[The prognostic value of free triiodothyronine/free thyroxine ratio in patients hospitalized with heart failure].

Objective: To investigate the effect of free triiodothyronine/free thyroxine (FT3/FT4) ratio on the prognosis of patients with heart failure (HF). Methods: A total of 3 527 patients hospitalized in the Heart Failure Center of Fuwai Hospital from March 2009 to June 2018 were analyzed in our study. Patients were divided into two groups according to median of FT3/FT4 ratio: low FT3/FT4 group (n=1 764, FT3/FT4<2.15) and high FT3/FT4 group (n=1 763, FT3/FT4≥2.15). The primary endpoint was defined as a composite endpoint of all-cause death or heart transplantation or implantation of a left ventricular assist device. The baseline characteristics of patients with different FT3/FT4 ratio groups were compared, and a multivariate Cox proportional hazard regression model was used to analyze the relationship between FT3/FT4 ratio and the prognosis of hospitalized patients with HF. Results: The age of the total population was (56.8±16.0) years, and 2 544 cases (72.1%) were males. The median follow-up time was 2.79 (1.00, 5.03) years, and a total of 1 542 end-point events were recorded at the final follow-up. The mean ages of patients in the low FT3/FT4 group and high FT3/FT4 group were (58.8±16.5) and (54.8±15.2) years (P<0.001), respectively; and the cumulative survival rates were 38.4% and 61.9%, respectively (P<0.001). FT3 (HR=0.72, 95%CI: 0.63-0.84, P<0.001), FT3/FT4 (HR=0.76, 95%CI: 0.65-0.87, P<0.001) was associated with all-cause death, heart transplantation, or LVAD implantation in patients with heart failure. HR values (95%CI) of FT3/FT4 ratio predicting the risk of composite endpoint in the subgroup of left ventricular ejection fraction (LVEF)<40%, 40% to 49%, and≥50% were 0.91 (0.77-1.08), 0.83 (0.50-1.39), and 0.65 (0.50-0.85), respectively (P interaction=0.045). Conclusions: Low FT3 and low FT3/FT4 are important correlative factors for poor prognosis in hospitalized HF patients, especially in patients with LVEF≥50%.

[Clinical features and prognosis of patients hospitalized with heart failure and low T3 syndrome].

Objective: To investigate the association between triiodothyronine (T3) and inflammatory factors, and its potential effect on long-term outcomes in hospitalized patients with heart failure (HF). Methods: A total of 2 475 patients with HF admitted in Heart Failure Care Unit were consecutively enrolled in this retrospective cohort study from December 2006 to June 2018. Patients were divided into low T3 syndrome group (n=610, 24.6%) and normal thyroid function group (n=1 865, 75.4%). The median follow-up time was 2.9 (1.0, 5.0) years. A total of 1 048 all-cause deaths were recorded at the final follow-up. The effects of free T3 (FT3) and high-sensitivity C-reactive protein (hsCRP) on the risk of all-cause death were evaluated by Cox regression analysis and Kaplan-Meier analysis. Results: The age of the total population was 19-95 (57±16) years, 1 823 cases (73.7%) were male. Compared to those with normal thyroid function, albumin [(36.5±5.4) vs. (40.7±4.7) g/L], hemoglobin [(129.4±25.1) vs. (140.6±20.6) g/L], total cholesterol [3.6 (3.0, 4.4) vs. 4.2 (3.5, 4.9) mmol/L] (all P<0.001) were lower, Whereas age [(60.5±16.0) vs. (55.2±15.4) years], creatinine [105.0 (83.6, 137.0) vs. 87.8 (75.6, 106.3) mmol/L], log N-terminal B-type natriuretic peptide [(8.2±1.3) vs. (7.2±1.4) ng/L] were higher in LT3S patients (all P<0.001). In Kaplan-Meier survival analysis, patients with lower FT3 and higher hsCRP had significantly lower cumulative survival (P<0.001), lower FT3 combined with higher hsCRP subgroup had the highest risk of all-cause death (Ptrend<0.001). In multivariate Cox regression analysis, LT3S was an independent predictor of all-cause mortality (HR=1.40, 95%CI 1.16-1.69, P<0.001). Conclusion: LT3S is an independent predictor of poor prognosis in patients with heart failure. FT3 combined with hsCRP improve the predictive value of all-cause death in hospitalized patients with heart failure.

miR-34b inhibits the migration/invasion and promotes apoptosis of non-small-cell lung cancer cells by YAF2.

