Human blastocysts are comprised of the first three cell lineages of the embryo: trophectoderm, epiblast and primitive endoderm, all of which are essential for early development and organ formation. However, due to ethical concerns and restricted access to human blastocysts, a comprehensive understanding of early human embryogenesis is still lacking. To bridge this knowledge gap, a reliable model system that recapitulates early stages of human embryogenesis is needed. Here we developed a three-dimensional (3D), two-step induction protocol for generating blastocyst-like structures (EPS-blastoids) from human extended pluripotent stem (EPS) cells. Morphological and single-cell transcriptomic analyses revealed that EPS-blastoids contain key cell lineages and are transcriptionally similar to human blastocysts. Furthermore, EPS-blastoids are similar with human embryos that were cultured for 8 or 10 days in vitro, in terms of embryonic structures, cell lineages and transcriptomic profiles. In conclusion, we developed a scalable system to mimic human blastocyst development, which can potentially facilitate the study of early implantation failure that induced by developmental defects at early stage.

IntroductionThe efficacy of long-term noninvasive positive pressure ventilation (NPPV) in stable hypercapnic COPD patients with respiratory failure remains unclear. The aim of this meta-analysis was to critically assess the efficacy of long-term NPPV on mortality, acute exacerbation, exercise capacity, symptoms and significant physiological parameters (lung function, respiratory muscle function and gas exchange).Patients and methodsWe performed an electronic literature search using the PubMed, Cochrane Library, Embase, OVID and Chinese Biomedical Literature Database in May 2017. Studies comparing treatment effects of NPPV with oxygen therapy in stable hypercapnic COPD patients with respiratory failure were conducted, and at least one of the following parameters were reviewed: frequency of acute exacerbation, mortality, lung function, respiratory muscle function, gas exchange, exercise capacity.ResultsSeven studies with 810 subjects were identified. The partial pressure of arterial carbon dioxide (PaCO2) significantly decreased in patients who received long-term NPPV (weighted mean difference [WMD] −3.73, 95% CI: −5.83 to −1.64, P=0.0005). No significant difference was found in mortality, partial pressure of arterial oxygen (PaO2), frequency of acute exacerbation, lung function, respiratory muscle function and exercise capacity. The subgroup analysis showed that NPPV significantly improved the survival of patients when it was targeted at greatly reducing hypercapnia (WMD 0.35, 95% CI: 0.19 to 0.64, P=0.0006).ConclusionThe results indicate that long-term NPPV decreases the PaCO2 of stable hypercapnic COPD patients with respiratory failure and improves mortality with the aim of reducing PaCO2.

Endocrine therapy is the main treatment option for estrogen receptor-positive (ER+) breast cancer (BC). Compared with other clinical subtypes, ER+ BC patients usually have a more favorable prognosis. However, almost all ER+ BCpatients develop endocrine resistance and disease progression eventually. A large number of studies based on liquid biopsy suggest that ESR1 mutations may play a key role in this process. For patients with ER+ metastatic BC (MBC), ESR1 is an important prognostic factor and may associate with the resistance to endocrine therapy, like aromatase inhibitors. The advances of sequencing technologies allow us to conduct longitudinal monitoring of disease and unveil the clinical implications of each ESR1 sub-clone in ER+ MBC. Moreover, since the ESR1-related endocrine resistance has not been fully addressed by existing agents, more potent cornerstone drugs should be developed as soon as possible. Herein, we reviewed the recent progress of detecting ESR1 mutations based on liquid biopsy and different sequencing technologies in ER+ MBC and discussed its clinical impacts and prospects.

PurposeTo compare the efficacy and safety between pyrotinib (Pyr) and trastuzumab emtansine (T-DM1) in pre-treated human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) patients.MethodsA comprehensive literature search of the PubMed, EMBASE, and Web of Science was performed in August 2020. Randomized clinical trials comparing the efficacy and safety between different anti-HER2 regimens in patients pre-treated with trastuzumab (Tra) and a taxane in metastatic settings (≤second-line treatment) were included. A fixed effects network meta-analysis based on the Bayesian inferential framework was conducted for progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grade ≥3 adverse events (AEs). Values of surface under cumulative ranking probability curve (SUCRA) were calculated to offer a ranking of all regimens.ResultsTwelve studies with 4,353 subjects were identified. Nine regimens were included into the network: T-DM1, lapatinib-capecitabine (Lap-Cap), Tra-Cap, Cap, neratinib (Ner), pertuzumab (Per)-Tra-Cap, Pyr-Cap, atezolizumab (Ate)-T-DM1, and Ner-Cap. For PFS, Pyr-Cap was more favorable than T-DM1 (hazard ratio, 95% confidence interval: 0.77, 0.70–0.86), Lap-Cap (0.64, 0.59–0.69), Tra-Cap (0.63, 0.56–0.70), Cap (0.50, 0.45–0.56), Ner (0.59, 0.51–0.69), Per-Tra-Cap (0.68, 0.59–0.79), and Ner-Cap (0.72, 0.64–0.81). For OS, Pyr-Cap showed further improvement than Lap-Cap (hazard ratio, 95% confidence interval: 0.71, 0.52–0.99), Cap (0.68, 0.49–0.96), and Ner (0.65, 0.45–0.94). For ORR, Pyr-Cap was significantly superior than Cap (odds ratio, 95% confidence interval: 7.87, 1.22–56.51). No significant difference was observed in grade ≥3 AEs among all the regimens. Pyr-Cap ranked in the highest in PFS, OS, ORR, and grade ≥3 AEs (SUCRA = 99.4, 89.7, 86.4, and 89.3%).ConclusionsThese results indicate that Pyr may be more effective than T-DM1 in HER2+ MBC patients pre-treated with Tra and a taxane. However, it may be associated with more grade ≥3 AEs.