Publications by authors named "Zhiyuan Wu"

163 Publications

Sex-specific association of BMI change with stroke in middle-aged and older adults with type 2 diabetes.

Nutr Metab Cardiovasc Dis 2021 Jul 24. Epub 2021 Jul 24.

China-Japan Union Hospital of Jilin University, Jilin University, China. Electronic address:

Background And Aims: We aimed to evaluate the association between BMI change and stroke in middle-aged and older adults with type 2 diabetes and identify sex differences.

Methods And Results: The China Health and Retirement Longitudinal Study is an ongoing national population-based cohort study. Participants aged 45 or above with type 2 diabetes were enrolled and followed for stroke incidence. BMI change was defined as BMI at 2013-BMI at 2011. Of 1774 participants (mean [SD] age in 2011, 60.23 [8.88] years), 795 (44.8 %) were men. A total of 112 incident stroke cases were confirmed up to 2018. The incidence rate of stroke was similar between men and women (6.79 % vs 5.92 %, P = 0.516). BMI increase was independently associated with an increased stroke risk (adjusted odds ratio, 1.15; 95 % CI, 1.05-1.31) in men, while this positive association was not significant in women (adjusted odds ratio, 1.12; 95 % CI, 0.98-1.29). In addition, the positive dose-response relationship between BMI increase and stroke was observed only in men.

Conclusion: Among middle-aged and older adults with type 2 diabetes, there is a sex-specific association of BMI change with stroke. An increase in BMI could result in a higher risk of incident stroke in men.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2021.07.007DOI Listing
July 2021

Single-cell transcriptome analysis of diffuse large B cells in cerebrospinal fluid of central nervous system lymphoma.

iScience 2021 Sep 11;24(9):102972. Epub 2021 Aug 11.

Department of Clinical Laboratory, Huashan Hospital, Fudan University, Shanghai, China.

Diffuse large B cells in the cerebrospinal fluid (CSF-DLBCs) have offered great promise for the diagnostics and therapeutics of central nervous system lymphoma (CNSL) leptomeningeal involvement. To explore the phenotypic states of CSF-DLBCs, we analyzed the transcriptomes of more than one thousand CSF-DLBCs from six patients with CNSL diffuse large B-cell lymphoma (DLBCL) using Smart-seq2 single-cell RNA sequencing. CSF-DLBCs were defined based on abundant expression of B-cell markers, the active cell proliferation and energy metabolism properties, and immunoglobulin light chain restriction. We identified inherent heterogeneity of CSF-DLBCs, which were mainly manifested in cell cycle state, cancer-testis antigen expression, and classification based on single-cell germinal center B-cell signature. In addition, the 16 upregulated genes in CSF-DLBCs compared to various normal B cells showed great possibility in the homing effect of the CNS-DLBCL for the leptomeninges. Our results will provide insight into the mechanism research and diagnostic direction of CNSL-DLBCL leptomeningeal involvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.isci.2021.102972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387906PMC
September 2021

Booster immunization improves the generation of T follicular helper (Tfh) cells specific to hepatitis B surface antigen (HBsAg) after prenatal HBsAg exposure.

Vaccine 2021 Aug 16. Epub 2021 Aug 16.

State Key Lab of Molecular Oncology & Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, PR China. Electronic address:

Breakthrough infections of hepatitis B virus (HBV) after neonatal vaccination occurred in some adolescents and young adults who were born to mothers with hepatitis B surface antigen (HBsAg). We aimed to determine the impacts of prenatal HBsAg exposure on the generation of T follicular helper (Tfh) cells and antibodies (anti-HBs) specific to HBsAg. To mimic human prenatal HBsAg exposure, we mated female Alb1-HBV (HBV-M) mice with male C57BL/6J mice. Of their first filial generation (F1), HBV-M/F1 expressed HBsAg in liver tissues and blood, and HBV-M/F1 mice exposed HBsAg in amniotic fluid. At their four weeks old, each HBV-M/F1 mouse was immunized with hepatitis B vaccine containing 5 μg HBsAg subcutaneously. Both HBV-M/F1 and HBV-M/F1 mice had reduced generation of HBsAg-specific CD4CXCR5PD1 Tfh cells and CD138IgD plasma cells in comparison with C57BL/6J mice. Results of coculturing the Tfh cells with B cells that were isolated from different strains of mice indicated that CD4 T cell activation in response to HBsAg was critical for anti-HBs generation after prenatal HBsAg exposure. When interleukin (IL) 21 was supplemented, the generation of HBsAg-specific Tfh and plasma cells in HBV-M/F1 mice was improved, while supplementation showed little effect in HBV-M/F1 mice. In HBV-M/F1 mice, HBV vaccine booster improved the generation of Tfh cells and plasma cells, and enhanced anti-HBs production. CONCLUSION: Impaired generation of HBsAg-specific Tfh cells and plasma cells after prenatal HBsAg exposure can be improved by HBV vaccine booster, most likely increasing IL-21 production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2021.08.020DOI Listing
August 2021

Preliminary Experience With a Novel Metallic Segmented Transcordal Stent Modified With Three-Dimensional Printing for Inoperable Malignant Laryngotracheal Stenosis.

Front Oncol 2021 26;11:619781. Epub 2021 Jul 26.

Department of Radiology, RuiJin Hospital/Lu Wan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: This study aims to assess the feasibility of a novel metallic segmented transcordal stent modified with three-dimensional (3D) printing for treating inoperable malignant laryngotracheal stenosis and the tolerability of the stent.

Methods: This was a retrospective study. The stents were individually customized with the aid of 3D printing model based on the anatomic features of each patient's airway. The stent was composed of two separate segments that corresponded to the larynx and the upper trachea. The stents were barrel-shaped at the proximal end to prevent migration. The proximal end of the stent was located slightly above the vocal cord. The technical and clinical success of stenting procedure, patient tolerability, and stent-related complications of patients were evaluated.

