Publications by authors named "Xiaoqiang Liu"

276 Publications

Identification of a Novel PPAR Signature for Predicting Prognosis, Immune Microenvironment, and Chemotherapy Response in Bladder Cancer.

PPAR Res 2021 30;2021:7056506. Epub 2021 Dec 30.

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

Background: Mounting evidence has confirmed that peroxisome proliferator-activated receptors (PPARs) played a crucial role in the development and progression of bladder cancer (BLCA). The purpose of this study is to comprehensively investigate the function and prognostic value of PPAR-targeted genes in BLCA.

Methods: The RNA sequencing data and clinical information of BLCA patients were acquired from The Cancer Genome Atlas (TCGA). The differentially expressed PPAR-targeted genes were investigated. Cox analysis and least absolute shrinkage and selection operator (LASSO) analysis were performed for screening prognostic PPAR-targeted genes and constructing the prognostic PPAR signature and then validated by GSE13507 cohort and GSE32894 cohort. A nomogram was constructed to predict the outcomes of BLCA patients in combination with PPAR signature and clinical factors. Gene set enrichment analysis (GSEA) and immune cell infiltration were implemented to explore the molecular characteristics of the signature. The Genomics of Drug Sensitivity in Cancer (GDSC) database was used to predict the chemotherapy responses of the prognostic signature. The candidate small molecule drugs targeting PPAR-targeted genes were screened by the CMAP database.

Results: We constructed and validated the prognostic signature comprising of 4 PPAR-targeted genes (CPT1B, CALR, AHNAK, and FADS2), which was an independent prognostic biomarker in BLCA patients. A nomogram based on the signature and clinical factors was established in the TCGA set, and the calibration plots displayed the excellent predictive capacity. GSEA analysis indicated that PPAR signature was implicated in multiple oncogenic signaling pathways and correlated with tumor immune cell infiltration. Patients in the high-risk groups showed greater sensitivity to chemotherapy than those in the low-risk groups. Moreover, 11 candidate small molecule drugs were identified for the treatment of BLCA.

Conclusion: We constructed and validated a novel PPAR signature, which showed the excellent performance in predicting prognosis and chemotherapy sensitivity of BLCA patients.
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http://dx.doi.org/10.1155/2021/7056506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8749226PMC
December 2021

Identification of Key microRNAs in Diabetes Mellitus Erectile Dysfunction Rats with Stem Cell Therapy by Bioinformatic Analysis of Deep Sequencing Data.

World J Mens Health 2022 Jan 2. Epub 2022 Jan 2.

Department of Urology, Tianjin Medical University General Hospital, Tianjin, China.

Purpose: Diabetes mellitus erectile dysfunction (DMED) is a common resulting complication of diabetes. Studies have shown mesenchymal stem cell (MSC)-based therapy was beneficial in alleviating erectile function of DMED rats. While the pathogenesis of DMED and the mechanism MSCs actions are unclear.

Materials And Methods: We constructed a rat model of DMED with or without intracavernous injection of MSCs, and performed microRNA (miRNA) sequencing of corpora cavernosa tissues.

Results: We identified three overlapping differentially expressed miRNAs (rno-miR-1298, rno-miR-122-5p, and rno-miR-6321) of the normal control group, DMED group, and DMED+MSCs group. We predicted 285 target genes of three miRNAs through RNAhybrid and miRanda database and constructed a miRNA-target gene network through Cytoscape. Next, we constructed protein-protein interaction networks through STRING database and identified the top 10 hub genes with highest connectivity scores. Five GO terms including cellular response to growth factor stimulus (GO:0071363), ossification (GO:0001503), response to steroid hormone (GO:0048545), angiogenesis (GO:0001525), positive regulation of apoptotic process (GO:0043065), and one Reactome pathway (Innate Immune System) were significantly enriched by 10 hub genes using the Metascape database. We selected the GSE2457 dataset to validate the expression of hub genes and found only the expression of B4galt1 was statistically different (p<0.001). B4galt1 was highly expressed in penile tissues of diabetic rats and would be negatively regulated by rno-miR-1298.

Conclusions: Three key miRNAs were identified in DMED rats with stem cell therapy and the miR-1298/B4GalT1 axis might exert function in stem cell therapy for ED.
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http://dx.doi.org/10.5534/wjmh.210147DOI Listing
January 2022

Immunosuppressive effects of dimethyl fumarate on dendritic cell maturation and migration: a potent protector for coronary heart disease.

Immunopharmacol Immunotoxicol 2022 Jan 12:1-8. Epub 2022 Jan 12.

Department of Cardiology, Shanghai General Hospital of Nanjing Medical University, Shanghai, China.

Dendritic cells (DCs), as a bridge between innate and adaptive immunity, play key roles in atherogenesis, particularly in plaque rupture, the underlying pathophysiologic cause of myocardial infarction. Targeting DC functions, including maturation and migration to atherosclerotic plaques, may be a novel therapeutic approach to atherosclerotic disease. Dimethyl fumarate (DMF), an agent consisting of a combination of fumaric acid esters, in current study were found to be able to suppress DC maturation by reducing the expression of costimulatory molecules and MHC class II and by blocking cytokine secretion. In addition, DMF efficiently inhibited the migration of activated DCs and by reducing the expression of chemokine receptor 7 (CCR7). Additionally, DMF efficiently inhibited the expression of the costimulatory molecule CD86, as well as the chemokine receptor CCR7 and the C-X-C motif chemokine receptor 4 (CXCR4), in healthy donor-derived purified DCs that had been stimulated by ST-segment elevation myocardial infarction (STEMI) patient serum. This study points to the potent therapeutic value of DMF for protecting against cardiovascular disease by suppressing DC functions.
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http://dx.doi.org/10.1080/08923973.2021.2025245DOI Listing
January 2022

Nrf2/HO-1 pathway is involved the anti-inflammatory action of intrauterine infusion of platelet-rich plasma against lipopolysaccharides in endometritis.

Immunopharmacol Immunotoxicol 2022 Jan 3:1-10. Epub 2022 Jan 3.

Reproductive Medicine Center, Qingdao Women and Children's Hospital, Qingdao, P. R. China.

Objective(s): Endometritis is the inflammatory response of the uterine lining which is linked to infertility. Administration of platelet-rich plasma (PRP) represents a well-recommended strategy for the treatment of endometrium-associated infertility. In this study, we set to characterize the role and molecular mechanism of PRP intrauterine infusion in mice with endometritis.

Methods: A mouse model of endometritis was established using lipopolysaccharide (LPS). Mouse endometrial epithelial cells were obtained in primary culture. PRP-treated cells were assayed for proliferative and apoptotic activities. Moreover, iNOS expression and chemokine and inflammatory factor contents in cells were assessed using RT-qPCR and ELISA. The mice were subjected to PRP intrauterine infusion. The expression of genes related to uterine development was analyzed by qPCR and the ki-67 content and caspase-3 activation in endometrial tissues were examined by immunohistochemistry. Finally, the Nrf2/HO-1 pathway activity in tissues was examined by Western blot.

Results: LPS induced inflammatory cell recruitment and tissue damage in the endometrium of mice, along with significantly increased levels of inflammatory and chemokine factors. PRP significantly enhanced endometrial epithelial cell activity, decreased apoptosis, and reduced inflammatory factor secretion. In addition, PRP intrauterine infusion significantly increased the expression of genes related to uterine development, promoted tissue proliferation, decreased apoptosis, and diminished inflammatory response in endometrial tissues of mice. PRP intrauterine infusion significantly elevated Nrf2/HO-1 pathway activity in endometrial epithelial cells and tissues.

