Publications by authors named "Xiao Chang"

195 Publications

Interobserver variability in target volume delineation in definitive radiotherapy for thoracic esophageal cancer: a multi-center study from China.

Radiat Oncol 2021 Jun 9;16(1):102. Epub 2021 Jun 9.

Department of Radiation Oncology, Beijing Hospital, National Center of Gerontology, Beijing, 100730, People's Republic of China.

Purpose: To investigate the interobserver variability (IOV) in target volume delineation of definitive radiotherapy for thoracic esophageal cancer (TEC) among cancer centers in China, and ultimately improve contouring consistency as much as possible to lay the foundation for multi-center prospective studies.

Methods: Sixteen cancer centers throughout China participated in this study. In Phase 1, three suitable cases with upper, middle, and lower TEC were chosen, and participants were asked to contour a group of gross tumor volume (GTV-T), nodal gross tumor volume (GTV-N) and clinical target volume (CTV) for each case based on their routine experience. In Phase 2, the same clinicians were instructed to follow a contouring protocol to re-contour another group of target volume. The variation of the target volume was analyzed and quantified using dice similarity coefficient (DSC).

Results: Sixteen clinicians provided routine volumes, whereas ten provided both routine and protocol volumes for each case. The IOV of routine GTV-N was the most striking in all cases, with the smallest DSC of 0.37 (95% CI 0.32-0.42), followed by CTV, whereas GTV-T showed high consistency. After following the protocol, the smallest DSC of GTV-N was improved to 0.64 (95% CI 0.45-0.83, P = 0.005) but the DSC of GTV-T and CTV remained constant in most cases.

Conclusion: Variability in target volume delineation was observed, but it could be significantly reduced and controlled using mandatory interventions.
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http://dx.doi.org/10.1186/s13014-020-01691-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188796PMC
June 2021

Antibody-based CCR5 blockade protects Macaques from mucosal SHIV transmission.

Nat Commun 2021 06 7;12(1):3343. Epub 2021 Jun 7.

Vaccine & Gene Therapy Institute, Portland, OR, USA.

In the absence of a prophylactic vaccine, the use of antiretroviral therapy (ART) as pre-exposure prophylaxis (PrEP) to prevent HIV acquisition by uninfected individuals is a promising approach to slowing the epidemic, but its efficacy is hampered by incomplete patient adherence and ART-resistant variants. Here, we report that competitive inhibition of HIV Env-CCR5 binding via the CCR5-specific antibody Leronlimab protects rhesus macaques against infection following repeated intrarectal challenges of CCR5-tropic SHIV. Injection of Leronlimab weekly at 10 mg/kg provides significant but partial protection, while biweekly 50 mg/kg provides complete protection from SHIV acquisition. Tissue biopsies from protected macaques post challenge show complete CCR5 receptor occupancy and an absence of viral nucleic acids. After Leronlimab washout, protected macaques remain aviremic, and adoptive transfer of hematologic cells into naïve macaques does not transmit viral infection. These data identify CCR5 blockade with Leronlimab as a promising approach to HIV prophylaxis and support initiation of clinical trials.
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http://dx.doi.org/10.1038/s41467-021-23697-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184841PMC
June 2021

Comparison of Two Major Staging Systems in Predicting Survival and Recommendation of Postoperative Radiotherapy Based on the 11th Japanese Classification for Esophageal Carcinoma After Curative Resection: A Propensity Score-Matched Analysis.

Ann Surg Oncol 2021 May 9. Epub 2021 May 9.

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: The aim of this study was to compare the prognostic predictive power of the 11th Japan Esophageal Society (JES) staging system with the 8th edition of the American Joint Committee on Cancer (AJCC) staging system in patients with thoracic esophageal squamous cell carcinoma (TESCC), and to estimate the survival benefits of postoperative radiotherapy (PORT) based on a substage of the JES staging system.

Methods: Area under the curve (AUC) values of the receiver operating characteristic curve were calculated to evaluate prognostic efficacy. Propensity score matching (PSM) analysis was conducted to balance the two groups (surgery only [S group] or surgery plus PORT [S+RT group]) across substages of the 11th JES staging system according to independent prognostic factors for overall survival (OS) identified using Cox proportional hazards regression.

Results: A total of 2960 patients were eligible. The 5-year OS AUC for the 8th AJCC staging system was significantly higher than that for the 11th JES staging system (0.701 vs. 0.675, p < 0.001). Before PSM, PORT significantly improved 5-year OS rates for patients in stage III and IVA by 9.1% (p < 0.001) and 21.1% (p < 0.001), respectively. After PSM, the 5-year OS rates in stage II, III, and IVA of the S+RT group were significantly higher than those in the S group (70.9%, 39.7%, and 35.1% vs. 57.8%, 27.2%, and 10.3%, respectively; p < 0.001).

Conclusion: The 11th JES staging system was less capable of predicting prognosis than the 8th AJCC staging system and patients in stage III of the JES staging system were highly recommended to undergo PORT.
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http://dx.doi.org/10.1245/s10434-021-10046-6DOI Listing
May 2021

Combined application of genetic and polygenic risk scores for type 1 diabetes risk prediction.

Diabetes Obes Metab 2021 May 5. Epub 2021 May 5.

Centre for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

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http://dx.doi.org/10.1111/dom.14419DOI Listing
May 2021

Concurrent chemoradiotherapy versus radiotherapy alone for patients with locally advanced esophageal squamous cell carcinoma in the era of intensity modulated radiotherapy: a propensity score-matched analysis.

Thorac Cancer 2021 Jun 5;12(12):1831-1840. Epub 2021 May 5.

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: To investigate the survival benefit of concurrent chemoradiotherapy (CCRT) for patients with locally advanced esophageal squamous cell carcinoma (ESCC) during the years of intensity-modulated radiotherapy (IMRT).

