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BACKGROUNDS: Chronic recurrent multifocal osteomyelitis (CRMO) is a rare inflammatory disease. OBJECTIVE: This report aims to analyze the clinical characteristics of CRMO and enhance clinicians' comprehension. We present 3 atypical cases, highlighting their unique clinical features, diagnostic challenges, and effective treatment strategies. METHODS: We retrieved 3 CRMO cases in our hospital from September 2019 to August 2022. The clinical features were analyzed retrospectively, and relevant literatures were reviewed. RESULTS: All 3 cases initially presented with bone pain, normal leucocyte counts, negative rheumatoid factors and no signs of sclerotic or hyperostotic lesions. Case 1, a 12-year-old girl, exhibited concurrent acne on the forehead and historic necrotizing lymphadenitis, a previously unreported association with CRMO. Case 2, a 14-year-old boy, tested positive for human leukocyte antigen-B27 and displayed scoliosis along with multifocal osteomyelitis. Case 3, a 9-year-old girl, presented with scoliosis, and chest computed tomography revealed changes in the T8 vertebral body, initially suggesting Langerhans cell histiocytosis. Bone biopsy was conducted in case 1 and case 3, revealing chronic inflammation. All 3 cases affected long bones, pelvis, and vertebra, involving 8, 6 and 5 bones, respectively, identified by magnetic resonance imaging. Genetic analysis was undertaken in cases 1 and 2 but no pathogenic mutations were identified. Upon the confirmation of a CRMO diagnosis, all patients were initiated on a treatment regimen comprising nonsteroidal anti-inflammatory drugs and tumor necrosis factor-α inhibitors. In cases 1 and 2, due to the severity of their bone pain, they were also administered to disease-modifying anti-rheumatic drugs, specifically methotrexate. All 3 patients achieved remission of bone pain. To gain a more comprehensive understanding of CRMO, we conducted a thorough review of relevant literature. CONCLUSION: CRMO is a rare autoinflammatory bone disorder with diverse clinical presentations and a lack of specific laboratory tests, which leads to potency to misdiagnosis or delayed diagnosis. By raising awareness and improving diagnostic criteria, physicians are now better equipped to identify CRMO. We contribute to share our understanding of CRMO by presenting 3 cases with untypical clinical features, highlighting the importance of recognizing this rare condition for timely and effective management.
Subject(s)
Osteomyelitis , Humans , Osteomyelitis/diagnosis , Osteomyelitis/drug therapy , Female , Child , Adolescent , Male , Magnetic Resonance ImagingABSTRACT
Developing coalbed methane (CBM) aligns with global climate change policies and sustainable energy development. Currently, methods for testing gas and water production profiles in CBM wells are diverse. A downhole constant-flow thermal mass flowmeter (TMF) was designed to address the difficulty of testing gas production above the liquid level in low-yield CBM wells. A computational fluid dynamics model with a 125 mm diameter pipe was established to study the TMF's temperature field and thermal equilibrium time as the gas flow rate changes. The relationship curve between temperature, thermal equilibrium time, and flow rate changes was obtained. The effect of the TMF's installation angle and position in the wellbore on resolution was discussed. Experimental research on a multiphase flow simulation apparatus showed that the TMF has good response capability and testing accuracy in a gas environment. Measuring downhole flow rates using the thermal flow meters is feasible and meets the testing requirements of CBM wells.
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OBJECTIVE: Increasing evidence has shown that the microbiota-gut-brain axis (MGB) is involved in the mechanism of major depressive disorder (MDD). However, the relationship between the gut microbiome and brain function in MDD patients has not been determined. Here, we intend to identify specific changes in the gut microbiome and brain function in first-episode, drug-naïve MDD patients and then explore the associations between the two omics to elucidate how the MGB axis plays a role in MDD development. METHODS: We recruited 38 first-episode, drug-naïve MDD patients and 37 healthy controls (HC). The composition of the fecal microbiome and neural spontaneous activity alterations were examined using 16S rRNA gene amplicon sequencing analysis and regional homogeneity (ReHo). Spearman correlation analyses were conducted to assess the associations between the gut microbiome and brain function. RESULTS: Compared with HC, MDD patients exhibited distinct alterations in the gut microbiota and elevated ReHo in the frontal regions. In the MDD group, a positive relationship was noted between the relative abundance of Blautia and the HAMD-17 and HAMA scores, as well as between the relative abundance of Oxalobacteraceae and the HAMD-17 score. The relative abundances of Porphyromonadaceae and Parabacteroides were negatively correlated with the ReHo values of frontal regions. LIMITATIONS: Our study utilized a cross-sectional design, and the number of subjects was relatively small. CONCLUSION: We found that some specific gut microbiomes were associated with frontal function, and others were associated with clinical symptoms in MDD patients, which may support the role of the MGB axis underlying MDD.