Conclusion: PRP intrauterine infusion significantly inhibited endometrial cell injury and alleviated the inflammatory response through activating the Nrf2/HO-1 pathway.
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http://dx.doi.org/10.1080/08923973.2021.2012483DOI Listing
January 2022

Functional Preservation and Oncologic Control following Robot-Assisted versus Laparoscopic Radical Prostatectomy for Intermediate- and High-Risk Localized Prostate Cancer: A Propensity Score Matched Analysis.

J Oncol 2021 21;2021:4375722. Epub 2021 Dec 21.

Department of Urology, The First Affiliated Hospital of Nanchang University, Yongwai Street 17, Nanchang, Jiangxi Province, China.

Aim: To evaluate the urinary continence (UC), erectile function, and cancer control obtained following robot-assisted radical prostatectomy (RARP) and laparoscopic radical prostatectomy (LRP) for intermediate- and high-risk localized prostate cancer (PCa).

Materials And Methods: 232 patients bearing intermediate- and high-risk localized PCa were enrolled in this study. Perioperative, functional, and oncological outcomes were analyzed after applying the propensity score matched method.

Results: Within the matched cohort, the RARP group was corrected with a significantly shorter mean operative time than the LRP group ( < 0.001). Patients in the RARP arm were also at a lower risk of ≤ Grade II complications than those in the LRP group ( = 0.036). Meanwhile, the proportions of transfusion and ≥ Grade II complications in the RARP group were similar to those in the LRP group ( = 0.192 and  = 1.000, respectively). No significant differences regarding the rates of pT3 disease and positive surgical margin existed between the two groups. RARP versus LRP tended to a significantly higher percentage of UC recovery within the follow-up period. Significant differences were also found between the RARP and LRP arms in terms of erectile function at postoperative 6 months and the last follow-up ( = 0.013 and  = 0.009, respectively). Statistical comparability in biochemical recurrence-free survival was observed between the two groups ( = 0.228).

Conclusions: For the surgical management of intermediate- and high-risk localized PCa, RARP tended to a lower risk of ≤ Grade II complications and superior functional preservation without cancer control being compromised than LRP.
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http://dx.doi.org/10.1155/2021/4375722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714374PMC
December 2021

CCDC40 mutation as a cause of infertility in a Chinese family with primary ciliary dyskinesia.

Medicine (Baltimore) 2021 Dec;100(51):e28275

Department of Urology, Tianjin Medical University General Hospital, Tianjin, China.

Trial Design: Primary ciliary dyskinesia (PCD) is a genetical disease that inherited in an autosomal-recessive way. Its clinical manifestations (such as male infertility) are mainly caused by defects of motion-related cilia that encoded by mutated genes. Although some mutation has been verified, a number of mutations of PCD remain elusive. The main purpose of this study is to identify mutant genes in a Chinese family with PCD, and to verify the safety and effectiveness of intracytoplasmic sperm injection (ICSI) of infertility caused by PCD.

Methods: Imaging examination was used to exclude pulmonary inflammation and visceral translocation. Semen analysis was used to assess the quality of the proband's sperm. Transmission electron microscopy (TEM) was conducted to assess the ultrastructure of flagella and cilia. Targeted next generation sequencing and Sanger sequencing and qPCR (real-time quantitative polymerase chain reaction detecting system) were applied to identified mutation of Chinese Family suspected of having PCD. Viable sperm were selected by hypo-osmotic swelling test (HOST) for ICSI.

Results: We report 2 novel mutations in CCDC40 gene (c.1259delA and EX17_20 deletion) resulted in immobility of sperm and infertility of the proband. These mutations were confirmed in the proband's sister (heterozygous) and his parents (recessive carrier) by Sanger sequencing and qPCR. All the spermatozoa from the proband were immotile. Ultrastructural defects were found in flagella and cilia of proband and his sister. Viable sperms were selected by HOST for ICSI and fertilized 9 of 21 eggs. Two frozen embryos were transplanted and a healthy 3500 g boy was delivered at 40 + 4 weeks' gestation. And then, we summarized the genes related to PCD and the mutant sites of CCDC40 gene.

Conclusion: We reported 2 novel mutants in CCDC40 gene (c.1259delA and EX17_20 deletion), which could be candidates for genetic diagnosis in PCD patients. The combination of targeted next generation sequencing and Sanger sequencing may be a useful tool to diagnose PCD. ICSI is a considerable method in treatment of infertility caused by PCD.
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http://dx.doi.org/10.1097/MD.0000000000028275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8702141PMC
December 2021

The Role of Critical N6-Methyladenosine-Related Long Non-Coding RNAs and Their Correlations with Immune Checkpoints in Renal Clear Cell Carcinoma.

Int J Gen Med 2021 14;14:9773-9787. Epub 2021 Dec 14.

Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, People's Republic of China.

Purpose: This study aimed to evaluate the functions of critical N6-methyladenosine (m6A)-related long non-coding RNAs (lncRNAs) and their correlations with immunotherapeutic targets in clear cell renal cell carcinoma (ccRCC).

Methods: m6A-related lncRNAs were analyzed using the dataset from The Cancer Genome Atlas database via Pearson correlation analysis. Then, their prognostic functions in patients with ccRCC were determined via univariate Cox analysis. A prognostic m6A-related lncRNA signature (MRLS) in ccRCC was established using the least absolute shrinkage and selection operator (LASSO) Cox regression model. In addition, the correlations between these prognostic m6A-related lncRNAs with immune checkpoints were further evaluated in clinical samples.

Results: MRLS was established by the LASSO Cox regression model on the basis of seven prognostic m6A-related lncRNAs. The risk score for each patient was calculated using the MRLS model, and the patients were further stratified into high- and low-risk subgroups. The MRLS model was validated with a robust prognostic ability by the stratification analysis. On the basis of age, grade, stage, and risk score, a nomogram was developed with a strong reliability in forecasting the overall survival percentages of the patients with ccRCC. Moreover, seven prognostic m6A-related lncRNAs enrolled in the MRLS model were found to be correlated with various immunotherapeutic targets, namely, PD-1, PD-L1, CTLA4, and LAG3, and the expression levels of which in the high-risk subgroup were significantly higher than those in the low-risk subgroup. The significant correlations between LINC00342 and the aforementioned immunotherapeutic targets were also confirmed in clinical samples.

Conclusion: In this study, seven m6A-related lncRNAs were identified as potential biomarkers for forecasting the prognosis of patients with ccRCC and evaluating the efficacy of immunotherapy for these patients. Furthermore, a prognostic and predictive MRLS model with a high reliability was constructed to predict the overall survival probability of patients with ccRCC.
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http://dx.doi.org/10.2147/IJGM.S344771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8684405PMC
December 2021

Identification of a novel signature based on unfolded protein response-related gene for predicting prognosis in bladder cancer.

Hum Genomics 2021 12 20;15(1):73. Epub 2021 Dec 20.

Department of Urology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, People's Republic of China.

Background: The unfolded protein response (UPR) served as a vital role in the progression of tumors, but the molecule mechanisms of UPR in bladder cancer (BLCA) have been not fully investigated.

