Publications by authors named "Gang Yin"

206 Publications

Response of net primary productivity to grassland phenological changes in Xinjiang, China.

PeerJ 2021 30;9:e10650. Epub 2021 Apr 30.

College of Resource and Environment Sciences, Key Laboratory of Oasis Ecology, Xinjiang University, Urumqi, China.

Determining the relationship between net primary productivity (NPP) and grassland phenology is important for an in-depth understanding of the impact of climate change on ecosystems. In this study, the NPP of grassland in Xinjiang, China, was simulated using the Carnegie-Ames-Stanford approach (CASA) model with Moderate Resolution Imaging Spectroradiometer (MODIS) grassland phenological (MCD12Q2) data to study trends in phenological metrics, grassland NPP, and the relations between these factors from 2001-2014. The results revealed advancement of the start of the growing season (SOS) for grassland in most regions (55.2%) in Xinjiang. The percentage of grassland area in which the end of the growing season (EOS) was delayed (50.9%) was generally the same as that in which the EOS was advanced (49.1%). The percentage of grassland area with an increase in the length of the growing season (LOS) for the grassland area (54.6%) was greater than that with a decrease in the LOS (45.4%). The percentage of grassland area with an increase in NPP (61.6%) was greater than that with a decrease in NPP (38.4%). Warmer regions featured an earlier SOS and a later EOS and thus a longer LOS. Regions with higher precipitation exhibited a later SOS and an earlier EOS and thus a shorter LOS. In most regions, the SOS was earlier, and spring NPP was higher. A linear statistical analysis showed that at various humidity () levels, grassland NPP in all regions initially increased but then decreased with increasing LOS. At higher levels of , when NPP gradually increased, the LOS gradually decreased.
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http://dx.doi.org/10.7717/peerj.10650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092107PMC
April 2021

Efficiency Comparison of Public Hospitals under Different Administrative Affiliations in China: A Pilot City Case.

Healthcare (Basel) 2021 Apr 8;9(4). Epub 2021 Apr 8.

Department of Health Administration, School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.

This study seeks to measure the efficiency disparity and productivity change of tertiary general public hospitals in Wuhan city, central China from the perspective of administrative affiliations by using panel data from 2013 to 2017. Sample hospitals were divided into three categories, namely provincial hospitals, municipal hospitals, and other levels of hospitals. Data envelopment analysis with bootstrapping technique was used to estimate efficiency scores, and a sensitive analysis was performed by varying the specification of model by considering undesirable outputs to test robustness of estimation, and efficiency evolution analysis was carried out by using the Malmquist index. The results indicated that the average values of provincial hospitals and municipal hospitals have experienced efficiency improvement over the period, especially after the initiation of Pilot Public Hospital Reform, but hospitals under other affiliations showed an opposite trend. Meanwhile, differences of administrative subordination in technical efficiency of public hospitals emerged, and the disparity was likely to grow over time. The higher efficiency of hospitals affiliated with municipality, as compared with those governed by province and under other administrative affiliations, may be attributed to better governance and organization structure.
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http://dx.doi.org/10.3390/healthcare9040437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068233PMC
April 2021

Efficiency and productivity of county-level traditional Chinese medicine hospitals in Hubei Province, China: A retrospective study based on 17 years of panel data.

Int J Health Plann Manage 2021 Apr 22. Epub 2021 Apr 22.

Department of Health Administration, School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: The county-level traditional Chinese medicine hospitals have significantly expanded in recent decades. This study aims to assess the changes in the efficiency and productivity of the county-level traditional Chinese medicine hospitals and explore the possible causes of such changes.

Methods: Sixty one hospitals spanning from 2001 to 2017 were selected as samples in this study. And a slacks-based measure of super-efficiency in Data Envelopment Analysis and Malmquist index were used to respectively measure the changes in the efficiency and productivity.

Results: The scale of sample hospitals in Hubei continuously expanded from 2001 to 2017. The mean values of technical efficiency, pure technical efficiency and scale efficiency in 2017 were 0.686, 0.74 and 0.933, respectively. The technical efficiency changes in 2017 was 1.97 times that of 2001, and the technological changes in 2017 was 1.45 times that of 2001.

Conclusions: The medical environment and resources have been greatly improved due to the expansion of the sample hospitals, but the technical efficiency value indicates that the operation efficiency of sample hospitals still needs to be significantly improved. Decision-makers are advised to attach importance to the efficiency of operation management and consider the impact of multiple factors on the change in productivity.
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http://dx.doi.org/10.1002/hpm.3171DOI Listing
April 2021

A Beam Projection-Based Modified Gamma Analysis Scheme for Clinically Interpretable Pre-Treatment Dose Verification.

Dose Response 2021 Apr-Jun;19(2):15593258211001676. Epub 2021 Apr 8.

Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, China.

Purpose: To investigate a novel gamma analysis system for dose verification results in terms of clinical significance.

Methods And Materials: The modified scheme redefined the computational domain of the conventional gamma analysis with the projections of beams and the regions of interest (ROI). We retrospectively studied 6 patients with the conventional and the modified gamma analysis schemes while compared their performances. The cold spots ratio of the planning target volume (PTV) and the hot spots ratio of the organs at risk (OAR) were also computed by the modified scheme to assess the clinical significance.

Results: The result of the gamma passing rate in the modified method was conformable to that in the conventional method with a cut-off threshold of 5%. The cold spots ratio of PTV and hot spots ratio of OAR were able to be evaluated by the modified scheme. For an introduced 7.1% dose error, the discrimination ratio in gamma passing rate of the conventional method was lower than 2%, while it was improved to 5% by the modified method.

Conclusions: The modified gamma analysis scheme had a comparable quality as the conventional scheme in terms of dose inspection. Besides, it could improve the clinical significance of the QA result and provide the assessment for ROI-specific discrepancy. The modified scheme could also be conveniently integrated into the conventional dose verification process, benefiting the less developed regions where high-end 3D dose verification devices are not affordable.
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http://dx.doi.org/10.1177/15593258211001676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040583PMC
April 2021

MEF2A transcriptionally upregulates the expression of ZEB2 and CTNNB1 in colorectal cancer to promote tumor progression.

Oncogene 2021 May 16;40(19):3364-3377. Epub 2021 Apr 16.

Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China.

Colorectal cancer (CRC) is one of the leading cancers worldwide, accounting for high morbidity and mortality. The mechanisms governing tumor growth and metastasis in CRC require detailed investigation. The results of the present study indicated that the transcription factor (TF) myocyte enhancer factor 2A (MEF2A) plays a dual role in promoting proliferation and metastasis of CRC by inducing the epithelial-mesenchymal transition (EMT) and activation of WNT/β-catenin signaling. Aberrant expression of MEF2A in CRC clinical specimens was significantly associated with poor prognosis and metastasis. Functionally, MEF2A directly binds to the promoter region to initiate the transcription of ZEB2 and CTNNB1. Simultaneous activation of the expression of EMT-related TFs and Wnt/β-catenin signaling by MEF2A overexpression induced the EMT and increased the frequency of tumor formation and metastasis. The present study identified a new critical oncogene involved in the growth and metastasis of CRC, providing a potential novel therapeutic target for CRC intervention.
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http://dx.doi.org/10.1038/s41388-021-01774-wDOI Listing
May 2021

Prognostic significance of myocardial fibrosis and CMR characteristics in bicuspid aortic valve with moderate and severe aortic insufficiency.

