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关键词： AQP4-ab   anti-aquaporin 4 antibodies   ARD   autoimmune rheumatic disease   EBV   Epstein-Barr virus   HR   hazard ratio   IBD   inflammatory bowel disease   ICD   International Classification of Diseases   ICD-10   International Classification of Diseases, Tenth revision   IL   interleukin   KNHIS   Korean National Health Insurance Service   MS   multiple sclerosis   NMOSD   neuromyelitis optica spectrum disorder   RA   rheumatoid arthritis   RID   rare intractable disease   RR   relative risk   SLE   systemic lupus erythematosus   SS   Sjögren syndrome  

摘要： Objective: To investigate the risk of autoimmune rheumatic diseases (ARDs) in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) compared with a control population using the Korean National Health Insurance Service database. Patients and Methods: The MS/NMOSD cohorts were collected from patients registered in the Korean National Health Insurance Service database between January 1, 2010, and December 31, 2017, using the International Classification of Diseases, Tenth Revision diagnosis codes and information in the Rare Intractable Disease management program. The incidence rate and risk of ARDs that occurred after a 1year lag period was calculated and compared with that of control cohorts matched for age, sex, hypertension, diabetes mellitus, and dyslipidemia in a 1:10 ratio. Results: The incidence rates of ARDs in MS and NMOSD were 3.56 and 9.13 per 1000 person-years, respectively. The hazard ratios (HRs) of ARDs in MS and NMOSD were 5.35 (95% CI, 3.50 to 8.19) and 9.13 (95% CI, 5.83 to 14.28), respectively. The risk of Beh & ccedil;et disease (HR, 17.24;95% CI, 4.12 to 72.14), systemic lupus erythematosus (HR, 12.25;95% CI, 4.12 to 36.44), Sj & ouml;gren syndrome (HR, 6.16;95% CI, 1.80 to 21.04), and seropositive rheumatoid arthritis (HR, 3.32;95% CI, 1.78 to 6.19) was increased in MS. In NMOSD, the risk of Sj & ouml;gren syndrome (HR, 82.63;95% CI, 19.00 to 359.38), systemic lupus erythematosus (HR, 30.85;95% CI, 6.23 to 152.80), Beh & ccedil;et disease (HR, 15.36;95% CI, 2.57 to 91.93), and seropositive rheumatoid arthritis (HR, 3.86;95% CI, 1.80 to 8.31) was increased. Conclusion: The risk of ARDs was increased in MS/NMOSD, and the risk of each ARD differed between MS and NMOSD.

摘要： The well-known side effects of long-term immunosuppressive treatment after solid organ transplantation (SOT) represent a substantial burden of morbidity and lead to increased mortality of transplanted patients with respect to the general population. Operational tolerance through donor hematopoietic chimerism in SOT recipients has been reported to be possible, with long-term success even in the presence oftransient or mixed chimerism1-4. Favorable results have been mainly obtained in human leukocyte antigen (HLA)-identical or haploidentical transplants5,6 whereas mixed chimerism is rarely sustained in HLA-disparate settings, as is the case of most SOT from either living or deceased donors. Although feasible, combined bone marrow and SOT from the same HLA-disparate donor is associated with high risks of graft-versus-host disease and mortality that are not acceptable for patients who are candidates for SOT. In addition, the optimal timing and the technical issues of harvesting hematopoietic stem cells (HSC) from deceased organ donors are still to be defined7,8, while considering the complexity of the sequence of multi-organ procurement in the operating room. Despite being a "third-party" from an immunological point ofview, banked cord blood units (CBU), currently available for use in allogeneic hematopoietic stem cell transplantation (HSCT), may represent an interesting source of HSC for the purpose of immune tolerance after SOT, whenever a permissive HLA match exists between the CBU, the deceased organ donor and the final recipient. To provide some potential basis for future immune tolerance protocols, we describe the actual HLA match between a sample of deceased multi-organ donors in Italy and all the CBU banked in the Italian Cord Blood Network (ITCBN).

关键词： IL-1 beta   Sleep   Cigarette smoking   Cerebrospinal fluid   Neuroinflammation  

摘要： Objective: Inflammatory factors and cigarette smoking have been associated with sleep disorders but molecular mechanisms that regulate sleep, specifically the role of interleukin-1 beta (IL-1 beta), remain controversial. Individuals' cerebrospinal fluid (CSF) IL-1 beta, smoking behavior, and sleep data were collected to investigate how smoking may influence the relationship between CSF IL-1 beta and sleep via moderation analysis. Methods: A total of 191 Chinese male patients, including 104 non-smokers and 87 active smokers, scheduled for anterior cruciate ligament reconstructive surgery, were recruited. Pittsburgh Sleep Quality Index (PSQI) scores were collected prior to surgery, and CSF samples were obtained during preoperative lumbar puncture. Results: Active smokers compared to non-smokers exhibited higher scores across various subdimensions of PSQI, specifically poorer sleep quality, increased sleep latency, reduced sleep efficiency, and heightened sleep disturbance (all p < 0.05). Positive correlations were observed between CSF IL-1 beta levels and PSQI total scores, as well as several subdimensions of sleep (all p < 0.05) in non-smokers. In contrast, a negative correlation was observed between CSF IL-1 beta levels and sleep efficiency scores (p < 0.05) among active smokers. Moderation analysis revealed that smoking negatively moderated the relationship between CSF IL-1 beta and sleep, particularly in PSQI total scores (beta =-0.95, p < 0.001), sleep latency scores (beta =-1.05, p < 0.001), and sleep disturbance scores (beta =-0.45, p < 0.05). Conclusions: The current study found that smoking disrupts multiple subdimensions of sleep and moderates the effect of the neuroinflammatory factor CSF IL-1 beta on PSQI sleep latency and sleep disturbance scores.

