Objective     To investigate the left ventricular reverse remodeling (LVRR) in patients with aortic valve insufficiency with reduced ejection fraction (AIrEF) and aortic valve insufficiency with preserved ejection fraction (AIpEF) after transcatheter aortic valve replacement (TAVR). Methods    The clinical and follow-up data of patients who underwent TAVR in the Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from 2018 to 2021 were retrospectively analyzed. According to the guideline, the patients with left ventricular ejection fraction<55% were allocated to an AIrEF group, and the patients with left ventricular ejection fraction≥55% were allocated to an AIpEF group. Results    A total of 50 patients were enrolled. There were 19 patients in the AIrEF group, including 15 males and 4 females with a mean age of 74.5±7.1 years. There were 31 patients in the AIpEF group, including 19 males and 12 females with a mean age of 72.0±4.8 years. All patients underwent TAVR successfully. Echocardiographic results showed that TAVR significantly promoted LVRR in the patients. Significant LVRR occurred in the early postoperative period (the first day after the surgery) in both groups. It remained relatively stable after the LVRR in the early postoperative period (the first day after surgery) in the AIpEF patients, while it continued to occur in the early postoperative period (the first day after surgery) to three months after the surgery in the AIrEF patients, and then remained relatively stable. Compared to preoperative values, AIrEF patients had a reduction in the average left ventricular end-diastolic volume index and left ventricular end-systolic volume index by 16.8 mL/m2 (P=0.003) and 8.6 mL/m2 (P=0.005), respectively, and the average left ventricular end-diastolic diameter index and end-systolic diameter index decreased by 2.5 mm/m2 (P=0.003) and 1.9 mm/m2 (P=0.003), respectively on the first day after the surgery. In comparison to the first day after the surgery, AIrEF patients experienced an average increase of 12.1% in the left ventricular ejection fraction three months after the surgery (P<0.001). Conclusion    TAVR has achieved good therapeutic effects in patients with aortic valve insufficiency, significantly promoting the LVRR in patients, and has better curative effects in AIrEF patients.

Objective To investigate the molecular mechanism of taurine regulating the polarization of M2 macrophages by mitophagy. Methods THP-1 cells were divided into four groups: M0 group (THP-1 cells were treated by 100 nmol/L phorbol myristate ester for 48 hours to polarize into M0), M2 group (THP-1 cells were induced to polarize into M2 macrophages by 20 ng/mL interferon-4 (IL-4) for 48 hours), M2 combined with taurine groups (added with 40 or 80 mmol/L taurine on the basis of M2 macrophages). The mRNA expression of mannose receptor C type 1(MRC-1), C-C motif chemokine ligand 22(CCL22) and dendritic cell-specific ICAM-3 grabbing non-integrin (CD209) in M2 macrophages were detected by quantitative real-time PCR. Mitochondrial and lysosome probes were used to detect the number of mitochondria and lysosomes by multifunction microplate reader and confocal laser scanning microscope. The level of mitochondrial membrane potential (MMP) was detected by JC-1 MMP assay kit. The expression of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blot analysis. Results Compared with M0 group, the expression of MRC-1, CCL22, CD209 and PINK1, the number of mitochondria and the level of MMP in M2 group were significantly increased, whereas the number of lysosomes and LC3II/LC3I ratio were decreased. Compared with M2 group, the expressions of MRC-1, CCL22 and CD209, the number of mitochondria and the level of MMP in M2 combined with taurine group dropped significantly while the number of lysosomes was found increased, and the protein expression of PINK1 and LC3II/LC3I ratio were also increased. Conclusions The polarization of M2 macrophages is regulated by taurine to prevent excessive polarization via reducing the level of MMP, improving the level of mitophagy, reducing the number of mitochondria, and inhibiting the mRNA expression of polarization markers in M2 macrophages.
Mitophagy ; Taurine ; Macrophages/metabolism* ; Protein Kinases/metabolism* ; RNA, Messenger