Results: Ten patients with dyspnea caused by malignant laryngotracheal stenosis underwent implantation of such stents. Technical and clinical success of the stenting procedure were achieved in all patients. For all patients, basic communication in life could be maintained by speaking softly. During follow-up, one patient showed intolerance to the stent, and the stent was retrieved 2 weeks after stenting. Stent migration was found in one patient, and the position of the stent was readjusted. Granulation tissue proliferation was found in two patients and was treated with cryotherapy by bronchoscopy. There were no deaths associated with stenting.

Conclusions: The individually customized metallic segmented transcordal stent is feasible and tolerable for patients with inoperable malignant laryngotracheal stenosis. The implantation of this stent may serve as a novel alternative treatment for patients who are not suitable for surgery or tracheotomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.619781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350761PMC
July 2021

The Rs6983267 G Variant Contributes to Increased Sepsis Susceptibility in a Southern Chinese Population.

Infect Drug Resist 2021 4;14:2969-2976. Epub 2021 Aug 4.

Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, People's Republic of China.

Purpose: Accumulating evidence demonstrates that genetic susceptibility genes can be used as biomarkers to assess sepsis susceptibility, and genetic variation is associated with susceptibility and clinical outcomes in patients with sepsis and inflammatory disease. Although studies have shown that the lncRNA is involved in inflammatory diseases, it remains unclear whether gene polymorphisms are associated with susceptibility to inflammatory diseases, such as sepsis, in children.

Methods: We genotyped the rs6983267 polymorphism in 474 cases (pediatric sepsis) and 678 controls using TaqMan methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of associations.

Results: Our results indicate that the rs6983267 T > G polymorphism is significantly associated with an increased risk of sepsis in children (TG and TT: adjusted OR = 1.311, 95% CI = 1.016-1.743, GG and TT: adjusted OR = 1.444, 95% CI = 1.025-2.034 dominant model: GG/TG vs TT adjusted OR = 1.362, 95% CI = 1.055-1.756). Furthermore, the risk effect was more pronounced in children younger than 60 months who were male and who had sepsis.

Conclusion: We found that the gene polymorphism rs6983267 T > G may be associated with an increased risk of pediatric sepsis in southern China. A larger multicenter study should be performed to confirm these results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IDR.S311717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349528PMC
August 2021

A male-ABCD algorithm for hepatocellular carcinoma risk prediction in HBsAg carriers.

Chin J Cancer Res 2021 Jun;33(3):352-363

State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Objective: Hepatocellular carcinoma (HCC) development among hepatitis B surface antigen (HBsAg) carriers shows gender disparity, influenced by underlying liver diseases that display variations in laboratory tests. We aimed to construct a risk-stratified HCC prediction model for HBsAg-positive male adults.

Methods: HBsAg-positive males of 35-69 years old (N=6,153) were included from a multi-center population-based liver cancer screening study. Randomly, three centers were set as training, the other three centers as validation. Within 2 years since initiation, we administrated at least two rounds of HCC screening using B-ultrasonography and α-fetoprotein (AFP). We used logistic regression models to determine potential risk factors, built and examined the operating characteristics of a point-based algorithm for HCC risk prediction.

Results: With 2 years of follow-up, 302 HCC cases were diagnosed. A male-ABCD algorithm was constructed including participant's age, blood levels of GGT (γ-glutamyl-transpeptidase), counts of platelets, white cells, concentration of DCP (des-γ-carboxy-prothrombin) and AFP, with scores ranging from 0 to 18.3. The area under receiver operating characteristic was 0.91 (0.90-0.93), larger than existing models. At 1.5 points of risk score, 26.10% of the participants in training cohort and 14.94% in validation cohort were recognized at low risk, with sensitivity of identifying HCC remained 100%. At 2.5 points, 46.51% of the participants in training cohort and 33.68% in validation cohort were recognized at low risk with 99.06% and 97.78% of sensitivity, respectively. At 4.5 points, only 20.86% of participants in training cohort and 23.73% in validation cohort were recognized at high risk, with positive prediction value of 22.85% and 12.35%, respectively.

Conclusions: Male-ABCD algorithm identified individual's risk for HCC occurrence within short term for their HCC precision surveillance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21147/j.issn.1000-9604.2021.03.07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286891PMC
June 2021

Acupuncture-Related Therapies for Parkinson's Disease: A Meta-Analysis and Qualitative Review.

Front Aging Neurosci 2021 1;13:676827. Epub 2021 Jul 1.

Evidence-Based Medicine and Data Science Centre, Guangzhou University of Chinese Medicine, Guangzhou, China.

This systematic review and meta-analysis aimed to assess the effects of the combination of acupuncture-related therapies with conventional medication compared with conventional medication in patients with Parkinson's disease (PD). A literature search within eight databases [including Medline, Embase, the Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP, and Wanfang Database] was performed covering a time frame from their inception to August 2020. Randomized controlled trials (RCTs) comparing acupuncture-related therapies combined with conventional medication vs. conventional medication in patients with PD were eligible. Two authors independently assessed the risk of bias. Assessments were performed with the total and subscales scores of the Unified Parkinson's Disease Rating Scale (UPDRS), 39-item Parkinson's Disease Questionnaire (PDQ-39), the dosage of Madopar, Mini-Mental State Examination (MMSE), and 17-item Hamilton Depression Scale (HAMD). Data were analyzed by adopting the Cochrane Collaboration's RevMan 5.4 (Review Man, Copenhagen, Denmark); and mean effect sizes and 95% confidence intervals were estimated. Tests for heterogeneity were used to assess differences in treatment effects across different types of acupuncture used. Sixty-six trials met the inclusion criteria, of which 61 trials provided data for the meta-analysis. We defined high-quality articles as those with a low risk of bias in four or more domains; and only 10 (15.15%) articles were of high quality. Compared with the controls, acupuncture-related therapies with conventional medication achieved a benefit in the primary outcomes of UPDRS (motor subscore: -3.90, -4.33 to -3.49, < 0.01; total score: -7.37 points, -8.91 to -5.82, < 0.001; activities of daily living subscore: -3.96, -4.96 to -2.95, < 0.01). For the subgroup difference test among the effects of different acupuncture methods, significant differences existed in outcomes with the UPDRS-III, UPDRS-I, UPDRS-IV, and PDQ-39 scores and Madopar dosage, while non-significant differences existed with the UPDRS-total, UPDRS-II, HAMD, and MMSE scores. Acupuncture-related therapies combined with conventional medication may benefit individuals with PD. Our review findings should be considered with caution because of the methodological weaknesses in the included trials. Future, large randomized trials of acupuncture-related therapies for PD with high methodological quality are warranted. Identifier CRD42021228110.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnagi.2021.676827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282198PMC
July 2021

Application of an Anomaly Detection Model to Screen for Ocular Diseases Using Color Retinal Fundus Images: Design and Evaluation Study.

