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Background: Osteoporosis (OP), affecting millions around the globe, is a prevalent degenerative condition of the bones characterized by a decrease in bone mineral density (BMD) and an increase in bone fragility. A novel anthropometric measure, the Body Roundness Index (BRI), provides a more accurate assessment of body fat distribution compared to traditional metrics. Using data from the National Health and Nutrition Examination Survey (NHANES), this study aims to explore the relationship between BRI and total BMD in U.S. adults aged 20 and above. Methods: Data from NHANES (2011-2018) were examined, encompassing 9,295 participants following exclusions. Dual-energy X-ray absorptiometry (DXA) was employed to measure BMD. BRI was calculated using waist circumference (WC) and height. The study accounted for variables such as demographic traits, physical exam results, lab test findings, and survey responses. Weighted multivariable linear regression models and smooth curve fitting methods were utilized to assess the relationship between BRI and total BMD. Results: The research found a notable inverse relationship between BRI and total BMD. In the model with full adjustments, an increase of one unit in BRI was linked to a 0.0313 g/cm2 reduction in total BMD (P < 0.0001). Moreover, an inflection point was identified at BRI = 9.5229, where each one-unit rise in BRI beyond this threshold corresponded to a more substantial decrease in total BMD (0.0363 g/cm2). Analysis by subgroups revealed that this negative association was consistent across most demographic and health-related categories. Conclusions: The results demonstrate a notable inverse relationship between BRI and total BMD, indicating that a higher BRI could be associated with lower BMD and a potentially greater risk of developing OP. This underscores the significance of accounting for body fat distribution in preventing OP and advocates for the use of BRI as a valuable marker for early intervention approaches.
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Diagnosis of intravascular large B-cell lymphoma (IVLBCL) is a challenge due to its heterogeneous clinical presentation and lack of specific markers. This retrospective study investigated the utility of circulating tumour DNA (ctDNA) sequencing for diagnosing IVLBCL and analysing its mutation landscape. A cohort of 34 IVLBCL patients enrolled and underwent plasma ctDNA targeted sequencing. The median plasma ctDNA concentration was 135.0 ng/mL, significantly higher than that in diffuse large B-cell lymphoma (DLBCL) controls. Correlations were found between ctDNA concentration and disease severity indicators, LDH and SF. Mutation analysis revealed frequent mutations in B-cell receptor and NF-κB signalling pathways, including MYD88 (56%), CD79B (44%), TNFAIP3 (38%) and IRF4 (29%). CNS involvement was significantly related with BCL6 and CD58 mutation. Patients with complicated hemophagocytic lymphohistiocytosis had significantly higher mutation rates in B2M. Comparison with DLBCL subtypes showed distinctive mutation profiles in IVLBCL. Moreover, plasma ctDNA detected more mutations with higher variant allele fraction than tissue DNA, suggesting its superiority in sensitivity and accessibility. Dynamic monitoring of ctDNA during treatment correlated with therapeutic responses. This study revealed the role of ctDNA in IVLBCL diagnosis, mutation analysis, and treatment monitoring, offering a promising avenue for improving patient diagnosis in this rare lymphoma subtype.
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Biomarcadores Tumorais , DNA Tumoral Circulante , Linfoma Difuso de Grandes Células B , Mutação , Humanos , DNA Tumoral Circulante/genética , DNA Tumoral Circulante/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/sangue , Análise Mutacional de DNA/métodos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Adulto , Estudos Retrospectivos , Idoso de 80 Anos ou maisRESUMO
Pd(II)-catalyzed enantioselective C-H activation has emerged as a versatile platform for constructing point, axial, and planar chirality. Herein, we present an unexpected discovery of a Pd-catalyzed enantioselective cascade ß,γ-methylene C(sp3)-H diarylation of free carboxylic acids using bidentate chiral mono-protected amino thioether ligands (MPAThio), enabling one-step synthesis of a complex chiral 9,10-dihydrophenanthrenes scaffolds with high enantioselectivity. In this process, two methylene C(sp3)-H bonds and three C(sp2)-H bonds were activated, leading to the formation of four C-C bonds and two chiral centers in one pot. A plausible catalytic pathway starts with enantioselective ß,γ-dehydrogenation to form chiral ß,γ-cyclohexene. Intriguingly, this olefin serves as a norbornene-type reagent (presumably assisted by the carboxyl directing effect), relaying two successive Catellani arylation reactions and a C-H alkylation reaction to furnish chiral 9,10-dihydrophenanthrenes along with meta-selective homocoupling products of iodoarene.