Subject(s)
Brain-Gut Axis , Depressive Disorder, Major , Gastrointestinal Microbiome , Humans , Depressive Disorder, Major/microbiology , Depressive Disorder, Major/physiopathology , Gastrointestinal Microbiome/physiology , Female , Male , Adult , Brain-Gut Axis/physiology , Feces/microbiology , Brain/physiopathology , RNA, Ribosomal, 16S/genetics , Magnetic Resonance Imaging , Young Adult , Case-Control StudiesABSTRACT
BACKGROUND: The glandular trichomes of tobacco (Nicotiana tabacum) can efficiently produce secondary metabolites. They act as natural bioreactors, and their natural products function to protect plants against insect-pests and pathogens and are also components of industrial chemicals. To clarify the molecular mechanisms of tobacco glandular trichome development and secondary metabolic regulation, glandular trichomes and glandless trichomes, as well as other different developmental tissues, were used for RNA sequencing and analysis. RESULTS: By comparing glandless and glandular trichomes with other tissues, we obtained differentially expressed genes. They were obviously enriched in KEGG pathways, such as cutin, suberine, and wax biosynthesis, flavonoid and isoflavonoid biosynthesis, terpenoid biosynthesis, and plant-pathogen interaction. In particular, the expression levels of genes related to the terpenoid, flavonoid, and wax biosynthesis pathway mainly showed down-regulation in glandless trichomes, implying that they lack the capability to synthesize certain exudate compounds. Among the differentially expressed genes, 234 transcription factors were found, including AP2-ERFs, MYBs, bHLHs, WRKYs, Homeoboxes (HD-ZIP), and C2H2-ZFs. These transcription factor and genes that highly expressed in trichomes or specially expressed in GT or GLT. Following the overexpression of R2R3-MYB transcription factor Nitab4.5_0011760g0030.1 in tobacco, an increase in the number of branched glandular trichomes was observed. CONCLUSIONS: Our data provide comprehensive gene expression information at the transcriptional level and an understanding of the regulatory pathways involved in glandular trichome development and secondary metabolism.
Subject(s)
Gene Expression Profiling , Gene Expression Regulation, Plant , Nicotiana , Trichomes , Trichomes/genetics , Trichomes/metabolism , Trichomes/growth & development , Nicotiana/genetics , Nicotiana/metabolism , Nicotiana/growth & development , Transcriptome , Plant Proteins/genetics , Plant Proteins/metabolism , Genes, Plant , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
BACKGROUND: Patients receiving PD-(L)1 inhibitors frequently encounter unusual side effects known as immune-related adverse events (irAEs). However, the correlation of irAEs development with clinical response in small cell lung cancer (SCLC) is unknown. METHOD: This retrospective study enrolled 244 stage IV SCLC patients who receiving PD-(L)1 inhibitors from 3 cancer centers. The correlation of irAEs with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: 140 in 244 (57%) patients experienced irAEs, with 122 (87.1%) experiencing one and 18 (12.9%) experiencing two or more. Compared to patient without irAEs, those developing irAEs had higher ORR (73.6% vs. 52.9%, P < 0.001) and DCR (97.9% vs. 79.8%, P < 0.001), as well as prolonged median PFS (8.8 vs. 4.5 months, P < 0.001) and OS (23.2 vs. 21.6 months, P < 0.05). Among the different spectra of irAEs, thyroid dysfunction, rash, and pneumonitis were the most powerful indicator for improved PFS. When analyzed as a time-dependent covariate, the occurrence of irAEs was associated with significant improvement in PFS rather than in OS. Furthermore, patients experiencing multisystem irAEs displayed a longer PFS and OS compared with single-system irAEs and the irAE-free ones. IrAEs grade and steroid use did not impact the predictive value of irAEs on PFS. CONCLUSION: The presence of irAEs predicts superior clinical benefit in SCLC. Patients who develop multi-system irAEs may have an improved survival than those developed single-system irAEs and no-irAEs. This association persists even when systemic corticosteroids were used for irAEs management.
