TOX promotes follicular helper T cell differentiation in patients with primary Sjögren's syndrome.

OBJECTIVES: Whether naive CD4+ T cells are dysregulated and associated with the overactivation of CD4+ T cells in primary SS (pSS) remains unclear. We aimed to explore the role and underlying mechanism of naive CD4+ T cells in pSS. METHODS: We examined the activation, proliferation and differentiation of naive CD4+ T cells from pSS patients and healthy controls. Differentially expressed genes were identified using RNA sequencing, and were overexpressed or silenced to determine the gene regulating follicular helper T (Tfh) cells. Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) with chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) was performed to explore the epigenetic mechanism. Naive CD4+ T cells were treated with pSS-related cytokines to explore the upstream signalling pathway. RESULTS: pSS naive CD4+ T cells had higher potentials of activation, proliferation and differentiation towards Tfh cells. Thymocyte selection-associated high mobility group box protein (TOX) was upregulated in pSS naive CD4+ T cells and promoted T cell activation and Tfh cell polarization. TOX silencing in pSS naive CD4+ T cells downregulated B cell lymphoma 6 (BCL6) expression and altered levels of multiple Tfh-associated genes. ChIP-seq analysis implied that TOX bound to the BCL6 locus, where there were accessible regions found by ATAC-seq. IFN-α induced TOX overexpression, which was attenuated by Janus kinase (JAK) and signal transducer and activator of transcription 1 (STAT1) inhibitors. CONCLUSION: Our data suggest that TOX in pSS naive CD4+ T cells is upregulated, which facilitates Tfh cell differentiation. Mechanistically, IFN-α induces TOX overexpression in naive CD4+ T cells through JAK-STAT1 signalling and TOX regulates BCL6 expression. Therefore, IFN-α-JAK-STAT1 signalling and TOX might be potential therapeutic targets in pSS.

Methylprednisolone pulse therapy promotes the differentiation of regulatory T cells by inducing the apoptosis of CD4+ T cells in patients with systemic lupus erythematosus.

OBJECTIVES: To investigate the differentiation of regulatory T cells (Tregs) induced by methylprednisolone (MP) pulse therapy in patients with Systemic Lupus Erythematosus (SLE). METHODS: We enrolled 30 patients with SLE and analyzed peripheral blood mononuclear cells (PBMCs) before and after MP pulse therapy. Peripheral Tregs, apoptosis of PBMCs subsets, and TGFß production by monocytes was quantified by flow cytometry. Proliferation and IFN-γ production of CD4+ T cells were measured. Furthermore, TGFß1 production by human monocyte-derived macrophages (HMDM) stimulated with MP-treated CD4+ T cells were quantified by ELISA. RESULTS: Peripheral Tregs was significantly increased after MP pulse therapy (6.76 ± 1.46% vs. 3.82 ± 1.02%, p < 0.01), with an expansion of Nrp1- induced Tregs (4.54 ± 0.46% vs. 1.75 ± 0.38%, p < 0.01). Proliferation and IFN-γ production of CD4+ T cells were significantly decreased after MP pulse therapy. MP pulse therapy induced CD4+ T cell apoptosis (early apoptosis, 26.34 ± 3.54% vs. 14.81 ± 2.89%, p < 0.01) and TGFß expression on monocytes (6.02% vs. 2.45%, p < 0.01). Furthermore, MP induced CD4+ T cell apoptosis in vitro, which stimulated HMDM to produce TGFß. Moreover, elevated TGFß level in supernatant from HMDM stimulated with MP-treated CD4+ T cells promoted Tregs differentiation. CONCLUSIONS: MP pulse therapy induces CD4+ T cell apoptosis, which promotes monocytes to produce TGFß and further facilitates Tregs differentiation. Newly-differentiated Tregs suppress proliferation and IFN-γ production of CD4+ T cells and contribute to immunoregulatory milieu after MP pulse therapy.