Methods: Medical records of 1089 patients with ESCC who received IMRT from January 2005 to December 2017 were retrospectively reviewed. A total of 617 patients received CCRT, 472 patients received radiotherapy (RT) alone. Propensity score matching (PSM) method was used to eliminate baseline differences between the two groups. Survival and toxicity profile were evaluated afterward.

Results: After a median follow-up time of 47.9 months (3.2-149.8 months), both overall survival (OS) and progression-free survival (PFS) of the CCRT group were better than those of the RT alone group, either before or after PSM. After PSM, the 1-, 3-, and 5-year OS of RT alone and CCRT groups were 59.0% versus 70.2%, 27.7% versus 40.5% and 20.3% versus 33.1%, respectively (p < 0.001). The 1-, 3-, and 5-year PFS were 39.4% versus 49.0%, 18.3% versus 30.4% and 10.5% versus 25.0%, respectively (p < 0.001). The rates of ≥ grade 3 leukopenia and radiation esophagitis in the CCRT group were higher than that of RT alone group (p < 0.05). There was no significant difference in the probability of radiation pneumonitis between the two groups (p = 0.167). Multivariate Cox analysis indicated that female, EQD2 ≥60 Gy and concurrent chemotherapy were favorable prognostic factors for both OS and PFS.

Conclusions: Concurrent chemotherapy can bring survival benefits to patients with locally advanced ESCC receiving IMRT. For patients who cannot tolerate concurrent chemotherapy, RT alone is an effective alternative with promising results.
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http://dx.doi.org/10.1111/1759-7714.13971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201542PMC
June 2021

Genetic correlations between COVID-19 and a variety of traits and diseases.

Innovation (N Y) 2021 May 29;2(2):100112. Epub 2021 Apr 29.

The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

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http://dx.doi.org/10.1016/j.xinn.2021.100112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081576PMC
May 2021

Machine Learning Reduced Gene/Non-Coding RNA Features That Classify Schizophrenia Patients Accurately and Highlight Insightful Gene Clusters.

Int J Mol Sci 2021 Mar 25;22(7). Epub 2021 Mar 25.

Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

RNA-seq has been a powerful method to detect the differentially expressed genes/long non-coding RNAs (lncRNAs) in schizophrenia (SCZ) patients; however, due to overfitting problems differentially expressed targets (DETs) cannot be used properly as biomarkers. This study used machine learning to reduce gene/non-coding RNA features. Dorsolateral prefrontal cortex (dlpfc) RNA-seq data from 254 individuals was obtained from the CommonMind consortium. The average predictive accuracy for SCZ patients was 67% based on coding genes, and 96% based on long non-coding RNAs (lncRNAs). Machine learning is a powerful algorithm to reduce functional biomarkers in SCZ patients. The lncRNAs capture the characteristics of SCZ tissue more accurately than mRNA as the former regulate every level of gene expression, not limited to mRNA levels.
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http://dx.doi.org/10.3390/ijms22073364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037538PMC
March 2021

Clinical practice and outcome of radiotherapy for advanced esophageal squamous cell carcinoma between 2002 and 2018 in China: the multi-center 3JECROG Survey.

Acta Oncol 2021 May 1;60(5):627-634. Epub 2021 Apr 1.

Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Purpose: To determine the survival and prognostic factors of esophageal squamous cell carcinoma (ESCC) patients undergoing radical (chemo)radiotherapy in the era of three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) in China.

Material And Methods: The Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) conducted the first nationwide survey of nine institutions. Detailed information was accumulated on 5185 patients with ESCC who received definitive 3DCRT/IMRT between 2002 and 2018. Relevant prognostic factors were evaluated to assess their influence on overall and progression-free survivals.

Results: After a median follow-up time of 47.0 (0.9-157.4) months, the 1-year, 2-year, 3-year and 5-year overall survival rates of the whole group were 69.8%, 46.6%, 37.9% and 30.1%. The 1-year, 2-year, 3-year, and 5-year progression-free survival rates were 54.1%, 36.6%, 30.5% and 24.9%. Multivariate analysis demonstrated that sex, clinical stage, treatment modality and radiation dose were prognostic factors for OS. The survival of patients who received concurrent chemoradiotherapy (CCRT) was better than that of patients who received radiotherapy alone or sequential chemoradiotherapy. Patients receiving adjuvant chemotherapy after CCRT had a better OS than patients receiving CCRT alone. Patients receiving higher radiation dose had a better OS than those patients receiving low-dose radiotherapy.

Conclusions: The survival of ESCC patients undergoing radical (chemo)radiotherapy was relatively satisfactory in the era of 3DCRTand IMRT. As the largest-scale multicenter research on esophageal cancer radiotherapy conducted in China, this study establishes national benchmarks and helps to provide references for subsequent related researches.
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http://dx.doi.org/10.1080/0284186X.2021.1902564DOI Listing
May 2021

China artificial joint annual data report.

Chin Med J (Engl) 2020 Nov 3;134(6):752-753. Epub 2020 Nov 3.

Department of Orthopaedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

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http://dx.doi.org/10.1097/CM9.0000000000001196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990009PMC
November 2020

Rare Recurrent Variants in Noncoding Regions Impact Attention-Deficit Hyperactivity Disorder (ADHD) Gene Networks in Children of both African American and European American Ancestry.

Genes (Basel) 2021 Feb 22;12(2). Epub 2021 Feb 22.

Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with poorly understood molecular mechanisms that results in significant impairment in children. In this study, we sought to assess the role of rare recurrent variants in non-European populations and outside of coding regions. We generated whole genome sequence (WGS) data on 875 individuals, including 205 ADHD cases and 670 non-ADHD controls. The cases included 116 African Americans (AA) and 89 European Americans (EA), and the controls included 408 AA and 262 EA. Multiple novel rare recurrent variants were identified in exonic regions, functionally classified as stop-gains and frameshifts for known ADHD genes. Deletion in introns of the protocadherins families and the ncRNA were identified in two independent EA ADHD patients. A meta-analysis of the two ethnicities for differential ADHD recurrent variants compared to controls shows a small number of overlaps. These results suggest that rare recurrent variants in noncoding regions may be involved in the pathogenesis of ADHD in children of both AA and EA ancestry; thus, WGS could be a powerful discovery tool for studying the molecular mechanisms of ADHD.
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http://dx.doi.org/10.3390/genes12020310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927037PMC
February 2021

MONTAGE: a new tool for high-throughput detection of mosaic copy number variation.

BMC Genomics 2021 Feb 24;22(1):133. Epub 2021 Feb 24.

Department of Pediatrics, Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA.

Background: Not all cells in a given individual are identical in their genomic makeup. Mosaicism describes such a phenomenon where a mixture of genotypic states in certain genomic segments exists within the same individual. Mosaicism is a prevalent and impactful class of non-integer state copy number variation (CNV). Mosaicism implies that certain cell types or subset of cells contain a CNV in a segment of the genome while other cells in the same individual do not. Several studies have investigated the impact of mosaicism in single patients or small cohorts but no comprehensive scan of mosaic CNVs has been undertaken to accurately detect such variants and interpret their impact on human health and disease.

Results: We developed a tool called Montage to improve the accuracy of detection of mosaic copy number variants in a high throughput fashion. Montage directly interfaces with ParseCNV2 algorithm to establish disease phenotype genome-wide association and determine which genomic ranges had more or less than expected frequency of mosaic events. We screened for mosaic events in over 350,000 samples using 1% allele frequency as the detection limit. Additionally, we uncovered disease associations of multiple phenotypes with mosaic CNVs at several genomic loci. We additionally investigated the allele imbalance observations genome-wide to define non-diploid and non-integer copy number states.

Conclusions: Our novel algorithm presents an efficient tool with fast computational runtime and high levels of accuracy of mosaic CNV detection. A curated mosaic CNV callset of 3716 events in 2269 samples is presented with comparability to previous reports and disease phenotype associations. The new algorithm can be freely accessed via: https://github.com/CAG-CNV/MONTAGE .
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http://dx.doi.org/10.1186/s12864-021-07395-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905641PMC
February 2021

Effect of broflanilide on the phytophagous mite Tetranychus urticae and the predatory mite Typhlodromips swirskii.

Pest Manag Sci 2021 Jun 15;77(6):2964-2970. Epub 2021 Mar 15.

College of Plant Protection, Nanjing Agricultural University, Nanjing, P.R. China.

Background: Two-spotted spider mite (TSSM), Tetranychus urticae Koch, is one of the most serious pests of agricultural crops. Broflanilide exhibits high lethality against various pests and has been marketed worldwide under the Vedira and Tenebenal brands in 2020. Nevertheless, little information has been reported about its effects on agricultural mites.

Results: Broflanilide displayed higher toxicity to TSSM eggs (24 h LC , 1.015 mg L ) and adult females (24 h LC , 2.062 mg L ) than commercial acaricides, including cyflumetofen, bifenazate, and profenofos. In contrast, the adverse effects of broflanilide on the predatory mite, Typhlodromips swirskii Athias-Henriot, was lower than those of fenpyroximate and abamectin. In the sublethal effect study, while adult females were treated with broflanilide, the number of eggs and longevity were reduced in LC and LC treatments; when eggs were treated with broflanilide, the egg duration and deutonymph duration were prolonged in LC treatment. A significant decrease in the total life span and duration and fecundity of adult females was observed in LC and LC treatments. Furthermore, the number of eggs per adult female was significantly reduced from 103.48 ± 3.69 in the control group to 69.42 ± 2.22 and 48.33 ± 1.75 in LC and LC treatments, respectively. In the greenhouse bioassay, broflanilide 5% suspension concentrate (MCI-8007) showed excellent acaricidal activity to TSSM, with 99.22% corrected control, compared with the MCI-8007 untreated group.

Conclusion: Our results indicated that broflanilide has a high acaricidal activity to TSSM and significant inhibition to fecundity of adult female, and could be considered as a potential alternative for TSSM management. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.6335DOI Listing
June 2021

Inference of gene regulatory networks using pseudo-time series data.

Bioinformatics 2021 Feb 12. Epub 2021 Feb 12.

Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310012, China.

Motivation: Inferring gene regulatory networks (GRNs) from high-throughput data is an important and challenging problem in systems biology. Although numerous GRN methods have been developed, most have focused on the verification of the specific data set. However, it is difficult to establish directed topological networks that are both suitable for time-series and non-time-series datasets due to the complexity and diversity of biological networks.

Results: Here, we proposed a novel method, GNIPLR (Gene networks inference based on projection and lagged regression) to infer GRNs from time-series or non-time-series gene expression data. GNIPLR projected gene data twice using the LASSO projection (LSP) algorithm and the linear projection (LP) approximation to produce a linear and monotonous pseudo-time series, and then determined the direction of regulation in combination with lagged regression analyses. The proposed algorithm was validated using simulated and real biological data. Moreover, we also applied the GNIPLR algorithm to the liver hepatocellular carcinoma (LIHC) and bladder urothelial carcinoma (BLCA) cancer expression datasets. These analyses revealed significantly higher accuracy and AUC values than other popular methods.

Availability: The GNIPLR tool is freely available at https://github.com/zyllluck/GNIPLR.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab099DOI Listing
February 2021

Diffusion MRI derived free-water imaging measures in patients with schizophrenia and their non-psychotic siblings.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Jul 2;109:110238. Epub 2021 Jan 2.

