Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury, but this approach is limited by their poor viability after transplantation. The present study was to investigate whether trimetazidine (TMZ) could improve survival of MSCs in an ex vitro model of hypoxia, as well as survival, differentiation, and subsequent activities of transplanted MSCs in rat hearts with acute myocardial infarction (AMI). MSCs at passage 3 were examined for their viability and apoptosis under a transmission electron microscope, and by using flow cytometry following culture in serum-free medium and exposure to hypoxia (5% CO(2), 95% N(2)) for 12 h with or without TMZ. Thirty Wistar rats were divided into 3 groups (n=10 each group), including group I (AMI control), group II (MSCs transplantation alone), and group III (TMZ+MSCs). Rat MSCs (4×10(7)) were injected into peri-infarct myocardium (MSCs group and TMZ+MSCs group) 30 min after coronary artery ligation. The rats in TMZ+MSCs group were additionally fed on TMZ (2.08 mg·kg(-1)·day(-1)) from day 3 before AMI to day 28 after AMI. Cardiac structure and function were assessed by echocardiography at 28th day after transplantation. Blood samples were collected before the start of TMZ therapy (baseline), and 24 and 48 h after AMI, and inflammatory cytokines (CRP, TNF-α) were measured. Then the survival and differentiation of transplanted cells in vivo were detected by immunofluorescent staining. The cellular apoptosis in the peri-infarct region was detected by using TUNEL assay. Furthermore, apoptosis-related proteins (Bcl-2, Bax) within the post-infarcted myocardium were detected by using Western blotting. In hypoxic culture, the TMZ-treated MSCs displayed a two-fold decrease in apoptosis under serum-free medium and hypoxia environment. In vivo, cardiac infarct size was significantly reduced, and cardiac function significantly improved in MSCs and TMZ+MSCs groups as compared with those in the AMI control group. Combined treatment of TMZ with MSCs implantation demonstrated further decreased MSCs apoptosis, further increased MSCs viability, further decreased infarct size, and further improved cardiac function as compared with MSCs alone. The baseline levels of inflammatory cytokines (CRP, TNF-α) had no significant difference among the groups. In contrast, all parameters at 24 h were lower in TMZ+MSCs group than those in MSCs group. Furthermore, Western blotting indicated that the expression of anti-apoptotic protein Bcl-2 was up-regulated, while the pro-apoptotic protein Bax was down-regulated in the TMZ+MSCs group, compared with that in the MSCs group. It is suggested that implantation of MSCs combined with TMZ treatment is superior to MSCs monotherapy for MSCs viability and cardiac function recovery.

Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury,but this approach is limited by their poor viability after transplantation.The present study was to investigate whether trimetazidine (TMZ) could improve survival of MSCs in an ex vitro model of hypoxia,as well as survival,differentiation,and subsequent activities of transplanted MSCs in rat hearts with acute myocardial infarction (AMI).MSCs at passage 3 were examined for their viability and apoptosis under a transmission electron microscope,and by using flow cytometry following culture in serum-free medium and exposure to hypoxia (5％ CO2,95％ N2) for 12 h with or without TMZ.Thirty Wistar rats were divided into 3 groups (n=10 each group),including group Ⅰ (AMI control),group Ⅱ (MSCs transplantation alone),and group Ⅲ (TMZ+MSCs).Rat MSCs (4×107) were injected into peri-infarct myocardium (MSCs group and TMZ+MSCs group) 30 min after coronary artery ligation.The rats in TMZ+MSCs group were additionally fed on TMZ (2.08 mg·kg-1·day-1) from day 3 before AMI to day 28 after AMI.Cardiac structure and function were assessed by echocardiography at 28th day after transplantation.Blood samples were collected before the start of TMZ therapy (baseline),and 24 and 48 h after AMI,and inflammatory cytokines (CRP,TNF-α) were measured.Then the survival and differentiation of transplanted cells in vivo were detected by immunofluorescent staining.The cellular apoptosis in the peri-infarct region was detected by using TUNEL assay.Furthermore,apoptosis-related proteins (Bcl-2,Bax) within the post-infarcted myocardium were detected by using Western blotting.In hypoxic culture,the TMZ-treated MSCs displayed a two-fold decrease in apoptosis under serum-free medium and hypoxia environment.In vivo,cardiac infarct size was significantly reduced,and cardiac function significantly improved in MSCs and TMZ+MSCs groups as compared with those in the AMI control group.Combined treatment of TMZ with MSCs implantation demonstrated further decreased MSCs apoptosis,further increased MSCs viability,further decreased infarct size,and further improved cardiac function as compared with MSCs alone.The baseline levels of inflammatory cytokines (CRP,TNF-α) had no significant difference among the groups.In contrast,all parameters at 24 h were lower in TMZ+MSCs group than those in MSCs group.Furthermore,Western blotting indicated that the expression of anti-apoptotic protein Bcl-2 was up-regulated,while the pro-apoptotic protein Bax was down-regulated in the TMZ+MSCs group,compared with that in the MSCs group.It is suggested that implantation of MSCs combined with TMZ treatment is superior to MSCs monotherapy for MSCs viability and cardiac function recovery.