Downregulation of Programmed Death-1 Pathway Promoting CD8 + T Cell Cytotoxicity in Primary Biliary Cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is an autoimmune disease. CD8 + T cell (CTLs) cytotoxicity played a crucial rule in of PBC with unclear detailed pathogenesis. AIMS: The role of the programmed death-1 (PD-1) pathway in CD8 + T cell cytotoxicity in patients with PBC was determined. METHODS: We recruited 69 patients with PBC and 57 healthy controls (HCs). PD-1 pathway in peripheral CD8 + T cells and related cytokines were detected, and gene expression levels were detected. Immunofluorescence staining of PD-1/PD-L1 was performed on liver tissue. PD-1 ± CTLs were cocultured with human intrahepatic biliary epithelial cells (HiBECs) to measure CTL cytotoxicity, proliferation and cytokine levels and HiBEC apoptosis. The upstream signaling pathway of PD-1 was detected. RESULTS: PBC patients exhibited Tbet gene upregulation and PD-1 downregulation in CTLs, with PD-1 expression reduced in CTLs and PD-L1 reduced in the liver portal region relative to HCs. Higher plasma IL-10, interferon-γ and transforming growth factor-ß concentrations were observed in the PBC group than the HC group. In CTL and HiBEC coculture experiment, compared with PD-1- CTLs, PD-1 + CTLs exhibited weaker cytotoxicity, less proliferation and lower cytokine production. When the system was blocked by anti-PD-1 antibodies, these effects were antagonized. CONCLUSIONS: PD-1 expression in CD8 + T cells decreased, and PD-1 pathway-related cytokines changed in patients with PBC. PD-1/PD-L1 pathway silencing increased CD8 + T cell proliferation, related cytokine production and CTL cytotoxic effects on HiBECs in coculture experiment. The PD-1/PD-L1 pathway might represent an important pathway in the immunological mechanism underlying PBC.

Aberrant distribution of CD3+CD56+ NKT-like cells in patients with primary Sjögren's syndrome.

OBJECTIVES: To elucidate the potential role of CD3+CD56+ NKT-like cells in the pathogenesis of primary Sjögren's syndrome (pSS). METHODS: We enrolled pSS patients and healthy controls and examined the peripheral population, the surface chemokine receptors and the proinflammatory cytokine production of NKT-like cells by flow cytometry. The infiltration of NKT-like cells in the labial salivary gland (LSG) was examined by immunofluorescence. Serum and tissue levels of CX3CL1 were detected by Cytometric Bead Array and immunohistochemistry, respectively. The chemotaxis of NKT-like cells was examined by transwell migration assay. RESULTS: Peripheral NKT-like cells from pSS patients were significantly lower than those from HC (3.09±2.35% vs. 5.37±4.06%, p=0.0002), which was negatively correlated with European League Against Rheumatism Sjögren's Syndrome Disease Activity index. NKT-like cells infiltrated into the LSG of pSS patients. Serum and LSG epithelial CX3CL1 levels were higher in pSS patients than those in HC, which promoted the chemotaxis of the NKT-like cells. NKT-like cells from pSS patients expressed a higher level of CD69, and secreted high level of TNF-α and IFN-γ, which was promoted by CX3CL1 in vitro. CONCLUSIONS: NKT-like cells decreased in peripheral and infiltrated into the LSG of the pSS patients, which could be driven by CX3CL1-CX3CR1 axis. NKT-like cells might be implicated in the pathogenesis of pSS.

Elevated EPSTI1 promote B cell hyperactivation through NF-κB signalling in patients with primary Sjögren's syndrome.

