The development and initial validation of IgG4-related disease damage index: a consensus report from Chinese IgG4-RD Consortium.

OBJECTIVE: To develop and conduct an initial validation of the Damage Index for IgG4-related disease (IgG4-RD DI). METHODS: A draft of index items for assessing organ damages in patients with IgG4-RD was generated by experts from the Chinese IgG4-RD Consortium (CIC). The preliminary DI was refined using the Delphi method, and a final version was generated by consensus. 40 IgG4-RD cases representing four types of clinical scenarios were then selected, each with two time points of assessment for at least 3 years of follow-up. 48 rheumatologists from 35 hospitals nationwide were invited to evaluate organ damage using the CIC IgG4-RD DI. The intraclass correlation coefficient (ICC) and the Kendall-W coefficient of concordance (KW) were used to assess the inter-rater reliability. The criterion validity of IgG4-RD DI was tested by calculating the sensitivity and specificity of raters. RESULTS: IgG4-RD DI is a cumulative index consisting of 14 domains of organ systems, including a total of 39 items. The IgG4-RD DI was capable of distinguishing stable and increased damage across the active disease subgroup and stable disease subgroup. In terms of scores at baseline and later observations by all raters, overall consistency in scores at baseline and later observations by all raters was satisfactory. ICC at the two time points was 0.69 and 0.70, and the KW was 0.74 and 0.73, respectively. In subgroup analysis, ICC and KW in all subgroups were over 0.55 and 0.61, respectively. The analysis of criterion validity showed a good performance with a sensitivity of 0.86 (95% CI 0.82 to 0.88), a specificity of 0.79 (95% CI 0.76 to 0.82) and an area under the curve of 0.88 (95% CI 0.85 to 0.91). CONCLUSION: The IgG4-RD DI is a useful approach to analyse disease outcomes, and it has good operability and credibility. It is anticipated that the DI will become a useful tool for therapeutic trials and studies of prognosis in patients with IgG4-RD.

Giant peritoneal loose body and its protein composition: a case report.

Peritoneal loose body (PLB) is a kind of lesions located in the abdominal cavity or pelvic cavity, which is rare and difficult to diagnose. The diameter of PLB is mostly 0.5-2.5 cm. Most PLBS are asymptomatic. Here we reported a case of giant PLB in the pelvis and analyzed its structure and protein composition. Surgical exploration revealed a white oval mass (4.5*4*3 cm) in the pelvic cavity. After the mass was removed, the symptoms of hematuria disappeared and the patient was discharged on the second postoperative day. Histochemical staining showed that PLB was mainly composed of collagen and scattered calcification. The protein components of PLB were detected by proteome analysis, and a variety of proteins related to collagen deposition and calcification were identified in PLB.

Correlation between oxygenation status of extra-synovial tissue of wrist and disease activity in rheumatoid arthritis: a photoacoustic imaging study.

OBJECTIVES: Rheumatoid arthritis (RA) is characterized by hypoxia in the synovial tissue. While photoacoustic imaging (PA) offers a method to evaluate tissue oxygenation in RA patients, studies exploring the link between extra-synovial tissue of wrist oxygenation and disease activity remain scarce. We aimed to assess synovial oxygenation in RA patients using a multimodal photoacoustic-ultrasound (PA/US) imaging system and establish its correlation with disease activity. METHODS: A retrospective study was conducted on 111 patients with RA and 72 healthy controls from 2022 to 2023. Dual-wavelength PA imaging quantified oxygen saturation (So2) levels in the synovial membrane and peri-wrist region. Oxygenation states were categorised as hyperoxia, intermediate oxygenation, and hypoxia based on So2 values. The association between oxygenation levels and the clinical disease activity index was evaluated using a one-way analysis of variance, complemented by the Kruskal-Wallis test with Bonferroni adjustment. RESULTS: Of the patients with RA, 39 exhibited hyperoxia, 24 had intermediate oxygenation, and 48 had hypoxia in the wrist extra-synovial tissue. All of the control participants exhibited the hyperoxia status. Oxygenation levels in patients with RA correlated with clinical metrics. Patients with intermediate oxygenation had a lower disease activity index compared with those with hypoxia and hyperoxia. CONCLUSION: A significant correlation exists between wrist extra-synovial tissue oxygenation and disease activity in patients with RA.