Methods: We identified differentially expressed unfolded protein response-related genes (UPRRGs) between BLCA samples and normal bladder samples in the Cancer Genome Atlas (TCGA) database. Univariate Cox analysis and the least absolute shrinkage and selection operator penalized Cox regression analysis were used to construct a prognostic signature in the TCGA set. We implemented the validation of the prognostic signature in GSE13507 from the Gene Expression Omnibus database. The ESTIMATE, CIBERSORT, and ssGSEA algorithms were used to explore the correlation between the prognostic signature and immune cells infiltration as well as key immune checkpoints (PD-1, PD-L1, CTLA-4, and HAVCR2). GDSC database analyses were conducted to investigate the chemotherapy sensitivity among different groups. GSEA analysis was used to explore the potential mechanisms of UPR-based signature.

Results: A prognostic signature comprising of seven genes (CALR, CRYAB, DNAJB4, KDELR3, CREB3L3, HSPB6, and FBXO6) was constructed to predict the outcome of BLCA. Based on the UPRRGs signature, the patients with BLCA could be classified into low-risk groups and high-risk groups. Patients with BLCA in the low-risk groups showed the more favorable outcomes than those in the high-risk groups, which was verified in GSE13507 set. This signature could serve as an autocephalous prognostic factor in BLCA. A nomogram based on risk score and clinical characteristics was established to predict the over survival of BLCA patients. Furthermore, the signature was closely related to immune checkpoints (PD-L1, CTLA-4, and HAVCR2) and immune cells infiltration including CD8 T cells, follicular helper T cells, activated dendritic cells, and M2 macrophages. GSEA analysis indicated that immune and carcinogenic pathways were enriched in high-risk group.

Conclusions: We identified a novel unfolded protein response-related gene signature which could predict the over survival, immune microenvironment, and chemotherapy response of patients with bladder cancer.
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http://dx.doi.org/10.1186/s40246-021-00372-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686253PMC
December 2021

Exploring the Mechanism of Action of Canmei Formula Against Colorectal Adenoma Through Multi-Omics Technique.

Front Cell Dev Biol 2021 29;9:778826. Epub 2021 Nov 29.

Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Canmei formula (CMF) is a traditional Chinese medicine compound with definite effect on the prevention and treatment of colorectal adenoma (CRA). CMF can prevent the transformation of intestinal inflammation to cancer. This study explored the mechanism of action of CMF in anti-CRA using multi-omics techniques. The mice were randomly divided into four groups: blank group (Control), high-fat diet (HFD) + AOM/DSS colorectal adenoma model (ADH) groups, Canmei formula treatment group (ADH-CMF) and sulfasalazine treatment group (Sul). Except for the blank group, ADH model was established in the other three groups by intraperitoneal injection with AOM reagent, and then mice were given 2.5% DSS in free drinking water and high-fat diet. The mice in the blank group and ADH groups were intragastrically perfused with normal saline, and the mice in the other two groups were treated with corresponding drugs for 20 weeks. During this period, the changes of physical signs of mice in each group were observed. The differentially expressed genes and proteins in the Control group, ADH group and ADH-CMF group were detected by RNA-seq transcriptome sequencing and Tandem Mass Tags (TMT) quantitative proteomics. After the combined analysis and verification, the key targets were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Moreover, the changes of intestinal flora in mice of the three groups were examined. A total of 2,548 differential genes were obtained by transcriptomics analysis, and 45 differential proteins were obtained by proteomics analysis. The results of proteomics data and experimental verification showed that CMF mainly affected the Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase (LHPP) target. GO analysis showed that the targets of CMF were involved in the biological processes such as cellular process, metabolic process and biological regulation. KEGG analysis showed that those genes were involved in oxidative phosphorylation, cell senescence, and metabolic pathways. Studies have shown that LHPP overexpression impeded colorectal cancer cell growth and proliferation , and was associated with a change in PI3K/AKT activity. The results of 16S DNA high-throughput sequencing showed that CMF could effectively regulate the abundance of Bifidobacterium, Candidatus_Saccharimonas and Erysipelatoclostridium in the intestinal flora at the genus level. CMF regulates LHPP via the PI3K/AKT signaling pathway. CMF affects the abundance of specific intestinal flora and can regulate the disorder of intestinal flora to achieve the role of prevention and treatment of CRA.
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http://dx.doi.org/10.3389/fcell.2021.778826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672438PMC
November 2021

Immunogenicity and safety of inactivated enterovirus A71 vaccines in children aged 6-35 months in China: a non-inferiority, randomised controlled trial.

Lancet Reg Health West Pac 2021 Nov 2;16:100284. Epub 2021 Nov 2.

National Immunization Programme, Chinese Center for Disease Control and Prevention, Beijing, China.

Background: China's three inactivated enterovirus A71 (EV-A71) vaccines are the first and currently world's only EV-A71 vaccines approved by a national regulatory authority and used to prevent EV-A71 associated diseases. The three vaccines vary by vaccine strain, manufacturing cell substrate, and antigen dose, but no head-to-head comparisons of these vaccines have been done. We compared immunogenicity of the vaccines in children 6-35 months old.

Methods: We recruited healthy children aged 6-35 months who lived in a study site county into a multicentre, open-label, non-inferiority, three-group, randomised controlled trial that was conducted in five counties in China. Enrolled children were randomly assigned (1:1:1) to receive two doses of one of the three EV-A71 vaccines. The primary outcome was the proportion of children with EV-A71 neutralizing antibody seroconversion 4 weeks after the second dose; a secondary outcome was adverse events in the 4 weeks after each dose. Analyses of immunogenicity included all children who completed the study (per-protocol analysis). Safety analysis included all children completed safety follow-up after at least one. We used a 10% margin to establish non-inferiority. This trial was registered on a World Health Organization platform: Chinese Clinical Trial Registry (ChiCTR1900026663).

Findings: 1631 children were assessed for eligibility between Nov 4 and Nov 20, 2019. Of 1500 (92%) enrolled children, 500 were assigned to vaccine group A, B, or C; 483 in group A,484 in group B, and 487 in group C completed the study. Before dose one, the seropositive rates in groups A, B, and C were 9.7%, 7.2%, and 7.0%. Four weeks after the second dose, seroconversion rates of groups A, B, and C were 98.8%, 99.4% and 99.8% - mutually non-inferior in all two-group comparisons. There were no serious adverse events in any group and no evidence of a difference among the three groups in the incidence of local adverse event or systemic adverse event. Fever was the most common adverse event. All children with reported adverse events recovered.

Interpretation: Non-inferior and high seroconversion rates and equivalent safety of three EV-A71 vaccines supports use any of these vaccines to prevent EV-A71-associated diseases. These results may be useful for regulators, vaccine policy makers, and immunization programmes in China and in countries where EV-A71 is endemic.
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http://dx.doi.org/10.1016/j.lanwpc.2021.100284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579145PMC
November 2021

Independent Factors Affecting Postoperative Short-Term Urinary Continence Recovery after Robot-Assisted Radical Prostatectomy.

J Oncol 2021 28;2021:9523442. Epub 2021 Nov 28.

Department of Urology, The First Affiliated Hospital of Nanchang University, Yongwai Street 17, Nanchang, Jiangxi, China.

