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OBJECTIVES: This study aimed to analyse the immune cell profiles of adult-onset Still's disease (AOSD) and to stratify disease-associated endotypes. METHODS: We included 95 cases of treatment-naïve patients with AOSD and 66 cases of healthy controls. Patients with AOSD were classified via an unbiased hierarchical cluster analysis based on circulating immune cells. Their clinical and laboratory characteristics, treatment management, systemic scores and outcomes were then analysed. RESULTS: The proportions of neutrophils and CD8+ T cells were significantly higher while monocytes and natural killer and CD4+ T cells were decreased in patients with AOSD (all P < 0.005). Unbiased hierarchical cluster analysis classified 95 AOSD into three endotype-based groups: group 1 had the highest percentage of neutrophils (neu-dominant group), group 2 had the highest percentage of monocytes (mono-dominant group) and group 3 had the highest percentage of CD8+ T cells (CD8-dominant group). Patients in group 3 had the highest systemic score at diagnosis and were more likely to have pulmonary infiltrates, pericarditis, splenomegaly and poorer treatment responses. A correlation study revealed that the CD4 to CD8 ratio was negatively correlated with the systemic score and positively correlated with treatment response in patients with AOSD (P = 0.001 and P = 0.0091). During the 24.6 (15.2) months of follow-up, the highest total number of disease flares occurred in group 3 (P < 0.0001). CONCLUSION: Hierarchical cluster analysis of peripheral immune cells classified AOSD into three disease-related endotypes. Group 3 showed higher systemic score and poorer treatment responses.
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Enfermedad de Still del Adulto , Adulto , Humanos , Enfermedad de Still del Adulto/tratamiento farmacológico , Biomarcadores , Linfocitos T CD8-positivos , Monocitos , Análisis por ConglomeradosRESUMEN
OBJECTIVES: This study evaluated the characteristics of serosal involvement in adult-onset Still's disease (AOSD). METHODS: Patients meeting the Yamaguchi classification criteria were classified into AOSD with and without serosal involvement according to their manifestations and sonography/radiography. Clinical data was retrospectively reviewed from 102 patients with AOSD in two centres. RESULTS: Forty-two patients (41.2%) had serosal involvement. The frequencies of pulmonary infiltrate and impaired liver function were significantly higher in patients with serosal involvement (p = .002 and p = .007, respectively), who also had a higher modified systemic score (p = .009). In addition, the percentages of CD3+ T cells (p < .001) and, especially, the CD8+ T cells (p = .004) were significantly increased in the peripheral blood of AOSD patients with serosal involvement. Notably, patients with serosal involvement were more likely to develop macrophage activation syndrome (p = .047) and a chronic pattern (p = .016) during the follow-up. CONCLUSIONS: Patients with serosal involvement demonstrated the more severe disease activity and different immune phenotypes; these patients were more likely to develop macrophage activation syndrome, and they may require more aggressive treatment at an early time to control their systemic inflammation.
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Enfermedades Pulmonares , Síndrome de Activación Macrofágica , Enfermedad de Still del Adulto , Humanos , Estudios Retrospectivos , Enfermedad de Still del Adulto/complicaciones , Enfermedad de Still del Adulto/diagnóstico por imagen , Enfermedad de Still del Adulto/tratamiento farmacológico , InflamaciónRESUMEN
BACKGROUND: To identify the genetic mutation of a four-generation autosomal dominant congenital cataract family in China. METHODS: Targeted region sequencing containing 778 genes associated with ocular diseases was performed to screen for the potential mutation, and Sanger sequencing was used to confirm the mutation. The homology model was constructed to identify the protein structural change, several online software were used to predict the mutation impact. CLUSTALW was used to perform multiple sequence alignment from different species. RESULTS: A novel heterozygous mutation, GJA8 NM_005267.5: c.124G > A, p.(E42K) was found, which cosegregated with congenital cataract phenotype in this family. Bioinformatics analysis of the mutation showed that the surface potential diagram of proteins changed. Several online programs predicted the mutation was 'Pathogenic', 'Damaging', 'Disease causing' or 'Deleterious'. CONCLUSIONS: A novel mutation NM_005267.5(GJA8):c.124G > A was identified in our study. Our finding can broaden the mutation spectrum of GJA8, enrich the phenotype-genotype correlation of congenital cataract and help to better understand the genetic background of congenital cataract.
