Publications by authors named "Xia Ding"

225 Publications

Circadian Rhythm Gene PER3 Negatively Regulates Stemness of Prostate Cancer Stem Cells via WNT/β-Catenin Signaling in Tumor Microenvironment.

Front Cell Dev Biol 2021 18;9:656981. Epub 2021 Mar 18.

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

Prostate cancer (PCa) cells are heterogeneous, containing a variety of cancer cells with phenotypical and functional discrepancies in the tumor microenvironment, where prostate cancer stem cells (PCSCs) play a vital role in PCa development. Our earlier studies have shown that ALDHCD44 (DP) PCa cells and the corresponding ALDHCD44 (DN) PCa cells manifest as PCSCs and non-PCSCs, respectively, but the underlying mechanisms regulating stemness of the PCSCs are not completely understood. To tackle this issue, we have performed RNA-Sequencing and bioinformatic analysis in DP (versus DN) cells in this study. We discovered that, PER3 (period circadian regulator 3), a circadian rhythm gene, is significantly downregulated in DP cells. Overexpression of PER3 in DP cells significantly suppressed their sphere- and colony-forming abilities as well as tumorigenicity in immunodeficient hosts. In contrast, knockdown of PER3 in DN cells dramatically promoted their colony-forming and tumor-initiating capacities. Clinically, PER3 is downregulated in human prostate cancer specimens and PER3 expression levels are highly correlated with the prognosis of the PCa patient. Mechanistically, we observed that low levels of PER3 stimulates the expression of BMAL1, leading to the phosphorylation of β-catenin and the activation of the WNT/β-catenin pathway. Together, our results indicate that PER3 negatively regulates stemness of PCSCs via WNT/β-catenin signaling in the tumor microenvironment, providing a novel strategy to treat PCa patients.
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http://dx.doi.org/10.3389/fcell.2021.656981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012816PMC
March 2021

Dynamic P-MRI and P-MRS of lower leg muscles in heart failure patients.

Sci Rep 2021 Apr 1;11(1):7412. Epub 2021 Apr 1.

Bernard and Irene Schwartz Center for Biomedical Imaging, New York University Langone Medical Center, 660 1st Ave, 4th Floor, New York, NY, 10016, USA.

Impaired oxidative metabolism is one of multi-variate factors leading to exercise intolerance in heart failure patients. The purpose of the study was to demonstrate the use of dynamic P magnetic resonance spectroscopy (MRS) and P magnetic resonance imaging (MRI) techniques to measure PCr resynthesis rate post-exercise as a biomarker for oxidative metabolism in skeletal muscle in HF patients and controls. In this prospective imaging study, we recruited six HF patients and five healthy controls. The imaging protocol included P-MRS, spectrally selective 3D turbo spin echo for P-MRI, and Dixon multi-echo GRE for fat-water imaging on a 3 T clinical MRI scanner. All the subjects were scanned pre-exercise, during plantar flexion exercise, and post-exercise recovery, with two rounds of exercise for P -MRS and P-MRI, respectively. Unpaired t-tests were used to compare P-MRS and P-MRI results between the HF and control cohorts. The results show that PCr resynthesis rate was significantly slower in the HF cohort compared to the controls using P-MRS (P = 0.0003) and P-MRI (P = 0.0014). P-MRI showed significant differences between the cohorts in muscle groups (soleus (P = 0.0018), gastrocnemius lateral (P = 0.0007) and gastrocnemius medial (P = 0.0054)). The results from this study suggest that P-MRS/P-MRI may be used to quantify lower leg muscle oxidative metabolism in HF patients, with P-MRI giving an additional advantage of allowing further localization of oxidative metabolism deficits. Upon further validation, these techniques may serve as a potentially useful clinical imaging biomarker for staging and monitoring therapies in HF-patients.
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http://dx.doi.org/10.1038/s41598-021-86392-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016929PMC
April 2021

Machine learning-assisted decision-support models to better predict patients with calculous pyonephrosis.

Transl Androl Urol 2021 Feb;10(2):710-723

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

Background: To develop a machine learning (ML)-assisted model capable of accurately identifying patients with calculous pyonephrosis before making treatment decisions by integrating multiple clinical characteristics.

Methods: We retrospectively collected data from patients with obstructed hydronephrosis who underwent retrograde ureteral stent insertion, percutaneous nephrostomy (PCN), or percutaneous nephrolithotomy (PCNL). The study cohort was divided into training and testing datasets in a 70:30 ratio for further analysis. We developed 5 ML-assisted models from 22 clinical features using logistic regression (LR), LR optimized by least absolute shrinkage and selection operator (Lasso) regularization (Lasso-LR), support vector machine (SVM), extreme gradient boosting (XGBoost), and random forest (RF). The area under the curve (AUC) was applied to determine the model with the highest discrimination. Decision curve analysis (DCA) was used to investigate the clinical net benefit associated with using the predictive models.

Results: A total of 322 patients were included, with 225 patients in the training dataset, and 97 patients in the testing dataset. The XGBoost model showed good discrimination with the AUC, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.981, 0.991, 0.962, 1.000, 1.000, and 0.989, respectively, followed by SVM [AUC =0.985, 95% confidence interval (CI): 0.970-1.000], Lasso-LR (AUC =0.977, 95% CI: 0.958-0.996), LR (AUC =0.936, 95% CI: 0.905-0.968), and RF (AUC =0.920, 95% CI: 0.870-0.970). Validation of the model showed that SVM yielded the highest AUC (0.977, 95% CI: 0.952-1.000), followed by Lasso-LR (AUC =0.959, 95% CI: 0.921-0.997), XGBoost (AUC =0.958, 95% CI: 0.902-1.000), LR (AUC =0.932, 95% CI: 0.878-0.987), and RF (AUC =0.868, 95% CI: 0.779-0.958) in the testing dataset.

Conclusions: Our ML-based models had good discrimination in predicting patients with obstructed hydronephrosis at high risk of harboring pyonephrosis, and the use of these models may be greatly beneficial to urologists in treatment planning, patient selection, and decision-making.
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http://dx.doi.org/10.21037/tau-20-1208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947454PMC
February 2021

Comparison of contrast-enhanced ultrasound versus conventional ultrasound-guided percutaneous nephrolithotomy in patients with nondilated collecting system: a randomized controlled trial.

Eur Radiol 2021 Feb 26. Epub 2021 Feb 26.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Objective: To compare the safety, effectiveness, and feasibility of contrast-enhanced ultrasound (CEUS) versus conventional ultrasound-guided percutaneous nephrolithotomy (PCNL) in patients with nondilated collecting system.

Methods: Between July 2018 and July 2020, 160 kidney stone patients with nondilated collecting system planned for PCNL were randomly assigned into two groups, CEUS with retrograde ureteral contrast injection and conventional ultrasound with retrograde ureteral normal saline injection. Patient's demographics, the success rate of puncture, success rate of a single-needle puncture, number of punctures, puncture time, perioperative outcomes, stone-free rate, and incidence of complications were compared.

