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@#Objective To analyze the factors influencing the occurrence of subclinical leaflet thrombosis (SLT) after percutaneous aortic valve replacement using balloon-expandable valve (Sapien3, S3). Methods Retrospective analysis was made on 62 patients with severe aortic stenosis undergoing percutaneous aortic valve replacement using S3 in our center from September 2020 to June 2022. Patients with a history of vascular atherosclerosis or with significant increase or insignificant decrease of aortic valve flow or gradient pressure during follow-up were selected for CT examination. Results A total of 26 patients were finally included, with an average age of 70.31±8.90 years, and the male proportion was higher (n=15, 57.69%). Among them, 5 patients had SLT. Compared with the non-SLT group, patients in the SLT group were older (68.52±8.80 years vs. 77.80±4.66 years, P=0.007). The age factor (≥75 years) and the diameter of the ascending aorta were associated with SLT (both P<0.05). Conclusion The incidence of SLT is higher in the elderly patients. It is speculated that SLT is related to the characteristics of short balloon dilation valves and low blood flow dynamics of valve racks.
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As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-β-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-β receptor type-1 (TGFβR1) and abrogated the kinase activity of TGFβR1, thereby blocking the TGF-β-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFβR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFβR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFβR1 were found to be crucial for the interaction of ITSN with TGFβR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-β-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFβR1 in TNBC metastasis, but also provide a leading compound targeting TGFβR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFβR1 inhibitor.
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Objective:To observe the changes in percentages and subsets of invariant nature kiler T (iNKT) cells in adipose and related tissues at different stages of obesity, and analyze the role of iNKT cells during chronic inflammation in adipose tissues in a mouse model of obesity established with high-fat diet.Methods:Changes in mouse body weight, mental state, glucose tolerance and insulin tolerance were recorded. Hematoxylin and eosin (HE) staining was used to observe pathological changes in adipose tissues. Flow cytometry was performed to detect the percentages and subsets of iNKT cells as well as the percentages and subtypes of macrophages. The levels of cytokines in serum samples and the culture supernatants of lymphocytes in adipose tissues were detected with CBA. The expression of related proteins in adipose tissues was detected by Western blot.Results:(1) The volume of adipose cells increased significantly after four weeks of high-fat feeding, but the infiltration of inflammatory cells was not obvious. Significantly increased infiltration of inflammatory cells was observed after 12 weeks of high-fat feeding. (2) High-fat feeding could reduce the percentage of iNKT cells, increase the proportion of iNKT1 subgroup and decrease the proportion of iNKT10 subgroup in adipose tissues. The proportion of iNKT1 subgroup in thymus increased, but that of iNKT2 subgroup decreased. The percentage of macrophages and the proportion of M1 subgroup in adipose tissues increased, while the proportion of M2 subgroup decreased, which were more obvious after 12 weeks of high-fat feeding. (3) High-fat feeding resulted in decreased expression of E4BP4 and arginase-1 (Arg-1) in adipose tissues and increased expression of inducible nitric oxide synthase (iNOS). (4) High-fat feeding significantly increased the pro-inflammatory cytokines and decreased the anti-inflammatory cytokines in mouse serum and culture supernatants of lymphocytes in adipose tissues with more significant changes observed after 12 weeks of high-fat feeding.Conclusions:Increased iNKT1 and decreased iNKT10 in obese adipose tissues might be closely related to the increased M1 polarization and the imbalance of iNKT subsets might be involved in the progression of chronic inflammation in obese adipose tissues.
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Objective@#To investigate the effect factors of liver enzymes elevation by monitoring the liver function changes before and after intraportal islet transplantation.@*Methods@#16 diabetic patients who received intraportal islet transplantation in our hospital were analyzed. The levels of aspartic aminotransferase (AST), alanine aminotransferase (ALT)and total bilirubin (TBil)were monitored after islet transplantation.@*Results@#Among those 16 diabetic patients who received intraportal islet transplantation, 11 patients showed an increased AST and 8 patients showed an increased ALT, among which a 2.5-fold increase in AST was observed in 4 patients and over 1.5-fold elevation of ALT was observed in 3 patients. The level of TBil were in the normal range before and after transplantation in all patients. Transplanted tissue volume of islet was the main factor for significantly increased AST (P<0.05) in this study. It is also shown that the change in portal pressure is related to the AST elevation after islet transplantation.@*Conclusions@#The amount of transplanted islet tissue volume is related to the liver enzymes elevation after intraportal islet transplantation. Therefore, the improvement of the purity of islet to reduce the amount of transplanted tissue could be benefit to prevent the liver injury after islet transplantation. Meanwhile, the purified islets should be injected as slowly as possible to maintain a stable portal pressure.
ABSTRACT
Objective To investigate the effect factors of liver enzymes elevation by monitoring the liver function changes before and after intraportal islet transplantation .Methods 16 diabetic patients who received intraportal islet transplantation in our hospital were analyzed .The levels of aspartic aminotransferase (AST ) ,alanine aminotransferase (ALT )and total bilirubin (TBil)were monitored after islet transplantation .Results Among those 16 diabetic patients who received intraportal islet transplantation ,11 patients showed an increased AST and 8 patients showed an increased ALT ,among which a 2 .5-fold increase in AST was observed in 4 patients and over 1 .5-fold elevation of ALT was observed in 3 patients .The level of TBil were in the normal range before and after transplantation in all patients . Transplanted tissue volume of islet was the main factor for significantly increased AST (P< 0 .05) in this study .It is also shown that the change in portal pressure is related to the AST elevation after islet transplantation .Conclusions The amount of transplanted islet tissue volume is related to the liver enzymes elevation after intraportal islet transplantation .Therefore ,the improvement of the purity of islet to reduce the amount of transplanted tissue could be benefit to prevent the liver injury after islet transplantation .Meanwhile ,the purified islets should be injected as slowly as possible to maintain a stable portal pressure .