Eur Radiol 2021 Apr 16. Epub 2021 Apr 16.

MR Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road No 167, Xicheng District, 100037, Beijing, China.

Objectives: This study attempted to evaluate the characteristics and prognostic value of myocardial fibrosis (MF) in aortic insufficiency (AI) patients with bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) by cardiac magnetic resonance (CMR).

Methods: A total of 314 adults with CMR-diagnosed AI were retrospectively retrieved. Of them, 166 patients with moderate or severe AI were included and divided into two groups: BAV group (N = 46) and a TAV group (N = 120). The presence and characteristics of MF were assessed with CMR. The patients were followed for adverse clinical events. The prognostic capability of the parameters was assessed using Cox regression model.

Results: LV fibrosis was more common in the BAV group than in the TAV group (65.2% vs. 45.0%; p = 0.020). There was a strong association between BAV and MF even after adjusting for clinical and imaging variables (odds ratio: 3.57; p = 0.031). Kaplan-Meier analysis showed a higher rate of clinical adverse events in AI+BAV patients with MF during a median follow-up of 4.7 years. Multivariate Cox regression analysis showed that late gadolinium enhancement (LGE) was an independent predictor of clinical adverse outcome.

Conclusion: MF is more common in AI with BAV than with TAV and is a predictor of clinical adverse events.

Key Points: • The presence and extent of late gadolinium enhancement of left ventricular were more common and severer in the bicuspid aortic valve group than in the tricuspid aortic valve group in aortic insufficiency patients. • Bicuspid aortic valve was an independent factor for myocardial fibrosis in aortic insufficiency patients. • Late gadolinium enhancement could be used as an independent predictor of adverse clinical events in this population.
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http://dx.doi.org/10.1007/s00330-021-07823-yDOI Listing
April 2021

LncRNA XIST upregulates TRIM25 via negatively regulating miR-192 in hepatitis B virus-related hepatocellular carcinoma.

Mol Med 2021 04 15;27(1):41. Epub 2021 Apr 15.

Department of Interventional Radiology, Huaian Hospital of Huai'an City, No. 161 Zhenhuailou East Road, Huai'an City, 223200, Jiangsu Province, People's Republic of China.

Background: Long non-coding RNA (lncRNA) XIST has been implicated in the progression of a variety of tumor diseases. The purpose of this study was to explore the molecular role of lncRNA XIST in human hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).

Methods: The expression levels of lncRNA XIST, miR-192 and TRIM25 in HBV-related HCC tissues and HepG2.2.15 cells were detected by qRT-PCR. Biological information and luciferin gene reporter assay were performed to detect the interaction among lncRNA XIST, miR-192 and TRIM25. CCk-8 assay, wound healing assay and colony formation assay were conducted to detect the proliferation and migration ability of HepG2.2.15 cells.

Results: qRT-PCR results showed that the expression levels of lncRNA XIST were remarkably increased in HBV-related HCC tissues and HepG2.2.15 cells. In addition, miR-192 was a direct target gene of lncRNA XIST, and the expression of miR-192 and lncRNA XIST were negatively correlated. Moreover, overexpression of miR-192 observably inhibited the proliferation and migration of HCC cells, while overexpression of lncRNA XIST showed an opposite effect. Furthermore, TRIM25 was a direct target of miR-192, and lncRNA XIST could up-regulate the expression of TRIM25 by targeting miR-192.

Conclusion: LncRNA XIST could up-regulate the expression of TRIM25 by targeting and binding to miR-192, thus accelerating the occurrence and development of HCC.
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http://dx.doi.org/10.1186/s10020-021-00278-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050905PMC
April 2021

MiR-129-5p promotes radio-sensitivity of NSCLC cells by targeting SOX4 and RUNX1.

Curr Cancer Drug Targets 2021 Apr 14. Epub 2021 Apr 14.

Department of Interventional Radiology, The Third People's Hospital of Yancheng, Yancheng 224001, Jiangsu. China.

Background: Dysregulation of microRNAs (miRNAs) figures prominently in radio-sensitivity of non-small cell lung cancer (NSCLC). MiR-129-5p can block the development of a variety of tumors. However, whether miR-129-5p modulates radio-sensitivity of NSCLC cells remains unknown.

Objective: This study was aimed to explore the role and the underlying mechanism of miR-129-5p in the radiosensitivity of NSCLC.

Methods: Radio-resistant NSCLC cell lines (A549-R and H1299-R) were constructed using A549 and H1299 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to quantify miR-129-5p, SRY-box transcription factor 4 (SOX4) mRNA, and RUNX family transcription factor 1 (RUNX1) mRNA expression levels. Cell apoptosis and cell cycle were detected by flow cytometry. Cell counting kit-8 (CCK-8) assay and colony formation experiments were used to measure cell proliferation. γ-H2AX was examined by Western blot to confirm DNA injury. Dual-luciferase reporter experiments were applied to analyze the interactions among miR-129-5p, RUNX1, and SOX4.

Results: In A549-R and H1299-R cells, compared with the wild type cell lines, miR-129-5p expression was remarkably reduced while SOX4 and RUNX1 expressions were increased. The transfection of miR-129-5p into NSCLC cell lines, markedly induced cell apoptosis, DNA injury, and cell cycle arrest, and inhibited cell proliferation and colony formation. RUNX1 and SOX4 were validated as target genes of miR-129-5p, and the restoration of RUNX1 or SOX4 could counteract the influence of miR-129-5p on A549-R cells.

Conclusion: MiR-129-5p sensitizes A549-R and H1299-R cells to radiation by targeting RUNX1 and SOX4.
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http://dx.doi.org/10.2174/1568009621666210415094350DOI Listing
April 2021

The herbal agent plantamajoside, exerts a potential inhibitory effect on the development of hepatocellular carcinoma.

Exp Ther Med 2021 Jun 31;21(6):573. Epub 2021 Mar 31.

Department of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China.

Plantamajoside (PMS), a major component of , has several pharmacological properties, including anti-proliferative, anti-inflammatory and anti-tumor effects. However, the effects of PMS on hepatocellular carcinoma (HCC) have yet to be determined. The aim of the present study was to investigate the effects of PMS on HCC and elucidate the underlying mechanism. All assays were conducted using 5 groups, namely control, sorafenib, and PMS 100, 50, and 25 µg/ml groups. Cell proliferation was determined by the MTT assay. Cell migration was evaluated with the wound healing and Transwell assays, respectively. Cell apoptosis and cell cycle distribution were evaluated via flow cytometry. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis and western blotting were used to further investigate the mechanism of action of PMS. Sorafenib and PMS both significantly attenuated the proliferation and migration of HCC cells, and markedly promoted cell apoptosis. PMS induced cell cycle arrest in the G0/G1 phase. The efficacy of PMS increased in a dose-dependent manner. Further study evaluated the expression of peroxisome proliferator-activated receptor (PPARγ), nuclear factor (NF)-κB and cyclooxygenase (Cox-2) using RT-qPCR analysis and western blotting. The results demonstrated that PMS promoted the expression of PPARγ and suppressed the expression of NF-κB and Cox-2. In conclusion, PMS was shown to affect cell proliferation, migration, apoptosis and cell cycle distribution. Furthermore, PMS promoted the expression of PPARγ and inhibited the expression of NF-κB and Cox-2, which may be the mechanism underlying its biological effects. Based on the results of the present study, PMS appears to be a promising agent for HCC therapy.
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http://dx.doi.org/10.3892/etm.2021.10005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027734PMC
June 2021

SEC61G is upregulated and required for tumor progression in human kidney cancer.