Results: The success rate of a single-needle puncture for CEUS-guided PCNL was higher than that in the conventional ultrasound group (88.5% vs. 73.7%, p = 0.02). Patients performed with CEUS-guided PCNL required less needle passes (p = 0.02), shorter needle puncture time (p = 0.031), and shorter channel establishment time (p = 0.04) than those guided with conventional ultrasound. The postoperative hemoglobin decrease in the CEUS-guided PCNL group was less than that of the control group (p = 0.02). There was no significant difference in operating time, length of hospital stays, kidney function change, and complications between the two groups (p > 0.05). The 1-month stone-free rate was 94.9% in the CEUS group and 90.8% in the control group (p > 0.05).

Conclusions: Compared with conventional ultrasound, CEUS-guided PCNL may facilitate ultrasound-guided PCNL for patients without hydronephrosis, and benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop.

Trial Registration: Chinese Clinical Trial Registry: ChiCTR1800016981 KEY POINTS: • Compared with conventional ultrasound, CEUS-guided PCNL is a safe and efficacious procedure for kidney stone patients with nondilated collecting system. • Compared with conventional ultrasound, CEUS-guided PCNL benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop. • CEUS-guided PCNL associated with the more accurate needle puncture and acceptable complications.
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http://dx.doi.org/10.1007/s00330-021-07804-1DOI Listing
February 2021

Head-on collision of compressional shocks in two-dimensional Yukawa systems.

Phys Rev E 2021 Jan;103(1-1):013202

Center for Soft Condensed Matter Physics and Interdisciplinary Research, School of Physical Science and Technology, Soochow University, Suzhou 215006, China.

The head-on collision of compressional shocks in two-dimensional dusty plasmas is investigated using both molecular dynamical and Langevin simulations. Two compressional shocks are generated from the inward compressional boundaries in simulations. It is found that, during the collision of shocks, there is a generally existing time delay of shocks τ, which diminishes monotonically with the increasing compressional speed of boundaries, corresponding to the time resolution of the studied system. Dispersive shock waves (DSWs) are generated around the shock front for some conditions. It is also found that the period of the DSW decreases monotonically with the inward compressional speed of boundaries, more substantially than the time delay of shocks τ. When the inward compressional speed of boundaries increases further, the DSWs gradually vanish. We speculate that, for these high compressional speeds of boundaries, the period of the DSW might be reduced to a comparable timescale of the time delay of shocks τ, i.e., the time resolution of our studied system, or even shorter, thus the DSW reasonably vanishes.
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http://dx.doi.org/10.1103/PhysRevE.103.013202DOI Listing
January 2021

Baicalin Induces Apoptosis and Suppresses the Cell Cycle Progression of Lung Cancer Cells Through Downregulating Akt/mTOR Signaling Pathway.

Front Mol Biosci 2020 28;7:602282. Epub 2021 Jan 28.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

Baicalin, as a natural active ingredient extracted and isolated from the traditional Chinese medicine Georgi., has been potentially used in various areas for its antioxidative, antitumor, anti-inflammatory, and anti-proliferative activities. Although several studies have reported the antitumor effects of baicalin against various cancer types, its beneficial effects on lung cancer have not yet been elucidated. Therefore, the therapeutic effects and molecular mechanisms of baicalin on lung cancer cell lines H1299 and H1650 were investigated. Here, the results of its antitumor activity were shown. We found that Akt/mTOR pathway inhibition was the essential determinant in baicalin-induced cell cycle arrest. Furthermore, when the Akt Agonist SC79 or Akt plasmid transfection was performed, the antitumor effect of baicalin was significantly abrogated in both H1299 and H1650 cells. In conclusion, we found that baicalin exerted its antitumor activity mainly by inducing Akt-dependent cell cycle arrest and promoting apoptosis, which show great potential for developing a new drug for lung cancer treatment.
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http://dx.doi.org/10.3389/fmolb.2020.602282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876332PMC
January 2021

Comparison of wild rice (Oryza longistaminata) tissues identifies rhizome-specific bacterial and archaeal endophytic microbiomes communities and network structures.

PLoS One 2021 8;16(2):e0246687. Epub 2021 Feb 8.

School of Life Sciences, Nanchang University, Nanchang, Jiangxi, China.

Compared with root-associated habitats, little is known about the role of microbiota inside other rice organs, especially the rhizome of perennial wild rice, and this information may be of importance for agriculture. Oryza longistaminata is perennial wild rice with various agronomically valuable traits, including large biomass on poor soils, high nitrogen use efficiency, and resistance to insect pests and disease. Here, we compared the endophytic bacterial and archaeal communities and network structures of the rhizome to other compartments of O. longistaminata using 16S rRNA gene sequencing. Diverse microbiota and significant variation in community structure were identified among different compartments of O. longistaminata. The rhizome microbial community showed low taxonomic and phylogenetic diversity as well as the lowest network complexity among four compartments. Rhizomes exhibited less phylogenetic clustering than roots and leaves, but similar phylogenetic clustering with stems. Streptococcus, Bacillus, and Methylobacteriaceae were the major genera in the rhizome. ASVs belonging to the Enhydrobacter, YS2, and Roseburia are specifically present in the rhizome. The relative abundance of Methylobacteriaceae in the rhizome and stem was significantly higher than that in leaf and root. Noteworthy type II methanotrophs were observed across all compartments, including the dominant Methylobacteriaceae, which potentially benefits the host by facilitating CH4-dependent N2 fixation under nitrogen nutrient-poor conditions. Our data offers a robust knowledge of host and microbiome interactions across various compartments and lends guidelines to the investigation of adaptation mechanisms of O. longistaminata in nutrient-poor environments for biofertilizer development in agriculture.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246687PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870070PMC
February 2021

Amblyopia and Refractive Status in Congenital Ptosis: The Effect and Timing of Surgical Correction.

Ann Plast Surg 2021 Feb 1. Epub 2021 Feb 1.

From the Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, the People's Republic of China.

Purpose: The aim of this study was to explore the effect of congenital ptosis on the visual function of patients and observe the improvement in visual function after the correction of ptosis at different surgical times.

Methods: We performed a retrospective study of 265 patients (346 eyes) with congenital ptosis at the same hospital. Each patient underwent an ophthalmic examination, including optometry and measurement of the affected palpebral fissure height and upper eyelid margin reflex distance. Preoperative clinical and morphologic data were compared with postoperative data.

Results: The refractive error of the patient population was significantly different from that of the general population (P < 0.01). The rates of strabismus and amblyopia were 12.45% and 36.98%, respectively, in the ptosis patients, both of which are higher than the rates in the general population (P < 0.01), especially for unilaterally affected patients and patients with the optical axis covered. The refractive error of patients younger than 5 years was improved postoperatively (P < 0.05). The number of cases of amblyopia and strabismus was reduced, as was the percentage of cases of with-the-rule astigmatism (P < 0.05).

Conclusion: Congenital ptosis can result in refractive error, strabismus, and amblyopia, which could seriously impair the visual function of patients. The impairment is more pronounced in unilaterally affected patients. Surgery is conducive to the recovery of visual function, especially in patients younger than 5 years. Satisfactory curative effects can be obtained before the age of 3 years; thus, unilaterally affected patients, severely affected patients, and patients with impaired visual function should undergo surgery as soon as possible.
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http://dx.doi.org/10.1097/SAP.0000000000002677DOI Listing
February 2021

Potential effect of Maxing Shigan decoction against coronavirus disease 2019 (COVID-19) revealed by network pharmacology and experimental verification.