BACKGROUND: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterised by aberrant B cell hyperactivation, whose mechanism is partially understood. METHODS: We performed whole transcriptome sequencing of B cells from three pSS patients and three matched healthy controls (HC). Differentially expression genes (DEGs) were confirmed with B cells from 40 pSS patients and 40 HC by quantitative PCR and western blot. We measured the proliferation potential and immunoglobulins production of siRNA-transfected or plasmid-transfected B cells stimulated with cytosine-phosphate-guanine (CpG) or anti-IgM. We also explored Toll-like receptor 9 (TLR9) signalling to reveal the potential mechanism of B cell hyperactivation in pSS. RESULTS: We identified 77 upregulated and 32 downregulated DEGs in pSS B cells. We confirmed that epithelial stromal interaction (EPST1) expression in pSS B cells was significantly higher than that from HCs. EPSTI1-silencing B cells stimulated with CpG were less proliferated and produced lower level of IgG and IgM comparing with control B cells. EPSTI1-silencing B cells expressed lower level of p-p65 and higher level of IκBα, and B cells with overexpressed EPSTI1 showed higher level of p-p65 and lower level of IκBα. Finally, IκBα degradation inhibitor Dehydrocostus Lactone treatment attenuated p65 phosphorylation promoted by EPSTI1. CONCLUSION: Elevated EPSTI1 expression in pSS B cells promoted TLR9 signalling activation and contributed to the abnormal B cell activation, which was promoted by facilitating p65 phosphorylation and activation of NF-κB signalling via promoting IκBα degradation. EPSTI1 might be implicated in pSS pathogenesis and was a potential therapeutic target of pSS.

Preparation of ultrathin carbon-coated CdS nanobelts for advanced Li and Na storage.

In this paper, we report a simple hydrothermal method for preparation of ultrathin carbon-coated CdS (CdS@C) nanobelts. The CdS@C nanobelts show superior electrochemical properties as an anode material for Li-ion batteries. The optimized CdS@C composites deliver a reversible capacity around 910 mAhg-1 and 48 mAhg-1 at 0.1 Ag-1 and 30.0 Ag-1, respectively. Moreover, the optimized nanobelts are also potential materials for Na storage. A stable capacity around 240 mAhg-1 is obtained at 0.1 Ag-1, even after 100 cycles.

MR spectroscopy for assessing the effects of oxytocin on marrow adipogenesis induced by glucocorticoid in rabbits.

BACKGROUND: Previous studies suggest that oxytocin (OT) negatively modulates adipogenesis while promoting osteogenesis in vitro. Because of its effects on marrow stromal cells, OT might have potential utility in therapy for glucocorticoid-induced osteoporosis (GIO). PURPOSE: To explore the effects of OT on marrow adipogenesis in a rabbit model of GIO. MATERIAL AND METHODS: Thirty-six-month-old female New Zealand rabbits were randomly assigned to the control, GIO, and GIO + OT groups. Magnetic resonance (MR) spectroscopy and multi-detector computed tomography (MDCT) were performed to detect marrow fat content (MFC) and bone mineral density (BMD) at baseline, and 1, 2, and 3 months. After 3 months of treatment, marrow adipocytes were quantitatively evaluated by histopathology. RESULTS: In the GIO group, MFC substantially increased from 34.1% to 43.2% at month 1, and it was maintained until month 3 (by 59.2%, all P <0.01). MFC values in the GIO group were significantly different from the control and OT-treated groups over time. Early OT treatment reversed marrow adiposity to levels of the controls. BMD values were significantly lower in the GIO group at months 2 and 3 compared to the controls; however, partial recovery of vertebral BMD (87.1% of baseline) and femoral BMD (89.3% of baseline) in the OT-treated group were observed. The mean diameter and density of adipocyte and percentage of adipocyte area increased by 30.0%, 70.1%, and 88.9%, respectively (all P <0.05) in the GIO group, but remained unchanged in the OT-treated group. CONCLUSION: Early OT treatment was sufficient to eliminate glucocorticoid-induced marrow adiposity.

The global state of research in stem cells therapy for spinal cord injury (2003-2022): a visualized analysis.

Objective: Our study aimed to visualize the global status and frontiers in stem cell therapy for spinal cord injury by using bibliometric methodology. Methods: Publication citation information related to stem cell therapy for spinal cord injury (SCI) studies between 2003 and 2022 was retrieved from the Web of Science Core Collection database. For the visualized study, VOS viewer software and Graph Pad Prism 9.5 were used to perform bibliometric analysis of included data and publication number statistics in stem cell therapy for the SCI domain. Results: A total of 6,686 publications were retrieved. The USA and China made the highest contributions to global research with the highest number of citations and link strength. The journal Experimental Neurology ranks as the top journal, combining the publication amount and bibliometrics results. The University of Toronto, based in Canada, was the first-ranking institution. The directions of the current study could be divided into five clusters. The research of Transplantation and Regenerative Medicine and Neurosciences Mechanism Research may be the emerging frontiers in this domain. Conclusion: In summary, stem cell therapy for spinal cord injuries is poised for more valuable advances.

