[Application of 18F-FDG PET/CT in rheumatic diseases].

OBJECTIVE: To explore the application of 18F-flurodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in rheumatic diseases, to compare these different imaging features, and to describe the current PET/CT imaging status in clinical practice. METHODS: A total of 486 cases in our department from January 2012 to December 2018 were enrolled in this study, and 18F-FDG PET/CT examination was performed in all the patients. The clinical use of 18F-FDG PET/CT was retrospectively analyzed to discuss the clinical application and its imaging characteristics of rheumatic diseases. Categorical data were used to ascertain prevalence statistics, whereas continuous data were used to delineate means and standard deviations. Independent sample t test, Chi square test and Mann-Whitney U test were used for statistical analysis. A P-value of < 0.05 was considered significant. RESULTS: (1) From 2012 to 2018, totally 486 patients in the Department of Rheumatology and Immunology underwent 18F-FDG PET/CT examination, accounting for 5.30% of the total number of PET/CT examinations in the whole hospital. In this study, 304 of the 486 patient were female (62.55%), 182 of them were male (37.45%), the average age of the patients was (53.21±18.81) years, and the proportion of the patients aged 45-65 (227/486, 46.71%) was the highest group. (2) Three leading purposes of the PET/CT examination in our department were to exclude cancers (55.56%), assist in diagnosis (24.60%) and evaluate the disease activity (19.84%). (3) Of the 486 patients who underwent 18F-FDG PET/CT, 327 cases might indicate a differential diagnosis of rheumatic disease, of which, 292 cases were highly suggestive of diagnosis, including 61 cases of myositis, 60 cases of vasculitis, 37 cases of adult still's disease, 32 cases of IgG4 related diseases, 30 cases of rheumatoid arthritis, 22 cases of Sjögren's syndrome, 22 cases of systemic lupus erythematosus, and 9 cases of rheumatic polymyalgia; the remaining 35 cases only prompted the possibility of autoimmune disease. Of the 486 patients, 74 cases suggested the diagnosis of cancers, 25 cases indicated the diagnosis of infectious diseases, while 60 cases could not show any diagnostic values. Ten patients with rheumatic disease were followed up with a post-treatment repeat PET/CT, and the findings in remission showed reduced 18F-FDG metabolic activity as well as a reduction in the extent of metabolic hypertrophic lesions. CONCLUSION: There are some typical sign of 18F-FDG PET/CT for diffuse connective tissue diseases, therefore 18F-FDG PET/CT has auxi-liary effect on the classification diagnosis of rheumatic diseases, especially for the exclusion of cancers.

Rheumatoid arthritis patients harbour aberrant enteric bacteriophages with autoimmunity-provoking potential: a paired sibling study.

OBJECTIVES: Viruses have been considered as important participants in the development of rheumatoid arthritis (RA). However, the profile of enteric virome and its role in RA remains elusive. This study aimed to investigate the atlas and involvement of virome in RA pathogenesis. METHODS: Faecal samples from 30 pairs of RA and healthy siblings that minimise genetic interferences were collected for metagenomic sequencing. The α and ß diversity of the virome and the virome-bacteriome interaction were analysed. The differential bacteriophages were identified, and their correlations with clinical and immunological features of RA were analysed. The potential involvement of these differential bacteriophages in RA pathogenesis was further investigated by auxiliary metabolic gene annotation and molecular mimicry study. The responses of CD4+ T cells and B cells to the mimotopes derived from the differential bacteriophages were systemically studied. RESULTS: The composition of the enteric bacteriophageome was distorted in RA. The differentially presented bacteriophages correlated with the immunological features of RA, including anti-CCP autoantibody and HLA-DR shared epitope. Intriguingly, the glycerolipid and purine metabolic genes were highly active in the bacteriophages from RA. Moreover, peptides of RA-enriched phages, in particular Prevotella phage and Oscillibacter phage could provoke the autoimmune responses in CD4+ T cells and plasma cells via molecular mimicry of the disease-associated autoantigen epitopes, especially those of Bip. CONCLUSIONS: This study provides new insights into enteric bacteriophageome in RA development. In particular, the aberrant bacteriophages demonstrated autoimmunity-provoking potential that would promote the occurrence of the disease.

MDSCs are important osteoclast precursors primed by B cells in rheumatoid arthritis.