Department of Psychiatry, University Medical Center Utrecht (UMCU), UMCU Brain Center, Utrecht, the Netherlands; Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Boston, USA.

Free-water imaging is a diffusion MRI technique that separately models water diffusion hindered by fiber tissue and water that disperses freely in the extracellular space. Studies using this technique have shown that schizophrenia is characterized by a lower level of fractional anisotropy of the tissue compartment (FA) and higher free-water fractional volume (FW). It is unknown, however, whether such abnormalities are an expression of pre-existing (genetic) risk for schizophrenia or a manifestation of the illness. To investigate the contribution of familial risk factors to white matter abnormalities, we used the free-water imaging technique to assess FA and FW in a large cohort of 471 participants including 161 patients with schizophrenia, 182 non-psychotic siblings, and 128 healthy controls. In this sample, patients did not show significant differences in FA as compared to controls, but did exhibit a higher level of FW relative to both controls and siblings in the left uncinate fasciculus, superior corona radiata and fornix / stria terminalis. This increase in FW was found to be related to, though not solely explained by, ventricular enlargement. Siblings did not show significant FW abnormalities. However, siblings did show a higher level of FA as compared to controls and patients, in line with results of a previous study on the same data using conventional DTI. Taken together, our findings suggest that extracellular free-water accumulation in patients is likely a manifestation of established disease rather than an expression of familial risk for schizophrenia and that super-normal levels of FA in unaffected siblings may reflect a compensatory process.
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http://dx.doi.org/10.1016/j.pnpbp.2020.110238DOI Listing
July 2021

Biosafety and biocompatibility assessment of Prussian blue nanoparticles and .

Nanomedicine (Lond) 2020 11 12;15(27):2655-2670. Epub 2020 Nov 12.

Key Laboratory of Study & Discovery of Small Targeted Molecules of Hunan Province School of Medicine, Hunan Normal University, Changsha 410125, PR China.

To investigate the effects of the different morphological characteristics of Prussian blue nanoparticles PB NPs) on their biocompatibility and biosafety. PB NPs with different sizes, shapes and charges were synthesized and their biosafety and biocompatibility performance were systematically compared and . Increased size and positive charge of PB NPs adversely affected cell viability, while improving their peroxidase activity and photothermal conversion efficiency. analysis demonstrated good biocompatibility of PB NPs, without retention in the organs, but increased size retarded their metabolism. Meanwhile, increased size and positive charge adversely affected hepatic and renal function. This comprehensive exploration of biosafety and biocompatibility provides strong evidences for the use of PB NPs as nanodrug carrier and/or imaging agent.
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http://dx.doi.org/10.2217/nnm-2020-0191DOI Listing
November 2020

Association of DLL1 with type 1 diabetes in patients characterized by low polygenic risk score.

Metabolism 2021 01 4;114:154418. Epub 2020 Nov 4.

The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Division of Pulmonary Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. Electronic address:

Type 1 diabetes (T1D) is a heterogeneous disease. This study identified T1D cases with low polygenic risk score (PRS) to better represent T1D cases with less prominent autoimmune response (T1bD), and performed a gene-based association study to identify novel susceptibility loci in two independent cohorts, characterized by low PRS. The Notch ligand Delta-like 1 gene (DLL1) was identified with genome-wide significance in both cohorts, highlighting the roles of DLL1 genetic variants in T1D patients with low PRS, supported by functional evidence from a recent study by Rubey et al.
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http://dx.doi.org/10.1016/j.metabol.2020.154418DOI Listing
January 2021

Mitochondrial DNA haplogroups and risk of attention deficit and hyperactivity disorder in European Americans.

Transl Psychiatry 2020 11 2;10(1):370. Epub 2020 Nov 2.

Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Although mitochondrial dysfunction has been implicated in the pathophysiology of attention deficit and hyperactivity disorder ADHD, the role of mitochondrial DNA (mtDNA) has not been extensively investigated. To determine whether mtDNA haplogroups influence risk of ADHD, we performed a case-control study comprising 2076 ADHD cases and 5078 healthy controls, all of whom were European decedents recruited from The Children's Hospital of Philadelphia (CHOP). Associations between eight major European mtDNA Haplogroups and ADHD risk were assessed in three independent European cohorts. Meta-analysis of the three studies indicated that mtDNA haplogroups K (odds ratio = 0.69, P = 2.24 × 10, P = 1.79 × 10) and U (odds ratio = 0.77, P = 8.88 × 10, P = 7.11 × 10) were significantly associated with reduced risk of ADHD. In contrast, haplogroup HHV* (odds ratio = 1.18, P = 2.32 × 10, P = 0.019) was significantly associated with increased risk of ADHD. Our results provide novel insight into the genetic basis of ADHD, implicating mitochondrial mechanisms in the pathophysiology of this relatively common psychiatric disorder.
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http://dx.doi.org/10.1038/s41398-020-01064-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608630PMC
November 2020

Bioinspired Anti-Oil-Fouling Hierarchical Structured Membranes Decorated with Urchin-Like α-FeOOH Particles for Efficient Oil/Water Mixture and Crude Oil-in-Water Emulsion Separation.

ACS Appl Mater Interfaces 2020 Nov 3;12(45):50962-50970. Epub 2020 Nov 3.

State Key Laboratory of Heavy Oil Processing, School of Materials Science and Engineering, China University of Petroleum, Qingdao, Shandong 266580, P. R. China.