Global genomic diversity and conservation of SARS-CoV-2 since the COVID-19 outbreak.

IMPORTANCE: Our results indicate that most severe acute respiratory syndrome coronavirus 2 genomes sampled from patients had a mutation rate ≤1.07 ‰ and genome-tail proteins (including S protein) were the main sources of genetic polymorphism. The analysis of the virus-host interaction network of genome-tail proteins showed that they shared some antiviral signaling pathways, especially the intracellular protein transport pathway.

Single-cell communication patterns and their intracellular information flow in synovial fibroblastic osteoarthritis and rheumatoid arthritis.

BACKGROUND: Synovial fibroblasts are critical for maintaining homeostasis in major autoimmune diseases involving joint inflammation, including osteoarthritis and rheumatoid arthritis. However, little is known about the interactions among different cell subtypes and the specific sets of signaling pathways and activities that they trigger. METHODS: Using social network analysis, pattern recognition, and manifold learning approaches, we identified patterns of single-cell communication in OA (osteoarthritis) and RA (rheumatoid arthritis). RESULTS: Our results suggest that OA and RA have distinct cellular communication patterns and signaling pathways. The LAMININ (Laminin) and COLLAGEN (Collagen) pathways predominate in osteoarthritis, while the EGF (Epidermal growth factor), NT (Neurotrophin) and CDH5 (Cadherin 5) pathways predominate in rheumatoid arthritis, with a central role for THY1 (Thy-1 cell surface antigen) +CDH11 (Cadherin 11) + cells. The OA opens the PDGF (Platelet-derived growth factors) pathway (driver of bone angiogenesis), the RA opens the EGF pathway (bone formation) and the SEMA3 (Semaphorin 3A) pathway (involved in immune regulation). Interestingly, we found that OA no longer has cell types involved in the MHC complex (Major histocompatibility complex) and their activity, whereas the MHC complex functions primarily in RA in the presentation of inflammatory antigens, and that the complement system in OA has the potential to displace the function of the MHC complex. The specific signaling patterns of THY1+CDH11+ cells and their secreted ligand receptors are more conducive to cell migration and lay the foundation for promoting osteoclastogenesis. This subpopulation may also be involved in the accumulation of lymphocytes, affecting the recruitment of immune cells. Members of the collagen family (COL1A1 (Collagen Type I Alpha 1 Chain), COL6A2 (Collagen Type VI Alpha 2 Chain) and COL6A1 (Collagen Type VI Alpha 1 Chain)) and transforming growth factor (TGFB3) maintain the extracellular matrix in osteoarthritis and mediate cell migration and adhesion in rheumatoid arthritis, including the PTN (Pleiotrophin) / THBS1 (Thrombospondin 1) interaction. CONCLUSION: Increased understanding of the interaction networks between synovial fibroblast subtypes, particularly the shared and unique cellular communication features between osteoarthritis and rheumatoid arthritis and their hub cells, should help inform the design of therapeutic agents for inflammatory joint disease.

Coordinated Priming of NKG2D Pathway by IL-15 Enhanced Functional Properties of Cytotoxic CD4+CD28- T Cells Expanded in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder, and numerous aberrations of T cell responses have been reported and were implicated in its pathophysiology. Recently, CD4-positive T cells with cytotoxic potential were shown to be involved in autoimmune disease progression and tissue damage. However, the effector functions of this cell type and their potential molecular mechanisms in SLE patients remain to be elucidated. In this study, we find that cytotoxic CD4+CD28- T cells are expanded in SLE patients with flow cytometry analysis, and the percentage of CD4+CD28- T cells positively correlates with the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI). Furthermore, our study suggests that interleukin-15 (IL-15) promotes the expansion, proliferation, and cytotoxic function of CD4+CD28- T cells in SLE patients through activation of the Janus kinase3-STAT5 pathway. Further study indicates that IL-15 not only mediates the upregulation of NKG2D, but also cooperates with the NKG2D pathway to regulate the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. Together, our study demonstrated that proinflammatory and cytolytic CD4+CD28- T cells expand in SLE patients. The pathogenic potential of these CD4+CD28- T cells is driven by the coupling of the IL-15/IL-15R signaling pathway and the NKG2D/DAP10 signaling pathway, which may open new avenues for therapeutic intervention to prevent SLE progression.