Osteoclast-mediated bone erosion and deformation represent significant pathological features in rheumatoid arthritis (RA). Myeloid-derived suppressor cells (MDSCs) and B cells have emerged as key contributors to the progression of RA. Nevertheless, their involvement, especially the interaction in RA osteoclastogenesis remains elusive. In this study, our results revealed a marked expansion of MDSCs in RA patients, and importantly, their abundance was positively correlated with radiographic damage evaluated by the Sharp/van der Heijde score. Notably, MDSCs derived from both RA patients and arthritic mice exhibited a heightened propensity to differentiate into osteoclasts compared with those from healthy individuals. Intriguingly, we observed that B cells from RA patients could augment the osteoclastogenic potential of MDSCs, which was also observed in arthritic mice. The impact of B cells on MDSC-mediated osteoclastogenesis was found to be most pronounced in switched memory B cells, followed by CD21low B cells and naïve B cells. MDSCs from B-cell-deficient mice exhibited diminished capacity to differentiate into osteoclasts, accompanied by distinct gene expression profiles associated with osteoclastogenesis. Taken together, our findings suggested that MDSCs were important osteoclast precursors primed by B cells in RA, serving as novel therapeutic targets for the persistent disease.

ChatGPT's ability to generate realistic experimental images poses a new challenge to academic integrity.

The rapid advancements in large language models (LLMs) such as ChatGPT have raised concerns about their potential impact on academic integrity. While initial concerns focused on ChatGPT's writing capabilities, recent updates have integrated DALL-E 3's image generation features, extending the risks to visual evidence in biomedical research. Our tests revealed ChatGPT's nearly barrier-free image generation feature can be used to generate experimental result images, such as blood smears, Western Blot, immunofluorescence and so on. Although the current ability of ChatGPT to generate experimental images is limited, the risk of misuse is evident. This development underscores the need for immediate action. We suggest that AI providers restrict the generation of experimental image, develop tools to detect AI-generated images, and consider adding "invisible watermarks" to the generated images. By implementing these measures, we can better ensure the responsible use of AI technology in academic research and maintain the integrity of scientific evidence.

Immunological role of Gas6/TAM signaling in hemostasis and thrombosis.

The immune system is an emerging regulator of hemostasis and thrombosis. The concept of immunothrombosis redefines the relationship between coagulation and immunomodulation, and the Gas6/Tyro3-Axl-MerTK (TAM) signaling pathway builds the bridge across them. During coagulation, Gas6/TAM signaling pathway not only activates platelets, but also promotes thrombosis through endothelial cells and vascular smooth muscle cells involved in inflammatory responses. Thrombosis appears to be a common result of a Gas6/TAM signaling pathway-mediated immune dysregulation. TAM TK and its ligands have been found to be involved in coagulation through the PI3K/AKT or JAK/STAT pathway in various systemic diseases, providing new perspectives in the understanding of immunothrombosis. Gas6/TAM signaling pathway serves as a breakthrough target for novel therapeutic strategies to improve disease management. Many preclinical and clinical studies of TAM receptor inhibitors are in process, confirming the pivotal role of Gas6/TAM signaling pathway in immunothrombosis. Therapeutics targeting the TAM receptor show potential both in anticoagulation management and immunotherapy. Here, we review the immunological functions of the Gas6/TAM signaling pathway in coagulation and its multiple mechanisms in diseases identified to date, and discuss the new clinical strategies that may generated by these roles.

Transmural Flow Upregulates PD-L1 Expression in Microvascular Networks.

Endothelial programmed death-ligand 1 (PD-L1) expression is higher in tumors than in normal tissues. Also, tumoral vasculatures tend to be leakier than normal vessels leading to a higher trans-endothelial or transmural fluid flow. However, it is not clear whether such elevated transmural flow can control endothelial PD-L1 expression. Here, a new microfluidic device is developed to investigate the relationship between transmural flow and PD-L1 expression in microvascular networks (MVNs). After treating the MVNs with transmural flow for 24 h, the expression of PD-L1 in endothelial cells is upregulated. Additionally, CD8 T cell activation by phytohemagglutinin (PHA) is suppressed when cultured in the MVNs pre-conditioned with transmural flow. Moreover, transmural flow is able to further increase PD-L1 expression in the vessels formed in the tumor microenvironment. Finally, by utilizing blocking antibodies and knock-out assays, it is found that transmural flow-driven PD-L1 upregulation is controlled by integrin αVß3. Overall, this study provides a new biophysical explanation for high PD-L1 expression in tumoral vasculatures.