Designing and constructing a stable water-retention layer acting as the isolation between the oil and membrane surface holds great significance for solving the membrane fouling problems in oil/water separation, including common layered oil/water mixtures, immiscible oil-in-water emulsions, and even high-viscosity crude oil-in-water emulsions. Inspired by the self-cleaning property of sea urchin thorns, a bioinspired anti-oil-fouling hierarchically structured membranes decorated with urchin-like α-FeOOH particles was successfully prepared via the layer-by-layer (LBL) self-assembly method, maintaining numerous effective micro-nanopores. The hierarchical structured membrane exhibited superior superhydrophilicity/underwater superoleophobicity, high water-retention ability, and preferable anti-oil-fouling properties. Furthermore, the biomimetic membrane with controllable pore sizes could not only separate common layered oil/water mixtures but also effectively separate immiscible surfactant-stabilized oil-in-water emulsions of both low-viscosity crude oil and high-viscosity crude oil with an ultrahigh water flux up to 2598.4 L m h and an outstanding separation efficiency of 98.5%, revealing its promising prospect in oily wastewater treatment.
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http://dx.doi.org/10.1021/acsami.0c11677DOI Listing
November 2020

Analysing the meta-interaction between pathways by gene set topological impact analysis.

BMC Genomics 2020 Oct 27;21(1):748. Epub 2020 Oct 27.

College of Agronomy, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.

Background: Pathway analysis is widely applied in transcriptome analysis. Given certain transcriptomic changes, current pathway analysis tools tend to search for the most impacted pathways, which provides insight into underlying biological mechanisms. Further refining of the enriched pathways and extracting functional modules by "crosstalk" analysis have been proposed. However, the upstream/downstream relationships between the modules, which may provide extra biological insights such as the coordination of different functional modules and the signal transduction flow have been ignored.

Results: To quantitatively analyse the upstream/downstream relationships between functional modules, we developed a novel GEne Set Topological Impact Analysis (GESTIA), which could be used to assemble the enriched pathways and functional modules into a super-module with a topological structure. We showed the advantages of this analysis in the exploration of extra biological insight in addition to the individual enriched pathways and functional modules.

Conclusions: GESTIA can be applied to a broad range of pathway/module analysis result. We hope that GESTIA may help researchers to get one additional step closer to understanding the molecular mechanism from the pathway/module analysis results.
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http://dx.doi.org/10.1186/s12864-020-07148-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592530PMC
October 2020

A new index (A/G) associated with early complications of radical cystectomy and intestinal urinary diversion.

Urol Oncol 2021 May 6;39(5):301.e11-301.e16. Epub 2020 Oct 6.

Department of Urology, Chinese PLA General Hospital, Beijing, China. Electronic address:

Objectives: To put forward a new index (A/G, the postoperative ratio of albumin to blood glucose) associated with complications occurring within 30-day of radical cystectomy and intestinal urinary diversion (RC-IUD).

Patients And Methods: The charts of 565 patients undergoing RC-IUD at our single center between 2008 and 2018 were reviewed. All baseline information and perioperative data were collected. We finally picked up 360 of them with complete postoperative laboratory test results to find a new index. Early complications (within 30-day) after surgery were graded using the standardized Clavien-Dindo scale. Single and multivariate logistic regression determined the association between perioperative variables and post RC-IUD complications.

Results: A total of 485 men and 80 women with a median age of 61 years and BMI of 24.8 were included. As for intestinal urinary diversion, most patients (n = 513, 90.8%) received ileal conduits, 47 (8.3%) received Ileal orthotopic neobladders and 5 received Mainz pouch bladders (0.9%). Robotic surgeries were conducted in 311(55.0%) patients and other 254 (45.0%) accepted laparoscopic surgeries. Available laboratory markers were obtained from 359 cases. Postoperative complications occurred in 129 patients (22.8%), including 117 (90.7%) Minor (Clavien I or Clavien II events) complications, and 12 (9.3%) major (Clavien III or greater events) complications. A single logistic regression identified 4 variables associated with postoperative complications, including hypertension, surgical procedures, postoperative A/G, operating time, and blood loss. A further multivariate logistic regression identified 2 significant indices: operating time and postoperative A/G. Moreover, we built a receiver operating characteristic curve of A/G to identify a threshold of 3.65 as a new indicator of postoperative complication.

Conclusions: We put forward a new index named A/G associated with complications after radical cystectomy, not singular considering albumin or blood glucose any more. This novel related index may provide an early alert for RC-IUD patients thus aiding in directing individual rehabilitation and improving postoperative outcomes after RC-IUD.
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http://dx.doi.org/10.1016/j.urolonc.2020.09.023DOI Listing
May 2021

S-1-Based Chemoradiotherapy Followed by Consolidation Chemotherapy With S-1 in Elderly Patients With Esophageal Squamous Cell Carcinoma: A Multicenter Phase II Trial.

Front Oncol 2020 28;10:1499. Epub 2020 Aug 28.

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Intensive treatments can often not be administered to elderly patients with esophageal squamous cell carcinoma (ESCC), leading to a poorer prognosis. This multi-center phase II trial aimed to determine the toxicity profile and efficiency of S-1-based simultaneous integrated boost radiotherapy (SIB-RT) followed by consolidation chemotherapy with S-1 in elderly ESCC patients and to evaluate the usefulness of comprehensive geriatric assessment (CGA). We prospectively enrolled 46 elderly patients (age ≥ 70 years) with histopathologically proven ESCC. The patients underwent pretreatment CGA followed by SIB-RT (dose, 59.92 Gy/50.4 Gy) in 28 daily fractions administered using intensity-modulated radiotherapy or volumetric-modulated arc therapy. S-1 was orally administered (40-60 mg/m) concurrently with radiotherapy and 4-8 weeks later, for up to four 3-week cycles at the same dose. The median survival time was 22.6 months. The 1- and 2-year overall survival rates were 80.4 and 47.8%, respectively. The overall response rate was 78.3% (36/46). The incidence of grade 3-4 toxicities was 28% (13/46). The most common grade 3-4 toxicities were radiation esophagitis (5/46, 10.9%), nausea (4/46, 8.7%), anorexia (3/46, 6.5%), and radiation pneumonitis (3/46, 6.5%). There were no grade 5 toxicities. CGA identified that 48.8% of patients were at risk for depression and 65.5% had malnutrition. Concurrent S-1 treatment with SIB-RT followed by 4 cycles of S-1 monotherapy yielded satisfactory tumor response rates and manageable toxicities in selected elderly patients with ESCC. Pretreatment CGA uncovered numerous health problems and allowed the provision of appropriate supportive care. www.ClinicalTrials.gov, identifier: NCT02979691.
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http://dx.doi.org/10.3389/fonc.2020.01499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484368PMC
August 2020

A multicenter prospective phase III clinical randomized study of simultaneous integrated boost intensity-modulated radiotherapy with or without concurrent chemotherapy in patients with esophageal cancer: 3JECROG P-02 study protocol.

