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Objective:To evaluate the fetal heart shape and function in tetralogy of Fallot (TOF) by fetal heart quantitative analysis (fetal HQ).Methods:A total of 52 fetuses with TOF diagnosed by fetal echocardiography and 200 normal fetuses matched with their gestational weeks from March 2020 to March 2022 at Sir Run Run Shaw Hospital, Zhejiang University were retrospectively evaluated. The basic parameters of fetal cardiac blood vessels in the two groups were measured by fetal HQ technology and conventional M-mode ultrasound technology: aortic valve diameter(AV), pulmonary artery valve diameter(PV), main pulmonary artery diameter (MPA) and Z-score. The overall morphometric measurements including end-diastolic length diameter, transverse diameter, area, and global spherical index (GSI) of the fetal heart in the 4-chamber view(4CV), area and length of the right and left ventricles and their ratios. Measurements of left and right ventricular function included ejection fraction (EF), fraction area change rate (FAC), tricuspid annular plane systolic excursion (TAPSE), left and right ventricular global longitudinal strain (GLS), and left and right ventricular end-diastolic diameter (ED), spherical index (SI), and fractional shortening rate (FS) of 24-segments. The differences of above parameters between TOF group and control group were compared. In addition, the relationships between the absolute value of left and right ventricular GLS of TOF fetus and PV/AV, PV Z-score and MPA Z-score were analyzed. The optimal critical values of GSI, left ventricular EF and left ventricular FAC of TOF fetus were determined by ROC curve, and their corresponding sensitivity and specificity were obtained.Results:Compared with control group, there were significant differences in 4CV end-diastolic length, area, GSI, left ventricular area, left ventricular length, left ventricular EF, left ventricular FAC and left ventricular GLS in TOF group (all P<0.05). There were significant differences in ED between left ventricular 15-24 segments and right ventricular 1-21 segments (all P<0.05). There were significant differences in SI between left ventricular 1-16 segments, 21-24 segments and all segments of right ventricle (all P<0.05). The differences in FS were statistically significant (all P<0.05) when comparing all segments of the left ventricle and 1-2 segments of the right ventricular, and the remaining parameters were not statistically significant (all P>0.05). The left ventricular GLS absolute value of TOF fetuses was positively correlated with PV/AV, PV Z-score and MPA Z-score( rs=0.338, 0.441 and 0.458, all P<0.05), the right ventricular GLS absolute value of TOF fetuses was positively correlated with PV AV, PV Z-score and MPA Z-score( rs=0.418, 0.368 and 0.338, all P<0.05). The optimal critical values of GSI, left ventricular EF, and left ventricular FAC in the diagnosis of fetal TOF were 1.19, 59.05%, and 44.4%, respectively. At this time, the sensitivities of diagnosis of TOF were 0.78, 0.75, and 0.80, respectively. The specificities were 0.88, 0.88 and 0.83, respectively. The areas under ROC curve were 0.89, 0.88 and 0.89, respectively. Conclusions:Fetal HQ technology can provide a simple and reliable quantitative evaluation of fetal heart shape and function, and provide certain theoretical parameters for the study of fetal heart shape and function.
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Autophagy is a crucial biological process of eukaryotes, which is involved in cell growth, survival and energy metabolism, while the premise of the autophagy function is activated autophagic flux. It has been confirmed that impaired autophagic flux promotes pathogenesis of many chronic inflammatory diseases, especially cancer, neurodegenerative disease and tissue fibrosis, therefore the analysis of autophagic flux state is important for revealing autophagy function and the mechanism of autophagy related diseases. Given that autophagy is a dynamic process with multiple steps, it is very hard to observe the real state of autophagic flux. Summarized here is the novel concept and current approach to detect autophagic flux. This knowledge is crucial for the researching of the biological function of autophagy, and may provide some strategies for developing autophagy-related drug.
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Retinoid X receptor (RXR) acts as ligand-dependent transcription factors playing an important role in regulating a serial of physiological processes,such as embryo development and organ homeostasis.At the molecular level,RXRs exert their functions by inter-activating with multiple signal pathways to regulate target gene expression which control cell growth,differentiation,survival and death.The interference in the network of RXR and other signal pathways has turned RXR into an attractive drug target.
