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  • Frontiers Media SA  (619)
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  • 1
    Online Resource
    Online Resource
    Using two-step cluster analysis to classify inpatients with primary biliary cholangitis based on autoantibodies: A real-world retrospective study of 537 patients in China
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 13 ( 2023-1-4)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2023-1-4)
    Abstract: A variety of autoantibodies have been detected in primary biliary cholangitis (PBC), while the presence of autoantibody clusters and their clinical significance have not been fully understood. We aimed at defining autoantibody clusters and to better understand the clinical features and prognosis of PBC patients based on autoantibody clusters under real-world conditions. Methods We retrospectively analyzed 788 inpatients with PBC evaluated between October 2008 and July 2019, and included 537 patients. Nineteen autoantibodies which were measured routinely were investigated for cluster analysis. Two-step clustering, Kaplan-Meier survival, and Cox regression analyses were used. Results Five clusters were defined. A cluster of antinuclear antibodies (ANA) and anti-gp210 positive patients were identified with a high rate of cirrhosis at baseline and low survival rate; a cluster of ANA, anti-centromere antibodies (ACA) and/or anti-CENP-B female dominant patients with older disease onset, low level of platelet count at baseline, high rate of hepatic decompensation, and low survival rate was also characterized; and another cluster of anti-mitochondrial antibodies (AMA) and/or AMA-M2, anti-Ro52 and a high rate of anti-gp210 positive patients were identified with a high proportion of male patients and low survival rate. A subgroup of patients with anti-SSA and/or anti-SSB coexists with SjS was also identified; patients with only AMA and/or AMA-M2-positive with a benign clinical outcome and relatively high complication of non-alcoholic fatty liver disease (NAFLD) were also identified. Only anti-gp210 was considered as a significant predictor for poor outcomes especially in patients with cirrhosis. Conclusion Clustering methods allow the identification of distinct autoantibody profiles of PBC that form clinical subsets and can be useful for personalized approaches to diagnosis, clinical management, and the prediction of clinical outcomes. Anti-gp210 was the strongest predictive factor for poor outcomes especially in PBC patients with cirrhosis under real-world conditions.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2022.1098076
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 2
    Online Resource
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    DataSheet_2.zip
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-9-20)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-9-20)
    Abstract: The human leukocyte antigen (HLA) susceptibility gene is the main genetic risk factor for primary biliary cholangitis (PBC). The prognosis of patients with PBC is linked to gut microbiota dysbiosis. However, whether the HLA alleles are associated with the gut microbiota distribution and disease severity remains unknown. Methods A cohort of 964 Chinese patients with PBC was enrolled at Beijing YouAn Hospital, Beijing, China. High-resolution genotyping of the HLA class I and class II loci from 151 of these patients was performed using sequence-based PCR. Stool samples were collected from 43 of the 151 fully HLA-typed patients to analyze their microbiota compositions via 16S RNA gene sequencing. Results Of the 964 patients, the male:female ratio was 114:850, and 342 of these patients (35.5%) had already developed liver cirrhosis (LC) before enrollment. Patients with PBC showed a significantly higher frequency of HLA DRB1*08:03 than did the controls (21.2% vs. 9.0%, P =0.0001). HLA- DRB1*03:01 , DRB1*07:01 , DRB1*14:05 , and DRB1*14:54 frequencies were also increased but did not reach significance after Bonferroni’s correction. Conversely, the DQB1*03:01 frequency was significantly lower in patients with PBC than in the controls (24.5% vs. 39.2%, P =0.0010). The patients’ gut microbiota were analyzed from four perspectives. The microbial community abundances were significantly lower in FHRAC-positive patients (patients with a combination of five HLA DRB1 high-risk alleles) than in FHRAC-negative patients ( P & lt;0.05). Of the top 10 microbial genera, Lachnospiraceae_incertae_sedis was higher in the FHRAC-positive patients than in the FHRAC-negative patients ( P & lt;0.05). linear discriminant analysis (LDA) effect-size (LEfSe) analysis showed different microbes at different levels in the FHRAC-negative patients but not in the FHRAC-positive patients. DQB1*03:01 -positive patients contained mostly Lactobacillaceae at the family level. A comparison of the FHRAC-positive patients with and without liver cirrhosis showed that the abundances of Veillonella were significantly higher in patients with cirrhosis and FHRAC than in those without cirrhosis and are FHRAC-negative. Conclusion The HLA class II genes may influence the gut microbiota compositions in patients with PBC. Differential gut microbiota were expressed at different taxonomic levels. Some bacterial abundances may be increased in FHRAC-positive patients with PBC and cirrhosis.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.984697