Objective To observe the rat cardiac size and cardiac function changes before and after trimetazidine administration plus bone-marrow stem cells transplanting through echocardiography.Methods Forty wistar rats were divided into the following 4 groups randomly:control group (T),myocardial infarction group (Ⅱ),bone marrow stem calls transplantation group (Ⅲ),and bone marrow stem cells transplantation plus trimetazidine administration group(Ⅳ).The rats' left anterior coronary artery in group Ⅱ,Ⅲ and Ⅳwas ligated to produce myocardial infarction model,then bone-marrow stem cells were injected around the infarcted area into the later two groups.Furthermore,rats in group Ⅳ were administrated with trimetazidine.The size and systolic function of the hearts were measured 4 weeks after transplantation.The left ventricular systolic pressure(LVSP) and the end-diastolic pressure(LVEDP) were also measured at the end of experiment.Results The left ventricular diameter of rats in group Ⅲ and Ⅳ was smaller than that in group Ⅱ,and the ventricular systolic function increased,LVSP increased and LVEDP decreased statistically in group Ⅲ and Ⅳ.the amelioration of cardiac size and function was significantly notable in group Ⅳ than that in group Ⅲ.Conclusions Bone marrow stem cells transplantation can release the enlargement of left ventricle and improve cardiac function after myocardial infarction.The therapeutic efficacy can be further elevated if administrated with trimetazidine simultaneously.

Objective:To investigate the correlation between neutrophil/lymphocyte ratio (NLR) combined with low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C) and severity of coronary lesions in patients with acute coronary syndrome (ACS).Methods:Patients who were diagnosed with ACS due to chest pain and received emergency coronary angiography in the First Affiliated Hospital of University of Science and Technology of China and the Affiliated Hospital of Anhui Medical University from January 2017 to June 2020 were enrolled in the final analysis. The data of gender, age, body mass index (BMI), past history, emergency blood routine indicators [neutrophil (NEU), lymphocyte (LYM), monocyte (MON), eosinophil (EOS), basophil (BAS), red blood cell (RBC), mean corpuscular volume (MCV), blood red cell distribution width (RDW), mean platelet volume (MPV), platelet volume distribution width (PDW)], blood lipid index [triglyceride (TG), total cholesterol (TC), HDL-C, LDL-C, very low-density lipoprotein cholesterol (VLDL-C)], and coronary angiography were collected. The results of coronary angiography were evaluated by the Gensini score. According to the Gensini score, the patients were divided into the control group (Gensini score = 0, 55 cases) and the study group (Gensini score > 0, 889 cases), and then the patients in the study group were divided into the low-Gensini-score group (Gensini score < 66, 419 cases) and the high-Gensini-score group (Gensini score ≥ 66, 470 cases). The differences in the general baseline data of the four groups were compared, and the correlation between the statistically significant data and the Gensini score was linearly analyzed, and then the combined diagnostic factors (NLR combined with LDL-C/HDL-C ratio) were obtained by Logistic regression analysis. The receiver operator characteristic curve (ROC curve) was used to evaluate the predictive value of NLR combined with LDL-C/HDL-C ratio in predicting the severity of coronary artery lesions in patients with ACS. Finally, multivariate linear regression analysis was used to establish the predictive model between NLR combined with LDL-C/HDL-C ratio and Gensini score.Results:A total of 944 patients were finally included. The differences in gender, age, BMI, hypertension, diabetes, smoking history, NEU, LYM, MON, EOS, RDW, TC, HDL-C, LDL-C, NLR, LDL-C/HDL-C ratio between the control group and the study group were statistically significant. The differences in BMI, hypertension, diabetes, smoking history, NEU, LYM, MON, EOS, TG, TC, HDL-C, LDL-C, NLR and LDL-C/HDL-C ratio between the low-Gensini-score group and the high-Gensini-score group were statistically significant. Linear regression analysis showed that compared with other indicators, the correlation between NLR, LDL-C/HDL-C ratio and Gensini score was stronger in the study group ( r values were 0.634 and 0.663, respectively, both P < 0.05). Binary Logistic regression analysis of the indicators related to Gensini score showed that NEU, LYM, HDL-C and LDL-C were independent risk factors for coronary stenosis in patients with ACS [odds ratio ( OR) were 0.189, 10.309, 13.993, 0.251, 95% confidence intervals (95% CI) were 0.114-0.313, 4.679-22.714, 3.402-57.559, 0.121-0.519, respectively, all P < 0.05]. ROC curve analysis showed that NLR combined with LDL-C/HDL-C ratio had higher predictive value in predicting the severity of coronary lesions in ACS patients [area under the ROC curve (AUC) was 0.952, 95% CI was 0.93-0.969], when the cutoff value was -3.152, the sensitivity was 98.20%, and the specificity was 81.60%. According to the results of multivariate linear regression analysis, the prediction model between NLR, LDL-C/HDL-C ratio and Gensini score was established, and the formula was Gensini score = -7.772+15.675×LDL-C/HDL-C ratio+8.288×NLR ( R2 = 0.862). Conclusion:There is a significant correlation between emergency NLR combined with LDL-C/HDL-C ratio and Gensini score in patients with ACS at admission, which has a certain predictive value for the severity of coronary artery stenosis in patients with ACS, and can be used as a predictor for evaluating the severity of coronary artery disease.

