Publications by authors named "Yu Xu"

1,093 Publications

  • Page 1 of 1

Discovery and validation of methylation signatures in circulating cell-free DNA for early detection of esophageal cancer: a case-control study.

BMC Med 2021 Oct 13;19(1):243. Epub 2021 Oct 13.

Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, Henan Province, China.

Background: Plasma cell-free DNA (cfDNA) methylation has shown promising results in the early detection of multiple cancers recently. Here, we conducted a study to investigate the performance of cfDNA methylation in the early detection of esophageal cancer (ESCA).

Methods: Specific methylation markers for ESCA were identified and optimized based on esophageal tumor and paired adjacent tissues (n = 24). Age-matched participants with ESCA (n = 85), benign esophageal diseases (n = 10), and healthy controls (n = 125) were randomized into the training and test sets to develop a classifier to differentiate ESCA from healthy controls and benign esophageal disease. The classifier was further validated in an independent plasma cohort of ESCA patients (n = 83) and healthy controls (n = 98).

Results: In total, 921 differentially methylated regions (DMRs) between tumor and adjacent tissues were identified. The early detection classifier based on those DMRs was first developed and tested in plasma samples, discriminating ESCA patients from benign and healthy controls with a sensitivity of 76.2% (60.5-87.9%) and a specificity of 94.1% (85.7-98.4%) in the test set. The performance of the classifier was consistent irrespective of sex, age, and pathological diagnosis (P > 0.05). In the independent plasma validation cohort, similar performance was observed with a sensitivity of 74.7% (64.0-83.6%) and a specificity of 95.9% (89.9-98.9%). Sensitivity for stage 0-II was 58.8% (44.2-72.4%).

Conclusion: We demonstrated that the cfDNA methylation patterns could distinguish ESCAs from healthy individuals and benign esophageal diseases with promising sensitivity and specificity. Further prospective evaluation of the classifier in the early detection of ESCAs in high-risk individuals is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12916-021-02109-yDOI Listing
October 2021

Neuroprotective effects of dopamine D2 receptor agonist on neuroinflammatory injury in olfactory bulb neurons in vitro and in vivo in a mouse model of allergic rhinitis.

Neurotoxicology 2021 Oct 5;87:174-181. Epub 2021 Oct 5.

Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address:

Available evidence indicates that dopamine D2 receptor modulates the neurotoxic effects induced by glutamate. However, neurotoxicity mediated by AMPA-subtype glutamate receptor has rarely been studied in the olfactory bulb. This study mainly explores the neuroprotective effects of dopamine D2 receptor agonist on AMPA receptor-mediated neurotoxicity in the olfactory bulb in a mouse model of allergic rhinitis (AR) with olfactory dysfunction (OD). In our study, we found that AR with OD was closely associated with increased surface expression of the AMPA receptor GluR1, reduced surface expression of GluR2, and apoptosis damage in the olfactory bulb in vivo. Quinpirole (a dopamine D2 receptor agonist) improved olfactory function in mice, ameliorated apoptosis injury in the olfactory bulb but not in the olfactory mucosa, and inhibited the internalization of GluR2-containing AMPA receptor in vitro and in vivo. In addition, phosphorylation plays a crucial role in the regulation of AMPA receptor trafficking. Our results showed that quinpirole reduced the phosphorylation of GluR1 S845 and GluR2 S880 in olfactory bulb neurons in vitro, but it had no obvious effect on GluR1 S831. Therefore, dopamine D2 receptor agonist may inhibit the phosphorylation of GluR1 S845 and GluR2 S880, thereby reducing AMPA receptor-mediated neurotoxicity and alleviating neurotoxic injury to the olfactory bulb caused by AR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuro.2021.10.001DOI Listing
October 2021

Cyclic helix B peptide promotes random-pattern skin flap survival via TFE3-mediated enhancement of autophagy and reduction of ROS levels.

Br J Pharmacol 2021 Oct 8. Epub 2021 Oct 8.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Background And Purpose: Necrosis of random-pattern skin flaps limits their clinical application. Helix B surface peptide (HBSP) protects tissues from ischemia-reperfusion injury; however, the short plasma half-life of HBSP limits its applications. Cyclic helix B peptide (CHBP) was synthesized in the present study, and the role of CHBP in flap survival and the underlying mechanism were investigated.

Experimental Approach: Flap viability was evaluated by survival area analysis, laser doppler blood flow, and histological analysis. RNA sequencing was used to identify the mechanisms relevant to the role of CHBP. Western blotting, real-time quantitative PCR, immunohistochemistry, and immunofluorescence were used to assay the levels of autophagy, oxidative stress, pyroptosis, necroptosis, and molecules related to the adenosine 5'-monophosphate-activated protein kinase (AMPK)-transient receptor potential mucolipin 1 (TRPML1)-calcineurin signaling pathway.

Key Results: The results indicated that CHBP promoted the survival of random-pattern skin flaps. The results of RNA sequencing analysis indicated that autophagy, oxidative stress, pyroptosis, and necroptosis were involved in the ability of CHBP to promote skin flap survival. Restoration of autophagy flux and enhanced resistance to oxidative stress contributed to inhibition of pyroptosis and necroptosis. Increased autophagy and inhibition of oxidative stress in the ischemic flaps are regulated by transcription factor E3 (TFE3). A decrease in the levels of TFE3 caused a reduction in autophagy flux and accumulation of ROS and eliminated the protective effect of CHBP. Moreover, CHBP regulated the activity of TFE3 via the AMPK-TRPML1-calcineurin signaling pathway.

Conclusion And Implications: CHBP promotes skin flap survival by upregulating autophagy and inhibiting oxidative stress in the ischemic flap and may have potential clinical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bph.15702DOI Listing
October 2021

Long-Term Glycemic Variability Is Associated With Arterial Stiffness in Chinese Adults.

Front Endocrinol (Lausanne) 2021 16;12:711540. Epub 2021 Sep 16.

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: The aim of the study was to investigate the association between the visit-to-visit variability (VVV) of fasting plasma glucose (FPG) and arterial stiffness in Chinese adults.