J Med Internet Res 2021 Jul 13;23(7):e27822. Epub 2021 Jul 13.

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China.

Background: The supervised deep learning approach provides state-of-the-art performance in a variety of fundus image classification tasks, but it is not applicable for screening tasks with numerous or unknown disease types. The unsupervised anomaly detection (AD) approach, which needs only normal samples to develop a model, may be a workable and cost-saving method of screening for ocular diseases.

Objective: This study aimed to develop and evaluate an AD model for detecting ocular diseases on the basis of color fundus images.

Methods: A generative adversarial network-based AD method for detecting possible ocular diseases was developed and evaluated using 90,499 retinal fundus images derived from 4 large-scale real-world data sets. Four other independent external test sets were used for external testing and further analysis of the model's performance in detecting 6 common ocular diseases (diabetic retinopathy [DR], glaucoma, cataract, age-related macular degeneration, hypertensive retinopathy [HR], and myopia), DR of different severity levels, and 36 categories of abnormal fundus images. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of the model's performance were calculated and presented.

Results: Our model achieved an AUC of 0.896 with 82.69% sensitivity and 82.63% specificity in detecting abnormal fundus images in the internal test set, and it achieved an AUC of 0.900 with 83.25% sensitivity and 85.19% specificity in 1 external proprietary data set. In the detection of 6 common ocular diseases, the AUCs for DR, glaucoma, cataract, AMD, HR, and myopia were 0.891, 0.916, 0.912, 0.867, 0.895, and 0.961, respectively. Moreover, the AD model had an AUC of 0.868 for detecting any DR, 0.908 for detecting referable DR, and 0.926 for detecting vision-threatening DR.

Conclusions: The AD approach achieved high sensitivity and specificity in detecting ocular diseases on the basis of fundus images, which implies that this model might be an efficient and economical tool for optimizing current clinical pathways for ophthalmologists. Future studies are required to evaluate the practical applicability of the AD approach in ocular disease screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/27822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317033PMC
July 2021

lncRNA GAU1 Induces GALNT8 Overexpression and Potentiates Colorectal Cancer Progression.

Gastroenterol Res Pract 2021 17;2021:5960821. Epub 2021 Jun 17.

Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China.

lncRNA is a key epigenetic regulator in biological processes. In the human cancer transcriptome library MiTranscriptome, we identified as the top upregulated lncRNA in colorectal cancer (CRC) by sample set enrichment analysis (overexpression ranking percentile = 99.75%, < 10), which is coexpressed with the potential oncogene (Spearman rho = 0.67, = 2.44 × 10, TCGA dataset = 184). Experimental data revealed that regulates the expression of . The overexpression of either or significantly promotes the cell cycle and proliferation of CRC cell lines and correlates with poor prognosis in patients with CRC ( = 3.04 × 10), while silencing of or suppressed the cancer cell proliferation and induced the CRC cell line resistance to oxaliplatin treatment. Our results suggested that the previously less studied and may play as CRC prognosis markers and potential targets for chemotherapy treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5960821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233076PMC
June 2021

Association of TyG index and TG/HDL-C ratio with arterial stiffness progression in a non-normotensive population.

Cardiovasc Diabetol 2021 07 6;20(1):134. Epub 2021 Jul 6.

Beijing Municipal Key Laboratory of Clinical Epidemiology, Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China.

Background: Cross-sectional studies have reported that insulin resistance (IR) is associated with arterial stiffness. However, the relationship between IR and arterial stiffness progression remains unclear. This study aims to evaluate the association of triglyceride glucose (TyG) index and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio with arterial stiffness progression in a non-normotensive population.

Methods: A total of 1895 prehypertensive (systolic pressure 120-139 mmHg or diastolic pressure 80-90 mmHg) or hypertensive (systolic pressure ≥ 140 mmHg or diastolic pressure ≥ 90 mmHg or using antihypertensive medication) participants were enrolled in 2013 and 2014, and followed until December 31, 2019. Arterial stiffness progression was measured by brachial-ankle pulse wave velocity (baPWV) change (absolute difference between baseline and last follow-up), baPWV change rate (change divided by following years), and baPWV slope (regression slope between examination year and baPWV).

Results: During a median follow-up of 4.71 years, we observed an increasing trend of baPWV in the population. There were linear and positive associations of the TyG index and TG/HDL-C ratio with the three baPWV parameters. The difference (95% CI) in baPWV change (cm/s) comparing participants in the highest quartile versus the lowest of TyG index and TG/HDL-C ratio were 129.5 (58.7-200.0) and 133.4 (52.0-214.9), respectively. Similarly, the evaluated baPWV change rates (cm/s/year) were 37.6 (15.3-60.0) and 43.5 (17.8-69.2), while the slopes of baPWV were 30.6 (9.3-51.8) and 33.5 (9.0-58.0). The observed association was stronger in the hypertensive population.

Conclusion: Our study indicates that the TyG index and TG/HDL-C ratio are significantly associated with arterial stiffness progression in hypertensive population, not in prehypertensive population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12933-021-01330-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262008PMC
July 2021

Potential Role of Hsp70 and Activated NK Cells for Prediction of Prognosis in Glioblastoma Patients.

Front Mol Biosci 2021 17;8:669366. Epub 2021 May 17.

Department of Radiation Oncology, School of Medicine, Technical University Munich (TUM), Munich, Germany.

