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Background: Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) is caused by UNC13D variants. The clinical manifestations of FHL3 are highly diverse and complex. Some patients exhibit atypical or incomplete phenotypes, making accurate diagnosis difficult. Our study aimed to broaden the understanding of the atypical FHL3 clinical spectrum. Methods: In our study, we analyzed in detail the clinical features of four Chinese patients with UNC13D variants. Additionally, we conducted a comprehensive review of the existing literature on previously reported atypical manifestations and summarized the findings. Results: Two of our patients presented with muscle involvement, while the other two had hematological involvement; none of them met the diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). However, protein expression and functional analysis ultimately confirmed diagnostic criteria for FHL3 in all patients. From the literature we reviewed, many atypical FHL3 patients had neurological involvement, especially isolated neurological manifestations. At the same time, arthritis and hypogammaglobulinemia were also prone to occur. Conclusion: Our study highlights that the expression of the Munc13‐4 protein may not fully indicate the pathogenicity of UNC13D variants, whereas CD107a analysis could be more sensitive for disease diagnosis. These findings contribute to a broader understanding of the FHL3 clinical spectrum and may offer new insights into the underlying pathogenesis of UNC13D variants. It is crucial to prioritize the timely and accurate diagnosis of atypical patients, as they may often be overlooked among individuals with rheumatic or hematological diseases. [ABSTRACT FROM AUTHOR]

Key Clinical Message: While adenomyosis is commonly associated with a mild risk of thrombotic complications, the presence of additional thrombophilia factors can increase this risk, particularly in individuals with severe symptoms and elevated CA125 levels. [ABSTRACT FROM AUTHOR]

Astragaloside IV (AS‐IV) has exhibited pivotal anti‐cancer efficacy in multiple types of cancer, including colorectal cancer (CRC). Meanwhile, circular RNA (circRNA) circ_0001615 has been reported to be involved in the malignant development of CRC. Herein, this study is expected to figure out the interaction between circ_0001615 and AS‐IV on CRC progression. The 50% inhibition concentration (IC50), proliferation, apoptosis, and migration were detected by Cell Counting Kit‐8 (CCK‐8), 5‐ethynyl‐2′‐deoxyuridine (EdU), flow cytometry, and wound healing assays. The expression of related proteins was examined by western blot. Circ_0001615, microRNA‐873‐5p (miR‐873‐5p), and LIM and SH3 protein 1 (LASP1) levels were detected by real‐time quantitative polymerase chain reaction (RT‐qPCR). The binding between miR‐873‐5p and circ_0001615, or LASP1, was predicted by Starbase, followed by verification by dual‐luciferase reporter and RNA immunoprecipitation (RIP) assays. The biological role of circ_0001615 and AS‐IV on CRC tumor growth was detected by the xenograft tumor model in vivo. According to the IC50 of AS‐IV in CRC cells, the 100 ng/mL AS‐IV treatment for 24 h was chosen for the following research: Our data confirmed that AS‐IV is a beneficial anti‐cancer agent in CRC cells. Furthermore, circ_0001615 and LASP1 expression were increased, and miR‐873‐5p was decreased in CRC patients and cell lines, whereas their expression exhibited an opposite trend in AS‐IV‐treated cells. Functionally, applying AS‐IV might act as a beneficial anti‐cancer effect by downregulating circ_0001615 in CRC cells in vitro. Mechanically, circ_0001615 serves as a sponge for miR‐873‐5p to affect LASP1 expression. In addition, AS‐IV inhibited CRC cell growth in vivo by modulating circ_0001615. Overall, AS‐IV could mitigate CRC development, at least in part, through the circ_0001615/miR‐873‐5p/LASP1 axis. These findings support a theoretical basis for an in‐depth study of the function of AS‐IV and the clinical treatment of CRC. [ABSTRACT FROM AUTHOR]

This article discusses a case of polyarticular juvenile idiopathic arthritis (JIA) with rice body formation in a 4-year-old female patient. The patient presented with painless swelling in the right ankle and left knee, along with limited movement and localized elevated skin temperature. Laboratory tests revealed abnormal levels of C-reactive protein, D-dimer, and erythrocyte sedimentation rate. Imaging showed extensive abnormal nodular signals in the joints, which were diagnosed as rice body synovitis. The patient was treated with anti-inflammatory medication and showed significant improvement in swelling. Rice body formation is a rare inflammatory disorder associated with systemic disease, and it is suggested to be caused by synovial microinfarcts or fibrin aggregation in the joint cavity. This is the first reported case of polyarticular JIA with rice bodies, and the prognosis is generally good with appropriate treatment. The article concludes that surgery combined with medication is the best treatment approach for this condition. [Extracted from the article]