Proteomics profiling and lysine malonylation analysis in primary Sjogren's syndrome.

Primary Sjogren's Syndrome (pSS) is a chronic autoimmune disease, with unclear pathogenies. Lysine-malonylation (Kmal) as a novel post-translational modification (PTMs) was found associated with metabolic, immune, and inflammatory processes. For purpose of investigating the proteomic profile and functions of kmal in pSS, liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based analysis and bioinformatics analysis are performed based on twenty-eight pSS patients versus twenty-seven healthy controls (HCs). A total of 331 down-regulated proteins and 289 up-regulated proteins are observed in differentially expressed proteins (DEPs) of pSS. We discover the expression of transforming growth factor beta-1 (TGFB1) and CD40 ligand downregulate which enriches in the inflammatory associated pathway. Expression of signal transducer and activator of transcription 1-alpha/beta (STAT1) show upregulation and enrich in type I interferon signaling pathway and IL-27-mediated signaling pathway. In differentially malonylated proteins (DMPs) of pSS, we identify 3 proteins are down-regulated in 7 sites and 18 proteins are up-regulated in 19 sites. Expression of malonylated integrin-linked kinase (ILK) significantly enrich in the focal adhesion pathway. Together, our data provide evidence that downregulation of TGFB1 and CD40LG play a critical role in the inflammatory process of pSS, while upregulation of STAT1 may be associated with IL-27 immunity and pSS immune dysfunction. Moreover, kmal modification at the kinase domain of ILK may destabilize ILK that thus contributing to pSS pathogenies by regulating the focal adhesion pathway. SIGNIFICANCE: Our research offered the first characterization of Kmal, a newly identified form of lysine acylation in pSS, as well as proteomic data on individuals with pSS. In this study, we found that several key DMPs were associated with focal adhesion pathway, which contributes to the development of pSS. The present results provide an informative dataset for the future exploration of Kmal in pSS.

Screening biomarkers for Sjogren's Syndrome by computer analysis and evaluating the expression correlations with the levels of immune cells.

Background: Sjögren's syndrome (SS) is a systemic autoimmune disease that affects about 0.04-0.1% of the general population. SS diagnosis depends on symptoms, clinical signs, autoimmune serology, and even invasive histopathological examination. This study explored biomarkers for SS diagnosis. Methods: We downloaded three datasets of SS patients' and healthy pepole's whole blood (GSE51092, GSE66795, and GSE140161) from the Gene Expression Omnibus (GEO) database. We used machine learning algorithm to mine possible diagnostic biomarkers for SS patients. Additionally, we assessed the biomarkers' diagnostic value using the receiver operating characteristic (ROC) curve. Moreover, we confirmed the expression of the biomarkers through the reverse transcription quantitative polymerase chain reaction (RT-qPCR) using our own Chinese cohort. Eventually, the proportions of 22 immune cells in SS patients were calculated by CIBERSORT, and connections between the expression of the biomarkers and immune cell ratios were studied. Results: We obtained 43 DEGs that were mainly involved in immune-related pathways. Next, 11 candidate biomarkers were selected and validated by the validation cohort data set. Besides, the area under curves (AUC) of XAF1, STAT1, IFI27, HES4, TTC21A, and OTOF in the discovery and validation datasets were 0.903 and 0.877, respectively. Subsequently, eight genes, including HES4, IFI27, LY6E, OTOF, STAT1, TTC21A, XAF1, and ZCCHC2, were selected as prospective biomarkers and verified by RT-qPCR. Finally, we revealed the most relevant immune cells with the expression of HES4, IFI27, LY6E, OTOF, TTC21A, XAF1, and ZCCHC2. Conclusion: In this paper, we identified seven key biomarkers that have potential value for diagnosing Chinese SS patients.