Step into the era of large multimodal models: a pilot study on ChatGPT-4V(ision)'s ability to interpret radiological images.

BACKGROUND: The introduction of ChatGPT-4V's 'Chat with images' feature represents the beginning of the era of large multimodal models (LMMs), which allows ChatGPT to process and answer questions based on uploaded images. This advancement has the potential to transform how surgical teams utilize radiographic data, as radiological interpretation is crucial for surgical planning and postoperative care. However, a comprehensive evaluation of ChatGPT-4V's capabilities in interpret radiological images and formulating treatment plans remains to be explored. PATIENTS AND METHODS: Three types of questions were collected: (1) 87 USMLE-style questions, submitting only the question stems and images without providing options to assess ChatGPT's diagnostic capability. For questions involving treatment plan formulations, a five-point Likert scale was used to assess ChatGPT's proposed treatment plan. The 87 questions were then adapted by removing detailed patient history to assess its contribution to diagnosis. The diagnostic performance of ChatGPT-4V was also tested when only medical history was provided. (2) We randomly selected 100 chest radiography from the ChestX-ray8 database to test the ability of ChatGPT-4V to identify abnormal chest radiography. (3) Cases from the 'Diagnose Please' section in the Radiology journal were collected to evaluate the performance of ChatGPT-4V in diagnosing complex cases. Three responses were collected for each question. RESULTS: ChatGPT-4V achieved a diagnostic accuracy of 77.01% for USMLE-style questions. The average score of ChatGPT-4V's treatment plans was 3.97 (Interquartile Range: 3.33-4.67). Removing detailed patient history dropped the diagnostic accuracy to 19.54% (P<0.0001). ChatGPT-4V achieved an AUC of 0.768 (95% CI: 0.684-0.851) in detecting abnormalities in chest radiography, but could not specify the exact disease due to the lack of detailed patient history. For cases from 'Diagnose Please' ChatGPT provided diagnoses consistent with or very similar to the reference answers. CONCLUSION: ChatGPT-4V demonstrated an impressive ability to combine patient history with radiological images to make diagnoses and directly design treatment plans based on images, suggesting its potential for future application in clinical practice.

Elevated expression of hsa_circ_0000479 in neutrophils correlates with features of systemic lupus erythematosus.

OBJECTIVE: Accumulating evidence suggests that differentially expressed circular RNAs (circRNAs) play critical roles in immune cells of systemic lupus erythematosus (SLE) patients. Hsa_circ_0000479 has been studied in the field of cancer and infection, whereas seldom studied in autoimmune diseases. The aim of this study was to investigate the role and clinical value of neutrophil hsa_circ_0000479 in SLE. METHODS: The expression levels of hsa_circ_0000479 in both healthy individuals and SLE patients' neutrophils were detected by qPCR and compared with those in peripheral blood mononuclear cells (PBMCs) . In addition, the correlation of hsa_circ_0000479 levels in neutrophils with the clinical and immunological features of SLE patients was also analysed. RESULTS: The expression levels of hsa_circ_0000479 in the patients with SLE were significantly higher in neutrophils than that of PBMCs, and also significantly higher than that in healthy controls (HCs). Moreover, the expression levels of hsa_circ_0000479 in neutrophils were negatively associated with absolute neutrophil count and complement 3 (C3), whereas positively correlated with anti-dsDNA and anti-nucleosome antibodies in SLE. In addition, SLE patients with higher levels of hsa_circ_0000479 demonstrated more several clinical manifestations, including Raynaud's phenomenon, alopecia and leucopenia. CONCLUSIONS: Hsa_circ_0000479 is up-regulated in neutrophils of SLE patients, and is also associated with several important laboratory indicators and clinical manifestations, suggesting that hsa_circ_0000479 in neutrophils was one of probable factors involved in the pathogenesis of SLE with potential clinical value.

Hsa_circ_0000479 was expressed in neutrophils and was considerably higher than that of PBMCs in SLE patients.The neutrophil hsa_circ_0000479 was correlated with laboratory parameters, including NEUT, C3, anti-dsDNA antibodies and AnuA, in addition to being associated with Raynaud's phenomenon, alopecia, and leucopenia in patients with SLE.Hsa_circ_0000479 in neutrophils may play an influential role in SLE patients and will be important to understand the pathogenesis, stratification and treatment in SLE.