Developing highly efficient earth‐abundant alternatives to traditional noble metal catalysts is essential for clean and sustainable energy‐conversion and energy‐storage technologies, yet still challenging in limited active sites and weak resistance to electrochemical corrosion. Herein, density‐functional theory calculations demonstrate that hexagonal boron nitride (h‐BN), albeit often being considered inert, can generate boron‐active radicals at defective sites by forming heterogeneous structures with graphene‐containing point vacancies, leading to a substantial electron delocalization and charge transfer, indicating a superior catalytic activity. Experimentally, the van der Waals heterostructure is rationally designed with h‐BN nanosheets (BNNs) anchored on reduced graphene oxide (rGO) as strongly coupled composite catalysts. Despite the poor conductivity in BN and lower catalytic activity in rGO, the created heterostructures demonstrate unexpected, improved oxygen evolution reaction (OER) activity with excellent stability in alkaline electrolyte. Qualitative analysis of the valence band offset and theoretical calculation reveal that the formation of heterostructures can significantly drive the electron transfer between C and B atoms near the vacancies across the interface and cause a half‐metallic property of BN, decreasing the free energy barrier of four‐electron OER kinetics. Herein, the synthetic schemes of h‐BNNs are guided as highly active metal‐free OER electrocatalysts. [ABSTRACT FROM AUTHOR]

Background and aims: Diagnosis of leptomeningeal metastasis (LM) is challenging. In our previous study, CEACAM6 mRNA was found to be highly expressed in the circulating tumor cells of cerebrospinal fluid (CSF) from patients with lung adenocarcinoma with LM (LUAD‐LM). The aim of this study was to identify whether CEACAM6 could be used as a biomarker for LUAD‐LM. Materials and methods: The level of CEACAM6 was determined by enzyme‐linked immunosorbent assay (ELISA) in CSF from 40 LUAD‐LM and 44 normal controls, and additional serum samples from 138 LUAD patients, including 12 LUAD‐LM patients, and 30 healthy controls. Carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21‐1) and neuron‐specific enolase (NSE) levels in the CSF and sera were detected by chemiluminescent immunoassay. Receiver operating characteristic curve was plotted to evaluate the diagnostic performance for LUAD‐LM. Results: CSF CEACAM6 level was higher in LUAD‐LM than that in normal controls. In serum, LUAD patients had a higher level of CAECAM6 than healthy controls, and LM patients had the highest level among them. Serum CEACAM6 had a higher AUC than CEA in differentiating LM from non‐LM in LUAD patients (0.95 vs. 0.64, p < 0.001). Conclusion: CEACAM6 may serve as a potential biomarker in diagnosing LUAD‐LM. [ABSTRACT FROM AUTHOR]

Background: TYK2 deficiency is a rare primary immunodeficiency disease caused by loss‐of‐function mutations of TYK2 gene, which is initially proposed as a subset of hyper‐IgE syndrome (HIES). However, accumulating evidence suggests TYK2‐deficient patients do not necessarily present with HIES characteristics, indicating a vacuum of knowledge on the exact roles of TYK2 in human immune system. Method: Pathogenic effects of patients were confirmed by qRT‐PCR, Western blot, and protein stability assays. The responses to cytokines including IFN‐α/β/γ, IL‐6, IL‐10, IL‐12, and IL‐23 of peripheral blood mononuclear cells (PBMCs) from these patients were detected by Western blot, qRT‐PCR, and flow cytometry. The differentiation of T and B cells was detected by flow cytometry. Results: We described five more TYK2‐deficient cases presenting with or without hyper‐IgE levels, atopy, and distinct pathogen infection profile, which are caused by novel TYK2 mutations. These mutations were all found by high‐throughput sequencing and confirmed by Sanger sequencing. The patients showed heterogeneous responses to various cytokine treatments, including IFN‐α/β/γ, IL‐6, IL‐10, IL‐12, and IL‐23. The homeostasis of lymphocytes is also disrupted. Conclusion: Based on our findings, we propose that TYK2 works as a multi‐tasker in orchestrating various cytokine signaling pathways, differentially combined defects which account for the expressed clinical manifestations. [ABSTRACT FROM AUTHOR]

