Publications by authors named "Kun Xia"

507 Publications

Blood Neurofilament Light Chain in Genetic Ataxia: A Meta-Analysis.

Mov Disord 2021 Sep 14. Epub 2021 Sep 14.

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

Background: No comprehensive meta-analysis has ever been performed to assess the value of neurofilament light chain (NfL) as a biomarker in genetic ataxia.

Objective: We conducted a meta-analysis to summarize NfL concentration and evaluate its utility as a biomarker in genetic ataxia.

Methods: Studies were included if they reported NfL concentration of genetic ataxia. We used log (mean ± SD) NfL to describe mean raw value of NfL. The effect size of NfL between genetic ataxia and healthy controls (HC) was expressed by mean difference. Correlation between NfL and disease severity was calculated.

Results: We identified 11 studies of 624 HC and 1006 patients, here referred to as spinocerebellar ataxia (SCA1, 2, 3, 6, and 7), Friedreich ataxia (FRDA), and ataxia telangiectasia (A-T). The concentration of blood NfL (bNfL) elevated with proximity to expected onset, and progressively increased from asymptomatic to preclinical to clinical stage in SCA3. Compared with HC, bNfL levels were significantly higher in SCA1, 2, 3, and 7, FRDA, as well as A-T, and the difference increased with the advancing disease in SCA3. bNfL levels correlated with disease severity in SCA3. There was a significant correlation between bNfL and longitudinal progression in SCA3. Additionally, bNfL increased with age in HC, yet this is probably masked by higher disease-related effects on bNfL in genetic ataxia.

Conclusions: bNfL can be used as a potential biomarker to predict disease onset, severity, and progression of genetic ataxia. Reference-value setting of bNfL should be divided according to age. © 2021 International Parkinson and Movement Disorder Society.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mds.28783DOI Listing
September 2021

Rare NRXN1 missense variants identified in autism interfered protein degradation and Drosophila sleeping.

J Psychiatr Res 2021 Sep 2;143:113-122. Epub 2021 Sep 2.

Center for Medical Genetics and Hunan Provincial Key Laboratory for Medical Genetics, School of Life Sciences, Central South University, Changsha, China; CAS Center for Excellence in Brain Science and Intelligences Technology (CEBSIT), Shanghai, China; Key Laboratory of Medical Information Research, Central South University, Changsha, Hunan, China. Electronic address:

NRXN1 is involved in synaptogenesis and have been implicated in Autism spectrum disorders. However, many rare inherited missense variants of NRXN1 have not been thoroughly evaluated. Here, functional analyses in vitro and in Drosophila of three NRXN1 missense mutations, Y282H, L893V, and I1135V identified in ASD patients in our previous study were performed. Our results showed these three mutations interfered protein degradation compared with NRXN1-WT protein. Expressing human NRXN1 in Drosophila could lead to abnormal circadian rhythm and sleep behavior, and three mutated proteins caused milder phenotypes, indicating the mutations may change the function of NRXN1 slightly. These findings highlight the functional role of rare NRXN1 missense variants identified in autism patients, and provide clues for us to better understand the pathogenesis of abnormal circadian rhythm and sleep behavior of other organisms, including humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpsychires.2021.09.013DOI Listing
September 2021

The autism risk gene CNTN4 modulates dendritic spine formation.

Hum Mol Genet 2021 Aug 20. Epub 2021 Aug 20.

Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.

Contactin 4 (CNTN4) is a crucial synaptic adhesion protein that belongs to the contactin superfamily. Evidence from both human genetics and mouse models suggests that synapse formation and structural deficits strongly correlate with neurodevelopmental disorders, including autism. In addition, several lines of evidence suggest that CNTN4 is associated with the risk of autism. However, the biological functions of CNTN4 in neural development and disease pathogenesis are poorly understood. In this study, we investigated whether and how CNTN4 is autonomously involved in the development of dendrites and dendritic spines in cortical neurons. Disruption of Cntn4 decreased the number of excitatory synapses, which led to a reduction in neural activity. Truncated proteins lacking the signal peptide, FnIII domains, or GPI domain lacked the ability to regulate dendritic spine formation, indicating that CNTN4 regulates dendritic spine density through a mechanism dependent on FnIII domains. Importantly, we revealed that autism-related variants lacked the ability to regulate spine density and neural activity. In conclusion, our study suggests that CNTN4 is essential for promoting dendrite growth and dendritic spine formation and that disruptive variants of CNTN4 interfere with abnormal synapse formation and may increase the risk of autism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddab233DOI Listing
August 2021

Characteristics of immune and inflammatory responses among different age groups of pediatric patients with COVID-19 in China.

World J Pediatr 2021 Aug 2;17(4):375-384. Epub 2021 Aug 2.

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

Background: Severe cases of coronavirus disease 2019 (COVID-19) among pediatric patients are more common in children less than 1 year of age. Our aim is to address the underlying role of immunity and inflammation conditions among different age groups of pediatric patients.

Methods: We recruited pediatric patients confirmed of moderate COVID-19 symptoms, admitted to Wuhan Children's Hospital from January 28th to April 1st in 2020. Patients were divided into four age groups (≤ 1, 1-6, 7-10, and 11-15 years). Demographic information, clinical characteristics, laboratory results of lymphocyte subsets test, immune and inflammation related markers were all evaluated.

Results: Analysis included 217/241 (90.0%) of patients with moderate clinical stage disease. Average recovery time of children more than 6 years old was significantly shorter than of children younger than 6 years (P = 0.001). Reduced neutrophils and increased lymphocytes were significantly most observed among patients under 1 year old (P < 0.01). CD19+ B cells were the only significantly elevated immune cells, especially among patients under 1 year old (cell proportion: n = 12, 30.0%, P < 0.001; cell count: n = 13, 32.5%, P < 0.001). While, low levels of immune related makers, such as immunoglobulin (Ig) G (P < 0.001), IgA (P < 0.001), IgM (P < 0.001) and serum complement C3c (P < 0.001), were also mostly found among patients under 1 year old, together with elevated levels of inflammation related markers, such as tumor necrosis factor γ (P = 0.007), interleukin (IL)-10 (P = 0.011), IL-6 (P = 0.008), lactate dehydrogenase (P < 0.001), and procalcitonin (P = 0.007).