Serum proteome and metabolome uncover novel biomarkers for the assessment of disease activity and diagnosing of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting thousands of people. There are still no effective biomarkers for SLE diagnosis and disease activity assessment. We performed proteomics and metabolomics analyses of serum from 121 SLE patients and 106 healthy individuals, and identified 90 proteins and 76 metabolites significantly changed. Several apolipoproteins and the metabolite arachidonic acid were significantly associated with disease activity. Apolipoprotein A-IV (APOA4), LysoPC(16:0), punicic acid and stearidonic acid were correlated with renal function. Random forest model using the significantly changed molecules identified 3 proteins including ATRN, THBS1 and SERPINC1, and 5 metabolites including cholesterol, palmitoleoylethanolamide, octadecanamide, palmitamide and linoleoylethanolamide, as potential biomarkers for SLE diagnosis. Those biomarkers were further validated in an independent cohort with high accuracy (AUC = 0.862 and 0.898 for protein and metabolite biomarkers respectively). This unbiased screening has led to the discovery of novel molecules for SLE disease activity assessment and SLE classification.

Metabolic profiling of patients with different idiopathic inflammatory myopathy subtypes reveals potential biomarkers in plasma.

Idiopathic inflammatory myopathy (IIM) are heterogeneous autoimmune diseases that primarily affect the proximal muscles. IIM subtypes include dermatomyositis (DM), polymyositis (PM), and anti-synthetase syndrome (ASS). Metabolic disturbances may cause irreversible structural damage to muscle fibers in patients with IIM. However, the metabolite profile of patients with different IIM subtypes remains elusive. To investigate metabolic alterations and identify patients with different IIM subtypes, we comprehensively profiled plasma metabolomics of 46 DM, 13 PM, 12 ASS patients, and 30 healthy controls (HCs) using UHPLC-Q Exactive HF mass spectrometer. Multiple statistical analyses and random forest were used to discover differential metabolites and potential biomarkers. We found that tryptophan metabolism, phenylalanine and tyrosine metabolism, fatty acid biosynthesis, beta-oxidation of very long chain fatty acids, alpha-linolenic acid and linoleic acid metabolism, steroidogenesis, bile acid biosynthesis, purine metabolism, and caffeine metabolism are all enriched in the DM, PM, and ASS groups. We also found that different subtypes of IIM have their unique metabolic pathways. We constructed three models (five metabolites) to identify DM, PM, ASS from HC in the discovery and validation sets. Five to seven metabolites can distinguish DM from PM, DM from ASS, and PM from ASS. A panel of seven metabolites can identify anti-melanoma differentiation-associated gene 5 positive (MDA5 +) DM with high accuracy in the discovery and validation sets. Our results provide potential biomarkers for diagnosing different subtypes of IIM and a better understanding of the underlying mechanisms of IIM.

Iterative double-differential direct-sequence spread spectrum reception in underwater acoustic channel with time-varying Doppler shifts.

Conventional double differential phase-shift keying modulation amplifies the phase noise and performs poorly under the time-varying direct-sequence spread-spectrum (DSSS) communication system. Therefore, the authors propose an iterative reception for DSSS communication in time-varying underwater acoustic channels. First, bit-interleaved coded modulation with iterative decoding integrated with multi-symbol differential detection is used. Second, this paper uses cross correlation method to estimate and track the Doppler shift of each symbol. Based on Doppler estimates, a dynamic linear prediction model is proposed to estimate and track the channel phase variation. Third, an algorithm for adaptive selection of reference signals is utilized to recover the magnitude attenuation of correlation peaks. Numerical simulation results demonstrate that the proposed reception achieves around 9 dB gain compared to conventional differential decision reception under constant acceleration of 0.14 m/s2. During the acoustic communication experiment in Songhua Lake, the proposed reception was tested by using a moving source at a speed of 1-6 knots at 2-m depth and the farthest distance between the transceivers is 2.8 km. The proposed reception achieves only one frame error from a total of 205 frames collected in the lake experiment, and it also achieves error-free communications over 96 frames during a 10 km depth deep-sea experiment.

Clinical Significance of Different Profiles of anti-Ro Antibodies in Connective Tissue Diseases.