BMC Cancer 2020 Sep 22;20(1):901. Epub 2020 Sep 22.

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Background: Since the development of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy (IMRT), no prospective study has investigated whether concurrent chemoradiotherapy (SIB-IMRT with 60 Gy) remains superior to radiotherapy (SIB-IMRT) alone for unresectable esophageal cancer (EC). Furthermore, the optimal therapeutic regimen for patients who cannot tolerate concurrent chemoradiotherapy is unclear. We recently completed a phase I/II radiation dose-escalation trial using simultaneous integrated boost (SIB), elective nodal irradiation, and concurrent chemotherapy for unresectable EC. We now intend to conduct a prospective, phase III, randomized study of SIB-IMRT with or without concurrent chemotherapy. We aim to find a safe, practical, and effective therapeutic regimen to replace the conventional segmentation (1.8-2.0 Gy) treatment mode (radiotherapy ± chemotherapy) for unresectable EC.

Methods: This two-arm, open, randomized, multicenter, phase III trial will recruit esophageal squamous cell carcinoma patients (stage IIA-IVB [UICC 2002]; IVB only with metastasis to the supraclavicular or celiac lymph nodes). In all, 164 patients will be randomized using a 1:1 allocation ratio, and stratified by study site and disease stage, especially the extent of lymph node metastasis. Patients in the SIB arm will receive definitive SIB radiotherapy (95% planning target volume/planning gross tumor volume, 50.4 Gy/59.92 Gy/28 f, equivalent dose in 2-Gy fractions = 60.62 Gy). Patients in the SIB + concurrent chemotherapy arm will receive definitive SIB radiotherapy with weekly paclitaxel and a platinum-based drug (5-6 weeks). Four cycles of consolidated chemoradiotherapy will also be recommended. The primary objective is to compare the 1-year, 2-year, and 3-year overall survival of the SIB + chemotherapy group and SIB groups. Secondary objectives include progression-free survival, local recurrence-free rate, completion rate, and adverse events. Detailed radiotherapy protocol and quality-assurance procedures have been incorporated into this trial.

Discussion: In unresectable, locally advanced EC, a safe and effective total radiotherapy dose and reasonable segmentation doses are required for the clinical application of SIB-IMRT + two-drug chemotherapy. Whether this protocol will replace the standard treatment regimen will be prospectively investigated. The effects of SIB-IMRT in patients with poor physical condition who cannot tolerate definitive chemoradiotherapy will also be investigated.

Trial Registration: clinicaltrials.gov ( NCT03308552 , November 1, 2017).
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http://dx.doi.org/10.1186/s12885-020-07387-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510301PMC
September 2020

Urachal Carcinoma: Are Lymphadenectomy and Umbilectomy Necessary?

Med Sci Monit 2020 Sep 22;26:e927913. Epub 2020 Sep 22.

Department of Urology/State Key Laboratory of Kidney Diseases, Chinese People's Liberation Army (PLA) General Hospital/PLA Medical School, Beijing, China (mainland).

BACKGROUND The aim of this study was to explore the impact of lymphadenectomy and umbilectomy on long-term survival and progression-free survival (PFS) of patients with urachal carcinoma. MATERIAL AND METHODS We performed a retrospective analysis of 39 patients with urachal carcinoma. Clinicopathologic outcomes were evaluated, and overall survival (OS) and PFS were assessed by Kaplan-Meier method and Cox regression analysis. RESULTS Thirty-four (87.2%) patients underwent partial cystectomy, and 3 (7.7%) patients underwent radical cystectomy with en bloc urachal resection. Eighteen (46.2%) patients underwent lymphadenectomy and 27 (69.2%) patients had umbilectomy. Multivariate analysis showed that tumor size (P=0.011), Mayo stage (P=0.012), and umbilectomy (P=0.007) were the independent prognostic factors for OS. The median overall survival time was 67 months. The differentiation degree of tumor (P=0.049), Mayo stage (P=0.004), and umbilectomy (P=0.046) were the independent prognostic factors for PFS. Lymph node resection was not a predictor of OS. Patients had poorer prognosis when the tumor invaded the entire wall, including the mucous layer, muscular layer, and serous layer of the bladder compared with those that invaded only the muscular layer (P=0.014). CONCLUSIONS Lymph node metastases and failure to undergo umbilectomy were the independent prognostic factors for OS and PFS. Lymph node resection was not a predictor of OS. Patients had poorer prognosis when the tumor invaded the entire wall of the bladder compared with those that invaded the muscular layer.
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http://dx.doi.org/10.12659/MSM.927913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519942PMC
September 2020

Non-coding structural variation differentially impacts attention-deficit hyperactivity disorder (ADHD) gene networks in African American vs Caucasian children.

Sci Rep 2020 09 17;10(1):15252. Epub 2020 Sep 17.

Center for Applied Genomics, Children's Hospital of Philadelphia, 3615 Civic Center Blvd, Abramson Building, Philadelphia, PA, 19104, USA.