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Site-selective C(sp3)-H oxidation is of great importance in organic synthesis and drug discovery. γ-C(sp3)-H lactonization of free carboxylic acids provides the most straightforward means to prepare biologically important lactone scaffolds from abundant and inexpensive carboxylic acids; however, a versatile catalyst for this transformation with a broad substrate scope remains elusive. Herein, we report a simple yet broadly applicable and scalable γ-lactonization reaction of free aliphatic acids enabled by a copper catalyst in combination with inexpensive Selectfluor as the oxidant. This lactonization reaction exhibits compatibility with tertiary, benzylic, allylic, methylene, and primary γ-C-H bonds, affording access to a wide range of structurally diverse lactones such as spiro, fused, and bridged lactones. Notably, exclusive γ-methylene C-H lactonization of cycloalkane carboxylic acids and cycloalkane acetic acids was observed, giving either fused or bridged γ-lactones that are difficult to access by other methods. δ-C-H lactonization was only favored in the presence of tertiary δ-C-H bonds. The synthetic utility of this methodology was demonstrated by the late-stage functionalization of amino acids, drug molecules, and natural products, as well as a two-step total synthesis of (iso)mintlactones (the shortest synthesis reported to date).
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OBJECTIVE: Psoriasis is an immune-mediated skin disease where the IL-17 signaling pathway plays a crucial role in its development. Chronic circadian rhythm disorder in psoriasis pathogenesis is gaining more attention. The relationship between IL and 17 signaling pathway and skin clock genes remains poorly understood. METHODS: GSE121212 with psoriatic lesion and healthy controls was used as the exploration cohort for searching analysis. Datasets GSE54456, GSE13355, GSE14905, GSE117239, GSE51440, and GSE137218 were applied to validation analysis. Single-cell RNA sequencing (scRNA-seq) dataset GSE173706 was used to explore the F3 expression and related pathway activities in single-cell levels. Through intersecting with high-expression DEGs, F3 was selected as the signature skin circadian gene in psoriasis for further investigation. Functional analyses, including correlation analyses, prediction of transcription factors, protein-protein interaction, and single gene GSEA to explore the potential roles of F3. ssGSEA algorithm was performed to uncover the immune-related characteristics of psoriasis. We further explored F3 expression in the specific cell population in scRNA-seq dataset, besides this, AUCell analysis was performed to explore the pathway activities and the results were further compared between the specific cell cluster. Immunohistochemistry experiment, RT-qPCR was used to validate the location and expression of F3, small interfering RNA (siRNA) transfection experiment in HaCaT, and transcriptome sequencing analysis were applied to explore the potential function of F3. RESULTS: F3 was significantly down-regulated in psoriasis and interacted with IL-17 signaling pathway. Low expression of F3 could upregulate the receptor of JAK-STAT signaling, thereby promoting keratinocyte inflammation. CONCLUSION: Our research revealed a bidirectional link between the skin circadian gene F3 and the IL-17 signaling pathway in psoriasis, suggesting that F3 may interact with the IL-17 pathway by activating JAK-STAT within keratinocytes and inducing abnormal intracellular inflammation.
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Interleucina-17 , Queratinócitos , Psoríase , Transdução de Sinais , Pele , Psoríase/genética , Psoríase/imunologia , Humanos , Interleucina-17/metabolismo , Interleucina-17/genética , Queratinócitos/metabolismo , Queratinócitos/imunologia , Pele/patologia , Pele/imunologia , Pele/metabolismo , Relógios Circadianos/genética , Biomarcadores/metabolismo , Índice de Gravidade de Doença , Células HaCaTRESUMO
A high-performance planar structure metal-semiconductor-metal-type solar-blind photodetector (SBPD) was fabricated on the basis of (010)-plane ß-Ga2O3 thermally oxidized from nonpolar (110)-plane GaN. A full width at half maximum of 0.486° was achieved for the X-ray rocking curve associated with (020)-plane ß-Ga2O3, which is better than most reported results for the heteroepitaxially grown (-201)-plane ß-Ga2O3. As a result of the relatively high crystalline quality, a dark current as low as 6.30 × 10-12 A was achieved at 5 V, while the photocurrent reached 1.86 × 10-5 A under 254 nm illumination at 600 µW/cm2. As a result, the photo-to-dark current ratio, specific detectivity, responsivity, and external quantum efficiency were calculated to be 2.95 × 106, 2.39 × 1012 Jones, 3.72 A/W, and 1815%, respectively. Moreover, the SBPD showed excellent repeatability and stability in the time-dependent photoresponse characteristics with fast relaxation time constants for the rise and decay processes of only 0.238 and 0.062 s, respectively. This study provides a promising approach to fabricate the device-level (010)-plane ß-Ga2O3 film and a new way for the epitaxial growth of (010)-plane ß-Ga2O3 and (110)-plane GaN as mutual substrates.
