Optimizing FSH Concentration Modulation in the Short-Acting GnRH-a Long Protocol for IVF/ICSI: A Retrospective Study.

INTRODUCTION: Exogenous gonadotropin (Gn) is given to regulate follicle-stimulating hormone (FSH) levels to achieve optimal ovarian response in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The objective of this study was to analyze the optimal degree of change in FSH blood concentration with ovarian responsiveness in a short-acting gonadotropin-releasing hormone agonist (GnRH-a) long protocol for IVF/ICSI. METHODS: This retrospective study was conducted at Changzhou Maternity and Child Health Hospital's Reproductive Center from May 2017 to May 2023. A total of 794 ovarian stimulation cycles for IVF/ICSI using the short-acting GnRH-a long protocol was included. Ovarian responsiveness was assessed based on the number of follicles > 14 mm on human chorionic gonadotropin (HCG) trigger day, refine-follicular output rate (Refine-FORT) and good quality embryos. Delta 1 referred to the change in FSH level between days 6-8 of gonadotropin usage and baseline FSH, while Delta 2 referred to the change in FSH level between HCG trigger day and days 6-8 of gonadotropin usage. Simple and multiple linear regression analysis were performed to adjust for confounding factors. RESULTS: The number of follicles > 14 mm on HCG trigger day was found to be the most suitable indicator for evaluating ovarian responsiveness compared to the number of follicles > 16 mm and the number of retrieved oocytes. When Delta 1 ranged from 1.94 to 3.37, the number of follicles > 14 mm on HCG trigger day was the highest. When Delta 1 ranged from 3.37 to 5.90, the Refine-FORT was the highest. However, when Delta 1 exceeded 5.90, the number of follicles > 14 mm on HCG trigger day, Refine-FORT and good quality embryo all significantly decreased. On the other hand, when Delta 2 was ≤ - 1.58, the number of follicles > 14 mm on HCG trigger day and the Refine-FORT were both the highest. CONCLUSION: This study identifies optimal Delta 1 and Delta 2 ranges for effective ovarian responsiveness in a short-acting GnRH-a long protocol for IVF/ICSI and introduces the novel measure of the number of follicles > 14 mm on HCG trigger day. The optimal range for Delta 1 was 1.94 to 3.37, and Delta 2 should be < - 1.58 for achieving a higher number and quality of oocytes.

Experimental Study on the Dry Drilling Nickel-Based Superalloy of CrAlYN Coated Carbide Bit.

Nickel-based superalloy is regarded as one of the materials with the poorest cutting and drilling performance. Additionally, there is much less research on the drilling of it. This paper aims to study the drilling performance of dry drilling nickel-based superalloy with uncoated and CrAlYN coated carbide bit. First of all, the primary and secondary factors influencing the machining performance of dry drilling nickel-base superalloy uncoated carbide bit were explored through an orthogonal test. Secondly, the self-prepared CrAlYN coated carbide drills, and uncoated drills were compared and analyzed from perspectives of service life, drilling force, drilling temperature, drill surface topography, failure mechanism, and machining surface quality. The research results are as follows: the drilling temperature is the primary factor affecting the drilling performance under dry drilling conditions. CrAlYN coating can obviously prolong the service life of tools, reduce the drilling force and drilling temperature, and improve the machining surface quality at lower rotational speeds. Moreover, the coated cemented carbide bit has a similar failure mode to the uncoated cemented carbide bit after the CrAlYN coating falls off in the wear zone of cemented carbide bit, which is mainly bonding wear on the rear tool surface and the front tool surface.

Diagnosis and functional prediction of microbial markers in tumor tissues of sporadic colorectal cancer patients associated with the MLH1 protein phenotype.

Objective: Most patients with sporadic colorectal cancer (SCRC) develop microsatellite instability because of defects in mismatch repair (MMR). Moreover, the gut microbiome plays a vital role in the pathogenesis of SCRC. In this study, we assessed the microbial composition and diversity of SCRC tumors with varying MutL protein homolog 1 (MLH1) status, and the effects of functional genes related to bacterial markers and clinical diagnostic prediction. Methods: The tumor microbial diversity and composition were profiled using high-throughput sequencing of the 16S ribosomal RNA (rRNA) gene V4 region. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) software and BugBase tool were used to predict the functional roles of the microbiome. We aimed to construct a high-accuracy model to detect and evaluate the area under the receiver operating characteristic curve with candidate biomarkers. Results: The study included 23 patients with negative/defective MLH1 (DM group) and 22 patients with positive/intact MLH1 (IM group). Estimation of alpha diversity indices showed that the Shannon index (p = 0.049) was significantly higher in the DM group than in the controls, while the Simpson index (p = 0.025) was significantly lower. At the genus level, we observed a significant difference in beta diversity in the DM group versus the IM group. Moreover, the abundance of Lachnoclostridium spp. and Coprococcus spp. was significantly more enriched in the DM group than in the IM group (q < 0.01 vs. q < 0.001). When predicting metagenomes, there were 18 Kyoto Encyclopedia of Genes and Genomes pathways and one BugBase function difference in both groups (all q < 0.05). On the basis of the model of diagnostic prediction, we built a simplified optimal model through stepwise selection, consisting of the top two bacterial candidate markers (area under the curve = 0.93). Conclusion: In conclusion, the genera Lachnoclostridium and Coprococcus as key species may be crucial biomarkers for non-invasive diagnostic prediction of DM in patients with SCRC in the future.

MicroRNA-21 Regulates PI3K/Akt/mTOR Signaling by Targeting TGFßI during Skeletal Muscle Development in Pigs.

MicroRNAs (miRNAs), which are short (22-24 base pairs), non-coding RNAs, play critical roles in myogenesis. Using Solexa deep sequencing, we detected the expression levels of 229 and 209 miRNAs in swine skeletal muscle at 90 days post-coitus (E90) and 100 days postnatal (D100), respectively. A total of 138 miRNAs were up-regulated on E90, and 31 were up-regulated on D100. Of these, 9 miRNAs were selected for the validation of the small RNA libraries by quantitative RT-PCR (RT-qPCR). We found that miRNA-21 was down-regulated by 17-fold on D100 (P<0.001). Bioinformatics analysis suggested that the transforming growth factor beta-induced (TGFßI) gene was a potential target of miRNA-21. Both dual luciferase reporter assays and western blotting demonstrated that the TGFßI gene was regulated by miRNA-21. Co-expression analysis revealed that the mRNA expression levels of miRNA-21 and TGFßI were negatively correlated (r = -0.421, P = 0.026) in skeletal muscle during the 28 developmental stages. Our results revealed that more miRNAs are expressed in prenatal than in postnatal skeletal muscle. The miRNA-21 is a novel myogenic miRNA that is involved in skeletal muscle development and regulates PI3K/Akt/mTOR signaling by targeting the TGFßI gene.