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  • 1
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 94, No. 8 ( 2023-08), p. 605-613
    Abstract: To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. Methods A retrospective observational study was conducted in 121 patients (2016–2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). Results Among cohort A (male:female=79:42; median age: 42 (14–78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p 〈 0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00–5352.00) vs 700.00 (76.70–2899.00), p 〈 0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23] , p =0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0–6) vs 0 (0–3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). Conclusions Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 1480429-3
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  • 2
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    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-8-2)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-8-2)
    Abstract: Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a newly defined meningoencephalomyelitis. The pathogenesis of GFAP-A is not well understood. The present study measured the expression levels of 200 serological cytokines in GFAP-A patients, NMOSD patients and healthy controls (HCs). The correlations between serum cytokine levels and clinical information in GFAP-A patients were analyzed. A total of 147 serological proteins were differentially expressed in GFAP-A patients compared to HCs, and 33 of these proteins were not observed in NMOSD patients. Serum levels of EG-VEGF negatively correlated with GFAP antibody titers, MIP-3 alpha positively correlated with clinical severity in GFAP-A patients, and LIGHT positively correlated with WBC counts and protein levels in the CSF of GFAP-A patients. These results suggest that GFAP and AQP4 astrocytopathy share some common pathology related to TNF signaling. Serum MIP 3 alpha may be a biomarker to assess clinical severity and a potential target for therapy of autoimmune GFAP astrocytopathy.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 3
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    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Bioengineering and Biotechnology Vol. 8 ( 2020-4-8)
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 8 ( 2020-4-8)
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2719493-0
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  • 4
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    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Cell and Developmental Biology Vol. 8 ( 2021-1-28)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 8 ( 2021-1-28)
    Abstract: Lung cancer is the first cause of cancer death, and gene copy number variation (CNV) is a vital cause of lung cancer progression. Prognosis prediction of patients followed by medication guidance by detecting CNV of lung cancer is emerging as a promising precise treatment in the future. In this paper, the differences in CNV and gene expression between cancer tissue and normal tissue of lung adenocarcinoma (LUAD) from The Cancer Genome Atlas Lung Adenocarcinoma data set were firstly analyzed, and greater differences were observed. Furthermore, CNV-driven differentially expressed long non-coding RNAs (lncRNAs) were screened out, and then, a competing endogenous RNA (ceRNA) regulatory network related to the gene CNV was established, which involved 9 lncRNAs, seven microRNAs, and 178 downstream messenger RNAs (mRNAs). Pathway enrichment analyses sequentially performed revealed that the downstream mRNAs were mainly enriched in biological pathways related to cell division, DNA repair, and so on, indicating that these mRNAs mainly affected the replication and growth of tumor cells. Besides, the relationship between lncRNAs and drug effects was explored based on previous studies, and it was found that LINC00511 and LINC00942 in the CNV-associated ceRNA network could be used to determine tumor response to drug treatment. As examined, the drugs affected by these two lncRNAs mainly targeted metabolism, target of rapamycin signaling pathway, phosphatidylinositol-3-kinase signaling pathway, epidermal growth factor receptor signaling pathway, and cell cycle. In summary, the present research was devoted to analyzing CNV, lncRNA, mRNA, and microRNA of lung cancer, and nine lncRNAs that could affect the CNV-associated ceRNA network we constructed were identified, two of which are promising in determining tumor response to drug treatment.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2737824-X
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Pediatrics Vol. 10 ( 2022-8-26)
    In: Frontiers in Pediatrics, Frontiers Media SA, Vol. 10 ( 2022-8-26)
    Abstract: Spastic paraplegia type 54 (SPG54) is a rare inherited autosomal recessive disorder, and a complex hereditary spastic paraplegia (HSP) caused by mutations in the phospholipase DDHD2 gene. SPG54 is characterized by early onset of spastic paraplegia, intellectual disability and dysplasia of corpus callosum. Case presentation We report a 9 years and 5 months old Chinese girl with progressive spasm of the lower limbs, muscle weakness and intellectual disability. Brain magnetic resonance imaging (MRI) showed periventricular leukomalacia and thinning of the corpus callosum. According to the Wechsler Intelligence Scale, her IQ is 42. By whole exome sequencing, novel compound heterozygous missense mutations in the DDHD2 gene [c.168G & gt;C, p.(Trp56Cys) and c.1505T & gt;C, p.(Phe502Ser)] were identified in the proband. Comparative amino acid sequence alignment across different species revealed that Trp56 and Phe502 in the DDHD2 protein were highly conserved during evolution. And multiple in silico prediction tools suggested that both mutations were deleterious. Conclusions Our study reports a very rare case of complicated HSP caused by two novel compound heterozygous mutations in the DDHD2 gene. Our findings expand the genetic spectrum of SPG54.