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Micro-LED is considered an emerging display technology with significant potential for high resolution, brightness, and energy efficiency in display applications. However, its decreasing pixel size and complex manufacturing process create challenges for its integration with driving units. Recently, researchers have proposed various methods to achieve highly integrated micro-structures with driving unit. Researchers take advantage of the high performance of the transistors to achieve low power consumption, high current gain, and fast response frequency. This paper gives a review of recent studies on the new integration methods of micro-LEDs with different types of transistors, including the integration with BJT, HEMT, TFT, and MOSFET.
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Psoriasis is a recurrent and protracted disease that severely impacts the patient's physical and mental health. Thus, there is an urgent need to explore its pathogenesis to identify therapeutic targets. The expression level of protein tyrosine phosphatase nonreceptor type 2 (PTPN2) was analyzed by immunohistochemistry techniques in psoriatic tissues and imiquimod-induced psoriatic mouse models. PTPN2 and signal transducer and activator of transcription 3 (STAT3) were overexpressed or silenced in human keratinocytes or an interleukin (IL)-6-induced psoriasis HaCaT cell model using overexpression plasmid transfection or small interfering RNA technology in vitro, and the effects of PTPN2 on STAT3, HaCaT cell function, and autophagy levels were investigated using reverse transcription-quantitative polymerase chain reaction, Western blot, Cell Counting Kit 8, 5-ethynyl-20-deoxyuridine, flow cytometry, and transmission electron microscopy. PTPN2 expression was found to be significantly downregulated in psoriatic tissues. Then, the in vitro antipsoriatic properties of PTPN2 were investigated in an IL-6-induced psoriasis-like cell model, and the results demonstrated that inhibition of keratinocyte proliferation by PTPN2 may be associated with elevated STAT3 dephosphorylation and autophagy levels. These findings provide novel insights into the mechanisms of autophagy in psoriatic keratinocytes and may be essential for developing new therapeutic strategies to improve inflammatory homeostasis in psoriatic patients.
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Psoríase , Fator de Transcrição STAT3 , Animais , Humanos , Camundongos , Linhagem Celular , Proliferação de Células , Queratinócitos/metabolismo , Queratinócitos/patologia , Monoéster Fosfórico Hidrolases/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 2/genética , Proteína Tirosina Fosfatase não Receptora Tipo 2/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 2/farmacologia , Psoríase/tratamento farmacológico , Fator de Transcrição STAT3/metabolismoRESUMO
N-Aryl (iso)quinolones are of increasing interest in material and medicinal chemistry, although general routes for their provision remain underexplored, especially when compared with its N-alkyl counterparts. Herein, we report a modular and transition-metal-free, aryne-induced three-component coupling protocol that allows the facile synthesis of structurally diverse N-aryl (iso)quinolones from readily accessible halo-(iso)quinolines in the presence of water. Preliminary results highlight the applicability of our method through scale-up synthesis, downstream derivatization, and flexible synthesis involving other types of aryne precursors.
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CD19-chimeric antigen receptor T-cell (CAR T-cell) therapy has improved the outcomes of relapsed/refractory large B cell lymphoma significantly. However, about 50% of patients relapsed post-CAR-T therapy. Late relapse composed of 1/3 to 1/2 of CAR-T cell therapy failure, with no previous reports of isolated relapse in immune-privileged sites. Here, we report the first case series of late-onset post CAR-T cell therapy isolated central nervous system (CNS) relapses, in systemic relapsed/refractory large B cell lymphoma patients. With these cases, we suggest that additional CNS prophylaxis should be administrated for primary refractory patients on CAR-T cell therapy with previous neurological involvements, multiple extra-nodular lesions, and high CNS-IPI score pre-CAR, as well as early disappearance of circulating CAR-T cells post infusion.