Type 1 interferon signature in peripheral blood mononuclear cells and monocytes of idiopathic inflammatory myopathy patients with different myositis-specific autoantibodies.

Background: Myositis-specific autoantibodies (MSAs) are clinically used to diagnose and define idiopathic inflammatory myopathy (IIM) subsets. However, the underlying pathogenic mechanisms of patients with different MSAs remain unclear. Methods: A total of 158 Chinese patients with IIM and 167 gender- and age-matched healthy controls (HCs) were enrolled. Transcriptome sequencing (RNA-Seq) was performed with peripheral blood mononuclear cells (PBMCs), followed by the identification of differentially expressed genes (DEGs) and analysis of gene set enrichment analysis, immune cell infiltration, and WGCNA. Monocyte subsets and related cytokines/chemokines were quantified. The expressions of interferon (IFN)-related genes were validated using qRT-PCR and Western blot in both PBMCs and monocytes. We also performed correlation analysis and ROC analysis to explore the potential clinical significance of the IFN-related genes. Results: There were 1,364 genes altered in patients with IIM, including 952 upregulated and 412 downregulated genes. The type I interferon (IFN-I) pathway was remarkably activated in patients with IIM. Compared with patients with other MSAs, IFN-I signatures were significantly activated in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibodies. In total, 1,288 hub genes associated with IIM onset were identified using WGCNA, including 29 key DEGs associated with IFN signaling. The patients had more CD14brightCD16- classical, CD14brightCD16+ intermediate, and fewer CD14dimCD16+ non-classical monocyte subsets. Plasma cytokines like IL-6 and TNF and chemokines including CCL3 and MCPs increased. The validation of IFN-I-related gene expressions was consistent with the findings from RNA-Seq. The IFN-related genes were correlated with laboratory parameters and helpful for IIM diagnosis. Conclusion: Gene expressions were remarkably altered in the PBMCs of IIM patients. Anti-MDA5+ IIM patients had a more pronounced activated IFN signature than others. Monocytes exhibited a proinflammatory feature and contributed to the IFN signature of IIM patients.

Plasma proteomic profiling reveals KRT19 could be a potential biomarker in patients with anti-MDA5+ dermatomyositis.

OBJECTIVE: To investigate the immune response-related protein profiling in plasma of patients with idiopathic inflammatory myopathies (IIMs), especially in anti-MDA5+ dermatomyositis (DM). METHODS: A total of 166 IIM patients and 107 healthy controls (HCs) were enrolled in our study. Ninety-two plasma immune response-related proteins were detected by Olink proteomics in 36 IIM patients and 25 HCs. The expression of plasma KRT19 was validated in another 130 IIM patients, 82 HCs, and 55 other rheumatic diseases. RESULTS: A total of 46 differentially expressed proteins were detected, including 12 upregulated proteins and 34 downregulated proteins in IIM patients compared with HCs. Pathway analysis revealed lactoferrin danger signal response pathway, TLR4 signaling and tolerance, infection, and IL-10 signaling pathway were activated. The immune response-related protein profiling significantly altered in anti-MDA5+ DM patients, with LAMP3, HSD11B1, and KRT19 significantly increased, while SH2D1A, ITGA11, TRIM21, CD28, ITGB6, and HEXIM1 tremendously decreased. In addition, KRT19 was significantly increased in IIM patients, especially in anti-MDA5+ DM patients with the diagnostic value of a significant area under the ROC curve of 0.881. CONCLUSION: Immune response-related proteins are significantly altered in patients with anti-MDA5+ DM patients. KRT19 could be a potential biomarker for anti-MDA5+ DM patients. Key Points • What is already known on this topic? Anti-MDA5+ DM is a distinctive subtype of IIM. Plasma immune response-related proteins panel needs to be investigated. • What this study adds? Plasma protein profiling of immune response-related proteins significantly altered in patients with idiopathic inflammatory myopathies (IIM), especially in anti-MDA5+ DM patients. • How this study might affect research, practice, or policy? KRT19 could be a potential biomarker in patients with anti-MDA5+ dermatomyositis.