Subject(s)
Immune Checkpoint Inhibitors , Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Retrospective Studies , Male , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/immunology , Small Cell Lung Carcinoma/mortality , Female , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Lung Neoplasms/mortality , Middle Aged , Aged , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Adult , Aged, 80 and over , Treatment Outcome , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , Progression-Free SurvivalABSTRACT
Objective: To explore the clinical characteristics and treatment outcomes of children with central nervous system (CNS) involvement in eosinophilic granulomatosis with polyangiitis (EGPA). Methods: A child who presented with EGPA complicated by CNS involvement was admitted to our hospital in June 2023. The clinical features were analyzed retrospectively, and relevant literatures were reviewed to provide a comprehensive overview of this condition. Results: A ten-year-old girl, who had a history of recurrent cough and asthma accompanied by peripheral blood eosinophilia for eight months, was admitted to our hospital. On admission, spotted papules were visible on her hands and feet, bilateral pulmonary rales were audible. The laboratory examination revealed that the proportion of eosinophils (EOS) exceeded 10% of white blood cells, the anti-neutrophil cytoplasmic antibody (MPO-ANCA) was positive, the immunoglobulin G level was 15.80g/L, and the immunoglobulin E level was greater than 2500.00IU/mL. The imaging examination showed multiple patchy and nodular high-density shadows in both lungs as well as sinusitis. Pulmonary function tests indicated moderate ventilation and diffusion dysfunction. Bone marrow cytology demonstrated a significant increase in the proportion of eosinophils. Skin pathology confirmed leukocytoclastic vasculitis. During the hospitalization, the child had a convulsion. The magnetic resonance imaging (MRI) scan of the brain showed multiple abnormal signal shadows in the bilateral cerebral cortex and the electroencephalogram (EEG) showed epileptic waves. Following the administration of methylprednisolone pulse therapy in combination with cyclophosphamide treatment, her cough and asthma resolved, the skin rash disappeared without any further convulsions. We found that only a young EGPA patient with CNS involvement had been previously reported. The previously reported case began with long-term fever, weight loss, and purpuric rash. Both patients responded well to treatment with glucocorticoids and cyclophosphamide, experiencing significant improvement in their clinical symptoms and normalization of their peripheral blood eosinophils. Conclusion: The diagnosis of EGPA in children can be challenging. When a child is affected by EGPA, it is essential to remain vigilant for signs of CNS involvement. The treatment with glucocorticoids and cyclophosphamide is effective in managing EGPA in children.
Subject(s)
Churg-Strauss Syndrome , Humans , Female , Child , Churg-Strauss Syndrome/diagnosis , Churg-Strauss Syndrome/drug therapy , Churg-Strauss Syndrome/complications , Churg-Strauss Syndrome/immunology , Treatment Outcome , Granulomatosis with Polyangiitis/drug therapy , Granulomatosis with Polyangiitis/diagnosis , Granulomatosis with Polyangiitis/complications , Granulomatosis with Polyangiitis/immunology , Cyclophosphamide/therapeutic use , Antibodies, Antineutrophil Cytoplasmic/immunology , Antibodies, Antineutrophil Cytoplasmic/bloodABSTRACT
OBJECTIVE: To explore the clinical characteristics and genetic etiology for a child with atypical Hemolytic uremic syndrome (aHUS) in conjunct with nephrotic level proteinuria. METHODS: A child patient who had visited the Affiliated Hospital of Qingdao University on June 25, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing of the child and his parents. RESULTS: The child, an 8-month-old male, had presented mainly with edema, oliguria, hematuria, nephrotic level proteinuria, anemia, thrombocytopenia, increased creatinine and urea, hypercholesterolemia but normal complement levels. Genetic testing revealed that he has harbored compound heterozygous variants of the DGKE gene, namely c.12_18dupGAGGCGG (p.P7fs*37) and c.1042G>T (p.D348Y), which were respectively inherited from his father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as likely pathogenic and variant of uncertain significance, respectively. By combining his clinical manifestations and results of genetic testing, the child was diagnosed with aHUS with nephrotic level proteinuria. CONCLUSION: For infants and young children with aHUS in conjunct with nephrotic level proteinuria, variants of the DGKE gene should be screened. Above finding has expanded the mutational spectrum of the DGKE gene.