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Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/etiologia , Linfoma Difuso de Grandes Células B/terapia , Proteínas Adaptadoras de Transdução de Sinal , Antígenos CD19 , Sistema Nervoso Central , Doença Crônica , Imunoterapia Adotiva/efeitos adversos , RecidivaRESUMO
BACKGROUND: Scalp psoriasis seriously affects the appearance and psychological status of patients. The aim of this study was to investigate the effect and potential mechanism of RPL9 and TIFA in scalp psoriasis, so as to provide a precise and effective way for the clinical treatment of scalp psoriasis. METHODS: The Gene Expression Omnibus (GEO) database was employed to download the GSE75343 dataset to search for differentially expressed genes (DEGs) in scalp psoriasis through Sangerbox. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) enrichment analysis, functional enrichment analysis, immune cell infiltration analysis, immune responses and correlation analysis with 12 hub genes were performed. Then, STRING was used to develop a protein-protein interaction (PPI) network, used Cytoscape to locate hub genes, and SVM-RFE and random forest were utilized to identified RPL9 as the targeted gene. TIFA-RPL9 interaction predictions were made viathe Open Targets Platform and Uniprot. Further, the RPL9 and TIFA expression, molecular mechanism, and function were assessed in scalp psoriasis. RESULTS: Immunohistochemistry, qPCR, and western blotting verified that RPL9 and TIFA were highly expressed in lesional tissues of scalp psoriasis and IL17A-stimulated HaCaT cells. RPL9 knockdown effectively suppressed the proliferative capacity of IL17A-stimulated HaCaT cells in the CCK8 assay. The co-immunoprecipitation results revealed that RPL9 could interact with TIFA in IL17A-stimulated HaCaT cells. In qPCR and western blotting, RPL9 knockdown significantly inhibited TIFA at the mRNA and protein levels in IL17A-stimulated HaCaT cells. In ELISA, the secretion of TNF-α was markedly inhibited after downregulating RPL9 in IL17A-stimulated HaCaT cells. CONCLUSION: To our knowledge, we have elucidated the expression and role of RPL9 and TIFA in scalp psoriatic skin and keratinocytes, and our findings confirm that RPL9 might act as a candidate therapeutic target for scalp psoriasis.
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Psoríase , Couro Cabeludo , Humanos , Couro Cabeludo/metabolismo , Mapas de Interação de Proteínas/genética , Queratinócitos/metabolismo , Biomarcadores/metabolismo , Psoríase/genética , Psoríase/metabolismoRESUMO
We proposed a "Ni sacrifice" method to fabricate Al-based highly reflective p-electrode in the ultraviolet spectral region for AlGaN-based deep-ultraviolet light-emitting diodes (DUV-LEDs). The "Ni sacrifice" p-electrode could have a high optical reflectivity of around 90% at the DUV spectral region below 300â nm. Compared to Ni/Au, indium tin oxide (ITO), and Pd p-contacts, the "Ni sacrifice" led to a higher resistivity of p-contacts and a slightly higher operated voltage of the DUV-LEDs (within 0.6â V at 20â mA). Although the electrical performance was degraded slightly, the light output power and external quantum efficiency of the DUV-LEDs could be improved by utilizing the "Ni sacrifice" p-electrode. Besides, we introduced a grid of vias in the device mesa and reduced the diameter of the vias to achieve an enhanced peak external quantum efficiency (EQE) up to 1.73%. And the wall-plug efficiency (WPE) of DUV-LEDs with a "Ni sacrifice" p-electrode was higher than that of Ni/Au p-electrode DUV-LEDs at low currents. These results highlight the great potential of the proposed "Ni sacrifice" reflective p-electrode for use in DUV-LEDs.
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α,ß-Dehydrogenation of aliphatic acids has been realized through both enolate and ß-C-H metalation pathways. However, the synthesis of isolated ß,γ-unsaturated aliphatic acids via dehydrogenation has not been achieved to date. Herein, we report the ligand-enabled ß,γ-dehydrogenation of abundant and inexpensive free aliphatic acids, which provides a new synthetic disconnection as well as a versatile platform for the downstream functionalization of complex molecules at remote γ-sites. A variety of free aliphatic acids, including acyclic and cyclic systems with ring sizes from five-membered to macrocyclic, undergo efficient dehydrogenation. Notably, this protocol features good chemoselectivity in the presence of more accessible α-C-H bonds and excellent regioselectivity in fused bicyclic scaffolds. The utility of this protocol has been demonstrated by the late-stage functionalization of a series of bioactive terpene natural products at the γ-sites. Further functionalization of the ß,γ-double bond allows for the installation of covalent warheads, including epoxides, aziridines, and ß-lactones, into complex natural product scaffolds, which are valuable for targeted covalent drug discovery.