J Ethnopharmacol 2021 May 26;271:113854. Epub 2021 Jan 26.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Liangxiang University Town, Fangshan District, Beijing, 102488, China. Electronic address:

Ethnopharmacological Relevance: Since the occurrence of coronavirus disease 2019 (COVID-19) in Wuhan, China in December 2019, COVID-19 has been quickly spreading out to other provinces and countries. Considering that traditional Chinese medicine (TCM) played an important role during outbreak of SARS and H1N1, finding potential alternative approaches for COVID-19 treatment is necessary before vaccines are developed. According to previous studies, Maxing Shigan decoction (MXSGD) present a prominent antivirus effect and is often used to treat pulmonary diseases. Furthermore, we collected 115 open prescriptions for COVID-19 therapy from the National Health Commission, State Administration of TCM and other organizations, MXSGD was identified as the key formula. However, the underlying molecular mechanism of MXSGD against COVID-19 is still unknown.

Aim Of The Study: The present study aimed to evaluate the therapeutic mechanism of MXSGD against COVID-19 by network pharmacology and in vitro experiment verification, and screen the potential components which could bind to key targets of COVID-19 via molecular docking method.

Materials And Methods: Multiple open-source databases related to TCM or compounds were employed to screen active ingredients and potential targets of MXSGD. Network pharmacology analysis methods were used to initially predict the antivirus and anti-inflammatory effects of MXSGD against COVID-19. IL-6 induced rat lung epithelial type Ⅱ cells (RLE-6TN) damage was established to explore the anti-inflammatory damage activity of MXSGD. After MXSGD intervention, the expression level of related proteins and their phosphorylation in the IL-6 mediated JAK-STAT signaling pathway were detected by Western blot. Molecular docking technique was used to further identify the potential substances which could bind to three key targets (ACE2, Mpro and RdRp) of COVID-19.

Results: In this study, 105 active ingredients and 1025 candidate targets were selected for MXSGD, 83 overlapping targets related to MXSGD and COVID-19 were identified, and the protein-protein interaction (PPI) network of MXSGD against COVID-19 was constructed. According to the results of biological enrichment analysis, 63 significant KEGG pathways were enriched, and most of them were related to signal transduction, immune system and virus infection. Furthermore, according the relationship between signal pathways, we confirmed MXSGD could effectively inhibit IL-6 mediated JAK-STAT signal pathway related protein expression level, decreased the protein expression levels of p-JAK2, p-STAT3, Bax and Caspase 3, and increased the protein expression level of Bcl-2, thereby inhibiting RLE-6TN cells damage. In addition, according to the LibDock scores screening results, the components with strong potential affinity (Top 10) with ACE2, Mpro and RdRp are mainly from glycyrrhiza uralensis (Chinese name: Gancao) and semen armeniacae amarum (Chinese name: Kuxingren). Among them, amygdalin was selected as the optimal candidate component bind to all three key targets, and euchrenone, glycyrrhizin, and glycyrol also exhibited superior affinity interactions with ACE2, Mpro and RdRp, respectively.

Conclusion: This work explained the positive characteristics of multi-component, multi-target, and multi-approach intervention with MXSGD in combating COVID-19, and preliminary revealed the antiviral and anti-inflammatory pharmacodynamic substances and mechanism of MXSGD, which might provide insights into the vital role of TCM in the prevention and treatment of COVID-19.
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http://dx.doi.org/10.1016/j.jep.2021.113854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835541PMC
May 2021

Expression profiles, biological functions and clinical significance of circRNAs in bladder cancer.

Mol Cancer 2021 01 4;20(1). Epub 2021 Jan 4.

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

Circular RNAs (circRNAs), which are single-stranded closed-loop RNA molecules lacking terminal 5' caps and 3' poly(A) tails, are attracting increasing scientific attention for their crucial regulatory roles in the occurrence and development of various diseases. With the rapid development of high-throughput sequencing technologies, increasing numbers of differentially expressed circRNAs have been identified in bladder cancer (BCa) via exploration of the expression profiles of BCa and normal tissues and cell lines. CircRNAs are critically involved in BCa biological behaviours, including cell proliferation, tumour growth suppression, cell cycle arrest, apoptosis, invasion, migration, metastasis, angiogenesis, and cisplatin chemoresistance. Most of the studied circRNAs in BCa regulate cancer biological behaviours via miRNA sponging regulatory mechanisms. CircRNAs have been reported to be significantly associated with many clinicopathologic characteristics of BCa, including tumour size, grade, differentiation, and stage; lymph node metastasis; tumour numbers; distant metastasis; invasion; and recurrence. Moreover, circRNA expression levels can be used to predict BCa patients' survival parameters, such as overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). The abundance, conservation, stability, specificity and detectability of circRNAs render them potential diagnostic and prognostic biomarkers for BCa. Additionally, circRNAs play crucial regulatory roles upstream of various signalling pathways related to BCa carcinogenesis and progression, reflecting their potential as therapeutic targets for BCa. Herein, we briefly summarize the expression profiles, biological functions and mechanisms of circRNAs and the potential clinical applications of these molecules for BCa diagnosis, prognosis, and targeted therapy.
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http://dx.doi.org/10.1186/s12943-020-01300-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780637PMC
January 2021

Predicting Prostate Cancer Upgrading of Biopsy Gleason Grade Group at Radical Prostatectomy Using Machine Learning-Assisted Decision-Support Models.

Cancer Manag Res 2020 22;12:13099-13110. Epub 2020 Dec 22.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.

Objective: This study aimed to develop a machine learning (ML)-assisted model capable of accurately predicting the probability of biopsy Gleason grade group upgrading before making treatment decisions.

Methods: We retrospectively collected data from prostate cancer (PCa) patients. Four ML-assisted models were developed from 16 clinical features using logistic regression (LR), logistic regression optimized by least absolute shrinkage and selection operator (Lasso) regularization (Lasso-LR), random forest (RF), and support vector machine (SVM). The area under the curve (AUC) was applied to determine the model with the highest discrimination. Calibration plots and decision curve analysis (DCA) were performed to evaluate the calibration and clinical usefulness of each model.

Results: A total of 530 PCa patients were included in this study. The Lasso-LR model showed good discrimination with an AUC, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.776, 0.712, 0.679, 0.745, 0.730, and 0.695, respectively, followed by SVM (AUC=0.740, 95% confidence interval [CI]=0.690-0.790), LR (AUC=0.725, 95% CI=0.674-0.776) and RF (AUC=0.666, 95% CI=0.618-0.714). Validation of the model showed that the Lasso-LR model had the best discriminative power (AUC=0.735, 95% CI=0.656-0.813), followed by SVM (AUC=0.723, 95% CI=0.644-0.802), LR (AUC=0.697, 95% CI=0.615-0.778) and RF (AUC=0.607, 95% CI=0.531-0.684) in the testing dataset. Both the Lasso-LR and SVM models were well-calibrated. DCA plots demonstrated that the predictive models except RF were clinically useful.

Conclusion: The Lasso-LR model had good discrimination in the prediction of patients at high risk of harboring incorrect Gleason grade group assignment, and the use of this model may be greatly beneficial to urologists in treatment planning, patient selection, and the decision-making process for PCa patients.
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http://dx.doi.org/10.2147/CMAR.S286167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765752PMC
December 2020

FangNet: Mining herb hidden knowledge from TCM clinical effective formulas using structure network algorithm.

