ABSTRACT
Embryo quality is a critical determinant of clinical outcomes in assisted reproductive technology (ART). A recent clinical trial investigating preimplantation DNA methylation screening (PIMS) revealed that whole genome DNA methylation level is a novel biomarker for assessing ART embryo quality. Here, we reinforced and estimated the clinical efficacy of PIMS. We introduce PIMS-AI, an innovative artificial intelligence (AI) based model, to predict the probability of an embryo producing live birth and subsequently assist ART embryo selection. Our model demonstrated robust performance, achieving an area under the curve (AUC) of 0.90 in cross-validation and 0.80 in independent testing. In simulated embryo selection, PIMS-AI attained an accuracy of 81% in identifying viable embryos for patients. Notably, PIMS-AI offers significant advantages over conventional preimplantation genetic testing for aneuploidy (PGT-A), including enhanced embryo discriminability and the potential to benefit a broader patient population. In conclusion, our approach holds substantial promise for clinical application and has the potential to significantly improve the ART success rate.
ABSTRACT
BACKGROUND: Preoperative anemia is an important pillar of perioperative patient blood management. However, there was no literature comprehensively described the current situation of preoperative anemia in China. METHODS: We conducted a national retrospective cross-sectional study to assess the prevalence and intervention of preoperative anemia in Chinese adults. Data were from the National Preoperative Anemia Database based on hospital administration data from January 1, 2013 to December 31, 2018. FINDINGS: A total of 797,002 patients were included for analysis. Overall, 27.57% (95% CI 27.47-27.67) of patients had preoperative anemia, which varied by gender, age, regions, and type of operation. Patients who were female, age over 60 years old, from South China, from provinces with lower per capita GDP, underwent operations on the lymphatic and hematopoietic system, with laboratory abnormalities were more likely to have a high risk of preoperative anemia. Among patients with preoperative anemia, 5.16% (95% CI 5.07-5.26) received red blood cell transfusion, 7.79% (95% CI 7.67-7.91) received anemia-related medications such as iron, erythropoietin, folic acid or vitamin B12, and 12.25% (95% CI 12.10-12.40) received anemia-related therapy (red blood cell transfusion or anemia-related medications) before operation. The probability of preoperative RBC transfusion decreased by 54.92% (OR 0.46, 95% CI 0.46-0.47) as each 10-g/L increase in preoperative hemoglobin. Patients with preoperative hemoglobin less than 130 g/L was associated with longer hospital stay and more hospital costs. Patients with severe preoperative anemia given iron preoperatively had lower intra/post-operative RBC transfusion rate, shorter length of stay and less hospitalization costs, but no similar correlation was found in patients with mild and moderate preoperative anemia and patients given erythropoietin preoperatively. INTERPRETATION: Our present study shows that preoperative anemia is currently a relatively prevalent problem that has not been fully appreciated in China. More researches will be required to optimize the treatment of preoperative anemia. FUNDING: National Natural Science Foundation of China and the Logistics Support Department of the Central Military Commission.
ABSTRACT
Cervical cancer is currently one of the major threats to women's health. The overexpression of heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as the biomarker has been investigated in various cancers. In our previous study, we found that lobaplatin induced apoptosis and cell cycle arrest via downregulation of proteins including hnRNP A2/B1 in cervical cancer cells. However, the underlying relationship between hnRNP A2/B1 and cervical cancer remained largely unknown. hnRNP A2/B1 knockdown in HeLa and CaSki cells was performed by shRNA transfection. The expression of hnRNP A2/B1 was detected by western blot and Quantitative Realtime PCR. Cell proliferation, migration, invasion and the IC50 of lobaplatin and irinotecan were determined by MTT assay, Transwell assay, Plate colony formation assay and wound healing assay. Flow cytometry was perfomed to investigate cell apoptosis and the cell cycle. The expression of PI3K, AKT, pAKT, p21, p27, caspase3, cleaved caspase3 were revealed by western blot. Nude mouse xenograft model was undertaken with HeLa cells and the xenograft tumor tissue samples were analyzed for the expression of PCNA and Ki67 by immunohistochemistry and the cell morphology was evaluated by hematoxylin and eosin (H&E). Results revealed that hnRNP A2/B1 was successfully silenced in HeLa and CaSki cells. hnRNP A2/B1 knockdown significantly induced the suppression of proliferation, migration, invasion and also enhancement of apoptosis and reduced the IC50 of lobaplatin and irinotecan. The expression of p21, p27 and cleaved caspase3 in shRNA group were significantly upregulated and the expression of pAKT was reduced both in vitro and in vivo. The results of immunohistochemistry showed that PCNA and Ki67 were significantly downregulated in vivo. The growth of nude mouse xenograft tumor was significantly reduced by hnRNP A2/B1 knockdown. Taken together, these data indicate that inhibition of hnRNP A2/B1 in cervical cancer cells can inhibit cell proliferation and invasion, induce cellcycle arrestment and trigger apoptosis via PI3K/AKT signaling pathway. In addition, after silencing hnRNP A2/B1 can increase the sensitivity of cervical cancer cells to lobaplatin and irinotecan.
