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Aims: The impact of macrovascular and microvascular complications, the common vascular complications of type 2 diabetes, on long-term mortality has been well evaluated, but the impact of different complications of newly diagnosed type 2 diabetes (diagnosed within the past 2 years) on long-term mortality has not been reported. We aimed to investigate the relationship between all-cause mortality and vascular complications in U.S. adults (aged ≥ 20 years) with newly diagnosed type 2 diabetes., Methods: We used data from the 1999-2018 National Health and Nutritional Examination Surveys (NHANES). Cox proportional hazard models was used to assess hazard ratios (HR) and 95% confidence intervals for all-cause mortality., Results: A total of 928 participants were enrolled in this study. At a mean follow-up of 10.8 years, 181 individuals died. In the fully adjusted model, the hazard ratio (HR) (95% confidence interval [CI]) of all-cause mortality for individuals with any single complication compared with those with newly diagnosed type 2 diabetes without complications was 2.24 (1.37, 3.69), and for individuals with two or more complications was 5.34 (3.01, 9.46).Co-existing Chronic kidney disease (CKD) and diabetic retinopathy (DR) at baseline were associated with the highest risk of death (HR 6.07[2.92-12.62]), followed by CKD and cardiovascular disease (CVD) (HR 4.98[2.79-8.89]) and CVD and DR (HR 4.58 [1.98-10.57])., Conclusion: The presence of single and combined diabetes complications exerts a long-term synergistic adverse impact on overall mortality in newly diagnosed U.S. adults with type 2 diabetes, underscoring the importance of comprehensive complication screening to enhance risk stratification and treatment., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Anti-DNER antibody is associated with paraneoplastic cerebellar degeneration (PCD) and Hodgkin's disease (HD). However, recent studies reported cases absence of HD and that non-tumor anti-DNER antibody-associated ataxia was not well characterized. We present a case of acute cerebellar ataxia and nystagmus with detected anti-DNER antibody. Brain magnetic resonance imaging (MRI) showed cerebellar atrophy. High titer of anti-DNER antibody was detected in CSF and serum. Positron emission tomography (PET) scanning was unremarkable at a 10-month follow up. The patient improved significantly after immunosuppressive therapy with intravenous steroids, immunoglobulin followed by rituximab. Our study suggest that the presence of such anti-neuronal antibodies might not come along with malignancy and that early onset non-tumor patients are more likely to have a better outcome after immunotherapy. Early diagnosis and timely immunosuppressive therapy may prove beneficial for these patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Myasthenia gravis (MG) is an autoimmune disease characterized by generalized skeletal muscle contraction weakness due to autoantibodies targeting neural-muscular junctions. Here, we investigated the relationship between key cytokines and MG type, disease course, antibodies, and comorbidities., Method: Cytokine levels in serum samples collected from MG (n = 45) and healthy control (HC, n = 38) patients from January 2020 to June 2022 were quantified via flow cytometry., Results: Levels of IL-6 were higher in the MG group versus healthy individuals (p = 0.026) and in patients with generalized versus ocular MG (p = 0.019). IL-6 levels were positively correlated with QMG score. In patients with MG with both AChR and Titin antibodies, serum levels of sFas and granulysin were higher than in those with AChR alone (p = 0.036, and p = 0.028, respectively). LOMG had a reduction in serum levels of IL-2 compared to EOMG (p = 0.036). LOMG patients with diabetes had lower serum levels of IL-2, IL-4, and IFN-γ (p = 0.044, p = 0.038, and p = 0.047, respectively) versus those without diabetes. sFas in the MG with Abnormal thymus were reduced compared to those in MG with Normal thymus (p = 0.008)., Conclusions: This study revealed a positive correlation between IL-6 level and MG status. Serum cytokine levels of the AChR + Titin MG group differed from those of the AChR group. LOMG had a lower IL-2 level. Comorbidities affect some cytokines in peripheral blood in MG serum., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Cysteinyl aspartate-specific proteinase-1 (caspase-1) is a multifunctional inflammatory mediator in many inflammation-related diseases. Previous studies show that caspase-1 inhibitors produce effective therapeutic outcomes in a rat model of myasthenia gravis. However, tissue toxicity and unwanted off-target effects are the major disadvantages limiting their clinical application as therapeutic agents. This study shows that dendritic cell-derived extracellular vesicles (EVs) loaded with a caspase-1 inhibitor (EVs-VX-765) are phagocytized mainly by macrophages, and caspase-1 is precisely expressed in macrophages. Furthermore, EVs-VX-765 demonstrates excellent therapeutic effects through a macrophage-dependent mechanism, and it notably inhibits the level of interleukin-1β and subsequently inhibits Th17 response and germinal center (GC) reactions. In addition, EVs-VX-765 demonstrates better therapeutic effects than routine doses of VX-765, although drug loading is much lower than routine