OBJECTIVE: To investigate and analyze the effect of CXC chemokine receptor 1/2 (CXCR1/2) targeting inhibitor Reparixin combined with cytarabine (Ara-C) on the malignant biological behaviors of acute myeloid leukemia cells and its effect on the expression of the CXCR family, while exploring the accompanying molecular mechanism, providing scientific basis and reference for new molecular markers and targeted therapy for AML. METHODS: Acute myeloid leukemia U937 cells were treated with different concentrations of Reparixin, Ara-C alone or in combination, and the cell morphology was observed under an inverted microscope; Wright-Giemsa staining was used to detect cell morphological changes; CCK-8 method was used to detect cell proliferation; the ability of cell invasion was detected by Transwell chamber method; the ability of colony formation was detected by colony formation assay; cell apoptosis was detected by Hoechst 33258 fluorescent staining and Annexin V/PI double-staining flow cytometry; monodansylcadaverine(MDC) staining was used to detect cell autophagy; the expression of apoptosis, autophagy and related signaling pathway proteins was detected by Western blot and the expression changes of CXCR family were detected by real-time quantitative polymerase chain reaction (qRT-PCR). RESULTS: Reparixin could inhibit the proliferation, invasion, migration and clone formation ability of U937 cells. Compared with the single drug group, when U937 cells were intervened by Reparixin combined with Ara-C, the malignant biological behaviors such as proliferation, invasion and colony formation were significantly decreased, and the levels of apoptosis and autophagy were significantly increased (P<0.01). After Reparixin combined with Ara-C intervenes in U937 cells, it can up-regulate the expression of the pro-apoptotic protein Bax and significantly down-regulate the expression of the anti-apoptotic protein Bcl-2, and also hydrolyze and activate Caspase-3, thereby inducing cell apoptosis. Reparixin combined with Ara-C could up-regulate the expressions of LC3Ⅱ and Beclin-1 proteins in U937 cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P<0.01). MDC result showed that the green granules of vesicles increased significantly, and a large number of broken cells were seen (P<0.01). Reparixin combined with Ara-C can significantly inhibit the phosphorylation level of PI3K, AKT and NF-κB signaling molecule, inhibit the malignant biological behavior of cells by inhibiting the activation of PI3K/AKT/NF-κB pathway, and induce programmed cell death. Ara-C intervention in U937 cells had no effect on the expression of CXCR family (P>0.05). The expression of CXCR1, CXCR2, and CXCR4 mRNA could be down-regulated by Reparixin single-agent intervention in U937 cells (P<0.05), and the expression of CXCR2 was more significantly down-regulated than the control group and other CXCRs (P<0.01). When Reparixin and Ara-C intervened in combination, the down-regulated levels of CXCR1 and CXCR2 were more significant than those in the single-drug group (P<0.01), while the relative expressions of CXCR4 and CXCR7 mRNA had no significant difference compared with the single-drug group (P>0.05). CONCLUSION Reparixin combined with Ara-C can synergistically inhibit the malignant biological behaviors of U937 cells such as proliferation, invasion, migration and clone formation, and induce autophagy and apoptosis. The mechanism may be related to affecting the proteins expression of Bcl-2 family and down-regulating the proteins expression of CXCR family, while inhibiting the PI3K/AKT/NF-κB signaling pathway.
Humans ; U937 Cells ; Cytarabine/therapeutic use* ; Receptors, Interleukin-8A ; NF-kappa B ; Proto-Oncogene Proteins c-akt ; Phosphatidylinositol 3-Kinases ; Leukemia, Myeloid, Acute/genetics* ; Apoptosis ; Cell Proliferation ; Apoptosis Regulatory Proteins ; Proto-Oncogene Proteins c-bcl-2 ; RNA, Messenger ; Cell Line, Tumor