Subject(s)
Atypical Hemolytic Uremic Syndrome , Thrombocytopenia , Infant , Female , Humans , Child , Male , Child, Preschool , Atypical Hemolytic Uremic Syndrome/genetics , Atypical Hemolytic Uremic Syndrome/diagnosis , Mutation , Genetic Testing , Thrombocytopenia/genetics , Proteinuria/geneticsABSTRACT
Cell therapy is an important topic in the field of regeneration medicine that is gaining attention within the scientific community. However, its potential for treatment in coronary heart disease (CHD) has yet to be established. Several various strategies, types of cells, routes of distribution, and supporting procedures have been tried and refined to trigger heart rejuvenation in CHD. However, only a few of them result in a real considerable promise for clinical usage. In this review, we give an update on techniques and clinical studies of cell treatment as used to cure CHD that are now ongoing or have been completed in the previous five years. We also highlight the emerging efficacy of stem cell treatment for CHD. We specifically examine and comment on current breakthroughs in cell treatment applied to CHD, including the most effective types of cells, transport modalities, engineering, and biochemical approaches used in this context. We believe the current review will be helpful for the researcher to distill this information and design future studies to overcome the challenges faced by this revolutionary approach for CHD.
Subject(s)
Coronary Disease , Humans , Coronary Disease/therapy , Cell- and Tissue-Based Therapy , Heart , Stem Cell Transplantation/methods , Regenerative MedicineABSTRACT
OBJECTIVE: The aim of this study is to identify whether low lupus disease activity status (LLDAS) and clinical remission (CR) of belimumab plus standard of care (SoC) therapy are achievable goals in childhood-onset SLE (cSLE). METHODS: This multicentre, one arm pre-post intervention study was conducted at 15 centers in China. The primary end point was to describe the proportion of patients who achieved LLDAS and CR after 3, 6, and 12 months after treatment with belimumab plus SoC therapy. A multiple regression model was used to impute missing data. A Poisson regression model was used to calculate the effect of belimumab treatment on the reduced risk of serious diseases and the incidence of new damage. RESULT: 193 (92.2% female) with active cSLE from 15 centers were included. At 3, 6 and 12 months, the proportion of LLDAS (CR) was 12.4% (1.0%), 25.6% (4.5%) and 70.3% (29.7%), respectively. The mean SELENA-SLEDAI score decreased from 11.0 at baseline to 3.7, 2.9 and 1.7 at 3, 6, and 12 months. At baseline, all patients received steroids at a mean (SD) prednisone equivalent dose of 31.0 (18.2) mg/day, which decreased to 19.4 (10.8) mg/day at month 3, 12.6 (7.2) mg/day at month 6 and 6.7 (5.3) mg/day at month 12. The symptoms and immunological indicators were also significantly improved. CONCLUSION: This is the first and largest sample size prospective clinical intervention study of cSLE patients treated with belimumab in China. LLDAS and CR were attainable treat-to-target of belimumab plus SoC therapy in cSLE.