Comput Struct Biotechnol J 2021 4;19:62-71. Epub 2020 Dec 4.

Beijing University of Chinese Medicine, ChaoYang District, Beijing 100029, China.

The use of herbs to treat various human diseases has been recorded for thousands of years. In Asia's current medical system, numerous herbal formulas have been repeatedly verified to confirm their effectiveness in different periods, which is a great resource for drug innovation and discovery. Through the mining of these clinical effective formulas by network pharmacology and bioinformatics analysis, important biologically active ingredients derived from these natural products might be discovered. As modern medicine requires a combination of multiple drugs for the treatment of complex diseases, previously clinical formulas are also combinations of various herbs according to the main causes and accompanying symptoms. However, the herbs that play a major role in the treatment of diseases are always unclear. Therefore, how to rank each herb's relative importance and determine the core herbs, is the first step to assisting herb selection for active ingredients discovery. To solve this problem, we built the platform FangNet, which ranks all herbs on their relative topological importance using the PageRank algorithm, based on the constructed symptom-herb network from a collection of clinical empirical prescriptions. Three types of herb hidden knowledge, including herb importance rank, herb-herb co-occurrence, and associations to symptoms, were provided in an interactive visualization. Moreover, FangNet has designed role-based permission for teams to store, analyze, and jointly interpret their clinical formulas, in an easy and secure collaboration environment, aiming at creating a central hub for massive symptom-herb connections. FangNet can be accessed at http://fangnet.org or http://fangnet.herb.ac.cn.
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http://dx.doi.org/10.1016/j.csbj.2020.11.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753081PMC
December 2020

A novel comprehensive predictive model for obstructive pyonephrosis patients with upper urinary tract stones.

Int J Clin Exp Pathol 2020 1;13(11):2758-2766. Epub 2020 Nov 1.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, Hubei, China.

Background: Calculous pyonephrosis tended not to be accurately diagnosed before operations. It is mostly confirmed during percutaneous nephrolithotripsy or percutaneous nephrostomy. We aimed to evaluate the risk factors for predicting obstructive pyonephrosis patients with upper urinary tract stones.

Methods: Clinical data of 322 patients with upper urinary tract stones and obstructive hydronephrosis were retrospectively searched and analyzed in our study. The patients were divided into two groups; pyonephrosis and non-pyonephrosis groups. Both disease related factors and infection-associated indicators were analyzed. Univariate and multivariate logistic analyses were performed on preoperative variables. Accordingly, ROC curves were drawn, and a novel comprehensive model was constructed to predict the pyonephrosis.

Outcomes: Compared to the non-pyonephrosis group, patients in the pyonephrosis group showed statistical differences in sex, urinary tract infection (UTI) within 3 months, stone density, computerized tomography (CT) value of hydronephrosis, serum creatinine, hydronephrosis, contralateral kidney severe hydronephrosis or atrophy, preoperative white blood cells, neutrophils, serum C-reactive protein, urine leukocyte, nitrite, and urine culture revealed statistical difference (<0.05). Univariate analysis showed that there were significant differences for sex, UTI history, degree of hydronephrosis, contralateral severe hydronephrosis or atrophy, serum creatinine, and CT value of hydronephrosis (<0.001). Multivariate analysis demonstrated several independent risk factors for pyonephrosis, including degree of hydronephrosis (=0.02), CT value of hydronephrosis (=0.001), urine leukocyte (=0.002), urine culture (=0.001) and blood neutrophils (=0.009). Based on these risk factors, we constructed a novel comprehensive model and confirmed it was an effective method to predict pyonephrosis (AUC, 0.970). Bootstrapped calibration curves showed no untoward deviation in both training and validation dataset (mean absolute error of 0.027, 0.036).

Conclusions: Hydronephrosis, CT value of hydronephrosis, blood neutrophils, urine leukocyte, and urine culture were independent risk factors to predict pyonephrosis. The novel comprehensive model was found to be an effective method to predict pyonephrosis and needed to be further confirmed in prospective studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716127PMC
November 2020

Shen-Fu Decoction could ameliorate intestinal permeability by regulating the intestinal expression of tight junction proteins and p-VASP in septic rats.

J Ethnopharmacol 2021 Mar 18;268:113562. Epub 2020 Nov 18.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address:

Ethnopharmacological Relevance: Shen-Fu Decoction (SFD), a classic Traditional Chinese paired herb formulation, has been widely used for the treatment of sepsis in China. This study was carried out to assess the effects of SFD in sepsis-induced intestinal permeability and intestinal epithelial tight junction damage in rats with sepsis.

Materials And Methods: A rat model of sepsis was created by cecal ligation and puncture (CLP). Rats in Sham and CLP + vehicle groups received equal distilled water, while rats in SFD group were treated by gavage of SFD (3 mg/kg, twice a day) for 72h. Mortality, sepsis-induced peritoneal inflammation, intestinal and liver histopathology damage, intestinal permeability (serum FITC-dextran and D-lactate), serum LPS, serum inflammation (PCT, TNF-α, and IL-6), and liver function (AST and ALT) were evaluated. The levels of zonula occluden (ZO-1), Occludin, Claudin-1 were analyzed by Real-time quantitative PCR and Western blotting (WB) respectively. Vasodilator-stimulated phosphoprotein (VASP) and p-VASP in intestinal epithelium were analyzed by WB.

Results: Our study showed that SFD markedly reduced the mortality rate of CLP rats, prevented intestine and liver damage, relieved sepsis-induced intestinal permeability and inflammation elevation, ameliorated sepsis-induced impaired intestinal permeability by regulating the expression of ZO-1, Occludin, Claudin-1 and p-VASP.

Conclusions: The herbal formula SFD may be useful for reducing sepsis-induced organic damage and mortality by ameliorating the condition of sepsis-induced intestinal permeability by regulating tight junction proteins and p-VASP.
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http://dx.doi.org/10.1016/j.jep.2020.113562DOI Listing
March 2021

AhR activation attenuates calcium oxalate nephrocalcinosis by diminishing M1 macrophage polarization and promoting M2 macrophage polarization.

Theranostics 2020 25;10(26):12011-12025. Epub 2020 Oct 25.