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Catarata , Conexinas , Secuencia de Bases , Catarata/congénito , Catarata/genética , Conexinas/genética , Análisis Mutacional de ADN , Humanos , Mutación , Mutación Missense , LinajeRESUMEN
Introduction: Psoriasis is an immune-mediated systemic disease. Neutrophils are enriched in psoriasis lesions and can form neutrophil extracellular traps (NETs) to activate keratinocytes. Receptor-interacting protein kinase RIPK1 and RIPK3 are involved in necroptosis and NET formation. Aim: To elucidate whether RIPK1 regulates circulating neutrophils to form NETs and inflammation in psoriasis. Material and methods: Blood samples of psoriasis patients (n = 20) and healthy controls (n = 20) were detected by flow cytometry. The expression level of RIPK1/3 in isolated circulating neutrophils from psoriasis patients (n = 17) and healthy controls (n = 17) was examined by quantitative real-time PCR. SYTOX Green dye and PicoGreen reagent were used to detect NET formation and DNA release in neutrophils under the stimulation of phorbol 12-myristate 13-acetate (PMA) and necrostain-1 (Nec-1). Correlation analysis was performed between RIPK1/3 expression and Psoriasis Area Severity Index (PASI), neutrophil-to-lymphocyte ratio (NLR). Results: RIPK1 and RIPK3 expression in protein levels were decreased in monocytes and neutrophils from peripheral blood of psoriasis patients. In isolated psoriasis neutrophils, RIPK1 and Caspase8 mRNA were downregulated while RIPK3 and MLKL mRNA were elevated, leading to the necroptosis pathway. In addition, RIPK1-inhitor-necrostatin-1 (Nec-1) enhanced NETosis in psoriasis neutrophils in vitro. More importantly, there is a negative correlation between RIPK1 and psoriasis disease severity. Conclusions: Our data demonstrated that downregulated RIPK1 expression in psoriasis neutrophils may enhance NET generation. RIPK1 may be identified as a novel therapeutic target in psoriasis.
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BACKGROUND: The etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16 s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free (GF) mice. RESULTS: Compared to the healthy controls, we found no significant different microbial diversity but some significantly different species in SLE patients including Turicibacter genus and other 5 species. Fecal transfer from SLE patients to GF mice caused GF mice to develop a series of lupus-like phenotypic features, including increased serum autoimmune antibodies, imbalanced cytokines, altered distribution of immune cells in mucosal and peripheral immune response, and upregulated expression of genes related to SLE in recipient mice that received SLE fecal microbiota transplantation (FMT). Moreover, the metabolism of histidine was significantly altered in GF mice treated with SLE patient feces, as compared to those which received healthy fecal transplants. CONCLUSIONS: Overall, our results describe a causal role of aberrant gut microbiota in contributing to the pathogenesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms intertwined with autoimmune activation in SLE.
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Autoinmunidad/inmunología , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Inflamación/inmunología , Lupus Eritematoso Sistémico/microbiología , Animales , Femenino , Vida Libre de Gérmenes , Histidina/metabolismo , Humanos , Ratones , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: To explore the molecular genetic cause of a four-generation autosomal dominant retinitis pigmentosa family in China. METHODS: Targeted region sequencing was performed to detect the potential mutation, and Sanger sequencing was used to validate the mutation. Multiple sequence alignment from different species was performed by CLUSTALW. The structures of wild-type and the mutant RHO were modeled by Swiss-Model Server and shown using a PyMOL Molecular Graphic system. RESULTS: A novel heterozygous nonsense mutation (c.1015 A > T, p.Lys339Ter, p.K339X) within RHO, which cosegregated with retinitis pigmentosa phenotype was detected in this family. Bioinformatics analysis showed the mutation was located in a highly conserved region, and the mutation was predicted to be pathogenic. CONCLUSIONS: We identified a novel heterozygous nonsense mutation of RHO gene in a Chinese family with retinitis pigmentosa by target region sequencing and our bioinformatics analysis indicated that the mutation is pathogenic. Our results can broaden the spectrum of RHO gene mutation and enrich the phenotype-genotype correlation of retinitis pigmentosa.