OBJECTIVE: To investigate the effect of pure Chinese herbal extract Mangiferin on the malignant biological behaviors of multiple myeloma (MM) cells, and to analyze the molecular mechanism of the anti-myeloma effect of Mangiferin, so as to provide experimental basis for MM replacement therapy. METHODS: U266 and RPMI8226 of human MM cell lines were intervened with different concentrations of Mangiferin. Cell proliferation was detected by CCK-8 method. Annexin V/PI double staining flow cytometry was used to detect cell apoptosis. Western blot was used to detect the expression of apoptosis and related signaling pathway proteins, and real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of matrix metalloproteinase (MMP) and CXC chemokine receptor (CXCR) family. RESULTS: Mangiferin could inhibit the proliferation activity of U266 and RPMI8226 cells and induce cells apoptosis. After Mangiferin intervened in U266, RPMI8226 cells for 48 h, the expression of Bcl-2 family pro-apoptotic protein Bax was up-regulated, while the expression of survivin and Bcl-xL proteins was down-regulated and caspase-3 was hydrolyzed and activated to promote cell apoptosis, besides, the expression of Bcl-2 protein in U266 cells was also significantly down-regulated to induce apoptosis (P<0.05). After Mangiferin intervenes in MM cells, it can not only increase the expression level of tumor suppressor p53, but also induce programmed cell death of MM cells by inhibiting the expression of anti-apoptotic molecules and down-regulating the phosphorylation levels of AKT and NF-κB. In addition, after the intervention of Mangiferin, the expressions of CXCR4, MMP2 and MMP9 in U266 cells were down-regulated (P<0.05), while there is no effect on the expressions of CXCR2, CXCR7 and MMP13 (P>0.05). However, the expressions of CXCR4, MMP9, and MMP13 in RPMI8226 cells were down-regulated (P<0.01), the expression of MMP2 was weakly affected, and the expression of CXCR2 and CXCR7 was basically not affected (P>0.05). CONCLUSION Mangiferin can inhibit the proliferation and induce apoptosis of MM cells, and its mechanism may be related to inhibiting the activation of NF-κB signaling pathway, affecting the expression of Bcl-2 family proteins, and inhibiting the expression of core members of MMP and CXCR family.
Humans ; Matrix Metalloproteinase 2 ; Matrix Metalloproteinase 9 ; Matrix Metalloproteinase 13 ; Cell Line, Tumor ; NF-kappa B ; Multiple Myeloma/pathology* ; Cell Proliferation ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Objective    To summarize the experience and efficacy of "one-stop" left atrial appendage clipping (LAAC) combined with transcatheter aortic valve replacement (TAVR) for patients with atrial fibrillation (AF) and aortic valve disease. Methods     From April 2018 to March 2021, 16 patients with AF and severe aortic valve disease underwent "one-stop" LAAC and TAVR in our department. All patients had long-standing persistent AF. There were 10 males and 6 females with an average age of 77.2±6.2 years. CHA2DS2-VASc score was 4.4±0.8 points, and HAS-BLED score was 3.5±0.7 points. Results    All patients successfully underwent "one-stop" LAAC combined with TAVR. There was no death during perioperative and follow-up periods. The length of the left atrial appendage base measured during the operation was 37.8±3.5 mm. The types of atrial appendage clip were 35 mm (n=3), 40 mm (n=8) and 45 mm (n=5). The time required for clipping the left atrial appendage (from skin cutting to skin suturing) was 25.7±3.8 min. There was no stroke or bleeding of important organs during the perioperative period. The average hospital stay was 6.8±2.0 d. The follow-up time was 19.6±10.1 months, during which there was no patient of cerebral hemorrhage or cerebral infarction. During the administration of warfarin, 2 patients had subcutaneous ecchymosis and 1 patient had gingival bleeding. Conclusion    "One-stop" LAAC combined with TAVR can be safely and effectively used to treat AF and aortic valve disease patients with high risk of thromboembolism and anticoagulant bleeding. The early and middle-term curative effect is satisfactory.

Objective    To explore the effect and safety of surgical treatment for hypertrophic obstructive cardiomyopathy (HOCM) with mitral regurgitation (MR) through right mini-thoracotomy. Methods    From January 2008 to June 2018, 54 patients with HOCM and moderate-to-severe MR underwent modified Morrow procedure and edge-to-edge mitral valvuloplasty through right mini-thoracotomy, including 31 males and 23 females, with an average age of 47.1±12.6 years. All patients had systolic anterior motion (SAM) phenomenon. Preoperative left ventricular outflow tract pressure gradient (LVOTPG) was 93.6±32.8 mm Hg, interventricular septum thickness (IVST) was 24.8±2.8 mm. Results    Surgeries in all patients were completed successfully. No early death or interventricular septal perforation occurred. One (1.9%) patient received permanent pacemaker implantation due to the complete atrial-ventricular block. At discharge, postoperative LVOTPG (18.1±6.2 mm Hg) and IVST (14.5±2.1 mm) were significantly decreased compared with the preoperative values (P<0.05). No MR or SAM was observed in all patients. The follow-up time was 6-132 months, and during this period, no death, MR or SAM occurred. The average LVOTPG was 19.4±5.7 mm Hg, and the average IVST was 14.2±1.5 mm. Conclusion    Morrow procedure and edge-to-edge mitral valvuloplasty through right mini-thoracotomy is a safe and effective method for treatment of HOCM with moderate-to-severe MR.