Proinflammatory phenotype of B10 and B10pro cells elicited by TNF-α in rheumatoid arthritis.

OBJECTIVES: B10 and B10pro cells suppress immune responses via secreting interleukin (IL)-10. However, their regulators and underlying mechanisms, especially in human autoimmune diseases, are elusive. This study aimed to address these questions in rheumatoid arthritis (RA), one of the most common highly disabling autoimmune diseases. METHODS: The frequencies and functions of B10 and B10pro cells in healthy individuals and patients with RA were first analysed. The effects of proinflammatory cytokines, particularly tumour necrosis factor (TNF)-α on the quantity, stability and pathogenic phenotype of these cells, were then assessed in patients with RA before and after anti-TNF therapy. The underlying mechanisms were further investigated by scRNA-seq database reanalysis, transcriptome sequencing, TNF-α-/- and B cell-specific SHIP-1-/- mouse disease model studies. RESULTS: TNF-α was a key determinant for B10 cells. TNF-α elicited the proinflammatory feature of B10 and B10pro cells by downregulating IL-10, and upregulating interferon-γ and IL-17A. In patients with RA, B10 and B10pro cells were impaired with exacerbated proinflammatory phenotype, while anti-TNF therapy potently restored their frequencies and immunosuppressive functions, consistent with the increased B10 cells in TNF-α-/- mice. Mechanistically, TNF-α diminished B10 and B10pro cells by inhibiting their glycolysis and proliferation. TNF-α also regulated the phosphatidylinositol phosphate signalling of B10 and B10pro cells and dampened the expression of SHIP-1, a dominant phosphatidylinositol phosphatase regulator of these cells. CONCLUSIONS: TNF-α provoked the proinflammatory phenotype of B10 and B10pro cells by disturbing SHIP-1 in RA, contributing to the disease development. Reinstating the immunosuppressive property of B10 and B10pro cells might represent novel therapeutic approaches for RA.

Evaluation of the psychometrics of the Social Impact Scale and its association with depression among asymptomatic COVID-19 carriers.

BACKGROUND: COVID-19 carriers experience psychological stresses and mental health issues such as varying degrees of stigma. The Social Impact Scale (SIS) can be used to measure the stigmatisation of COVID-19 carriers who experience such problems. AIMS: To evaluate the reliability and validity of the Chinese version of the SIS, and the association between stigma and depression among asymptomatic COVID-19 carriers in Shanghai, China. METHOD: A total of 1283 asymptomatic COVID-19 carriers from Shanghai Ruijin Jiahe Fangcang Shelter Hospital were recruited, with a mean age of 39.64 ± 11.14 years (59.6% male). Participants completed questionnaires, including baseline information and psychological measurements, the SIS and Self-Rating Depression Scale. The psychometrics of the SIS and its association with depression were examined through exploratory factor analysis, confirmatory factor analysis and receiver operating characteristic analysis. RESULTS: The average participant SIS score was 42.66 ± 14.61 (range: 24-96) years. Analyses suggested the model had four factors: social rejection, financial insecurity, internalised shame and social isolation. The model fit statistics of the four-factor SIS were 0.913 for the comparative fit index, 0.902 for the Tucker-Lewis index and 0.088 for root-mean-square error of approximation. Standard estimated factor loadings ranged from 0.509 to 0.836. After controlling for demographic characteristics, the total score of the 23-item SIS predicted depression (odds ratio: 1.087, 95% CI 1.061-1.115; area under the curve: 0.84, 95% CI 0.788-0.892). CONCLUSIONS: The Chinese version of the SIS showed good psychometric properties and can be used to assess the level of perceived stigma experienced by asymptomatic COVID-19 carriers.

Antibody production relies on the tRNA inosine wobble modification to meet biased codon demand.