Despite rapid progress in the treatment of many cancers, glioblastoma remains a devastating disease with dismal prognosis. The aim of this study was to identify chaperone- and immune-related biomarkers to improve prediction of outcome in glioblastoma. Depending on its intra- or extracellular localization the major stress-inducible heat shock protein 70 (Hsp70) fulfills different tasks. In the cytosol Hsp70 interferes with pro-apoptotic signaling pathways and thereby protects tumor cells from programmed cell death. Extracellular Hsp70 together with pro-inflammatory cytokines are reported to stimulate the expression of activatory NK cell receptors, recognizing highly aggressive human tumor cells that present Hsp70 on their cell surface. Therefore, intra-, extracellular and membrane-bound Hsp70 levels were assessed in gliomas together with activatory NK cell receptors. All gliomas were found to be membrane Hsp70-positive and high grade gliomas more frequently show an overexpression of Hsp70 in the nucleus and cytosol. Significantly elevated extracellular Hsp70 levels are detected in glioblastomas with large necrotic areas. Overall survival (OS) is more favorable in patients with low Hsp70 serum levels indicating that a high Hsp70 expression is associated with an unfavorable prognosis. The data provide a first hint that elevated frequencies of activated NK cells at diagnosis might be associated with a better clinical outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2021.669366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165168PMC
May 2021

Highly recurrent CBS epimutations in gastric cancer CpG island methylator phenotypes and inflammation.

Genome Biol 2021 06 1;22(1):167. Epub 2021 Jun 1.

Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8, College road, Singapore, 169857, Singapore.

Background: CIMP (CpG island methylator phenotype) is an epigenetic molecular subtype, observed in multiple malignancies and associated with the epigenetic silencing of tumor suppressors. Currently, for most cancers including gastric cancer (GC), mechanisms underlying CIMP remain poorly understood. We sought to discover molecular contributors to CIMP in GC, by performing global DNA methylation, gene expression, and proteomics profiling across 14 gastric cell lines, followed by similar integrative analysis in 50 GC cell lines and 467 primary GCs.

Results: We identify the cystathionine beta-synthase enzyme (CBS) as a highly recurrent target of epigenetic silencing in CIMP GC. Likewise, we show that CBS epimutations are significantly associated with CIMP in various other cancers, occurring even in premalignant gastroesophageal conditions and longitudinally linked to clinical persistence. Of note, CRISPR deletion of CBS in normal gastric epithelial cells induces widespread DNA methylation changes that overlap with primary GC CIMP patterns. Reflecting its metabolic role as a gatekeeper interlinking the methionine and homocysteine cycles, CBS loss in vitro also causes reductions in the anti-inflammatory gasotransmitter hydrogen sulfide (HS), with concomitant increase in NF-κB activity. In a murine genetic model of CBS deficiency, preliminary data indicate upregulated immune-mediated transcriptional signatures in the stomach.

Conclusions: Our results implicate CBS as a bi-faceted modifier of aberrant DNA methylation and inflammation in GC and highlights HS donors as a potential new therapy for CBS-silenced lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-021-02375-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170989PMC
June 2021

Triglyceride glucose index and carotid atherosclerosis incidence in the Chinese population: A prospective cohort study.

Nutr Metab Cardiovasc Dis 2021 06 20;31(7):2042-2050. Epub 2021 Apr 20.

Beijing Municipal Key Laboratory of Clinical Epidemiology, Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China. Electronic address:

Background And Aims: The association of the triglyceride glucose (TyG) index with carotid atherosclerosis has not been reported in longitudinal studies. The present study aimed to investigate whether the TyG index increases the risk of carotid atherosclerosis incidence.

Methods And Results: This study included data from the Beijing Health Management Cohort (BHMC; n = 6955) and the Beijing Physical Examination Cohort (BPEC; n = 8473). Participants without a history of carotid atherosclerosis who underwent health examination in 2011 or 2012 were annually followed until 2019. The TyG index was denoted as ln [triglycerides (mmol/L)∗fasting glucose (mmol/L)/2]. During a median follow-up of 5.02 years and 5.36 years, 1441 individuals in the BHMC group and 2181 individuals in the BPEC group developed carotid plaque, respectively. The adjusted hazard ratios (HRs) of the continuous TyG index were 1.253 (95% CI, 1.044 to 1.505) and 1.252 (95% CI, 1.091 to 1.437) for the BHMC and BPEC groups, respectively. Individuals in the highest quartile of the TyG index were associated with an increased risk of carotid plaque compared with those in the lowest quartile (BHMC: HR, 1.366; 95% CI, 1.101 to 1.695, P for trend = 0.010; BPEC: HR, 1.379; 95% CI, 1.196 to 1.591, P for trend = 0.013).

Conclusion: These findings suggested that a higher TyG index increases the risk of carotid atherosclerosis incidence in the general population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2021.03.027DOI Listing
June 2021

Flavopereirine Suppresses the Progression of Human Oral Cancer by Inhibiting the JAK-STAT Signaling Pathway via Targeting LASP1.

Drug Des Devel Ther 2021 22;15:1705-1716. Epub 2021 Apr 22.

Department of Oral and Maxillofacial Surgery, Fujian Provincial Hospital, Fuzhou City, Fujian Province, 350001, People's Republic of China.

Objective: Flavopereirine has been identified to be a potential anti-cancer agent in several types of human cancer. This study aimed to investigate the anti-cancer activity of flavopereirine in oral cancer.

Methods: The effect of flavopereirine on cell viability of human oral cancer cell lines (BcaCD885 and Tca8113) was evaluated by MTT assay and colony formation assay. Cell apoptosis and cell cycle distribution were detected by flow cytometry. Cell invasion and migration were evaluated by Transwell assay. The expression of LASP1, JAK2, p-JAK2, STST3, p-STST3, STST5 and p-STST5 was evaluated by qRT-PCR and Western blot. In addition, the xenograft mouse model was constructed to determine the anti-cancer role of flavopereirine in vivo.

Results: Flavopereirine significantly inhibited cell proliferation, invasion, migration and EMT process of BcaCD885 and Tca8113 cells, while promoted cell apoptosis in vitro. Flavopereirine markedly decreased the expression levels of p-JAK2, p-STST3 and p-STST5, while increased the expression levels of LASP1. In addition, downregulation of LASP1 significantly increased the expression levels of p-JAK2, p-STAT3 and p-STAT5 compared with si-NC in BcaCD885 cells. Moreover, flavopereirine was found to decrease tumor weight and volume of xenograft tumors in vivo.