The deregulated cross‐talk between airway epithelial cells with subepithelial fibroblasts during inflammation drives the pathogenesis of asthma. Bioinformatics analysis and luciferase activity assay suggested that B cell lymphoma‐2 (BCL2) and CXC ligand 12 (CXCL12) are potential targets of miR‐23a. The aim of this study was to elucidate the effect of microRNA‐23a (miR‐23a) on BCL2, and CXCL12 in asthma. In E3 rats, miR‐23a was upregulated in lung tissues after antigen‐induced pulmonary inflammation during acute and chronic inflammation. Immunohistochemistry showed downregulation of BCL2 in the epithelium and of CXCL12 in subepithelial fibroblasts and smooth muscle cells. Treatment of isolated cells with miR‐23a mimic or inhibitor modified the expression of BCL2 and of CXCL12 in the expected cell type‐specific manner. Moreover, in epithelial cells, interleukin‐4 upregulated miR‐23a expression and thereby decreased the expression of BCL2, while increasing the caspase‐3 expression, which was followed by apoptosis. In fibroblasts, the expression of miR‐23a was increased by thymic stromal lymphopoietin (TSLP). Consequently, the CXCL12 expression was abrogated. The phosphorylation of CREB was also downregulated by TSLP through the action of miR‐23a. This study describes a novel mechanism, where miR‐23a is an important cell type‐specific regulator for asthma‐associated airway wall remodeling parameter. Thus, miR‐23a may present a potential new target for the therapy of asthma. [ABSTRACT FROM AUTHOR]

Aim To investigate the clinical features and prognoses of children who develop reversible posterior encephalopathy syndrome ( RPES) during treatment for nephrotic syndrome ( NS). Methods The clinicoradiological characteristics and prognoses of 51 patients with NS, including 21 with RPES and 30 without, were analyzed. Results Compared with the controls, the RPES patients exhibited a higher rate of tacrolimus ( P = 0.01) and cyclosporine ( P = 0.02) treatment; higher-dose prednisolone ( P = 0.01) treatment; higher systolic blood pressure ( P = 0.04), serum cholesterol ( P = 0.03), and proteinuria ( P < 0.01); and lower serum albumin levels ( P = 0.03). Hypertension was present in 85.7% of RPES patients. The clinical manifestations of RPES included an altered mental status, seizures, headaches, nausea and vomiting, and visual impairment. Electroencephalography findings included slow waves and focal sharp or/and spiked waves; magnetic resonance imaging showed lesions localized in the occipital, parietal, frontal, temporal lobes and the cerebellum and brainstem; and magnetic resonance angiography revealed vertebral artery narrowing. All RPES patients recovered completely with timely and appropriate therapy. Conclusion Hypertension, calcineurin inhibitor and high-dose steroid treatments, high serum cholesterol and proteinuria levels, and low serum albumin levels can predispose children with NS to RPES, although both the clinical and imaging outcomes are satisfactory. [ABSTRACT FROM AUTHOR]

Background Juvenile idiopathic arthritis ( JIA) has three major onset types with widely varying clinical features: systemic, polyarticular and pauciarticular. We assessed natural killer ( NK) cell function and killer cell immunoglobulin-like receptor ( KIR) genotypes in patients with different JIA subtypes. Methods Peripheral blood samples from 72 children with active JIA (systemic, 25; polyarticular, 24; pauciarticular, 23) and 25 controls were used for flow cytometric assessments of NK cell count, cytotoxicity, perforin, granzyme B, interferon ( IFN)-γ and tumour necrosis factor ( TNF)-α. Samples from 220 children with JIA (systemic, 84; polyarticular, 72; pauciarticular, 64) and 150 controls were used for KIR2 DS2, KIR2 DS4, KIR3 DS1, KIR2 DL1, KIR2 DL2, KIR2 DL3 and KIR3 DL1 typing by polymerase chain reaction with sequence-specific oligonucleotide probes. Results Compared with the controls, the patients with systemic JIA showed lower NK cell counts, cytotoxicity and perforin and granzyme B expression (p < 0.05), while the patients with pauci- and polyarticular JIA showed higher perforin and granzyme B expression (p < 0.05). NK cells produced higher level of TNF-α while lower level of IFN-γ in the pauci- and polyarticular JIA groups than in the systemic JIA group (p < 0.05). No significant differences in KIR gene frequencies were found between the JIA subgroups and healthy controls, except for the positive frequency and locus frequency of KIR2 DS4, which were lower in the systemic JIA group. Conclusions Compared with poly- and pauciarticular JIA, systemic JIA is associated with decreased NK cell function, more IFN-γ and less TNF-α secretion of NK cell and lower KIR2 DS4 frequency. [ABSTRACT FROM AUTHOR]

High-purity nanoparticles ZnS has been successfully synthesized using a simple coupling reaction process of biological reduction and chemical precipitation mediated with EDTA referred to as the CRBRCP-EDTA process. This research investigated the optimum conditions of the transformation of SO [ABSTRACT FROM AUTHOR]