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Codón sin Sentido , Retinitis Pigmentosa , China/epidemiología , Heterocigoto , Humanos , Linaje , Retinitis Pigmentosa/genéticaRESUMEN
Elevated intraocular pressure, a major risk factor of glaucoma, is caused by the abnormal function of trabecular outflow pathways. Human trabecular meshwork (HTM) tissue plays an important role in the outflow pathways. However, the molecular mechanisms that how TM cells respond to the elevated IOP are largely unknown. We cultured primary HTM cells on polyacrylamide gels with tunable stiffness corresponding to Young's moduli ranging from 1.1 to 50 kPa. Then next-generation RNA sequencing (RNA-seq) was performed to obtain the transcriptomic profiles of HTM cells. Bioinformatics analysis revealed that genes related to glaucoma including DCN, SPARC, and CTGF, were significantly increased with elevated substrate stiffness, as well as the global alteration of HTM transcriptome. Extracellular matrix (ECM)-related genes were selectively activated in response to the elevated substrate stiffness, consistent with the known molecular alteration in glaucoma. Human normal and glaucomatous TM tissues were also obtained to perform RNA-seq experiments and supported the substrate stiffness-altered transcriptome profiles from the in vitro cell model. The current study profiled the transcriptomic changes in human TM cells upon increasing substrate stiffness. Global change of ECM-related genes indicates that the in vitro substrate stiffness could greatly affect the biological processes of HTM cells. The in vitro HTM cell model could efficiently capture the main pathogenetic process in glaucoma patients, and provide a powerful method to investigate the underlying molecular mechanisms.
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Glaucoma/metabolismo , Malla Trabecular/metabolismo , Transcriptoma , Biomarcadores/metabolismo , Biología Computacional , Módulo de Elasticidad , Matriz Extracelular/metabolismo , Perfilación de la Expresión Génica , Marcadores Genéticos , Humanos , Presión Intraocular , Presión , RNA-Seq , Especificidad por SustratoRESUMEN
BACKGROUND: To explore the molecular genetic cause of a four-generation autosomal dominant congenital cataract family in China. METHODS: Targeted region sequencing was performed to screen for the potential mutation, and Sanger sequencing was used to confirm the mutation. The homology model was constructed to identify the protein structural change, PolyPhen-2 and Provean were used to predict the mutation impact. Functional and cellular analysis of the wild and mutant GJA8 were performed in DF-1 cells by western blotting, dye uptake assay, immunofluorescence, Annexin V-FITC staining. RESULTS: A novel heterozygous mutation (c.205G > A; p.Ala69Thr) was identified within GJA8, which cosegregated with congenital cataract phenotype in this family. Bioinformatics analysis showed the mutation was located in a highly conserved region, and the mutation was predicted to be pathogenic. Function analysis indicated that the mutation inhibited GJA8 hemichannel activity, reduced cell tolerance to oxidative stress, changed the protein distribution pattern and inhibited the cell growth. CONCLUSIONS: We have identified a novel missense mutation in GJA8 (c.205G > A, p.Ala69Thr) in a four-generation Chinese family and our results will further broaden the gene mutation spectrum of GJA8.