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

Calcium oxalate (CaOx) crystal can trigger kidney injury, which contributes to the pathogenesis of nephrocalcinosis. The phenotypes of infiltrating macrophage may impact CaOx-mediated kidney inflammatory injury as well as crystal deposition. How aryl hydrocarbon receptor (AhR) regulates inflammation and macrophage polarization is well understood; however, how it modulates CaOx nephrocalcinosis remains unclear. Mice were intraperitoneally injected with glyoxylate to establish CaOx nephrocalcinosis model with or without the treatment of AhR activator 6-formylindolo(3,2-b)carbazole (FICZ). Positron emission tomography computed tomography (PET-CT) imaging, Periodic acid-Schiff (PAS) staining, and polarized light optical microscopy were used to evaluate kidney injury and crystal deposition in mice kidney. Western blotting, immunofluorescence, chromatin immunoprecipitation, microRNA-fluorescence hybridization, and luciferase reporter assays were applied to analyze polarization state and regulation mechanism of macrophage. AhR expression was significantly upregulated and negatively correlated with interferon-regulatory factor 1 (IRF1) and hypoxia inducible factor 1-alpha (HIF-1α) levels in a murine CaOx nephrocalcinosis model following administration of FICZ. Moreover, AhR activation suppressed IRF1 and HIF-1α levels and decreased M1 macrophage polarization . In terms of the mechanism, bioinformatics analysis and chromatin immunoprecipitation assay confirmed that AhR could bind to miR-142a promoter to transcriptionally activate miR-142a. In addition, luciferase reporter assays validated that miR-142a inhibited IRF1 and HIF-1α expression by directly targeting their 3'-untranslated regions. Our results indicated that AhR activation could diminish M1 macrophage polarization and promote M2 macrophage polarization to suppress CaOx nephrocalcinosis via the AhR-miR-142a-IRF1/HIF-1α pathway.
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http://dx.doi.org/10.7150/thno.51144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667681PMC
October 2020

Combined multiple clinical characteristics for prediction of discordance in grade and stage in prostate cancer patients undergoing systematic biopsy and radical prostatectomy.

Pathol Res Pract 2020 Nov 1;216(11):153235. Epub 2020 Oct 1.

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

Background: The present study aimed to develop three nomograms by incorporating multiple clinical characteristics to identify those prostate cancer (PCa) patients with high probability of incorrect biopsy Gleason grade group (GG) before making treatment decisions.

Methods: We retrospectively collected data from PCa patients who underwent systematic biopsy and radical prostatectomy from January 2015 to December 2019 at Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology. Univariable and multivariable logistic regression analyses were preformed to identify independent risk factors associated with upgrading, upstaging and downgrading. By incorporating selected clinical parameters with high predictive value, we constructed three nomograms to predict the probability of upgrading, upstaging and downgrading. Discrimination of nomograms was evaluated by receiver operating characteristic (ROC) analysis with corresponding area under the curve (AUC). Decision curve analysis (DCA) and calibration curves were performed to evaluate calibration and the clinical usefulness of nomograms. Performance of the three nomograms was validated in the testing dataset.

Results: There were 585 PCa patients in total enrolled in this study who met the inclusion criteria. Of the 585 patients, the disease of 262 (44.8 %) was upgraded and 68 (11.6 %) was downgraded, and the disease of 67 (11.5 %) was upstaged. With regard to findings of multivariable analyses, patients' age and biopsy GG (GG 2, GG 3, GG 4 versus GG 1) were significantly associated with upgrading. Moreover, maximum diameter of the index lesion (D-max), clinical T stage (cT3a, cT3b versus cT1-2), number of positive cores and total tumor length were significantly associated with upstaging. Furthermore, d-max, %fPSA (> 0.16 versus ≤ 0.16) and biopsy GG (GG 3, GG 4, GG 5 versus GG 2) were independent predictors of downgrading. The three nomograms displayed good calibration in respective calibration plots. ROC analyses showed good discrimination with satisfactory AUC values and DCA plots demonstrated that the upgrading-risk nomogram, upstaging-risk nomogram and downgrading-risk nomogram were all clinically useful.

Conclusions: The upgrading-risk nomogram, upstaging-risk nomogram, and downgrading-risk nomogram were developed and correctly predicted the probability of incorrect Gleason grade group assigned to patients undergoing systematic biopsy.
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http://dx.doi.org/10.1016/j.prp.2020.153235DOI Listing
November 2020

Added Value of Biparametric MRI and TRUS-Guided Systematic Biopsies to Clinical Parameters in Predicting Adverse Pathology in Prostate Cancer.

Cancer Manag Res 2020 24;12:7761-7770. Epub 2020 Aug 24.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.

Objective: To develop novel models for predicting extracapsular extension (EPE), seminal vesicle invasion (SVI), or upgrading in prostate cancer (PCa) patients using clinical parameters, biparametric magnetic resonance imaging (bp-MRI), and transrectal ultrasonography (TRUS)-guided systematic biopsies.

Patients And Methods: We retrospectively collected data from PCa patients who underwent standard (12-core) systematic biopsy and radical prostatectomy. To develop predictive models, the following variables were included in multivariable logistic regression analyses: total prostate-specific antigen (TPSA), central transition zone volume (CTZV), prostate-specific antigen (PSAD), maximum diameter of the index lesion at bp-MRI, EPE at bp-MRI, SVI at bp-MRI, biopsy Gleason grade group, and number of positive biopsy cores. Three risk calculators were built based on the coefficients of the logit function. The area under the curve (AUC) was applied to determine the models with the highest discrimination. Decision curve analyses (DCAs) were performed to evaluate the net benefit of each risk calculator.

Results: A total of 222 patients were included in this study. Overall, 83 (37.4%), 75 (33.8%), and 107 (48.2%) patients had EPE, SVI, and upgrading at final pathology, respectively. The addition of bp-MRI data improved the discrimination of models for predicting SVI (0.807 vs 0.816) and upgrading (0.548 vs 0.625) but not EPE (0.766 vs 0.763). Similarly, models including clinical parameters, bp-MRI data, and information on systematic biopsies achieved the highest AUC in the prediction of EPE (0.842), SVI (0.913), and upgrading (0.794), and the three corresponding risk calculators yielded the highest net benefit.

Conclusion: We developed three easy-to-use risk calculators for the prediction of adverse pathological features based on patient clinical parameters, bp-MRI data, and information on systematic biopsies. This may be greatly beneficial to urologists in the decision-making process for PCa patients.
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http://dx.doi.org/10.2147/CMAR.S260986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457849PMC
August 2020

Experimental Investigation of the Physical Properties and Microstructure of Slate under Wetting and Drying Cycles Using Micro-CT and Ultrasonic Wave Velocity Tests.

Sensors (Basel) 2020 Aug 27;20(17). Epub 2020 Aug 27.

Three Gorges Research Center for Geo-Hazards of the Ministry of Education, China University of Geosciences, Wuhan 430074, China.

Cyclic wetting and drying processes have been considered as important factors that accelerate the weathering process and have deteriorative effects on rock properties. In the present study, a fully nondestructive and noninvasive testing approach utilizing micro-CT and ultrasonic wave velocity tests was employed to investigate the microstructure of slate under wetting and drying cycles. We studied variations in the physical properties, including the dry weight and the velocities of P- and S-waves versus the number of wetting and drying cycles. The internal microstructural distributions were visualized and quantified by the 3D reconstruction and hybrid image segmentation of CT images. The degree of deterioration caused by wetting and drying cycles was reflected by exponential decreases of physical properties, including dry weight and velocities of the P- and S-waves. Parameters relating to the microfracture diameter, volume, etc. were quantified. The nondestructive and noninvasive testing approach utilizing micro-CT and ultrasonic wave velocity tests has potential for the detection and visualization of the internal microstructure of rock under wetting and drying cycles.
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http://dx.doi.org/10.3390/s20174853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506867PMC
August 2020

Evaluation of Hemodynamic Change by Indocyanine Green-FLOW 800 Videoangiography Mapping: Prediction of Hyperperfusion Syndrome in Patients with Moyamoya Disease.

Oxid Med Cell Longev 2020 11;2020:8561609. Epub 2020 Aug 11.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.