Methods: We performed a cohort study involving 2002 Chinese adults with no history of myocardial infarction or stroke. All the participants attended three visits (the baseline visit in 2008, the 2 visit in 2009 and the 3 visit in 2013). We used four measures to define the VVV of FPG across the three visits: the standard deviation (SD), the coefficient of variation (CV), the average successive variability (ASV) and the variability independent of the mean (VIM). We used brachial-ankle pulse wave velocity (ba-PWV) to measure arterial stiffness at the 2 and the 3 visits.

Results: Compared with the lowest tertile of all the four measurements of VVV of FPG, significantly increased levels of ba-PWV change, ratio of ba-PWV change and the occurrence of the elevated ba-PWV were found in the highest tertile. The odds ratio (OR) and 95% confidence interval (CI) comparing participants in the highest tertile . the lowest tertile of FPG-SD was 1.37 (1.01-1.86) for risks of having elevated ba-PWV, even after adjustment for covariates including the mean FPG. Similar results were found for FPG-CV and FPG-VIM.

Conclusion: Greater long-term variability of FPG was associated with an increased risk of arterial stiffness, suggesting that the VVV of FPG could be used for an early detection of subclinical atherosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2021.711540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481863PMC
September 2021

Photothermal microfluidic-assisted self-cleaning effect for a highly reusable SERS sensor.

Opt Lett 2021 Oct;46(19):4714-4717

The synergistic integration of optofluidic and surface enhanced Raman scattering (SERS) sensing is a new analytical technique that provides a number of unique characteristics for enhancing the sensing performance and simplifying the design of microsystems. Here, we propose a reusable optofluidic SERS sensor by integrating Au nanoisland substrate (AuNIS)-coated fiber into a microfluidic chip. Through both systematic experimental and theoretical analysis, the sensor enables efficient self-cleaning based on its optical-to-heat-hydrodynamic energy conversion property. Besides, the sensor exhibits the instrument detection limit down to 10/ and enhancement factor of 10 for Rhodamine 6G. Our optofluidic SERS sensor with such a photothermal microfluidic-assisted self-cleaning method has the advantages of portability, simple operation, and high cleaning efficiency, which will provide a new, to the best of our knowledge, concept and approach for cost-effective and reusable sensors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OL.434468DOI Listing
October 2021

Early kidney injury predicts disease progression in patients with COVID-19: a cohort study.

BMC Infect Dis 2021 Sep 27;21(1):1012. Epub 2021 Sep 27.

Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), NO.30 Gaotanyan Street, Chongqing, 400038, People's Republic of China.

Background: The receptor of severe respiratory syndrome coronavirus 2 (SARS-CoV-2), angiotensin-converting enzyme 2, is more abundant in kidney than in lung tissue, suggesting that kidney might be another important target organ for SARS-CoV-2. However, our understanding of kidney injury caused by Coronavirus Disease 2019 (COVID-19) is limited. This study aimed to explore the association between kidney injury and disease progression in patients with COVID-19.

Methods: A retrospective cohort study was designed by including 2630 patients with confirmed COVID-19 from Huoshenshan Hospital (Wuhan, China) from 1 February to 13 April 2020. Kidney function indexes and other clinical information were extracted from the electronic medical record system. Associations between kidney function indexes and disease progression were analyzed using Cox proportional-hazards regression and generalized linear mixed model.

Results: We found that estimated glomerular filtration rate (eGFR) and creatinine clearance (Ccr) decreased in 22.0% and 24.0% of patients with COVID-19, respectively. Proteinuria was detected in 15.0% patients and hematuria was detected in 8.1% of patients. Hematuria (HR 2.38, 95% CI 1.50-3.78), proteinuria (HR 2.16, 95% CI 1.33-3.51), elevated baseline serum creatinine (HR 2.84, 95% CI 1.92-4.21) and blood urea nitrogen (HR 3.54, 95% CI 2.36-5.31), and decrease baseline eGFR (HR 1.58, 95% CI 1.07-2.34) were found to be independent risk factors for disease progression after adjusted confounders. Generalized linear mixed model analysis showed that the dynamic trajectories of uric acid was significantly related to disease progression.

Conclusion: There was a high proportion of early kidney function injury in COVID-19 patients on admission. Early kidney injury could help clinicians to identify patients with poor prognosis at an early stage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-021-06576-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474921PMC
September 2021

Oncologic safety of laparoscopic surgery for women with apparent early-stage uterine serous carcinoma: A multi-institutional retrospective cohort study.

Int J Gynaecol Obstet 2021 Sep 24. Epub 2021 Sep 24.

Department of Obstetrics and Gynecology, Enshi Clinical College of Wuhan University, Enshi, China.

Objective: To compare the long-term survival outcomes of patients with apparent early-stage uterine serous carcinoma (USC) who underwent laparoscopic staging surgery with those who underwent open surgical staging.

Methods: A total of 295 patients from four Chinese teaching hospitals were included. Overall survival (OS) and disease-free survival (DFS) were estimated and compared using the Kaplan-Meier method and the log-rank test among patients after laparoscopic surgery or open surgery. The Cox proportional hazards regression model was applied to adjust for potential confounding factors.

Results: For patients with apparent early-stage USC, laparoscopic surgery was associated with deteriorated DFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.15-2.93, P = 0.012), and there was no significant difference in OS between the two groups (HR 1.74, 95% CI 0.99-3.08, P = 0.056). However, after adjusting for confounding factors, the surgical approach was not an independent prognostic factor for DFS (adjusted HR 1.16, 95% CI 0.63-2.12, P = 0.636) and OS (adjusted HR 1.11, 95% CI 0.52-2.38, P = 0.794) in apparent early-stage USC.

Conclusion: For apparent early-stage USC, laparoscopic surgery is safe. This needs to be confirmed by future prospective clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijgo.13942DOI Listing
September 2021

Liver Fibrosis Index FIB-4 Is Associated With Mortality in COVID-19.

Hepatol Commun 2021 Mar 10;5(3):434-445. Epub 2020 Dec 10.

Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Coronavirus disease 2019 (COVID-19) is associated with adverse outcomes, including need for invasive mechanical ventilation and death in people with risk factors. Liver enzyme elevation is commonly seen in this group, but its clinical significance remains elusive. In this study, we calculated the Fibrosis-4 (FIB-4) score for a cohort of hospitalized patients with COVID-19 and assessed its association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, inflammatory cytokine levels, and clinical outcome. A total of 202 hospitalized participants who tested positive for SARS-CoV-2 by nasopharyngeal sampling were included in this analysis. FIB-4 was calculated for each participant using the alanine aminotransferase, aspartate aminotransferase, age, and platelet count. We evaluated the association between FIB-4 and mortality using both multivariate logistic regression and Cox proportional hazards model. Correlations between FIB-4 and SARS-CoV-2 RNA and cytokine levels were evaluated using the Spearman test. Among the 202 participants, 22 died. The median FIB-4 in participants who survived and died were 1.91 and 3.98 (P < 0.001 by Mann-Whitney U test), respectively. Each one-unit increment in FIB-4 was associated with an increased odds of death (odds ratio, 1.79; 95% confidence interval, 1.36, 2.35; P < 0.001) after adjusting for baseline characteristics including sex, body mass index, hypertension, diabetes, and history of liver diseases. During hospitalization, FIB-4 peaked and then normalized in the survival group but failed to normalize in the death group. FIB-4 was positively correlated with the level of SARS-CoV-2 viral load and monocyte-associated cytokines, especially interleukin-6 and interferon gamma-induced protein 10. Conclusion: FIB-4 is associated with mortality in COVID-19, independent of underlying conditions including liver diseases. FIB-4 may be a simple and inexpensive approach to risk-stratify individuals with COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep4.1650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753559PMC
March 2021

NAD+ biosynthetic impairment and urinary metabolomic alterations observed in hospitalized adults with COVID-19-related acute kidney injury.

Kidney Int Rep 2021 Sep 14. Epub 2021 Sep 14.

Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School.

Introduction: Acute kidney injury (AKI) is common in COVID-19 and associated with increased morbidity and mortality. We investigated alterations in the urine metabolome to test the hypothesis that impaired nicotinamide adenine dinucleotide (NAD+) biosynthesis and other deficiencies in energy metabolism in the kidney, previously characterized in ischemic, toxic, and inflammatory etiologies of AKI, will be present in COVID-19-associated AKI.

Methods: This is a case-control study among two independent populations of adults hospitalized with COVID-19: a critically ill population in Boston, Massachusetts, and a general population in Birmingham, Alabama. Cases had AKI stages 2 or 3 by Kidney Disease Improving Global Outcomes criteria; controls had no AKI. Metabolites were measured by liquid chromatography - mass spectrometry.

Results: Fourteen cases and 14 controls were included from Boston, and 8 cases and 10 controls from Birmingham. Increased urinary quinolinate-to-tryptophan ratio, seen with impaired NAD+ biosynthesis, was present in cases at each location and pooled across locations (median [IQR]: 1.34 [0.59-2.96] in cases, 0.31 [0.13-1.63] in controls, p=0.0013). Altered energy metabolism and purine metabolism contributed to a distinct urinary metabolomic signature that differentiated patients with and without AKI (supervised random forest class error: 2/28 in Boston, 0/18 in Birmingham).

Conclusion: Urinary metabolites spanning multiple biochemical pathways differentiate AKI vs. non-AKI in patients hospitalized with COVID-19, and suggest a conserved impairment in NAD+ biosynthesis which may present a novel therapeutic target to mitigate COVID-19-associated AKI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ekir.2021.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439094PMC
September 2021

FOXC1 modulates stem-like cell properties and chemoresistance through Hedgehog and EMT signaling in gastric adenocarcinoma.

Mol Ther 2021 Sep 14. Epub 2021 Sep 14.

Department of Gastric Surgery, Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China, 350001. Electronic address:

Chemoresistance is the major cause of gastric adenocarcinoma (GA) treatment failure. The mechanisms underlying chemoresistance remain incompletely understood. Here, we sought to identify genes differentially expressed between chemoresistant and chemosensitive GA and to validate the function of the top hit. High-throughput RNA sequencing was performed to detect chemoresistance-related genes. The function of the only gene overexpressed in both chemoresistant tumors and tumor tissue relative to normal gastric epithelia, FOXC1, was examined in GA cells, mouse xenograft models, and patient-derived organoid (PDO) systems, focusing on cancer stem-like cell (CSC) phenotypes, metastasis, and chemoresistance. FOXC1 was expressed at significantly higher levels in GA patient tumors that were resistant to chemotherapy, and high FOXC1 tumor expression was significantly correlated with poor survival among patients undergoing resection (p=0.011). FOXC1 activity was significantly higher in spheroid-forming or CD44+ GA CSCs than in unselected cells. Inhibition of FOXC1 decreased the expression of CD44 and Sox2, decreased spheroid size by 78-82%, and decreased spheroid number (>100 μm) by 75-86%. GA CSC chemotherapy resistance was reversed with FOXC1 inhibition in vitro, in vivo, and in patient-derived organoids (PDOs). Mechanistic studies indicated that FOXC1 acts via the Hedgehog and epithelial-to-mesenchymal transition (EMT) pathways. Our results imply that FOXC1 mediates the CSC phenotypes, metastasis, and chemotherapy resistance of GA through Hedgehog and EMT signaling. FOXC1 inhibitors may thus represent a novel strategy to overcome chemoresistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ymthe.2021.09.009DOI Listing
September 2021

Genomic alteration profiles of lung cancer and their relationship to clinical features and prognosis value using individualized genetic testing.

J Thorac Dis 2021 Aug;13(8):5007-5015

Department of Oncology, The 4th Hospital of Hebei Medical University, Shijiazhuang, China.

Background: This study aimed to use a panel targeting 197 genes and 38 fusions to observe the features of gene variations in lung cancer patients, as well as their prognostic values.

Methods: Patients admitted to our hospital between 2016 and 2017 were enrolled. All patients received OseqTM-Drug genetic testing using peripheral venous blood, followed by 1-2 years of observation.