Conclusion: Flavopereirine inhibited the progression of oral cancer through inactivating the JAK/STAT signaling pathway by upregulating LASP1, suggesting that flavopereirine might be a potential anti-cancer agent for oral cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S284213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076722PMC
April 2021

Small organic molecules accelerate the expansion of regulatory T cells.

Bioorg Chem 2021 06 20;111:104908. Epub 2021 Apr 20.

Department of Pediatric Intensive Care Unit, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Joint Center for Infection and Immunity, Guangzhou Medical University, 510623 Guangzhou, China. Electronic address:

The regulatory T cells (T cells) expressing CD4 + CD25 + FOXP3 + markers are indispensable for the initiation of immune homeostasis and tolerance to self-antigens in both mice and humans. A decrease in regulatory T cells leads to various autoimmune pathologies. Herein, we report three low molecular weight, small organic molecules as a new series of T proliferators TRP-1-3. These small molecules were tested for their proliferative effect on regulatory T cells. It was found that TRP-1 (Oleracein E) strongly accelerates the T proliferation in vitro in a concentration-dependent manner. The effect was evident for all subsets of T cells tested, including naturally occurring, thymus-derived and peripherally-induced or adaptive T, indicating an effect independent of the maturation site. Importantly, increased T cells numbers by TRP-1 correlated with improved CD4 + CD25 + FOXP3 + expression in vitro, while propidium iodide-based staining showed low TRP-1-induced cytotoxicity. Molecular docking plus simulation studies of these TRP-1-3 with IL-2R, mTOR and TCR receptors suggest a TCR-based T cells activation mechanism. Because of its high T cells activities and low cellular cytotoxicity, TRP-1-3 may be useful in stimulating ex-vivo/in-vivo, T cell-specific responses for therapeutic applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2021.104908DOI Listing
June 2021

Immunological effect of irreversible electroporation on hepatocellular carcinoma.

BMC Cancer 2021 Apr 21;21(1):443. Epub 2021 Apr 21.

Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Background: This study intends to investigate the immunological effects of tumor ablation with irreversible electroporation (IRE).

Methods: We evaluated the systemic immune response in patients with hepatocellular carcinoma (HCC) after IRE treatment. Furthermore, we analyzed the tumor infiltrating T lymphocytes and the level of serum cytokines in IRE and control groups of tumor-bearing mice.

Results: We observed that IRE induced an increase in WBC, neutrophil and monocyte counts and a decrease in lymphocyte count 1 day post-IRE and returned to baseline values within 7 days in the patients. Meanwhile, circulating CD4 T cell subsets, but not CD8, decreased 1 day post-IRE. The activated T cells and natural killer (NK) cells increased, and regulatory T (Treg) cells decreased. Furthermore, a significant increase in cytotoxic CD8 T cells infiltration was observed on ablative tumors in mice. The level of serum IFN-γ also significantly increased in the IRE group.

Conclusions: Our study demonstrated that IRE upregulated activated T cells and downregulated Tregs in the peripheral blood of patients. Meanwhile, the results from the animal model indicated that IRE could induce antitumor adaptive immunity dominated by the infiltration of cytotoxic CD8 T cells into the tumors, accompanied by reduced Tregs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-021-08176-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061072PMC
April 2021

Customization of stent design for treating malignant airway stenosis with the aid of three-dimensional printing.

Quant Imaging Med Surg 2021 Apr;11(4):1437-1446

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

Background: The treatment of malignant stenosis involving the carina or bronchi is challenging due to complicated anatomy with individual variation, which makes it necessary to customize stents for each patient. Therefore, this study aims to evaluate the feasibility of a novel metallic segmented airway stent customized with the aid of three-dimensional (3D) printing for such cases.

Methods: The stents were individually customized with the aid of a 3D printed mold based on computed tomography (CT) images according to the anatomical features of the airway. A segmented design was applied on the junction part of the main stem and the branches to fit the dynamic changes of the carina angle. In 12 patients with airway stenosis caused by malignancies including esophageal cancer (EC) and lung cancer (LC), the stents were implanted. The technical and clinical success of the stenting procedure, Hugh-Jones (HJ) classification, Karnofsky performance status (KPS), and stent-related complications of patients were evaluated.

Results: The stenting procedure was technically successful in all patients, and 11 patients showed significant palliation of dyspnea after stenting. The HJ and KPS classification of patients after stent insertion improved significantly compared with those before stenting (P=0.003 and P=0.006, respectively). During follow-up, granulation tissue proliferation and sputum retention were found in two and four patients, respectively.

Conclusions: This study shows that the implantation of a novel stent designed with the aid of 3D printing is feasible for relieving dyspnea and improving performance status of patients with inoperable malignant stenosis involving the carina or bronchi.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/qims-20-727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930692PMC
April 2021

CDC42EP3 promotes colorectal cancer through regulating cell proliferation, cell apoptosis and cell migration.

Cancer Cell Int 2021 Mar 16;21(1):169. Epub 2021 Mar 16.

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

Background: Nowadays, colorectal cancer (CRC) is one of the most commonly diagnosed malignant tumors worldwide, the incidence rate of which is still increasing year by year. Herein, the objective of this study is to investigate whether CDC42EP3 has regulatory effects in CRC.

Methods: First, CDC42EP3 knockdown cell model based on HCT116 and RKO cell lines was successfully constructed, which was further used for constructing mouse xenotransplantation models. Importantly, effects of CDC42EP3 knockdown on proliferation, colony formation, apoptosis, and migration of CRC were accessed by MTT assay, EdU staining assay, colony formation assay, Flow cytometry, and Transwell assay.

Results: As the results, we showed that CDC42EP3 was significantly upregulated in CRC, and its high expression was associated with tumor progression. Furthermore, knockdown of CDC42EP3 could inhibit proliferation, colony formation and migration, and promote apoptosis of CRC cells in vitro. In vivo results further confirmed knockdown of CDC42EP3 attenuated tumor growth in CRC. Interestingly, the regulation of CRC by CDC42EP3 involved not only the change of a variety of apoptosis-related proteins, but also the regulation of downstream signaling pathway.