Objective: Anti-Ro60 and anti-Ro52 antibodies are associated with different connective tissue diseases (CTDs). However, the clinical significance of anti-Ro antibodies is not always consistent among different global regions. The aim of this study was to investigate the clinical characteristics of patients with anti-Ro antibodies. Methods: A total of 1596 inpatients with anti-Ro antibodies were included in the study. Demographic, clinical, and serological data were compared between individuals with different profiles of anti-Ro antibodies: patients with anti-Ro52 antibodies alone, patients with anti-Ro60 antibodies alone, and patients with combined anti-Ro52 and anti-Ro60 antibodies. Results: Of the 1596 patients, 1362 (85.3%) were female, the mean age was 45.5 years, and systemic lupus erythematosus (SLE) (46.0%) and Sjogren's syndrome (SS) (19.0%) were the most common CTD diagnoses. Among the patients with anti-Ro52 antibodies alone, idiopathic inflammatory myopathy (18.8%) and SLE (17.6%) were the most common CTD diagnoses. The coexistent autoantibodies of this group were significantly lower compared with those of the other two groups, while the presence of anti-Jo1 antibodies were significantly higher compared with those of the other two groups (3.7% vs. 0.6% vs. 1.9%, p = 0.029). In addition, the patients with isolated anti-Ro52 antibodies were more likely to suffer from interstitial lung disease (35.5% vs. 11.3% vs. 13.7%, p < 10-4) and pulmonary arterial hypertension (10.1% vs. 5.3% vs. 3.6%, p = 0.001) compared with the other two groups of patients. Compared with patients with isolated anti-Ro52 or anti-Ro60 antibodies, the patients with combined anti-Ro52 and anti-Ro60 antibodies were more likely to suffer from xerophthalmia and xerostomia. Furthermore, hypocomplementemia, hyperglobulinemia, and proteinuria were particularly prevalent in patients with anti-Ro60 antibodies. Conclusion: Different profiles of anti-Ro antibodies were significantly associated with clinical phenotypic features in CTDs, indicating the potential diagnostic and prognostic value of these antibodies in clinical practice.

Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice.

BACKGROUND: Glyphosate (GLY), as the active ingredient of the most widely used herbicide worldwide, is commonly detected in the environment and living organisms, including humans. Its toxicity and carcinogenicity in mammals remain controversial. Several studies have demonstrated the hepatotoxicity of GLY; however, the underlying cellular and molecular mechanisms are still largely unknown. METHODS: Using single-cell RNA sequencing (scRNA-seq), immunofluorescent staining, and in vivo animal studies, we analyzed the liver tissues from untreated and GLY-treated mice. RESULTS: We generated the first scRNA-seq atlas of GLY-exposed mouse liver. GLY induced varied cell composition, shared or cell-type-specific transcriptional alterations, and dysregulated cell-cell communication and thus exerted hepatotoxicity effects. The oxidative stress and inflammatory response were commonly upregulated in several cell types. We also observed activation and upregulated phagocytosis in macrophages, as well as proliferation and extracellular matrix overproduction in hepatic stellate cells. CONCLUSIONS: Our study provides a comprehensive single-cell transcriptional picture of the toxic effect of GLY in the liver, which offers novel insights into the molecular mechanisms of the GLY-associated hepatotoxicity.

Clinical significance of anti-rheumatoid arthritis 33 antibody in patients with systemic lupus erythematosus.

Although anti-rheumatoid arthritis (RA) 33 antibodies have been reported to be present in various connective tissue diseases (CTDs), the clinical significance of anti-RA33 in CTDs is still obscure. This study was performed to explore the clinical significance of anti-RA33 in CTDs, especially systemic lupus erythematosus (SLE). A total of 565 patients with positive anti-nuclear antibodies who had been tested for anti-RA33 were included in this study and were further classified into RA33-positive and RA33-negative groups. The association between anti-RA33 and the clinical features of CTDs was examined. Receiver operating characteristic (ROC) analysis was performed to explore the diagnostic value of anti-RA33 in SLE and SLE-related organ involvement. The results showed that SLE was the most common disease in CTD patients positive for anti-RA33 (48.8%). Compared with the RA33-negative group, higher proportions of SLE-associated antibodies and SLE patients with a high disease activity as well as lower levels of serum complement components were observed in the RA33-positive group (all p < 0.05). Furthermore, CTD patients with positive anti-RA33 were more likely to suffer from mucocutaneous and hematological involvement as well as interstitial lung disease (all p < 0.05). ROC analysis revealed an area under the curve value of 0.634 (95% confidence interval: 0.587-0.681) for anti-RA33 in the diagnosis of SLE, with a specificity and sensitivity of 92.9% and 13.5%, respectively. Taken together, this study reveals a significant association between anti-RA33 and the clinical features of CTDs, especially SLE, indicating a potential clinical significance of anti-RA33 in the management of SLE.