Mol Med Rep 2021 Jun 13;23(6). Epub 2021 Apr 13.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.

Kidney cancer is a malignant tumor of the urinary system. Although the 5‑year survival rate of patients with kidney cancer has increased by ~30% in recent years due to the early detection of low‑grade tumors using more accurate diagnostic methods, the global incidence of kidney cancer continues to increase every year. Therefore, identification of novel and efficient candidate genes for predicting the prognosis of patients with kidney cancer is important. The present study aimed to investigate the role of SEC61 translocon subunit‑γ (SEC61G) in kidney cancer. The Cancer Genome Atlas database was screened to obtain the expression profile of SEC61G and identify its association with kidney cancer prognosis. Furthermore, the effect of SEC61G knockdown on kidney cancer cell proliferation, migration, invasion and apoptosis was investigated using a Cell Counting Kit‑8 assay, wound healing assay, Transwell assay and flow cytometry. The results demonstrated that compared with healthy tissues, SEC61G was upregulated in human kidney tumor tissues, which was associated with poor prognosis. In addition, SEC61G knockdown significantly inhibited kidney cancer cell proliferation, migration and invasion compared with the negative control (NC) group. Furthermore, E‑cadherin expression was significantly upregulated, and N‑cadherin and β‑catenin expression levels were significantly downregulated in SEC61G‑knockdown kidney cancer cells compared with the NC group. In addition, compared with the NC group, SEC61G knockdown significantly promoted cell apoptosis in a caspase‑dependent manner. The aforementioned results suggested that SEC61G might serve as a proto‑oncogene to promote kidney tumor progression. Therefore, the present study provided a novel candidate gene for predicting the prognosis of patients with kidney cancer.
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http://dx.doi.org/10.3892/mmr.2021.12066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047765PMC
June 2021

An efficient primary screening of COVID-19 by serum Raman spectroscopy.

J Raman Spectrosc 2021 Feb 19. Epub 2021 Feb 19.

Department of Radiation Oncology Sichuan Cancer Hospital & Institute Chengdu China.

The outbreak of COVID-19 coronavirus disease around the end of 2019 has become a pandemic. The preferred method for COVID-19 detection is the real-time polymerase chain reaction (RT-PCR)-based technique; however, it also has certain limitations, such as sample-dependent procedures with a relatively high false negative ratio. We propose a safe and efficient method for screening COVID-19 based on Raman spectroscopy. A total of 177 serum samples are collected from 63 confirmed COVID-19 patients, 59 suspected cases, and 55 healthy individuals as a control group. Raman spectroscopy is adopted to analyze these samples, and a machine learning support-vector machine (SVM) method is applied to the spectrum dataset to build a diagnostic algorithm. Furthermore, 20 independent individuals, including 5 asymptomatic COVID-19 patients and 5 symptomatic COVID-19 patients, 5 suspected patients, and 5 healthy patients, were sampled for external validation. In these three groups-confirmed COVID-19, suspected, and healthy individuals-the distribution of statistically significant points of difference showed highly consistency for intergroups after repeated sampling processes. The classification accuracy between the COVID-19 cases and the suspected cases is 0.87 (95% confidence interval [CI]: 0.85-0.88), and the accuracy between the COVID-19 and the healthy controls is 0.90 (95% CI: 0.89-0.91), while the accuracy between the suspected cases and the healthy control group is 0.68 (95% CI: 0.67-0.73). For the independent test dataset, we apply the obtained SVM model to the classification of the independent test dataset to have all the results correctly classified. Our model showed that the serum-level classification results were all correct for independent test dataset. Our results suggest that Raman spectroscopy could be a safe and efficient technique for COVID-19 screening.
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http://dx.doi.org/10.1002/jrs.6080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014023PMC
February 2021

Have you ever heard of Human Papillomavirus (HPV) vaccine? The awareness of HPV vaccine for college students in China based on meta-analysis.

Hum Vaccin Immunother 2021 Mar 31:1-12. Epub 2021 Mar 31.

Department of Ideological and Political Education, School of Marxism, Harbin Medical University, Harbin, China.

: To evaluate the awareness of College Students (CSs) of HPV vaccine in China and provide evidence-based recommendations for HPV vaccine's publicity and promotion. Web of Science, PubMed, Science of Direct, EBSCO, China National Knowledge Infrastructure and Wanfang Data were searched. A random effects meta-analysis was conducted to determine pooled estimates of Awareness Rate (AR) for HPV vaccine. Of the 36 studies included, the estimated AR of HPV vaccine was 40.27% (95% : 30.86%, 50.06%) among Chinese CSs. The AR of HPV vaccine was stratified by factors as gender, major, area, city, survey time, and sampling method of the study. The pooled AR of HPV vaccine among CSs was as follows: 44.17% (95% : 31.65%, 57.09%) and 31.93% (95% : 13.25%, 54.30%) for females and males; 44.47% (95% : 29.90%, 59.55%) and 12.02% (95% : 7.69%, 17.15%) for medical-related and nonmedical majors; 44.47% (95% : 28.71-60.82%) and 41.16% (95% : 26.48-56.64%) for Eastern and Midwestern region; 48.86% (95% : 30.63-67.25%) and 33.19% (95% : 22.27-45.12%) for first-tier and second- and third-tier city; 29.67 (95% : 11.44-52.16%) and 38.81 (95% : 27.14-51.21%) for AR before and after HPV vaccine entered in China; 51.51% (95% : 32.21%, 70.53%) and 26.21% (95% : 17.41%, 36.10%) for nonrandom and random sampling. This review indicates that awareness of HPV vaccine among CSs remains relatively low in China compared with European countries. Our findings may provide useful information to better understand the HPV vaccine awareness status among Chinese CSs.
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http://dx.doi.org/10.1080/21645515.2021.1899731DOI Listing
March 2021

MRI Characteristics, Prevalence, and Outcomes of Hypertrophic Cardiomyopathy with Restrictive Phenotype.

Radiol Cardiothorac Imaging 2020 Aug 13;2(4):e190158. Epub 2020 Aug 13.

Department of Magnetic Resonance Imaging (S.L., B.W., G.Y., S.Z., M.L.), Key Laboratory of Cardiovascular Imaging (Cultivation), Chinese Academy of Medical Sciences, Beijing, China (M.L., G.Y.); Department of Cardiology (L.S.), Department of Echocardiography (Y.J.), and Heart-Lung Testing Center (J.H.), State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China; and Department of Radiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (B.W.).

Purpose: To investigate the MRI characteristics, prevalence, and outcomes of hypertrophic cardiomyopathy (HCM) with restrictive phenotype.