Antibodies are produced at high rates to provide immunoprotection, which puts pressure on the B cell translational machinery. Here, we identified a pattern of codon usage conserved across antibody genes. One feature thereof is the hyperutilization of codons that lack genome-encoded Watson-Crick transfer RNAs (tRNAs), instead relying on the posttranscriptional tRNA modification inosine (I34), which expands the decoding capacity of specific tRNAs through wobbling. Antibody-secreting cells had increased I34 levels and were more reliant on I34 for protein production than naïve B cells. Furthermore, antibody I34-dependent codon usage may influence B cell passage through regulatory checkpoints. Our work elucidates the interface between the tRNA pool and protein production in the immune system and has implications for the design and selection of antibodies for vaccines and therapeutics.

Traumatic acid inhibits ACSL4 associated lipid accumulation in adipocytes to attenuate high-fat diet-induced obesity.

Obesity is a major health concern that lacks effective intervention strategies. Traumatic acid (TA) is a potent wound-healing agent in plants, considered an antioxidant food ingredient. This study demonstrated that TA treatment significantly reduced lipid accumulation in human adipocytes and prevented high-fat diet induced obesity in zebrafish. Transcriptome sequencing revealed TA-activated fatty acid (FA) degradation and FA metabolism signaling pathways. Moreover, western blotting and quantitative polymerase chain reaction showed that TA inhibited the expression of long-chain acyl-CoA synthetase-4 (ACSL4). Overexpression of ACSL4 resulted in the reversal of TA beneficiary effects, indicating that the attenuated lipid accumulation of TA was regulated by ACSL4 expression. Limited proteolysis-mass spectrometry and microscale thermophoresis were then used to confirm hexokinase 2 (HK2) as a direct molecular target of TA. Thus, we demonstrated the molecular basis of TA in regulating lipid accumulation and gave the first evidence that TA may function through the HK2-ACSL4 axis.

Transcriptomics profiling reveal the heterogeneity of white and brown adipocyte.

The marker genes associated with white adipocytes and brown adipocytes have been previously identified; however, these markers have not been updated in several years, and the differentiation process of preadipocytes remains relatively fixed. Consequently, there has been a lack of exploration into alternative differentiation schemes. In this particular study, we present a transcriptional signature specific to brown adipocytes and white adipocytes. Notably, our findings reveal that ZNF497, ZIC1, ZFY, UTY, USP9Y, TXLNGY, TTTY14, TNNT3, TNNT2, TNNT1, TNNI1, TNNC1, TDRD15, SOX11, SLN, SFRP2, PRKY, PAX3KLHL40, PAX3, INKA2-AS1, SOX11, and TDRD15 exhibit high expression levels in brown adipocytes. XIST, HOXA10, PCAT19, HOXA7, PLSCR3, and AVPR1A exhibited high expression levels in white adipocytes, suggesting their potential as novel marker genes for the transition from white to brown adipocytes. Furthermore, our analysis revealed the coordinated activation of several pathways, including the PPAR signaling pathway, focal adhesion, retrograde endocannabinoid signaling, oxidative phosphorylation, PI3K-Akt signaling pathway, and thermogenesis pathways, in brown adipocytes. Moreover, in contrast to prevailing culture techniques, we conducted a comparative analysis of the differentiation protocols for white preadipocytes and brown preadipocytes, revealing that the differentiation outcome remained unaffected by the diverse culture schemes employed. However, the expression levels of certain marker genes in both adipocyte types were found to be altered. This investigation not only identified potential novel marker genes for adipocytes but also examined the impact of different differentiation methods on preadipocyte maturation. Consequently, these findings offer significant insights for further research on the differentiation processes of diverse adipocyte subtypes.

Identifying central symptom clusters and correlates in children with acute leukemia undergoing chemotherapy: a network analysis.

Background: Previous studies have examined symptom clusters in children with acute leukemia, yet a knowledge gap persists regarding central symptom clusters and their influencing factors. By identifying these central clusters and associated factors, healthcare providers can enhance their understanding and effective management of symptoms. Our study seeks to address this gap by identifying symptom clusters, exploring central clusters, and investigating the demographic and health-related factors associated with these clusters in children with acute leukemia undergoing chemotherapy. Methods: A total of 586 children with acute leukemia from January 2021 to April 2023 were recruited from China. They were investigated using Memorial Symptom Assessment Scale 10-18 during chemotherapy. The principal component analysis was used to identify the symptom clusters. An association network was conducted to describe the relationships among symptoms and clusters. A multiple linear model was used to investigate the associated factors for the severity of overall symptoms and each symptom cluster. Results: Five clusters were identified, including oral and skin cluster, somatic cluster, self-image disorder cluster, gastrointestinal cluster and psychological cluster. Gastrointestinal cluster was the most central symptom cluster. Age, sex, clinical classification, number of having chemotherapy and education degree and marital status of the primary caregiver are associated with the severity of these five symptom clusters. Conclusion: Our study highlights the importance of evaluating symptom clusters in children with acute leukemia during chemotherapy. Specifically, addressing gastrointestinal symptoms is crucial for effective symptom management and overall care.