Proteomics Analysis of Plasma-Derived Exosomes Unveils the Aberrant Complement and Coagulation Cascades in Dermatomyositis/Polymyositis.

Dermatomyositis and polymyositis (DM/PM) are systemic autoimmune diseases characterized by proximal muscle weakness. The underlying pathogenetic mechanism of this disease remains under-researched. Here, using proteomics analysis, a great overlap of differentially expressed plasma exosomal proteins involved in the complement and coagulation cascade pathway, including FGA, FGB, FGG, C1QB, C1QC, and VWF, was identified in DM/PM patients versus healthy controls. Correlation analysis showed that the expression levels of complement-associated proteins (C1QB and C1QC) correlated positively with CRP, ESR, and platelet count. ROC curve analysis demonstrated that complement and coagulation cascade-associated proteins could be strong predictors for DM/PM. In addition, we also identified several other proteins that were differentially expressed in DM and PM. The selected candidate proteins were further validated by parallel reaction monitoring (PRM) and enzyme-linked immunosorbent assay (ELISA). Together, our findings indicate that these exosome-derived proteins might participate in microvascular damage in DM/PM through the activation of the complement and coagulation cascade pathway and function as biomarkers for the clinical diagnosis of DM/PM.

Gene regulatory network study of rheumatoid arthritis in single-cell chromatin landscapes of peripheral blood mononuclear cells.

OBJECTIVES: Assays for transposase-accessible chromatin with single-cell sequencing (scATAC-seq) contribute to the progress in epigenetic studies. The purpose of our project was to discover the transcription factors (TFs) that were involved in the pathogenesis of rheumatoid arthritis (RA) at a single-cell resolution using epigenetic technology. METHODS: Peripheral blood mononuclear cells of seven RA patients and seven natural controls were extracted nuclei suspensions for library construction. Subsequently, scATAC-seq was performed to generate a high-resolution map of active regulatory DNA for bioinformatics analysis. RESULTS: We obtained 22 accessible chromatin patterns. Then, 10 key TFs were involved in RA pathogenesis by regulating the activity of mitogen-activated protein kinase. Consequently, two genes (PTPRC and SPAG9) regulated by 10 key TFs were found, which may be associated with RA disease pathogenesis, and these TFs were obviously enriched in RA patients (P < .05, fold change value > 1.2). With further quantitative polymerase chain reaction validation on PTPRC and SPAG9 in monocytes, we found differential expression of these two genes, which were regulated by eight TFs [ZNF384, HNF1B, DMRTA2, MEF2A, NFE2L1, CREB3L4 (var. 2), FOSL2::JUNB (var. 2), and MEF2B], showing highly accessible binding sites in RA patients. CONCLUSIONS: These findings demonstrate the value of using scATAC-seq to reveal transcriptional regulatory variation in RA-derived peripheral blood mononuclear cells, providing insights into therapy from an epigenetic perspective.

Omnidirectional-Sensor-System-Based Texture Noise Correction in Large-Scale 3D Reconstruction.