Cellular dysfunction caused by vesicle transport is associated with a variety of diseases.The trans-Golgi network(TGN)to endosome transport is an important pathway of vesicle transport,and its defects leading to protein balance disorders has been linked to many diseases such as cancer,neurodegenerative diseases and diabetes mellitus.Gol-gi-associated gamma-adaptin ear-containing ADP-ribosylation factor-binding protein 2(GGA2)is a crucial protein in-volved in TGN-endosomal transport.It plays a significant role in the regulation of several diseases,including cancer,Al-zheimer disease,type 2 diabetes mellitus and cerebral ischemia,by mediating protein transport with important biological significance.This article provides an overview of the molecular structure of GGA2,its role in regulating clathrin-mediated protein transport between TGN and endosomes,and its potential implications for a variety of diseases.

Objective: The purpose is to investigate the validity of a surgical technique that utilizes autologous costal cartilage grafts in primary rhinoplasty for female patients. Methods: From July 2015 to July 2017, 137 cases received primary rhinoplasty with various types of grafts originated from autologous costal cartilage to correct the unpleasant nasal appearances including low dorsum, poorly defined nasal tip and wide alar base. Results: With 6 to 36 months follow-up, six patients(4.3%) exhibited noticeable changes in nasal contour due to graft warping. Revision surgeries were commenced to correct those minor deformities, resulting in satisfactory outcome.All other cases presented significant improvements of the nasal appearance. Conclusions Autologous costal cartilage is a good source for primary rhinoplasty cases.

Objective:To explore the risk factors of bladder recurrence in patients with upper urinary tract urothelial carcinoma (upper tract urothelial carcinoma, UTUC).Methods:We retrospectively analyzed the data of 815 patients underwent radical nephroureterectomy for upper tract urothelial carcinoma between June 2009 to June 2019.There were 519 males and 340 females, aged from 26-93 years old(average 66.5±9.6 years old). 396 patients were renal pelvic caicinoma.463 patients were ureteral caicinoma.675 patients were accompanied with hydronephrosis.664 patients were accompanied with preoperative gross hematuria. Preoperative diagnostic ureteroscopy was performed in 323 cases.283 patients had the history of smoking.48 patients were con-comitant with bladder carcinoma at the first diagnosis. Univariate analysis and logistic multivariate regression analysis were used to investigate the risk factors for bladder recurrence after UTUC radical surgery.Results:Among the 859 patients, 407 (47.4%) had low-stage tumor (T is/T a/T 1), 452 (52.6%) had high-stage tumor (T 2-T 4), 110 (12.8%) had low-stage tumor (G 1/G 2), and 749 (87.2%) had high-stage tumor (G 3). 126 (17.2%) of 859 patients had relapse during the follow-up period, the average follow-up time was 17 months, the median recurrence time was 12 months, 101(80.1%) of the relapse occurred within 2 years after operation. In univariate analysis, lower tumor stage ( P=0.047), higher tumor grade ( P=0.043), preoperative hematuria symptom ( P=0.023) and preoperative diagnostic ureteroscopy ( P=0.002) were closely related to bladder recurrence. Taking the above factors into the logistic multivariate regression analysis showed that tumor staging T is/T s/T 1 ( B=0.476, P=0.019), tumor grade G 3( B=0.848, P=0.024), preoperative hematuria symptom ( B=0.521, P=0.048), preoperative diagnostic ureteroscopy( B=0.521, P=0.002) were independent risk factors of postoperative recurrence of bladder. Conclusion:lower tumor stage, higher tumor grade, preoperative hematuria symptom and preoperative diagnostic ureteroscopy are the independent risk factors of postoperative bladder recurrence in patients with UTUC. Routine intravesical chemotherapy should be performed in patients with UTUC with the above risk factors, and routine diagnostic ureteroscopy is not recommended.