Tyro3 receptor tyrosine kinase contributes to pathogenic phenotypes of fibroblast-like synoviocytes in rheumatoid arthritis and disturbs immune cell balance in experimental arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by synovitis and joint damage, the underlying causes of which remain unclear. Our prior investigations revealed a notable correlation between the expression of Tyro3 Protein Tyrosine Kinase (Tyro3TK) and the progression of RA. To further elucidate the pathogenic role of Tyro3TK in RA, we analyzed the influence of Tyro3TK on pathogenic phenotypes of RA fibroblast like synoviocyte (FLS) in vitro and compared disease severity, joint damages and immunological parameters of K/BxN serum transfer arthritis (STA) in Tyro3TK-/- deficient mice and wild type controls. Our findings underscored the remarkable effectiveness of Tyro3TK blockade, as evidenced by diminished secretion of inflammatory cytokines and matrix metalloproteinases (MMPs), curtailed migration and invasiveness of RAFLS, and attenuated differentiation of pathogenic helper T cell subsets mediated by RAFLS. Correspondingly, our in vivo investigations illuminated the more favorable outcomes in Tyro3TK-deficient mice, characterized by reduced joint pathology, tempered synovial inflammation, and restored immune cell equilibrium. These data suggested that Tyro3TK might contribute to aggravated autoimmune arthritis and immunological pathology and act as a potential therapeutic target for RA.

Exploring core symptoms and interrelationships among symptoms in children with acute leukemia during chemotherapy: A network analysis.

PURPOSE: Children with acute leukemia have suffered from a considerable symptom burden during chemotherapy. However, few studies have focused on exploring the mechanisms among symptoms in children with acute leukemia. Our study aims to explore core symptoms and describe the interrelationships among symptoms in children with acute leukemia during chemotherapy. METHODS: From January 2021 to March 2023, 469 children with acute leukemia were recruited from 20 Chinese cities. The Memorial Symptom Assessment Scale 10-18 (MSAS 10-18) was used to evaluate the prevalence and severity of symptoms during chemotherapy. A network analysis was performed by the R software based on 31 symptoms. Centrality indices and density were used to explore core symptoms and describe interrelationships among symptoms in the network during chemotherapy. RESULTS: Worrying and feeling irritable were the central symptoms across the three centrality indices, including strength, closeness, and betweenness. Lack of energy was the most prevalent symptom; however, it was less central than other symptoms. The density of the "induction and remission" network significantly differed from other cycles' counterparts (p < 0.001). Global strength was greater in the " ≥ 8 years group " network than the " < 8 years group " network (p = 0.023). CONCLUSION: Network analysis provides a novel approach to identifying the core symptoms and understanding the interrelationships among symptoms. Our study indicates the need to assess emotional symptoms in children with acute leukemia during chemotherapy, especially during the induction and remission phases, as well as in older children. Future research is imperative to construct trajectories of dynamic symptom networks and centrality indices in longitudinal data to investigate the causal relationships among symptoms.

Machine learning algorithms to predict intraoperative hemorrhage in surgical patients: a modeling study of real-world data in Shanghai, China.