Conclusion: The higher rate of severe cases and long course of COVID-19 among children under 1 year old may be due to the lower production of antibodies and serum complements of in this age group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12519-021-00440-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328122PMC
August 2021

SLC39A5 dysfunction impairs extracellular matrix synthesis in high myopia pathogenesis.

J Cell Mol Med 2021 Sep 24;25(17):8432-8441. Epub 2021 Jul 24.

Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.

High myopia is one of the leading causes of visual impairment worldwide with high heritability. We have previously identified the genetic contribution of SLC39A5 to nonsyndromic high myopia and demonstrated that disease-related mutations of SLC39A5 dysregulate the TGF-β pathway. In this study, the mechanisms underlying SLC39A5 involvement in the pathogenesis of high myopia are determined. We observed the morphogenesis and migration abnormalities of the SLC39A5 knockout (KO) human embryonic kidney cells (HEK293) and found a significant injury of ECM constituents. RNA-seq and qRT-PCR revealed the transcription decrease in COL1A1, COL2A1, COL4A1, FN1 and LAMA1 in the KO cells. Further, we demonstrated that TGF-β signalling, the regulator of ECM, was inhibited in SLC39A5 depletion situation, wherein the activation of receptor Smads (R-Smads) via phosphorylation was greatly blocked. SLC39A5 re-expression reversed the phenotype of TGF-β signalling and ECM synthesis in the KO cells. The fact that TGF-β signalling was zinc-regulated and that SLC39A5 was identified as a zinc transporter urged us to check the involvement of intracellular zinc in TGF-β signalling impairment. Finally, we determined that insufficient zinc chelation destabilized Smad proteins, which naturally inhibited TGF-β signalling. Overall, the SLC39A5 depletion-induced zinc deficiency destabilized Smad proteins, which inhibited the TGF-β signalling and downstream ECM synthesis, thus contributing to the pathogenesis of high myopia. This discovery provides a deep insight into myopic development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.16803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419198PMC
September 2021

Genetic etiology of a Chinese ataxia cohort: Expanding the mutational spectrum of hereditary ataxias.

Parkinsonism Relat Disord 2021 Aug 10;89:120-127. Epub 2021 Jul 10.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China; Laboratory of Medical Genetics, Central South University, Changsha, China; School of Basic Medical Science, Central South University, Changsha, China. Electronic address:

Introduction: Hereditary ataxias demonstrate a high degree of clinical and genetic heterogeneity. Understanding the genetic etiology of hereditary ataxias is crucial for genetic counseling and clinical management.

Methods: The clinical and genetic data of patients with familial or sporadic ataxias who referred to our tertiary medical center were retrospectively analyzed. Probands in this study underwent SCA repeat expansion panel firstly to screen for repeat expansion SCAs; those with negative results had NGS-targeted panels or WES testing to detect conventional mutations.

Results: A total of 223 patients were enrolled from 206 families. 5 kinds of coexisting SCA repeat expansions were observed (SCA3/SCA17, SCA3/SCA8, SCA2/SCA8, SCA3/SCA12 and SCA8/SCA12) in 12 patients from 8 families, among which SCA2/SCA8, SCA8/SCA12 and SCA3/SCA12 were reported for the first time. The coexistence of expanded SCA3 with SCA17 alleles was the most common in our study. NGS identified pathogenic/likely pathogenic variants in 12 ataxia causative genes in 13 probands. Spastic paraplegia ataxia was the most common diagnosis. Six novel mutations were detected in five ataxia-related genes.

Conclusion: Coexistence may not specific to a certain SCA subtype and the frequency might have been underestimated before. SCA repeat expansion panel should be considered in patients with overlapping SCA features. In addition, our study broadened the conventional mutation spectrum in ataxia-related genes. These results facilitate a better understanding of the genetic basis for hereditary ataxias.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.parkreldis.2021.07.010DOI Listing
August 2021

Identification of the Largest SCA36 Pedigree in Asia: with Multimodel Neuroimaging Evaluation for the First Time.

Cerebellum 2021 Jul 15. Epub 2021 Jul 15.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.

Spinocerebellar ataxias (SCAs) are a large group of hereditary neurodegenerative diseases characterized by ataxia and dysarthria. Due to high clinical and genetic heterogeneity, many SCA families are undiagnosed. Herein, using linkage analysis, WES, and RP-PCR, we identified the largest SCA36 pedigree in Asia. This pedigree showed some distinct clinical characteristics. Cognitive impairment and gaze palsy are common and severe in SCA36 patients, especially long-course patients. Although no patients complained of hearing loss, most of them presented with hearing impairment in objective auxiliary examination. Voxel-based morphometry (VBM) demonstrated a reduction of volumes in cerebellum, brainstem, and thalamus (corrected P < 0.05). Reduced volumes in cerebellum were also found in presymptomatic carriers. Resting-state functional MRI (R-fMRI) found reduced ReHo values in left cerebellar posterior lobule (corrected P < 0.05). Diffusion tensor imaging (DTI) demonstrated a reduction of FA values in cerebellum, midbrain, superior and inferior cerebellar peduncle (corrected P < 0.05). MRS found reduced NAA/Cr values in cerebellar vermis and hemisphere (corrected P < 0.05). Our findings could provide new insights into management of SCA36 patients. Detailed auxiliary examination are recommended to assess hearing or peripheral nerve impairment, and we should pay more attention to eye movement and cognitive changes in patients. Furthermore, for the first time, our multimodel neuroimaging evaluation generate a full perspective of brain function and structure in SCA36 patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12311-021-01304-0DOI Listing
July 2021

Evaluation of Peripheral Immune Activation in Amyotrophic Lateral Sclerosis.

Front Neurol 2021 24;12:628710. Epub 2021 Jun 24.

