Objective To observe the feasibility of transesophageal echocardiography(TEE)combined with agitated saline contrast echocardiography(ASCE)for identifying morphological characteristics of high-risk patent foramen ovale(PFO)and evaluating the risk of PFO related stroke.Methods Totally 212 PFO patients diagnosed by TEE combined with ASCE were enrolled,including 100 cases with cryptogenic stroke(CS)(CS group)and 112 without CS(non-CS group).Anatomical morphological characteristics of PFO were comparatively analyzed between groups to screen the independent factors of CS.Results In CS group,the left and right atrial opening diameters of PFO were all larger than those in non-CS group in both resting-state and stimulated state.The aortic root diameter in CS group was larger than that in non-CS group,and the incidence of atrial septal aneurysm(ASA),high activity of the atrial septum,inferior vena cava valve or Chiari network,large amount of right-to-left-shunt(RLS)in stimulated state,and multiple outlets of the oval valve in CS group were all higher than those in non-CS group(all P＜0.05).Logistic regression analysis showed that ASA,high atrial septal activity,large amount of RLS and multiple oval valve outlets were all independent factors associated with CS(OR=0.211,0.384,0.999,0.199,all P＜0.05).Conclusion TEE combined with ASCE could identify anatomical characteristics of high-risk PFO and assess the risk of PFO related stroke.

Objective To observe the feasibility of transesophageal echocardiography(TEE)combined with agitated saline contrast echocardiography(ASCE)for identifying morphological characteristics of high-risk patent foramen ovale(PFO)and evaluating the risk of PFO related stroke.Methods Totally 212 PFO patients diagnosed by TEE combined with ASCE were enrolled,including 100 cases with cryptogenic stroke(CS)(CS group)and 112 without CS(non-CS group).Anatomical morphological characteristics of PFO were comparatively analyzed between groups to screen the independent factors of CS.Results In CS group,the left and right atrial opening diameters of PFO were all larger than those in non-CS group in both resting-state and stimulated state.The aortic root diameter in CS group was larger than that in non-CS group,and the incidence of atrial septal aneurysm(ASA),high activity of the atrial septum,inferior vena cava valve or Chiari network,large amount of right-to-left-shunt(RLS)in stimulated state,and multiple outlets of the oval valve in CS group were all higher than those in non-CS group(all P＜0.05).Logistic regression analysis showed that ASA,high atrial septal activity,large amount of RLS and multiple oval valve outlets were all independent factors associated with CS(OR=0.211,0.384,0.999,0.199,all P＜0.05).Conclusion TEE combined with ASCE could identify anatomical characteristics of high-risk PFO and assess the risk of PFO related stroke.

OBJECTIVE To prepare curcumin /berberine co -loaded self -microemulsion drug delivery system （CUR/BER- SMEDDS）and evaluate its physicochemical properties and in vitro anti-tumor effects . METHODS Using CUR and BER as model drug，based on the screening of the type of oil phase ，emulsifier，co emulsifier and their mass ratio ，the formulation of CUR/BER - SMEDDS were optimized by central composite design -response surface methodology ，taking particle size and drug loading as evaluation parameters ，with the mass percentage of oil phase and the mass ratio of emulsifier to co emulsifier as factors ，and verification test was conducted . CUR/BER-SMEDDS prepared by optimized formulation were evaluated in terms of physicochemical properties，in vitro dissolution and in vitro anti-tumor effects . RESULTS The optimized formulation of CUR/BER -SMEDDS included that the oil phase was medium chain triglyceride （30.97%），the emulsifier was polyoxyl 40 hydrogenated castor oil （46.77%），the co emulsifier was polyethylene glycol 400（22.26%），and the mass ratio of emulsifier to co emulsifier was 2.10∶1. The validation experiments showed that mean particle size of CUR/BER -SMEDDS was（58.90±5.41）nm，the average drug loading was（94.94±3.87）mg/g，and the relative deviations from the predicted values were －2.90% and －0.14%，respectively. The CUR/ BER-SMEDDS prepared by optimal formulation was light yellow ，clear and transparent liquid after emulsified with water ，and its particles were spherical . The results of dissolution test in vitro showed that after SMEDDS was made ，the cumulative dissolution of CUR in artificial intestinal fluid and artificial gastric fluid and that of BER in artificial intestinal fluid were significantly higher than those of its raw material . Results of in vitro anti-tumor experiment showed that IC 50 values of CUR/BER -SMEDDS for PC -3 cells and DU -145 cells were （17.38±2.84）and（20.89±1.26）μmol/L，which were all lower than those of CUR and EBR significantly （P＜0.05）.CONCLUSIONS The optimized prepar ation process of CUR/BER -SMEDDS is stable and feasible . The drug release of CUR/BER-SMEDDS is more complete than that of single drug，and has stronger anti -prostate cancer effect in vitro .

