Tumor perfusion enhancement effect combined with programmed cell death-Ligand 1 antibody improves the immune microenvironment of solid tumors / 中华超声影像学杂志

Objective:To investigate the tumor perfusion enhancement induced by low intensity ultrasound stimulated microbubble cavitation (USMC) combined with programmed cell death-Ligand 1(PD-L1) antibody on improving the immune microenvironment of solid tumors.Methods:Tumor-bearing mice were divided into 4 groups: Control ( n=26) group, USMC ( n=27) group, anti-PD-L1 ( n=27) group and USMC+ anti-PD-L1 ( n=27) group. USMC treatment was performed with a VINNO 70 ultrasound theranostics system. Tumor perfusion was evaluated by contrast-enhanced ultrasound (CEUS). The anti-tumor efficacy was assessed by the tumor growth curve and the survival time of mice. The number and function of CD8 + T cells, the differentiation of CD4 + T cells, the proportion of MDSC and the phenotype distribution of TAM in tumors were analyzed by flow cytometry. The content of CXCL9, CXCL10 and HIF-1α in tumor were detected by ELISA. The expression of VEGF in tumor tissues was analyzed by immunofluorescence. Results:CEUS showed that the values of PI and AUC of tumors were significantly increased after USMC compared with before USMC (all P<0.05). USMC combined with anti-PD-L1 therapy did suppress the tumor progression. FCM showed the number, the expression of proliferation antigen Ki67, the secretion of IFN-γ and Granzyme B of CD8 + T cells in tumors were higher in combined group than those in other three groups after therapy (all P<0.05). Meantime, the proportion of Th1 was rose while Tregs and MDSC were declined and the polarization of TAM was toward M1 type by combined therapy. ELISA analysis showed that the combined therapy also increased the concentration of CXCL9, CXCL10 and decreased the content of HIF-1α in tumors (all P<0.05). Meanwhile, the immunofluorescence expression of VEGF was significantly lower in combined group than that in the control group after treatment ( P<0.05). Conclusions:Tumor perfusion enhancement by USMC combined with PD-L1 antibody therapy could improve tumor immune microenvironment and USMC might be a novel effective method for potentiating PD-L1 antibody immunotherapy.

Post-infectious inflammatory disease in MIS-C features elevated cytotoxicity signatures and autoreactivity that correlates with severity

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children. Here, we define immune abnormalities in MIS-C compared to adult COVID-19 and pediatric/adult healthy controls using single-cell RNA sequencing, antigen receptor repertoire analysis, unbiased serum proteomics, and in vitro assays. Despite no evidence of active infection, we uncover elevated S100A-family alarmins in myeloid cells and marked enrichment of serum proteins that map to myeloid cells and pathways including cytokines, complement/coagulation, and fluid shear stress in MIS-C patients. Moreover, NK and CD8 T cell cytotoxicity genes are elevated, and plasmablasts harboring IgG1 and IgG3 are expanded. Consistently, we detect elevated binding of serum IgG from severe MIS-C patients to activated human cardiac microvascular endothelial cells in culture. Thus, we define immunopathology features of MIS-C with implications for predicting and managing this SARS-CoV2-induced critical illness in children.

Single-Cell Omics Reveals Dyssynchrony of the Innate and Adaptive Immune System in Progressive COVID-19

A dysregulated immune response against the SARS-CoV-2 virus plays a critical role in severe COVID-19. However, the molecular and cellular mechanisms by which the virus causes lethal immunopathology are poorly understood. Here, we utilize multiomics single-cell analysis to probe dynamic immune responses in patients with stable or progressive manifestations of COVID-19, and assess the effects of tocilizumab, an anti-IL-6 receptor monoclonal antibody. Coordinated profiling of gene expression and cell lineage protein markers reveals a prominent type-1 interferon response across all immune cells, especially in progressive patients. An anti-inflammatory innate immune response and a pre-exhaustion phenotype in activated T cells are hallmarks of progressive disease. Skewed T cell receptor repertoires in CD8+ T cells and uniquely enriched V(D)J sequences are also identified in COVID-19 patients. B cell repertoire and somatic hypermutation analysis are consistent with a primary immune response, with possible contribution from memory B cells. Our in-depth immune profiling reveals dyssynchrony of the innate and adaptive immune interaction in progressive COVID-19, which may contribute to delayed virus clearance and has implications for therapeutic intervention.

Echocardiographic features and outcome of restrictive foramen ovale in fetuses without cardiac malformations / 中华超声影像学杂志

Objective To investigate the clinical significance of restrictive foramen ovale ( RFO ) monitored by fetal echocardiography during the middle to late stage of pregnancy . Methods The detection rate ,echocardiographic features and outcome in fetuses with RFO without cardiac malformations from 7319 pregnant women received prenatal echocardiography were retrospectively reviewed and analyzed . Results RFO was found in 40 of 7319 (0 .55％ ) fetuses . The inclusion criteria including a narrow right to left shunt of less than 2 .5 mm in diameter across atrial septum , enlarged right atrium , increased right-to-left ventricular size ratio ,and increased size ratio of main pulmonary artery to aorta were present in 40 fetuses . The direct ultrasound characters of RFO included limited opening of oval valve ( 70％ ) and foramen ovale diameter less than 2 .5 mm (30％ ) . And atrial septal aneurysm ( 62 .5％ ) ,redundant primum atrial septum (57 .5％ ) ,abnormal ductus arteriosus ( 57 .5％ ) might also be present commonly in RFO . As the gestational weeks increased , the size ratio of right-to-left atrium , right-to-left ventricle and the main pulmonary artery to aorta also increased significantly( P =0 .004 , P <0 .001 , P <0 .001) . Among the 40 fetuses with RFO ,21 cases ( 52 .5％ ) gave birth in full term ,8 cases ( 20％ ) which were detected severe tricuspid regurgitation gave birth in early cesarean section ,5 cases ( 12 .5％ ) had induced labor and 6 cases (15％ ) were lost in the follow-up . Of the 29 newborns ,only 1 case died of heart failure ,and the other 28 subjects recovered both from heart structure or cardiac function within four months . Conclusions RFOwithout cardiac malformations presents echocardiographic features characterized by a narrow right to left shunt of less than 2 .5 mm in diameter across atrial septum . Fetal echocardiography can monitor the dynamic change of fetal heart structure and function based on the increase of right heart load and decrease of left heart volume ,which has important clinical significance for assessing fetal intrauterine condition and prognosis .

Practical application and thinking of distance learning system in ultrasound medicine / 中华医学教育探索杂志

As the real-time and dynamic ultrasound images play an important role in the distance education of ultrasound medicine, the learning system is more dependent on the technology of modern net-work information. By using the DGX protocol, we have constructed an ultrasonic distance education system composed of 5 main operating terminals, which has ensured the reliable and adaptive window transmission, and has realized the optimization of the coding and decoding technology. At the same time, we have used the system to carry out ultrasonic distance education to medical students, the staff of our ultrasound department and the ultrasound doctors in other hospitals, and have achieved good results in practical application.