Background: Our team had firstly applied the transvesical approach to robot-assisted radical prostatectomy (RARP) in patients afflicted with localized prostate cancer (PCa). The present study aims to present the postoperative recovery of urinary continence (UC) following the anterior, transvesical, and posterior approaches to RARP for localized PCa and evaluate the independent predictors to early UC recovery after RARP.

Methods: Patients harboring localized PCa and receiving anterior, transvesical, and posterior approaches to RARP between January 2017 and June 2020 were enrolled in this analysis. Results on UC recovery were compared between these three approaches with the Kaplan-Meier method. All clinical and pathological variables were further analyzed via univariable and multivariable regression analysis to determine the independent factors contributing to short-term UC recovery after RARP.

Results: A total of 135, 73, and 66 instances were included in the anterior, transvesical, and posterior groups, respectively. Over the postoperative follow-up period, both the transvesical and posterior approaches showed an advantage over the anterior approach in promoting postoperative UC recovery (both values <0.001). Three months after surgery, 55 (40.7%), 4 (5.5%), and 5 (7.6%) patients failed to UC in the anterior, transvesical, and posterior groups, respectively. Patient age, preoperative PSA, prostate volume, biopsy Gleason score, surgical approach, extended lymph node dissection technique, nerve-sparing technique, and positive lymph node were related to UC status based on univariable analyses ( < 0.05). Multivariable analysis results point patient age, prostate volume, surgical approach, and nerve-sparing technique as independent factors that affect postoperative UC recovery after RARP.

Conclusions: The application of transvesical approach to RARP for localized PCa could obtain promising outcomes in terms of postoperative UC recovery. In addition, surgical strategies encompassing the nerve-sparing technique and the Retzius-sparing procedures, namely, the transvesical or posterior approach, during RARP could independently enable early achievement of postoperative continence.
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http://dx.doi.org/10.1155/2021/9523442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645355PMC
November 2021

The Prognosis of Leptin rs2167270 G > A (G19A) Polymorphism in the Risk of Cancer: A Meta-Analysis.

Front Oncol 2021 18;11:754162. Epub 2021 Nov 18.

Department of Urology, Tianjin Medical University General Hospital, Tianjin, China.

Background: Although the effect of the LEP G19A (rs2167270) polymorphism on cancers is assumed, the results of its influence have been contradictory. A meta-analysis was conducted to precisely verify the relationships between LEP G19A and the development of digestion-related cancers.

Methods: Investigators systematically searched the literature in PubMed, Embase, and Web of Science and used STATA software 14.0 for the meta-analysis. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the associations. Subgroup analyses stratified by ethnicity, cancer type, and cancer system were further conducted to assess the relationship between the LEP G19A polymorphism and digestion-related cancers.

Results: In the overall population, we found a significant relationship with overall cancer (allele comparison: OR = 0.921, = 0.000; dominant comparison: OR = 0.923, = 0.004; recessive comparison: OR = 0.842, = 0.000; homozygote model: OR = 0.0843, = 0.001). In a subgroup analysis conducted by ethnicity, we obtained significant results in Asians (Asian allele comparison: OR = 0.885, = 0.000; dominant comparison: OR = 0.862, = 0.000; homozygote model: OR = 0.824, = 0.039; and heterozygote comparison: OR = 0.868, = 0.000) but not in Caucasians. In a subgroup analysis conducted by cancer type and cancer system, we obtained significant results that the LEP G19A polymorphism may decrease the risk of colorectal cancer, esophageal cancer, digestive system cancer, and urinary system cancer.

Conclusions: This meta-analysis revealed that the LEP G19A polymorphism may decrease the risk of cancer.
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http://dx.doi.org/10.3389/fonc.2021.754162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637904PMC
November 2021

Hydro-morphodynamics triggered by extreme riverine floods in a mega fluvial-tidal delta.

Sci Total Environ 2022 Feb 2;809:152076. Epub 2021 Dec 2.

State Key Laboratory of Estuarine and Coastal Research, East China Normal University, Shanghai 200241, China.

Maintaining accretion and progradation in a mega delta is crucial to its geomorphic stability and ecology. Extreme riverine floods can disturb hydro-sediment dynamics with great damage to the deltaic landscape, as for instance deltaic erosion. Nowadays, most mega deltas suffer from sediment starvation. Understanding the impact of extreme floods is a priority to determine the long-term fate of deltaic systems. Herein, we used the Delft 3D model and field data to study the hydraulics and morphodynamics of the 2016 extreme riverine floods in the South Passage (SP) of the Yangtze Delta. Results reveal that extreme floods can increase water levels, velocities, and bed shear stresses in an inner estuarine channel and mouth bar, while the flood has a weak effect in offshore areas. High-energy floods trigger strong tidal asymmetry and Euler residual currents, which intensifies downstream suspended sediment transport and bottom riverbed erosion. In comparison with those during extreme floods in 2016, net erosion after floods passed away was generated with seaward weakened magnitudes, the corresponding mean bathymetric erosion thickness was 19.97 cm, 12.71 cm and 4.62 cm in inner estuarine channel, mouth bar and offshore area, respectively. Even though the seaward deposition patches were due to lower scouring effect and converged sediment. Hydrodynamic increments in deeper channels were more significant, while shoals and deeper areas were strongly eroded with the lowest erosion between -5 m to -6 m isobath. These results further clarified the bathymetric patterns with highlights of extreme riverine floods that can amplify the sediment-insufficient risks in such mega fluvial-tidal delta.
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http://dx.doi.org/10.1016/j.scitotenv.2021.152076DOI Listing
February 2022

Fibrin gel-assisted stone extraction in retrograde intrarenal surgery.

BJU Int 2021 Dec 2. Epub 2021 Dec 2.

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

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http://dx.doi.org/10.1111/bju.15651DOI Listing
December 2021

Antibacterial and antibiofilm activity of Lagotis brachystachya extract against extended-spectrum β-lactamases-producing Escherichia coli from broiler chickens.

Poult Sci 2022 Jan 21;101(1):101555. Epub 2021 Oct 21.

College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address:

Lagotis brachystachya Maxim (L. brachystachya) is an herb widely used in traditional Tibetan medicine. In the present study, the antibacterial activity of L. brachystachya extract to extended-spectrum-lactamases (ESBLs)-producing E. coli was determined by Kirby-Bauer disc diffusion, minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) methods as well as time-kill curve assay. Meanwhile, the biofilm inhibition and eradication effects of L. brachystachya extract on the ESBLs-producing E. coli were evaluated by crystal violet staining, and further confirmed by confocal laser scanning microscope (CLSM) and scanning electron microscopy (SEM). The results indicated that L. brachystachya extract exhibited moderate antibacterial activity, with diameter of inhibition zones varying from 15.4 to 20.3 mm, and the MIC and MBC values were 6.25 to 25 mg/mL and 12.5 to 100 mg/mL, respectively. Time-kill curve showed that 4 × MIC level of L. brachystachya extract concentration of was able to kill 99.9% of ESBLs-producing E. coli after 16 h treatment. The biofilm inhibition rate and eradication rate for the ESBLs-producing E. coli were 35.66 to 79.91% and 22.18 to 56.21% at MIC level of extract concentration, respectively. CLSM images showed that the biofilm became thinner as the ESBLs-producing E. coli isolate exposed to L. brachystachya extract with a concentration-dependent manner from 1/4 × MIC to MIC compared with the control isolate. SEM images indicated that L. brachystachya extract at 1/2 × MIC and MIC levels could evidently inhibit the biofilm formation or eradicate the mature biofilms. The effect of L. brachystachya highlights its potential of antibacterial and antibiofilm activities against the ESBLs-producing E. coli.
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http://dx.doi.org/10.1016/j.psj.2021.101555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637138PMC
January 2022

Comparative analysis of physiological, agronomic and transcriptional responses to drought stress in wheat local varieties from Mongolia and Northern China.