Materials And Methods: A total of 2592 consecutive patients with HCM were evaluated to identify individuals who fulfilled the diagnostic criteria of restrictive phenotype. Thirty-four patients with HCM (mean age, 41 years ± 16 [standard deviation]; range, 21-62 years, 16 men) with restrictive phenotype were retrospectively identified. Thirty-four patients with HCM with the same age and sex distributions were randomly selected as a control group. Kaplan-Meier survival curves were compared using log-rank statistics for survival analysis.

Results: The anteroposterior diameters of the left and right atria were 55 mm ± 5 and 61 mm ± 9, respectively, which were larger than those of the control group ( < .001). The maximum wall thickness in the restrictive group was lower than that in the control group (16 mm ± 2 vs 19 mm ± 3, < .001). No significant difference was found in late gadolinium enhancement fraction between the restricted phenotype and the control group (15% ± 8 vs 13% ± 7, = .376). The 5-year event-free survival from any cause of death and cardiac transplantation was 81% in the restrictive group, compared with 94% in the control group (log-rank = .018).

Conclusion: Restrictive phenotype is a rare subtype of HCM and is associated with severe clinical symptoms and poor prognosis. The MRI features of this phenotype include mild to moderate left ventricular hypertrophy, markedly enlarged atria, moderate myocardial fibrosis, and pericardial effusion.© RSNA, 2020.
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http://dx.doi.org/10.1148/ryct.2020190158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977807PMC
August 2020

CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism.

Front Cell Dev Biol 2021 4;9:641271. Epub 2021 Mar 4.

Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.

B-cell acute lymphocytic leukemia (B-ALL), a common blood cancer in children, leads to high mortality. Cyclin-dependent kinase 9 inhibitor (CDK9i) effectively attenuates acute myeloid leukemia and chronic lymphoblastic leukemia by inducing apoptosis and inhibiting cell proliferation. However, the effect of CDK9i on B-ALL cells and the underlying mechanisms remain unclear. In this study, we showed that CDK9i induced the apoptosis of B-ALL cells by activating the apoptotic pathways. In addition, CDK9i restrained the glycolytic metabolism of B-ALL cells, and CDK9i-induced apoptosis was enhanced by co-treatment with glycolysis inhibitors. Furthermore, CDK9i restained the glycolysis of B-ALL cell lines by markedly downregulating the expression of glucose transporter type 1 (GLUT1) and the key rate-limiting enzymes of glycolysis, such as hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA). Moreover, cell apoptosis was rescued in B-ALL cells with over-expressed c-Myc after treatment with CDK9i, which is involved in the enhancement of glycolytic metabolism. In summary, our findings suggest that CDK9 inhibitors induce the apoptosis of B-ALL cells by inhibiting c-Myc-mediated glycolytic metabolism, thus providing a new strategy for the treatment of B-ALL.
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http://dx.doi.org/10.3389/fcell.2021.641271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969802PMC
March 2021

Luteolin delays photoreceptor degeneration in a mouse model of retinitis pigmentosa.

Neural Regen Res 2021 Oct;16(10):2109-2120

Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, Guangdong Province; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China.

Luteolin is neuroprotective for retinal ganglion cells and retinal pigment epithelial cells after oxidative injury, whereby it can inhibit microglial neurotoxicity. Therefore, luteolin holds the potential to be useful for treatment of retinal diseases. The purpose of this study was to investigate whether luteolin exhibits neuroprotective effects on rod cells in rd10 mice, a slow photoreceptor-degenerative model of retinitis pigmentosa. Luteolin (100 mg/kg) intraperitoneally injected daily from postnatal day 14 (P14) to P25 significantly enhanced the visual performance and retinal light responses of rd10 mice at P25. Moreover, it increased the survival of photoreceptors and improved retinal structure. Mechanistically, luteolin treatment attenuated increases in reactive oxygen species, photoreceptor apoptosis, and reactive gliosis; increased mRNA levels of anti-inflammatory cytokines while lowering that of pro-inflammatory and chemoattractant cytokines; and lowered the ratio of phospho-JNK/JNK. Application of the JNK inhibitor SP600125 exerted a similar protective effect to luteolin, suggesting that luteolin delays photoreceptor degeneration and functional deterioration in rd10 mice through regulation of retinal oxidation and inflammation by inhibiting the JNK pathway. Therefore, luteolin may be useful as a supplementary treatment for retinitis pigmentosa. This study was approved by the Qualified Ethics Committee of Jinan University, China (approval No. IACUC-20181217-02) on December 17, 2018.
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http://dx.doi.org/10.4103/1673-5374.303537DOI Listing
October 2021

Precontoured Locking Compression Plate with Titanium Alloy Cable System: In Treatment of Neer Type IIb Distal Clavicle Fracture.

Orthop Surg 2021 Apr 22;13(2):451-457. Epub 2021 Jan 22.

Department of Orthopedic Surgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Objective: To describe a new method which involves anatomical distal clavicle plate fixation and titanium alloy cable system-augmented coracoclavicular ligament reconstruction to manage Neer type IIb distal clavicle fracture.

Methods: Between January 2013 and June 2018, 28 patients with acute Neer type IIb lateral clavicle fracture were treated by a new method - precontoured locking compressive distal clavicular plate fixation of the fracture combined with titanium alloy cable system-augmented reconstruction of the coracoclavicular ligament. There were 11 females and 17 males treated in this way. There were 15 cases of the right side and 13 of the left. The mean age of the patients was 48.5 years (range, 18-78 years). The mean time from injury to surgery was 3.9 days (range, 1-7 days). After completing the preoperative examinations and evaluations, surgeries were performed for all these patients, anatomical distal clavicle plates were used for fractures, and titanium alloy cables were implanted for the augmented reconstruction of coracoclavicular ligaments. Postoperative protocols, including arm sling management and rehabilitative activities, were unified and recommended to all the patients. These patients were followed up for at least 1 year. The mean duration of postoperative follow-up was 23.3 months (range, 12-52 months). At the last follow-up, the coracoclavicular distances were recorded and shoulder functional outcomes were assessed by the Constant scores and the Fudan University Shoulder Scores (FUSSs) questionnaires.

Results: Radiographic bony unions were achieved in all patients within 20 weeks. Functional and radiographic outcomes were retrospectively evaluated. The mean coracoclavicular distance was 9.61 ± 0.61 mm on the injured side vs 9.62 ± 0.57 mm on the contralateral uninjured side. The mean Constant score and mean FUSS were 90.1 ± 6.6 (range, 68-98) and 86.1 ± 7.2 (range, 64-95) respectively, which indicating good restoration of function and high level of satisfaction for both the patients and their physical therapists. There were a few major complications, including one delayed healing of the skin, one severe shoulder stiffness, three incidences of moderate shoulder stiffness, and five incidences of symptomatic hardware. There is no deep infections, neurovascular injuried, delayed union or nonunion, peri-implant fracture, loss of reduction, implant malposition or failure, or other severe complications.

