Guanyu Jiang

INTRODUCTION: Early detection of pneumothorax in multiple trauma patients is critically important. It can be argued that the efficacy of ultrasonography (US) for detection of pneumothorax is enhanced if it is performed and interpreted directly by the clinician in charge of the patients. The aim of this study was to assess the ability of emergency department clinicians to perform bedside US to detect and assess the size of the pneumothorax in patients with multiple trauma. METHODS: Over a 14 month period, patients with multiple trauma treated in the emergency department were enrolled in this prospective study. Bedside US was performed by emergency department clinicians in charge of the patients. Portable supine chest radiography (CXR) and computed tomography (CT) were obtained within an interval of three hours. Using CT and chest drain as the gold standard, the diagnostic efficacy of US and CXR for the detection of pneumothorax, defined as rapidity and accuracy (sensitivity, specificity, positive predictive value, negative predictive value), were compared. The size of the pneumothorax (small, medium and large) determined by US was also compared to that determined by CT. RESULTS: Of 135 patients (injury severity score = 29.1 +/- 12.4) included in the study, 83 received mechanical ventilation. The time needed for diagnosis of pneumothorax was significantly shorter with US compared to CXR (2.3 +/- 2.9 versus 19.9 +/- 10.3 minutes, p < 0.001). CT and chest drain confirmed 29 cases of pneumothorax (21.5%). The diagnostic sensitivity, specificity, positive and negative predictive values and accuracy for US and radiography were 86.2% versus 27.6% (p < 0.001), 97.2% versus 100% (not significant), 89.3% versus 100% (not significant), 96.3% versus 83.5% (p = 0.002), and 94.8% versus 84.4% (p = 0.005), respectively. US was highly consistent with CT in determining the size of pneumothorax (Kappa = 0.669, p < 0.001). CONCLUSION: Bedside clinician-performed US provides a reliable tool and has the advantages of being simple and rapid and having higher sensitivity and accuracy compared to chest radiography for the detection of pneumothorax in patients with multiple trauma.

Metabolic reprogramming is one of the most important hallmarks of malignant tumors. Specifically, lipid metabolic reprogramming has marked impacts on cancer progression and therapeutic response by remodeling the tumor microenvironment (TME). In the past few decades, immunotherapy has revolutionized the treatment landscape for advanced cancers. Lipid metabolic reprogramming plays pivotal role in regulating the immune microenvironment and response to cancer immunotherapy. Here, we systematically reviewed the characteristics, mechanism, and role of lipid metabolic reprogramming in tumor and immune cells in the TME, appraised the effects of various cell death modes (specifically ferroptosis) on lipid metabolism, and summarized the antitumor therapies targeting lipid metabolism. Overall, lipid metabolic reprogramming has profound effects on cancer immunotherapy by regulating the immune microenvironment; therefore, targeting lipid metabolic reprogramming may lead to the development of innovative clinical applications including sensitizing immunotherapy.

Immune checkpoint blockade (ICB) therapy has achieved breakthroughs in the treatment of advanced non-small cell lung cancer (NSCLC). Nevertheless, the low response due to immuno-cold (i.e., tumors with limited tumor-infiltrating lymphocytes) tumor microenvironment (TME) largely limits the application of ICB therapy. Based on the glycolytic/cholesterol synthesis axis, a stratification framework for EGFR-WT NSCLC was developed to summarize the metabolic features of immuno-cold and immuno-hot tumors. The cholesterol subgroup displays the worst prognosis in immuno-cold NSCLC, with significant enrichment of the cholesterol gene signature, indicating that targeting cholesterol synthesis is essential for the therapy for immuno-cold NSCLC. Statin, the inhibitor for cholesterol synthesis, can suppress the aggressiveness of NSCLC in vitro and in vivo and can also drastically reverse the phenotype of immuno-cold to an inflamed phenotype in vivo. This change led to a higher response to ICB therapy. Moreover, both our in-house data and meta-analysis further support that statin can significantly enhance ICB efficacy. In terms of preliminary mechanisms, statin could transcriptionally inhibit PD-L1 expression and induce ferroptosis in NSCLC cells. Overall, we reveal the significance of cholesterol synthesis in NSCLC and demonstrate the improved therapeutic efficacy of ICB in combination with statin. These findings could provide a clinical insight to treat NSCLC patients with immuno-cold tumors.

Schizophrenia is a debilitating familial neuropsychiatric disorder which affects 1% of people worldwide. Although the heritability for schizophrenia approaches 80% only a small proportion of the overall genetic risk has been accounted for, and to date only a limited number of genetic loci have been definitively implicated. We have identified recently through genetic and in vitro functional studies, a novel serine/threonine kinase gene, unc-51-like kinase 4 (ULK4), as a rare risk factor for major mental disorders including schizophrenia. Now using the approach of in utero gene transfer we have discovered that Ulk4 plays a key modulatory role in corticogenesis. Knockdown of Ulk4 leads to significantly decreased cell proliferation in germinal zones and profound deficits in radial migration and neurite ramification. These abnormalities can be reversed successfully by Ulk4 gene supplementation. Ulk4 also regulated acetylation of α-tubulin, an important post-translational modification of microtubules. We conclude that Ulk4 plays an essential role in normal brain development and when defective, the risk of neurodevelopmental disorders such as schizophrenia is increased.