BACKGROUND:Tyrosine kinase inhibitors,as well as other types of small-molecule cancer drugs,can cause severe cardiotoxicity. OBJECTIVE:To perform a heart safety re-evaluation by observing the effects of antitumor drugs on isolated heart electrocardiograph,cardiac action potential and associated ion channels and cytotoxicity. METHODS:Extracorporeal cardiac perfusion was given to the isolated rabbit heart using Langendorff perfusion:Sunitinib(0.3,3,10 μmol/L),Crizotinib(0.3,1,3 μmol/L),and Doxorubicin(1,30 μmol/L)were perfused sequentially for 120 minutes to record electrocardiograph and left ventricular pressure.A blank control group was set for comparison.Manual patch clamp was used to record the effects of Crizotinib,Sunitinib,Doxorubicin on hERG,Cav1.2,Nav1.5 channel currents and action potential in human induced pluripotent stem cell derived cardiomyocytes.Adenosine triphosphate level in human induced pluripotent stem cell derived cardiomyocytes was detected by CellTiter-Glo luminescent cell viability assay. RESULTS AND CONCLUSION:Isolated rabbit heart using Langendorff perfusion:Compared with the blank ontrol group,Sunitinib and Crizotinib at≥3 μmol/L decreased heart rate(P<0.01)and prolonged QT/QTc interval(P<0.01),and reduced left ventricular pressure to different extents.Manual patch clamp recording:Compared with the blank control group,Sunitinib and Crizotinib at 3 μmol/L inhibited the activities of hERG,Nav1.5 and Cav1.2 channels and significantly prolonged the duration of action potential(P<0.01).According to the analysis of the test article,the difference between the labeled concentration and the measured concentration of the recovered solution was not significant.Cell viability assays:Compared with the blank control group,adenosine triphosphate content in human induced pluripotent stem cell derived cardiomyocytes significantly decreased after treatment with Sunitinib(IC50=4.64 μmol/L),Doxorubicin(IC50=4.21 μmol/L)and Crizotinib(IC50=2.87 μmol/L),indicating that cell viability significantly decreased(P<0.01).To conclude,this study successfully established an early cardiac safety evaluation method for antitumor drugs,which provides good support and help for the subsequent development of antitumor drugs.

Objective:To investigate the therapeutic effect of comprehensive geriatric assessment(CGA) in elderly patients with chronic heart failure(CHF) complicated with sarcopenia, and to provide a theoretical reference for clinical application.Methods:This study was a prospective randomized controlled study. 110 elderly CHF patients with myopenia admitted to the Third People's Hospital of Hefei from January 2019 to February 2022 were selected. Using the random number table method, 56 cases were divided into an observation group and 54 cases into a control group. Before treatment, the control group of patients underwent a selective single assessment based on the hospital's requirements and the patient's actual situation, including a fall risk assessment, nutritional risk screening checklist assessment, and routine medication to improve cardiac function and prognosis; Before treatment, the patients in the observation group were assessed with CGA, including the assessment of physical function, mental and psychological status, multiple drug management, pain, Sleep disorder, and social environment. According to the assessment results, individual diagnosis and treatment plans were formulated, implemented, and dynamically adjusted. The two groups were treated for 12 weeks. The general information, treatment compliance, B-type brain natriuretic peptide (BNP) level, left ventricular Ejection fraction (LVEF), 6 min walking distance (6MWD), arm strength of upper limbs and 6 m walking speed, clinical efficacy and prognosis of the two groups were compared before and after treatment. The measurement data is represented by xˉ± s, group t-tests are used for inter group comparison, and paired t-tests are used for intra group comparison before and after treatment; Counting data is represented as an example (%), and inter group comparisons are made using χ 2 test, non parametric rank sum test was used for inter group comparison of hierarchical data. Results:There was no statistically significant difference in gender, age, course of CHF, smoking, alcohol consumption, number of comorbidities, cardiac function grading, and treatment compliance between the two groups of patients (all P>0.05), indicating comparability. Before treatment, there was no statistically significant difference in plasma BNP, LVEF, 6MWD, upper limb grip strength, and 6-meter walking speed between the two groups of patients (all P>0.05); After treatment, the BNP of both groups of patients was lower than before treatment and the observation group was lower than the control group. LVEF, 6MWD, upper limb grip strength, and 6-meter walking speed were all higher than before treatment and the observation group was higher than the control group [(343.45±34.95) ng/L vs (387.09±46.96) ng/L, (49.61±7.11)% vs (42.94±5.72)%, (348.92±37.73) m vs (297.74±43.48) m, (22.64±3.82) kg vs (19.48±3.88) kg, (0.97±0.10) m/s vs (0.83±0.12) m/s], The differences were statistically significant ( t-values were 5.51, -5.40, -6.60, -4.31, -6.60, all P<0.001). After 12 weeks of treatment, there was no statistically significant difference in clinical efficacy between the two groups of patients ( P=0.216), but the overall poor prognosis rate in the follow-up observation group was lower than that in the control group [7.14%(4/56) vs 22.22% (12/54)], and the difference was statistically significant (χ 2=5.03, P=0.025). Conclusions:Developing, implementing, and dynamically adjusting the individualized treatment plan involving CGA can improve the prognosis of elderly CHF patients with sarcopenia, help improve cardiac function, increase grip strength and somatic function, and reduce the risk of major adverse cardiovascular events ,all-cause mortality in elderly patients with CHF combined with sarcopeni and has certain clinical application value.