Objective    To summarize the application and clinical effect of left anterior minimally invasive thoracotomy to surgical repair of subarterial ventricular septal defect (VSD) in children. Methods    From October 2015 to April 2019, 21 children with subarterial VSD underwent surgical repair via left anterior minimally invasive thoracotomy. There were 13 males and 8 females, aged 5-13 (9.1±2.2) years, and weighing 22-55 (35.6±9.5) kg. The diameter of subarterial VSD was 4-15 (9.1±3.3) mm. Eight patients had right coronary valve prolapse, and 4 aortic valve regurgitation (3 mild and 1 mild-to-moderate). The minimally invasive surgery was performed via left parasternal thoracotomy through the second or third intercostal space. The peripheral perfusion was performed with femoral arterial and venous cannulation. After aortic cross-clamp (ACC), subarterial VSD was performed with direct suture of patch closure through an incision on the root of pulmonary artery. Results    All patients successfully underwent surgical repair (patch closure, n=15; direct suture, n=6) of subarterial VSD through left anterior minimally invasive thoracotomy. The cardiopulmonary bypass time was 45-68 (57.1±6.3) min. The ACC time was 23-40 (32.6±4.7) min. The postoperative ventilation time was 5-9 (6.3±1.3) h, postoperative in-hospital time was 5-8 (5.7±1.0) d and drainage volume was 33-105 (57.5±17.7) mL in postoperative 24 h. No death, residual VSD shunt, atrioventricular block, wound infection or thoracic deformity occurred during the perioperation or follow-up. Only one patient still had trivial aortic valve regurgitation. Conclusion    Left anterior minimally invasive thoracotomy could be safely and effectively applied to surgical repair of subarterial VSD in children, with satisfactory early- and mid-term outcomes.

Objective To explore the role of Galectin3 in transforming growth factor-β(TGF-β)-induced epithelial-mesenchymal transition (EMT) in A549 cells. Methods Galectin3 was over-expressed in an A549 cell line. EMT was induced in lung cancer A549 cells by adding TGF-β. The expressions of Galectin3,E-cadherin,and vimentin were determined by Western blot. The protein expression of E-cadherin and the morphological changes of the cells were detected by immunofluorescence. Cellular proliferation was analyzed with cell counting kit-8,and the cellular migration and invasion was measured by scratches healing and Transwell assay,respectively.Results When only Galectin3 was over-expressed in A549 cell line,the expression levels of EMT-related proteins such as E-cadherin and vimentin were not changed,and the abilities of cellular proliferation,invasion,and migration were not changed either. When the EMT was induced by TGF-β in A549 cells,the E-cadherin expression was down-regulated and the vimentin expression was up-regulated in A549 cells with Galectin3 over-expression. There was no significant change in cellular proliferation,whereas the abilities of cellular invasion and migration were enhanced.Conclusion The TGF-β-induced EMT in A549 cells can be enhanced by Galectin3.

Under global cerebral ischemia, the effect of different brain temperature on cerebral ischemic injury was studied. Male Sprague-Dawley rats were divided into normothermic (37-38°C) ischemia, mild hypothermic (31-32°C) ischemia, hyperthermic (41-42°C) ischemia and sham-operated groups. Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model and brain temperature was maintained at defined level for 60 min after 20-min ischemia. The expression of c-fos protein and the levels of malondialdehyde (MDA) and lactate in brain regions were detected by immunochemistry and spectrophotometrical methods, respectively. C-fos positive neurons were found in the hippocampus and cerebral cortex after cerebral ischemia reperfusion. Mild hypothermia increased the expression of c-fos protein in both areas, whereas hyperthermia decreased the expression of c-fos protein in the hippocampus at 24 h reperfusion, and the cerebral cortex at 48 h reperfusion when compared to normothermic conditions. In normothermic, mild hypothermic and hyperthermic ischemia groups, the levels of MDA and lactate in brain tissue were increased at 24, 48 and 72 h reperfusion following 20-min ischemia as compared with the sham-operated group (P<0.01). The levels of MDA and lactate in mild hypothermic group were significantly lower than those in normothermic group (P<0.01). It is suggested that brain temperature influences the translation of the immunoreactive protein product of c-fos after global cerebral ischemia, and MDA and lactate are also affected by hypothermia and hyperthermia.
Animals ; Body Temperature ; Brain ; blood supply ; metabolism ; physiopathology ; Brain Ischemia ; metabolism ; physiopathology ; Cerebral Cortex ; blood supply ; metabolism ; physiopathology ; Hippocampus ; blood supply ; metabolism ; physiopathology ; Immunochemistry ; Lactic Acid ; metabolism ; Male ; Malondialdehyde ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Proto-Oncogene Proteins c-fos ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; physiopathology ; Spectrophotometry ; Temperature ; Time Factors ; Tumor Suppressor Protein p53 ; metabolism