and invasion via miR-342-3p/ID4 axis. The results indicated that SNHG7 as a potential target for clinical treatment of PC.
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http://dx.doi.org/10.1186/s13578-019-0290-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431029PMC
March 2019

Should a standard lymphadenectomy include the No. 9 lymph nodes for body and tail pancreatic ductal adenocarcinoma?

Pancreatology 2019 Apr 15;19(3):414-418. Epub 2019 Mar 15.

Department of General Surgery, Ruijin Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China. Electronic address:

Objectives: This study aimed to use a retrospective data base to investigate whether a standard lymphadenectomy during distal pancreatectomy should include the No. 9 lymph nodes (LNs) for resectable pancreatic ductal adenocarcinoma (PDAC) located in the body and tail of the pancreas.

Methods: Data from 169 patients undergoing curative distal pancreatectomy for PDAC between Jan 1, 2013 and Dec 31, 2016 were collected. According to the tumor location, patients were divided into three groups: pancreatic neck tumor, pancreatic body and tail tumor with margin-to-bifurcation-distance (MTBD) ≤ 2.5 cm and pancreatic body and tail tumor with MTBD > 2.5 cm. The metastatic rate of the No. 9 LNs was compared among the 3 groups. The survival outcomes were analyzed.

Results: The involvement rate for No. 9 LNs was 20.7% (6/29) for pancreatic neck tumors, 17.6% (15/85) for body and tail tumors with MTBD ≤ 2.5 cm and 1.8% (1/55) for MTBD > 2.5 cm. The No. 9 LNs were significantly more frequently involved in neck or body and tail tumors with MTBD ≤2.5 cm than with the cases with MTBD >2.5 cm (OR 0.082, P = 0.016). No. 9 LN involvement was not associated with worse survival compared with survival associated with involvement of other LNs (P = 0.780).

Conclusions: For PDAC located in the neck or in the body and tail of the pancreas with MTBD ≤ 2.5 cm, the involvement rate for No. 9 LNs is high. Standard lymphadenectomy should include the No. 9 LNs.
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http://dx.doi.org/10.1016/j.pan.2019.03.005DOI Listing
April 2019

Resection of pancreatic metastatic renal cell carcinoma: experience and long-term survival outcome from a large center in China.

Int J Clin Oncol 2019 Jun 7;24(6):686-693. Epub 2019 Mar 7.

Department of General Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, No.197 Ruijin Number Two Road, Huangpu District, Shanghai, 200025, People's Republic of China.

Purpose: This study aimed to determine the outcome of pancreatic metastatic renal cell carcinoma (PmRCC) after treatment and share the relevent results.

Methods: In total, 13 patients with PmRCC were diagnosed and treated in our institution from December 2013 to October 2017. We retrospectively reviewed the records and analyzed the patient demographics, perioperative outcomes, and overall survival. Simultaneously, our experience including treatment and misdiagnosis was shared.

Results: The median time between nephrectomy and reoperation for pancreatic recurrence was 11 years (range 1-20 years). Four patients had multiple tumors and nine patients had solitary tumor. Five patients accepted distal pancreatectomy, and five patients underwent pancreaticoduodenectomy. One patient underwent total pancreatectomy, one patient underwent duodenum-preserving pancreatic head resection plus distal pancreatectomy, and one patient underwent exploratory laparotomy and gastrointestinal bypass due to widespread metastasis with clear obstructive symptoms. The misdiagnosis rate of preoperative diagnosis at our center was 69.2% (9/13). The median follow-up duration was 26 months (range 7-53 months, until June 2018). By the end of follow-up, 12 patients were alive and one patient died of gastrointestinal bleeding within 1 month after surgery.

Conclusions: PmRCCs are uncommon, but pancreatic metastasectomy has a relatively good prognosis and may, therefore, be a good therapeutic choice for patients with PmRCCs. Because PmRCC occurs long after the primary tumor resection, long-term follow-up is necessary. Besides, detailed medical history and specific manifestation in imaging features could contribute to avoiding misdiagnosis.
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http://dx.doi.org/10.1007/s10147-019-01399-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525119PMC
June 2019

RNAm5Cfinder: A Web-server for Predicting RNA 5-methylcytosine (m5C) Sites Based on Random Forest.