    Type of Medium: Online Resource
    ISSN: 2296-2360
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2711999-3
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  • 6
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2021
    In:  BMC Pediatrics Vol. 21, No. 1 ( 2021-12)
    In: BMC Pediatrics, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-12)
    Abstract: The Raynaud-Claes type of X-linked syndromic mental retardation (MRXSRC) is a very rare condition, by intellectual disability ranged from borderline to profound, impaired language development, brain abnormalities, facial dysmorphisms and seizures. MRXSRC is caused by variants in CLCN4 which encodes the 2Cl − /H + exchanger ClC-4 prominently expressed in brain. Case presentation We present a 3-year-old Chinese girl with intellectual disability, dysmorphic features, brain abnormalities, significant language impairment and autistic features. Brain magnetic resonance imaging (MRI) showed a thin corpus callosum, a mega cisterna magna and ventriculomegaly. Whole exome sequencing (WES) was performed to detect the molecular basis of the disease. It was confirmed that this girl carried a novel heterozygous missense variant (c.1343C  〉  T, p.Ala448Val) of CLCN4 gene, inherited from her mother. This variant has not been registered in public databases and was predicted to be pathogenic by multiple in silico prediction tools. Conclusion Our investigation expands the phenotype spectrum for CLCN4 variants with syndromic X-linked intellectual disability, which help to improve the understanding of CLCN4 -related intellectual disability and will help in genetic counselling for this family.
    Type of Medium: Online Resource
    ISSN: 1471-2431
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2041342-7
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  • 7
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    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Pediatrics Vol. 11 ( 2023-2-24)
    In: Frontiers in Pediatrics, Frontiers Media SA, Vol. 11 ( 2023-2-24)
    Abstract: Biallelic TENM3 variants were recently reported to cause non-syndromic microphthalmia with coloboma-9 (MCOPCB9) and microphthalmia and/or coloboma with developmental delay (MCOPS15). To date, only eight syndromic and non-syndromic microphthalmia cases with recessive TENM3 variants have been reported. Herein, we report two unrelated new cases with biallelic variants in TENM3 , widening the molecular and clinical spectrum. Regarding patient 1, WES revealed compound heterozygous variants in the TENM3 gene: c.3847_3855del; p.Leu1283_Ser1285del and c.3698_3699insA; p.Thr1233Thrfs*20 in the index patient, who was presenting with bilateral microphthalmia, congenital cataract, microcephaly, and global developmental delay. Regarding patient 2, compound missense heterozygous variants in the TENM3 gene were identified: c.941C  & gt; T; p.Ala314Val and c.6464T  & gt; C; p.Leu2155Pro in the 3-year-old boy, who presented with congenital esotropia, speech delay, and motor developmental delay. The clinical features of these two cases revealed high concordance with the previously reported cases, including microphthalmia and developmental delay. The presence of microcephaly in our patient potentially expands the neurologic phenotype associated with loss of function variants in TENM3 , as microcephaly has not previously been described. Furthermore, we present evidence that missense variants in TENM3 are associated with similar, but milder, ocular features.