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Objective To analysis the cause of primary graft failure of unrelated cord blood transplantation with high-dose of CD34 + cells in treatment of acute myelocytic leukemia (AML) /myelodysplastic syndrome (MDS).Methods A 4-year-old girl was diagnosed AML/MDS at the Department of Pediatric Hematology and Oncology of West China Second University Hospital of Sichuan University. She presented completely remission after induction and consolidation chemotherapy.She received unrelated partially human leukocyte antigen (HLA)-mismatched cord blood transplantation.We investigated the treatment outcomes of UCBT and associated complications.Results The patient suffered primary graft failure and then received secondary haploidentical hematopoietic stem cell transplantation (HSCT)from her mother.However,she suffered fatal multiresistant Acinetobacter spp septicemia.She died due to respiratory failure on 7 d after the second transplantation.Conclusions In this case,hematopoietic stem cells with high dose of CD34 + cells could not overcome the risk of primary graft failure and HLA disparity.The patient's primary graft failure was associated with platelet transfusion refractoriness and potent immunologic dysfunction,especially the anti-HLA donor specific antibodies before unrelated cord blood transplantation.
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TLR2 activity plays an important role in the pathogenesis of autoimmune diseases, tumor carcinogenesis and cardio-cerebrovascular diseases. To establish a TLR2 receptor-based cell screening model, NF-kappaB promoter-driven luciferase reporter plasmids were transfected into human embryonic kidney cells (HEK293) stably expressing human TLR2 and co-receptors CD14, TLR1 and TLR6. Single clones were then isolated and characterized. Using this screening system, a human TLR2-binding peptide C8 was obtained from the Ph.D.-7 Phage Display Peptide Library through biopanning and rapid analysis of selective interactive ligands (BRASIL). The binding characteristic of C8 with human TLR2 was evaluated by ELISA, flow cytometry and immunofluorescence. The NF-kappaB luciferase activity assay showed that C8 could activate the TLR2/TLR1 signaling pathway and induce the production of cytokines TNF-alpha and IL-6. In conclusion, the TLR2 receptor-based cell screening system is successfully established and a new TLR2-binding peptide is identified by using this system.
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DEDD is a member of the death-effector domain protein family. DEDD inhibits the Smad3 mediated transcriptional activity and participates in the regulation of apoptosis. In this study, how the death-effector domain of DEDD participates in the regulation of Smad3 activity and apoptosis has been further investigated. Immunoblotting, immunofluorescence and immunoprecipitation had been used to detect the effects of the full length DEDD and its two truncated mutants, N-DEDD and C-DEDD on Smad3 subcellular distribution, phosphorylation, and interaction between Smad4. The effects of the full length DEDD and its two truncated mutants on cell apoptosis and proliferation had also been explored by flow cytometry and MTT assay. It showed that DEDD and N-DEDD inhibit TGF-beta1 induced Smad3 nuclear translocation and the formation of Smad3-Samd4 complex. DEDD and its two mutants can induce cell apoptosis and inhibit cell proliferation. These results suggested that DEDD inhibits the activity of Smad3 through its death-effector domain. Both the two truncated mutants of DEDD participate in the regulation of apoptosis and cell proliferation.
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Objective To compare the clinical features of cytomegalovirus (CMV) infection and CMV disease after allogeneic hematopoietic stem-cell transplantation (HSCT) from HLA haploidentical related doors vs.HLA-matched sibling donors.Methods A total of 327 patients who received allogeneic HSCT from Jan.2011 to Dec.2011 were enrolled.There were 312 patients who had complete serological data before HSCT including 216 cases of HLA haploidentical related HSCT and 96 cases of HLA-matched sibling HSCT.Monitoring of CMV antigenemia was performed by using real-time quantitative (RQ) PCR after transplantation.Risk factors were compared by univariate and multivariate analysis.Results The cumulative incidence of CMV infection and CMV disease was (80.1 ± 2.7) ％ and (8.7 ± 2.0) ％ in HLA haploiddentical HSCT group,and (21.1 ± 4.9) ％ and 0 in HLA-matched sibling HSCT group respectively,and the difference was statistically significant between the two groups (P＜0.01).Univariate analysis revealed that HLA haploidentical related HSCT,less than 20 years of age,high risk disease,CMV-IgG serum positivity in patients or donors,acute graft-versus-host disease (aGVHD),EB viremia,and hemorrhagic cystitis were the risk factors of CMV infection.HLA haploidentical related SCT and hemorrhagic cystitis were the risk factors for CMV disease.Multivariate analysis showed that patients less than 20 years of age had a significantly high incidence of CMV infection.Patients from HLA-matched sibling HSCT,low risk disease,aGVHD,hemorrhagic cystitis had a significantly low incidence of CMV infection.Conclusion Compared with patients receiving HLA-matched sibling HSCT,those who received HLA haploidentical related HSCT had significantly high incidence of CMV infection and CMV disease,which were correlated with incidence of hemorrhagic cystitis.