Results: For all included patients, 32 genes were observed with mutations. EGFR exhibited the highest mutation rate (46.5%), followed by TP53. The majority of patients carried only one mutant gene. Interestingly, 18 (41.8%) patients showed no mutations, and some cases carried mutations in six genes simultaneously. There was no statistical relationship between mutations and demographic influence. Pathological subtypes were associated with mutations including , and . A significant correlation was observed between mutant genes and stage at diagnosis, however this requires further confirmation as there was only one case in these mutations: , and . For the 33 patients with lymph node metastases at the time of diagnosis, no correlation with any gene mutant was found. Finally, no associations between the survival or prognosis indices (1-year survival, 1-year progression, progression free survival (PFS), and overall survival (OS)) were observed with gene mutations.

Conclusions: Together, individualized genetic testing is a feasible and minimally invasive approach in cancer genetic analysis. However, gene mutation detection has a limited efficacy in the prediction of prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jtd-21-1031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411145PMC
August 2021

Plasma levels of amino acids and derivatives in retinopathy of prematurity.

Int J Med Sci 2021 27;18(15):3581-3587. Epub 2021 Aug 27.

Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Retinopathy of prematurity (ROP) is a retinal disease that causes blindness in premature infants. This study aimed to reveal the changes in amino acids and derivatives in the plasma of ROP patients compared with premature infants without ROP. Metabolomics targeting amino acids and their derivatives was conducted to assess their plasma levels in ROP patients (=58) and premature infants without ROP (=25), and KEGG pathway analysis was used to identify the involved pathways. Among the 31 assessed metabolites, the levels of 4 amino acids were significantly altered in the ROP group. Creatinine was downregulated in the plasma of the ROP patients, while the levels of citrulline, arginine, and aminoadipic acid were upregulated in the ROP group. Significant correlations were identified between the ROP stage and plasma levels of citrulline, creatinine, and aminoadipic acid. The involved pathways included biosynthesis of amino acids, arginine and proline metabolism, and arginine biosynthesis. The plasma levels of citrulline, creatinine, arginine, and aminoadipic acid were significantly changed in ROP patients. These metabolites could be considered potential biomarkers of ROP, and their related metabolic pathways might be involved in ROP pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijms.63603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436098PMC
August 2021

Non-alcoholic fatty liver disease, metabolic goal achievement with incident cardiovascular disease and eGFR-based chronic kidney disease in patients with prediabetes and diabetes.

Metabolism 2021 Sep 10;124:154874. Epub 2021 Sep 10.

Karamay Municipal People's Hospital, Xinjiang, China.

Aims/hypothesis: We aimed to evaluate the effect of NAFLD on the risk of incident cardiovascular disease (CVD) and estimated glomerular filtration rate (eGFR)-based chronic kidney disease (CKD), and further test the joint effects and interactions between NAFLD status and individual metabolic element, as well as the total 'ABCs' metabolic goal achievement, on the CVD and CKD risk among 101,296 patients with prediabetes or diabetes from a prospective cohort study.

Methods: We conducted the study based on the China Cardiometabolic Disease and Cancer Cohort (4C) study, a large-scale, population-based prospective cohort. After excluding alcohol abuse and other cause of hepatic diseases, we used fatty liver index (FLI) ≥ 60 as a proxy of NAFLD and stratified the probability of fibrosis by aspartate transaminase/alanine transaminase ratio (AAR) with cut-offs of 0.8 and 1.4. 'ABCs' metabolic goal was defined as subjects who had HbA1c < 6.5% (A), SBP/DBP < 130/80 mmHg (B), and LDL-C < 100 mg/dL (C). During 3.8 years follow-up, we validated 2340 CVD events based on medical records and identified 1943 participants developed CKD based on centrally tested eGFR.

Results: The multivariable adjusted hazard ratios (HRs) were 1.15 (95% confidence interval (CI), 1.05-1.27) for CVD events and 1.33 (95% CI, 1.20-1.48) for CKD among NAFLD patients, compared with participants without NAFLD. Of NAFLD patients, relative to individuals with low AAR (<0.8), those with high AAR (≥1.4) were more likely to experience CVD events [1.62 (1.21-2.18)] and CKD [1.63 (1.17-2.28)]. Participants with NAFLD and comorbid poorly controlled metabolic risk factors had higher risk of CVD events or CKD than having either alone, with a significant interaction between poor glycemic control and NAFLD on the risk of vascular complications.

Conclusions: NAFLD was associated with incident CVD and CKD among patients with prediabetes or diabetes. Such associations were substantially modified by the comprehensive achievement of metabolic goal.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.metabol.2021.154874DOI Listing
September 2021

A Multicenter Study of Prevalence and Risk Factors for Allergic Rhinitis in Primary School Children in 5 Cities of Hubei Province, China.

Int Arch Allergy Immunol 2021 Aug 6:1-11. Epub 2021 Aug 6.

Department of Otolaryngology - Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.

Background: Few data are available concerning the prevalence and risk factors for allergic rhinitis (AR) in school children in Hubei Province which is located in the central part of China. This study investigated the epidemiological features of AR among school children in Hubei Province.

Methods: A cross-sectional questionnaire survey on AR in school children was carried out in 5 cities in Hubei Province by cluster sampling from June to September 2018. Questionnaires were filled out by children and their parents jointly. The diagnostic criteria of AR were according to the SFAR. Questions from the questionnaire were used to examine the pattern of AR. Logistic regression analysis was used to assess the risk factors for childhood allergies.

Results: The total prevalence rate of AR was 16.16%, with 24.31% (Wuhan), 4.34% (Xiangyang), 4.31% (Tianmen), 10.92% (Jingmen), and 11.42% (Huangshi), respectively. The prevalence of AR was positively correlated with gross domestic product per capita (p < 0.05). Multivariate analysis revealed that male, city of Wuhan, family history of allergy, food allergy, drug allergy, air purifier, exposure to dust, living in towns or urban area before 2 years old, maternal age for 26-35 years old, and frequent application of antibiotics increased the risk of AR, while daily outdoor time for 1-2 h, daily sleeping time >8 h, siblings, and breastfeeding for >6 months reduced the risk significantly.