Purpose: This study aimed to investigate the changes in microRNA-130a (miR-130a) and its correlation with cardiotoxicity during epirubicin/cyclophosphamide followed by docetaxel plus trastuzumab (EC-D+T) adjuvant chemotherapy in human epidermal growth factor receptor-2-positive (HER2+) breast cancer patients. Methods: A total of 72 HER2+ breast cancer patients who underwent resection and were scheduled to receive EC-D+T adjuvant therapy were consecutively enrolled. The expression of miR-130a and cardiotoxicity (defined as any of the following situations: 1) absolute decline of left ventricular ejection fraction (LVEF) ≥ 10% and LVEF < 53%; 2) heart failure; 3) acute coronary artery syndromes; and 4) fatal arrhythmia) were assessed every 3 months throughout the 15-month EC-D+T treatment. Results: The accumulating cardiotoxicity rate was 12 (16.7%), of which the incidence of heart failure, acute coronary syndrome, life-threatening arrhythmias, ΔLVEF ≥ 10%, and LVEF < 53% was 0 (0.0%), 1 (1.4%), 0 (0.0%), and 12 (16.7%), respectively. Baseline miR-130a expression was negatively correlated with LVEF (%) and positively correlated with cardiac troponin I. The expression of miR-130a gradually increased in both cardiotoxicity and noncardiotoxicity patients during EC-D+T treatment, while the increment of miR-130a was more obvious in cardiotoxicity patients compared with non-cardiotoxicity patients. Further logistic regression and receiver operating characteristic curve analysis indicated that miR-130a was an independent predictive factor for increased cardiotoxicity risk. Conclusion MiR-130a increases constantly and predicts high cardiotoxicity risk during ECD+T adjuvant chemotherapy in HER2+ breast cancer patients.

Purpose: This study aimed to investigate the changes in microRNA-130a (miR-130a) and its correlation with cardiotoxicity during epirubicin/cyclophosphamide followed by docetaxel plus trastuzumab (EC-D+T) adjuvant chemotherapy in human epidermal growth factor receptor-2-positive (HER2+) breast cancer patients. Methods: A total of 72 HER2+ breast cancer patients who underwent resection and were scheduled to receive EC-D+T adjuvant therapy were consecutively enrolled. The expression of miR-130a and cardiotoxicity (defined as any of the following situations: 1) absolute decline of left ventricular ejection fraction (LVEF) ≥ 10% and LVEF < 53%; 2) heart failure; 3) acute coronary artery syndromes; and 4) fatal arrhythmia) were assessed every 3 months throughout the 15-month EC-D+T treatment. Results: The accumulating cardiotoxicity rate was 12 (16.7%), of which the incidence of heart failure, acute coronary syndrome, life-threatening arrhythmias, ΔLVEF ≥ 10%, and LVEF < 53% was 0 (0.0%), 1 (1.4%), 0 (0.0%), and 12 (16.7%), respectively. Baseline miR-130a expression was negatively correlated with LVEF (%) and positively correlated with cardiac troponin I. The expression of miR-130a gradually increased in both cardiotoxicity and noncardiotoxicity patients during EC-D+T treatment, while the increment of miR-130a was more obvious in cardiotoxicity patients compared with non-cardiotoxicity patients. Further logistic regression and receiver operating characteristic curve analysis indicated that miR-130a was an independent predictive factor for increased cardiotoxicity risk. Conclusion MiR-130a increases constantly and predicts high cardiotoxicity risk during ECD+T adjuvant chemotherapy in HER2+ breast cancer patients.

Objective:To investigate the prognostic significance of introtumoral and peritumoral lymphangiogenesis in colorectal cancer.Methods:Lymphangiogenesis of 120 colorectal cancer specimens, as measured by lymphatic vessel density (LVD), were examined by immunostaining for podoplanin, a lymphatic specific marker. The mean number of lymphatic vessel in three hotspots was calculated in intratumoral and peritumoral areas as intratumoral LVD (LVDit) and peritumoral LVD (LVDpt) respectively. The association of LVDit and LVDpt with the clinicopathologic findings and prognosis were investigated.Results:Compared to the peritumoral lymphatics, the intratumoral lymphatics were small, collapsed and irregular. LVDit was positively correlated with tumor size ( t=2.673, P=0.009), tumor histologic grade ( t=-2.296, P=0.023), and overall survival (χ 2=4.386, P=0.036). LVDpt was associated with lymph node metastasis ( t=-4.053, P<0.001), tumor stage ( t=4.740, P=0.004) and overall survival (χ 2=5.806, P=0.016). Conclusions:LVDpt played an important role in lymph node metastasis, while LVDit was more correlated with tumor growth and histopathologic differentiation. Both LVDs contribute to colorectal cancer progression and predict poor prognosis.

