Purpose: This study aimed to compare cognitive, non-cognitive, and overall learning outcomes for sepsis and trauma resuscitation skills in novices with virtual patient simulation (VPS) versus in-person simulation (IPS). Methods: A randomized controlled trial was conducted on junior doctors in 1 emergency department from January to December 2022, comparing 70 minutes of VPS (n=19) versus IPS (n=21) in sepsis and trauma resuscitation. Using the nominal group technique, we created skills assessment checklists and determined Bloom’s taxonomy domains for each checklist item. Two blinded raters observed participants leading 1 sepsis and 1 trauma resuscitation simulation. Satisfaction was measured using the Student Satisfaction with Learning Scale (SSLS). The SSLS and checklist scores were analyzed using the Wilcoxon rank sum test and 2-tailed t-test respectively. Results: For sepsis, there was no significant difference between VPS and IPS in overall scores (2.0; 95% confidence interval [CI], -1.4 to 5.4; Cohen’s d=0.38), as well as in items that were cognitive (1.1; 95% CI, -1.5 to 3.7) and not only cognitive (0.9; 95% CI, -0.4 to 2.2). Likewise, for trauma, there was no significant difference in overall scores (-0.9; 95% CI, -4.1 to 2.3; Cohen’s d=0.19), as well as in items that were cognitive (-0.3; 95% CI, -2.8 to 2.1) and not only cognitive (-0.6; 95% CI, -2.4 to 1.3). The median SSLS scores were lower with VPS than with IPS (-3.0; 95% CI, -1.0 to -5.0). Conclusion For novices, there were no major differences in overall and non-cognitive learning outcomes for sepsis and trauma resuscitation between VPS and IPS. Learners were more satisfied with IPS than with VPS (clinicaltrials.gov identifier: NCT05201950).

Purpose: This study aimed to compare cognitive, non-cognitive, and overall learning outcomes for sepsis and trauma resuscitation skills in novices with virtual patient simulation (VPS) versus in-person simulation (IPS). Methods: A randomized controlled trial was conducted on junior doctors in 1 emergency department from January to December 2022, comparing 70 minutes of VPS (n=19) versus IPS (n=21) in sepsis and trauma resuscitation. Using the nominal group technique, we created skills assessment checklists and determined Bloom’s taxonomy domains for each checklist item. Two blinded raters observed participants leading 1 sepsis and 1 trauma resuscitation simulation. Satisfaction was measured using the Student Satisfaction with Learning Scale (SSLS). The SSLS and checklist scores were analyzed using the Wilcoxon rank sum test and 2-tailed t-test respectively. Results: For sepsis, there was no significant difference between VPS and IPS in overall scores (2.0; 95% confidence interval [CI], -1.4 to 5.4; Cohen’s d=0.38), as well as in items that were cognitive (1.1; 95% CI, -1.5 to 3.7) and not only cognitive (0.9; 95% CI, -0.4 to 2.2). Likewise, for trauma, there was no significant difference in overall scores (-0.9; 95% CI, -4.1 to 2.3; Cohen’s d=0.19), as well as in items that were cognitive (-0.3; 95% CI, -2.8 to 2.1) and not only cognitive (-0.6; 95% CI, -2.4 to 1.3). The median SSLS scores were lower with VPS than with IPS (-3.0; 95% CI, -1.0 to -5.0). Conclusion For novices, there were no major differences in overall and non-cognitive learning outcomes for sepsis and trauma resuscitation between VPS and IPS. Learners were more satisfied with IPS than with VPS (clinicaltrials.gov identifier: NCT05201950).