Conclusion: We found the apparent geographic variation of children allergies in Hubei Province. Both genetic and environment factors had impacts on the prevalence of AR in school children. Public policies should specifically target at the local risk factors for different areas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000517948DOI Listing
August 2021

Tie2 activation protects against prothrombotic endothelial dysfunction in COVID-19.

JCI Insight 2021 Sep 10. Epub 2021 Sep 10.

Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, United States of America.

Endothelial dysfunction accompanies the microvascular thrombosis commonly observed in severe COVID-19. Constitutively, the endothelial surface is anticoagulant, a property maintained at least in part via signaling through the Tie2 receptor. During inflammation, the Tie2 antagonist angiopoietin-2 (Angpt-2) is released from endothelial cells and inhibits Tie2, promoting a prothrombotic phenotypic shift. We sought to assess whether severe COVID-19 is associated with procoagulant endothelial dysfunction and alterations in the Tie2-angiopoietin axis. Primary human endothelial cells treated with plasma from patients with severe COVID-19 upregulated expression of thromboinflammatory genes, inhibited expression of antithrombotic genes, and promoted coagulation on the endothelial surface. Pharmacologic activation of Tie2 with the small molecule AKB-9778 reversed the prothrombotic state induced by COVID-19 plasma in primary endothelial cells. Lung autopsies from COVID-19 patients demonstrated a prothrombotic endothelial signature. Assessment of circulating endothelial markers in a cohort of 98 patients with mild, moderate, or severe COVID-19 revealed endothelial dysfunction indicative of a prothrombotic state. Angpt-2 concentrations rose with increasing disease severity and highest levels were associated with worse survival. These data highlight the disruption of Tie2-angiopoietin signaling and procoagulant changes in endothelial cells in severe COVID-19. Our findings provide rationale for current trials of Tie2-activating therapy with AKB-9778 in COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.151527DOI Listing
September 2021

Fasting plasma glucose and glucose fluctuation are associated with COVID-19 prognosis regardless of pre-existing diabetes.

Diabetes Res Clin Pract 2021 Sep 6;180:109041. Epub 2021 Sep 6.

Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 401120, People's Republic of China. Electronic address:

Aims: We aimed to investigate the role of Fasting Plasma Glucose (FPG) and glucose fluctuation in the prognosis of COVID-19 patients stratified by pre-existing diabetes.

Methods: The associations of FPG and glucose fluctuation indexes with prognosis of COVID-19 in 2,642 patients were investigated by multivariate Cox regression analysis. The primary outcome was in-hospital mortality; the secondary outcome was disease progression. The longitudinal changes of FPG over time were analyzed by the latent growth curve model in COVID-19 patients stratified by diabetes and severity of COVID-19.

Results: We found FPG as an independent prognostic factor of overall survival after adjustment for age, sex, diabetes and severity of COVID-19 at admission (HR: 1.15, 95% CI: 1.06-1.25, P = 1.02 × 10). Multivariate logistic regression analysis indicated that the standard deviation of blood glucose (SDBG) and largest amplitude of glycemic excursions (LAGE) were also independent risk factors of COVID-19 progression (P = 0.03 and 0.04, respectively). The growth trajectory of FPG over the first 3 days of hospitalization was steeper in patients with critical COVID-19 in comparison to moderate patients.

Conclusions: Hyperglycemia and glucose fluctuation were adverse prognostic factors of COVID-19 regardless of pre-existing diabetes. This stresses the importance of glycemic control in addition to other therapeutic management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.diabres.2021.109041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420085PMC
September 2021

Functional impairment of HIV-specific CD8 T cells precedes aborted spontaneous control of viremia.

Immunity 2021 Oct 7;54(10):2372-2384.e7. Epub 2021 Sep 7.

Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA; Institute for Medical Engineering and Sciences and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address:

Spontaneous control of HIV infection has been repeatedly linked to antiviral CD8 T cells but is not always permanent. To address mechanisms of durable and aborted control of viremia, we evaluated immunologic and virologic parameters longitudinally among 34 HIV-infected subjects with differential outcomes. Despite sustained recognition of autologous virus, HIV-specific proliferative and cytolytic T cell effector functions became selectively and intrinsically impaired prior to aborted control. Longitudinal transcriptomic profiling of functionally impaired HIV-specific CD8 T cells revealed altered expression of genes related to activation, cytokine-mediated signaling, and cell cycle regulation, including increased expression of the antiproliferative transcription factor KLF2 but not of genes associated with canonical exhaustion. Lymphoid HIV-specific CD8 T cells also exhibited poor functionality during aborted control relative to durable control. Our results identify selective functional impairment of HIV-specific CD8 T cells as prognostic of impending aborted HIV control, with implications for clinical monitoring and immunotherapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.immuni.2021.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516715PMC
October 2021

Integration of Molecular Inflammatory Interactome Analyses Reveals Dynamics of Circulating Cytokines and Extracellular Vesicle Long Non-Coding RNAs and mRNAs in Heroin Addicts During Acute and Protracted Withdrawal.

Front Immunol 2021 19;12:730300. Epub 2021 Aug 19.

National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China.

Heroin addiction and withdrawal influence multiple physiological functions, including immune responses, but the mechanism remains largely elusive. The objective of this study was to investigate the molecular inflammatory interactome, particularly the cytokines and transcriptome regulatory network in heroin addicts undergoing withdrawal, compared to healthy controls (HCs). Twenty-seven cytokines were simultaneously assessed in 41 heroin addicts, including 20 at the acute withdrawal (AW) stage and 21 at the protracted withdrawal (PW) stage, and 38 age- and gender-matched HCs. Disturbed T-helper(T)1/T2, T1/T17, and T2/T17 balances, characterized by reduced interleukin (IL)-2, elevated IL-4, IL-10, and IL-17A, but normal TNF-α, were present in the AW subjects. These imbalances were mostly restored to the baseline at the PW stage. However, the cytokines TNF-α, IL-2, IL-7, IL-10, and IL-17A remained dysregulated. This study also profiled exosomal long non-coding RNA (lncRNA) and mRNA in the plasma of heroin addicts, constructed co-expression gene regulation networks, and identified lncRNA-mRNA-pathway pairs specifically associated with alterations in cytokine profiles and T1/T2/T17 imbalances. Altogether, a large amount of cytokine and exosomal lncRNA/mRNA expression profiling data relating to heroin withdrawal was obtained, providing a useful experimental and theoretical basis for further understanding of the pathogenic mechanisms of withdrawal symptoms in heroin addicts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.730300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416766PMC
August 2021

High-quality Arabidopsis thaliana Genome Assembly with Nanopore and HiFi Long Reads.

