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Objective: To investigate whether letrozole pre‐treatment is non‐inferior to mifepristone pre‐treatment, followed by misoprostol, for complete evacuation in the medical treatment of first‐trimester missed miscarriage. Design: Prospective open‐label non‐inferiority randomised controlled trial. Setting: A university‐affiliated hospital. Population: We recruited 294 women diagnosed with first‐trimester missed miscarriage who opted for medical treatment. Methods: Participants were randomly assigned to: (i) the mifepristone group, who received 200 mg mifepristone orally followed 24–48 h later by 800 μg misoprostol vaginally; or (ii) the letrozole group, who received 10 mg letrozole orally once‐a‐day for 3 days, followed by 800 μg misoprostol vaginally on the third (i.e. last) day of letrozole administration. Main outcome measures: The primary outcome was the rate of complete evacuation without surgical intervention at 42 days post‐treatment. Secondary outcomes included induction‐to‐expulsion interval, adverse effects, women's satisfaction, number of doses of misoprostol required, duration of vaginal bleeding, pain score on the day of misoprostol administration and other adverse events. Results: The complete evacuation rates were 97.8% (95% CI 95.1%–100%) and 97.2% (95% CI 94.4%–99.9%) in the letrozole and mifepristone groups, respectively (p ≤ 0.001 for non‐inferiority). The mean induction‐to‐tissue expulsion interval in the letrozole group was longer compared with the mifepristone group (15.4 vs 9.0 h) (p = 0.03). The letrozole group had less heavy post‐treatment bleeding and an earlier return of menses. There were no statistically significant differences in the number of doses of misoprostol required, the duration of vaginal bleeding, the pain score on the day of misoprostol administration and the rate of other adverse events between the two groups. The majority of the women (91.2% and 93.9% in the letrozole and mifepristone groups, respectively) were satisfied with their treatment option. Conclusions: Letrozole is non‐inferior to mifepristone as a pre‐treatment, followed by misoprostol, for the medical treatment of first‐trimester missed miscarriage. [ABSTRACT FROM AUTHOR]

Statistic distribution of fatigue life data and its controls of cast Ti-47.5Al-2.5V-1.0Cr-0.2Zr (atom fraction/%) alloy were investigated. Fatigue tests were operated by means of load-controlled rotating bending fatigue tests (R=-1) performed at a frequency of 100 Hz at 750 ℃ in air. The fracture mechanism was analyzed by observing the fracture surface morphologies through scanning electron microscope,and the achieved fatigue life data were analyzed by Weibull statistics. The results show that the fatigue life data present a remarkable scatter ranging from 103 to 106 cycles, and distribute mainly in short and long life regime. The reason for this phenomenon is that the fatigue crack initiators are different with different specimens. The crack initiators for short-life specimens are caused by shrinkage porosity, and for long-life ones are caused by bridged porosity interface and soft-oriented lamellar interface. Based on the observation results of fracture surface, two-parameter Weibull distribution model for fatigue life data can be used for the prediction of fatigue life at a certain failure probability. It has also shown that the shrinkage porosity causes the most detrimental effect to fatigue life.

Background and Aim: Liver cancer stem cells (LCSCs) cause therapeutic refractoriness and relapse in hepatocellular carcinoma. Heat shock factor 1 (HSF1) plays versatile roles in multiple cancers. However, the role of HSF1 in LCSCs is not well understood. This study investigated the function and signal mechanisms of HSF1 in maintaining LCSC phenotypes. Methods: We established two LCSC lines, HepG2‐R and HuH‐7‐R. Constitutive activation of HSF1 was observed in these LCSCs. Specific short hairpin RNAs (shRNAs) and chemical inhibitors were used to identify the relationship between HSF1 expression and LCSCs phenotypes. Results: We revealed a concomitant activation modality involving HSF1 and STAT3 in LCSCs and liver cancer tissues. We also found that liver cancer patients whose HSF1 and STAT3 mRNA expression levels were high presented with unfavorable clinicopathological characteristics. Moreover, the secretion of interleukin‐8 (IL‐8) was elevated in the LCSC medium and was directly regulated by HSF1 at the transcriptional level. In turn, IL‐8 activated HSF1 and STAT3 signaling, and a neutralizing IL‐8 antibody inhibited HSF1 and STAT3 activity, reduced cancer stem cell marker expression, and decreased LCSC microsphere formation. Simultaneous intervention with HSF1 and STAT3 led to synergistically suppressed stemness acquisition and growth suppression in the LCSCs in vivo and in vitro. Conclusions: Our study indicates that IL‐8 mediates the crosstalk between the HSF1 and Stat3 signaling pathways in LCSCs and that the combined targeting of HSF1 and STAT3 is a promising treatment strategy for patients with advanced liver cancer. [ABSTRACT FROM AUTHOR]