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Catarata , Conexinas , Mutación Missense , Pueblo Asiatico , Catarata/congénito , Catarata/genética , China , Conexinas/genética , Análisis Mutacional de ADN , Proteínas del Ojo/genética , Humanos , Mutación , LinajeRESUMEN
BACKGROUND: To introduce a novel protocol to treat refractory acute primary angle closure (APAC): transscleral cyclophotocoagulation (TCP) followed by cataract surgery. METHODS: Thirteen APAC eyes (13 patients) were enrolled in this prospective case series as study group. All patients underwent emergency TCP (20 pulses of 2000 mW during 2000 ms applied to the inferior quadrant) followed by scheduled cataract surgery. They were compared to 13 age- and gender-matched patients treated with emergency phacotrabeculectomy. We recorded intraocular pressure (IOP), best corrected visual acuity (BCVA), and complications, and several ultrasound biomicroscopy (UBM) parameters before and after TCP. RESULTS: In the study group, IOP decreased from 51.5 ± 7.0 mmHg (mean ± standard deviation) before TCP to 16.4 ± 5.4 mmHg 1 day after TCP (P < 0.001). At 6 months, there was no significant difference in IOP between the study group (14.0 ± 3.4 mmHg) and control group (16.7 ± 4.3 mmHg; P = 0.090); IOP lowering medications were used by 0/13 in the study group and 2/13 patients in the control group (P = 0.48). At 6 months, there was no significant difference in BCVA between the study group and the control group (20/25 (20/200 to 20/25) and 20/30 (20/50 to 20/25), respectively; P = 1.0). The UBM parameters anterior chamber depth (P = 0.016), angle-opening distance at 500 µm (P = 0.011), and maximum ciliary body thickness (P < 0.001) increased significantly while the iris-ciliary process distance decreased significantly (P = 0.020) after TCP. CONCLUSIONS: TCP effectively lowers IOP and modifies the anterior chamber morphology in APAC; TCP followed by cataract surgery can be considered an alternative to treat refractory APAC but needs further evaluation. TRIAL REGISTRATION: This project was registered in Chinese Clinical Trial Registry (ChiCTR1800017475) at July, 31, 2018 (http://www.chictr.org.cn/edit.aspx?pid=29629&htm=4).
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Cuerpo Ciliar/cirugía , Glaucoma de Ángulo Cerrado/cirugía , Coagulación con Láser/métodos , Láseres de Semiconductores/uso terapéutico , Facoemulsificación , Enfermedad Aguda , Anciano , Cuerpo Ciliar/diagnóstico por imagen , Femenino , Glaucoma de Ángulo Cerrado/diagnóstico por imagen , Glaucoma de Ángulo Cerrado/fisiopatología , Humanos , Presión Intraocular/fisiología , Masculino , Microscopía Acústica , Persona de Mediana Edad , Estudios Prospectivos , Esclerótica , Microscopía con Lámpara de Hendidura , Tonometría Ocular , Trabeculectomía , Agudeza Visual/fisiologíaRESUMEN
BACKGROUND/AIMS: Neutrophil extracellular traps (NETs) are known to play an important role in systemic lupus erythematosus (SLE) by triggering innate and adaptive immune responses. The molecular mechanisms responsible for their formation in SLE are still unclear. In this study, we aim to characterize the role of the receptor-interacting protein kinase-1 (RIPK1), a homologous serine/threonine kinase previously implicated in the regulation of necroptosis and tissue injury, in decreasing neutrophil death and formation of NETs, and to investigate the clinical implications of RIPK1 in SLE. METHODS: Patients with SLE (n = 50) and healthy donors (n = 35) were enrolled in in vitro studies. Management of SLE patients was evaluated using the SLE disease activity index 2000 (SLEDAI-2K) score and laboratory variables. The mRNA level of RIPKs was measured by quantitative polymerase chain reaction (qPCR). Intracellular RIPK1 and RIPK3 production by peripheral blood leukocytes was detected by four-color flow cytometry and confirmed by automatic western blotting. TNF-α, IFN-γ, IL-1ß, IL-2, IL-8, IL-18, and RIPK1 were measured by enzyme-linked immunosorbent assay. Cell death was assayed by Sytox green dye from peripheral neutrophils stimulated by RIPK-1-stabilizer necrostatin-1 (nec-1) and phorbol 12-myristate 13-acetate (PMA). Immunofluorescence staining and confocal microscopy were used to detect NET formation ex vivo. Quantification of NETs was determined by fluorescence spectrometry. RESULTS: IFN-γ, IL-1ß, IL-8, and IL-18 levels in serum were increased in SLE patients compared to controls. However, the expression of TNF-α, IL-2, and RIPK1 were decreased. In addition, we observed significant differences in the expression of RIPK1 in peripheral blood leukocytes. Of all the leukocytes, RIPK1 expression was significantly lower in neutrophils. Furthermore, we studied NETs formation in neutrophils of SLE with decreased RIPK1 expression, and these show increased susceptibility to NETosis, when stimulated with PMA and/or nec-1. Importantly, RIPK1 expression in neutrophils negatively correlated with ESR, CRP, 24-hour urine total protein, and the disease activity index in SLE. CONCLUSION: These data represent the first report of decreased RIPK1 expression in neutrophils of SLE patients and imply that RIPK1 may be involved in neutrophil death and NET formation. We suggest that RIPK1 is a potential biomarker to predict disease activity.