Genomics Proteomics Bioinformatics 2021 Sep 3. Epub 2021 Sep 3.

MOE Key Laboratory for Intelligent Networks & Network Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, 710049, China; School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China; School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an 710049, China; Genome Institute, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address:

Arabidopsis thaliana is an important and long-established model species for plant molecular biology, genetics, epigenetics, and genomics. However, the latest version of reference genome still contains significant number of missing segments. Here, we report a high-quality and almost complete Col-0 genome assembly with two gaps (Col-XJTU) using combination of Oxford Nanopore Technology ultra-long reads, PacBio high-fidelity long reads, and Hi-C data. The total genome assembly size is 133,725,193 bp, introducing 14.6 Mb of novel sequences compared to the TAIR10.1 reference genome. All five chromosomes of Col-XJTU assembly are highly accurate with consensus quality (QV) scores > 60 (ranging from 62 to 68), which are higher than those of TAIR10.1 reference (QV scores ranging from 45 to 52). We have completely resolved chromosome (Chr) 3 and Chr5 in a telomere-to-telomere manner. Chr4 has been completely resolved except the nucleolar organizing regions, which comprise long repetitive DNA fragments. The Chr1 centromere (CEN1), reportedly around 9 Mb in length, is particularly challenging to assemble due to the presence of tens of thousands of CEN180 satellite repeats. Using the cutting-edge sequencing data and novel computational approaches, we assembled about 4 Mb of sequence for CEN1 and a 3.5-Mb-long CEN2. We investigated the structure and epigenetics of centromeres. We detected four clusters of CEN180 monomers, and found that the centromere-specific histone H3-like protein (CENH3) exhibits a strong preference for CEN180 cluster 3. Moreover, we observed hypomethylation patterns in CENH3-enriched regions. We believe that this high-quality genome assembly, Col-XJTU, would serve as a valuable reference to better understand the global pattern of centromeric polymorphisms, as well as genetic and epigenetic features in plants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gpb.2021.08.003DOI Listing
September 2021

Serum Total Bilirubin and Risk of Progressing Diabetes: A Prospective Cohort Study.

Biomed Environ Sci 2021 Aug;34(8):632-636

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3967/bes2021.087DOI Listing
August 2021

Competing endogenous RNA network associated with oxygen-induced retinopathy: Expression of the network and identification of the MALAT1/miR-124-3p/EGR1 regulatory axis.

Exp Cell Res 2021 Aug 29;408(1):112783. Epub 2021 Aug 29.

Department of Ophthalmology, Xinhua Hospital, Affiliated to Medicine School of Shanghai Jiaotong University, No. 1665, Kongjiang Road, Shanghai, 200092, China. Electronic address:

Retinopathy of prematurity (ROP) is a severe retinal dysfunction in prematurely born babies. The relationship between non-coding RNAs and retinopathy of prematurity (ROP) remain unclear. Microarray analysis of lncRNAs, miRNAs, and mRNAs was conducted in a mouse model of ROP. A competing endogenous RNA (ceRNA) network was constructed. The relationship among MALAT1, miR-124-3p, and Early growth response protein 1 (EGR1) was assessed in hypoxia-induced primary human umbilical vein endothelial cells (HUVECs) and ROP mouse model. In the study, we found 2252 lncRNAs, 1239 mRNAs, and 36 miRNAs were differentially regulated. ceRNA network consisting of 21 lncRNAs, 10 miRNAs, and 19 mRNAs was established. Of the most down-regulated miRNAs, miR-124-3p was selected for additional study. miR-124-3p ceased the migration and proliferation of primary HUVECs in hypoxic conditions, and directly suppressed EGR1. Additionally, MALAT1 directly sponged miR-124-3p. Knockdown of MALAT1 decreased EGR1 expression and inhibited the migration and proliferation of primary HUVECs in hypoxia. Furthermore, these changes were rescued by depletion of miR-124-3p. In vivo, intravitreal injection of miR-124-3p, shMALAT1 decreased EGR1 expression and markedly suppressed retinal neovascularization in OIR models. Intravitreal injection of shMALAT1 and miR-124-3p antagomir at the same time can promote retinal neovascularization, which reversed the suppression of retinal neovascularization functioned by shMALAT1. In conclusion, the expression profiles of lncRNAs and miRNAs and the ceRNA network in a mouse model of ROP may be indicative of the underlying mechanisms of retinal angiogenesis and neural activity. The MALAT1/miR-124-3p/EGR1 regulatory axis is partly responsible for retinal neovascularization, which may provide a novel theoretical basis for the pathogenesis of ROP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yexcr.2021.112783DOI Listing
August 2021

Type I, II, and III Interferon Signatures Correspond to Coronavirus Disease 2019 Severity.

J Infect Dis 2021 09;224(5):777-782

Liver Center, GI Division, Massachusetts General Hospital, Boston, Massachusetts, USA.

We analyzed plasma levels of interferons (IFNs) and cytokines, and expression of IFN-stimulated genes in peripheral blood mononuclear cells in patients with coronavirus disease 2019 of varying disease severity. Patients hospitalized with mild disease exhibited transient type I IFN responses, while intensive care unit patients had prolonged type I IFN responses. Type II IFN responses were compromised in intensive care unit patients. Type III IFN responses were induced in the early phase of infection, even in convalescent patients. These results highlight the importance of early type I and III IFN responses in controlling coronavirus disease 2019 progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiab288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244575PMC
September 2021

Causal associations of obesity with chronic kidney disease and arterial stiffness: a Mendelian randomization study.

J Clin Endocrinol Metab 2021 Aug 27. Epub 2021 Aug 27.

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: Observational studies have associated obesity with chronic kidney disease (CKD) and arterial stiffness, but the causality remains unclear. We aimed to investigate the causality of obesity with CKD and arterial stiffness using Mendelian randomization (MR) analysis.