Plant Physiol Biochem 2022 Jan 17;170:23-35. Epub 2021 Nov 17.

Key Laboratory of Plant Resources, Institute of Botany, Chinese Academy of Sciences, Beijing, 100093, China. Electronic address:

Drought is one of the major abiotic stresses that threaten wheat production worldwide, especially in the Mongolian Plateau and adjacent regions. This study aims to find local wheat varieties with high yields and drought resistance at various developmental stages based on agronomic traits and drought resistance indices analysis and explore the underlining molecular mechanisms by transcriptome analysis. Our results revealed that drought stress started at the seedling stage has a greater impact on crop yields. Four types of drought responses were found among the tested varieties. Type 1 and type 2 show low tolerance to drought stress despite high or low yield in control condition, type 3 exhibits high yield under control condition but dropped significantly after drought, and type 4 displays relatively high and stable yields under control and drought conditions. Transcriptome analysis performed with the representative varieties of the four types revealed GO terms and KEGG pathways enriched among drought-triggered differential expressed genes (DEGs). A network containing 18 modules was constructed using weighted gene co-expression analysis (WGCNA). Ten modules were significantly correlated to yield by module-trait correlation, and 3 modules showed Darkhan 144 specific gene expression patterns. C2H2 zinc finger factor-recognized motifs were identified from the promoters of genes in these modules. qRT-PCR confirmed several key DEGs with specific expression patterns and physiological measurements validated the relatively low oxidative damage and high antioxidant capacity in the drought tolerant variety Dankhan 144. These findings provide an important basis for local agriculture and breeding of drought-tolerant high yield wheat varieties.
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http://dx.doi.org/10.1016/j.plaphy.2021.11.026DOI Listing
January 2022

Bioinformatics Analysis to Screen Key Targets of Curcumin against Colorectal Cancer and the Correlation with Tumor-Infiltrating Immune Cells.

Evid Based Complement Alternat Med 2021 12;2021:9132608. Epub 2021 Nov 12.

Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.

Purpose: Curcumin is a potential drug for the treatment of colorectal cancer (CRC). Its mechanism of action has not been elucidated. This study aims to investigate the mechanism of action of curcumin in the treatment of CRC via bioinformatics methods such as network pharmacology and molecular docking.

Methods: The targets of curcumin and CRC were obtained from the public databases. The component-targets network of curcumin in the treatment of CRC was constructed by Cytoscape v3.7.2. Through protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG), important targets and signaling pathways related to CRC treatment were identified. Finally, the results were verified by molecular docking, and the correlation between the key targets and tumor-infiltrating immune cells (TICs) was analyzed.

Results: A total of 30 potential targets of curcumin for CRC treatment were collected. The GO function enrichment analysis showed 140 items, and the KEGG pathway enrichment analysis showed 61 signaling pathways related to the regulation of protein kinase activity, negative regulation of apoptosis process, cancer signaling pathway, and PI3K-Akt signaling pathway. The molecular docking results showed that curcumin could be combined with AKT1, EGFR, and STAT3 more stably, and AKT1 has the strongest binding to curcumin. Bioinformatics analysis discovered that the expression of core targets AKT1, EGFR, and STAT3 in CRC was related to TICs.

Conclusion: This study explored the targets and pathways of curcumin in the treatment of CRC. The core targets are AKT1, EGFR, and STAT3. The study indicated that curcumin has preventive and treatment effects on CRC through multitarget and multipathway, which laid the foundation for follow-up research.
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http://dx.doi.org/10.1155/2021/9132608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604591PMC
November 2021

Amplified detection signal at a photoelectrochemical aptasensor with a poly(diphenylbutadiene)-BiOBr heterojunction and Au-modified CeO octahedrons.

Biosens Bioelectron 2022 Feb 28;197:113742. Epub 2021 Oct 28.

Department of Molecular Sciences, Macquarie University, Sydney, NSW 2109, Australia. Electronic address:

A major aspect of this work is the synergistic application of a poly(diphenylbutadiene)-BiOBr composite and a gold nanoparticle-linked CeO octahedron to develop a photoelectrochemical aptasensor with an easily measurable detection signal change. Specifically, poly(diphenylbutadiene) nanofiber-immobilised BiOBr flower-like microspheres were developed as a hybrid material with a heterojunction that facilitates high visible light absorption and efficient photo-generated charge separation, which are essential features for sensitive photoelectrochemical sensors. The model analyte acetamiprid was attached via its specific aptamer on the aptasensor. Separately, a gold nanoparticle-linked CeO octahedron was strategically used to significantly diminish the photocurrent by impeding electron transfer at the aptasensor surface. After acetamiprid binding, the CeO octahedrons were displaced from the aptasensor. This caused a weakened quenching effect and restored the photocurrent to accomplish an "on-off-on" detection mechanism. This photoelectrochemical aptasensor exhibited a detection limit of 0.05 pM over a linear range of 0.1 pM-10 μM acetamiprid. The use of an aptamer has provided good specificity to acetamiprid and anti-interference. In addition, an ∼5.8% relative standard deviation was estimated as the reproducibility of the photoelectrochemical aptasensor. Furthermore, nearly 90% of the initial photocurrent was still measurable after storing these aptasensors at room temperature for 4 weeks, demonstrating their stability.
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http://dx.doi.org/10.1016/j.bios.2021.113742DOI Listing
February 2022

Prognostic Factors Associated With Survival in Patients With Diffuse Astrocytoma.

Front Surg 2021 15;8:712350. Epub 2021 Oct 15.

Neurology Department, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.

Diffuse astrocytoma (DA) is a rare disease with inadequately understood epidemiological characteristics and prognosis. Identification of the factors associated with the survival in DA patients is therefore necessary. In this study, we aim to investigate the clinicopathological characteristics of DA to delineate factors influencing the survival of DA. A population-based cohort study was conducted, utilizing prospectively extracted data from the Surveillance, Epidemiology and End Results (SEER) database. Patients with histological diagnosis of DA in the SEER database from 1973 to 2017 were included. A total of 799 participants with DA were included, consisting of 95.9% fibrillary astrocytoma and 4.1% protoplasmic variants. The average age of participants was 41.9 years, with 57.2% being male. The majority of the population was white (87.5%). More than half (53.9%) of the patients were married. DA arose mostly in the cerebrum (63.8%). Around 71.6% of the population had received surgical treatment. The overall 1-, 3-, 5-, and 10-year survival rate were 73.7, 55.2, 49.4, and 37.6%, respectively. Kaplan-Meier analysis showed that age at diagnosis, marital status, primary tumor site, tumor size, and surgery was possibly associated with cancer-specific survival (CSS) ( < 0.05). Multivariate Cox proportional hazard analysis indicated that surgery was a protective factor whereas older age, larger tumor size, and tumor in the brainstem were harmful factors for patients with DA. Moreover, a nomogram predicting 5- and 10-year survival probability for DA was developed. Age, primary tumor site, tumor size, and surgery were associated with the survival of patients with DA.
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http://dx.doi.org/10.3389/fsurg.2021.712350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554054PMC
October 2021

Development and validation of a novel lipid metabolism-related gene prognostic signature and candidate drugs for patients with bladder cancer.