Purpose: This study aimed to compare cognitive, non-cognitive, and overall learning outcomes for sepsis and trauma resuscitation skills in novices with virtual patient simulation (VPS) versus in-person simulation (IPS). Methods: A randomized controlled trial was conducted on junior doctors in 1 emergency department from January to December 2022, comparing 70 minutes of VPS (n=19) versus IPS (n=21) in sepsis and trauma resuscitation. Using the nominal group technique, we created skills assessment checklists and determined Bloom’s taxonomy domains for each checklist item. Two blinded raters observed participants leading 1 sepsis and 1 trauma resuscitation simulation. Satisfaction was measured using the Student Satisfaction with Learning Scale (SSLS). The SSLS and checklist scores were analyzed using the Wilcoxon rank sum test and 2-tailed t-test respectively. Results: For sepsis, there was no significant difference between VPS and IPS in overall scores (2.0; 95% confidence interval [CI], -1.4 to 5.4; Cohen’s d=0.38), as well as in items that were cognitive (1.1; 95% CI, -1.5 to 3.7) and not only cognitive (0.9; 95% CI, -0.4 to 2.2). Likewise, for trauma, there was no significant difference in overall scores (-0.9; 95% CI, -4.1 to 2.3; Cohen’s d=0.19), as well as in items that were cognitive (-0.3; 95% CI, -2.8 to 2.1) and not only cognitive (-0.6; 95% CI, -2.4 to 1.3). The median SSLS scores were lower with VPS than with IPS (-3.0; 95% CI, -1.0 to -5.0). Conclusion For novices, there were no major differences in overall and non-cognitive learning outcomes for sepsis and trauma resuscitation between VPS and IPS. Learners were more satisfied with IPS than with VPS (clinicaltrials.gov identifier: NCT05201950).

Currently the main treatment of acute myeloid leukemia (AML) is chemotherapy combining hematopoietic stem cell transplantation. However, the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice. Thus, there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects. Here, we revealed that umbilical cord-derived mesenchymal stem cells (UC-MSC) efficiently induced AML cell differentiation by shuttling the neutrophil elastase (NE)-packaged extracellular vesicles (EVs) into AML cells. Interestingly, the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor (VDR) activation in UC-MSC. Chemical activation of VDR by using its agonist 1α,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model. Based on these discoveries, to evade the risk of hypercalcemia, we synthetized and identified sw-22, a novel non-steroidal VDR agonist, which exerted a synergistic pro-differentiation function with UC-MSC on mitigating the progress of AML. Collectively, our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.

Humans ; Neoplasms, Second Primary/epidemiology* ; Neoplasms/epidemiology* ; Risk Factors ; Prognosis

A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or off-target effects. Recently, the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology. Here, we propose a novel Siamese spectral-based graph convolutional network (SSGCN) model for inferring the protein targets of chemical compounds from gene transcriptional profiles. Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets, and the biological networks under different experiment conditions further complicate the situation, the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles. On a benchmark set and a large time-split validation dataset, the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map. Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound, or reversely, in finding novel inhibitors of a given target of interest.
Drug Delivery Systems ; Proteins ; Transcriptome

Metastasis is crucial for the mortality of non-small cell lung carcinoma (NSCLC) patients. The epithelial-mesenchymal transition (EMT) plays a critical role in regulating tumor metastasis. Glioma-associated oncogene 1 (Gli1) is aberrantly active in a series of tumor tissues. However, the molecular regulatory relationships between Gli1 and NSCLC metastasis have not yet been identified. Herein, we reported Gli1 promoted NSCLC metastasis. High Gli1 expression was associated with poor survival of NSCLC patients. Ectopic expression of Gli1 in low metastatic A549 and NCI-H460 cells enhanced their migration, invasion abilities and facilitated EMT process, whereas knock-down of Gli1 in high metastatic NCI-H1299 and NCI-H1703 cells showed an opposite effect. Notably, Gli1 overexpression accelerated the lung and liver metastasis of NSCLC in the intravenously injected metastasis model. Further research showed that Gli1 positively regulated Snail expression by binding to its promoter and enhancing its protein stability, thereby facilitating the migration, invasion and EMT of NSCLC. In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.