    DOI: 10.3389/fimmu.2022.984697.s001
    DOI: 10.3389/fimmu.2022.984697.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 3
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    Novel Mutations in the GTPBP3 Gene for Mitochondrial Disease and Characteristics of Related Phenotypic Spectrum: The First Three Cases From China
    Frontiers Media SA ; 2021
    In:  Frontiers in Genetics Vol. 12 ( 2021-7-1)
    Details
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 12 ( 2021-7-1)
    Abstract: Combined Oxidative Phosphorylation Deficiency 23 (COXPD23) caused by mutations in GTPBP3 gene is a rare mitochondrial disease, and this disorder identified from the Chinese population has not been described thus far. Here, we report a case series of three patients with COXPD23 caused by GTPBP3 mutations, from a severe to a mild phenotype. The main clinical features of these patients include lactic acidosis, myocardial damage, and neurologic symptoms. Whole genome sequencing and targeted panels of candidate human mitochondrial genome revealed that patient 1 was a compound heterozygote with novel mutations c.413C & gt; T (p. A138V) and c.509_510del (p. E170Gfs ∗ 42) in GTPBP3 . Patient 2 was a compound heterozygote with novel mutations c.544G & gt; T (p. G182X) and c.785A & gt; C (p.Q262P), while patient 3 was a compound heterozygote with a previously reported mutation c.424G & gt; A (p.E142K) and novel mutation c.785A & gt; C (p.Q262P). In conclusion, we first describe three Chinese individuals with COXPD23, and discuss the genotype-phenotype correlations of GTPBP3 mutations. Our findings provide novel information in the diagnosis and genetic counseling of patients with mitochondrial disease.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    URL: Article
    DOI: 10.3389/fgene.2021.611226
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606823-0
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  • 4
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    Online Resource
    DataSheet_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-6-11)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-6-11)
    Abstract: Epithelial-mesenchymal transition (EMT) plays an important role in the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We hypothesized that germline variants in the major EMT regulatory genes ( SNAIL1 , ZEB1 , ZEB2 , TWIST1 ) may influence the development of HBV-related HCC. We included 421 cases of HBsAg-positive patients with HCC, 1371 cases of HBsAg-positive subjects without HCC [patients with chronic hepatitis B (CHB) or liver cirrhosis (LC)] and 618 cases of healthy controls in the case-control study. Genotype, allele, and haplotype associations in the major EMT regulatory genes were tested. Environment-gene and gene-gene interactions were analysed using the non-parametric model-free multifactor dimensionality reduction (MDR) method. The SNAIL1 rs4647958T & gt;C was associated with a significantly increased risk of both HCC (CT+CC vs . TT: OR =1.559; 95% confidence interval [ CI ], 1.073-2.264; P =0.020) and CHB+LC (CT+CC vs . TT: OR =1.509; 95% CI , 1.145-1.988; P =0.003). Carriers of the TWIST1 rs2285681G & gt;C (genotypes CT+CC) had an increased risk of HCC (CG+CC vs . GG: OR =1.407; 95% CI , 1.065-1.858; P =0.016). The ZEB2 rs3806475T & gt;C was associated with significantly increased risk of both HCC ( P recessive =0.001) and CHB+LC ( P recessive & lt;0.001). The CG haplotype of the rs4647958/rs1543442 haplotype block was associated with significant differences between healthy subjects and HCC patients ( P =0.0347). Meanwhile, the CT haplotype of the rs2285681/rs2285682 haplotype block was associated with significant differences between CHB+LC and HCC patients ( P =0.0123). In MDR analysis, the combination of TWIST1 rs2285681, ZEB2 rs3806475, SNAIL1 rs4647958 exhibited the most significant association with CHB+LC and Health control in the three-locus model. Our results suggest significant single-gene associations and environment-gene/gene-gene interactions of EMT-related genes with HBV-related HCC.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2021.564477
    DOI: 10.3389/fonc.2021.564477.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 5
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    Spectrum of underlying diseases in syncope and treatment of neurally-mediated syncope in children and adolescents over the past 30 years: A single center study
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2022-11-28)
    Details
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-11-28)