Lipids Health Dis 2021 Oct 27;20(1):146. Epub 2021 Oct 27.

Department of Urology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Jiangxi, 330006, Nanchang, People's Republic of China.

Background: Bladder cancer (BLCA) is a common cancer associated with an unfavorable prognosis. Increasing numbers of studies have demonstrated that lipid metabolism affects the progression and treatment of tumors. Therefore, this study aimed to explore the function and prognostic value of lipid metabolism-related genes in patients with bladder cancer.

Methods: Lipid metabolism-related genes (LRGs) were acquired from the Molecular Signature Database (MSigDB). LRG mRNA expression and patient clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a signature for predicting overall survival of patients with BLCA. Kaplan-Meier analysis was performed to assess prognosis. The connectivity Map (CMAP) database was used to identify small molecule drugs for treatment. A nomogram was constructed and assessed by combining the signature and other clinical factors. The CIBERSORT, MCPcounter, QUANTISEQ, XCELL, CIBERSORT-ABS, TIMER and EPIC algorithms were used to analyze the immunological characteristics.

Results: An 11-LRG signature was successfully constructed and validated to predict the prognosis of BLCA patients. Furthermore, we also found that the 11-gene signature was an independent hazardous factor. Functional analysis suggested that the LRGs were closely related to the PPAR signaling pathway, fatty acid metabolism and AMPK signaling pathway. The prognostic model was closely related to immune cell infiltration. Moreover, the expression of key immune checkpoint genes (PD1, CTLA4, PD-L1, LAG3, and HAVCR2) was higher in patients in the high-risk group than in those in the low-risk group. The prognostic signature based on 11-LRGs exhibited better performance in predicting overall survival than conventional clinical characteristics. Five small molecule drugs could be candidate drug treatments for BLCA patients based on the CMAP dataset.

Conclusions: In conclusion, the current study identified a reliable signature based on 11-LRGs for predicting the prognosis and response to immunotherapy in patients with BLCA. Five small molecule drugs were identified for the treatments of BLCA patients.
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http://dx.doi.org/10.1186/s12944-021-01554-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8549165PMC
October 2021

Same total normal forms sperm counts of males from Lhasa and Shanghai, China.

Environ Sci Pollut Res Int 2021 Oct 26. Epub 2021 Oct 26.

Department of Urology, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.

Male infertility may be caused by genetic and/or environmental factors that impair spermatogenesis and sperm maturation. High-altitude (HA) hypoxic environments represent one of the most serious challenges faced by humans that reside in these areas. To assess the influence of the plateau environment on semen parameters, 2,798 males, including 1,111 native Tibetans and 1,687 Han Chinese individuals living in the plains (HCILP) who underwent pre-pregnancy checkups, were enrolled in this study. The semen samples of males were evaluated to determine conventional sperm parameters, sperm morphology, and sperm movement. Reproductive endocrine hormones (REHs) were detected in 474 males, including 221 Tibetans and 253 HCILP. Due to recurrent abortions in partners, the DNA fragmentation index (DFI) of 133 native Tibetans and 393 HCILP individuals was further compared. Luteinizing hormone (LH) (4.94 ± 2.12 vs. 3.29 ± 1.43 U/L), prolactin (11.34 ± 3.87 vs. 8.97 ± 3.48 nmol/L), E2/T (0.22 ± 0.11 vs 0.11 ± 0.05), median total sperm motility (61.20% vs. 51.56%), and DFI (23.11% vs. 7.22%) were higher in males from plateau areas while median progressive motility (PR) (35.60% vs. 41.12%), total number of PR sperms (51.61 vs. 59.63 mil/ejaculate), percentage of normal form sperms (3.70% vs. 6.00%), curvilinear velocity (36.10 vs. 48.97 μm/s), straight-line (rectilinear) velocity (14.70 vs. 31.52 μm/s), estradiol (103.82 ± 45.92 vs. 146.01 ± 39.73 pmol/L), progesterone (0.29 ± 0.27 vs. 2.22 ± 0.84 nmol/L), testosterone (4.90 ± 1.96 vs. 14.36 ± 5.24 nmol/L), and testosterone secretion index (ratio of testosterone to LH) (33.45 ± 22.86 vs 145.78 ± 73.41) were lower than those in males from the plains. There was no difference in median total sperm number (157.76 vs. 151.65 mil/mL), sperm concentration (52.40 vs. 51.79 mil/mL), volume (3.10 vs. 3.10 mL), total normal form sperms (5.91 vs. 6.58 mil/ejaculate, p50), and follicle-stimulating hormone (FSH) levels (4.13 ± 2.55 U/L vs 3.82 ± 2.35 U/L) between the two groups of males. The REH and sperm parameters of males from HA hypoxic environments were adaptively altered. Although the total number of PR sperm decreased and DFI increased, the Tibetan population that lives at HAs has been found to grown continuously and rapidly. These results supplement prior findings regarding the impact of HA on male reproductive function.
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http://dx.doi.org/10.1007/s11356-021-17083-4DOI Listing
October 2021

Research on the application of uniportal video-assisted thoracoscopic segmental resection of the lung in elderly patients with non-small cell lung cancer aged over 65 years.

Wideochir Inne Tech Maloinwazyjne 2021 Sep 4;16(3):571-579. Epub 2021 Jun 4.

Department of Thoracic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.

Introduction: The literature regarding the application of uniportal video-assisted thoracoscopic segmental resection of the lung in patients aged over 65 years with non-small cell lung cancer (NSCLC) is sparse. This paper reports 175 cases of uniportal video-assisted thoracoscopic segmental resection of the lung performed at one center, of which 63 patients were over 65 years old.

Aim: To investigate the safety and feasibility of uniportal video-assisted thoracoscopic segmental resection of the lung in elderly patients aged over 65 years with NSCLC.

Material And Methods: A retrospective analysis of 175 NSCLC patients who underwent uniport video-assisted thoracoscopic segmental resection of the lung in the center from August 2018 to August 2020 was conducted, and based on the age of 65 years, patients were divided into elderly and non-elderly groups. The general data and perioperative indicators of the two groups were compared.

Results: The procedures were completed in all patients without death or conversion to open surgery. In the general data of the two groups of patients, the prevalence of emphysema in the elderly group was significantly higher than that in the non-elderly group (p = 0.001). However, there was no statistically significant difference between the two groups in surgery time, intraoperative blood loss, thoracic drainage tube retention time, postoperative hospital stay, incision satisfaction, or postoperative complications (p > 0.05).

Conclusions: Uniportal video-assisted thoracoscopic segmental resection of the lung is feasible and safe in elderly patients with NSCLC aged over 65 years.
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http://dx.doi.org/10.5114/wiitm.2021.106829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512503PMC
September 2021

Functional and Oncological Outcomes Following Robot-Assisted and Laparoscopic Radical Prostatectomy for Localized Prostate Cancer With a Large Prostate Volume: A Retrospective Analysis With Minimum 2-Year Follow-Ups.

Front Oncol 2021 23;11:714680. Epub 2021 Sep 23.