OBJECTIVE: Lung cancer is the leading cause of cancer death in the world and microRNAs (miRNA) have been found to be involved in the initiation and development of cancer by acting as potential oncogenes or tumor suppressor genes. PATIENTS AND METHODS: In this study, we investigated the expression of miR-34b in non-small cell lung cancer (NSCLC) patients and discussed the molecular mechanism of miR-34b in the invasion and migration of A549 cells in vitro. RESULTS: Our results showed that miR-34b was significantly down-regulated in primary cancer tissues when compared with the normal lung tissues. The over-expression of miR-34b inhibited migration and invasion, and promoted apoptosis of A549 lung cancer cells. Furthermore, Luciferase reporter assay validated YY1-associated factor 2 (YAF2) as a direct target of miR-34b and YAF2 expression was significantly increased in clinical NSCLC tissue samples. In addition, the over-expression of miR-34b inhibited YAF2, p-Jak2, p-STAT3 and MMP2 protein expression and promoted caspase 3 protein expression in cancer cells. CONCLUSIONS: Our results suggest that miR-34b may inhibit migration and invasion of NSCLC cells by targeting YAF2. Thus, our findings provide new insight into the molecular mechanisms of lung cancer metastasis and miR-34b may serve as a potential target in the treatment of human lung cancer.

[The therapeutic effect of HSV1-hGM-CSF combined with doxorubicin on the mouse breast cancer model].

Objective: To evaluate the oncolytic effect of herpes simplex virus type 1 which carried recombined human granulocyte-macrophage colony-stimulating factor (HSV1-hGM-CSF) on the mouse breast cancer cell line 4T1 and compare the anticancer effects of HSV1-hGM-CSF, doxorubicin alone or combination on the breast cancer in mice. Methods: We investigated the cytotoxic effect on 4T1 cells in vitro, the cell growth, cell apoptosis and cell cycle of 4T1 cells treated with oncolytic HSV1-hGM-CSF at different MOIs (0, 0.5, 1 and 2) and doxorubicin at different concentrations (0, 2, 4 and 8 µg/ml). The effects of oncolytic HSV1-hGM-CSF and doxorubicin on the tumor growth, survival time and their side effects on the mouse breast cancer model were observed. Results: Both oncolytic HSV1-hGM-CSF and doxorubicin significantly inhibited the proliferation of 4T1 cells in vitro. Doxorubicin induced the G(2)/M phase arrest of 4T1 cells, while the cytotoxicity of oncolytic HSV1-hGM-CSF was no cell cycle-dependent.At day 16 after treatment with doxorubicin and HSV1-hGM-CSF, the tumor volume of 4T1 tumor bearing mice were (144.40±27.68)mm(3,) (216.80±57.18)mm(3,) (246.10±21.90)mm(3,) (327.50±44.24)mm(3,) (213.30±32.31)mm(3) and (495.80±75.87)mm(3) in the groups of doxorubicin combined with high dose HSV1-hGM-CSF, doxorubicin combined with low dose HSV1-hGM-CSF, doxorubicin alone, high dose HSV1-hGM-CSF alone, low dose HSV1-hGM-CSF alone and control, respectively.Compared with the control group, both doxorubicin and HSV1-hGM-CSF treatment exhibited significant reduction of primary tumor volume in vivo (P<0.001). The median survival times were 48, 50, 40, 42, 43 and 37 days in the six groups mentioned above, respectively. The median survival period of doxorubicin alone, high dose HSV1-hGM-CSF alone and low dose HSV1-hGM-CSF alone were significantly longer than that of control (P<0.05). Conclusion: Synergistic effect of sequential treatment with doxorubicin and oncolytic HSV1-hGM-CSF is observed in 4T1 mouse breast cancer.

Distinctive effects of carvedilol in the non-infarct zone: remodelling of the ligated rat heart linked to oxidative stress.

In this study, an experimental rat ligated heart model was used to observe the effect of treatment with carvedilol, metoprolol and metoprolol plus a highly selective alpha(1)-adrenergic blocking agent, bunazosin, after acute myocardial infarction (MI). Compared with an untreated MI group, all drug-treated groups demonstrated attenuation of inflammatory mediators, activation of nuclear factor-kappaB (NF-kappaB), and increased levels of mRNA and active protein for the collagenases matrix metallopeptidase (MMP)-8 and MMP-13 in the non-infarct zone of the ventricle, as well as inhibition of the increase of left ventricular end-diastolic pressure. Supplementation of metoprolol with bunazosin did not add greatly to the effects of metoprolol alone. Of the three drug treatments, carvedilol showed a uniquely potent antioxidant activity that may strengthen its capacity to inhibit oxidative stress, the release of inflammatory mediators and activation of NF-kappaB. This study may help provide a mechanistic explanation for the greater benefits shown by carvedilol compared with metoprolol in treating heart failure.