Previous studies of attention-deficit hyperactivity disorder (ADHD) have suggested that structural variants (SVs) play an important role but these were mainly studied in subjects of European ancestry and focused on coding regions. In this study, we sought to address the role of SVs in non-European populations and outside of coding regions. To that end, we generated whole genome sequence (WGS) data on 875 individuals, including 205 ADHD cases and 670 non-ADHD controls. The ADHD cases included 116 African Americans (AA) and 89 of European Ancestry (EA) with SVs in comparison with 408 AA and 262 controls, respectively. Multiple SVs and target genes that associated with ADHD from previous studies were identified or replicated, and novel recurrent ADHD-associated SV loci were discovered. We identified clustering of non-coding SVs around neuroactive ligand-receptor interaction pathways, which are involved in neuronal brain function, and highly relevant to ADHD pathogenesis and regulation of gene expression related to specific ADHD phenotypes. There was little overlap (around 6%) in the genes impacted by SVs between AA and EA. These results suggest that SVs within non-coding regions may play an important role in ADHD development and that WGS could be a powerful discovery tool for studying the molecular mechanisms of ADHD.
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http://dx.doi.org/10.1038/s41598-020-71307-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499198PMC
September 2020

Mutations in IPMN Cases: A Potential Prognostic Factor.

Gastroenterol Res Pract 2020 31;2020:1457452. Epub 2020 Aug 31.

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing 100730, China.

An intraductal papillary mucinous neoplasm (IPMN) is a common pancreatic precursor lesion, and it often harbors mutations in , , and . To clarify the molecular profiles of IPMNs, we conducted mutation analysis of , , and in 61 IPMN formalin-fixed, paraffin-embedded (FFPE) specimens. The mutation rates of codons 12, 13, and 61 in and codon 201 in were detected by Sanger sequencing. Next-generation sequencing was performed on , and the results were further verified by Sanger sequencing. We identified and mutations in 35 (57%) and 40 (66%) IPMN cases, respectively. mutations were significantly correlated with the morphologic subtype ( < 0.001) and were more prevalent in the intestinal subtype (93%) than in the gastric (55%) and pancreatobiliary subtypes (44%) but were absent in the oncocytic subtype. mutations were found in 5 cases (8%), all of which occurred in high-grade dysplasia and invasive lesions (2/5 and 3/5). All 5 cases harboring RNF43 mutations also exhibited GNAS mutations. RNF43 mutations were associated with a worse prognosis in invasive IPMN patients ( = 0.002), while KRAS and GNAS mutations did not affect the prognosis of patients.
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http://dx.doi.org/10.1155/2020/1457452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479465PMC
August 2020

Salvage chemoradiation therapy for recurrence after radical surgery or palliative surgery in esophageal cancer patients: a prospective, multicenter clinical trial protocol.

BMC Cancer 2020 Sep 14;20(1):877. Epub 2020 Sep 14.

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 South Panjiayuan lane, Chaoyang District, Beijing, 100021, China.

Background: Currently, adjuvant therapy is not recommended for patients with thoracic esophageal squamous cell cancer (TESCC) after radical surgery, and a proportion of these patients go on to develop locoregional recurrence (LRR) within 2 years. Besides, there is no evidence for salvage chemoradiation therapy (CRT) in patients with residual tumor after esophagectomy (R1/R2 resection). In addition, factors like different failure patterns and relationship with normal organs influence the decision for salvage strategy. Here, we aimed to design a modularized salvage CRT strategy for patients without a chance of salvage surgery according to different failure patterns (including R1/R2 resection), and further evaluated its efficacy and safety.

Methods: Our study was designed as a one arm, multicenter, prospective clinical trial. All enrolled patients were stratified in a stepwise manner based on the nature of surgery (R0 or R1/2), recurrent lesion diameter, involved regions, and time-to-recurrence, and were further assigned to undergo either elective nodal irradiation or involved field irradiation. Then, radiation technique and dose prescription were modified according to the distance from the recurrent lesion to the thoracic stomach or intestine. Ultimately, four treatment plans were established.

Discussion: This prospective study provided high-level evidence for clinical salvage management in patients with TESCC who developed LRR after radical surgery or those who underwent R1/R2 resection.

Trial Registration: Prospectively Registered. ClinicalTrials.gov NCT03731442 , Registered November 6, 2018.
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http://dx.doi.org/10.1186/s12885-020-07315-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488997PMC
September 2020

A non-anticoagulant heparin-like snail glycosaminoglycan promotes healing of diabetic wound.

Carbohydr Polym 2020 Nov 26;247:116682. Epub 2020 Jun 26.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. Electronic address:

Diabetic foot ulcer (DFU) is a common high-risk complication in patients with diabetes mellitus, but current drugs and therapies in management of this disease cannot meet the urgent clinical needs. In this study, a snail glycosaminoglycan (SGAG) from the cultured China white jade snail was purified and structurally clarified. This snail glycosaminoglycan is a regular sulfated polysaccharide, composed of iduronic acid (IdoA) and N-acetyl-glucosamine (GlcNAc) with the repeating sequence of →4)-α-GlcNAc (1→4)-α-IdoA2S (1→. The biological assays showed that SGAG had no anticoagulant activity for lacking specific heparin pentasaccharide sequence. The pharmacological experiments suggested that SGAG markedly accelerated the healing of full-thickness wounds in diabetic mice skin. Histologic and immunohistochemical analysis revealed that SGAG treatment alleviated the inflammation and dermal edema, and promoted angiogenesis. This is the first report applying the snail glycosaminoglycan to favor diabetic wound healing.
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http://dx.doi.org/10.1016/j.carbpol.2020.116682DOI Listing
November 2020

Unsupervised modeling and genome-wide association identify novel features of allergic march trajectories.

