Endoplasmic Reticulum Stress Response Mediator IRE-1α Promotes Host Dendritic Cells in Graft-versus-Host Disease Development.

Allogeneic hematopoietic cell transplantation is an effective treatment for hematologic malignancies, but the complications such as graft-versus-host disease (GVHD) can limit its benefit. The conditioning regimens before transplant, including chemotherapy or irradiation, can trigger endoplasmic reticulum stress. IRE-1α is a major endoplasmic reticulum stress mediator that can further activate both spliced XBP-1 (XBP-1s) and regulated IRE-1-dependent decay (RIDD). IRE-1α-XBP-1s signaling controls dendritic cell (DC) differentiation and Ag presentation, crucial in GVHD progression. In this study, we used DC-specific XBP-1-deficient mice as donors or recipients and observed that XBP-1s was crucial for host DCs in the induction of GVHD but dispensable for the graft-versus-leukemia response. To specifically target IRE-1α in the host, we treated recipient mice with the IRE-1α inhibitor B-I09 for 3 d prior to bone marrow transplantation, which significantly suppressed GVHD development while maintaining the graft-versus-leukemia effect. XBP-1-deficient or BI09-treated recipients showed reduced DC survival after irradiation and bone marrow transplantation. Inhibition of IRE-1α also led to a reduction in DC alloreactivity, subsequently decreasing the proliferation and activation of allogeneic T cells. With further study using RIDD-deficient DCs, we observed that RIDD was also required for optimal DC activation. Taken together, XBP-1s and RIDD both promote host DC survival and alloreactivity that contribute to GVHD development.

Risk factors and management of gastrointestinal bleeding in patients with or without antiplatelet and anticoagulation therapy: a multicenter real-world prospective study.

BACKGROUND: Antiplatelet and anticoagulation drugs complicate acute gastrointestinal bleeding (GIB) patients. Limited data about the risk factors and patient management has been presented. This study explored the association between previous antiplatelet or anticoagulant drug usage and clinical outcomes in GIB patients to improve awareness further and optimize treatment. METHODS: We conducted a multicenter, non-interventional, real-world prospective study in 106 hospitals in 23 provinces in China. GIB patients confirmed in the emergency department were included and were grouped according to previous drug histories. Univariate analysis, multivariate logistic regression, and multivariate stratification models were performed separately to investigate the associations. RESULTS: A total of 2299 patients (57.23 ± 17.21 years old, 68.3% male) were included, of whom 20.1% and 2.9% received antiplatelet and anticoagulation therapy, respectively. The all-cause 28-day mortality rates in patients without antiplatelet or anticoagulants, patients undergoing antiplatelet treatment, and patients with anticoagulation therapy were 2.8%, 4.6%, and 10.5%, respectively. After adjusting for confounding factors, both antiplatelet [odd ratio (OR), 2.92; 95% confidence interval (CI), 1.48-5.76; p = 0.002] and anticoagulation therapy (OR, 8.87; 95% CI, 3.02-26.02; p < 0.001) were associated with higher 28-day mortality. In the subgroup analysis, blood transfusion, especially red blood cell transfusion, in patients undergoing antiplatelet and anticoagulation therapy was associated with a decreased death risk. CONCLUSION: We confirmed an association between concurrent antiplatelet or anticoagulation therapy in GIB patients and elevated 28-day mortality. Blood transfusions could improve poor outcomes in such patients.

Prevalence and Associated Factors of Thyroid Nodules Among 52,003 Chinese 'Healthy' Individuals in Beijing: A Retrospective Cross-Sectional Study.

Introduction: The prevalence of thyroid nodules has been increasing, and there are few research data on the risk factors of thyroid nodules in the Chinese population. In this study, we aimed to determine the prevalence and risk factors of thyroid nodules by retrospectively investigating the physical examination records of a cohort of "healthy" individuals in Beijing, China. Methods: This was a retrospective cross-sectional study. The database of a Medical Examination Centre (MEC) was searched. Physical examination data, blood test data, and ultrasound examination data, etc., from 2015 to 2017 were accessed. Only those that recorded a thyroid ultrasound were included. Chi-square test and t-test were used to compare clinical features of individuals' age, gender, body mass index, blood pressure, blood glucose, blood lipids, uric acid, and presence of fatty liver. Risk factors for thyroid nodules were determined using multivariate logistic regression. Results: A total of 52,003 records, which included 19,901 cases with thyroid nodules, were examined. The overall prevalence rate was 38.3% (19,901/52,003): 30.2% (6,726/22,305) and 44.4% (13,175/29,698) in men and women, respectively. Of 52,003 cases, only 35,420 cases had records of all nodule-related metabolic abnormalities and were selected for cross-sectional determination of related risk factors of thyroid nodules. In male, relationships were found between thyroid nodules and increased age (p < 0.001), impaired fasting glucose (p = 0.044), diabetes (p = 0.047), decreased HDL-C (p = 0.018) and prostatic hyperplasia (p < 0.001). And in female, relationships were found between thyroid nodules and increased age (p < 0.001) and decreased HDL-C (p < 0.001). Conclusion: Thyroid nodules are common in China. This study found that thyroid nodules are associated with several metabolic indicators or metabolic diseases, although the mechanism is unclear. Further research is needed.

A novel predictor of unsustained return of spontaneous circulation in cardiac arrest patients through a combination of capnography and pulse oximetry: a multicenter observational study.

BACKGROUND: Unsustained return of spontaneous circulation (ROSC) is a critical barrier to survival in cardiac arrest patients. This study examined whether end-tidal carbon dioxide (ETCO2) and pulse oximetry photoplethysmogram (POP) parameters can be used to identify unsustained ROSC. METHODS: We conducted a multicenter observational prospective cohort study of consecutive patients with cardiac arrest from 2013 to 2014. Patients' general information, ETCO2, and POP parameters were collected and statistically analyzed. RESULTS: The included 105 ROSC episodes (from 80 cardiac arrest patients) comprised 51 sustained ROSC episodes and 54 unsustained ROSC episodes. The 24-hour survival rate was significantly higher in the sustained ROSC group than in the unsustained ROSC group (29.2% vs. 9.4%, P<0.05). The logistic regression analysis showed that the difference between after and before ROSC in ETCO2 (ΔETCO2) and the difference between after and before ROCS in area under the curve of POP (ΔAUCp) were independently associated with sustained ROSC (odds ratio [OR]=0.931, 95% confidence interval [95% CI] 0.881-0.984, P=0.011 and OR=0.998, 95% CI 0.997-0.999, P<0.001). The area under the receiver operating characteristic curve of ΔETCO2, ΔAUCp, and the combination of both to predict unsustained ROSC were 0.752 (95% CI 0.660-0.844), 0.883 (95% CI 0.818-0.948), and 0.902 (95% CI 0.842-0.962), respectively. CONCLUSION: Patients with unsustained ROSC have a poor prognosis. The combination of ΔETCO2 and ΔAUCp showed significant predictive value for unsustained ROSC.