Hematological malignancies in systemic lupus erythematosus: clinical characteristics, risk factors, and prognosis-a case-control study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic and complex multi-system autoimmune disorder. Higher risks of hematological malignancies (HM) were observed in SLE patients, which was associated with higher mortality. The mechanism and risk factors of HM oncogenesis in SLE patients are still under investigation. The aim of this study was to explore clinical characteristics, risk factors, and prognosis of SLE patients with or without HM in the Chinese population. METHODS: A retrospective, case-controlled study was conducted in 72 SLE patients between January 2013 and December 2020. Clinical and laboratory data were collected and compared between the two groups of patients with HM and those without HM. Logistic regression analysis was performed to determine risk factors of HM oncogenesis. The survival rate was estimated by Kaplan-Meier methods and Cox proportional hazards regression analysis. RESULTS: Among 72 SLE patients in this study, fifteen complicated with HM and 57 without HM were identified. The incidence rate of HM was approximately 0.24% with elevated standardized incidence ratios of lymphoma and leukemia (27.559 and 12.708, respectively). Patients with HM were older when diagnosed with SLE, with a higher frequency of infection and splenomegaly, lower levels of hemoglobin and high-density lipoprotein compared with those without HM. Fewer patients with HM expressed positive anti-dsDNA antibody (26.7% vs 66.7%, P = 0.005) or received hydroxychloroquine treatment (40.0% vs 86.0%, P = 0.001). Older age at SLE diagnosis (OR=1.122, 95% CI: 1.037-1.214) was regarded as an independent risk factor of HM oncogenesis. Female (RR= 0.219, 95% CI: 0.070-0.681) and hydroxychloroquine (RR= 0.281, 95% CI: 0.094-0.845) were protective factors of mortality in SLE patients. CONCLUSIONS: SLE patients with an older age are at an increased risk of HM carcinogenesis. The prognosis of male patients with SLE tends to be poorer whether complicated with HM. The association of antinuclear antibody spectrum, medication, and HM oncogenesis in SLE needs further investigation.

Circular RNA circHIPK3 Activates Macrophage NLRP3 Inflammasome and TLR4 Pathway in Gouty Arthritis via Sponging miR-561 and miR-192.

Increasing evidences indicate that circular RNAs (circRNAs) play important roles in regulating gene expressions in various diseases. However, the role of circRNAs in inflammatory response of gouty arthritis remains unknown. This study aims to investigate the role and underlying mechanism of circHIPK3 in inflammatory response of gouty arthritis. Quantitative real-time PCR was used to detect the expressions of circHIPK3, miR-192 and miR-561. Western blot was used to detect the protein levels of TLR4, NLRP3, nuclear factor-κB (NF-κB) related proteins, and Caspase-1. Dual luciferase reporter assay, RNA pull-down assay, and FISH assay were used to confirm the interaction between circHIPK3 and miR-192/miR-561. ELISA was used to detect interleukin (IL)-1ß and tumor necrosis factor (TNF)-α levels. circHIPK3 was elevated in synovial fluid mononuclear cells (SFMCs) from patients with gouty arthritis and monosodium urate (MSU)-stimulated THP-1 cells. circHIPK3 overexpression promoted the inflammatory cytokines levels in MSU-stimulated THP-1 cells, and circHIPK3 silencing obtained the opposite effect. Mechanistically, circHIPK3 sponged miR-192 and miR-561, and subsequently promoted the expressions of miR-192 and miR-561 target gene TLR4 and NLRP3. In vivo experiments confirmed circHIPK3 knockdown suppressed gouty arthritis. circHIPK3 sponges miR-192 and miR-561 to promote TLR4 and NLRP3 expressions, thereby promoting inflammatory response in gouty arthritis.