J Allergy Clin Immunol 2021 Feb 7;147(2):677-685.e10. Epub 2020 Jul 7.

Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, Pa; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa. Electronic address:

Background: The allergic march refers to the natural history of allergic conditions during infancy and childhood. However, population-level disease incidence patterns do not necessarily reflect the development of allergic disease in individuals. A better understanding of the factors that predispose to different allergic trajectories is needed.

Objective: Our aim was to determine the demographic and genetic features that are associated with the major allergic march trajectories.

Methods: Presence or absence of common allergic conditions (atopic dermatitis [AD], IgE-mediated food allergy [IgE-FA], asthma, and allergic rhinitis [AR]) was ascertained in a pediatric primary care birth cohort of 158,510 subjects. Hierarchic clustering and decision tree modeling were used to associate demographic features with allergic outcomes. Genome-wide association study was used to test for risk loci associated with specific allergic trajectories.

Results: We found an association between self-identified black race and progression from AD to asthma. Conversely, Asian or Pacific Islander race was associated with progression from AD to IgE-mediated food allergy, and white race was associated with progression from AD to AR. Genome-wide association study of trajectory groups identified risk loci associated with progression from AD to asthma (rs60242841) and from AD to AR (rs9565267, rs151041509, and rs78171803). Consistent with our epidemiologic associations, rs60242841 was more common in individuals of African ancestry than in individuals of European ancestry, whereas rs9565267 and rs151041509 were more common in individuals of European ancestry than in individuals of African ancestry.

Conclusion: We have identified novel associations between race and progression along distinct allergic trajectories. Ancestral genetic differences may contribute to these associations. These results uncover important health disparities, refine the concept of the allergic march, and represent a step toward developing individualized medical approaches for these conditions.
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http://dx.doi.org/10.1016/j.jaci.2020.06.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790850PMC
February 2021

Hsa_circ_001988 attenuates GC progression in vitro and in vivo via sponging miR-197-3p.

J Cell Physiol 2021 Jan 27;236(1):612-624. Epub 2020 Jun 27.

Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute and General Surgery Institute, The First Affiliated Hospital of China Medical University, Heping, Shenyang, Liaoning, China.

Hsa_circ_001988 has been identified as a tumor suppressor gene in several carcinomas. However, its expression pattern and role in gastric cancer (GC) have still remained elusive. This study aimed to explore the functions of hsa_circ_001988 in GC. Quantitative reverse transcription polymerase chain reaction assay was performed to assess the expressions of hsa_circ_001988, miR-197-3p, FBXW7, CCDC6, and U2AF65 in GC tissues. The correlation analysis was undertaken to find out the relationship between hsa_circ_001988 expression and clinicopathological factors. A series of cellular experiments were carried out to describe the effects of hsa_circ_001988 on GC in vivo and in vitro. Besides, RNA immunoprecipitation (RIP) assay was performed to verify the relationship among EIF4A3, U2AF65, and hsa_circ_001988. We first found that the expression of hsa_circ_001988 was decreased in 341 GC patients that was related to World Health Organization histological types, Lauren types, and tumor invasion depth (p < .05). Silencing of hsa_circ_001988 facilitated proliferation, colony formation, migration, and invasion of GC cells, while overexpression of hsa_circ_001988 reversed the effect on GC progression in vitro. Additionally, the results of subcutaneous xenotransplanted tumor model demonstrated that overexpressing hsa_circ_001988 significantly suppressed the subcutaneous tumor growth in vivo. Mechanistically, hsa_circ_001988 attenuated the miR-197-3p expression possibly due to its molecular sponge effect, and then, positively promoted FBXW7 expression. Afterwards, FBXW7 regulated the expressions of yes-associated protein 1, cyclinD1, CCDC6, and EMT-related proteins. Notably, RIP assay showed the enrichment relationship among EIF4A3, U2AF65, and hsa_circ_001988. Additionally, EIF4A3 or U2AF65 promoted cyclization of hsa_circ_001988 in GC. Hsa_circ_001988 inhibits the proliferation and metastasis of GC via modulating EIF4A3/U2AF65-mediated hsa_circ_001988/miR-197-3p/FBXW7 axis.
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http://dx.doi.org/10.1002/jcp.29888DOI Listing
January 2021

Hypoglycemic mechanism of polysaccharide from Cyclocarya paliurus leaves in type 2 diabetic rats by gut microbiota and host metabolism alteration.

Sci China Life Sci 2021 Jan 17;64(1):117-132. Epub 2020 Jun 17.

State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, Nanchang, 330047, China.

Diabetes mellitus is a serious threat to human health. Cyclocarya paliurus (Batal.) Iljinskaja (C.paliurus) is one of the traditional herbal medicine and food in China for treating type 2 diabetes, and the C. paliurus polysaccharides (CP) were found to be one of its major functional constituents. This research aimed at investigating the hypoglycemic mechanism for CP. It was found that CP markedly attenuated the symptoms of diabetes, and inhibited the protein expression of Bax, improved the expression of Bcl-2 in pancreas of diabetic rats, normalized hormones secretion and controlled the inflammation which contributed to the regeneration of pancreatic β-cell and insulin resistance. CP treatment increased the beneficial bacteria genus Ruminococcaceae UCG-005 which was reported to be a key genus for protecting against diabetes, and the fecal short-chain fatty acids levels were elevated. Uric metabolites analysis showed that CP treatment helped to protect with the diabetes by seven significantly improved pathways closely with the nutrition metabolism (amino acids and purine) and energy metabolism (TCA cycle), which could help to build up the intestinal epithelial cell defense for the inflammation associated with the diabetes. Our study highlights the specific mechanism of prebiotics to attenuate diabetes through multi-path of gut microbiota and host metabolism.
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http://dx.doi.org/10.1007/s11427-019-1647-6DOI Listing
January 2021