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Many inherited bone marrow failure syndromes (IBMFSs) present a high risk of transformation to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). During transformation of IBMFSs, hematopoietic stem and progenitor cells (HSPCs) with poor fitness gain ectopic, dysregulated self-renewal secondary to somatic mutations via undefined mechanisms. Here, in the context of the prototypical IBMFS Fanconi anemia (FA), we performed multiplexed gene editing of mutational hotspots in MDS-associated genes in human induced pluripotent stem cells (iPSCs) followed by hematopoietic differentiation. We observed aberrant self-renewal and impaired differentiation of HSPCs with enrichment of RUNX1 insertions and deletions (indels), generating a model of IBMFS-associated MDS. We observed that compared to the failure state, FA MDS cells show mutant RUNX1-mediated blunting of the G1/S cell cycle checkpoint that is normally activated in FA in response to DNA damage. RUNX1 indels also lead to activation of innate immune signaling, which stabilizes the homologous recombination (HR) effector BRCA1, and this pathway can be targeted to abrogate viability and restore sensitivity to genotoxins in FA MDS. Together, these studies develop a paradigm for modeling clonal evolution in IBMFSs, provide basic understanding of the pathogenesis of MDS, and uncover a therapeutic target in FA-associated MDS.
Subject(s)
Fanconi Anemia , Induced Pluripotent Stem Cells , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Humans , Fanconi Anemia/genetics , Fanconi Anemia/pathology , Fanconi Anemia/therapy , Congenital Bone Marrow Failure Syndromes/complications , Core Binding Factor Alpha 2 Subunit/genetics , Induced Pluripotent Stem Cells/pathology , Myelodysplastic Syndromes/pathology , Mutation , Leukemia, Myeloid, Acute/pathologyABSTRACT
BACKGROUNDS: Suicidal ideation (SI) is one of the most serious consequences of major depressive disorder (MDD). Understanding the unique mechanism of MDD with SI (MDD + S) is crucial for treatment development. While abundant research has studied MDD, past studies have not reached a consensus on the mechanism of MDD + S. The study aimed to investigate the abnormalities of the gray matter volumes (GMVs) and plasma IL-6 level in MDD + S to further reveal the mechanism of MDD + S. METHODS: We tested the plasma IL-6 level using Luminex multifactor assays and collected the Structural Magnetic Resonance Imaging (SMRI) data from 34 healthy controls (HCs), 36 MDD patients without SI (MDD - S) and 34 MDD + S patients. We performed a partial correlation between the GMVs of the brain regions with significant differences and plasma IL-6 level with age, sex, medication, scores of HAMD-17 and HAMA as the covariates. RESULTS: Compared with HCs and MDD - S, MDD + S had significantly decreased GMVs in the left cerebellum Crus I/II and significantly increased plasma IL-6 level; compared with HCs, both the MDD + S and MDD - S had significantly decreased GMVs in right precentral and postcentral gyri. No significant correlation was found between the GMVs and the plasma IL-6 level in the MDD + S and MDD - S, respectively. While the GMVs of the right precentral and postcentral gyri negatively correlated with the level of IL-6 in the whole MDD (r = -0.28, P = 0.03). The GMVs of the left cerebellum Crus I/II (r = -0.47, P = 0.02), and the right precentral and postcentral gyri (r = -0.42, P = 0.04) negatively correlated with the level of IL-6 in HCs. CONCLUSION: The altered GMVs and the plasma IL-6 level may provide a scientific basis to understand the pathophysiological mechanisms of MDD + S.
Subject(s)
Depressive Disorder, Major , Gray Matter , Humans , Gray Matter/pathology , Interleukin-6 , Suicidal Ideation , Brain , Magnetic Resonance ImagingABSTRACT
Phosphoenolpyruvate carboxykinase (PCK) plays a critical role in cytosolic gluconeogenesis, and defects in PCK1 cause a fasting-aggravated metabolic disease with hypoglycemia and lactic acidosis. However, there are two genes encoding PCK, and the role of the mitochondrial resident PCK (encoded by PCK2) is unclear, since gluconeogenesis is cytosolic. We identified three patients in two families with biallelic variants in PCK2. One has compound heterozygous variants (p.Ser23Ter/p.Pro170Leu), and the other two (siblings) have homozygous p.Arg193Ter variation. All three patients have weakness and abnormal gait, an absence of PCK2 protein, and profound reduction in PCK2 activity in fibroblasts, but no obvious metabolic phenotype. Nerve conduction studies showed reduced conduction velocities with temporal dispersion and conduction block compatible with a demyelinating peripheral neuropathy. To validate the association between PCK2 variants and clinical disease, we generated a mouse knockout model of PCK2 deficiency. The animals present abnormal nerve conduction studies and peripheral nerve pathology, corroborating the human phenotype. In total, we conclude that biallelic variants in PCK2 cause a neurogenetic disorder featuring abnormal gait and peripheral neuropathy.