BACKGROUND: Degeneration of the annulus fibrosus (AF), an important structure of the intervertebral disc, is one of the main causes of degenerative disc disease. Fabrication of scaffolds replicating the stratified microstructure of the AF is critical for the successful regeneration of AF. METHODS: In this study, we cultured rabbit AF-derived stem cells (AFSCs) using fabricated electrospun fibrous poly-Llactic acid scaffolds with different diameters. We applied cyclic tensile strain (CTS) on the scaffolds to regulate the differentiation of AFSCs into specific cell types that resided at the inner, middle, and outer zones of the AF. RESULTS: We found that the morphologies of AFSCs on the smaller-fiber-diameter scaffolds were nearly round, whereas spindle-like cells morphologies were observed on large-diameter scaffolds. CTS enhanced these phenomena and made the cells slender. The expression levels of collagen-I in cells increased as a function of the fiber diameter, whereas collagen-II and aggrecan exhibited opposite trends. Moreover, the application of CTS upregulated the gene expressions of collagen-I, collagen-II, and aggrecan. CONCLUSION Overlaying the scaffolds with different CTS-stimulated cells could eventually lead to engineered AF tissues with hierarchical structures that approximated the native AF tissue. Thus, the proposed methodologies could be potentially applied for AF regeneration.

BACKGROUND: Degeneration of the annulus fibrosus (AF), an important structure of the intervertebral disc, is one of the main causes of degenerative disc disease. Fabrication of scaffolds replicating the stratified microstructure of the AF is critical for the successful regeneration of AF. METHODS: In this study, we cultured rabbit AF-derived stem cells (AFSCs) using fabricated electrospun fibrous poly-Llactic acid scaffolds with different diameters. We applied cyclic tensile strain (CTS) on the scaffolds to regulate the differentiation of AFSCs into specific cell types that resided at the inner, middle, and outer zones of the AF. RESULTS: We found that the morphologies of AFSCs on the smaller-fiber-diameter scaffolds were nearly round, whereas spindle-like cells morphologies were observed on large-diameter scaffolds. CTS enhanced these phenomena and made the cells slender. The expression levels of collagen-I in cells increased as a function of the fiber diameter, whereas collagen-II and aggrecan exhibited opposite trends. Moreover, the application of CTS upregulated the gene expressions of collagen-I, collagen-II, and aggrecan. CONCLUSION Overlaying the scaffolds with different CTS-stimulated cells could eventually lead to engineered AF tissues with hierarchical structures that approximated the native AF tissue. Thus, the proposed methodologies could be potentially applied for AF regeneration.

Adult ; Endocarditis/surgery* ; Endocarditis, Bacterial/surgery* ; Hospital Mortality ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Young Adult