The evolution of cameras and LiDAR has propelled the techniques and applications of three-dimensional (3D) reconstruction. However, due to inherent sensor limitations and environmental interference, the reconstruction process often entails significant texture noise, such as specular highlight, color inconsistency, and object occlusion. Traditional methodologies grapple to mitigate such noise, particularly in large-scale scenes, due to the voluminous data produced by imaging sensors. In response, this paper introduces an omnidirectional-sensor-system-based texture noise correction framework for large-scale scenes, which consists of three parts. Initially, we obtain a colored point cloud with luminance value through LiDAR points and RGB images organization. Next, we apply a voxel hashing algorithm during the geometry reconstruction to accelerate the computation speed and save the computer memory. Finally, we propose the key innovation of our paper, the frame-voting rendering and the neighbor-aided rendering mechanisms, which effectively eliminates the aforementioned texture noise. From the experimental results, the processing rate of one million points per second shows its real-time applicability, and the output figures of texture optimization exhibit a significant reduction in texture noise. These results indicate that our framework has advanced performance in correcting multiple texture noise in large-scale 3D reconstruction.

Combined proteomics and single cell RNA-sequencing analysis to identify biomarkers of disease diagnosis and disease exacerbation for systemic lupus erythematosus.

Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease for which there is no cure. Effective diagnosis and precise assessment of disease exacerbation remains a major challenge. Methods: We performed peripheral blood mononuclear cell (PBMC) proteomics of a discovery cohort, including patients with active SLE and inactive SLE, patients with rheumatoid arthritis (RA), and healthy controls (HC). Then, we performed a machine learning pipeline to identify biomarker combinations. The biomarker combinations were further validated using enzyme-linked immunosorbent assays (ELISAs) in another cohort. Single-cell RNA sequencing (scRNA-seq) data from active SLE, inactive SLE, and HC PBMC samples further elucidated the potential immune cellular sources of each of these PBMC biomarkers. Results: Screening of the PBMC proteome identified 1023, 168, and 124 proteins that were significantly different between SLE vs. HC, SLE vs. RA, and active SLE vs. inactive SLE, respectively. The machine learning pipeline identified two biomarker combinations that accurately distinguished patients with SLE from controls and discriminated between active and inactive SLE. The validated results of ELISAs for two biomarker combinations were in line with the discovery cohort results. Among them, the six-protein combination (IFIT3, MX1, TOMM40, STAT1, STAT2, and OAS3) exhibited good performance for SLE disease diagnosis, with AUC of 0.723 and 0.815 for distinguishing SLE from HC and RA, respectively. Nine-protein combination (PHACTR2, GOT2, L-selectin, CMC4, MAP2K1, CMPK2, ECPAS, SRA1, and STAT2) showed a robust performance in assessing disease exacerbation (AUC=0.990). Further, the potential immune cellular sources of nine PBMC biomarkers, which had the consistent changes with the proteomics data, were elucidated by PBMC scRNAseq. Discussion: Unbiased proteomic quantification and experimental validation of PBMC samples from two cohorts of patients with SLE were identified as biomarker combinations for diagnosis and activity monitoring. Furthermore, the immune cell subtype origin of the biomarkers in the transcript expression level was determined using PBMC scRNAseq. These findings present valuable PBMC biomarkers associated with SLE and may reveal potential therapeutic targets.

Multisystem immune-related adverse events due to toripalimab: Two cases-based review.

Immune checkpoint inhibitors (ICIs) have significantly improved the survival of patients with advanced tumors. However, immune-related adverse events (irAEs) caused by ICIs, especially high-grade irAEs, are of growing concern. High-grade multisystem irAEs due to toripalimab, a programmed cell death-1 (PD-1) inhibitor, have been rarely reported. Two patients with malignant metastatic tumors were treated with anti-PD-1 immunotherapy. However, both patients developed high-grade multisystem irAEs based on myocarditis, with chest discomfort and malaise as the main clinical manifestation. Both patients had an elevation of cardiac enzymes, abnormal electrocardiography and left ventricular wall motion. Patient 2 was also diagnosed with organizing pneumonia. Immunotherapy was suspended. High-dose intravenous methylprednisolone was immediately initiated. The patients' symptoms were significantly relieved in a short period of time. Immunosuppressants were discontinued at the 6th month follow-up in patient 1 without relapse. However, patient 2 was lost to follow up due to financial reasons. To the best of our knowledge, this is the first report regarding ICI-associated myocarditis-pneumonia due to toripalimab, indicating the significance of early recognition and management of high-grade multisystem irAEs in clinical practice.