Neuromyelitis optica spectrum disorders (NMOSD) are rare inflammatory astrocytic diseases of the central nervous system (CNS). The roles of immune response gene-1 (IRG1) and the IRG1-itaconic acid-NLRP3 inflammatory pathway in the pathogenesis of NMOSD and the effects of 4-octyl itaconate (4-OI) on the NLRP3 inflammatory pathway in NMOSD are unclear. This study aimed to determine the role of IRG1 and the activation status of the NLRP3 inflammatory pathway in acute-onset NMOSD and to investigate the inhibitory effects of 4-OI on NLRP3 inflammasome activation via the IRG1-itaconic acid-NLRP3 pathway in monocytes and macrophages by using in vitro models.
Arsenic combined with all-trans retinoic acid (ATRA) is the standard of care for adult acute promyelocytic leukemia (APL). However, the safety and effectiveness of this treatment in pediatric patients with APL have not been reported on the basis of larger sample sizes.We conducted a multicenter trial at 38 hospitals in China. Patients with newly diagnosed APL were stratified into two risk groups according to baseline WBC count and FLT3-ITD mutation. ATRA plus arsenic trioxide or oral arsenic without chemotherapy were administered to the standard-risk group, whereas ATRA, arsenic trioxide, or oral arsenic plus reduced-dose anthracycline were administered to the high-risk group. Primary end points were event-free survival and overall survival at 2 years.We enrolled 193 patients with APL. After a median follow-up of 28.9 months, the 2-year overall survival rate was 99% (95% CI, 97 to 100) in the standard-risk group and 95% (95% CI, 90 to 100) in the high-risk group (P = .088). The 2-year event-free survival was 97% (95% CI, 93 to 100) in the standard-risk group and 90% (95% CI, 83 to 96) in the high-risk group (P = .252). The plasma levels of arsenic were significantly elevated after treatment, with a stable effective level ranging from 42.9 to 63.2 ng/mL during treatment. In addition, plasma, urine, hair, and nail arsenic levels rapidly decreased to normal 6 months after the end of treatment.Arsenic combined with ATRA is effective and safe in pediatric patients with APL, although long-term follow-up is still needed.
Early diagnosis of gestational diabetes mellitus (GDM) reduces the risk of adverse perinatal and maternal outcomes. At present, the value of serum adiponectin (ADP) and pregnancy-associated plasma protein A (PAPP-A) in clinical practice for the diagnosis of GDM in early pregnancy is unclear. To investigate the predictive value of serum ADP and PAPP-A in GDM. The electronic medical record data of all pregnant women from Zhongshan People's Hospital from 2018 to 2021 were retrospectively collected and divided into GDM group and control group according to whether GDM occurred. ADP and PAPP-A levels of the 2 groups were detected in early pregnancy, and the related factors of GDM were analyzed by binary logistic regression analysis. Receiver operating characteristic (ROC) curves of ADP and PAPP-A in predicting GDM in the early pregnancy were plotted and their clinical predictive value was analyzed. The significance level for all statistical tests is 0.05. Compared with the non-GDM group, the ADP of the GDM group was significantly lower than that of the non-GDM group [(8.19 ± 2.24) vs. (10.04 ± 2.73)]mg/L, the difference between groups was statistically significant (P < .05), and the multiple of median (MoM) of PAPP-A was significantly lower than that of the non-GDM group (1.13 ± 0.52) versus (1.45 ± 0.61) (P < .05). Binary logistic regression analysis showed that elevated serum ADP and PAPP-A levels were negatively correlated with the subsequent development of GDM [odds ratio (OR) 95% confidence interval (95% CI)] was 0.626 (0.536, 0.816), 0.934 (0.908, 0.961), respectively, P < .05.ROC curve analysis showed that the sensitivity and specificity of ADP and PAPP-A in predicting gestational diabetes were79.1% and 58.6%, respectively, 92.7% and 73.1%, and respectively. The area under curve (AUC) is 0.755 for ADP and 0.770 for PAPP-A. The AUC of the combined detection was 0.867, both of which were higher than that of single index diagnosis, and the sensitivity and specificity of the combined detection were 0.958 and 0.853, respectively. In summary, PAPP-A and ADP levels are independent related factors affecting the occurrence of GDM. The combined detection of PAPP-A and ADP should be utilized in diagnosing GDM to improve pregnancy outcomes for pregnant women.
Intracranial hemorrhage (ICH) is a rare but fatal central nervous system complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, factors that are predictive of early mortality in patients who develop ICH after undergoing allo-HSCT have not been systemically investigated. From January 2008 to June 2020, a total of 70 allo-HSCT patients with an ICH diagnosis formed the derivation cohort. Forty-one allo-HSCT patients with an ICH diagnosis were collected from 12 other medical centers during the same period, and they comprised the external validation cohort. These 2 cohorts were used to develop and validate a grading scale that enables the prediction of 30-day mortality from ICH in all-HSCT patients. Four predictors (lactate dehydrogenase level, albumin level, white blood cell count, and disease status) were retained in the multivariable logistic regression model, and a simplified grading scale (termed the LAWS score) was developed. The LAWS score was adequately calibrated (Hosmer-Lemeshow test, P > .05) in both cohorts. It had good discrimination power in both the derivation cohort (C-statistic, 0.859; 95% confidence interval, 0.776-0.945) and the external validation cohort (C-statistic, 0.795; 95% confidence interval, 0.645-0.945). The LAWS score is the first scoring system capable of predicting 30-day mortality from ICH in allo-HSCT patients. It showed good performance in identifying allo-HSCT patients at increased risk of early mortality after ICH diagnosis. We anticipate that it would help risk stratify allo-HSCT patients with ICH and facilitate future studies on developing individualized and novel interventions for patients within different LAWS risk groups.
Patients with hematogenous metastatic lung cancer displayed significantly increased platelet count and aggregation compared to lung cancer patients without hematogenous metastasis. The mechanism underlying the correlation between the lung cancer hematogenous metastasis and platelet activation remains unknown. In the present study, we explored the role of microRNA-223 (miR-223) derived from platelets in modulating lung cancer cell invasion. Our results demonstrated that platelets from NSCLC patients contain higher level of miR-223 than that from healthy subjects. The concentration of miR-223 in the platelet-secreted microvesicles (P-MVs) from NSCLC patients was also increased compared to that from healthy subjects. Incubation of human lung cancer A549 cells with P-MVs resulted in rapid delivery of miR-223 into A549 cells, in which platelet miR-223 targeted EPB41L3 and thus promoted A549 cell invasion. The effect of P-MVs on reducing EPB41L3 in A549 cells but promoting tumor cell invasion could be largely abolished by depletion of miR-223 via transfection with miR-223 antagomir. The role of EPB41L3 in inhibiting A549 cell invasion was further validated by directly downregulating EPB41L3 via transfecting cells with EPB41L3 siRNA or miR-223 mimic. Our study demonstrates for the first time that platelet-secreted miR-223 via P-MVs can promote lung cancer cell invasion via targeting tumor suppressor EPB41L3.
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