Conclusion: This combined method for the treatment of Neer type IIb distal clavicle fracture could yield high bony union rate, good functional outcome, and low complication rate. Further prospective randomized controlled studies are needed to confirm the benefits of this method of treatment.
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http://dx.doi.org/10.1111/os.12893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957404PMC
April 2021

Exosomes produced by adipose-derived stem cells inhibit schwann cells autophagy and promote the regeneration of the myelin sheath.

Int J Biochem Cell Biol 2021 Mar 6;132:105921. Epub 2021 Jan 6.

Department of Orthopedic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China. Electronic address:

Peripheral nerve injury (PNI) is encountered relatively commonly in the clinic and often results in long-term functional deficits. Research to develop methods to improve regeneration following nerve injury is ongoing. Numerous studies have shown that adipose-derived stem cells (ADSCs) promote the regeneration of peripheral nerve injury; however, the mechanism is unclear. Autophagy, a highly conserved intracellular process responsible for maintaining cellular homeostasis, and Schwann cells (SCs), play important roles in regeneration after PNI. In the present study, we explored the effect and mechanism of exosomes produced by adipose-derived stem cells (ADSC-Exos) on autophagy of SCs in PNI, as well as their effect on the regeneration of the nerve myelin sheath. The levels of autophagy and the expression of karyopherin subunit alpha 2 (Kpna2) in SCs increased markedly after the sciatic nerve was injured in SCs (SNI-SCs). The enhanced autophagy and the upregulated Kpna2 in SNI-SCs were inhibited after treatment with ADSC-Exos in vivo and in vitro. The effect of ADSC-Exos on inhibiting SC autophagy was blocked by overexpression of Kpna2 in SNI-SCs. Using quantitative real-time reverse transcription PCR, ADSC-Exos were demonstrated to contain a large amount of miRNA-26b, which was predicted to regulate Kpna2 on the TargetScan website. The effect of ADSC-Exos on inhibiting SCs autophagy was blocked after the silencing of miRNA-26b. Moreover, ADSC-Exos promoted the regeneration of the myelin sheath by inhibiting SC autophagy in rat SNI models. In conclusion, our results indicated that ADSC-Exos promote the regeneration of the myelin sheath by moderately reducing autophagy of injured SCs via miRNA-26b downregulation of Kpna2.
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http://dx.doi.org/10.1016/j.biocel.2021.105921DOI Listing
March 2021

The Etiological Heterogeneity of Bicuspid Aortopathy between Ascending and Root Morphotype.

Heart Surg Forum 2020 Dec 22;23(6):E913-E919. Epub 2020 Dec 22.

School of Aeronautics and Astronautics, Zhejiang University, Hangzhou, China.

Background: Valve-related hemodynamics and intrinsically regulated matrix proteases are 2 determined pathogenetic factors associated with medial elastin degeneration in bicuspid aortopathy. This study analyzed the association between elastic fiber deterioration and the 2 pathogenetic factors in ascending and root morphotypes, aiming to elucidate the etiological heterogeneity between the 2 morphotypes.

Methods: Four-dimensional flow cardiac magnetic resonance was used to measure the regional wall shear stress (WSS) on the ascending aorta, and matrix metalloproteinase (MMP) expression was assessed by immunoblotting. After histopathology analysis of aortic tissue, we assessed whether elevated regional WSS and increased MMP expression corresponded with medial elastin thinning.

Results: Increased regional WSS corresponded with medial elastin thinning in both morphotypes. Increased expression of different MMP isoforms corresponded with medial elastin degeneration in bicuspid aortopathy. The significantly increased expression of MMP-2 corresponded with a decrease of elastic fiber thickness in the ascending morphotype (P = .046), whereas elastic fiber thinning was associated with high levels of MMP-3 expression (P = .012) in the root morphotype. No association was observed between regional WSS and MMP expression.

Conclusion: There is no difference in the effect of valve-related hemodynamics between ascending and root morphotype, and MMPs are not involved in the process of elastic fiber degeneration induced by increased WSS. The increased expression of different MMP isoforms was observed in the context of elastic fiber degeneration between the 2 morphotypes, implying that heterogeneity between them is revealed in the different intrinsic pathway of medial elastin degradation.
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http://dx.doi.org/10.1532/hsf.3333DOI Listing
December 2020

Reference values of thoracic aorta and pulmonary artery diameters by age and gender in healthy Chinese adults assessed by cardiac magnetic resonance imaging: data from national center for cardiovascular diseases of China.

Int J Cardiovasc Imaging 2021 Apr 4;37(4):1423-1431. Epub 2021 Jan 4.

Department of Magnetic Resonance Imaging, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.

The aim of the study was to define normal ranges for thoracic aorta and pulmonary artery diameters relative to gender, age, body surface area (BSA) and body mass index (BMI) in healthy Chinese adults by cardiac magnetic resonance (CMR). We studied 200 healthy participants (100 men, 100 women; age range from 20-70) by using a 3.0-T CMR system. The diameters of the ascending aorta (AA), main pulmonary artery (PA), proximal descending aorta (DA) and Valsalva sinus (VAS) were measured manually by two experienced doctors on half-Fourier single-shot spin echo (HASTE) and balanced steady-state free precession (bSSFP) cine images. The mean value and age specific and gender adjusted normal limits were calculated. The linear regression analysis were performed between diameters and gender, age, BMI and BSA. The mean and 95% confidence interval(CI) of AA, PA, DA and VAS were 28.95 ± 4.61 mm(95% CI 19.92-37.99 mm), 22.41 ± 2.59 mm(95% CI 17.31-27.47 mm), 20.61 ± 2.96 mm(95% CI 14.81-26.42 mm), 31.15 ± 3.65 mm(95% CI 24.00-38.29 mm), respectively. The gender differences of all the parameters above were statistically significant (all p < 0.01). Both thoracic aorta and pulmonary artery dilates with the increase of age, while AA has the highest dilation rate. The mean PA/AA was 0.79 and showed no gender difference, but there was statistical difference among all age groups (p < 0.01). AA and DA had stronger association with age and BSA than BMI. Age- and gender-specific reference diameters of thoracic aorta and pulmonary artery were provided in healthy Chinese adults. Age and BSA have stronger effects on the ranges of diameters than BMI.
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http://dx.doi.org/10.1007/s10554-020-02116-9DOI Listing
April 2021

Comparative Study of Auto Plan and Manual Plan for Nasopharyngeal Carcinoma Intensity-Modulated Radiation Therapy.

Cancer Manag Res 2020 2;12:12439-12445. Epub 2020 Dec 2.

Department of Radiation Therapy, Sichuan Cancer Hospital, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, People's Republic of China.

Purpose And Objective: Auto planning might reduce the manual time required for the optimization and could also potentially improve the overall plan quality. The aim of this study is to demonstrate the statistical comparison of automatic (AU) and manually (MA) generated nasopharyngeal carcinoma (NPC) intensity-modulated radiation therapy (IMRT) plans.

Materials And Methods: The study included 105 nasopharyngeal carcinoma patients, admitted to our hospital. The patients underwent IMRT treatments. The clinically delivered plans were performed with Eclipse (Version 11.0) using manual optimization. The same plans were optimized successively in Pinnacle (version 9.10) treatment planning system using the auto plan software package module. D95 (dose of 95% volume) and D98 (dose of 98% volume) were calculated for the targets and maximum dose (Dmax) and mean dose (Dmean) for the organ at risks (OARs); moreover, the average doses of each target and OARs for 105 patients were evaluated.