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Ácidos Carboxílicos , Ácidos Graxos , Ligantes , Ácidos Carboxílicos/químicaRESUMO
Sulfilimines, the aza analogues of sulfoxides, are of increasing interest in medicinal and agrochemical research programs. However, the development of efficient routes for their synthesis has remained relatively unexplored. In this study, we report a transition metal-free, selective S-arylation reaction between sulfenamides and arynes, enabling the facile preparation of structurally diverse sulfilimines under mild and redox-neutral conditions in good yields. The application value of our method was further demonstrated by scale-up synthesis, downstream derivatization, and robustness screen.
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The achievement of sufficient substrate-metal catalyst affinity is a fundamental challenge for the development of synthetically useful C-H activation reactions of weakly coordinating native substrates. While hydrogen bonding has been harnessed to bias site selectivity in existing C(sp2)-H activation reactions, the potential for designing catalysts with hydrogen bond donors (HBDs) to enhance catalyst-substrate affinity and, thereby, facilitate otherwise unreactive C(sp3)-H activation remains to be demonstrated. Herein, we report the discovery of a ligand scaffold containing a remote amide motif that can form a favorable meta-macrocyclic hydrogen bonding interaction with the aliphatic acid substrate. The utility of this ligand scaffold is demonstrated through the development of an unprecedented C(sp3)-H bromination of α-tertiary and α-quaternary free carboxylic acids, which proceeds in exceedingly high mono-selectivity. The geometric relationship between the NHAc hydrogen bond donor and the coordinating quinoline ligand is crucial for forming the meta-macrocyclophane-like hydrogen bonding interaction, which provides a guideline for the future design of catalysts employing secondary interactions.
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Maintenance treatment is a pivotal part in the whole process management of multiple myeloma (MM), which further deepens response and improves survival. However, evidence of maintenance in non-transplant MM patients is inadequate in real-world practice. Here, we retrospectively analyzed the efficacy and survival of 375 non-transplant MM patients from 11 centers between 2010 and 2021 in north China. After a median of seven cycles of front-line regimens, there were 141, 79, and 155 patients receiving lenalidomide maintenance (L-MT), bortezomib maintenance (B-MT), or thalidomide maintenance (T-MT), respectively. Patients on L-MT and B-MT had significantly greater proportions of high-risk cytogenetic abnormalities (HRCAs) detected by fluorescence in situ hybridization (FISH), which was defined as 1q21 gain, 17p deletion, adverse immunoglobulin heavy chain (IgH) translocations. Although the progression-free survival (PFS) and overall survival (OS) were comparable among the three groups, L-MT and B-MT remedied the negative impact of HRCAs on survival (PFS of patients with HRCAs vs. patients without HRCAs: L-MT, 26.9 vs. 39.2 months, p=0.19; B-MT, 20.0 vs. 29.7 months, p=0.36; OS not reached in all groups). Patients with HRCAs in the T-MT group presented inferior clinical outcomes compared to standard-risk patients (PFS, 12.1 vs. 22.8 months, p=0.02, HR=1.8, 95% CI 1.0-3.4; OS, 54.9 months vs. NR, p<0.001, HR=3.2, 95% CI 1.5-7.0). Achieving complete response (CR) after induction therapy led to superior PFS compared to other degrees of response, regardless of maintenance medication. Furthermore, maintenance duration over 24 months correlated with favorable survival. Due to the large gap of transplant eligibility in China, optimizing maintenance therapy is important for non-transplant MM patients. In this real-world multi-centered study, our findings suggest that clinicians prefer to prescribe lenalidomide or bortezomib as maintenance therapy in high-risk settings, which are superior to thalidomide in non-transplant MM patients. Achievement of CR and maintenance duration over 2 years are positive factors that influence survival.