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

Accumulating evidence has revealed that immunity plays an important role in amyotrophic lateral sclerosis (ALS) progression. However, the results regarding the serum levels of immunoglobulin and complement are inconsistent in patients with ALS. Although immune dysfunctions have also been reported in patients with other neurodegenerative diseases, few studies have explored whether immune dysfunction in ALS is similar to that in other neurodegenerative diseases. Therefore, we performed this study to address these gaps. In the present study, serum levels of immunoglobulin and complement were measured in 245 patients with ALS, 65 patients with multiple system atrophy (MSA), 60 patients with Parkinson's disease (PD), and 82 healthy controls (HCs). Multiple comparisons revealed that no significant differences existed between patients with ALS and other neurodegenerative diseases in immunoglobulin and complement levels. Meta-analysis based on data from our cohort and eight published articles was performed to evaluate the serum immunoglobulin and complement between patients with ALS and HCs. The pooled results showed that patients with ALS had higher C4 levels than HCs. In addition, we found that the IgG levels were lower in early-onset ALS patients than in late-onset ALS patients and HCs, and the correlations between age at onset of ALS and IgG or IgA levels were significant positive. In conclusion, our data supplement existing literature on understanding the role of peripheral immunity in ALS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2021.628710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264193PMC
June 2021

Intelligent anti-epidemic mask based on KF and ECF fusion algorithm.

Electron Lett 2021 May 25. Epub 2021 May 25.

Department of Electrical Engineering University of Shanghai for Science and Technology Shanghai People's Republic of China.

In response to environmental pollution and the spread of Coronavirus Disease 2019 (COVID-19), this paper proposes a new type of smart mask design, and specifically proposes an optimized double closed-loop control method, especially an improved filtering fusion algorithm. Using the filtering fusion algorithm proposed in this paper, after the Kalman filter (KF) filters the raw data of the attitude sensor, explicit complementary filtering and data fusion are used to obtain the attitude angle of the body. At the same time, the obtained attitude angle is combined with acceleration and blood oxygen concentration to obtain the behaviour characteristic value. On this basis, the speed of the oxygen supply fan captured by the photoelectric sensor is used to form a closed loop with the characteristic value of the behaviour. Finally, the structure of the mask is upgraded and optimized through fluid mechanics simulation, and experiments have verified that the combination of the replaceable filter cloth, the intelligent control system and the ultraviolet disinfection device can effectively protect people's health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1049/ell2.12240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239796PMC
May 2021

Exploration of the Important Role of Microfibril-Associated Protein 4 Gene in Oral Squamous Cell Carcinoma.

Med Sci Monit 2021 Jul 2;27:e931238. Epub 2021 Jul 2.

Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital Central South University, Changsha, Hunan, China (mainland).

BACKGROUND Oral squamous cell carcinoma (OSCC) is a common tumor of the head and neck. Its treatment usually requires multiple modalities. Currently, there are no molecular biomarkers to guide these treatment strategies. Studies have shown that microfibril-associated protein 4 (MFAP4) is potentially useful for non-invasive assessment of various diseases; however, its biological function in tumors is still unknown. In this study, we propose that MFAP4 is a new prognostic target for OSCC. MATERIAL AND METHODS First, we collected OSCC data (GSE25099 and GSE30784 datasets) from the Gene Expression Omnibus (GEO) database and compared the differential expression of MFAP4 gene between the patients (tumor) and normal (control) groups. The comparison was done with University of California Santa Cruz Xena (https://xenabrowser.net/Datapages/), and we calculated the difference in MFAP4 gene expression between normal and tumor tissues in a pan-cancer analysis. Then, we compared the 2 groups with high and low expression of MFAP4 gene in terms of tumor mutation burden (TMB), miRNA regulation, and immune cell infiltration. RESULTS We found that the expression of MFAP4 gene was significantly decreased in tumors. Our research also showed that high expression of MFAP4 was related to better prognosis of patients and may be related to tumor gene mutation, miRNA regulation, and infiltration of different immune cells. CONCLUSIONS Our work provides evidence that expression of MFAP4 can be used as a prognostic biomarker for risk stratification of OSCC patients and elaborates on its relation with the regulation of TMB, miRNAs, and immune cell infiltration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/MSM.931238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259352PMC
July 2021

An Intelligent Self-Service Vending System for Smart Retail.

Sensors (Basel) 2021 May 20;21(10). Epub 2021 May 20.

Department of Electrical Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.

The traditional weighing and selling process of non-barcode items requires manual service, which not only consumes manpower and material resources but is also more prone to errors or omissions of data. This paper proposes an intelligent self-service vending system embedded with a single camera to detect multiple products in real-time performance without any labels, and the system realizes the integration of weighing, identification, and online settlement in the process of non-barcode items. The system includes a self-service vending device and a multi-device data management platform. The flexible configuration of the structure gives the system the possibility of identifying fruits from multiple angles. The height of the system can be adjusted to provide self-service for people of different heights; then, deep learning skill is applied implementing product detection, and real-time multi-object detection technology is utilized in the image-based checkout system. In addition, on the multi-device data management platform, the information docking between embedded devices, WeChat applets, Alipay, and the database platform can be implemented. We conducted experiments to verify the accuracy of the measurement. The experimental results demonstrate that the correlation coefficient R2 between the measured value of the weight and the actual value is 0.99, and the accuracy of non-barcode item prediction is 93.73%. In Yangpu District, Shanghai, a comprehensive application scenario experiment was also conducted, proving that our system can effectively deal with the challenges of various sales situations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s21103560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161222PMC
May 2021

Chinese Medicine Rescues Acute Respiratory Dyspnea Syndrome Caused by COVID-19: A Case Report.

Chin J Integr Med 2021 May 25. Epub 2021 May 25.

Department of Respiratory, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11655-021-3333-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143984PMC
May 2021

Targeted sequencing and integrative analysis of 3,195 Chinese patients with neurodevelopmental disorders prioritized 26 novel candidate genes.