Results: There is no significant difference in the homogeneity of the target between AU and MA treatment plans, while a significant difference is observed for what is concerning the OARs or most of OARs in 105 patients, OAR doses were significantly reduced in AU plan. For OARs which have no significant difference between AU and MA plans are highlighted, the mean dose of OARs in AU plans was at least not higher than MA plans.

Conclusion: Nasopharyngeal carcinoma IMRT plans made by an automatic planning tool met the clinical requirements for target prescription dose; moreover, the dose of normal tissues was lower than in MA plans. Clinical physicists' time can be saved and the influence of factors such as the lack of experience in treatment planning can be avoided.
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http://dx.doi.org/10.2147/CMAR.S226495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719327PMC
December 2020

Deep learning algorithm to improve hypertrophic cardiomyopathy mutation prediction using cardiac cine images.

Eur Radiol 2020 Nov 25. Epub 2020 Nov 25.

CAS Key Lab of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.

Objectives: The high variability of hypertrophic cardiomyopathy (HCM) genetic phenotypes has prompted the establishment of risk-stratification systems that predict the risk of a positive genetic mutation based on clinical and echocardiographic profiles. This study aims to improve mutation-risk prediction by extracting cardiovascular magnetic resonance (CMR) morphological features using a deep learning algorithm.

Methods: We recruited 198 HCM patients (48% men, aged 47 ± 13 years) and divided them into training (147 cases) and test (51 cases) sets based on different genetic testing institutions and CMR scan dates (2012, 2013, respectively). All patients underwent CMR examinations, HCM genetic testing, and an assessment of established genotype scores (Mayo Clinic score I, Mayo Clinic score II, and Toronto score). A deep learning (DL) model was developed to classify the HCM genotypes, based on a nonenhanced four-chamber view of cine images.

Results: The areas under the curve (AUCs) for the test set were Mayo Clinic score I (AUC: 0.64, sensitivity: 64.29%, specificity: 47.83%), Mayo Clinic score II (AUC: 0.70, sensitivity: 64.29%, specificity: 65.22%), Toronto score (AUC: 0.74, sensitivity: 75.00%, specificity: 56.52%), and DL model (AUC: 0.80, sensitivity: 85.71%, specificity: 69.57%). The combination of the DL and the Toronto score resulted in a significantly higher predictive performance (AUC = 0.84, sensitivity: 83.33%, specificity: 78.26%), compared with Mayo I (p = 006), Mayo II (p = 022), and Toronto score (p = 0.029).

Conclusions: The combination of the DL model, based on nonenhanced cine CMR images and the Toronto score yielded significantly higher diagnostic performance in detecting HCM mutations.

Key Points: • Deep learning method could enable the extraction of image features from cine images. • Deep learning method based on cine images performed better than established scores in identifying HCM patients with positive genotypes. • The combination of the deep learning method based on cine images and the Toronto score could further improve the performance of the identification of HCM patients with positive genotypes.
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http://dx.doi.org/10.1007/s00330-020-07454-9DOI Listing
November 2020

miR-375-3p contributes to hypoxia-induced apoptosis by targeting forkhead box P1 (FOXP1) and Bcl2 like protein 2 (Bcl2l2) in rat cardiomyocyte h9c2 cells.

Biotechnol Lett 2021 Feb 30;43(2):353-367. Epub 2020 Oct 30.

Department of Cardiology, Qingdao Central Hospital, No. 127, Siliu South Road, Qingdao, 266042, Shandong, China.

miRNAs have been pointed to play critical role in the development of congenital heart disease (CHD). miRNA-375-3p (miR-375-3p) was involved in cardiac dysfunction and cardiogenesis. However, no prior study had established a therapeutic role of miR-375-3p in CHD. We intended to investigate the effect and mechanism of miR-375-3p on apoptosis in hypoxic cardiomyocytes in vitro. Expression of miR-375-3p, forkhead box P1 (FOXP1) and Bcl2 like protein 2 (Bcl2l2) was detected using real-time quantitative PCR and western blot. Apoptosis was measured with MTT assay, flow cytometry and caspase-3 activity assay. The potential target binding between miR-375-3p and FOXP1/Bcl2l2 was predicted on DianaTools, and was validated by luciferase reporter assay and RNA pull-down assay. As a result, miR-375-3p was upregulated and FOXP1/Bcl2l2 was downregulated in maternal serum of women with fetal CHD and hypoxia-induced rat cardiomyocyte h9c2 cells. Hypoxia induced apoptosis rate elevation, caspase-3 activity promotion and viability inhibition in h9c2 cells; overexpression of miR-375-3p promoted, whereas knockdown of miR-375-3p antagonized hypoxia-induced effects in h9c2 cells. In addition, miR-375-3p was validated to negatively regulate FOXP1 and Bcl2l2 expression through target binding, and silencing of FOXP1 and Bcl2l2 could independently abate the anti-apoptosis role of miR-375-3p knockdown in hypoxic h9c2 cells. Collectively, blocking miR-375-3p suppressed hypoxia-evoked apoptosis of cardiomyocytes by targeting and upregulating FOXP1 and Bcl2l2. Our results might suggest maternal serum miR-375-3p as a potential biomarker for prenatal detection of fetal CHD.
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http://dx.doi.org/10.1007/s10529-020-03013-wDOI Listing
February 2021

Ku70 and Ku80 participate in LPS-induced pro-inflammatory cytokines production in human macrophages and monocytes.

Aging (Albany NY) 2020 10 27;12(20):20432-20444. Epub 2020 Oct 27.

Department of Stomatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

In human macrophages and monocytes, lipopolysaccharide (LPS) induces nuclear factor kappa B (NFκB) activation and pro-inflammatory cytokines production. We tested the possible involvement of Ku70 and Ku80 in the process. In THP-1 macrophages and primary human peripheral blood mononuclear cells (PBMCs), shRNA-induced double knockdown of Ku70 and Ku80 potently inhibited LPS-induced production of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6). Additionally, we developed CRISPR/Cas-9 gene-editing methods to knockout both Ku70 and Ku80 in THP-1 cells and PBMCs. Double knockout (DKO) largely inhibited LPS-induced pro-inflammatory cytokines production. Conversely, in THP-1 cells exogenous overexpression of both Ku70 and Ku80 enhanced the pro-inflammatory cytokines production by LPS. Ku70 and Ku80 co-immunoprecipitated with p65-p52 NFκB complex in the nuclei of LPS-treated THP-1 cells. Significantly, LPS-induced NFκB activation was inhibited by Ku70 plus Ku80 double knockdown or DKO. It was however enhanced with Ku70 and Ku80 overexpression. Together, Ku70 and Ku80 promote LPS-induced NFκB activation and pro-inflammatory response in THP-1 cells and human PBMCs.
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http://dx.doi.org/10.18632/aging.103845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655212PMC
October 2020

[Effect of electroacupuncture preconditioning on the expressions of NF-κB p65, IκBα and IKKβ in myocardial tissue of the rats with acute myocardial ischemia-reperfusion injury].

