Immunogenicity and safety of an egg culture-based quadrivalent inactivated non-adjuvanted subunit influenza vaccine in subjects ≥3 years: A randomized,multicenter, double-blind,active-controlled phase III,non-inferiority trial

Subunit influenza vaccine only formulated with surface antigen proteins has better safety profiles relative to split-virion influenza vaccine. Compared to the traditional quadrivalent split-virion influenza vaccine, a novel quadrivalent subunit influenza vaccine is urgently needed in China. We completed a phase 3, randomized, double-blind, active-controlled, non-inferiority clinical study at two sites in Henan Province, China. Eligible volunteers were split into four age cohorts (3–8 years, 9–17 years, 18–64 years, and ≥ 65 years, based on their dates of birth) and randomly assigned (1:1) to the subunit and the split-virion ecNAIIV4 groups. All volunteers were intramuscularly administered a single vaccine dose at baseline, and children aged 3–8 years received a boosting dose at day 28. And the immune response was evaluated by measuring hemagglutinin-inhibition antibody titers against the four vaccine strains in blood samples. Safety profiles had nonsignificant differences between the study groups in ≥ 3 years cohort. Most adverse reactions post-vaccination, both local and systemic, were mild to moderate and resolved within 3 days. And no serious adverse events occurred. The immunogenicity of the trial vaccine was non-inferior to the comparator. Further, a two-dose vaccine series can provide better seroprotection than that of a one-dose series in children aged 3–8 years, with clinically acceptable safety profiles.Clinical Trials Registration. ChiCTR2100049934.     

Temporal changes in extra-axial brain hematoma's signal intensity in magnetic resonance images of trauma patients: A preliminary,technical study

IntroductionDating the exact or estimated time of trauma is an important issue facing forensic medicine. Several clinical and radiological methods were used to achieve this purpose. In the recent study, we aimed to track the changes in the signal intensity of the extra-axial brain hematoma using magnetic resonance imaging (MRI) conventional sequences as well as diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC).Materials and methodsConsidering inclusion and exclusion criteria, all patients with blunt head trauma were involved. After proper management., stabilization, and resuscitation, the participants were assessed using conventional sequences of MRI and DWI twenty-four hours, forty-eight hours, and three weeks after the injury. Temporal changes of signal intensity were compared by Wilcoxon ranged test.ResultsSixteen patients sustaining blunt head trauma were included in this study. The study showed that during the time, diffusion restriction could be seen in an extraaxial hematoma. At the first 24 hours, the signal of hematoma was void in 87.5% of DWI and 100% of ADC. On the second day, they were hypo-signal in 75% of DWI and 100% 0f ADCs, and after three weeks, 100% of cases were hyper-signal in DWI and hypo-signal ADCs.ConclusionThis preliminary study has shown that the DWI can be used to detect and track the extra-axial hematoma. The signal intensity was void during the first twentyfour hours, although it became hypo-signal after 48 hours. Of note, the diffusion restriction is noted after three weeks.     

Preoperative Ozaki technique measures on tridimensional engineered root

BackgroundThe aortic valve neocuspidalization (AVNeo) is an innovative surgical technique aiming at the reconstruction of the aortic valve using autologous pericardium. One of the main criticisms to AVNeo is the longer duration of the aortic clamping time (ACT) as compared to standard aortic valve replacement due to the sizing of the valve neocusps.MethodsWe retrospectively enrolled 30 consecutives patients underwent AVNeo. For each patient we developed a 3D aortic root model (ARM) based on CT-scan datasets. We retrospectively compared the leaflets measurements performed during surgery with those obtained on the corresponding ARMs.ResultsIn 100% of cases no difference between the in vitro and in vivo measurements exceeded the acceptable error limit of 2 ?mm. The correlation of each single in vitro versus in vivo measurements demonstrates a strong coincidence between the two different methods of sizing (r ?> ?0,9, p ?< ?.0001). By analyzing the data considering the annulus perimeter and not the single cusp size, the perfect coincidence was to be found in 89.9% with a slight acceptable discrepancy (2 ?mm on total) in the remaining 10.1%.Conclusions3D-ARMs, printed from CT-scan, represent a reproducible process to obtain overlapping cusp sizes compared to those measured in-vivo, possibly reducing the ACT.     

