The value of speckle-tracking stratified strain combined with myocardial work measurement in evaluating left ventricular function in patients with heart failure with preserved ejection fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent progressive disease accompanied by poor quality of life, high utilization of medical resources, morbidity, and mortality. However, the role of left ventricular (LV) systolic dysfunction has yet to be well elaborated despite the preservation of the LV ejection fraction. This study aimed to explore the diagnostic value of speckle-tracking stratified strain combined with myocardial work (MW) measurement in evaluating LV systolic dysfunction in patients with HFpEF. Methods: A total of 125 study consecutive individuals, 64 HFpEF patients, and 61 controls were prospectively enrolled in the Fourth Affiliated Hospital of Harbin Medical University. In addition to the conventional echocardiographic parameters, LV stratified strain and MW parameters were statistically compared between the HFpEF and control groups. The global longitudinal strain (GLS) of the subendocardium, myocardium, and subepicardium (GLSendo, GLSmyo, and GLSepi); the transmural gradient (ΔGLS); the global myocardial work index (GWI), global myocardial work efficiency (GWE), global myocardial constructive work (GCW), and the global myocardial wasted work (GWW) were included. Area under the receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of these univariate and multivariable logistic models in detecting impaired LV systolic function in HFpEF. Ten-fold cross-validation was used to evaluate the generalizability of the predictive model. Results: Stratified strains values showed a gradient decline from GLSendo to GLSepi in both control and HFpEF patients. Compared with the control group, HFpEF patients had a significantly reduced GLSepi, GLSmyo, GLSendo, ΔGLS, GWI, GWE, and GCW and a significantly increased GWW (all P<0.001). In the derivation set, the optimal logistic model (combined stratified strain and MW variables) demonstrated the highest performance in predicting LV systolic function impairment in HFpEF patients. The best-performing model with a mean area under the curve (AUC) of 0.966 [95% confidence interval (CI): 0.88 to 1] accessed by 10-fold cross-validation. In the validation set, the AUC of the optimal logistic model was 0.933 (95% CI: 0.85 to 1), the sensitivity was 87%, and the specificity was 93%. Conclusions: Both speck-tracking stratified strain and MW measurement may sensitively detect impairment of LV myocardial function at an early stage for patients with HFpEF. Combining the two techniques may improve the quality of HFpEF diagnosis and may provide a reference value for the early diagnosis of HFpEF in the future.

Multistage delivery of CDs-DOX/ICG-loaded liposome for highly penetration and effective chemo-photothermal combination therapy.

Nanoparticles (NPs) have proven to be effective drug carriers in diagnosis and therapy of cancer. But, they faced a contradictory issue that NPs with large size appear weak tumor penetration, meanwhile small size resulted in poor tumor retention. Herein, we fabricated doxorubicin conjugated carbon dots (CDs-DOX) and indocyanine green (ICG)-loaded liposomes (ICG-LPs) named CDs-ICG-LPs using a modified reverse phase evaporation process, and with high incorporation in the aqueous core. The CDs-ICG-LPs exhibited good monodispersity, excellent fluorescence/size stability, and consistent spectra characteristics compared with free ICG or DOX. Moreover, the CDs-ICG-LPs showed higher temperature response, faster DOX release under laser irradiation. In the meantime, the fluorescence of DOX and ICG in CDs-ICG-LPs was also visualized for the process of subcellular location in vitro. In comparison with chemo or photothermal treatment alone, the combined treatment of CDs-ICG-LPs with laser irradiation synergistically induced the apoptosis and death of DOX-sensitive HepG2 cells. In vivo antitumor activities demonstrated CDs-ICG-LPs could reach higher antitumor activity compared with CDs-DOX and ICG-LPs for H22 tumor cells, and suppressed H22 tumor growth in vivo. Notably, no systemic toxicity occurrence was observed after repeated dose of CDs-ICG-LPs with laser irradiation. Hence, the well-defined CDs-ICG-LPs exhibited great potential in targeting cancer imaging and chemo-photothermal therapy.

MicroRNA-195 targets VEGFR2 and has a tumor suppressive role in ACHN cells via PI3K/Akt and Raf/MEK/ERK signaling pathways.

Increasing evidence indicates that dysregulation of miR-195 may contribute to the occurrence and development of multiple types of human malignancies. However, the function and the mechanism of miR-195 in clear cell renal cell carcinoma (ccRCC) are still not fully understood. In the present study, we used qRT-PCR to detect the expression of miR-195 in ccRCC tissues and normal kidney tissues. MTT assay was performed to detect the cell viability of miR-195. Migration and invasion were evaluated by Transwell migration and Matrigel invasion assays, respectively. Additionally, apoptosis levels were evaluated using TUNEL assays, and signaling pathway changes were determined by western blot analysis. We observed that miR-195 was downregulated in clear cell renal cell carcinoma samples compared with normal renal samples. We identified that overexpression of miR-195 inhibited ACHN cell viability, migration, invasion, and it also induced cell apoptosis by targeting VEGFR2 via PI3K/Akt and Raf/MEK/ERK signaling pathways. These findings indicate that miR-195 has a tumor suppressive role in ACHN cells and miR-195 may be a promising candidate target for prevention and treatment of renal cell carcinoma.