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Regulación hacia Abajo , Trampas Extracelulares/genética , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/patología , Neutrófilos/patología , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Muerte Celular , Citocinas/sangre , Femenino , Humanos , Lupus Eritematoso Sistémico/sangre , Masculino , Neutrófilos/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/análisisRESUMEN
Small RNA (microRNA or miRNA) is a kind of small noncoding single-stranded RNA that regulates complementary mRNA at the posttranscriptional level in eukaryotic organisms. As important regulatory factors, miRNAs play an important role in the occurrence and development of glaucoma and widely participate in regulating biological processes of glaucoma-related genes. This article reviews the connection between the aqueous humor, trabecular meshwork, the apoptosis of retinal ganglion cells, and miRNA.
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Glaucoma/metabolismo , MicroARNs/fisiología , Apoptosis/fisiología , Humor Acuoso/metabolismo , Humanos , Células Ganglionares de la Retina/metabolismo , Malla Trabecular/metabolismoRESUMEN
OBJECTIVE: To investigate the effect of allergic rhinitis (AR) and its intervention on disease condition and medications in patients with juvenile-onset systemic lupus erythematosus (JSLE). METHODS: The clinical data of 96 children diagnosed with JSLE were collected, and according to the presence or absence of AR or other allergic diseases, they were divided into AR group (n=44), non-AR group (n=20), and non-allergic group (n=32). The children in the AR group were randomly administered with or without intervention (n=22 each). All the children were given standard JSLE treatment. The systemic lupus erythematosus disease active index (SLEDAI) and application of hormones and immunosuppressants were compared between groups. RESULTS: The AR and non-AR groups had significantly higher SLEDAI scores, daily cumulative doses of glucocorticoids, and number of types of immunosuppressants used than the non-allergic group before treatment (P<0.05), while there were no significant differences between the AR and non-AR groups (P>0.05). After one month of treatment, the AR group with intervention had significantly lower SLEDAI scores and daily cumulative doses of glucocorticoids than the AR group without intervention (P<0.05), while there was no significant difference in the application of immunosuppressants between these two groups (P>0.05). After 3 and 6 months of treatment, the AR group with intervention had significantly lower SLEDAI scores, daily cumulative doses of glucocorticoids, and number of types of immunosuppressants than the AR group without intervention (P<0.05). CONCLUSIONS: JSLE combined with allergic diseases such as AR has an adverse effect on disease condition and treatment, and the intervention for AR helps with the control of JSLE.