[Abstract] Objective: To investigate the osteogenic differentiation characteristics of mesenchymal stem cell (MSC) derived from bone marrow in patients with myelodysplastic syndromes (MDS) and its clinical significance. Methods: Bone marrow samples from 30 cases of newly diagnosed untreated MDS patient atAffiliated Hospital of Heibei University were collected for this study. MSCs from MDS patients and normal subjects were isolated and cultured, and morphological characteristics of MSCs were observed in vitro; under proper conditions, MSCs were induced to differentiate into osteoblasts and adipocytes; The formation of calcium nodules at 14th day after osteogenic differentiation was observed by alizarin red staining; mRNA expressions of osteogenic differentiation transcription factors Ostefix and RUNX2 in undifferentiated MSCs, as well as the mRNAexpression of Jagged-1, which involved in the transformation from hematopoietic cells into leukemic cells, were detected by quantitative PCR. Results: The MSCs derived from patients with MDS were characterized with increased cell volume and decreased differentiation potential. Compared with the control group, the expression levels of osteogenic differentiation transcription factors Osterix and RUNX2 were significantly decreased (P < 0.05). Alizarin red staining showed that the content of calcium nodules in MDS group was significantly less than that in the normal control group, while the expression level of Jagged-1 was significantly higher (P < 0.05). Conclusion: MSCs derived from bone marrow of MDS patients showed significant increased cell volume, decreased differentiation potential and elevated Jagged-1 expression; all of these might play important roles in the .hematopoietic failure and progression to acute myeloid leukemia in MDS patients.

Objective The aim of this study was to investigate mutations of 41 STR loci. Methods 4546 bloodstain samples were typed from 1932 father–mother–child trios by using AGCU_21+1, AGCU_EX22 and GlobalFiler_ExpressTM amplification Kit. Calculate the mutation rates of STR loci. Results 154 mutations were identified at 32 of the 41 loci. The average mutation rate was 1.0×10-3per locus(95%CI: 0.8~1.1×10-3), and the mutations of SE33 was highest. 152(98.7%) mutation events were one-step mutation, 2(1.3%) events were two-steps. The mutation events occurred in 150 father–mother–child triplets. The mutations in 146(97.3%) triplets occurred at single locus, 8 mutations were observed at two loci in 4(2.7%) triplets simultaneously. 104 paternal and 22 maternal mutations could be determined under 79212 paternal and maternal allelictransfers. The ratio of paternal versus maternal mutations was 4.7:1, and 28 unassigned mutations were observed. Conclusion STR mutation are common in paternity testing, and we should pay more attention to it.

Objective To study the influence of CTP-OD1-HA and CTP-OD2-HA fusion peptides and combined with imatinib on proliferation of K562 cells.Methods K562 cells were treated with CTP-OD1-HA and CTP-OD2-HA peptides or together with imatinib.The proliferation of cells were detected and compared by MTT and clone formation methods.Results MTT examination demonstrated that CTP-OD1-HA and CTP-OD2-HA peptides could inhibit the proliferation of K562 cells,and the effect was more obvious when acted along with imatinib;Clone formation showed that CTP-OD1-HA and CTP-OD2-HA peptides suppressed the continuous colony forming ability of K562 cells.Conclusion CTP-OD1-HA and CTP-OD2-HA could specially inhibit the proliferation of K562 cells,and increase the sensitivity of imatinib.

Objective The objective of this study was to investigate the relationship between the expression of RAD18 and radiation resistance in glioblastoma multiforme(GBM)and to provide a new therapeutic target for improving the radiation resistance of GBM.Methods Human glioma A172 cells were transfected into blank and RAD18-containing plasmid vector.The cell proliferation of two groups after the same dose radiation was detected by cloning assay.The mRNA expression of RAD18 in primary and recurrent GBM samples after close proximity treatment were detected by qRT-PCR.All data were analyzed statistically.Results The proliferation of GBM cells transfected with RAD18 plasmid was higher than that of cells transfected with blank plasmid after radiation therapy(P<0.001).The expression level of RAD18 mRNA in recurrent GBM was higher than that in the untreated radioactive granules primary GBM(P<0.01).Conclusion The resistance of recurrent GBM to radiotherapy may be associated with the overexpression of RAD18 protein.