Objective:To explore the method of constructing nasal cartilage scaffold with fine refinement.Methods:From 2010 to 2018, 212 patients with nasal reconstruction were admitted to the Center of Rhinoplasty and Reconstructive Surgery Hospital of Chinese Academy of Medical Sciences.Results:The stent structure of all patients was composed of nasal dorsal graft, nasal alar support graft, nasal columella support graft, shield graft, lateral nasal cartilage support graft, hat graft, etc.Conclusions:The reconstructed nose presents a more delicate appearance after the later modification compared with the traditional simple l-shaped cartilage stent, and the patient satisfaction is high.

OBJECTIVETo detect memory B lymphocyte (Bm) in peripheral blood (PB) of immune-related pancytopenia (IRP).

METHODS86 patients with IRP and 11 health volunteers were enrolled in this study. Bm (CD5⁺ CD19⁺ CD27⁺) and bone marrow mononucleated cell antibodies (BMMNC-Ab) were determined via fluorescence-activated cell sorting, and clinical outcomes of these patients were analyzed.

RESULTS(1)43 initial patients achieved obvious remission in all 52 initial cases after conventional immunosuppression therapy. 16 relapsed patients with IRP received Rituximab (RTX) and 14 cases achieved obvious remission, among which 7 cases were refractory to conventional immunosuppression therapy, 5 cases exhibited obvious remission, and 2 cases did not respond. Other 18 relapsed cases received conventional immunosuppression therapy and 13 cases achieved obvious remission. (1)The level of Bm in PB in 52 initial patients with IRP was(1.81 ± 0.97)%, and no significant difference was observed between the initial patients and health volunteers (1.75 ± 0.55)% (P>0.05). The level of Bm in PB in 34 relapsed patients with IRP was obviously higher than that in the initial IRP patients and health volunteers (P<0.05). Significant difference was observed in the level of Bm in PB in 16 relapsed IRP patients between pre-therapy and post-therapy with RTX (P<0.05). No statistical difference was found between the remission and no-response groups in relapsed patients treated with RTX. RTX regimen produced more effective outcome than conventional immunosuppression therapy, which better eliminated Bm than the latter (P<0.05). Initial patients with IRP who relapsed within a two-year follow-up period had a lower level of Bm in PB compared with un-relapsed patients (P<0.05). Majority of BMMNC- Ab antibodies in relapsed patients were IgG (82.4%) and IgM (69.2%) autoantibodies in patients with initial IRP.

CONCLUSIONThe level of Bm in PB was associated with relapsed patients with IRP. Bm did not respond to conventional immunosuppression therapy,but responded to RTX.

Adolescent ; Adult ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; B-Lymphocyte Subsets ; immunology ; Female ; Humans ; Immunologic Memory ; Immunosuppression ; Male ; Middle Aged ; Pancytopenia ; immunology ; therapy ; Recurrence ; Rituximab ; Treatment Outcome ; Young Adult

OBJECTIVETo culture osteoblast in vitro and evaluate CCL3 receptor CCR1 expression in patients with multiple myeloma (MM).

METHODSBone marrow osteoblasts from MM patients were cultured in vitro with dexamethasone, β-sodium glycerophosphate and vitamin C, which were identified by alkaline phosphatase staining, Von Kossa's staining. The CCL3 receptor expression was evaluated by flow cytometry. The morphology and quantity of osteoblast were observed after exposure to CCL3.

RESULTSBone marrow osteoblasts from MM patients could be cultured in vitro and be identified by positive staining of alkaline phosphatase and Von Kossa's. MM-derived osteoblasts expressed higher levels of CCR1 (74.48 ± 7.31)%, compared with normal controls (48.35 ± 8.81)%. Calcium deposition of osteoblasts after exposure to CCL3 was less than that of controls.

CONCLUSIONBone marrow osteoblasts could be cultured in vitro from MM Patients. CCL3 may contribute to the development of myeloma bone disease.

Adult ; Aged ; Cells, Cultured ; Chemokine CCL3 ; pharmacology ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; pathology ; Osteoblasts ; cytology ; drug effects ; metabolism ; Receptors, CCR1 ; metabolism ; Young Adult