    Abstract: Syncope is the primary cause of transient loss of consciousness, which causes severe physical and mental burdens to children and adolescents. Objective The study was designed to analyze the spectrum of underlying diseases of syncope and treatment options for neurally-mediated syncope (NMS) in Chinese children and adolescents. Methods Medical records including history, physical examination, blood biochemistry, standing test, head-up tilt (HUTT), sitting-up test, electroencephalogram (EEG), electrocardiogram (ECG), and echocardiography were retrospectively studied in children and adolescents admitted to the National Pediatric Syncope Center, Department of Pediatrics, Peking University First Hospital between 1992 and 2021. All the data were collected from the Beijing Kaihua Medical Management System (Kaihua, Beijing, China). Children who met the syncope diagnostic criteria were enrolled in the study. The spectrum of the underlying diseases of syncope in children and adolescents and the treatment options of NMS were analyzed. Results A total of 1,947 children and adolescents with syncope were admitted, including 869 males (44.63%) and 1,078 females (55.37%) aged 1–18 years, with an average age of 11.1 ± 3.1 years. The number of children and adolescents with syncope displayed a gradually increasing trend between 1992 and 2021 except after 2020. NMS proportion increased, and the proportion of unexplained syncope decreased (χ 2 = 128.839, P & lt; 0.01). The treatment options of NMS mainly included autonomic nervous function exercise (549, 34.46%), oral rehydration salt (ORS; 445, 27.94%), metoprolol (219, 13.75%), midodrine (120, 7.53%), ORS plus metoprolol (139, 8.73%), ORS plus midodrine (120, 7.53%), and pacemakers (1, 0.06%). Patients with vasovagal syncope (VVS) coexisting with postural orthostatic tachycardia syndrome (POTS) were more likely to take pharmacological treatments than those with VVS or POTS only (χ 2 = 41.696, P & lt; 0.01). Conclusion The number of children with syncope displayed an increasing trend before 2020, and the proportion of unexplained syncope decreased. Autonomic nervous function exercise was the most common treatment for children and adolescents with NMS. Children with VVS coexisting with POTS were more likely to receive pharmacological treatments than those with either.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    DOI: 10.3389/fcvm.2022.1017505
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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  • 6
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    Table_6.doc
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-3-2)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-3-2)
    Abstract: Anaplastic lymphoma kinase (ALK) rearrangement status examination has been widely used in clinic for non-small cell lung cancer (NSCLC) patients in order to find patients that can be treated with targeted ALK inhibitors. This study intended to non-invasively predict the ALK rearrangement status in lung adenocarcinomas by developing a machine learning model that combines PET/CT radiomic features and clinical characteristics. Methods Five hundred twenty-six patients of lung adenocarcinoma with PET/CT scan examination were enrolled, including 109 positive and 417 negative patients for ALK rearrangements from February 2016 to March 2019. The Artificial Intelligence Kit software was used to extract radiomic features of PET/CT images. The maximum relevance minimum redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) logistic regression were further employed to select the most distinguishable radiomic features to construct predictive models. The mRMR is a feature selection method, which selects the features with high correlation to the pathological results (maximum correlation), meanwhile retain the features with minimum correlation between them (minimum redundancy). LASSO is a statistical formula whose main purpose is the feature selection and regularization of data model. LASSO method regularizes model parameters by shrinking the regression coefficients, reducing some of them to zero. The feature selection phase occurs after the shrinkage, where every non-zero value is selected to be used in the model. Receiver operating characteristic (ROC) analysis was used to evaluate the performance of the models, and the performance of different models was compared by the DeLong test. Results A total of 22 radiomic features were extracted from PET/CT images for constructing the PET/CT radiomic model, and majority of these features used were based on CT features (20 out of 22), only 2 PET features were included (PET percentile 10 and PET difference entropy). Moreover, three clinical features associated with ALK mutation (age, burr and pleural effusion) were also employed to construct a combined model of PET/CT and clinical model. We found that this combined model PET/CT-clinical model has a significant advantage to predict the ALK mutation status in the training group (AUC = 0.87) and the testing group (AUC = 0.88) compared with the clinical model alone in the training group (AUC = 0.76) and the testing group (AUC = 0.74) respectively. However, there is no significant difference between the combined model and PET/CT radiomic model. Conclusions This study demonstrated that PET/CT radiomics-based machine learning model has potential to be used as a non-invasive diagnostic method to help diagnose ALK mutation status for lung adenocarcinoma patients in the clinic.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
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    URL: Article
    URL: Article
    URL: Article
    URL: Article
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    URL: Article
    DOI: 10.3389/fonc.2021.603882
    DOI: 10.3389/fonc.2021.603882.s001
    DOI: 10.3389/fonc.2021.603882.s002
    DOI: 10.3389/fonc.2021.603882.s003
    DOI: 10.3389/fonc.2021.603882.s004
    DOI: 10.3389/fonc.2021.603882.s005