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Lupus Eritematoso Sistémico/tratamiento farmacológico , Rinitis Alérgica/complicaciones , Adolescente , Niño , Preescolar , Femenino , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Interleucina-17/sangre , Interleucinas , Lupus Eritematoso Sistémico/inmunología , Masculino , Índice de Severidad de la EnfermedadRESUMEN
UNLABELLED: We aimed to assess the influence of co-existing atopy on the prognosis of enthesitis-related arthritis (ERA). Patients diagnosed with ERA between March 2006 and August 2012 were enrolled in a prospective cohort study and followed for 2 years. Management of patients was evaluated using the American College of Rheumatology (ACR) pediatric (Pedi) 30/50/70 criteria and laboratory variables. A total of 151 ERA patients were enrolled at diagnosis and were divided into those with atopy (n = 62) and those without (n = 89). When compared with the non-atopic group, atopic patients had significantly more active joints at disease onset (4.72 vs. 3.75), more joints with limitation of motion (LOM) (1.45 vs. 0.87), more painful joints (3.61 vs. 2.80), and more swollen joints (1.02 vs. 0.69) (p < 0.05 for all comparisons). At 3, 6, 12, 18, and 24 months, fewer ERA patients with atopy reached the ACR Pedi 50 and 70 criteria (at 3 months, 25.8 vs. 60.7 % and 11.3 vs. 34.8 %, respectively; at 6 months, 50 vs. 77.5 % and 22.6 vs. 58.4 %, respectively; at 12 months, 53.2 vs. 70.8 % and 33.9 vs. 55.1 %, respectively; at 18 months, 62.9 vs. 86.5 % and 56.5 vs. 78.7 %, respectively; at 24 months, 66.1 vs. 89.9 % and 61.3 vs. 78.7 %, respectively; all p < 0.05). During the 2 years of follow-up, the number of flares was significantly higher in ERA patients with co-existing atopy (1.48 vs. 0.70, p < 0.05). CONCLUSION: Co-existing atopy in children with ERA may exert an adverse influence on ERA, with atopic patients manifesting more active disease at diagnosis and poorer outcome. \
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Artritis Juvenil/complicaciones , Hipersensibilidad/complicaciones , Adolescente , Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/fisiopatología , Niño , Preescolar , Estudios de Cohortes , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Hipersensibilidad/fisiopatología , Masculino , Pronóstico , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Pruebas CutáneasRESUMEN
Background: To explore the genetic defects of a Chinese family with complete Schubert-Bornschein type congenital stationary night blindness (CSNB). Methods: A Chinese family with complete Schubert-Bornschein type CSNB was enrolled in this study. The detailed ocular presentations of the patient were recorded. Targeted gene sequencing including 156 genes related to retinal diseases was used to detect the gene mutation. Sanger sequencing was performed to validate the potential pathogenic variants, and segregation analysis was performed on all available family members. Bioinformatics analysis was performed to predict the impact of the mutations. Results: By targeted gene sequencing and Sanger sequencing, we identified compound heterozygous mutations in GRM6: c.152G>T (p.Gly51Val) and c.727delG (p.Val243SerfsX21). Segregation analysis demonstrated that the mother of the proband carried the missense mutation (c.152G>T) while her father carried the frameshift mutation (c.727delG), indicating CSNB was autosomal recessively inherited in this family. Several bioinformatics prediction programs revealed the mutations were "Damaging" or "Disease Causing" and conservation analysis showed both the codons Gly51 and Val243 were highly conserved among species, suggesting the changes were pathogenic. Conclusion: By targeted gene sequencing and Sanger sequencing, we detected compound heterozygous mutations (c.152G>T, p.Gly51Val and c.727delG, p.Val243SerfsX21) in GRM6. The mutations co-segregated with the phenotype of the family members and are considered to be responsible for complete Schubert-Bornschein type CSNB. However, functional experiments in the future are needed to confirm the pathogenicity of the variants and to elucidate their exact molecular mechanisms causing CSNB.
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Objective: Clinical and prognostic features of Anti-MDA5-Positive Dermatomyositis (MDA5+ DM) are diverse. This study aimed to examine the peripheral immune cell profiles of patients with MDA5+ DM, identify disease endotypes related to the heterogeneous manifestations and prognosis, and guide individualized therapy regimen. Methods: This inpatient cohort included 123 patients with MDA5+ DM. Unsupervised hierarchical clustering analysis was used to derive disease endotypes from the circulating immune cell profiles on admission. Clinical symptoms, laboratory test results, inpatient treatments, and disease outcomes were then analyzed among the identified endotypes. Results: Three disease endotypes in MDA5+ DM were identified from peripheral immune cell profiles. Endotype1 had the highest percentages of CD4+ T cells and monocytes, and the lowest percentage of neutrophils; Endotype2 had the highest percentage of B cells; Endotype3 had the highest percentage of CD8+ T cells and NK cells. Clinical and prognostic heterogeneity of the endotypes were revealed. Endotype1 had the lowest 3-month mortality with the high incidence of periungual capillary changes. Endotype2 and Endotype3 had higher prevalence of rapidly progressive interstitial lung disease (RPILD) and mortality at 3 months than Endotype1. Meanwhile, Endotype3 had higher pneumocystis jiroveci and CMV viremia cases with significantly elevated of activated CD8+ T cells and multiple cytokines than Endotype1. Conclusion: Clustering analysis of peripheral immune cell profiles identified three different endotypes in MDA5+ dermatomyositis. Endotpye2 and 3 showed higher RPILD, 3-month mortality, pneumocystis jiroveci and CMV viremia.