Objective:To investigate the effects of oligodeoxynucleotide (ODN) MT01 on the morphology, proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs).Methods:The BMSCs of SD rat were isolated and cultured by direct adherence method . The extracted cells were identified by cell morphology of different generations, the expression of surface markers detected by flow cytometry and osteogenic differentiation potential. ODN MT01 group was set up in a gradient of concentrations (0.5, 1.0, 2.0, 4.0 μg/ml) and PBS group as control. Each group of experiments was repeated three times. The morphological changes of cell nucleus and cytoskeleton were fluorescent stained by DAPI and FITC-phalloidin, respectively. The proliferation activities of the BMSCs in different group were analyzed by CCK-8 assay at 1, 4 and 7 d. The degrees of osteogenic differentiation of BMSCs in different group were assessed via alkaline phosphatase (ALP) staining, ALP activity assay and alizarin red S staining respectively on the 7th and 21st days after cultured in osteogenic induction medium. Statistical differences between two groups and among groups were analyzed by t-test and one-way ANOVA, respectively. Differences were regarded as statistically significant when a P value of less than 0.05. Results:Flow cytometry showed that the BMSCs were positive for CD29 (99.8%) and CD44 (96.1%) while negative for CD11b (1.03%) and CD45 (1.74%). ALP staining and alizarin red S staining were positive at different stages of osteogenesis induction confirmed that BMSCs was able to differentiate into the osteoblast. The nucleus and cytoskeleton staining showed that BMSCs were shrunk and the extensibility was reduced when the concentration of ODN MT01 was 4.0 μg/ml. CCK-8 assay showed that the absorbance value of control group was 0.446±0.018, 1.0 μg/ml ODN MT01 was 0.505±0.019, 2.0 μg/ml ODN MT01 was 0.528±0.014 after cultured for 4 days. Compared with the control group, the difference is statistically significant ( t=2.954, 4.083, P=0.033, 0.008). The absorbance value of control group was 0.514±0.027, 1.0 μg/ml ODN MT01 was 0.607±0.007, and 2.0 μg/ml ODN MT01 was 0.636±0.023 after cultured for 7 days. Compared with the control group, the difference was statistically significant ( t=4.664, 6.091, P=0.009, 0.008). The proliferation ability of BMSCs was significantly higher than that of the control group. However, 4.0 μg/ml ODN MT01 (0.427±0.013) had an inhibitory effect on the proliferation ability of BMSCs ( t=4.332, P=0.0149). The blue mass and mineralized nodule improved significantly with the increase of ODN MT01 concentration during the induction of osteogenic differentiation of BMSCs. After cultured for 4 days, the result of ALP activity assay was similar to ALP staining. The activity value of ODN MT01 in the control group was 1.207±0.023, 0.5 μg/ml ODN MT01 was 1.747±0.095, 1.0 μg/ml ODN MT01 was 2.200±0.136, 2.0 μg/ml ODN MT01 was 3.560±0.088, 4.0 μg/ml ODN MT01 was 3.490±0.144. Compared with the control group, the difference was statistically significant ( t=4.313, 7.934, 18.800, 18.240; P=0.005, 0.001, <0.001, <0.001). But there was no difference between 2.0 and 4.0 μg/ml groups ( t=0.562, P=0.590). Conclusions:ODN MT01 with concentration of 2.0 μg/ml could significantly stimulate the proliferation and osteogenic differentiation of BMSCs without affecting the morphology of BMSCs.

Objective:To investigate the effects of oligodeoxynucleotide (ODN) MT01 on the morphology, proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs).Methods:The BMSCs of SD rat were isolated and cultured by direct adherence method . The extracted cells were identified by cell morphology of different generations, the expression of surface markers detected by flow cytometry and osteogenic differentiation potential. ODN MT01 group was set up in a gradient of concentrations (0.5, 1.0, 2.0, 4.0 μg/ml) and PBS group as control. Each group of experiments was repeated three times. The morphological changes of cell nucleus and cytoskeleton were fluorescent stained by DAPI and FITC-phalloidin, respectively. The proliferation activities of the BMSCs in different group were analyzed by CCK-8 assay at 1, 4 and 7 d. The degrees of osteogenic differentiation of BMSCs in different group were assessed via alkaline phosphatase (ALP) staining, ALP activity assay and alizarin red S staining respectively on the 7th and 21st days after cultured in osteogenic induction medium. Statistical differences between two groups and among groups were analyzed by t-test and one-way ANOVA, respectively. Differences were regarded as statistically significant when a P value of less than 0.05. Results:Flow cytometry showed that the BMSCs were positive for CD29 (99.8%) and CD44 (96.1%) while negative for CD11b (1.03%) and CD45 (1.74%). ALP staining and alizarin red S staining were positive at different stages of osteogenesis induction confirmed that BMSCs was able to differentiate into the osteoblast. The nucleus and cytoskeleton staining showed that BMSCs were shrunk and the extensibility was reduced when the concentration of ODN MT01 was 4.0 μg/ml. CCK-8 assay showed that the absorbance value of control group was 0.446±0.018, 1.0 μg/ml ODN MT01 was 0.505±0.019, 2.0 μg/ml ODN MT01 was 0.528±0.014 after cultured for 4 days. Compared with the control group, the difference is statistically significant ( t=2.954, 4.083, P=0.033, 0.008). The absorbance value of control group was 0.514±0.027, 1.0 μg/ml ODN MT01 was 0.607±0.007, and 2.0 μg/ml ODN MT01 was 0.636±0.023 after cultured for 7 days. Compared with the control group, the difference was statistically significant ( t=4.664, 6.091, P=0.009, 0.008). The proliferation ability of BMSCs was significantly higher than that of the control group. However, 4.0 μg/ml ODN MT01 (0.427±0.013) had an inhibitory effect on the proliferation ability of BMSCs ( t=4.332, P=0.0149). The blue mass and mineralized nodule improved significantly with the increase of ODN MT01 concentration during the induction of osteogenic differentiation of BMSCs. After cultured for 4 days, the result of ALP activity assay was similar to ALP staining. The activity value of ODN MT01 in the control group was 1.207±0.023, 0.5 μg/ml ODN MT01 was 1.747±0.095, 1.0 μg/ml ODN MT01 was 2.200±0.136, 2.0 μg/ml ODN MT01 was 3.560±0.088, 4.0 μg/ml ODN MT01 was 3.490±0.144. Compared with the control group, the difference was statistically significant ( t=4.313, 7.934, 18.800, 18.240; P=0.005, 0.001, <0.001, <0.001). But there was no difference between 2.0 and 4.0 μg/ml groups ( t=0.562, P=0.590). Conclusions:ODN MT01 with concentration of 2.0 μg/ml could significantly stimulate the proliferation and osteogenic differentiation of BMSCs without affecting the morphology of BMSCs.