Zhongguo Zhen Jiu 2020 Oct;40(10):1103-7

School of Acupuncture-Moxibustion and Tuina, Anhui University of CM, Hefei 230012; Research Institute of Acupuncture-Moxibustion and Meridian, Anhui Academy of Chinese Medical Sciences, Hefei 230038.

Objective: To observe the effect of electroacupuncture (EA) preconditioning on the expressions of nuclear transcription factors-kappa B (NF-κB) p65, NF-κB inhibitor (IκB) α and IκB kinase (IKK) β in rats with acute myocardial ischemia-reperfusion injury (MIRI) and to explore the mechanism of EA on heart meridian in relieving MIRI.

Methods: A total of 40 SD rats were randomized into a sham-operation group, a model group, an EA heart meridian group and an EA lung meridian group, 10 rats in each one. In the EA heart meridian group, acupuncture was applied to "Shenmen" (HT 7) and "Tongli" (HT 5). In the EA lung meridian group, acupuncture was applied to "Taiyuan" (LU 9) and "Lieque" (LU 7). In these two groups, EA was exerted for 20 min each time, 1 V in voltage and 2 Hz in frequency once a day. A total of 7-day EA stimulation was required before model duplication. In the model group, the EA heart meridian group and the EA lung meridian group, using ligating left anterior descending coronary artery to establish the acute MIRI models. In the sham-operation group, the chest was open, but no ligation was exerted, just the needle was penetrated through the corresponding sites for one time. The electrocardiogram (ECG) was detected and ST segment displacement was analyzed. Using Western blot method, the relative expressions of NF-κB p65, IκBα and IKKβ in myocardial tissue were determined in each group. Using ELISA method, the levels of serum IL-1β and IL-10 were determined in each group.

Results: Compared with the sham-operation group, ST segment displacement value was elevated 30 min after ligating and reperfusion for 120 min in the model group (<0.05), and the value in the EA heart meridian group was lower than the model group and the EA lung meridian group (<0.05). Compared with the sham-operation group, the expressions of NF-κB p65 and IKKβ in myocardial tissue were increased (<0.05) and the expression of IκBα reduced in the rats of the model group (<0.05). Compared with the model group, the expressions of NF-κB p65 and IKKβ in myocardial tissue were reduced (<0.05) and the expressions of IκBα increased in the rats of the EA heart meridian group and the EA lung meridian group (<0.05). Compared with the EA lung meridian group, the expressions of NF-κB p65 and IKKβ in myocardial tissue were reduced (<0.05) and the expression of IκBα increased in the rats of the EA heart meridian group (<0.05). Compared with the sham-operation group, the serum level of IL-1β was increased (<0.05) and IL-10 reduced in the model group (<0.05). Compared with the model group, the serum level of IL-1β was reduced (<0.05) and IL-10 increased in the EA heart meridian group and the level of IL-1β was was reduced in the EA lung meridian group (<0.05). Compared with the EA lung meridian group, the serum level of IL-1β was reduced (<0.05) and IL-10 increased in the EA heart meridian group (<0.05).

Conclusion: Electroacupuncture preconditioning at heart meridian acupoints obviously alleviates acute MIRI. IKK/IκB/NF-κB signaling pathway possibly participates in the protective mechanism of electroacupuncture preconditioning on acute MIRI.
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http://dx.doi.org/10.13703/j.0255-2930.20190811-k0004DOI Listing
October 2020

Genomic Analysis Reveals Novel Specific Metastatic Mutations in Chinese Clear Cell Renal Cell Carcinoma.

Biomed Res Int 2020 30;2020:2495157. Epub 2020 Sep 30.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Jinan Culture Road, Jinan, 250012 Shandong, China.

Clear cell renal cell carcinoma (ccRCC) accounts for more than 75% of renal cell carcinoma. Nearly 25% of ccRCC patients were diagnosed with metastasis. Though the genomic profile of ccRCC has been widely studied, the difference between localized and metastatic ccRCC was not clarified. Primary tumor samples and matched whole blood were collected from 106 sporadic patients diagnosed with renal clear cell carcinoma at Qilu Hospital of Shandong University from January 2017 to November 2019, and 17 of them were diagnosed with metastasis. A hybridization capture-based next-generation sequencing of 618 cancer-related genes was performed to investigate the somatic and germline variants, tumor mutation burden (TMB), and microsatellite instability (MSI). Five genes with significantly different prevalence were identified in the metastatic group, especially (17.65% vs. 0%) and (17.65% vs. 0%). The altered frequency of (0% vs. 27%) and (24% vs. 10%) differed between the metastatic and nonmetastatic groups, which may relate to the prognosis. Of these 106 patients, 42 patients (39.62%) had at least one alteration in DNA damage repair (DDR) genes, including 58.82% of metastatic ccRCC patients and 35.96% of ccRCC patients without metastasis. Ten pathogenic or likely pathogenic (P/LP) variants were identified in 11 sporadic clear cell renal cell carcinoma patients (10.38%), including rarely reported (n=1), (n=1), (n=1), (n=1), and (n=1). No significant difference in the ratio of P/LP variant carriers or TMB was identified between the metastatic and nonmetastatic groups. We found a unique genomic feature of Chinese metastatic ccRCC patients with a higher prevalence of alterations in DDR, , and Further investigated studies and drug development are needed in the future.
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http://dx.doi.org/10.1155/2020/2495157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545427PMC
May 2021

A newly defined risk signature, consisting of three mA RNA methylation regulators, predicts the prognosis of ovarian cancer.

Aging (Albany NY) 2020 Sep 20;12(18):18453-18475. Epub 2020 Sep 20.

Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.

N6-methyladenosine (mA) RNA methylation, involved in cancer initiation and progression, is dynamically regulated by the mA RNA methylation regulators. However, the expression of mA RNA methylation regulators in ovarian cancer and their correlation with prognosis remain elusive. Here, we demonstrated that the 18 central mA RNA methylation regulators were expressed differently between ovarian cancer (OC) and normal tissues. By applying consensus clustering, all ovarian cancer patient cases can be divided into three subgroups (cluster1/2/3) based on overall expression levels of all 18 mA RNA methylation regulators. We systematically analyzed the prognostic value of transcription levels of 18 mA RNA methylation regulators in ovarian cancer and found that insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), vir like mA methyltransferase associated (VIRMA), and zinc finger CCCH-type containing 13 (ZC3H13) yield the highest scores for predicting the prognosis of ovarian cancer. Accordingly, we derived a risk signature consisting of transcription levels of these three selected mA RNA methylation regulators as an independent prognostic marker for OC and validated our findings with data derived from a different ovarian cancer cohort. Moreover, by the Gene Set Enrichment Analysis (GSEA), we demonstrated that the three selected regulators were all correlated with pathways in cancer and WNT signaling pathways. In conclusion, mA RNA methylation regulators are vital participants in ovarian cancer pathology; and IGF2BP1, VIRMA, and ZC3H13 mRNA levels are valuable factors for prognosis prediction and treatment strategy development.
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http://dx.doi.org/10.18632/aging.103811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585096PMC
September 2020

HOXC10 promotes tumour metastasis by regulating the EMT-related gene Slug in ovarian cancer.