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Purpose: Psoriasis and atherosclerosis are immunometabolic diseases. This study aimed to integrate bioinformatics and updated public resources to find potential biological markers associated with atherosclerosis that can cause psoriasis. Patients and Methods: Microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened, and functional enrichment analysis was performed. We identified psoriasis and atherosclerosis common immune-related genes (PA-IRGs) by overlapping immune-related genes (IRGs) with genes in the module most associated with psoriasis and atherosclerosis obtained by weighted gene co-expression network analysis (WGCNAs). Receiver operating characteristic (ROC) was conducted to evaluate the predictive ability. The skin expression levels of diagnostic biomarkers were further verified by immunohistochemical staining. CIBERSORT, single-sample gene set enrichment analysis (ssGSEA), and Pearson's correlation analysis were applied to evaluate immune and lipid metabolism relationships in psoriatic tissues. In addition, a lincRNA-miRNA-mRNA network was constructed to find the pathogenesis in which diagnostic markers may be involved. Results: Four PA-IRGs (SELP, CD93, IL2RG, and VAV1) demonstrated the optimal diagnostic value, with an AUC above 0.8. The immune cell infiltration analysis showed that dendritic resting cells, NK cell activation, neutrophils, macrophages M2, macrophages M0, and B-cell memory were highly abundant in psoriasis. Immune response analysis showed that TNF family members, chemokine receptors, interferons, natural killer cells, and TGF-ß family members might be involved in psoriasis. Diagnostic biomarkers are strongly associated with various infiltrating immune cells, immune responses, and lipid metabolism. A lincRNA-miRNA-mRNA regulatory network consisting of 31 lincRNAs and 23 miRNAs was constructed. LINC00662 is involved in modulating four diagnostic biomarkers. Conclusion: This study identified atherosclerosis-related genes SELP, CD93, VAV1, and IL2RG as potential psoriasis diagnostic markers. Provide novel insights into the possible regulatory mechanisms involved in psoriasis.
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Objectives: Primary central nervous system lymphoma (PCNSL) usually has a poor prognosis. Cerebrospinal fluid (CSF) interleukin (IL)-10 has shown diagnostic, prognostic, and monitoring value in our previous studies. Cell-free circulating tumor DNA can be detected in the CSF of refractory/relapse cases and has also shown monitoring value. However, information about its monitoring value in newly diagnosed PCNSL patients and comparisons of CSF IL-10 and CSF cell-free DNA (cfDNA) are scarce. Methods: We performed next-generation sequencing on paraffin-embedded tissue and the serial CSF cfDNA of 10 newly diagnosed PCNSL patients and on the baseline CSF cfDNA of 11 other central nervous system lymphoma patients. We also monitored the CSF IL-10 levels of the 10 newly diagnosed PCNSL patients. Results: In seven newly diagnosed PCNSL patients with sufficient baseline CSF cfDNA, six had ≥1 mutated genes in their CSF cfDNA. The most common were MYD88(4/7), PIM1(3/7), MLL2(3/7), and ETV6(2/7). We also identified multiple somatic mutations, most commonly in PIM1. MYD88L265P can be detected in both tumor tissue and CSF cfDNA. The genomic profiles of CFS cfDNA were similar in PCNSL and PIOL patients. Newly diagnosed PCNSL patients with persistently positive cfDNA and negative IL-10 progressed quickly, while those with negative cfDNA and negative IL-10 were in maintenance therapy for more than 18 months. Two patients without cfDNA had increased CSF IL-10 concentrations before disease relapse. These results indicate that negative CSF cfDNA predicts better results, and persistently positive CSF cfDNA predicts disease progression earlier than conventional magnetic resonance imaging. Conclusion: In conclusion, CSF cfDNA is a potential predictor of relapse and progression, which complements the monitoring value of CSF IL-10 in newly diagnosed PCNSL patients.
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PURPOSE: To analyze the correlation between cerebrospinal fluid (CSF) interleukin-10 (IL-10) levels and the clinical characteristics in patients with vitreoretinal lymphoma (VRL). DESIGN: Retrospective observational case series. METHODS: Forty-one patients were diagnosed as VRL and underwent lumbar puncture for CSF examination. Aqueous humor cytokine detection, vitreous cytopathologic analysis, monoclonal gene rearrangement, and flow cytometry were performed. The CSF was assessed through biochemical and cytologic examination, flow cytometry, and cytokine detection. RESULTS: The median levels of aqueous humor IL-10 and IL-6 were 415.0 and 40.7 pg/mL. The median CSF levels of IL-10 and IL-6 were 35.7 and 3.5 pg/mL, respectively. IL-10 levels in CSF were higher than normal in 37 patients (90.2%) and higher in patients with intracranial lesions. The level of CSF IL-10 decreased after systemic treatment, and it rose before intracranial lesion onset or recurrence. The level of IL-10 in CSF was related to the duration of ocular symptoms, but was not related to the level of IL-10 in aqueous humor. There was no significant difference in CSF IL-10 levels between patients with and without anterior chamber inflammation or retinal lesions. In eyes with recurrent vitreoretinal lymphoma, the level of IL-10 in aqueous humor increased significantly, but there was no corresponding increase in the level of IL-10 in CSF. CONCLUSION: CSF IL-10 is a potentially important biomarker in VRL, especially in the monitoring of intracranial lesions.