Methods: We genotyped 14 body mass index (BMI)-associated variants validated in East Asians in 11384 Chinese adults. A genetic risk score based on the 14 variants and the 14 individual single nucleotide polymorphisms were respectively used as instrumental variables (IVs). CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m 2. Arterial stiffness was defined as brachial-ankle pulse wave velocity >1550 cm/s.

Results: Using the genetic risk score as the IV, we demonstrated causal relations of each 1-standard deviation increment in BMI with CKD (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.11-5.00) and arterial stiffness (OR: 1.71; 95% CI: 1.22-2.39). Using the 14 single nucleotide polymorphisms individually as IVs, each 1-standard deviation increment in BMI casually associated with CKD (OR: 2.58; 95% CI: 1.39-4.79) and arterial stiffness (OR: 1.87; 95% CI: 1.24-2.81) in the inverse-variance weighted analysis, and MR-Egger regression revealed no evidence of horizontal pleiotropy (Both P for intercept≥0.34). The causality between obesity and CKD was validated in two-sample MR analysis among Europeans (681275 of Genetic Investigation of ANthropometric Traits and 133413 of CKD Genetics).

Conclusions: This study provided novel insights into causality of obesity with CKD and arterial stiffness, highlighting the importance of weight management for primary prevention and control of subclinical vascular diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgab633DOI Listing
August 2021

Profound Treg perturbations correlate with COVID-19 severity.

Proc Natl Acad Sci U S A 2021 09;118(37)

Department of Immunology, Harvard Medical School, Boston, MA 02115;

The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We hypothesized that perturbations in FoxP3 T regulatory cells (Treg), key enforcers of immune homeostasis, contribute to COVID-19 pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype in severe COVID-19 patients, with an increase in Treg proportions and intracellular levels of the lineage-defining transcription factor FoxP3, correlating with poor outcomes. These Tregs showed a distinct transcriptional signature, with overexpression of several suppressive effectors, but also proinflammatory molecules like interleukin (IL)-32, and a striking similarity to tumor-infiltrating Tregs that suppress antitumor responses. Most marked during acute severe disease, these traits persisted somewhat in convalescent patients. A screen for candidate agents revealed that IL-6 and IL-18 may individually contribute different facets of these COVID-19-linked perturbations. These results suggest that Tregs may play nefarious roles in COVID-19, by suppressing antiviral T cell responses during the severe phase of the disease, and by a direct proinflammatory role.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2111315118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449354PMC
September 2021

INTRAVITREAL RANIBIZUMAB TREATMENT FOR ADVANCED FAMILIAL EXUDATIVE VITREORETINOPATHY WITH HIGH VASCULAR ACTIVITY.

Retina 2021 Sep;41(9):1976-1985

Department of Ophthalmology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Purpose: To determine the efficacy of intravitreal ranibizumab (IVR) treatment for advanced familial exudative vitreoretinopathy with high vascular activity.

Methods: The retrospective interventional case series included 28 eyes (20 patients) that had IVR in combination or not with other treatment, for Stage 3 to 5 familial exudative vitreoretinopathy with active fibrovascular proliferation and prominent subretinal exudation. Outcome measures were fundus features after treatment, associated clinical variables, and genetic mutations.

Results: The age of patients at the first IVR ranged from 0.2 to 36 months. An average of 1.3 IVR injections per eye were given. Familial exudative vitreoretinopathy regressed in 16 (57%) eyes and progressed in 12 eyes (43%) after IVR. Laser and/or vitrectomy was performed on 13 eyes. The retina was reattached in 22 eyes (78%) after 24 to 58 months follow-up. Clinical variables associated with progression after IVR were preexisting fibrovascular proliferation over one quadrant and persistent vascular activity after the initial injection (P < 0.05). Familial exudative vitreoretinopathy-causative genetic mutations in 11 patients were related to variable response to IVR treatment.

Conclusion: Intravitreal ranibizumab treatment may effectively regress advanced familial exudative vitreoretinopathy with high vascular activity in selected cases. Different treatment outcomes may be relevant to variable presentation and genetic heterogeneity of familial exudative vitreoretinopathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/IAE.0000000000003122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384247PMC
September 2021

Viral Load Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospitalized Individuals With Coronavirus Disease 2019.

Open Forum Infect Dis 2021 Aug 17;8(8):ofab153. Epub 2021 Apr 17.

Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) kinetics remain understudied, including the impact of remdesivir. In hospitalized individuals, peak sputum viral load occurred in week 2 of symptoms, whereas viremia peaked within 1 week of symptom-onset, suggesting early systemic seeding of SARS-CoV-2. Remdesivir treatment was associated with faster viral decay.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofab153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083268PMC
August 2021

Individual and combined cardiometabolic morbidities and the subsequent risk of cardiovascular events in Chinese adults.

J Clin Endocrinol Metab 2021 Aug 24. Epub 2021 Aug 24.

Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing, China.

Objectives: To investigate the associations between individual and combined cardiometabolic morbidities and incident cardiovascular events in Chinese adults.

Design: A prospective, nationwide, and population-based cohort study.

Participants: 133572 participants aged ≥ 40 years were included in the study.

Main Outcome Measures: Cardiovascular disease (CVD) events.

Results: Compared with participants without diabetes, hypertension and dyslipidemia, participants with only diabetes (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.32-1.90) or only hypertension (2.04; 1.82-2.28) exhibited significantly higher risk for CVD events, while participants with only dyslipidemia (0.97; 0.84-1.12) exhibited no significantly higher risk for CVD events. When analyzed collectively, participants with diabetes plus hypertension (HR, 2.67; 95%CI, 2.33-3.06), diabetes plus dyslipidemia (1.57; 1.32-1.87), and hypertension plus dyslipidemia (2.12; 1.88-2.39) exhibited significantly higher risk for CVD. Moreover, participants with the combination of diabetes, hypertension and dyslipidemia exhibited the highest risk for CVD events (HR, 3.06; 95%CI, 2.71-3.46). Multivariable-adjusted HRs (95% CIs) for CVD associated with diabetes based on fasting glucose ≥7.0 mmol/L, oral glucose tolerance test-2h glucose ≥11.1 mmol/L, and hemoglobin A1c ≥6.5% were 1.64 (1.51-1.78), 1.57 (1.45-1.69), and 1.54 (1.42-1.66), respectively; associated with hypertension based on systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mmHg were 1.89 (1.76-2.03) and 1.74 (1.60-1.88), respectively; associated with dyslipidemia based on total cholesterol ≥6.22 mmol/L, low-density lipoprotein cholesterol ≥4.14 mmol/L, high-density lipoprotein cholesterol <1.04 mmol/L, and triglycerides ≥2.26 mmol/L were 1.18 (1.08-1.30), 1.30 (1.17-1.44), 1.00 (0.92-1.09), and 1.10 (1.01-1.20), respectively.