Subject(s)
Peripheral Nervous System Diseases , Phosphoenolpyruvate Carboxykinase (ATP) , Mice , Animals , Humans , Phosphoenolpyruvate , Phosphoenolpyruvate Carboxykinase (ATP)/genetics , Phosphoenolpyruvate Carboxykinase (GTP)/genetics , Gluconeogenesis/genetics , Phosphoenolpyruvate Carboxylase/metabolism , Peripheral Nervous System Diseases/geneticsABSTRACT
BACKGROUND: To investigate the role of circNFIB in the alleviation of myocardial fibrosis by endogenous sulfur dioxide (SO2). METHODS: We stimulated cultured neonatal rat cardiac fibroblasts with transforming growth factor-ß1 (TGF-ß1) and developed an in vitro myocardial fibrosis model. Lentivirus vectors containing aspartate aminotransferase 1 (AAT1) cDNA were used to overexpress AAT1, and siRNA was used to silence circNFIB. The SO2, collagen, circNFIB, Wnt/ß-catenin, and p38 MAPK pathways were examined in each group. RESULTS: In the in vitro TGF-ß1-induced myocardial fibrosis model, endogenous SO2/AAT1 expression was significantly decreased, and collagen levels in the cell supernatant and type I and III collagen expression, as well as α-SMA expression, were all significantly increased. TGF-ß1 also significantly reduced circNFIB expression. AAT1 overexpression significantly reduced myocardial fibrosis while significantly increasing circNFIB expression. Endogenous SO2 alleviated myocardial fibrosis after circNFIB expression was blocked. We discovered that circNFIB plays an important role in the alleviation of myocardial fibrosis by endogenous SO2 by inhibiting the Wnt/ß-catenin and p38 MAPK pathways. CONCLUSION: Endogenous SO2 promotes circNFIB expression, which inhibits the Wnt/ß-catenin and p38 MAPK signaling pathways, consequently alleviating myocardial fibrosis.
Subject(s)
Transforming Growth Factor beta1 , beta Catenin , Rats , Animals , Transforming Growth Factor beta1/metabolism , beta Catenin/metabolism , Sulfur Dioxide/metabolism , Sulfur Dioxide/pharmacology , Fibrosis , Collagen , p38 Mitogen-Activated Protein KinasesABSTRACT
Hematopoiesis changes over life to meet the demands of maturation and aging. Here, we find that the definitive hematopoietic stem and progenitor cell (HSPC) compartment is remodeled from gestation into adulthood, a process regulated by the heterochronic Lin28b/let-7 axis. Native fetal and neonatal HSPCs distribute with a pro-lymphoid/erythroid bias with a shift toward myeloid output in adulthood. By mining transcriptomic data comparing juvenile and adult HSPCs and reconstructing coordinately activated gene regulatory networks, we uncover the Polycomb repressor complex 1 (PRC1) component Cbx2 as an effector of Lin28b/let-7's control of hematopoietic maturation. We find that juvenile Cbx2-/- hematopoietic tissues show impairment of B-lymphopoiesis, a precocious adult-like myeloid bias, and that Cbx2/PRC1 regulates developmental timing of expression of key hematopoietic transcription factors. These findings define a mechanism of regulation of HSPC output via chromatin modification as a function of age with potential impact on age-biased pediatric and adult blood disorders.
Subject(s)
Hematopoiesis , Hematopoietic Stem Cells , MicroRNAs , Polycomb Repressive Complex 1 , RNA-Binding Proteins , Adult , Animals , Child , Gene Regulatory Networks , Hematopoiesis/genetics , Hematopoietic Stem Cells/metabolism , Humans , Infant, Newborn , Lymphopoiesis , Mice , Polycomb Repressive Complex 1/genetics , Polycomb Repressive Complex 1/metabolism , Polycomb-Group Proteins/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolismABSTRACT
Polymer adhesives have emerged as a promising dielectric passivation layer in hybrid bonding for 3D integration, but they raise misalignment problems during curing. In this work, the synergistic effect of oxygen plasma surface activation and wetting is utilized to achieve bonding between completed cured polyimides. The optimized process achieves a void-less bonding with a maximum shear strength of 35.3 MPa at a low temperature of 250 °C in merely 2 min, significantly shortening the bonding period and decreasing thermal stress. It is found that the plasma activation generates hydrophilic groups on the polyimide surface, and the wetting process further introduces more -OH groups and water molecules on the activated polyimide surface. The synergistic process of plasma activation and wetting facilitates the bridging of polyimide interfaces to achieve bonding, providing an alternative path for adhesive bonding in 3D integration.