Objective: Hyperperfusion syndrome (HPS) after bypass surgery for moyamoya disease (MMD) mainly results from redistribution of blood flow, which leads to poor outcomes, while effective methods to predict HPS are still lacking. Indocyanine green (ICG) videoangiography can assess regional cerebral blood flow changes semiquantitatively with the application of FLOW 800 software. The purpose of this study was to investigate whether the intraoperative evaluation of local hemodynamic changes around anastomotic sites using FLOW 800 videoangiography mapping can predict the incidence of HPS and clinical outcomes.

Methods: Of the patients who were diagnosed with MMD in our hospital between August 2018 and December 2019, who underwent superficial temporal artery-middle cerebral artery bypass surgeries, we investigated 65 hemispheres (in 62 patients) in which intraoperative ICG analysis was performed using FLOW 800 (Zeiss Meditec, Oberkochen, Germany) to evaluate the local cerebral hemodynamics before and after anastomosis. Regions of interest were set at more than 2 points on the brain surface according to the location and situation of recipient arteries in the surgical area. Peak cerebral blood volume (CBV), regional cerebral blood flow (CBF), and time to peak (TTP) were calculated from the selected points. As the data were available intraoperatively, anastomoses were performed in a suitable area. According to the occurrence of HPS, patients were divided into the asymptomatic and symptomatic groups, from which hemodynamic parameters were compared. Furthermore, ROC analysis was performed to determine the diagnostic accuracy of change rates in CBV, CBF, and TTP (i.e., CBV, CBF, and TTP) for predicting HPS.

Results: Data from the 62 patients were analyzed, and all patients were closely assessed during hospitalization after the procedures. The values of CBV and CBF were significantly higher in the symptomatic group ( < 0.01), while TTP is slightly lower in the symptomatic group with no statistical differences ( = 0.72). Hemodynamic parameters including CBV and CBF, calculated by FLOW 800, had high sensitivity and specificity according to the ROC curve (CBV: AUC = 0.743, 95% CI, 0.605-0.881, = 0.002; CBF: AUC = 0.852, 95% CI, 0.750-0.954, < 0.01), which could be used as predictors for HPS.

Conclusions: Intraoperative ICG-FLOW 800 videoangiography mapping is a safe method which can reflect hemodynamic characteristics in the surgical area for MMD, the findings of which correlate with the occurrence of HPS. Parameters including CBV and CBF are proven to be efficient in the prediction of HPS.
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http://dx.doi.org/10.1155/2020/8561609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441439PMC
August 2020

Degradation of 5hmC-marked stalled replication forks by APE1 causes genomic instability.

Sci Signal 2020 08 18;13(645). Epub 2020 Aug 18.

Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.

Synthetic lethality between poly(ADP-ribose) polymerase (PARP) inhibition and deficiency is exploited to treat breast and ovarian tumors. However, resistance to PARP inhibitors (PARPis) is common. To identify potential resistance mechanisms, we performed a genome-wide RNAi screen in BRCA2-deficient mouse embryonic stem cells and validation in KB2P1.21 mouse mammary tumor cells. We found that resistance to multiple PARPi emerged with reduced expression of TET2 (ten-eleven translocation), which promotes DNA demethylation by oxidizing 5-methylcytosine (5mC) to 5-hydroxymethycytosine (5hmC) and other products. TET2 knockdown in BRCA2-deficient cells protected stalled replication forks (RFs). Increasing 5hmC abundance induced the degradation of stalled RFs in KB2P1.21 and human cancer cells by recruiting the base excision repair-associated apurinic/apyrimidinic endonuclease APE1, independent of the status. TET2 loss did not affect the recruitment of the repair protein RAD51 to sites of double-strand breaks (DSBs) or the abundance of proteins associated with RF integrity. The loss of TET2, of its product 5hmC, and of APE1 recruitment to stalled RFs promoted resistance to the chemotherapeutic cisplatin. Our findings reveal a previously unknown role for the epigenetic mark 5hmC in maintaining the integrity of stalled RFs and a potential resistance mechanism to PARPi and cisplatin.
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http://dx.doi.org/10.1126/scisignal.aba8091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575062PMC
August 2020

Ethnobotanical survey of medicinal plants in Gaomi, China.

J Ethnopharmacol 2021 Jan 8;265:113228. Epub 2020 Aug 8.

School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People's Republic of China. Electronic address:

Ethnopharmacological Relevance: The uses of medicinal plants have a long history and become one of the important sources of the health cares in Gaomi City, Shandong Province, China. However, limited studies have been done to identify these medicinal plant species and to scientifically document their associated traditional knowledge. Many species used by indigenous people could potentially represent a novel resource of medicine. The study can aid in further investigations of modern pharmacology and planning of the wild species conservation.

Aim Of The Study: The study aimed to investigate and record the medicinal plant taxa and their associated traditional knowledge in Gaomi City, China.

Materials And Methods: Field study was conducted from March 2018 to May 2019 with 184 residents of Gaomi City. Traditional medicinal plant specimens were collected from the field with the help of these residents and were identified and authenticated in the Herbarium of the School of Pharmacy, Binzhou Medical University. Ethnobotanical knowledge was collected by semi-structured face-to-face interviews. The quantitative data were analyzed by using the informant consensus factor (ICF) method and the number of citations.

Results: A total of 181 species belonging to 137 genera and 65 families were collected in Gaomi City. Asteraceae was the predominant family and Fabaceae took the second place. River basins and the southern hills in Gaomi were rich in vegetation. However, the cultivated area of medicinal plants only accounted for 10% of agricultural acreage. The main preparation method was decocting (170, 94.48%) and the most frequent mode of administration was oral (177, 97.97%). The highest numerical ICF value was recorded for treating endocrine, metabolic, and nutritional (ICF: 0.85) conditions. Seven of the medicinal plant species used by the people in Gaomi have not been reported previously in China. Verbena officinalis L. was found in Gaomi City, which is a new distribution record for this species.

Conclusions: People in Gaomi hold valuable knowledge about the use of medicinal plants; however, their knowledge has not been comprehensively documented. The therapeutic uses of the documented medicinal plants will provide a basis for further pharmacological and phytochemical investigations. Additionally, the result of this study indicated that the elder people in Gaomi have more traditional knowledge of plant medicines than the younger ones.
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http://dx.doi.org/10.1016/j.jep.2020.113228DOI Listing
January 2021

Construction and Analysis of Competing Endogenous RNA Networks for Breast Cancer Based on TCGA Dataset.

Biomed Res Int 2020 24;2020:4078596. Epub 2020 Jul 24.

Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong Province, China 261000.

Background: Long noncoding RNAs (lncRNAs) act as competing endogenous RNAs for microRNAs in cancer metastasis. However, the roles of lncRNA-mediated competing endogenous RNA (ceRNA) networks for breast cancer (BC) are still unclear. . The expression profiles of mRNAs, lncRNAs, and miRNAs with BC were extracted from The Cancer Genome Atlas database. Weighted gene coexpression network analysis was conducted to extract differentially expressed mRNAs (DEmRNAs) that might be core genes. Through miRWalk, TargetScan, and miRDB to predict the target genes, an abnormal lncRNA-miRNA-mRNA ceRNA network with BC was constructed. The survival possibilities of mRNAs, miRNAs, and lncRNAs for patients with BC were determined by Kaplan-Meier survival curves and Oncomine.

