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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]

Objective: To investigate the differences in myopia prevalence and ocular biometry in children and adolescents in Chongqing and Tibet, China., Design: Cross-sectional study., Setting: The study included children and adolescents aged 6-18 years in Chongqing, a low-altitude region, and in Qamdo, a high-altitude region of Tibet., Participants: A total of 448 participants in Qamdo, Tibet, and 748 participants in Chongqing were enrolled in this study., Methods: All participants underwent uncorrected visual acuity assessment, non-cycloplegic refraction, axial length (AL) measurement, intraocular pressure (IOP) measurement and corneal tomography. And the participants were grouped according to age (6-8, 9-11, 12-14 and 15-18 years group), and altitude of location (primary school students: group A (average altitude: 325 m), group B (average altitude: 2300 m), group C (average altitude: 3250 and 3170 m) and group D (average altitude: 3870 m))., Results: There was no statistical difference in mean age (12.09±3.15 vs 12.2±3.10, p=0.549) and sex distribution (males, 50.4% vs 47.6%, p=0.339) between the two groups. The Tibet group presented greater spherical equivalent (SE, -0.63 (-2.00, 0.13) vs -0.88 (-2.88, -0.13), p<0.001), shorter AL (23.45±1.02 vs 23.92±1.19, p<0.001), lower prevalence of myopia (39.7% vs 47.6%, p=0.008) and flatter mean curvature power of the cornea (Km, 43.06±1.4 vs 43.26±1.36, p=0.014) than the Chongqing group. Further analysis based on age subgroups revealed that the Tibet group had a lower prevalence of myopia and higher SE in the 12-14, and 15-18 years old groups, shorter AL in the 9-11, 12-14 and 15-18 years old groups, and lower AL to corneal radius of curvature ratio (AL/CR) in all age subgroups compared with the Chongqing group, while Km was similar between the two groups in each age subgroup. Simple linear regression analysis showed that SE decreased with age in both the Tibet and Chongqing groups, with the Tibet group exhibiting a slower rate of decrease (p<0.001). AL and AL/CR increased with age in both the Tibet and Chongqing groups, but the rate of increase was slower in the Tibet group (p<0.001 of both). Multiple linear regression analysis revealed that AL had the greatest effect on SE in both groups, followed by Km. In addition, the children and adolescents in Tibet presented thinner corneal thickness (CCT, p<0.001), smaller white to white distance (WTW, p<0.001), lower IOP (p<0.001) and deeper anterior chamber depth (ACD, p=0.015) than in Chongqing. Comparison of altitude subgroups showed that the prevalence of myopia (p=0.002), SE (p=0.031), AL (p=0.001) and AL/CR (p<0.001) of children at different altitudes was statistically different but the Km (p=0.189) were similar. The highest altitude, Tengchen County, exhibited the lowest prevalence of myopia and greatest SE among children, and the mean AL also decreased with increasing altitude., Conclusions: Myopia prevalence in Tibet was comparable with that in Chongqing for students aged 6-8 and 9-11 years but was lower and myopia progressed more slowly for students aged 12-14 and 15-18 years than in Chongqing, and AL was the main contributor for this difference, which may be related to higher ultraviolet radiation exposure and lower IOP in children and adolescents at high altitude in Tibet. Differences in AL and AL/CR between Tibet and Chongqing children and adolescents manifested earlier than in SE, underscoring the importance of AL measurement in myopia screening., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

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., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)