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BACKGROUND: IgA vasculitis is characterized by inflammation of the blood vessels, which can result in microvascular destruction and consequently renal damage. Transthyretin is a newly discovered angiogenesis regulator in promoting microvascular regeneration. This indicates that transthyretin may act as a potential predictor of IgAV as well as IgAVN. METHODS: This retrospective study included 125 patients newly diagnosed as IgAV with demographic and laboratory parameters. Of these, 78 patients had demonstrated internal organ damage and 47 patients with only skin and joint injury. Of 78 patients with organ impairment, 27 were diagnosed of renal involvement. Then we evaluated the relationship between NLR, total protein, albumin, globulin, transthyretin, B lymphocyte counts and the severity of IgAV. RESULTS: For patients with internal organ or renal involvement, the level of transthyretin were lower than non-internal organ damage group (p < 0.001 for both group). Remarkably, the NLR was only higher in patients with internal organ damage group (p = 0.019). Logistic regression analysis showed that NLR and transthyretin both were risk factors for internal organ involvement (OR = 1.768, 0.973 separately), and only transthyretin is the independent risk for renal involvement (OR = 0.981, p < 0.05). The ROC analysis showed an AUC of 0.626 for NLR, 0.815 for transthyretin in predicting organ damage, 0.755 for transthyretin in patients with renal involvement (p < 0.05, to all parameters). CONCLUSIONS: Transthyretin is a better predictor in predicting internal organ or renal involvement than NLR, and low plasma transthyretin concentration can increase the risk of renal involvement in IgAV patients.
Subject(s)
IgA Vasculitis , Nephritis , Child , Humans , Immunoglobulin A , Prealbumin , Retrospective StudiesABSTRACT
High-risk forms of B-acute lymphoblastic leukemia (B-ALL) remain a therapeutic challenge. Leukemia-initiating cells (LICs) self-renew and spark relapse and therefore have been the subject of intensive investigation; however, the properties of LICs in high-risk B-ALL are not well understood. Here, we use single-cell transcriptomics and quantitative xenotransplantation to understand LICs in MLL-rearranged (MLL-r) B-ALL. Compared with reported LIC frequencies in acute myeloid leukemia (AML), engraftable LICs in MLL-r B-ALL are abundant. Although we find that multipotent, self-renewing LICs are enriched among phenotypically undifferentiated B-ALL cells, LICs with the capacity to replenish the leukemic cellular diversity can emerge from more mature fractions. While inhibiting oxidative phosphorylation blunts blast proliferation, this intervention promotes LIC emergence. Conversely, inhibiting hypoxia and glycolysis impairs MLL-r B-ALL LICs, providing a therapeutic benefit in xenotransplantation systems. These findings provide insight into the aggressive nature of MLL-r B-ALL and provide a rationale for therapeutic targeting of hypoxia and glycolysis.
Subject(s)
Leukemia, Myeloid, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Glycolysis , Humans , Hypoxia , Leukemia, Myeloid, Acute/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/geneticsABSTRACT
Financial market and economic growth and development trends can be regarded as an extremely complex system, and the in-depth study and prediction of this complex system has always been the focus of attention of economists and other scholars. Emotion recognition algorithm is a pattern recognition technology that integrates a number of emerging science and technology, and has good non-linear system fitting capabilities. However, using emotion recognition algorithm models to analyze and predict financial market and economic growth and development trends can yield more accurate prediction results. This article first gives a detailed introduction to the existing financial development and economic growth status and development trend forecasting problems, and then gives a brief overview of the concept of emotion recognition algorithms. Then, it describes the emotion recognition methods, including statistical emotion recognition methods, mixed emotion recognition methods, and emotion recognition methods based on knowledge technology, and conducts in-depth research on the three algorithm models of statistical emotion recognition methods, they are the support vector machine algorithm model, the artificial neural network algorithm model, and the long and short-term memory network algorithm model. Finally, these three algorithm models are applied to the financial market and economic growth and development trend prediction experiments. Experimental results show that the average absolute error of the three algorithms is below 25, which verifies that the emotion recognition algorithm has good operability and feasibility for the prediction of financial market and economic growth and development trends.