Conclusions: Diabetes, hypertension and dyslipidemia showed additive associations with the risk of CVD events in middle-aged and elderly Chinese adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgab609DOI Listing
August 2021

Gestational hyperglycemia and the risk of cardiovascular diseases among elderly Chinese women: Findings from the REACTION study.

J Diabetes 2021 Aug 24. Epub 2021 Aug 24.

The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Background: Gestational hyperglycemia increases the risk of diabetes in later life. However, the risk of future cardiovascular diseases (CVD) related to gestational hyperglycemia remains inconclusive. The purpose of this study was to investigate the impact of gestational hyperglycemia on the subsequent risk of CVD and its modifying factors among elderly Chinese women.

Methods: We conducted a case-control study of elderly women from the baseline survey of Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. Women with gestational hyperglycemia (n = 82), and controls matched by age and study site (n = 410) were included. Information on CVD, including reported coronary heart disease, stroke, or myocardial infarction, was collected through an interviewer-assisted questionnaire.

Results: Women with gestational hyperglycemia were more likely to develop diabetes (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.50-4.18) and CVD (OR, 1.98; 95% CI, 1.05-3.74). Even without progressing to type 2 diabetes, gestational hyperglycemia was associated with an increased risk of CVD (OR, 2.88; 95% CI, 1.18-7.00). However, subgroup analysis indicated that compared with those without gestational hyperglycemia or hypertension, women with both gestational hyperglycemia and hypertension had higher risk of CVD (OR, 3.98; 95% CI, 1.65-9.58), whereas the risk estimate did not significantly change in women with gestational hyperglycemia alone (OR, 2.15; 95% CI, 0.71-6.57). Stratified analysis indicated that among those with overweight/obesity, inactive physical activity, or unhealthy dietary habits, gestational hyperglycemia increased the risk of CVD.

Conclusions: In elderly Chinese women, gestational hyperglycemia was associated with an increased risk of CVD in later life. This association was independent of the progression to diabetes and might be modified by lifestyle factors and hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1753-0407.13222DOI Listing
August 2021

Progress in Understanding Ferroptosis and Its Targeting for Therapeutic Benefits in Traumatic Brain and Spinal Cord Injuries.

Front Cell Dev Biol 2021 4;9:705786. Epub 2021 Aug 4.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Acute central nervous system (CNS) trauma, including spinal cord injury (SCI) and traumatic brain injury (TBI), always leads to severe sensory, motor and autonomic nervous system dysfunction due to a series of processes, including cell death, oxidative stress, inflammation, and excitotoxicity. In recent years, ferroptosis was reported to be a type of programmed cell death characterized by the consumption of polyunsaturated fatty acids and the accumulation of membrane lipid peroxides. The processes that induce ferroptosis include iron overload, imbalanced glutathione metabolism and lipid peroxidation. Several studies have indicated a novel association of ferroptosis and acute CNS trauma. The present paper reviews recent studies of the occurrence of ferroptosis, stressing the definition and process of ferroptosis and metabolic pathways related to ferroptosis. Furthermore, a summary of the existing knowledge of the role of ferroptosis in CNS trauma is presented. The aim here is to effectively understand the mechanisms underlying the occurrence of ferroptosis, as well as the relevant effect on the pathophysiological process of CNS trauma, to present a novel perspective and frame of reference for subsequent investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.705786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371332PMC
August 2021

Knockdown of Salusin- Improves Cardiovascular Function in Myocardial Infarction-Induced Chronic Heart Failure Rats.

Oxid Med Cell Longev 2021 10;2021:8896226. Epub 2021 Aug 10.

Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, Nanjing Medical University, Nanjing, Jiangsu 211166, China.

Salusin- is a biologically active peptide with 20 amino acids that exerts several cardiovascular activity-regulating effects, such as regulating vascular endothelial function and the proliferation of vascular smooth muscle cells. However, the regulatory effects of salusin- in myocardial infarction-induced chronic heart failure (CHF) are still unknown. The current study is aimed at investigating the effects of silencing salusin- on endothelial function, cardiac function, vascular and myocardial remodeling, and its underlying signaling pathways in CHF rats induced by coronary artery ligation. CHF and sham-operated (Sham) rats were subjected to tail vein injection of adenoviral vectors encoding salusin- shRNA or a control-shRNA. The coronary artery (CA), pulmonary artery (PA), and mesenteric artery (MA) were isolated from rats, and isometric tension measurements of arteries were performed. Compared with Sham rats, the plasma salusin-, leptin and visfatin levels and the salusin- protein expression levels of CA, PA, and MA were increased, while the acetylcholine- (ACh-) induced endothelium-dependent vascular relaxation of CA, PA, and MA was attenuated significantly in CHF rats and was improved significantly by salusin- gene knockdown. Salusin- knockdown also improved cardiac function and vascular and myocardial remodeling, increased endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) levels, and decreased NAD(P)H oxidase activity, NOX-2 and NOX-4 expression, and reactive oxygen species (ROS) levels in arteries in CHF rats. The effects of salusin- knockdown in CHF rats were attenuated significantly by pretreatment with the NOS inhibitor L-NAME. These results indicate that silencing salusin- contributes to the improvement of endothelial function, cardiac function, and cardiovascular remodeling in CHF by inhibiting NAD(P)H oxidase-ROS generation and activating eNOS-NO production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/8896226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373485PMC
August 2021
-->