International Journal of Medical Sciences最新文献

Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease, characterized by dysregulated immune response. HDAC3 is reported to be an epigenetic brake in inflammation, playing critical roles in macrophages. However, its role in IBD is unclear. In our study, we found HDAC3 was upregulated in CX3CR1-positive cells in the mucosa from IBD mice. Conditional knockout (cKO) of Hdac3 in CX3CR1 positive cells attenuated the disease severity of Dextran Sulfate Sodium (DSS)-induced colitis. In addition, inhibition of HDAC3 with RGFP966 could also alleviate the DSS-induced tissue injury and inflammation in IBD. The RNA sequencing results revealed that Hdac3 cKO restrained DSS-induced upregulation of genes in the pathways of cytokine-cytokine receptor interaction, complement and coagulation cascades, chemokine signaling, and extracellular matrix receptor interaction. We also identified that Guanylate-Binding Protein 5 (GBP5) was transcriptionally regulated by HDAC3 in monocytes by RNA sequencing. Inhibition of HDAC3 resulted in decreased transcriptional activity of interferon-gamma-induced expression of GBP5 in CX3CR1-positive cells, such as macrophages and microglia. Overexpression of HDAC3 upregulated the transcriptional activity of GBP5 reporter. Lastly, conditional knockout of Hdac3 in macrophages (Hdac3 mKO) attenuated the disease severity of DSS-induced colitis. In conclusion, inhibition of HDAC3 in macrophages could ameliorate the disease severity and inflammatory response in colitis by regulating GBP5-NLRP3 axis, identifying a new therapeutic avenue for the treatment of colitis.

Background: Hemoptysis is prevalent in acute pulmonary embolism (PE) and significantly influences clinical decision-making. Despite the increasing reports of PE in patients with autoimmune diseases, limited studies have investigated the association between acute PE with hemoptysis and autoimmune disease. Methods: The retrospective study aimed to investigate patients with autoimmune disease who presented with acute PE and hemoptysis at Peking Union Medical College Hospital (PUMCH) between January 2012 and October 2020. A comparative analysis was conducted between patients with and without hemoptysis, as well as between those with autoimmune diseases and those without. Clinical characteristics, PE severity stratification, the amount of hemoptysis, initial anticoagulation management, and prognosis were analyzed descriptively. Results: The study analyzed 896 patients diagnosed with acute PE, of whom 105 (11.7%) presented with hemoptysis. Hemoptysis in PE patients was frequently associated with autoimmune diseases (39%, 41/105), a younger patient population (42.0 vs. 52.7 years old, P =0.002), and a higher prevalence of low-risk PE (53.7 vs. 28.1, P=0.008) compared with non-autoimmune disease patients. Multivariate logistic analysis showed PE patients with primary or metastatic lung cancer, chest pain, age < 48 years old, chronic heart failure, autoimmune disease, pulmonary infection and male were more likely to develop hemoptysis. Patients were grouped based on maximum daily sputum blood volume and PE risk stratification. Most patients (73.2%) received therapeutic-dose anticoagulation. Poor prognosis is observed in patients with moderate to massive hemoptysis and intermediate-high-risk or high-risk PE. Conclusions: Hemoptysis is a relatively common manifestation in patients with PE, and its presence during the diagnostic workup of acute PE necessitates careful analysis of underlying comorbidities. In cases where hemoptysis occurs in individuals with autoimmune diseases in the context of PE, proactive management strategies targeting the primary disease are crucial. Therapeutic decisions should consider both PE severity stratification and the volume of hemoptysis.

Background: Predicting fall injuries can mitigate the sequelae of falls and potentially utilize medical resources effectively. This study aimed to externally validate the accuracy of the Saga Fall Injury Risk Model (SFIRM), consisting of six factors including age, sex, emergency transport, medical referral letter, Bedriddenness Rank, and history of falls, assessed upon admission. Methods: This was a two-center, prospective, observational study. We included inpatients aged 20 years or older in two hospitals, an acute and a chronic care hospital, from October 2018 to September 2019. The predictive performance of the model was evaluated by calculating the area under the curve (AUC), 95% confidence interval (CI), and shrinkage coefficient of the entire study population. The minimum sample size of this study was 2,235 cases. Results: A total of 3,549 patients, with a median age of 78 years, were included in the analysis, and men accounted for 47.9% of all the patients. Among these, 35 (0.99%) had fall injuries. The performance of the SFIRM, as measured by the AUC, was 0.721 (95% CI: 0.662-0.781). The observed fall incidence closely aligned with the predicted incidence calculated using the SFIRM, with a shrinkage coefficient of 0.867. Conclusions: The external validation of the SFIRM in this two-center, prospective study showed good discrimination and calibration. This model can be easily applied upon admission and is valuable for fall injury prediction.

Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against mouse abdominal aortic aneurysm (AAA) induced by both angiotensin II (AngII) and calcium phosphate (Ca₃(PO₄)₂) in vivo, which was characterized with lower incidence of mouse AAA. Moreover, histomorphological staining visually presented more intact elastic fiber and less collagen deposition in abdominal aortas of mice treated by glutamine. Further, we found glutamine inhibited the excessive production of reactive oxide species (ROS), activity of matrix metalloproteinase (MMP), M1 macrophage activation, and apoptosis of vascular smooth muscle cells (VSMCs) in suprarenal abdominal aortas of mice, what's more, the high expressions of MMP-2 protein, MMP-9 protein, pro-apoptotic proteins, and IL-6 as well as TNF-α in protein and mRNA levels in cells treated by AngII were down-regulated by glutamine. Collectively, these results revealed that glutamine protected against mouse AAA through inhibiting apoptosis of VSMCs, M1 macrophage activation, oxidative stress, and extracellular matrix degradation.

The Sodium-glucose co-transporter 2 (SGLT2) inhibitor is an anti-glycemic agent that frequently used in type 2 diabetes mellitus (T2DM) with antioxidant effects. Endometrial cancer (EC) is a common gynecological malignancy that correlates with oxidative stress. The aim in the present study is to survey the potential association between the SGLT2 inhibitor administration and the incidence of EC by the application of the National Health Insurance Research Database (NHIRD) of Taiwan. A retrospective cohort study was directed and the T2DM participants were divided into the SGLT2 inhibitors users and non-SGLT2 inhibitors users. After matching, a total of 163,668 and 327,336 participants were included into the SGLT2 inhibitors and control groups, respectively. The primary outcome is regarded as the development of EC according to the diagnostic, image, and procedure codes. Cox proportional hazard regression was employed to generate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of EC between the two groups. There were 422 and 876 EC events observed in the SGLT2 inhibitors and control groups, respectively. The SGLT2 inhibitors group demonstrated a significantly lower incidence of EC formation compared to the control groups (aHR: 0.87, 95% CI: 0.76-0.99). In the subgroup analysis, the correlation between SGLT2 inhibitor administration and lower rate of EC existed in the T2DM individuals with aged under 60. Moreover, the association between SGLT2 inhibitor administration and lower EC incidence only presented in the T2DM population with SGLT2 inhibitor administration under one year (aHR: 0.58, 95% CI: 0.45-0.73). In conclusion, the administration of SGLT2 inhibitors correlates to lower incidence of EC in T2DM population.