    DOI: 10.3389/fonc.2021.603882.s006
    DOI: 10.3389/fonc.2021.603882.s007
    DOI: 10.3389/fonc.2021.603882.s008
    DOI: 10.3389/fonc.2021.603882.s009
    DOI: 10.3389/fonc.2021.603882.s010
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 7
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    Inhibition of Connexin 43 and Phosphorylated NR2B in Spinal Astrocytes Attenuates Bone Cancer Pain in Mice
    Frontiers Media SA ; 2018
    In:  Frontiers in Cellular Neuroscience Vol. 12 ( 2018-5-8)
    Details
    In: Frontiers in Cellular Neuroscience, Frontiers Media SA, Vol. 12 ( 2018-5-8)
    Type of Medium: Online Resource
    ISSN: 1662-5102
    URL: Article
    DOI: 10.3389/fncel.2018.00129
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2452963-1
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  • 8
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    Changes of serofast status in HIV negative asymptomatic neurosyphilis patients after treatment
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-8-3)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-8-3)
    Abstract: Serofast status after therapy in syphilis patients is a common phenomenon. A proportion of patients who have serofast status exhibit abnormal cerebrospinal fluid test results, which can be defined as asymptomatic neurosyphilis (ANS); however, it remains unclear whether ANS patients can achieve serological cure after anti-neurosyphilis treatment as quickly as other serofast patients. In this study, non-treponemal pallidum antibody serological responses were studied in ANS and serofast control patients, and the cumulative rates of serological cure in the ANS group were 9.6, 22.1, 25.9, and 30.2% in 3, 6, 9, and 12 month after treatment, which were statistically higher than those of the serofast control group. The change gap in serological cure rates was even more pronounced within 6 months after treatment, but the majority of ANS patients had no change in serofast status at 12 months after treatment. Our study indicates that anti-neurosyphilis therapy can partially change the serofast status. As serofast status cannot easily be changed even under neurosyphilis treatment in the majority of patients, the pathogenesis of this condition needs further research.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    DOI: 10.3389/fmed.2022.938016
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 9
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    Data_Sheet_5.PDF
    Frontiers Media SA ; 2022
    In:  Frontiers in Neurology Vol. 13 ( 2022-5-26)
    Details
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2022-5-26)
    Abstract: Next generation sequencing results in an explosive identification of rare variants of RYR1 , making the correlation between phenotype and genotype complicated. We analyzed the data of 33 patients with RYR1 -related myopathy, attempting to elucidate correlations between phenotype, genotype, and protein structure of RyR1. Methods Clinical, histopathologic, and genetic data were evaluated, and variants were mapped to the cryo-EM RyR1 structure. The three-dimensional structure of the variant on RyR1 was analyzed. Results The clinical spectrum was highly variable regardless of the mode of inheritance. Recessive variations were associated with more severe feeding problems and respiratory insufficiency in infancy ( p & lt; 0.05). Forty pathogenic and likely pathogenic variations were identified, and 14 of them were novel. Missense was the most common variation type regardless of inheritance mode. Arginine (15/45) was the most frequently involved residue. All but one dominant variation clustered in Pore forming and pVSD domains, while recessive variations enriched in Bsol (7/25) and SPRYs (6/25) domains. Analysis of the spatial structure of variants showed that dominant variants may impact RyR1 mainly by breaking down hydrogen or electrovalent bonds (10/21); recessive variants located in different domains may impact the function of RyR1 through different pathways. Variants located in RyR1 coupling sites (PY1 & amp;2 and the outermost of Bsol) may cause the most severe clinical manifestation. Conclusion Clinical diversity of RYR1- related myopathy was impacted by the inheritance mode, variation type, and variant location. Dominant and recessive variants have different sensitive domains impacting the function of RyR1 through different pathways.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fneur.2022.870285
    DOI: 10.3389/fneur.2022.870285.s001
    DOI: 10.3389/fneur.2022.870285.s002
    DOI: 10.3389/fneur.2022.870285.s003
    DOI: 10.3389/fneur.2022.870285.s004
    DOI: 10.3389/fneur.2022.870285.s005
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564214-5
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  • 10
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    The Delivery of Extracellular Vesicles Loaded in Biomaterial Scaffolds for Bone Regeneration
    Frontiers Media SA ; 2020
    In:  Frontiers in Bioengineering and Biotechnology Vol. 8 ( 2020-8-19)
    Details
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 8 ( 2020-8-19)
    Type of Medium: Online Resource
    ISSN: 2296-4185
    URL: Article
    DOI: 10.3389/fbioe.2020.01015
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2719493-0
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