Results: We identified 2134 DEmRNAs, 1059 differentially expressed lncRNAs (DElncRNAs), and 86 differentially expressed miRNAs (DEmiRNAs). We then compose a ceRNA network for BC, including 72 DElncRNAs, 8 DEmiRNAs, and 12 DEmRNAs. After verification, 2 lncRNAs (LINC00466, LINC00460), 1 miRNA (Hsa-mir-204), and 5 mRNAs (TGFBR2, CDH2, CHRDL1, FGF2, and CHL1) were meaningful as prognostic biomarkers for BC patients. In the ceRNA network, we found that three axes were present in 10 RNAs related to the prognosis of BC, namely, LINC00466-Hsa-mir-204-TGFBR2, LINC00466-Hsa-mir-204-CDH2, and LINC00466-Hsa-mir-204-CHRDL1.

Conclusion: This study highlighted lncRNA-miRNA-mRNA ceRNA related to the pathogenesis of BC, which might be used for latent diagnostic biomarkers and therapeutic targets for BC.
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http://dx.doi.org/10.1155/2020/4078596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396095PMC
July 2020

A Hybrid Landslide Displacement Prediction Method Based on CEEMD and DTW-ACO-SVR-Cases Studied in the Three Gorges Reservoir Area.

Sensors (Basel) 2020 Jul 31;20(15). Epub 2020 Jul 31.

Faculty of Engineering, China University of Geosciences, Wuhan 430074, Hubei, China.

Accurately predicting the surface displacement of the landslide is important and necessary. However, most of the existing research has ignored the frequency component of inducing factors and how it affects the landslide deformation. Therefore, a hybrid displacement prediction model based on time series theory and various intelligent algorithms was proposed in this paper to study the effect of frequency components. Firstly, the monitoring displacement of landslide from the Three Gorges Reservoir area (TGRA) was decomposed into the trend and periodic components by complete ensemble empirical mode decomposition (CEEMD). The trend component can be predicted by the least square method. Then, time series of inducing factors like rainfall and reservoir level was reconstructed into high frequency components and low frequency components with CEEMD and -test, respectively. The dominant factors were selected by the method of dynamic time warping (DTW) from the frequency components and other common factors (e.g., current monthly rainfall). Finally, the ant colony optimization-based support vector machine regression (ACO-SVR) is utilized for prediction purposes in the TGRA. The results demonstrate that after considering the frequency components of landslide-induced factors, the accuracy of the displacement prediction model based on ACO-SVR is better than that of other models based on SVR and GA-SVR.
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http://dx.doi.org/10.3390/s20154287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435852PMC
July 2020

Association of Symptoms with Eating Habits and Food Preferences in Chronic Gastritis Patients: A Cross-Sectional Study.

Evid Based Complement Alternat Med 2020 9;2020:5197201. Epub 2020 Jul 9.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.

Purpose: There is a lack of research on the relationship between symptoms and dietary factors of chronic gastritis (CG) patients, and the contribution of dietary management in relieving symptoms of CG patients has not attracted enough attention. This study aimed to identify the associations between different symptoms and dietary factors. . All CG patients in this cross-sectional study were recruited from 3 hospitals in Beijing, China, from October 2015 to January 2016. Association Rule Mining analysis was performed to identify the correlations between gastrointestinal symptoms and dietary factors (including eating habits and food preferences), and subgroup analysis focused on gender differences.

Results: The majority of patients (58.17%) reported that their symptoms were related to dietary factors. About 53% reported that they had the habit of "eating too fast," followed by "irregular mealtimes" (29.66%) and "eating leftover food" (28.14%). Sweets (27.57%), spicy foods (25.10%), and meat (24.33%) were the most popular among all participants. Stomachache and gastric distention were the most common symptoms and were both associated with irregular mealtimes, irregular meal sizes, eating out in restaurants, meats, barbecue, fried foods, sour foods, sweets, snacks, and salty foods (support >0.05 and lift >1.0). Their most strongly associated factors were irregular meal sizes, barbecues, and snacks (lift >1.2). In addition, irregular mealtimes, salty foods, and sweet foods may be important diet factors influencing the symptoms in CG patients (support >0.05 and lift >1.0), as they were associated with almost all dyspeptic symptoms in the whole group and subgroup analyses. Furthermore, alcohol, barbecue, and spicy foods were associated with almost all symptoms for males (support >0.05 and lift >1.0), but sweets were the only dietary factor associated with all symptoms for females (support >0.05 and lift >1.0).

Conclusion: This study has provided new data for the association of symptoms with eating habits and food preferences in CG patients. The role of individual daily management schemes, such as dietary or lifestyle programs, needs more attention.
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http://dx.doi.org/10.1155/2020/5197201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368216PMC
July 2020

Celastrol inhibits ezrin-mediated migration of hepatocellular carcinoma cells.

Sci Rep 2020 07 9;10(1):11273. Epub 2020 Jul 9.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.

Progression of hepatocellular carcinoma involves multiple genetic and epigenetic alterations that promote cancer invasion and metastasis. Our recent study revealed that hyperphosphorylation of ezrin promotes intrahepatic metastasis in vivo and cell migration in vitro. Celastrol is a natural product from traditional Chinese medicine which has been used in treating liver cancer. However, the mechanism of action underlying celastrol treatment was less clear. Here we show that ROCK2 is a novel target of celastrol and inhibition of ROCK2 suppresses elicited ezrin activation and liver cancer cell migration. Using cell monolayer wound healing, we carried out a phenotype-based screen of natural products and discovered the efficacy of celastrol in inhibiting cell migration. The molecular target of celastrol was identified as ROCK2 using celastrol affinity pull-down assay. Our molecular docking analyses indicated celastrol binds to the active site of ROCK2 kinase. Mechanistically, celastrol inhibits the ROCK2-mediated phosphorylation of ezrin at Thr567 which harnesses liver cancer cell migration. Our findings suggest that targeting ROCK2-ezrin signaling is a potential therapeutic niche for celastrol-based intervention of cancer progression in hepatocellular carcinoma.
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http://dx.doi.org/10.1038/s41598-020-68238-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347585PMC
July 2020

Corrigendum to "Dysbiosis of gut microbiota is associated with gastric carcinogenesis in rats" [Biomed Pharmacother. 126 (2020) 110036].

Biomed Pharmacother 2020 08 29;128:110269. Epub 2020 May 29.

Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. Electronic address:

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http://dx.doi.org/10.1016/j.biopha.2020.110269DOI Listing
August 2020

Meta-Analysis of Paclitaxel-Based Chemotherapy Combined With Traditional Chinese Medicines for Gastric Cancer Treatment.