Conclusion: In conclusion, the role of CDC42EP3 in CRC was clarified and showed its potential as a target of innovative therapeutic approaches for CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12935-021-01845-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962261PMC
March 2021

PD-1 restrains IL-17A production from γδ T cells to modulate acute radiation-induced lung injury.

Transl Lung Cancer Res 2021 Feb;10(2):685-698

Central Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shen Zhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.

Background: Combining radiotherapy (RT) with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has been shown to enhance anti-tumor effects in the treatment of non-small cell lung carcinoma (NSCLC). Pulmonary toxicity is a major adverse effect of thoracic RT in NSCLC patients, whether it is administered alone or in combination with PD-1/PD-L1 inhibitors. This study aimed to evaluate the potential pulmonary toxicity of RT combined with concurrent PD-1 inhibitor and to clarify the underlying mechanisms.

Methods: Radiation-induced lung injury (RILI) was induced in C57BL/6 mice by given 24 Gy in three fractions on consecutive days, with or without concurrent injection of anti-PD-1 antibody. On days 3, 7, 14, and 28 after the first exposure to irradiation, lung tissue and peripheral blood samples were collected from the mice. Histological injury was analyzed, and inflammatory cell infiltration and interleukin (IL)-17A production in the lung tissues were quantified.

Results: Mice that received irradiation with concurrent administration of anti-PD-1 antibody had the highest histological score for RILI. In the murine lung tissues, the levels of PD-1 and IL-17A expression were increased in γδ T cells but not in the other CD3 T cells after irradiation. Concurrent blockade of PD-1 enhanced IL-17A production from γδ T cells in the lung tissues after irradiation. In the mice with acute RILI, concurrent administration of anti-PD-1 antibody exaggerated pulmonary inflammation, with significantly increased levels of neutrophilic infiltration and IL-17A detected in both the lung and blood.

Conclusions: PD-1 could restrain IL-17A production from γδ T cells to modulate acute RILI. The concurrent administration of anti-PD-1 antibody aggravates the severity of acute RILI. More attention should be paid to pulmonary toxicity in patients undergoing thoracic RT with concurrent anti-PD-1 immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/tlcr-20-838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947382PMC
February 2021

Texture feature-based machine learning classifier could assist in the diagnosis of COVID-19.

Eur J Radiol 2021 Apr 15;137:109602. Epub 2021 Feb 15.

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China; Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China. Electronic address:

Purpose: Differentiating COVID-19 from other acute infectious pneumonias rapidly is challenging at present. This study aims to improve the diagnosis of COVID-19 using computed tomography (CT).

Method: COVID-19 was confirmed mainly by virus nucleic acid testing and epidemiological history according to WHO interim guidance, while other infectious pneumonias were diagnosed by antigen testing. The texture features were extracted from CT images by two radiologists with 5 years of work experience using modified wavelet transform and matrix computation analyses. The random forest (RF) classifier was applied to identify COVID-19 patients and images.

Results: We retrospectively analysed the data of 95 individuals (291 images) with COVID-19 and 96 individuals (279 images) with other acute infectious pneumonias, including 50 individuals (160 images) with influenza A/B. In total, 6 texture features showed a positive association with COVID-19, while 4 features were negatively associated. The mean AUROC, accuracy, sensitivity, and specificity values of the 5-fold test sets were 0.800, 0.722, 0.770, and 0.680 for image classification and 0.858, 0.826, 0.809, and 0.842 for individual classification, respectively. The feature 'Correlation' contributed most both at the image level and individual level, even compared with the clinical factors. In addition, the texture features could discriminate COVID-19 from influenza A/B, with an AUROC of 0.883 for images and 0.957 for individuals.

Conclusions: The developed texture feature-based RF classifier could assist in the diagnosis of COVID-19, which could be a rapid screening tool in the era of pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejrad.2021.109602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883715PMC
April 2021

Integrated Analysis of Key Genes and Pathways Involved in Nonalcoholic Steatohepatitis Improvement After Roux-en-Y Gastric Bypass Surgery.

Front Endocrinol (Lausanne) 2020 2;11:611213. Epub 2021 Feb 2.

Department of General Surgery, Fourth Affiliated Hospital of China Medical University, Shenyang, China.

Background: As the incidence of nonalcoholic fatty liver disease (NAFLD) increases globally, nonalcoholic steatohepatitis (NASH) has become the second common cause of liver transplantation for liver diseases. Recent evidence shows that Roux-en-Y gastric bypass (RYGB) surgery obviously alleviates NASH. However, the mechanism underlying RYGB induced NASH improvement is still elusive.

Methods: We obtained datasets, including hepatic gene expression data and histologic NASH status, at baseline and 1 year after RYGB surgery. Differentially expressed genes (DEGs) were identified comparing gene expression before and after RYGB surgery in each dataset. Common DEGs were obtained between both datasets and further subjected to functional and pathway enrichment analysis. Protein-protein interaction (PPI) network was constructed, and key modules and hub genes were also identified.

Results: In the present study, GSE106737 and GSE83452 datasets were included. One hundred thirty common DEGs (29 up-regulated and 101 down-regulated) were identified between GSE106737 and GSE83452 datasets. KEGG analysis showed that mineral absorption, IL-17 signaling pathway, osteoclast differentiation, and TNF signaling pathway were significantly enriched. Based on the PPI network, , , , , , , , , , , , , and were identified as hub genes, and three functional modules were also extracted.

Conclusion: This study identifies the global gene expression change in the liver of NASH patients before and after RYGB surgery in a bioinformatic method. Our findings will contribute to the understanding of molecular biological changes underlying NASH improvement after RYGB surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2020.611213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884850PMC
May 2021

Anti-Na/K-ATPase immunotherapy ameliorates α-synuclein pathology through activation of Na/K-ATPase α1-dependent autophagy.

Sci Adv 2021 Jan 27;7(5). Epub 2021 Jan 27.