摘要： Ciprofloxacin (CIP) was found to enhance pegylated G-CSF therapy (PEG, Neulasta (R))-induced survival from 30% to 85% after ionizing radiation exposure. This combined therapy significantly mitigated radiation-induced brain hemorrhage through its capability to improve platelet recovery. This study tested whether this combined treatment also mitigated gastrointestinal damage from radiation. B6D2F1 female mice were exposed to Co-60 gamma radiation. CIP was fed daily to mice for up to 14 days. PEG was injected on day 1, and then weekly up to day 14. For the early time point study, blood, femurs, spleen, and ileum were collected on days 2, 4, 9, and 15 postirradiation. Bone marrow cells were counted;spleen weights and splenocyte counts were measured;and ileum histopathology was examined and analyzed. AKT, ERK, JNK, p38, claudin 2, NF-kB, Bax, Bcl-2, and gasdermin D were measured in ileum lysates using Western blotting while miR-34a was measured by reverse transcription followed by real-time-PCR, and citrulline was measured by colorimetric assay. In serum, interleukin-18 (IL-18) was measured by Luminex assay and complement protein 3 (C3) was detected by ELISA. The bacterial DNA load in livers was measured by real-time PCR. Radiation depleted bone marrow cells in femurs beginning day 2 through day 15 postirradiation, which was mitigated by PEG or CIP1PEG on day 9 through day 15 and by CIP on day 15, respectively. Radiation exposure led to decreased spleen weight on day 2 through day 15, while PEG or CIP1PEG significantly mitigated the reduction on day 9 through day 15. Radiation exposure reduced splenocyte counts on day 2 through day 15 postirradiation, but that was mitigated by PEG or CIP1PEG on day 15. Ileum histology showed that radiation decreased villus height on day 2 through day 15;CIP mitigated the reduction on day 15, whereas PEG1CIP mitigated it on day 2 through 15. Villus widths were increased on day 2 through day 15, while PEG1CIP effectively decreased them on

关键词： Non-HLA antibody   Donor-specific antibody   Human leukocyte antigen   Liver transplantation   Rejection  

摘要： Antibodies to HLA or non-HLA antigens are associated with detrimental outcomes in organ transplants. Here, we aim to examine whether donor-specific antibodies (DSA) and non-HLA antibodies are associated with rejection in a single-center cohort of 101 pediatric liver transplant (PLTx) recipients. Rejection was found in 50/101 biopsies (49.5 %). DSA was positive in 32 paired sera and associated with rejection (HR = 2.63[1.10-6.30]). Antibodies to 3 non-HLA antigens, SNRPB (small nuclear ribonucleoprotein polypeptides B), GSTT1 (Glutathione S-transferase theta-1), and Actin were associated with rejection. Rejection was found in 22/35 cases positive for any of the three non-HLA antibodies. The presence of DSA and non-HLA antibodies was associated with an augmented risk of rejection (HR = 6.32[1.57-25.30], p < 0.01]. In conclusion, DSA or non-HLA antibodies were associated with a higher risk for rejection in PLTx recipients. When they were detected concomitantly, the risk for rejection increased significantly, indicating the synergistic effect of actions.

关键词： Cardiovascular PhysiologyObesityhypertensionTNFsmooth muscle cellsendothelial cellsvascular inflammation  

摘要： Background: Endothelial dysfunction is a key contributor to obesity-induced hypertension. Obesity can cause chronic, low-grade inflammation, leading to abnormal blood vessel function. The release of inflammatory cytokines is commonly attributed to immune cells, but recent studies suggest that vascular cells can also release these cytokines. We tested the hypothesis that vascular wall-derived inflammatory cytokines act locally to impair endothelial function and elevate blood pressure in obesity. Methods: We used flow cytometry to analyze the levels of inflammatory cytokines in freshly isolated endothelial (ECs) and smooth muscle cells (SMCs) from small arteries of normal and obese mice. Additionally, we investigated whether endothelium- or smooth muscle-specific deletion of tumor necrosis factor (TNF) or TNF receptor I (TNFRI), or inhibition of TNFRI, rescues endothelial function and reduces blood pressure in obese mice. We also assessed the contribution of vascular TNF signaling in impairing endothelial function in arteries from obese patients. Results: We report a surprising signaling mechanism within the vascular wall, whereby TNF from SMCs acts locally on endothelial TNFRI to impair endothelial function and elevate blood pressure in obesity. TNF was selectively upregulated in SMCs from small arteries of obese mice and patients. SMC-derived TNF activated endothelial TNFRI signaling to increase the levels of inducible nitric oxide synthase and peroxynitrite, a reactive nitrogen species, in ECs. Peroxynitrite impaired Ca2+-influx signals in ECs and attenuated endothelium-dependent vasodilation, elevating blood pressure. Deletion of smooth muscle TNF or endothelial TNFRI, or inhibition of TNFRI, rescued endothelial function and reduced blood pressure in obesity. Conclusion: Overall, these findings show that paracrine SMC-to-EC signaling via TNF elevates blood pressure in obesity. Consequently, targeting smooth muscle TNF or endothelial TNFRI offers a potential approa