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Infecciones por Citomegalovirus , Dermatomiositis , Enfermedades Pulmonares Intersticiales , Humanos , Helicasa Inducida por Interferón IFIH1 , Linfocitos T CD8-positivos , Viremia/complicaciones , Infecciones por Citomegalovirus/complicacionesRESUMEN
Purpose: To evaluate abnormalities in serum and aqueous humor uric acid (UA) levels in primary angle closure glaucoma (PACG). Methods: Patients with PACG and age-similar and gender-similar controls (patients scheduled for cataract extraction) were enrolled prospectively. Serum UA levels were determined by enzymatic colorimetry; aqueous humor UA levels by Enzyme-Linked ImmunoSorbent Assay. A t-test was used to compare UA levels between PACG patients and controls, with one-way ANOVA used to compare levels across PACG subgroups with differing disease severity. Comparisons between PACG patients and controls were adjusted for systemic and ocular confounding factors using binary logistic regression. Results: In all, 131 PACG patients and 112 controls were included. The serum UA level was 266 ± 69 µmol/L in the PACG group and 269 ± 73 µmol/L in the control group (p = 0.71). The aqueous humor UA level was 35.4 ± 8.2 µmol/L in the PACG group and 53.9 ± 18.6 µmol/L in the control group (p < 0.001). This difference remained significant after adjusting for age, gender, systolic blood pressure, diastolic blood pressure, body mass index, axial length, central corneal thickness, anterior chamber depth, lens thickness, white-to-white distance, corneal endothelial cell density, and serum UA level (odds ratio: 0.88, 95 % confidence interval: 0.83-0.93, p < 0.001). Conclusion: Aqueous humor UA levels differ between PACG patients and controls, but serum UA levels do not. This indicates that local UA plays a role in the pathogenesis of PACG, but systemic UA does not.
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AIM: To analyze and compare the differences among ocular biometric parameters in Han and Uyghur populations undergoing cataract surgery. METHODS: In this hospital-based prospective study, 410 patients undergoing cataract surgery (226 Han patients in Tianjin and 184 Uyghur patients in Xinjiang) were enrolled. The differences in axial length (AL), anterior chamber depth (ACD), keratometry [steep K (Ks) and flat K (Kf)], and corneal astigmatism (CA) measured using IOL Master 700 were compared between Han and Uyghur patients. RESULTS: The average age of Han patients was higher than that of Uyghur patients (70.22±8.54 vs 63.04±9.56y, P<0.001). After adjusting for age factors, Han patients had longer AL (23.51±1.05 vs 22.86±0.92 mm, P<0.001), deeper ACD (3.06±0.44 vs 2.97±0.37 mm, P=0.001), greater Kf (43.95±1.40 vs 43.42±1.69 D, P=0.001), steeper Ks (45.00±1.47 vs 44.26±1.71 D, P=0.001), and higher CA (1.04±0.68 vs 0.79±0.65, P=0.025) than Uyghur patients. Intra-ethnic male patients had longer AL, deeper ACD, and lower keratometry than female patients; however, CA between the sexes was almost similar. In the correlation analysis, we observed a positive correlation between AL and ACD in patients of both ethnicities (rHan =0.48, rUyghur =0.44, P<0.001), while AL was negatively correlated with Kf (rHan =-0.42, rUyghur =-0.64, P<0.001) and Ks (rHan =-0.38, rUyghur =-0.66, P<0.001). Additionally, Kf was positively correlated with Ks (rHan =0.89, rUyghur =0.93, P<0.001). CONCLUSION: There are differences in ocular biometric parameters between individuals of Han ethnicity in Tianjin and those of Uyghur ethnicity in Xinjiang undergoing cataract surgery. These ethnic variances can enhance our understanding of ocular diseases related to these parameters and provide guidance for surgical procedures.