The incidence of thyroid carcinoma is increasing.Because of the special location,patients usually have cosmetic requirements for thyroid surgery.Compared with open surgery,improved Miccoli surgery,total endoscopic surgery,radiofrequency ablation and other minimally invasive surgery have obvious advantages in cosmetology,but the surgical indications are limited.Through incision design and protection,appropriate suture materials,standard suture methods and negative pressure drainage measures,we can effectively reduce the scar formation of open surgery,and improve the cosmetic results.Preoperative individualized treatment should be formulated according to the patient's actual situation,tumor nature,cosmetic needs,hospital conditions and other comprehensive factors.

To observe the results of different treatment of congenital heart disease (CHD) complicated with severe pneumonia in infants.
 Methods: A total of 27 infants with CHD and severe pneumonia were admitted to the Department of Pediatrics, Xiangya Hospital from January 2014 to December 2014, of whom 18 were male and 9 were female. The average age was 2.0-19.0(5.9±4.3) months, with an average body weight of 3.3-10.0 (5.8±1.8) kg. Infants were treated with a strategy of complete control of the lung infection before surgery (internal medicine group). From January 2015 to December 2015, 29 infants with same condition were admitted, of whom 15 were males and 14 females. The average age was 2.0-27.0 (6.1±3.9) months, with an average body weight of 3.1-8.0 (4.8±1.0) kg. Infants were treated with a strategy of combined treatment (combined treatment group), in which early surgical treatment were performed after a short time antibiotics and supportive treatment.
 Results: One nosocomial death in internal medicine group, with an average hospital stay for 3-26 (11±6) d. Further surgeries were performed in 5 patients after discharge with no surgical death. The mean preoperative hospital stay in combined treatment group was 1-21 (10±6) d. The mean total hospital stay for combined treatment group was 14-48 (24±9) d and the mean postoperative hospital stay was 6-35 (14±7) d. One patient died soon after surgery in combined treatment group. Thirty-day follow-up found that no other patient died in combined treatment group, and 6 patients died in internal medicine group. The 30-day mortality was 3.4% in combined treatment group and 22.2% in internal medicine group (P<0.01).
 Conclusion: Infant congenital heart disease complicated with severe pneumonia requires early surgical treatment, which contributed to the control of pulmonary infection and reduce mortality.
Female ; Heart Defects, Congenital ; therapy ; Humans ; Infant ; Length of Stay ; Male ; Pneumonia ; therapy ; Postoperative Period

Objective To investigate correlation between genetic polymorphisms of CDHR3 (rs6967330),GSDMB (rs2305480),IL-33 (rs928413),RAD50 (rs6871536) and IL1RL1 (rs1558641) and occurrence and severity of allergic asthma in Han population.Methods Genotype and allele frequencies were compared between 516 patients and 552 controls by Chi-square test.Correlation between genotype and FEV1,total IgE was analyzed.Results Compared with the controls,the allergic patients had significantly higher allergic G of rs928413 and allergic C of rs6871536 (P ＜0.001).Besides,allergic patients were found to have significantly lower frequency of allergic A of rs1558641 (P =0.007).Compared with other genotypes,patients with rs928413 genotype GG and rs1558641 genotype GG were significantly correlated with low FEV1％ and high level of serum total IgE.Conclusion Gene IL-33,IL1R1,and RAD50 are correlated with the risk of asthma in Han population.