Wiskott‐Aldrich syndrome (WAS) is an X‐linked primary immunodeficiency disease caused by a mutation in the WAS gene that encodes the WAS protein (WASp); up to 5‐10% of these patients develop inflammatory bowel disease (IBD). The mechanisms by which WASp deficiency causes IBD are unclear. Intestinal microbial dysbiosis and imbalances in host immune responses play important roles in the pathogenesis of polygenetic IBD; however, few studies have conducted detailed examination of the microbial alterations and their relationship with IBD in WAS. Here, we collected faecal samples from 19 children (all less than 2 years old) with WAS and samples from WASp‐KO mice with IBD and subjected them to 16S ribosomal RNA sequencing. We found that microbial community richness and structure in WAS children were different from those in controls; WAS children revealed reduced microbial community richness and diversity. Relative abundance of Bacteroidetes and Verrucomicrobiain in WAS children was significantly lower, while that of Proteobacteria was markedly higher. WASp‐KO mice revealed a significantly decreased abundance of Firmicutes. Faecal microbial dysbiosis caused by WASp deficiency is similar to that observed for polygenetic IBD, suggesting that WASp may play crucial function in microbial homoeostasis and that microbial dysbiosis may contribute to IBD in WAS. These microbial alterations may be useful targets for monitoring and therapeutically managing intestinal inflammation in WAS. [ABSTRACT FROM AUTHOR]

CD40 ligand (CD40L) deficiency is a rare but life‐threatening primary immunodeficiency caused by mutations in the CD40L gene. Here, we investigated a cohort of 40 genetically diagnosed CD40L‐deficient patients from the Chinese mainland, analysed their clinical and genetic data, and examined CD40L expression, the proportion of T cell subsets, B cell subsets and T follicular helper (Tfh) cells. The aim was to provide a complete picture of CD40L deficiency. Initial presentations of the patient cohort mainly involved recurrent fever (47.5%) and sinopulmonary infection (42.5%). Life‐threatening infections (42.5%), caused by various pathogens, were the most serious threats faced by CD40L‐deficient patients, while neutropenia (57.5%) remained the most common complication. Opportunistic infections, including Pneumocystis carinii pneumonia and invasive fungal disease associated with Talaromyces marneffei, were also common in the cohort. In addition, seven patients (17.5%) suffered BCGitis/BCGosis, which is a major problem facing a planned immunization programme in China. It was intriguing that reduced IgM levels were observed in 12.5% of patients, while normal or elevated IgA levels were shown in 47.5% of patients. Thirty‐seven unique mutations were identified in 40 patients; of these, 10 were novel. Furthermore, we observed a lower percentage of NK cells, Tfh cells, and central memory CD4+ T cells, and an extremely small class‐switched memory B cell population, in CD40L‐deficient patients. Patients who underwent hematopoietic stem cell transplantation experienced better disease remission. Taken together, our data establish the largest database about CD40L deficiency in China and provide genetic, immunologic and clinical information about Chinese CD40L‐deficient patients. [ABSTRACT FROM AUTHOR]

DOCK8 immunodeficiency syndrome (DIDS) is a combined immunodeficiency characterized by recurrent viral infections, severe atopy and early onset malignancy. Immunological abnormalities include lymphopenia, CD8+ T‐cell cytoskeleton dysfunction, defective B cell memory and variable serum immunoglobulin levels. Here, we analyse the B cell receptor repertoire (BCR) characteristics and antibody avidity of four DIDS patients, attempt to understand the dysregulated humoral immunity in DIDS patients with a normal antibody titre and suggest a scientific basis for intravenous immunoglobulin (IVIG) replacement therapy for these patients. We analysed BCR characteristics, including somatic hypermutation (SHM) frequency, using deep sequencing of multiplex PCR products derived from BCR heavy chain CDR3 regions from DIDS patients and controls. The antibody avidity of human tetanus and hemophilus influenza B antibodies was determined by ELISA using thiocyanate elution. IVIG replacement treatment and infection conditions were investigated retrospectively. We found skewing of the BCR repertoire and decreased antibody avidity in patients with DIDS. DIDS patients had fewer negatively charged amino acids than healthy controls. The SHM frequency of the IGHV3 gene was lower in patients with DIDS. Patients received regular IVIG therapy, resulting in fewer and less severe infections. We conclude that although IgG levels are normal in most DIDS patients, IVIG replacement therapy is still necessary. [ABSTRACT FROM AUTHOR]