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PURPOSE: To report a bilateral diffuse uveal melanocytic proliferation (BDUMP) patient whose initial presentation was glaucoma. METHODS: Clinical review of a BDUMP case. RESULTS: A 65-year-old woman presented with ocular pain of the left eye for 1 day and vision loss of the right eye for 1 week. An ophthalmological examination revealed increased intraocularr pressure in the left eye and shallow anterior chamber in both eyes. BDUMP was diagnosed following a series of auxiliary examinations. After 1.5 years of follow-up, progressive cataracts appeared, and the patient accepted cataract surgery in both eyes. Visual acuity improved from light perception to 20/100 in both eyes 1.5 years after cataract surgery, but declined to light perception again at the last follow-up. CONCLUSION: BDUMP can be initially presented as glaucoma, and cataract surgery can be considered in BDUMP patients in order to improve the patients' quality of life, even if exudative retinal detachment exists.
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Extracción de Catarata , Catarata , Glaucoma , Síndromes Paraneoplásicos Oculares , Anciano , Femenino , Humanos , Dolor Ocular/etiología , Glaucoma/diagnóstico , Glaucoma/etiología , Síndromes Paraneoplásicos Oculares/complicaciones , Síndromes Paraneoplásicos Oculares/diagnóstico , Catarata/complicaciones , Calidad de VidaRESUMEN
This study aimed to elucidate the immune status of systemic lupus erythematosus (SLE) patients with infections. We enrolled 253 SLE patients including 77 patients with infections. Clinical features and immunological parameters were analyzed, with particular reference to neutrophil CD64 (nCD64) expression, myeloid-derived suppressor cells (MDSCs), activated T cells and multiple cytokines. Among the 77 SLE patients with infections, 32 patients (41.56%) developed fever and 20 patients (25.97%) developed serositis, which were higher compared to the non-infection group. A considerably higher level of nCD64 was found in the infection group (4.65 vs 1.01, P < 0.001). In addition, the infection group exhibited higher percentages of total MDSCs (6.99 vs 4.30%, P = 0.003), polymorphonuclear MDSCs (PMN-MDSCs) (P = 0.032) and monocytic MDSCs (M-MDSCs) (P = 0.015). T cells were more activated during infections, with an elevated level of IL-2R (P < 0.001). Specifically, higher percentages of CD4+CD38+ T cells (55.73 vs 50.17%, P = 0.036), CD8+HLA-DR+ T cells (59.82 vs 47.99%, P < 0.001) and CD8+CD38+ T cells (68.59 vs 63.90%, P = 0.044) were identified in the infection group. Furthermore, the serum levels of IL-6, IL-8 and IL-10 were elevated in the infection group (all P < 0.001). Higher proportions of neutrophils, CD4+ and CD8+ T cells, and MDSCs were activated during infections in SLE patients. Additionally, the serum cytokines altered during infections, with noticeably elevated levels of IL-6, IL-8 and IL-10. Infections may lead to the amplification of immune alterations in SLE.
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Interleucina-10 , Lupus Eritematoso Sistémico , Humanos , Linfocitos T CD8-positivos/metabolismo , Interleucina-6 , Interleucina-8 , CitocinasRESUMEN
As the histology, physiology, and pathophysiology of eyes and kidneys show substantial overlap, it has been suggested that eye and kidney diseases, such as glaucoma and chronic kidney disease (CKD), may be closely interlinked. We review the relationship between CKD and various subtypes of glaucoma, including primary open-angle glaucoma, primary angle- closure glaucoma, normal tension glaucoma, pseudoexfoliation syndrome, and several glaucoma endophenotypes. We also discuss the underlying pathogenic mechanisms and common risk factors for CKD and glaucoma, including atherosclerosis, the renin-angiotensin system, genes and genetic polymorphisms, vitamin D deficiency, and erythropoietin. The prevalence of glaucoma appears elevated in CKD patients, and vice versa, and the literature points to many intriguing associations; however, the associations are not always confirmed, and sometimes apparently opposite observations are reported. Glaucoma and CKD are complex diseases, and their mutual influence is only partially understood.