J Genet Genomics 2021 04 1;48(4):312-323. Epub 2021 Apr 1.

Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing 100049, China; State Key Laboratory of Integrated Management of Pest Insects and Rodents, Chinese Academy of Sciences, Beijing 100101, China. Electronic address:

Neurodevelopmental disorders (NDDs) are a set of complex disorders characterized by diverse and co-occurring clinical symptoms. The genetic contribution in patients with NDDs remains largely unknown. Here, we sequence 519 NDD-related genes in 3,195 Chinese probands with neurodevelopmental phenotypes and identify 2,522 putative functional mutations consisting of 137 de novo mutations (DNMs) in 86 genes and 2,385 rare inherited mutations (RIMs) with 22 X-linked hemizygotes in 13 genes, 2 homozygous mutations in 2 genes and 23 compound heterozygous mutations in 10 genes. Furthermore, the DNMs of 16,807 probands with NDDs are retrieved from public datasets and combine in an integrated analysis with the mutation data of our Chinese NDD probands by taking 3,582 in-house controls of Chinese origin as background. We prioritize 26 novel candidate genes. Notably, six of these genes - ITSN1, UBR3, CADM1, RYR3, FLNA, and PLXNA3 - preferably contribute to autism spectrum disorders (ASDs), as demonstrated by high co-expression and/or interaction with ASD genes confirmed via rescue experiments in a mouse model. Importantly, these genes are differentially expressed in the ASD cortex in a significant manner and involved in ASD-associated networks. Together, our study expands the genetic spectrum of Chinese NDDs, further facilitating both basic and translational research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jgg.2021.03.002DOI Listing
April 2021

Anxiety and depression in spinocerebellar ataxia patients during the COVID-19 pandemic in China: A cross-sectional study.

J Clin Neurosci 2021 Jun 30;88:39-46. Epub 2021 Mar 30.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China. Electronic address:

Coronavirus disease 2019 (COVID-19) is currently a global concern, and the psychological impact cannot be overlooked. Our purpose was to evaluate the anxiety and depression in spinocerebellar ataxia (SCA) patients during the pandemic and to analyse the influencing factors. We conducted an online questionnaire survey among 307 SCA patients from China and selected 319 healthy people matched by sex and age as the control group. The questionnaire included general information, the self-rating anxiety scale (SAS), and the self-rating depression scale (SDS). The relevant factors included COVID-19 risk factors, age, sex, body mass index (BMI), educational background, disease course, score on the scale for the assessment and rating of ataxia (SARA), Mini-mental State Examination (MMSE) and International Cooperative Ataxia Rating Scale (ICARS). The proportion of SCA patients with anxiety was 34.9%, and the proportion with depression was 56.7%. The SAS and SDS scores of the SCA patients were significantly higher than those of the control group (SAS: 45.8 ± 10.1 vs. 40.6 ± 8.9, P < 0.01; SDS: 55.1 ± 12.2 vs. 43.6 ± 11.9, P < 0.01). In SCA3, the risk of exposure to COVID-19, educational level, disease course and the severity of ataxia may be factors affecting patients' mental health. More attention should be paid to the mental health of SCA patients during the COVID-19 pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2021.03.004DOI Listing
June 2021

G3BP1 may serve as a potential biomarker of proliferation, apoptosis, and prognosis in oral squamous cell carcinoma.

J Oral Pathol Med 2021 May 13. Epub 2021 May 13.

Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, China.

Background: G3BP1 is a prognostic biomarker for many types of cancers; however, its role in oral squamous cell carcinoma remains unclear. We investigated the role of G3BP1 as a potential biomarker for proliferation, apoptosis, and prognosis in oral squamous cell carcinoma.

Methods: We obtained samples of normal oral mucosa (n = 17), oral squamous cell carcinoma tissues (n = 61), and paired adjacent tissues (n = 47) from Xiangya Hospital for immunohistochemical evaluation to measure the expression of G3BP1, E-cadherin, Ki67, and Cleaved-caspase3. Using data from The Cancer Genome Atlas, we performed bioinformatics analysis to investigate the prognosis, functions, signaling pathways, and immune infiltrate significance related to G3BP1 in oral squamous cell carcinoma.

Results: The G3BP1 protein level was significantly upregulated in oral squamous cell carcinoma tissues and was also positively associated with Ki67 and negatively associated with Cleaved-caspase3. Based on information available in online database, the G3BP1 mRNA level was significantly higher in oral squamous cell carcinoma than in normal tissues. High G3BP1 mRNA levels were associated with poor overall survival rates in patients with oral squamous cell carcinoma. Enrichment analysis showed that G3BP1 was involved in the helicase/catalytic/ATPase activity functions and spliceosome/RNA transport/ cell cycle pathways. Furthermore, G3BP1 mRNA levels were positively associated with CD4 T-cell infiltration.

Conclusions: G3BP1 may serve as a potential biomarker for proliferation, apoptosis, and prognosis of oral squamous cell carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jop.13199DOI Listing
May 2021

Relationships between peripheral reactive hyperemia index with coronary plaque burden and prognosis in patients with unstable angina pectoris complicated with type 2 diabetes mellitus.

Ann Transl Med 2021 Apr;9(8):655

Heart Center, Beijing Chaoyang Hospital, Capital Medical University & Beijing Key Laboratory of Hypertension, Beijing, China.

Background: Coronary plaque burden (CPB) is an important prognostic factor in patients with unstable angina pectoris (UAP). Our current study aims to investigate the relationships between peripheral reactive hyperemia index (RHI) with CPB and prognosis in patients with UAP complicated with type 2 diabetes mellitus (T2DM).

Methods: The clinical data of 187 UAP-T2DM patients who were treated in our center from June 2017 to January 2019 were retrospectively collected. RHI, CPB, and other clinical features were measured. The patients were followed up for 18 months and then divided into an adverse cardiovascular event (ACE) group (n=71, with ACEs) and a control group (n=116, without ACEs). The differences in RHI, CPB, and other clinical features between these two groups were compared, and the potential correlation between RHI and CPB was analyzed.