Front Pharmacol 2020 27;11:132. Epub 2020 Feb 27.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

This study aimed to compare the efficacy and safety of traditional Chinese medicines (TCMs) combined with paclitaxel-based chemotherapy and paclitaxel-based chemotherapy alone for gastric cancer treatment. Literature searches (up to September 25, 2019) were performed using the Cochrane Library, EMBASE, PubMed, Chinese Science and Technology Journals (CQVIP), Wanfang, and China Academic Journals (CNKI) databases. Data from 14 randomized controlled trials (RCTs), with 1,109 participants, were included. The results indicated that, compared with paclitaxel-based chemotherapy alone, the combination of TCMs and paclitaxel-based chemotherapy significantly improved the tumor response rate (TRR; RR: 1.39; 95% CI: 1.24-1.57; < 0.001, = 12%), increased the quality of life based on the Karnofsky Performance Scale score (RR: 1.53; 95% CI: 1.19-1.96; < 0.001, = 0%), and reduced the side effects, such as neutropenia (RR: 0.68; 95% CI: 0.55-0.84; < 0.001, = 44%), leukopenia (RR: 0.69; 95% CI: 0.54-0.90; < 0.01, = 40%), thrombocytopenia (RR: 0.66; 95% CI: 0.46-0.96; < 0.05, = 32%), and nausea and vomiting (RR: 0.50; 95% CI: 0.32-0.80; < 0.01, = 85%). Hepatic dysfunction (RR: 0.63; 95% CI: 0.33-1.20; = 0.16, = 0%), neurotoxicity (RR: 0.64; 95% CI: 0.26-1.55; = 0.32, = 0%), and anemia (RR: 0.65; 95% CI: 0.40-1.04; = 0.07, = 0%) were similar between the two groups. Evidence from the meta-analysis suggested that compared with paclitaxel-based chemotherapy alone, the combination of TCMs and paclitaxel-based chemotherapy may increase the TRR, improve quality of life, and reduce multiple chemotherapy-related side effects in gastric cancer patients. Additional rigorously designed large RCTs are required to confirm the efficacy and safety of this treatment.
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http://dx.doi.org/10.3389/fphar.2020.00132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056897PMC
February 2020

Dysbiosis of gut microbiota is associated with gastric carcinogenesis in rats.

Biomed Pharmacother 2020 Jun 13;126:110036. Epub 2020 Mar 13.

Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. Electronic address:

Objectives: Although many studies have examined changes in gut microbiota composition in gastric carcinogenesis to clarify the mechanism of action of anticancer drugs, it is unclear whether animal models of gastric carcinogenesis adequately reflect the disease in humans.

Methods: To address this issue, the present study investigated changes in the gut microbiome profile of a rat model of gastric carcinogenesis established using a combination of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), sodium salicylate, irregular fasting, and ranitidine. The rats were divided into control (Normal), chronic non-atrophic gastritis (CNAG), chronic atrophic gastritis (CAG), precancerous lesion of gastric cancer (PLGC), and gastric cancer (GC) groups according to histopathological features. Gut microbiome in gastric carcinogenesis profiling was performed by 16S rRNA gene sequencing of rat feces samples.

Results: We found that gut bacterial species richness increased whereas species diversity decreased during gastric carcinogenesis, with the most significant changes detected in the PLGC group. Gut microbiota community composition differed across groups, with the greatest similarities observed between CNAG and CAG groups and between PLGC and GC groups. There were significant differences in taxonomic representation at the phylum level: the PLGC group had the highest ratio of Firmicutes/Bacteroidetes whereas the GC group had the highest abundance of Proteobacteria and Actinobacteria.

Conclusions: These results indicate that changes in the gut microbiome in a rat model of MNNG-induced gastric carcinogenesis are similar to those observed in humans, thus providing a useful tool for evaluating the efficacy and mechanism of action of novel monotherapies or drug combinations for the treatment of gastric carcinogenesis.
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http://dx.doi.org/10.1016/j.biopha.2020.110036DOI Listing
June 2020

Risk Factors for Urosepsis after Minimally Invasive Percutaneous Nephrolithotomy in Patients with Preoperative Urinary Tract Infection.

Biomed Res Int 2020 2;2020:1354672. Epub 2020 Jan 2.

Department of Urology, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan 430030, China.

The purpose of this study was to assess risk factors of urosepsis after minimally invasive percutaneous nephrolithotomy (MPCNL) for the treatment of upper urinary tract stones in patients with preoperative urinary tract infection (UTI) and to explore preventive measures. Between 2008 and 2016, patients with preoperative UTI who underwent MPCNL for upper urinary tract stones were retrospectively collected. Patients were divided into nonurosepsis and urosepsis groups. Perioperative outcomes of all patients were evaluated and compared between the two groups. Risk factors for post-MPCNL urosepsis were investigated using univariate and multivariate regression analysis. A total of 843 patients including 22 patients with postoperative urosepsis (urosepsis group) and 821 patients without urosepsis (nonurosepsis group) were finally included in this study. All patients with postoperative urosepsis were cured and discharged after treatment. In univariate analysis it was demonstrated that the incidence of urosepsis after MPCNL was significantly correlated with channel size (=0.001), surgical time (=0.003), as well as the tear of the collection system and percutaneous renal channel crossing the renal papilla (=0.004). Moreover, multivariate analysis showed that smaller channel size (OR = 11.192, 95% CI: 2.425-51.650, =0.002), longer surgical time (OR = 6.762, 95% CI: 1.712-17.844, =0.008), and tear of collection system and percutaneous renal channel crossing the renal papilla (OR = 5.531, 95% CI 1.228-14.469, =0.012) were independent risk factors for urosepsis following MPCNL in patients with preoperative UTI. In conclusion, in patients with preoperative UTI undergoing MPCNL for upper urinary tract stones, smaller channel size, prolonged operation time, as well as tear of the collection system and percutaneous renal channel crossing the renal papilla are independent risk factors for postoperative urosepsis. Therefore, it is indicated that, in clinical practice, it is of great significance to choose appropriate channel size and avoid renal injury and control surgical time to prevent the urosepsis after MPCNL in patients with preoperative UTI.
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http://dx.doi.org/10.1155/2020/1354672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970485PMC
September 2020

Index-based dietary patterns in relation to gastric cancer risk: a systematic review and meta-analysis.

Br J Nutr 2020 05 26;123(9):964-974. Epub 2019 Nov 26.

Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China.

Dietary indices are widely used in diet quality measurement, and the index-based dietary patterns are related to gastric cancer risk. To evaluate the relationship between different kinds of index-based dietary patterns and gastric cancer risk, we systematically searched four English-language databases and four Chinese-language databases. The quality of studies was assessed by the Newcastle–Ottawa Scale. Meta-analyses were performed to estimate the association between gastric cancer incidence and different types of index-based dietary patterns. The OR and hazard ratios (HR) of gastric cancer incidence were calculated by regression models in case–control studies and prospective cohort studies, respectively. The studies were pooled in the random effects model to calculate the summarised risk estimate of the highest quantile interval of dietary indices, taking the lowest as the referent. The dietary indices included different versions of Mediterranean diet score (MDS) and dietary inflammatory index (DII), healthy eating index, Chinese Food Pagoda score and food index score. The meta-analysis was carried out for studies on MDS and DII. The combined OR of gastric cancer for the highest MDS v. the referent was 0·42 (95 % CI 0·2, 0·86), and the combined HR was 0·89 (95 % CI 0·68, 1·17). The combined OR for DII was 2·11 (95 % CI 1·41, 3·15). Higher Mediterranean dietary pattern consumption might reduce gastric cancer risk, while higher inflammatory diet pattern consumption might increase gastric cancer risk.
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http://dx.doi.org/10.1017/S0007114519002976DOI Listing
May 2020