CXCL12-CXCR4-Mediated Chemotaxis Supports Accumulation of Mucosal-Associated Invariant T Cells Into the Liver of Patients With PBC.

Objectives: To explore the potential role of CD3+CD8+CD161high TCRVα7.2+ mucosal-associated invariant T (MAIT) cells in the pathogenesis of primary biliary cholangitis (PBC). Methods: We enrolled 55 patients with PBC, 69 healthy controls (HCs), and 8 patients with hepatic hemangioma. Circulating MAIT cells and their chemokine receptor profiles and cytokine production were quantified using flow cytometry. Liver-resident MAIT cells were examined by immunofluorescence staining. CXCL12-mediated chemotaxis of MAIT cells was measured using a transwell migration assay. Plasma interleukin (IL)-18 was measured using ELISA, and cytokine production in IL-18-stimulated MAIT cells was detected using flow cytometry. Result: Peripheral MAIT cells were found to be significantly lower in patients with PBC (3.0 ± 3.2% vs. 9.4 ± 8.0%, p < 0.01) and negatively correlated with alkaline phosphatase (ALP) levels (r = -0.3209, p < 0.05). Liver immunofluorescence staining suggested that MAIT cells might accumulate in PBC liver. MAIT cells from patients with PBC expressed higher levels of CXCR4 (84.8 ± 18.0% vs. 58.7 ± 11.4%, p < 0.01), and the expression of CXCL12 was higher in PBC liver. CXCL12 promoted MAIT cell chemotaxis (70.4 ± 6.8% vs. 52.2 ± 3.5%, p < 0.01), which was attenuated by CXCR4 antagonist. MAIT cells from PBC produced significantly more interferon-γ (IFN-γ) (88.3 ± 4.2% vs. 64.2 ± 10.1%, p < 0.01), tumor necrosis factor-α (TNF-α) (93.0 ± 1.1% vs. 80.1 ± 5.3%, p < 0.01), Granzyme B (89.3 ± 3.3% vs. 72.1 ± 7.0%, p < 0.01), and perforin (46.8 ± 6.6% vs. 34.8 ± 7.7%, p < 0.05). MAIT cells from PBC expressed higher levels of IL18-Rα (83.8 ± 10.2% vs. 58.3 ± 8.7%, p < 0.01). Plasma IL-18 was more abundant in patients with PBC (286.8 ± 75.7 pg/ml vs. 132.9 ± 78.1 pg/ml, p < 0.01). IL-18 promoted IFN-γ production in MAIT cells (74.9 ± 6.6% vs. 54.7 ± 6.7%, p < 0.01), which was partially attenuated by blocking IL-18R (68.6 ± 8.3% vs. 43.5 ± 4.2%, p < 0.01). Conclusion: Mucosal-associated invariant T cells from patients with PBC accumulated in the liver via CXCL12-CXCR4-mediated chemotaxis, produced pro-inflammatory cytokines, and contributed to portal inflammation, which was potentially mediated by elevated IL-18. Targeting MAIT cells might be a therapeutic approach for PBC.

Role of cell autophagy in the generation of IgM and hepatic fibrosis in primary biliary cholangitis.