Results: Compared with the control group, the ACE group had significantly lower RHI (1.21±0.32 1.59±0.35, P=0.000) and left ventricular ejection fraction (LVEF) (42.92%±7.78% 48.90%±6.76%, P=0.000) and a significantly higher left ventricular myocardial mass index (2.67±0.87 2.27±0.49 mg/g, P=0.000), carotid intima-media thickness (1.65±0.34 1.51±0.32 mm, P=0.000), number of coronary plaques (3.98±0.53 3.32±0.38, P=0.000), non-calcified plaque volume (32.89±12.56 22.58±9.97 mm, P=0.000), calcified plaque volume (4.89±1.29 3.88±1.05 mm, P=0.000), non-calcified plaque burden (5.70%±1.60% 3.18%±1.08%, P=0.000), and calcified plaque burden (0.90%±0.22% 0.65%±0.19%, P=0.000). Pearson linear correlation analysis showed that peripheral RHI was negatively correlated with plaque number, non-calcified plaque volume, calcified plaque volume, non-calcified plaque burden, and calcified plaque burden in patients with UAP complicated with T2DM (all P<0.05).

Conclusions: Decreased peripheral RHI is associated with ACEs and CPB in patients with UAP complicated with T2DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-21-657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106013PMC
April 2021

Extracellular Vesicles from Child Gut Microbiota Enter into Bone to Preserve Bone Mass and Strength.

Adv Sci (Weinh) 2021 05 17;8(9):2004831. Epub 2021 Feb 17.

Department of Orthopedics Xiangya Hospital Central South University Changsha Hunan 410008 China.

Recently, the gut microbiota (GM) has been shown to be a regulator of bone homeostasis and the mechanisms by which GM modulates bone mass are still being investigated. Here, it is found that colonization with GM from children (CGM) but not from the elderly (EGM) prevents decreases in bone mass and bone strength in conventionally raised, ovariectomy (OVX)-induced osteoporotic mice. 16S rRNA gene sequencing reveals that CGM reverses the OVX-induced reduction of (). Direct replenishment of is sufficient to correct the OVX-induced imbalanced bone metabolism and protect against osteoporosis. Mechanistic studies show that the secretion of extracellular vesicles (EVs) is required for the CGM- and -induced bone protective effects and these nanovesicles can enter and accumulate into bone tissues to attenuate the OVX-induced osteoporotic phenotypes by augmenting osteogenic activity and inhibiting osteoclast formation. The study identifies that gut bacterium mediates the CGM-induced anti-osteoporotic effects and presents a novel mechanism underlying the exchange of signals between GM and host bone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/advs.202004831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097336PMC
May 2021

Cross-Disorder Analysis of De Novo Mutations in Neuropsychiatric Disorders.

J Autism Dev Disord 2021 May 10. Epub 2021 May 10.

National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Xiangya Road, Kaifu District, Changsha, 410013, Hunan, China.

The clinical similarity among different neuropsychiatric disorders (NPDs) suggested a shared genetic basis. We catalogued 23,109 coding de novo mutations (DNMs) from 6511 patients with autism spectrum disorder (ASD), 4,293 undiagnosed developmental disorder (UDD), 933 epileptic encephalopathy (EE), 1022 intellectual disability (ID), 1094 schizophrenia (SCZ), and 3391 controls. We evaluated that putative functional DNMs contribute to 38.11%, 34.40%, 33.31%, 10.98% and 6.91% of patients with ID, EE, UDD, ASD and SCZ, respectively. Consistent with phenotype similarity and heterogeneity in different NPDs, they show different degree of genetic association. Cross-disorder analysis of DNMs prioritized 321 candidate genes (FDR < 0.05) and showed that genes shared in more disorders were more likely to exhibited specific expression pattern, functional pathway, genetic convergence, and genetic intolerance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10803-021-05031-7DOI Listing
May 2021

Harmine targets inhibitor of DNA binding-2 and activator protein-1 to promote preosteoclast PDGF-BB production.

J Cell Mol Med 2021 06 7;25(12):5525-5533. Epub 2021 May 7.

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

Osteoporosis is one of the most common metabolic bone diseases affecting millions of people. We previously found that harmine prevents bone loss in ovariectomized mice via increasing preosteoclast platelet-derived growth factor-BB (PDGF-BB) production and type H vessel formation. However, the molecular mechanisms by which harmine promotes preosteoclast PDGF-BB generation are still unclear. In this study, we revealed that inhibitor of DNA binding-2 (Id2) and activator protein-1 (AP-1) were important factors implicated in harmine-enhanced preosteoclast PDGF-BB production. Exposure of RANKL-induced Primary bone marrow macrophages (BMMs), isolated from tibiae and femora of mice, to harmine increased the protein levels of Id2 and AP-1. Knockdown of Id2 by Id2-siRNA reduced the number of preosteoclasts as well as secretion of PDGF-BB in RANKL-stimulated BMMs administrated with harmine. Inhibition of c-Fos or c-Jun (components of AP-1) both reversed the stimulatory effect of harmine on preosteoclast PDGF-BB production. Dual-luciferase reporter assay analyses determined that PDGF-BB was the direct target of AP-1 which was up-regulated by harmine treatment. In conclusion, our data demonstrated a novel mechanism involving in the production of PDGF-BB increased by harmine, which may provide potential therapeutic targets for bone loss diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.16562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184727PMC
June 2021

Osteocyte exosomes accelerate benign prostatic hyperplasia development.

Mol Cell Endocrinol 2021 07 29;531:111301. Epub 2021 Apr 29.

Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address:

Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men. BPH patients exhibit an increased risk of vertebral and hip fractures, which are most attributable to pre-existing osteoporosis. However, the relationship between BPH and osteoporosis is still unknown. Here we found that osteocytes, the most abundant bone cells, promoted BPH development by secreting exosomes. In vitro, osteocyte exosomes (OCY-Exo) directly promoted cell proliferation of a prostate epithelial cell line BPH-1 and a macrophage cell line RAW264.7, OCY-Exo also stimulated macrophage-induced proliferation of BPH-1 cells. In vivo, intramedullary injection of OCY-Exo accumulated in prostate. Intravenous administration of OCY-Exo exacerbated testosterone-induced BPH in C57BL/6J mice. Our study uncovers the role of OCY-Exo as a stimulator of BPH, suggesting a novel mechanism in bone-prostate communication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mce.2021.111301DOI Listing
July 2021

Extracellular Vesicles from Elicit Antitumor Immunity Against Prostate Cancer via Modulation of CD8 T Cells and Macrophages.

Int J Nanomedicine 2021 20;16:2949-2963. Epub 2021 Apr 20.

Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

Purpose: Prostate cancer (PCa) is one of the most common malignancies in males. Despite the success of immunotherapy in many malignant cancers, strategies are still needed to improve therapeutic efficacy in PCa. This study aimed to investigate the effects of -derived extracellular vesicles (-EVs) on PCa and elucidate the underlying immune-related mechanism.

Methods: -EVs were isolated by ultracentrifugation and intravenously injected to treat syngeneic PCa-bearing immune-competent mice. Immunophenotypic changes in immune cells, such as cytotoxic T lymphocytes and macrophages, were measured via flow cytometry analysis. Histological examination was used to detect morphological changes in major organs after -EVs treatments. In vitro, flow cytometry was performed to confirm the effects of -EVs on the activation of CD8 T cells. Quantitative PCR and immunofluorescence staining were carried out to test the impact of -EVs on macrophage polarization. Cell counting kit-8 (CCK-8) analysis, colony formation assays, and scratch wound healing assays were conducted to assess the effects of -EVs-treated macrophages on the proliferation and invasion of PCa cells. CCK-8 assays also confirmed the impact of -EVs on the viability of normal cells.

Results: Intravenous injection of -EVs in immune-competent mice reduced the tumor burden of PCa without inducing obvious toxicity in normal tissues. This treatment elevated the proportion of granzyme B-positive (GZMB) and interferon γ-positive (IFN-γ) lymphocytes in CD8 T cells and caused macrophage recruitment, with increased tumor-killing M1 macrophages and decreased immunosuppressive M2 macrophages. In vitro, -EVs increased the number of GZMBCD8 and IFN-γCD8 T cells and M1-like macrophages. In addition, conditioned medium from -EVs-treated macrophages suppressed the proliferation and invasion of prostate cells. Furthermore, the effective dose of -EVs was well-tolerated in normal cells.

Conclusion: Our study revealed the promising prospects of -EVs as an efficient and biocompatible immunotherapeutic agent for PCa treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IJN.S304515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068512PMC
June 2021

New Model for Estimation of the Age at Onset in Spinocerebellar Ataxia Type 3.

Neurology 2021 06 23;96(23):e2885-e2895. Epub 2021 Apr 23.

From the Department of Neurology (L.P., Z.C., M.L., L.L., H.P., Y.S., Y.P., Q.D., S.W., G.Z., L.W., H.Y., L.H., Y.X., Z.T., N.W., Y.G., X.H., L.S., J.L., B.T., H.J.), Department of Pathology (C.W.), National Clinical Research Center for Geriatric Disorders (Z.C., L.S., B.T., H.J.), Xiangya Hospital, Central South University; Department of Neurology (Z.L.), The Second Xiangya Hospital, Central South University; Key Laboratory of Hunan Province in Neurodegenerative Disorders (Z.C., L.S., J.L., B.T., H.J.), Center for Medical Genetics School of Life Sciences (K.X., J.L., C.C.), Hunan Key Laboratory of Medical Genetics (K.X., J.L., C.C.), School of Computer Science and Engineering (R.Q.), and School of Basic Medical Science (H.J.), Central South University, Changsha, Hunan, China; Department of Neurology (T.K.), University of Bonn; and German Center for Neurodegenerative Diseases (DZNE) (T.K.), Bonn, Germany.

Objectives: The aim of this study was to develop an appropriate parametric survival model to predict patient's age at onset (AAO) for spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) populations from mainland China.

Methods: We compared the efficiency and performance of 6 parametric survival analysis methods (exponential, weibull, log-gaussian, gaussian, log-logistic, and logistic) based on cytosine-adenine-guanine (CAG) repeat length at to predict the probability of AAO in the largest cohort of patients with SCA3/MJD. A set of evaluation criteria, including -2 log-likelihood statistic, Akaike information criterion (AIC), bayesian information criterion (BIC), Nagelkerke R-squared (Nagelkerke R^2), and Cox-Snell residual plot, were used to identify the best model.

Results: Among these 6 parametric survival models, the logistic model had the lowest -2 log-likelihood (6,560.12), AIC (6,566.12), and BIC (6,566.14) and the highest value of Nagelkerke R^2 (0.54), with the closest graph to the bisector Cox-Snell residual graph. Therefore, the logistic survival model was the best fit to the studied data. Using the optimal logistic survival model, we indicated the age-specific probability distribution of AAO according to the CAG repeat size and current age.

Conclusions: We first demonstrated that the logistic survival model provided the best fit for AAO prediction in patients with SCA3/MJD from mainland China. This optimal model can be valuable in clinical and research. However, the rigorous clinical testing and practice of other independent cohorts are needed for its clinical application. A unified model across multiethnic cohorts is worth further exploration by identifying regional differences and significant modifiers in AAO determination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000012068DOI Listing
June 2021

Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders.

Genome Med 2021 04 19;13(1):63. Epub 2021 Apr 19.

The Atwal Clinic: Genomic & Personalized Medicine, Jacksonville, FL, USA.

Background: With the increasing number of genomic sequencing studies, hundreds of genes have been implicated in neurodevelopmental disorders (NDDs). The rate of gene discovery far outpaces our understanding of genotype-phenotype correlations, with clinical characterization remaining a bottleneck for understanding NDDs. Most disease-associated Mendelian genes are members of gene families, and we hypothesize that those with related molecular function share clinical presentations.