Cardiac-type total anomalous pulmonary venous return is not benign

ObjectiveThe objective of this study was to investigate the association between morphological variation and postsurgical pulmonary vein (PV) stenosis (PPVS) in patients with cardiac total anomalous pulmonary venous connection (TAPVC).MethodsThis single-center, retrospective study included 168 pediatric patients who underwent surgical repair of cardiac TAPVC from 2013 to 2019 (connection to the coronary sinus [CS], n = 136; connection directly to the right atrium [RA], n = 32). Three-dimensional computed tomography modeling and geometric analysis were performed to investigate the morphological features; their relevance to the PPVS was examined.ResultsThe connection type had no association with PPVS (CS type: 18% vs right atrial type: 19%; P = .89) but there was a higher incidence of PPVS in patients with a single PV orifice than > 1 orifice (P < .001). Confluence-to-total PV area ratio (hazard ratio, 4.78, 95% CI, 1.86-12.32; P = .001) and length of drainage route (hazard ratio, 1.22; 95% CI, 1.14-1.31; P < .001) had a 4- and 1-fold increase in the risk for PPVS in the CS type after adjustment for age and preoperative pulmonary venous obstruction. In the right atrial type, those with anomalous PV return to the RA roof were more likely to develop PPVS than to the posterior wall of the RA (P < .001).ConclusionsThe number of inter-junction PV orifice correlated with PPVS development in cardiac TAPVC. The confluence-to-total PV ratio, length of drainage route, and anomalous PV return to the RA roof are important predictors for PPVS. Morphological subcategorization in this clinical setting can potentially assist in surgical decision-making.     

Small nucleolar RNA host gene 3 functions as a novel biomarker in liver cancer and other tumour progression

Cancer has become the most life-threatening disease in the world. Mutations in and aberrant expression of genes encoding proteins and mutations in noncoding RNAs, especially long noncoding RNAs (lncRNAs), have significant effects in human cancers. LncRNAs have no protein-coding ability but function extensively in numerous physiological and pathological processes. Small nucleolar RNA host gene 3 (SNHG3) is a novel lncRNA and has been reported to be differentially expressed in various tumors, such as liver cancer, gastric cancer, and glioma. However, the interaction mechanisms for the regulation between SNHG3 and tumor progression are poorly understood. In this review, we summarize the results of SNHG3 studies in humans, animal models, and cells to underline the expression and role of SNHG3 in cancer. SNHG3 expression is upregulated in most tumors and is detrimental to patient prognosis. SNHG3 expression in lung adenocarcinoma remains controversial. Concurrently, SNHG3 affects oncogenes and tumor suppressor genes through various mechanisms, including competing endogenous RNA effects. A deeper understanding of the contribution of SNHG3 in clinical applications and tumor development may provide a new target for cancer diagnosis and treatment.     

Dual-target inhibitors of bromodomain-containing protein 4 (BRD4) in cancer therapy: Current situation and future directions

Bromodomain-containing protein 4 (BRD4) is emerging as a therapeutic target that acts synergistically with other targets of small-molecule drugs in cancer. Therefore, the discovery of potential new dual-target inhibitors of BRD4 may be a promising strategy for cancer therapy. In this review, we highlight a series of strategies to design therapeutic dual-target inhibitors of BRD4 that focus on the synergistic functions of this protein. Drug combinations that exploit synthetic lethality, protein–protein interactions, functional complementarity, and blocking of resistance mechanisms could ultimately overcome the barriers inherent to the development of BRD4 inhibitors as future cancer drugs.