BACKGROUND: Prediction tools for various intraoperative bleeding events remain scarce. We aim to develop machine learning-based models and identify the most important predictors by real-world data from electronic medical records (EMRs). METHODS: An established database of surgical inpatients in Shanghai was utilized for analysis. A total of 51,173 inpatients were assessed for eligibility. 48,543 inpatients were obtained in the dataset and patients were divided into haemorrhage (N = 9728) and without-haemorrhage (N = 38,815) groups according to their bleeding during the procedure. Candidate predictors were selected from 27 variables, including sex (N = 48,543), age (N = 48,543), BMI (N = 48,543), renal disease (N = 26), heart disease (N = 1309), hypertension (N = 9579), diabetes (N = 4165), coagulopathy (N = 47), and other features. The models were constructed by 7 machine learning algorithms, i.e., light gradient boosting (LGB), extreme gradient boosting (XGB), cathepsin B (CatB), Ada-boosting of decision tree (AdaB), logistic regression (LR), long short-term memory (LSTM), and multilayer perception (MLP). An area under the receiver operating characteristic curve (AUC) was used to evaluate the model performance. RESULTS: The mean age of the inpatients was 53 ± 17 years, and 57.5% were male. LGB showed the best predictive performance for intraoperative bleeding combining multiple indicators (AUC = 0.933, sensitivity = 0.87, specificity = 0.85, accuracy = 0.87) compared with XGB, CatB, AdaB, LR, MLP and LSTM. The three most important predictors identified by LGB were operative time, D-dimer (DD), and age. CONCLUSIONS: We proposed LGB as the best Gradient Boosting Decision Tree (GBDT) algorithm for the evaluation of intraoperative bleeding. It is considered a simple and useful tool for predicting intraoperative bleeding in clinical settings. Operative time, DD, and age should receive attention.

Impaired regulatory function of granzyme B-producing B cells against T cell inflammatory responses in lupus mice.

OBJECTIVE: Recently, a new subtype of granzyme B (GrB)-producing Breg cells has been identified, which was proven to be involved in autoimmune disease. Our recent report demonstrated that GrB-producing Breg cells were correlated with clinical and immunological features of SLE. However, the effect of GrB-producing Breg cells in lupus mice is unclear. METHODS: GrB expression in naïve and lupus mouse B cells was analysed using flow cytometry, PCR, ELISA and ELISpot assays. To study the role of GrB-producing B cells in a lupus model, GrB knockout (KO) and wild-type (WT) mice were intraperitoneally injected with monoclonal cells from the mutant mouse strain B6.C-H-2bm12 (bm12) for 2 weeks. In addition, the function of GrB-producing Breg cells in naïve and lupus mice was further explored using in vitro B cells-CD4+CD25- T cell co-culture assays with GrB blockade/KO of B cells. RESULTS: B cells from the spleens of WT C57BL/6 (B6) mice could express and secret GrB (p<0.001). GrB-producing Breg cells from WT mice showed their regulatory functions on CD4+CD25- T cell. While the frequency of GrB-producing Breg cells was significantly decreased (p=0.001) in lupus mice (p<0.001). Moreover, GrB-producing Breg cells in lupus mice failed to suppress T cell-mediated proinflammatory responses, partially due to the impaired capacity of downregulating the T cell receptor-zeta chain and inducing CD4+CD25- T cell apoptosis. CONCLUSION: This study further revealed the function and mechanism of GrB-producing Breg cells in regulating T cell homeostasis in lupus mice and highlighted GrB-producing Breg cells as a therapeutic target in SLE.

Cybervictimization and non-suicidal self-injury among Chinese adolescents: The effect of depression and school connectedness.

Cybervictimization has been shown in many studies to be a risk factor for adolescent non-suicidal self-injurious behavior (NSSI). In this study we tested the roles of depression and school connectedness in this association. The Integrative Model of NSSI, Emotion Regulation and Interpersonal Relationship Model of NSSI, and Integrative Model of Social Media and Suicide provided the conceptual framework for the study. A sample of 1106 adolescents (M age = 13.17; SD = 0.69; 51.78% girls) completed anonymous questionnaires in their classrooms. The results of structural equation modeling showed that the positive association between cybervictimization and adolescent NSSI was mediated by depression. Moreover, this indirect link was stronger for adolescents with low vs. high school connectedness. The results have implications for intervention programs aimed at reducing NSSI among adolescents.

Refractory diarrhea in a patient with Sjogren's syndrome: A case report.

We present the case of a 66-year-old man with no abdominal symptoms other than chronic refractory diarrhea. Other causes for diarrhea were excluded. The positive results of anti-SSA antibodies, Schirmer's test, and the biopsy of minor salivary glands confirmed the diagnosis of Sjogren's syndrome. Moreover, during the course of treatment, the patient developed refeeding syndrome. His diarrhea and nutrition resolved with initiation of glucocorticoids. This case highlights that chronic refractory diarrhea can be the chief complaint and most severe symptom in patients with Sjogren's syndrome.