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Na/K-ATPase (NKA) plays important roles in maintaining cellular homeostasis. Conversely, reduced NKA activity has been reported in aging and neurodegenerative diseases. However, little is known about the function of NKA in the pathogenesis of Parkinson's disease (PD). Here, we report that reduction of NKA activity in NKAα1 mice aggravates α-synuclein-induced pathology, including a reduction in tyrosine hydroxylase (TH) and deficits in behavioral tests for memory, learning, and motor function. To reverse this effect, we generated an NKA-stabilizing monoclonal antibody, DR5-12D, against the DR region (DVEDSYGQQWTYEQR) of the NKAα1 subunit. We demonstrate that DR5-12D can ameliorate α-synuclein-induced TH loss and behavioral deficits by accelerating α-synuclein degradation in neurons. The underlying mechanism for the beneficial effects of DR5-12D involves activation of NKAα1-dependent autophagy via increased AMPK/mTOR/ULK1 pathway signaling. Cumulatively, this work demonstrates that NKA activity is neuroprotective and that pharmacological activation of this pathway represents a new therapeutic strategy for PD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abc5062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840131PMC
January 2021

LincRNA-immunity landscape analysis identifies EPIC1 as a regulator of tumor immune evasion and immunotherapy resistance.

Sci Adv 2021 Feb 10;7(7). Epub 2021 Feb 10.

Center for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Through an integrative analysis of the lincRNA expression and tumor immune response in 9,626 tumor samples across 32 cancer types, we developed a lincRNA-based immune response (LIMER) score that can predict the immune cells infiltration and patient prognosis in multiple cancer types. Our analysis also identified tumor-specific lincRNAs, including , that potentially regulate tumor immune response in multiple cancer types. Immunocompetent mouse models and in vitro co-culture assays demonstrated that induces tumor immune evasion and resistance to immunotherapy by suppressing tumor cell antigen presentation. Mechanistically, lincRNA interacts with the histone methyltransferase EZH2, leading to the epigenetic silencing of , , , and MHC-I genes. Genetic and pharmacological inhibition of EZH2 abolish immune-related oncogenic effect and its suppression of interferon-γ signaling. The -EZH2 axis emerges as a potential mechanism for tumor immune evasion that can serve as therapeutic targets for immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abb3555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875530PMC
February 2021

A retrospective study of CT-guided percutaneous irreversible electroporation (IRE) ablation: clinical efficacy and safety.

BMC Cancer 2021 Feb 5;21(1):124. Epub 2021 Feb 5.

Department of Radiology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, 197#, Rui Jin Er Road, Shanghai, 200025, People's Republic of China.

Background: To evaluate the clinical efficacy and safety of ablating renal cell carcinoma (RCC) by irreversible electroporation (IRE).

Methods: Fifteen patients (19 lesions) with RCC who underwent IRE were retrospectively reviewed. Seven patients had solitary kidneys. Two lesions were located in the renal hilus. One patient had chronic renal insufficiency. Percutaneous biopsy for histopathology was performed. The best puncture path plan was evaluated before CT-guided IRE. The estimated glomerular filtration rate (eGFR) was compared vs baseline at 1-2 months after the ablation. Contrast-enhanced computed tomography imaging changes were evaluated immediately after IRE. Contrast-enhanced computed tomography/magnetic resonance was performed 1 month, 3 months, 6 months, 12 months and every year thereafter. The complications after treatment were also reviewed.

Results: The success rate of the procedure was 100%. The median tumor size was 2.4 (IQR 1.3-2.9) cm, with an median score of 6 (IQR 5.5-8) per R.E.N.A.L. criteria (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior, and location relative to polar lines). Two cases (3 lesions) were punctured through the liver. In other cases, puncture was performed through the perirenal space. There were no severecomplications in interventional therapy. Transient gross hematuria occurred in 2 patients (centrally located). Self-limiting perinephric hematomas occurred in 1 patient. Needle puncture path metastasis was found in 1 patient 2.5 years after IRE. The subcutaneous metastasis was surgically removed, and there was no evidence of recurrence. There was no significant change in eGFR levels in terms of short- term clinical outcomes (t = 0.348, P = 0.733). At 6 months, all 15 patients with imaging studies available had no evidence of recurrence. At 1 year, 1 patient (1 of 15) was noted to have experienced needle tract metastasis and accepted salvage radiofrequency ablation (RFA) therapy.

Conclusions: IRE appears to be a safe and effective treatment for RCC that may offer a tissue-sparing method and complete ablation as an alternative therapy for RCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-021-07820-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866876PMC
February 2021

Heterogeneous electro-Fenton catalysis with self-supporting [email protected]/C cathode for shale gas fracturing flowback wastewater.

J Hazard Mater 2021 06 22;412:125208. Epub 2021 Jan 22.

School of Engineering, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA 6027, Australia. Electronic address:

Self-supporting electrodes have triggered great interests in improving electro-Fenton (EF) system for degradation of refractory organic pollutants. In this work, a novel self-supporting carbon fiber paper (CFP) electrode modified by transition metals, e.g. Fe and Mn, was fabricated and employed as a heterogeneous EF cathode. The prepared electrode exhibited excellent degradation for a number of typical organic pollutants along with superior stability. Remarkably, a high removal efficiency was achieved in the EF treatment of shale gas fracturing flowback wastewater. Results indicated that 65.2% TOC and 74.8% COD were eliminated after 4 h degradation. The residual COD value of the real wastewater was 80 mg L, meeting the emission requirement of the integrated wastewater discharge standard (COD<100 mg L) with a low specific energy consumption of 6.9kWhkgCOD. This work demonstrates a competing alternative for efficient decontamination of real wastewater using an electro-Fenton strategy with a low-cost electrode.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2021.125208DOI Listing
June 2021

Variation of IgG N-linked glycosylation profile in diabetic retinopathy.

J Diabetes 2021 Aug 18;13(8):672-680. Epub 2021 Feb 18.

Beijing Municipal Key Laboratory of Clinical Epidemiology, Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China.

Background: The relationship of immunoglobulin G (IgG) glycosylation with diabetes and diabetic nephropathy has been reported, but its role in diabetic retinopathy (DR) remains unclear. We aimed to investigate and validate the association of IgG glycosylation with DR.