Objective:To investigate the effects of different lipid-lowering regimens on blood lipids, endothelial function and safety in patients with unstable angina.Methods:Patients who admitted to Henan Provincial People's Hospital for unstable angina from September 2018 to May 2019 were randomly (random number) divided into the conventional treatment group, intensive statin group and intensive lipid-lowering group. Follow-up was performed at 1, 3, and 6 months after treatment according to the predetermined lipid-lowering regimen. Assessments included lipid profile, liver function, muscle enzymes, hypersensitive C-reactive protein (hs-CRP), endothelial function (reactive hyperemia index, RHI), ischemic events, myalgia, and discontinuation. The differences of the follow-up indicators among the three groups were analyzed.Results:A total of 375 patients were enrolled and randomly divided into three groups, 125 patients in each group. There were no significant differences in demographic data and medication among the three groups. At the 1st month, the low density lipoprotein cholesterin (LDL-C) compliance rate of the intensive statin group was significantly higher than those in the conventional treatment group ( χ2=3.939, P=0.047) and the intensive lipid-lowering group ( χ2=4.63, P=0.031). At the 3rd month, the reductions of LDL-C in the intensive statin group and the intensive lipid-lowering group were significantly better than that in the conventional treatment group( P<0.01). At the 6th month, the reduction rate of LDL-C in the intensive lipid-lowering group was higher than that in the intensive statin group ( q=4.332, P<0.01). At the 1st month, the improvement of hs-CRP and RHI in the intensive statin group was significantly better than that in the conventional treatment group( q=4.133, P<0.05). From the 3rd month of treatment, the incidence of cardiovascular events in the intensive statin group and the intensive lipid-lowering group showed a tendency to decrease compared with the conventional treatment group, but no statistically significant difference was found. At the 6th months of treatment, the withdrawal rates were significantly higher in the intensive statin group and the intensive lipid-lowering group than that in the conventional treatment group (χ 2=4.488, P=0.03 and χ2=5.039, P=0.02). There were no significant differences in the ratio of liver enzyme and muscle enzyme elevation and the incidence of myalgia among the three groups (all P>0.05). Conclusions:Intensive statin therapy can make LDL-C reach the standard in patients with unstable angina pectoris as soon as possible, significantly improve inflammation indicators and endothelial function, and has good safety.

INTRODUCTION: Flexible bronchoscopic intubation (FBI) is an important technique in managing an anticipated difficult airway, yet it is rarely performed and has a steep learning curve. We aim to evaluate if the integration of virtual reality gaming application into routine FBI training for emergency department doctors would be more effective than traditional teaching methods. METHODS: We conducted a randomised controlled trial to compare self-directed learning using the mobile application, Airway Ex* in the intervention group versus the control group without use of the mobile application. All participants underwent conventional didactic teaching and low-fidelity simulation with trainer's demonstration and hands-on practice on a manikin for FBI. Participants randomised to the intervention arm received an additional 30 minutes of self-directed learning using Airway Ex, preloaded on electronic devices while the control arm did not. The primary outcome was time taken to successful intubation. RESULTS: Forty-five physicians (20 junior and 25 senior physicians) were enrolled, with male predominance (57.8%, 26/45). There was no difference in time taken to successful intubation (median 48 seconds [interquartile range, IQR 41-69] versus 44 seconds [IQR 37-60], P=0.23) between the control and intervention groups, respectively. However, the intervention group received better ratings (median 4 [IQR 4-5]) for the quality of scope manipulation skills compared to control (median 4 [IQR 3-4], adjusted P=0.03). This difference remains significant among junior physicians in stratified analysis. CONCLUSION Incorporating virtual reality with traditional teaching methods allows learners to be trained on FBI safely without compromising patient care. Junior physicians appear to benefit more compared to senior physicians.

AIM: To investigate drug resistance of Acinetobacter baumannii strains isolated in the hospital from 2018 to 2019, and explore plasmid-mediated delivery of quinolones resistance genes (PMQR) in Acinetobacter baumannii, to provide references for the clinical therapy of infections and to analysis the genetic mechanisms of resistance by aid of molecular methods. METHODS: Bacteria were identified by VITEK-2 compact System, the results of antibiotics susceptibility test was determined by using microdilution method MIC. We amplified genes of qnrA, B, C, D, S, aac(6')-Ib and qepA on plasmid by PCR, and PCR products of each resistant gene for sequencing analysis were random selected. We analyzed the results of antibiotics susceptibility of 152 clinical isolates based on WHONET 5.6 software. RESULTS: In the past two years, 152 strains of Acinetobacter baumannii have been detected from clinical specimens. The antibiotics resistance rate of Acinetobacter baumannii isolates was an increasing trend year by year. PCR indicated that some strains of Acinetobacter baumannii have products of aac(6')-Ib and qnrB gene, 29.6%(45/152) strains carrying aac(6')-Ib and 1.3%(2/152) strains carrying qnrB; there were no products of qnrA, C, D, S and qepA genes on plasmid. CONCLUSION: The current drug-resistance rate among Acinetobacter baumannii strains in Hefei to common antibiotics is high, and PMQR carrying rate is low.