    Type of Medium: Online Resource
    ISSN: 2296-2360
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2711999-3
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  • 8
    In: Applied Geophysics, Springer Science and Business Media LLC
    Type of Medium: Online Resource
    ISSN: 1672-7975 , 1993-0658
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2277458-0
    SSG: 6,25
    SSG: 16,13
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  • 9
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P2-13-11-P2-13-11
    Abstract: Backgrounds: Since human epidermal growth factor receptor 2 (HER2)-positive breast cancers may have different HER2/CEP17 ratios and HER2 copy numbers, outcomes of HER2-positive breast cancer patients treated with anti-HER2 neoadjuvant chemotherapy (NACT) may be different. The aim of this study is to explore the relationship between different groups of HER2 fluorescence in situ hybridization (FISH) positive patterns and response to anti-HER2 NACT. Methods: 513 HER2-positive invasive breast cancers who received anti-HER2 NACT in Fudan University Shanghai Cancer Center, during January 2015 to September 2020, were collected. According to FISH results, 513 patients were divided into three groups. Group A: HER2/CEP17 & lt; 2.0 and HER2 average copy number ≥6.0; Group B: HER2/CEP17≥2.0 and HER2 average copy number ≥4.0 and & lt; 6.0; Group C: HER2/CEP17≥2.0 and HER2 average copy number ≥6.0. Clinicopathological characteristics and pathological complete response(pCR) rates of three groups were analyzed. Results: All 513 patients were treated with anti-HER2 NACT. The anti-HER2 treatment included trastuzumab in 463 (90.3%) patients, trastuzumab plus pertuzumab in 21 (4.1%) patients, trastuzumab plus lapatinib in 3 (0.6%) patients, and trastuzumab plus pyrotinib in 1 (0.2%) patient. 25 (4.9%) cases were unblinded in clinical trials, who were treated either with trastuzumab plus pertuzumab or with trastuzumab plus pyrotinib. Among 513 patients, 237 cases (46.2%)were luminal B (hormone receptor positive and HER2 positive) and 276 cases (53.8%) were hormone receptor negative and HER2 overexpressed (HER2 overexpression type). According to IHC results, cases with HER2 1+,2+ and 3+ were 8 (1.6%), 123 (24.0%) and 382(74.5%), respectively. Among them, 0.0%, 25.2%, and 48.7% achieved pCR (p & lt;0.001). The pCR rate of HER2 overexpression type was higher than that of luminal B type (54.0% vs 28.7%, P & lt;0.001). Lymph nodes with metastasis after NACT in luminal B type was higher than that of HER2 overexpression type (43.0% vs 21.4%, P & lt;0.001). According to HER2-FISH results, 11 cases (2.1%) were group A, 28 cases (5.5%) were group B and 474 cases (92.4%) were group C. Compared with the pCR rate of group A (36.4%) and group C (44.5%), the pCR rate in group B (7.1%) was significantly lower (p & lt;0.001). Conclusions: Among HER2-positive breast cancers, HER2 protein expression level was positively correlated with pCR rate. Luminal B(HER2+)patients benefited less from anti-HER2 NACT than HER2 overexpression patients. Although all were invasive breast cancers with positive HER2-FISH results, patients with HER2/CEP17≥2.0 and HER2 copy number ≥4.0 and & lt;6.0 seemed to respond less favorably to anti-HER2 NACT compared with other groups. The biological characteristics of this group of patients are worthy of further study. Citation Format: Hong Lv, Qian-Ming Bai, Yin Liu, Zhong-Hua Wang, Ruo-Hong Shui, Hong-Fen Lu, Xiao-Li Xu, Bao-Hua Yu, Xiao-Yu Tu, Rui Bi, Yu-Fan Cheng, Xiao-Yan Zhou, Zhi-Min Shao, Wen-Tao Yang. Response to anti-HER2 neoadjuvant chemotherapy in invasive breast cancers with different HER2 FISH-positive patterns [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-11.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 10
    In: The Lancet Gastroenterology & Hepatology, Elsevier BV, Vol. 7, No. 5 ( 2022-05), p. 388-390
    Type of Medium: Online Resource
    ISSN: 2468-1253
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
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