Sci Rep 2018 11 23;8(1):17299. Epub 2018 Nov 23.

Department of Biomedical Informatics, School of Basic Medical Sciences, Center for Noncoding RNA Medicine, Peking University, Beijing, China.

5-methylcytosine (m5C) is a common nucleobase modification, and recent investigations have indicated its prevalence in cellular RNAs including mRNA, tRNA and rRNA. With the rapid accumulation of m5C sites data, it becomes not only feasible but also important to build an accurate model to predict m5C sites in silico. For this purpose, here, we developed a web-server named RNAm5Cfinder based on RNA sequence features and machine learning method to predict RNA m5C sites in eight tissue/cell types from mouse and human. We confirmed the accuracy and usefulness of RNAm5Cfinder by independent tests, and the results show that the comprehensive and cell-specific predictors could pinpoint the generic or tissue-specific m5C sites with the Area Under Curve (AUC) no less than 0.77 and 0.87, respectively. RNAm5Cfinder web-server is freely available at http://www.rnanut.net/rnam5cfinder .
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http://dx.doi.org/10.1038/s41598-018-35502-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251864PMC
November 2018

CAPS Mutations Are Potentially Associated with Unexplained Recurrent Pregnancy Loss.

Am J Pathol 2019 01 17;189(1):124-131. Epub 2018 Oct 17.

Graduate School of Peking Union Medical College, Beijing, China; Center for Genetics, National Research Institute for Family Planning, Beijing, China.

Recurrent pregnancy loss (RPL) is a major concern for women's reproductive health. Several studies have proved that genetics is a major factor leading to unexplained RPL, but the maternal pathogenic genes involved in RPL remain largely unknown. A consanguineous family, including the parents who were cousins and their three daughters who had been diagnosed as having nonsyndromic unexplained RPL, was recruited in this study. A rare homozygous variant in calcyphosine (CAPS; ENST00000588776: c.377delC, p.Leu127Trpfs) might be the potential candidate variant for this RPL family through whole-exome sequencing. Sanger sequencing confirmed that the three affected sisters carried the homozygous p.Leu127Trpfs, whereas their parents carried the heterozygous p.Leu127Trpfs. CAPS encodes a Ca-binding protein and may play a role in the regulation of Ca transport. Although the precise underlying mechanisms remain unclear, the previous study suggested that they may be involved in cross talk between Ca signaling and cAMP-protein kinase A pathways, which are crucial to embryo implantation and pregnancy maintenance. Knockdown of CAPS expression might promote the expression of secreted phosphoprotein 1 and matrix metalloproteinase 9, and the release of prostaglandin E, which all played important roles in embryo implantation and early pregnancy maintenance. These results indicated that the autosomal recessive homozygous mutation, p.Leu127Trpfs, in CAPS might be a maternal effect causative mutation of RPL pathogenesis.
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http://dx.doi.org/10.1016/j.ajpath.2018.09.010DOI Listing
January 2019

LncRNADisease 2.0: an updated database of long non-coding RNA-associated diseases.

Nucleic Acids Res 2019 01;47(D1):D1034-D1037

Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, China.

Mounting evidence suggested that dysfunction of long non-coding RNAs (lncRNAs) is involved in a wide variety of diseases. A knowledgebase with systematic collection and curation of lncRNA-disease associations is critically important for further examining their underlying molecular mechanisms. In 2013, we presented the first release of LncRNADisease, representing a database for collection of experimental supported lncRNA-disease associations. Here, we describe an update of the database. The new developments in LncRNADisease 2.0 include (i) an over 40-fold lncRNA-disease association enhancement compared with the previous version; (ii) providing the transcriptional regulatory relationships among lncRNA, mRNA and miRNA; (iii) providing a confidence score for each lncRNA-disease association; (iv) integrating experimentally supported circular RNA disease associations. LncRNADisease 2.0 documents more than 200 000 lncRNA-disease associations. We expect that this database will continue to serve as a valuable source for potential clinical application related to lncRNAs. LncRNADisease 2.0 is freely available at http://www.rnanut.net/lncrnadisease/.
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http://dx.doi.org/10.1093/nar/gky905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324086PMC
January 2019