Aging (Albany NY) 2020 Sep 7;12(19):19375-19398. Epub 2020 Sep 7.

Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China.

The mortality rate of ovarian cancer is the highest among gynaecological cancers, primarily due to metastatic symptoms. Recent studies have shown that HOX genes are crucial in tumour progression, but the underlying mechanisms remain unclear. Here, HOXC10 expression was examined in ovarian cancer tissues. The function of HOXC10 in ovarian cancer metastasis was investigated and via intraperitoneal injection . A total of 158 ovarian cancer patients with adequate records were enrolled for analysis. HOXC10 was associated with metastasis and poor prognosis in ovarian cancer. , HOXC10 overexpression promoted ovarian cancer cell migration. Moreover, HOXC10 positively regulated Slug expression, altering the migration ability of cancer cells. Furthermore, our study showed that miR-222-3p was a suppressor of HOXC10. , a decrease in hepatic metastasis was seen in xenograft mice harbouring tumours with stable HOXC10 overexpression after miR-222-3p agomir (an overexpression reagent) injection. This study provides the first evidence that HOXC10 promotes ovarian cancer metastasis by regulating the transcription of the EMT-related gene Slug. Moreover, we found that HOXC10 is regulated by miR-222-3p. These data highlight the crucial role of HOXC10 in enhancing ovarian cancer metastasis and may provide a therapeutic target for ovarian cancer.
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http://dx.doi.org/10.18632/aging.103824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732328PMC
September 2020

Apical hypertrophic cardiomyopathy with left ventricular apical aneurysm: prevalence, cardiac magnetic resonance characteristics, and prognosis.

Eur Heart J Cardiovasc Imaging 2020 12;21(12):1341-1350

Department of Magnetic Resonance Imaging, Fuwai Hospital and National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beilishi Road No.167, Xicheng District, Beijing 100037, China.

Aims: Hypertrophic cardiomyopathy (HCM) with left ventricular apical aneurysm (LVAA) is associated with an increased risk of adverse cardiovascular events. However, the clinical significance of LVAA in apical HCM (ApHCM) has not been reported. This study aimed to investigate the prevalence, cardiac magnetic resonance (CMR) characteristics, and prognosis of LVAA in ApHCM patients.

Methods And Results: A total of 1332 consecutive ApHCM patients confirmed by CMR in our hospital were retrospectively analysed. LVAAs were identified in 31 patients of all ApHCM patients (2.3%, 31/1332). Besides, 31 age- and gender-matched ApHCM patients without LVAA were used for comparison. Of the 31 aneurysm patients (mean age, 53.8 ± 15.1 years old), 28 (90.3%) had clinical symptoms, and 3 (9.7%) had a family history of HCM. The rate of missed diagnosis of echocardiography for detecting LVAA was 64.5% (20/31), most (90%, 18/20) of unidentified LVAAs by echocardiography were small aneurysms (<20 mm). Compared with ApHCM patients without LVAA, the proportion of systolic mid-cavity obstruction and late gadolinium enhancement (LGE) presence, and the LGE extent in ApHCM patients with LVAA were significantly higher (all P<0.05). The Kaplan-Meier curves showed that the event-free survival rate in ApHCM patients with LVAA was significantly lower than that in ApHCM patients without LVAA (log rank, P = 0.010).

Conclusion: ApHCM with LVAA is a very rare condition, which is often missed by echocardiography and could be reliably detected with CMR and is associated with a higher risk of adverse cardiovascular events compared with ApHCM without LVAA.
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http://dx.doi.org/10.1093/ehjci/jeaa246DOI Listing
December 2020

Reducing Neuron Apoptosis in the Pontine Micturition Center by Nerve Root Transfer for Restoration of Micturition Function after Spinal Cord Injury.

Biomed Res Int 2020 4;2020:5615097. Epub 2020 Aug 4.

Department of Orthopedic Surgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China.

Objective: The rate of neuronal apoptosis increases after spinal cord injury (SCI). Anastomosing the normal nerve roots above the SCI level to the injured sacral nerve roots can enhance the functional recovery of neurons. Therefore, we evaluated the effect of sacral nerve root transfer after SCI on pontine neuronal survival.

Methods: Sprague-Dawley rats were randomly divided into three groups: Group A, reconstruction of afferent and efferent nerve pathways of the bladder after SCI; Group B, SCI only; and Group C, control group. We examined pontine neuronal morphology using hematoxylin and eosin (H&E) staining after SCI and nerve transfer. Bcl-2 and Bax protein expression changes in the pontine micturition center were quantified by immunohistochemistry. The number of apoptotic neurons was determined by TUNEL staining. We examined pontine neuronal apoptosis by transmission electron microscopy (TEM) at different time points.

Results: H&E staining demonstrated that the number of neurons had increased in Group A, but more cells in Group B displayed nuclear pyknosis, with the disappearance of the nucleus. Compared with Group B, Group A had significantly higher Bcl-2 expression, significantly lower Bax expression, and a significantly higher Bcl-2/Bax ratio. The number of apoptotic neurons and neuron bodies in Group A was significantly lower than that in Group B, as indicated by TUNEL staining and TEM.

Conclusions: These findings demonstrate that lumbosacral nerve transfer can reduce neuronal apoptosis in the pontine micturition center and enhance functional recovery of neurons. This result further suggests that lumbosacral nerve transfer can be used as a new approach for reconstructing bladder function after spinal cord injury.
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http://dx.doi.org/10.1155/2020/5615097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424370PMC
May 2021

Integrated Analysis of Prognostic and Immune Associated Integrin Family in Ovarian Cancer.

Front Genet 2020 17;11:705. Epub 2020 Jul 17.

Department of Pathology, Xiangya Hospital, Central South University, Changsha, China.

Human integrin receptors are important for cell-cell and cell-matrix adhesion in normal epithelial cells. Emerging evidences have indicated integrin members are involved in cancer development and progression as well. However, the expression patterns and clinical significance of the whole integrin family in ovarian cancer (OC) have not yet been well understood. In the present study, we utilized the public datasets including GEPIA, GEO, ONCOMINE, cBioPortal, Kaplan-Meier Plotter, TIMER databases, to analyze the expression and prognostic value of integrin members in OC. We found ITGA3/B4/B6/B7/B8 were abnormally overexpressed in OC; ITGA6 was good prognosis predictor in OC; ITGA3/ B4/B8 were poor prognosis predictor specially in advanced OC patients; elevated ITGA3/B4 might promote metastasis and elevated ITGA3/B8 might promote platinum resistance of OC; ITGA3 and ITGB4 might synergistically or independently regulate cell adhesion and proliferation; ITGA4/AL/AM/AX/B2/B7 showed strong correlations with various tumor immune infiltrates (TILs), especially with pro-tumor immunes cell types like monocyte, M2 macrophage and exhaustion T cells infiltration; ITGAL/AM/B2/B7 and residing memory CD8+ T cells marker ITGAE were specially associated with early OC patients outcome. Our results implied that ITGA3/B4 were important prognostic markers of advanced OC, ITGAL/AM/ B2/B7 were immune associated prognosis markers of early OC, together they might render important therapeutic targets for OC.
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http://dx.doi.org/10.3389/fgene.2020.00705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379341PMC
July 2020