Methods: We tested our hypothesis by considering gene families that have multiple members with an enrichment of de novo variants among NDDs, as determined by previous meta-analyses. One of these gene families is the heterogeneous nuclear ribonucleoproteins (hnRNPs), which has 33 members, five of which have been recently identified as NDD genes (HNRNPK, HNRNPU, HNRNPH1, HNRNPH2, and HNRNPR) and two of which have significant enrichment in our previous meta-analysis of probands with NDDs (HNRNPU and SYNCRIP). Utilizing protein homology, mutation analyses, gene expression analyses, and phenotypic characterization, we provide evidence for variation in 12 HNRNP genes as candidates for NDDs. Seven are potentially novel while the remaining genes in the family likely do not significantly contribute to NDD risk.

Results: We report 119 new NDD cases (64 de novo variants) through sequencing and international collaborations and combined with published clinical case reports. We consider 235 cases with gene-disruptive single-nucleotide variants or indels and 15 cases with small copy number variants. Three hnRNP-encoding genes reach nominal or exome-wide significance for de novo variant enrichment, while nine are candidates for pathogenic mutations. Comparison of HNRNP gene expression shows a pattern consistent with a role in cerebral cortical development with enriched expression among radial glial progenitors. Clinical assessment of probands (n = 188-221) expands the phenotypes associated with HNRNP rare variants, and phenotypes associated with variation in the HNRNP genes distinguishes them as a subgroup of NDDs.

Conclusions: Overall, our novel approach of exploiting gene families in NDDs identifies new HNRNP-related disorders, expands the phenotypes of known HNRNP-related disorders, strongly implicates disruption of the hnRNPs as a whole in NDDs, and supports that NDD subtypes likely have shared molecular pathogenesis. To date, this is the first study to identify novel genetic disorders based on the presence of disorders in related genes. We also perform the first phenotypic analyses focusing on related genes. Finally, we show that radial glial expression of these genes is likely critical during neurodevelopment. This is important for diagnostics, as well as developing strategies to best study these genes for the development of therapeutics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-021-00870-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056596PMC
April 2021

GPCards: An integrated database of genotype-phenotype correlations in human genetic diseases.

Comput Struct Biotechnol J 2021 22;19:1603-1611. Epub 2021 Mar 22.

National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Genotype-phenotype correlations are the basis of precision medicine of human genetic diseases. However, it remains a challenge for clinicians and researchers to conveniently access detailed individual-level clinical phenotypic features of patients with various genetic variants. To address this urgent need, we manually searched for genetic studies in PubMed and catalogued 8,309 genetic variants in 1,288 genes from 17,738 patients with detailed clinical phenotypic features from 1,855 publications. Based on genotype-phenotype correlations in this dataset, we developed an user-friendly online database called GPCards (http://genemed.tech/gpcards/), which not only provided the association between genetic diseases and disease genes, but also the prevalence of various clinical phenotypes related to disease genes and the patient-level mapping between these clinical phenotypes and genetic variants. To accelerate the interpretation of genetic variants, we integrated 62 well-known variant-level and gene-level genomic data sources, including functional predictions, allele frequencies in different populations, and disease-related information. Furthermore, GPCards enables automatic analyses of users' own genetic data, comprehensive annotation, prioritization of candidate functional variants, and identification of genotype-phenotype correlations using custom parameters. In conclusion, GPCards is expected to accelerate the interpretation of genotype-phenotype correlations, subtype classification, and candidate gene prioritisation in human genetic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.csbj.2021.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042245PMC
March 2021

Targeted sequencing and integrative analysis to prioritize candidate genes in neurodevelopmental disorders.

Mol Neurobiol 2021 Aug 15;58(8):3863-3873. Epub 2021 Apr 15.

Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, China.

Neurodevelopmental disorders (NDDs) are a group of diseases characterized by high heterogeneity and frequently co-occurring symptoms. The mutational spectrum in patients with NDDs is largely incomplete. Here, we sequenced 547 genes from 1102 patients with NDDs and validated 1271 potential functional variants, including 108 de novo variants (DNVs) in 78 autosomal genes and seven inherited hemizygous variants in six X chromosomal genes. Notably, 36 of these 78 genes are the first to be reported in Chinese patients with NDDs. By integrating our genetic data with public data, we prioritized 212 NDD candidate genes with FDR < 0.1, including 17 novel genes. The novel candidate genes interacted or were co-expressed with known candidate genes, forming a functional network involved in known pathways. We highlighted MSL2, which carried two de novo protein-truncating variants (p.L192Vfs*3 and p.S486Ifs*11) and was frequently connected with known candidate genes. This study provides the mutational spectrum of NDDs in China and prioritizes 212 NDD candidate genes for further functional validation and genetic counseling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-021-02377-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280036PMC
August 2021

Psychometric properties of the Chinese Parent Version of the Autism Spectrum Rating Scale: Rasch analysis.

Autism 2021 Oct 12;25(7):1872-1884. Epub 2021 Apr 12.

Children's Hospital of Fudan University, China.

Lay Abstract: The Autism Spectrum Rating Scale is a behavioural rating scale completed by parents and teachers that is useful for identifying children with an autism spectrum disorder. The development of a modified Autism Spectrum Rating Scale suitable for use in China is important for the identification of children in China with an autism spectrum disorder. In this study, we examined the Modified Chinese Autism Spectrum Rating Scale using a statistical technique known as Rasch analysis. Rasch analysis tests whether the questionnaire meets the standards for modern scientific measurement. We used Rasch analysis to examine data from 2013 children in China including 420 diagnosed with an autism spectrum disorder who had been rated by a parent or grandparent. After removing a small number of items (questions), the Modified Chinese Autism Spectrum Rating Scale met the stringent criteria for Rasch measurement. The availability of a reliable and precise tool for assessing behaviours characteristic of an autism spectrum disorder in Chinese children will improve the identification and diagnosis of autism spectrum disorder in China, thus enabling better provision of support services.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/13623613211004054DOI Listing
October 2021

Customized de novo mutation detection for any variant calling pipeline: SynthDNM.