Methods: We analyzed the IgG N-linked glycosylation profile and primarily selected candidate glycans by lasso (least absolute shrinkage and selection operator) regression analysis in the discovery population. The findings were validated in the replication population using a binary logistics model. The association between the significant glycosylation panel and clinical features was illustrated with Spearman's coefficient. The results were confirmed by sensitivity analyses.

Results: Among 16 selected glycan candidates using lasso, two IgG glycans (GP15, GP20) and two derived traits (IGP32, IGP54) were identified and validated to be significantly associated with DR (P < .05), and the combined adjusted odds ratios (ORs) were 0.587, 0.613, 1.970, and 0.593, respectively. The glycosylation panel showed a weak correlation with clinical features, except for age. In addition, the results remained consistent when the subjects with prediabetes were excluded from the controls, and the adjusted ORs were 0.677, 0.738, 1.597, and 0.678 in the whole population. Furthermore, in the 1:3 rematched population, a significant association was observed, apart from GP20.

Conclusions: The IgG glycosylation profile, reflecting an aging and pro-inflammatory status, was significantly associated with DR. The variation in the IgG glycome deserves more attention in diabetic complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1753-0407.13160DOI Listing
August 2021

Chitinase 3 like 1 (CHI3L1) is a regulator of smooth muscle cell physiology and atherosclerotic lesion stability.

Cardiovasc Res 2021 Jan 20. Epub 2021 Jan 20.

Division of Vascular Surgery, Stanford University School of Medicine, Stanford, USA.

Aims: Atherosclerotic cerebrovascular disease underlies the majority of ischemic strokes and is a major cause of death and disability. While plaque burden is a predictor of adverse outcomes, plaque vulnerability is increasingly recognized as a driver of lesion rupture and risk for clinical events. Defining the molecular regulators of carotid instability could inform the development of new biomarkers and/or translational targets for at-risk individuals.

Methods And Results: Using two independent human endarterectomy biobanks, we found that the understudied glycoprotein, Chitinase 3 like 1 (CHI3L1), is upregulated in patients with carotid disease compared to healthy controls. Further, CHI3L1 levels were found to stratify individuals based on symptomatology and histopathological evidence of an unstable fibrous cap. Gain- and loss-of-function studies in cultured human carotid artery smooth muscle cells (SMCs) showed that CHI3L1 prevents a number of maladaptive changes in that cell type, including phenotype switching towards a synthetic and hyperproliferative state. Using two murine models of carotid remodelling and lesion vulnerability, we found that knockdown of Chil1 resulted in larger neointimal lesions comprised by de-differentiated SMCs that failed to invest within and stabilize the fibrous cap. Exploratory mechanistic studies identified alterations in potential downstream regulatory genes, including large tumor suppressor kinase 2 (LATS2), which mediates macrophage marker and inflammatory cytokine expression on SMCs, and may explain how CHI3L1 modulates cellular plasticity.

Conclusion: CHI3L1 is upregulated in humans with carotid artery disease and appears to be a strong mediator of plaque vulnerability. Mechanistic studies suggest this change may be a context-dependent adaptive response meant to maintain vascular SMCs in a differentiated state and to prevent rupture of the fibrous cap. Part of this effect may be mediated through downstream suppression of LATS2. Future studies should determine how these changes occur at the molecular level, and whether this gene can be targeted as a novel translational therapy for subjects at risk of stroke.

Translational Perspective: Taken together, CHI3L1 has the potential to become a new translational target for cardiovascular disease. With further studies to understand its full causal relationship to inflammatory pathways, it could have a role in the diagnosis and management of patients with cerebrovascular disease at risk for stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cvr/cvab014DOI Listing
January 2021

Long-term effects of fine particulate matter exposure on the progression of arterial stiffness.

Environ Health 2021 01 6;20(1). Epub 2021 Jan 6.

School of Public Health, Capital Medical University, Beijing, 100069, China.

Background: Prior studies have investigated the association of PM exposure with arterial stiffness measured by ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV), of which conclusions are inconsistent. Moreover, limited evidence is available on the contributory role of PM exposure on the arterial stiffness index.

Methods: We used the population data from the Beijing Health Management Cohort and conducted a longitudinal analysis. The annual average concentration of PM for 35 air pollutant monitoring sites in Beijing from 2014 to 2018 was used to estimate individual exposure by different interpolation methods. Multivariate logistic regression and linear regression were conducted to assess the association of annual average PM concentration with the incidence of higher baPWV, the progression of ABI, and baPWV, respectively.

Results: The association between PM exposure and incidence of higher baPWV was not significant (OR = 1.11, 95% CI: 0.82-1.50, P = 0.497). There was - 0.16% (95% CI: - 0.43-0.11%) decrease in ABI annually and 1.04% (95% CI: 0.72-1.37%) increase in baPWV annually with each increment of 10 μg/m average PM concentration.

Conclusions: Long-term exposure to PM was associated with the progression of arterial stiffness in Beijing. This study suggests that improvement of air quality may help to prevent arterial stiffness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12940-020-00688-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789369PMC
January 2021

Fast automated detection of COVID-19 from medical images using convolutional neural networks.

Commun Biol 2021 01 4;4(1):35. Epub 2021 Jan 4.

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China.

Coronavirus disease 2019 (COVID-19) is a global pandemic posing significant health risks. The diagnostic test sensitivity of COVID-19 is limited due to irregularities in specimen handling. We propose a deep learning framework that identifies COVID-19 from medical images as an auxiliary testing method to improve diagnostic sensitivity. We use pseudo-coloring methods and a platform for annotating X-ray and computed tomography images to train the convolutional neural network, which achieves a performance similar to that of experts and provides high scores for multiple statistical indices (F1 scores > 96.72% (0.9307, 0.9890) and specificity >99.33% (0.9792, 1.0000)). Heatmaps are used to visualize the salient features extracted by the neural network. The neural network-based regression provides strong correlations between the lesion areas in the images and five clinical indicators, resulting in high accuracy of the classification framework. The proposed method represents a potential computer-aided diagnosis method for COVID-19 in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42003-020-01535-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782580PMC
January 2021
-->