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Objective: This study aimed to investigate the efficacy and safety of belimumab for treating children with refractory childhood-onset systemic lupus erythematosus (cSLE). Methods: Twenty-six cSLE patients who received belimumab treatment in our hospital from January 2020 to September 2021 (23 of them for more than 52 weeks) were enrolled in this study. Their clinical and laboratory data, assessment of disease activity, glucocorticoid dosage, and treatment-emergent adverse events (TEAEs) were retrieved for analysis. The paired samples t-test and the nonparametric test were used to compare the baseline and post-treatment data. Results: The mean age of onset was 10.3 ± 2.4 years old; the mean disease duration was 41.6 ± 37.4 months; the median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 10 (P 25, P 75: 3, 17); and the mean Physician's Global Assessment (PGA) score at baseline was 1.9 ± 1.0. Compared with the baseline values, there was a significant decrease in the 24-h urine protein quantifications at 24 and 52 weeks of treatment (P<0.05) as well as an elevated complement (C) 3 and C4 levels at 4, 12, 24, and 52 weeks of treatment. In addition, the SLEDAI-2K and PGA scores as well as the percentage of CD19+ B cells were significantly decreased at 12, 24, and 52 weeks of treatment compared with the baseline values (P<0.05). The dosage of glucocorticoid at 4, 12, 24, and 52 weeks of treatment was significantly less than that at baseline or the previous follow-up (P<0.05). At 52 weeks, 14 subjects (53.8%) achieved Lupus Low Disease Activity State (LLDAS), and 4 subjects (15.4%) reached clinical remission (CR). At the last follow-up, 16 subjects (61.5%) achieved LLDAS, and 10 subjects (38.5%) reached CR. Conclusions: Belimumab treatment can significantly improve laboratory indicators, reduce disease activity, and decrease the dosage of glucocorticoid required in children with cSLE. Moreover, it has a good safety profile.
Subject(s)
Antibodies, Monoclonal, Humanized , Glucocorticoids , Lupus Erythematosus, Systemic , Child , Humans , Glucocorticoids/adverse effects , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Retrospective Studies , Severity of Illness Index , Treatment Outcome , Antibodies, Monoclonal, Humanized/adverse effectsABSTRACT
Background: The aim of this study was to report the clinical features and mutations in a patient with autosomal-inherited Alport syndrome (AS). Methods: We examined the clinical data, mutation analysis results, and family tree of a patient with autosomal-inherited AS, who had nephrotic syndrome as her first manifestation. Results: The proband was a girl of 11 months who presented with nephritic and nephrotic syndromes including gross hematuria but had a normal renal function. Her treatment course was complicated by steroid resistance and a poor response to cyclosporine A and cyclophosphamide pulse therapy. Renal biopsy was performed 2 years after disease onset; light microscopy showed glomerular segmental mesangio-proliferative lesions, and type IV collagen staining showed the loss of the α3 chain in the glomerular and tubular basement membrane (GBM and TBM) and α5 chain loss in the GBM. Electron microscopy showed uneven GBM thickness, with the dense basement membrane (BM) layer obviously delaminated and torn, showing a typical "lace-like" change. The segmental BM was loosened and widened. Her father did not develop microscopic hematuria until 10 years later, while her grandmother had asymptomatic hematuria and proteinuria when the proband was diagnosed. We detected a new COL4A4 mutation in the proband, namely c.1715delG (p.G572Vfs * 81) in exon 24. Her father and grandmother carried the same mutation, but her mother and sister did not. Conclusions: We found a new potentially pathogenic mutation of COL4A4 in a patient with autosomal-inherited AS, which presented as nephrotic syndrome in infancy.