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

Objective: We aimed to analyze the perioperative, functional, and oncologic outcomes following robot-assisted radical prostatectomy (RARP) and laparoscopic radical prostatectomy (LRP) for patients with localized prostate cancer (PCa) characterized by a large prostate volume (PV; ≥50 ml) over a minimum of 2 years follow-up.

Materials And Methods: Patients undergoing RARP and LRP for localized PCa with a large PV were included in the final analysis. The perioperative, functional, and oncologic outcomes were analyzed between the two groups.

Results: All operations were successfully completed without open conversion in both groups. The mean operative time and estimated blood loss in the RARP group were significantly decreased compared to those in the LRP group (139.4 . 159.0 min, = 0.001, and 124.2 . 157.3 ml, = 0.003, respectively). Patients in the RARP arm had significantly lower proportions of grade II or lower and of higher than grade II postoperative complications compared with those in the LRP group (7.9% . 17.1%, = 0.033, and 1.6% . 6.7%, = 0.047, respectively). No significant differences in terms of the rates of pT3 disease, positive surgical margin, and positive lymph node were noted between the two groups. Moreover, no significant difference in the median specimen Gleason score was observed between the RARP and LRP groups (6 . 7, = 0.984). RARP . LRP resulted in higher proportions of urinary continence upon catheter removal (48.4% . 33.3%, = 0.021) and at 3 (65.1% . 50.5%, = 0.025) and 24 (90.5% . 81.0%, = 0.037) months post-operation. The median erectile function scores at 6 and 24 months post-operation in the RARP arm were also significantly higher than those in the LRP arm (15 . 15, = 0.042, and 15 . 13, = 0.026, respectively). Kaplan-Meier analyses indicated that the biochemical recurrence-free survival and accumulative proportion of continence were statistically comparable between the two groups ( = 0.315 and = 0.020, respectively).

Conclusions: For surgically managing localized PCa with a large prostate (≥50 ml), RARP had a tendency toward a lower risk of postoperative complications and better functional preservation without cancer control being compromised when compared to LRP.
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http://dx.doi.org/10.3389/fonc.2021.714680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495117PMC
September 2021

Effects of a helium cold atmospheric plasma on bonding to artificial caries-affected dentin.

Dent Mater J 2021 Oct 1. Epub 2021 Oct 1.

Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology.

This study investigated the effects of a helium cold atmospheric plasma (CAP) on the bonding performance and surface modification of the caries-affected dentin (CAD). Artificial CAD was created by pH-cycling. The microtensile bond of CAD were examined before and after CAP treatments at 24 h and after 2-year aging. The effects of surface modification were studied with contact-angle measurement, scanning electron microscopy and X-ray photoemission spectroscopy. Thirty-second CAP treatment increased the immediate bond strength of CAD to a level that was statistically the same as sound dentin, and slowed the aging process of the bonding as well. The CAP treatment induced modified CAD surface with increased wettability, cleaner appearance, and increased percentage of the mineral-associated elements and oxygen. This research demonstrated that the helium CAP jet treatments of 30 s and 45 s improved the bond strength of the artificial CAD, and was considerably effective in its surface modification.
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http://dx.doi.org/10.4012/dmj.2021-091DOI Listing
October 2021

Development and Validation of Prognostic Nomograms for Elderly Patients with Osteosarcoma.

Int J Gen Med 2021 14;14:5581-5591. Epub 2021 Sep 14.

Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.

Background: The aim of the current study was to construct prognostic nomograms for individual risk prediction in elderly patients with osteosarcoma.

Methods: Data for 816 elderly patients (≥40 years old) with osteosarcoma between 2004 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) database were randomly assigned to training (N=573) and internal validation (N=243) sets. The essential clinical predictors were identified based on least absolute shrinkage and selection operator (Lasso) Cox regression. Nomograms were constructed to predict the 1-, 3-, and 5-year cancer-specific survival (CSS) and overall survival (OS).

Results: Our LASSO regression analyses of the training set yielded five clinicopathological features (age, chemotherapy, surgery, AJCC stage, and summary stage) in the training cohort for the prognosis of elderly patients with osteosarcoma, while grade was only associated with OS and M stage was only associated with CSS. Construction of nomograms based on these predictors was performed to evaluate the prognosis of elderly patients with osteosarcoma. The C-index, calibration and decision curve analysis also showed the satisfactory performance of these nomograms for prognosis prediction.

Conclusion: The constructed nomograms are helpful tools for exactly predicting the prognosis of elderly patients with osteosarcoma, which could enable patients to be more accurately managed in clinical practice.
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http://dx.doi.org/10.2147/IJGM.S331623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449646PMC
September 2021

Transcriptomic and Proteomic Study on the High-Fat Diet Combined With AOM/DSS-Induced Adenomatous Polyps in Mice.

Front Oncol 2021 26;11:736225. Epub 2021 Aug 26.

Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Objective: To screen and identify molecular targets and bacteria genus leading to adenomatous polyps in mouse induced by high-fat diet (HFD) +AOM/DSS using omics technology.

Methods: The molecular targets of colorectal adenoma disease were obtained from the GeneCards and OMIM database. The SPF C57BL mice were randomly divided into blank (Control) and AOM/DSS+HFD colorectal adenoma model (ADH) groups. The ADH model group was intraperitoneally injected with AOM reagent. Then, mice were given with 2.5% DSS (in free drinking water) and high-fat diet to establish the mouse model. During this period, the changes of physical signs of mice in each group were observed. After the end of modeling, HE staining was used to evaluate the histopathological change of mice. The differentially expressed genes and proteins in the Control group and ADH group were detected by RNA-seq transcriptome sequencing and Tandem Mass Tags (TMT) quantitative proteomics. The histological results were analyzed by intersection with the intestinal adenoma molecular targets obtained from the database. Moreover, the changes of intestinal flora in the two groups were examined. The correlation between targets and differential bacteria was analyzed and verified by Parallel Reaction Monitoring (PRM) to comprehensively evaluate the mouse model of adenomatous polyp induced by AOM/DSS+HFD.

Results: The general condition and histopathological results of mice confirmed that the ADH mouse model was successfully established and tubular adenoma was formed. A total of 604 genes and 42 proteins related to intestinal adenoma were obtained by histological analysis and database intersection analysis. The intestinal microflora of ADH mice was different from that of normal mice, and the constituents and abundance of intestinal flora were similar to those of human intestinal adenoma. GATA4 and LHPP were selected as potential pathological markers of the model mice by correlation analysis of targets and intestinal flora. The results of PRM verification were highly consistent with the results of RNA-Seq transcriptome sequencing and TMT analysis.

Conclusion: The pathological results, molecular pathological markers and the changes of intestinal flora suggest that the mouse ADH model is ideal for studying the transformation of inflammatory cancer. The ADH model will be helpful for understanding the occurrence and development of human colorectal cancer at the transcriptomic and proteomic level.
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http://dx.doi.org/10.3389/fonc.2021.736225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427437PMC
August 2021

Robot-Assisted versus Laparoscopic Partial Nephrectomy for Giant Sporadic Renal Angiomyolipomas of ≥7 cm: A Propensity Score-Matched Analysis.

J Oncol 2021 26;2021:6395876. Epub 2021 Aug 26.

Department of Urology, The First Affiliated Hospital of Nanchang University, Yongwai Street 17, Nanchang City, Jiangxi Province, China.

Background: To compare the perioperative and functional outcomes between robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) for giant sporadic renal angiomyolipomas (AMLs) of ≥7 cm.