Bioinformatics 2021 Apr 2. Epub 2021 Apr 2.

Department of Psychiatry, University of California San Diego, La Jolla, California United States of America.

Motivation: As sequencing technologies and analysis pipelines evolve, de novo mutations(DNMs) calling tools must be adapted. Therefore, a flexible approach is needed that can accurately identify de novo mutations from genome or exome sequences from a variety of datasets and variant calling pipelines.

Results: Here, we describe SynthDNM, a random-forest based classifier that can be readily adapted to new sequencing or variant-calling pipelines by applying a flexible approach to constructing simulated training examples from real data. The optimized SynthDNM classifiers predict de novo SNPs and indels with robust accuracy across multiple methods of variant calling.

Availability: SynthDNM is freely available on Github (https://github.com/james-guevara/synthdnm).

Supplementary Information: Supplementary data are available at Bioinformatics online.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/btab225DOI Listing
April 2021

Cross-Disorder Analysis of De Novo Variants Increases the Power of Prioritising Candidate Genes.

Life (Basel) 2021 Mar 12;11(3). Epub 2021 Mar 12.

National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha 410008, China.

De novo variants (DNVs) are critical to the treatment of neurodevelopmental disorders (NDDs). However, effectively identifying candidate genes in small cohorts is challenging in most NDDs because of high genetic heterogeneity. We hypothesised that integrating DNVs from multiple NDDs with genetic similarity can significantly increase the possibility of prioritising the candidate gene. We catalogued 66,186 coding DNVs in 50,028 individuals with nine types of NDDs in cohorts with sizes spanning from 118 to 31,260 from Gene4Denovo database to validate this hypothesis. Interestingly, we found that integrated DNVs can effectively increase the number of prioritised candidate genes for each disorder. We identified 654 candidate genes including 481 shared candidate genes carrying putative functional variants in at least two disorders. Notably, 13.51% (65/481) of shared candidate genes were prioritised only via integrated analysis including 44.62% (29/65) genes validated in recent large cohort studies. Moreover, we estimated that more novel candidate genes will be prioritised with the increase in cohort size, in particular for some disorders with high putative functional DNVs per individual. In conclusion, integrated DNVs may increase the power of prioritising candidate genes, which is important for NDDs with small cohort size.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/life11030233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001830PMC
March 2021

Impact of Prior Digestive System Disease on In-Hospital Gastrointestinal Bleeding in Patients with Acute Myocardial Infarction.

Risk Manag Healthc Policy 2021 22;14:1233-1239. Epub 2021 Mar 22.

Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People's Republic of China.

Objective: Patients presenting with acute myocardial infarction (AMI) with prior digestive system disease are more likely to suffer from gastrointestinal (GI) bleeding than those without these diseases. However, few articles reported how the different conditions of the digestive tract produced different risks of GI bleeding.

Methods: A single-center study on 7464 patients admitted for AMI from December 2010 to June 2019 in the Beijing Chaoyang Heart Center was retrospectively examined. Patients with major GI bleeding (n = 165) were compared with patients without (n = 7299). Univariate and multivariate logistic regression models were constructed to test the association between GI bleeding and prior diseases of the digestive tract, including gastroesophageal reflux disease, chronic gastritis, peptic ulcer, hepatic function damage, diseases of the colon and rectum, and gastroenterological tract tumors.

Results: Of the 7464 patients (mean age, 63.4; women, 25.6%; STEMI, 58.6%), 165 (2.2%) experienced major GI bleeding, and 1816 (24.3%) had a history of digestive system disease. The risk of GI bleeding was significantly associated with peptic ulcer (OR = 4.19, 95% CI: 1.86-9.45) and gastroenterological tumor (OR = 2.74, 95% CI: 1.07-7.04), indicated by multivariate logistic regression analysis.

Conclusion: Preexisting peptic ulcers and gastroenterological tract tumors rather than other digestive system diseases were indicators of gastrointestinal bleeding in patients with AMI who undergo standard antithrombotic treatment during hospitalization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/RMHP.S299169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997586PMC
March 2021

mutations in folate-related genes associated with common developmental disorders.

Comput Struct Biotechnol J 2021 1;19:1414-1422. Epub 2021 Mar 1.

National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Folate deficiency is an environmental risk factor for several developmental disorders. mutations (DNMs) also play important etiological roles in various developmental disorders. However, it remains unclear whether DNMs in folate-related genes (FRGs) contribute to developmental disorders. We obtained a list of 1,821 FRGs from folate metabolism pathways and the Comparative Toxicogenomics Database, along with data concerning DNMs in 15,404 cases and 3,391 controls from the Gene4Denovo database. We used a TADA-Denovo model to prioritize candidate disease-associated FRGs, and characterized these genes in terms of genic intolerance, functional networks, and expression patterns. Compared with the controls, FRGs were significantly enriched in likely damaging DNMs (ldDNMs) in patients with developmental disorders (1.54 ≤ odds ratio ≤ 3.39,  ≤ 0.0075). Furthermore, FRGs with ldDNMs rather than with likely non-damaging DNMs (lndDNMs) overlapped significantly among the five developmental disorders included in the datasets. The TADA-Denovo model prioritized 96 candidate disease-associated FRGs, which were intolerant to genetic variants. Their functional networks mainly involved pathways associated with chromatin modification, organ development, and signal transduction pathways. , , , and emerged as hub FRGs from the protein-protein interaction network. These candidate disease-associated FRGs are preferentially expressed in the excitatory neurones during embryonic development, and in the cortex, cerebellum, striatum, and amygdala during foetal development. Overall, these findings show that DNMs in FRGs are associated with the risk of developmental disorders. Further research on these DNMs may facilitate the discovery of developmental disorder biomarkers and therapeutic targets, enabling detailed, personalized, and precise folate treatment plan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.csbj.2021.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966843PMC
March 2021
-->