[Analysis of risk factors for preeclampsia in pregnancies complicated with chronic aplastic anemia].

OBJECTIVE: To investigate the risk factors for preeclampsia(PE) in pregnancies complicated with chronic aplastic anemia (CAA) by analyzing the obstetric management and pregnancy outcome. METHODS: Retrospectively review the clinical data including the obstetric management, the laboratory findings and the pregnancy outcome of 41 pregnant women complicated with CAA, all of whom were hospitalized in Peking University People's Hospital from May 2002 to February 2011. Multiple logistic regression was used to explore the risk factors associated with PE. RESULTS: (1) Twenty-eight patients were diagnosed before conception while 13 were diagnosed during gestation. Eleven patients including all the 7 who were categorized as severe CAA presented with mild bleeding in the third trimester. (2) The medians of white blood cell counts, hemoglobin concentrations and platelet counts were 5.0×109/L, 66.0 g/L and 12.0×109/L respectively. (3) The obstetric management consisted of strict assessment, intensive surveillance and follow-up, appropriate supportive measures, timely recognition of complications, and delivery when necessary. Twenty-one patients received supportive transfusions. Ten patients developed PE, all of whom were diagnosed as severe PE (SPE). Twelve patients suffered postpartum hemorrhage, and 3 of them had blood loss more than 1000 ml. All were conservatively treated in success. (4) The median gestational age of delivery was 37 weeks. Sixteen cases delivered before 37 weeks and 5 delivered before 34 weeks. Two patients developed SPE at 29 weeks and 30 weeks respectively, and both of the neonates died for severe asphyxia. The birth weight of the live neonates ranged from 1500 to 3660 g. (5) The postpartum follow-up period ranged from 6 months to 7 years. Thirty-three patients got improvement without dependence on transfusions. Four achieved no remission and still needed intermittent transfusions. Four were lost in follow-up. (6) Significant differences were found in the bleeding tendency, the platelet counts and the delivery weeks when comparing the patients developing PE and those without PE. No differences were found with regard to the age, the gestational age of first visit, the percentage of patients diagnosed before conception, the percentage of severe CAA, the choice of treatment, the white blood cell counts and the hemoglobin level. The Multiple logistic regression showed that the platelet count less than 10×109/L was an independent risk factor for CAA patients developing PE (P = 0.006). CONCLUSIONS: Most pregnancies complicated with CAA could achieve good maternal and fetal outcome, when intensive prenatal care and supportive management are provided. SPE is the most common complication. The platelet count less than 10×109/L is perhaps an independent risk factor for CAA patients developing PE.

[Prediction of chemoresistance in epithelial ovarian cancer by clinical factors].

OBJECTIVE: To compare the clinical features and prognosis among patients with different chemosensitivity and determine the specific clinical influencing factors of chemotherapeutic resistance. METHODS: In references to the 2010 NCCN clinical practice guidelines on ovarian cancer and in accordance with the length of disease-free interval, 244 patients were divided into 3 groups: platinum-resistant, partially sensitive and platinum-sensitive. The differences of clinical features, treatment and prognosis were compared among these 3 groups. RESULTS: The resistant, partially sensitive, sensitive rates to platinum-based chemotherapy were 23.4%, 13.5% and 63.1% respectively. Such factors as age, pathological type, primary tumor size. intraperitoneal chemotherapy and venous chemotherapy regimen had no effect on the responses to the combination platinum-based chemotherapy. The platinum-resistant percentage of advanced stage patients without optimal cytoreductive surgery was higher (P < 0.01). The poorly differentiated rate of partially sensitive patients was higher than that of platinum-sensitive ones (P < 0.05). The CA125 level and lymph node metastasis rate of platinum-resistant patients were higher than those of platinum-sensitive patients (P < 0.05, P < 0.01). The 5-year survival rates of resistant, partially sensitive and sensitive patients were 9.5%, 38.4% and 81.9% respectively. There were statistics differences in overall survival and progression-free survival among the 3 groups (P < 0.01). CONCLUSION: Advanced ovarian cancer, poor differentiation, lymph node-positivity, CA125 rising above 1000 × 10(3) U/L and suboptimal cytoreductive surgery would lead to the occurrences of resistance or partially sensitivity. Clinical factors have some reference values for the prediction of resistance. But it is impossible to accurately determine chemoresistance.