doses, consequently reducing tissue toxicity. In conclusion, this study's findings suggest that EV-mediated delivery of caspase-1 inhibitors is effective for treating myasthenia gravis and is promising for clinical applications., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Methylglyoxal (MGO) is a highly reactive metabolite generated by glycolysis. Although abnormal accumulation of MGO has been reported in several autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, the role of MGO in autoimmune diseases has not yet been fully investigated. In this study, we found that the intracellular MGO levels increased in activated immune cells, such as microglia and lymphocytes. Treatment with MGO inhibited inflammatory cell accumulation in the spinal cord and ameliorated the clinical symptoms in EAE mice. Further analysis indicated that MGO suppressed M1-polarization of microglia cells and diminished their inflammatory cytokine production. MGO also inhibited the ability of microglial cells to recruit and activate lymphocytes by decreasing chemokine secretion and expression of co-stimulatory molecules. Furthermore, MGO negatively regulated glycolysis by suppressing glucose transporter 1 expression. Mechanically, we found that MGO could activate nuclear factor erythroid 2-related factor 2 (NRF2) pathway and NRF2 could bind to the promoter of IκBζ gene and suppressed its transcription and subsequently pro-inflammatory cytokine production. In conclusion, our results showed that MGO acts as an immunosuppressive metabolite by activating the NRF2-IκBζ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The surface topography index (STI) has great potential in both routine computed tomography (CT) scan and emerging optical imaging systems. However, the diagnostic accuracy and stability of the STI as a deformity severity assessment index has not been fully confirmed. Therefore, the aim of the present study was to determine the diagnostic performance of the STI as a novel deformity severity assessment index for pectus excavatum., Methods: The present study consisted of 722 chest CT images from a single center. The standard CT index (CTI) and STI were calculated for all patients. The between-group difference and the level of compliance between the CTI and STI was analyzed by t -test and Pearson correlation. The diagnostic value and optimum discriminatory values of the CTI and STI were calculated by a receiver-operating characteristic (ROC) curve and DeLong's test., Results: The distributions of the CTI and STI were similar and showed a slight overlap between the pectus excavatum (PE) and non-PE groups. Both the CTI and STI significantly differed between the 2 groups (P<0.001). The STI demonstrated a strong Pearson correlation with the CTI (r=0.91, 95% confidence interval: 0.88-0.91, P<0.001). The ROC curves showed that STI =1.58 (sensitivity: 0.93, specificity: 0.95) could be considered equivalent to CTI =2.72 (sensitivity: 0.93, specificity: 0.97) as the optimum discriminatory values. DeLong's test showed no significant difference in the ROC curve results between the CTI and STI (Z=0.90, P=0.37)., Conclusions: The STI has comparative discrimination ability in PE diagnosis and deformity severity assessment when used with the standard CTI. The STI as a novel index is not only an ideal evaluation metric of PE deformity but also an objective trait for PE patients just as weight and height for everyone., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tp-21-282). The authors have no conflicts of interest to declare., (2021 Translational Pediatrics. All rights reserved.)

Background: Severe pectus excavatum (PE) may be concomitant with congenital cystic lung lesions (CCLLs) that also require surgery. It is ideal to correct these two deformities concurrently, but the safety and efficacy of a simultaneous surgical technique remain unknown., Methods: Between 2007 and 2017, 635 patients with severe PE were admitted at our medical center. Eight patients underwent minimally invasive repair of PE and lobectomy simultaneously. The patient characteristics and operative data were analyzed and compared with another group of patients who underwent lobectomy alone for contemporaneous CCLLs., Results: The severity of PE (mean Haller index 5.70) and CCLLs were confirmed by computed tomography (CT). Simultaneous minimally invasive repair and lobectomy were performed successfully. There were no significant differences in the mean blood loss (14 mL/kg), the mean weaning time from mechanical ventilation (900 minutes) and the mean hospital stay (16 days) (P>0.05). The mean operative time (170 minutes) was extended, as expected (P=0.02). With a mean follow-up of 22 months, the overall cosmetic results were good., Conclusions: Simultaneous minimally invasive repair and lobectomy appears to be a technically safe and reliable method for the treatment of concurrent PE and CCLLs, although further studies are needed in the long-term follow-up., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Three hundred and ninety five residents in a desert area were examined with chest radiographs and 28 cases with siliceous pneumoconiosis were found. The prevalence of siliceous pneumoconiosis was 7.09%, and that over 40 years of age was 21%. The histological findings of lungs from a camel living in that area for 20 years also confirmed to have siliceous pneumoconiosis.