OBJECTIVE: Autophagy in the immune and autoimmune diseases has been concerned more and more. We investigated the potential role of cell autophagy of B cells generating IgM in primary biliary cholangitis (PBC), and explored the relationship between the cell autophagy of hepatic stellate cells (HSCs) and hepatic fibrosis in PBC. METHODS: We examined the aggregation degree of microtubule-associated protein light chain 3II (LC3II) in B cells of PBC (n = 21), health control (HC, n = 15) and disease control (DC, n = 8, active hepatitis B). The expression level of p62/SQSTM1 (p62) in B cells was detected by flow cytometry. ELISA was adopted to detect the level of IgM in the B cell culture supernatant under the basal condition, activated condition(stimulated by pokeweed mitogen, PWM) and inhibited condition(inhibited by autophagy inhibitor, 3-methyladenine, 3-MA) respectively. We detected the expression of α-smooth muscle actin (α-SMA), the infiltration level of LC3II, transforming growth factor-ß (TGF-ß), platelet-derived growth factor-bb (PDGF-bb), and collagen I in the hepatic tissues of five PBC patients and two HC individuals. RESULTS: When B cells were stimulated and activated by PWM, the expression of p62 increased, and the mean fluorescence intensity (MFI, 2404.8 ± 689.0) of p62 in PBC was lower than that in HC (2966.8 ± 488.9,P = 0.0227). Under 3-MA treatment, the MFI expressed of p62 in B cells weakened. The reduction difference in PBC (466.4 ± 214.9) was smaller than that in HC (1166.6 ± 231.2, P = 0.0000) and DC (1184.8 ± 197.7, P = 0.0001). The level of generating IgM in the PBC group was obviously higher than that in the HC group (65.7 ± 15.4 vs. 49.5 ± 20.4 ng/ml, P = 0.0357). Before and after B cells were treated with 3-MA, the peak level of IgM did not significantly diminish in PBC and DC (65.7 ± 15.4 vs. 59.6 ± 18.7 ng/ml, P = 0.2965; 50.1 ± 17.4 vs. 48.4 ± 12.3 ng/ml, P = 0.8336). The immunohistochemical result revealed that the expression level of collagen I, α-SMA, TGF-ß and PDGF-bb in PBC was higher than that in HC, but the expression of LC3II was lower. Similarly, immunofluorescence assay revealed that the fluorescence intensity of collagen I was higher but LC3II was lower in PBC than that in HC. CONCLUSION: The high level autophagy of B cells from PBC patients is one important factor to synthesize and secrete IgM. Hepatic fibrosis of PBC is probably associated with the weakened autophagy of HSCs. Key Points • High-level autophagy of B cells in PBC patients is an important factor to synthesize and secrete IgM. • Pro-fibrogenic cytokines in PBC influence the increase of collagen-I through HSC autophagy, and promote the occurrence and development of hepatic fibrosis.

Anatomical study of the coracoid process in Mongolian male cadavers using the Latarjet procedure.

BACKGROUND: The Latarjet procedure addresses recurrent anterior shoulder instability in the context of a significant bony defect. However, the bony and soft tissue anatomy of the coracoid in coracoid transfer procedures has not yet been defined in Mongolian men. The aims of this study were to describe the soft tissue attachments of the coracoid regarding the bony anatomy, define the average amount of bone available for coracoid transfer, analyze the characteristics of the pectoralis minor and coracoid, and study the relationship between the bony dimensions of the coracoid and body length in Mongolian men. METHODS: We dissected 30 shoulders from 15 male Mongolian cadavers, exposing the coracoid process and attached anatomical structures including the lateral clavicle and acromion, then measured the bony dimensions of the coracoid and the locations and sizes of the coracoid soft tissue footprints. RESULTS: The mean length of the coracoid available for transfer was 23.93 ± 2.32 mm. The mean length of the coracoid was 42.10 ± 2.3 mm, and the mean width and height of the coracoid midpoint were 15.29 ± 1.70 mm and 11.61 ± 1.98 mm, respectively. The pectoralis minor was part of the joint capsule and passed over the coracoid in some samples. The mutation rate of the pectoralis minor footprint, which was asymmetrical and irregular, was 23.33 %. Statistical analysis involved a multiple linear regression equation. CONCLUSIONS: The average amount of bone available for use in coracoid transfer in Mongolian men was less than that of other populations. Mutation of the pectoralis minor may induce intraoperative capsule injury because this muscle passes over the coracoid deep to the joint capsule of the glenohumeral joint and constitutes part of the shoulder joint, strengthening the joint. Statistically, higher coracoids appeared in shorter patients and longer coracoids appeared in taller patients. Surgically, great care should be taken to consider a patient's height to precisely implement the congruent-arc Latarjet technique.