Materials And Methods: Patients with sporadic renal AMLs of ≥7 cm who underwent RAPN or LPN in the First Affiliated Hospital of Nanchang University between 2015 and 2020 were retrospectively analyzed. Propensity score matching (1 : 1) was performed to adjust for potential baseline confounders. Perioperative and functional outcomes of the RAPN and LPN groups were collected and compared.

Result: After propensity score matching, no statistically significant differences in baseline characteristics were found between the groups (41 vs. 41). Within the matched cohort, the warm ischemia time (WIT) in the RAPN group was significantly shorter than that in the LPN group (21 vs. 27 min, < 0.001). In addition, the RAPN group was associated with improved postoperative renal function (72.8 vs. 69.8 mL/min/1.73 m, =0.045). WIT and preoperative renal function are independent predictors of renal function at 6 months postoperatively, and renal score and operation method are independent predictors of WIT.

Conclusion: RAPN and LPN are safe and feasible minimally invasive treatments for sporadic giant renal AMLs, but RAPN is associated with shorter WIT and better postoperative renal functional preservation. WIT and preoperative renal function are independent predictors of renal function at 6 months postoperatively, while the RENAL score and surgical method are independent risk factors to WIT. For giant and complex renal AMLs, RAPN is the first choice when condition permits.
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http://dx.doi.org/10.1155/2021/6395876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416378PMC
August 2021

Prognostic significance of bladder neck involvement in non-muscle-invasive bladder cancer: A SEER database analysis with 19,919 patients.

Cancer Med 2021 10 23;10(19):6868-6880. Epub 2021 Aug 23.

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

Purpose: To study prognostic values of bladder neck involvement (BNI) and survival outcomes in non-muscle-invasive bladder cancer (NMIBC).

Method And Materials: The national Surveillance, Epidemiology, and End Results database (2004-2015) was applied to gain further insight into the prognostic values of BNI and 19,919 patients diagnosed with NMIBC were included in our study. We used the Kaplan-Meier method with the log-rank test and subgroup analyses to evaluate cancer-specific survival (CSS) and overall survival (OS). In addition, the multivariable Cox proportional hazard model and propensity score matching (PSM) were utilized.

Results: In all, 3446 patients with BNI and 16,473 patients with sites except for bladder neck were enrolled in our study. Compared with other sites, a tendency toward a higher proportion of higher grade (p < 0.001), bigger tumor size (p < 0.001), and more patients with T1 and Tis stage (p < 0.001) was seen in BNI group. After 1:1 PSM, 3425 matched pairs were selected. Under the survival analyses, the BNI group had a lower survival probability in both OS (p = 0.0056) and CSS analyses (p < 0.0001) in NMIBC patients. However, in the subgroup analysis, only observed in the Ta and T1 stage in terms of CSS (all p < 0.05), and patients with Tis stage failed to show statistical survival differences (p > 0.05). In addition, subgroups stratified by tumor size and grade all revealed poor prognosis of BNI in NMIBC patients. Moreover, better survival outcomes of OS were observed in BNI patients who received radical cystectomy (p = 0.02) or chemotherapy (p < 0.001) multivariable Cox regression after PSM revealed that the BNI group had a higher risk of overall mortality (OM) (BNI vs. other sites hazards ratios [HR]: 1.127, 95% CI: 1.154-1.437, p < 0.001) and cancer-specific mortality (CSM) (BNI vs. other sites HR: 1.127, 95% CI: 1.039-1.223, p < 0.001), while before PSM, similar situations were only existed in CSM (BNI vs. other sites HR: 1.288, 95% CI: 1.154-1.437, p < 0.001).

Conclusions: The prognosis of BNI was poorer than that of the other sites. BNI was an independent risk factor for OM and CSM in patients with NMIBC, especially for those with Ta or T1 stage.
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http://dx.doi.org/10.1002/cam4.4219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495274PMC
October 2021

SP1-mediated transcriptional activation of PTTG1 regulates the migration and phenotypic switching of aortic vascular smooth muscle cells in aortic dissection through MAPK signaling.

Arch Biochem Biophys 2021 10 13;711:109007. Epub 2021 Aug 13.

Department of Neurology, First Affiliated Hospital of Shantou University Medical College, Shantou, 515000, China. Electronic address:

Pituitary tumor-transforming gene 1 (PTTG1) has been found to be associated with the process of cell proliferation and invasion, and is highly expressed in aortic dissection (AD). However, its potential role and underlying mechanism in AD remain uncertain. This study aims at elucidating the roles of specificity protein 1 (SP1) and PTTG1 in the migration and phenotypic switching of aortic vascular smooth muscle cells (VSMCs) in AD. Aortic samples were collected from 35 patients with AD for examination of PTTG1 expression in the tissues by qPCR, western blot and immunofluorescence. Human aortic vascular smooth muscle cells (HAVSMCs) were stimulated with platelet-derived growth factor-BB (PDGF-BB) to establish the cellular model of AD. PTTG1 expression in VSMCs was also examined by qPCR and western blot. Cell viability was detected by CCK-8, cell proliferation by EdU staining and cell migration by wound healing and transwell. Western blot was then performed to assay migration-related proteins. After interference with PTTG1, the levels of smooth muscle pthenotypic switch markers smooth muscle protein 22 alpha (SM22-α) and osteopontin (OPN) were detected by qPCR, western blot and immunofluorescence. The binding of SP1 and PTTG1 was verified with dual-luciferase reporter assay and chromatin immunoprecipitation assay (ChIP). PTTG1 overexpression was found in AD patients. Interference with PTTG1 attenuated the proliferation and migration of PDGF-BB-stimulated HAVSMCs, in addition to their switching from contractile phenotype to synthetic phenotype. Transcription factor SP1 was up-regulated in PDGF-BB-stimulated HAVSMCs, combined with PTTG1 promoter sequence and regulated PTTG1 expression, whose overexpression reversed the effects of PTTG1 interference on cell proliferation, migration and phenotypic switching. SP1 transcriptional activation of PTTG1 activated MAPK/ERK signaling pathway. In conclusion, SP1 transcriptional activation of PTTG1 regulates the migration and phenotypic transformation of HAVSMCs in AD by MAPK Signaling.
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http://dx.doi.org/10.1016/j.abb.2021.109007DOI Listing
October 2021

Comment on "Altered Expression of Long Non-coding RNAs in Peripheral Blood Mononuclear Cells of Patients with Alzheimer's Disease".

Mol Neurobiol 2021 Nov 14;58(11):5722-5723. Epub 2021 Aug 14.

School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.

We read with great interest the article by Kurt and colleagues. The authors, using microarray in clinical samples, found altered expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) of patients with Alzheimer's disease (AD). The findings from this study may open a door to the understanding of AD pathogenesis targeted by lncRNAs. In our opinion, it is necessary to further clarify the data analysis strategy of this study. According to the authors' description, they seem to use unadjusted p values and fold change of expression values when defining significantly differentially expressed lncRNAs in PBMCs of subjects with probable AD and healthy control groups. However, due to the characteristics of lncRNA and high false positives caused by multiple comparisons, t-test is not suitable for high-level microarray analysis. It seems that a specialized high-level microarray analysis method is essential to reach a reliable result. Accurate analysis results will provide a convincing basis for subsequent experiments.
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http://dx.doi.org/10.1007/s12035-021-02513-8DOI Listing
November 2021
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