The prognostic value of preoperative systemic inflammatory response index in predicting outcomes of acute type A aortic dissection patients underwent surgical treatment.

Background: The systemic inflammatory response index (SIRI) is a novel inflammatory-immune biological marker that has prognostic value in various cardiovascular diseases. This study aims to investigate the relationship between SIRI and short-term and long-term prognosis in patients with acute type A aortic dissection (AAAD) underwent surgical treatment. Methods: We conducted a retrospective analysis of patients with AAAD who underwent emergency surgical treatment at our center. Through multifactorial logistics regression analysis and cox proportional hazards regression analysis, we identified SIRI as an independent risk factor for major adverse events (MAEs) and long-term aorta-related adverse events (ARAEs) post-surgery. The optimal cutoff value of preoperative SIRI was determined using receiver operating characteristic (ROC) curve analysis, and patients were divided into low SIRI group and high SIRI group. The prognostic outcomes at different time points post-surgery for the two groups of patients were analyzed using Kaplan-Meier survival analysis, and the significance was determined by log-rank test. Results: A total of 691 AAAD patients were included in this study. Among them, 50 patients (7.2%) died within 30 days post-surgery, and 175 patients (25.3%) experienced MAEs. A total of 641 patients were followed up, with an average follow-up time of 33.5 ± 17.5 months, during which 113 patients (17.6%) experienced ARAEs. The results of multifactorial logistics regression analysis and cox proportional hazards regression analysis showed that SIRI was an independent risk factor for postoperative MAEs (OR=3.148, 95%CI[1.650-6.006], p<0.001) and ARAEs (HR=2.248, 95%CI[1.050-4.809], p<0.037). Kaplan-Meier analysis demonstrated that the MAEs-free survival in the high SIRI group was significantly lower than that in the low SIRI group, and a similar trend was observed in the ARAEs-free survival during follow-up (log-rank test, p<0.001). Conclusion: Preoperative SIRI is significantly associated with the short-term and long-term prognosis of AAAD patients underwent emergency open surgery, demonstrating its valuable prognostic value. Therefore, preoperative SIRI is a reliable biological marker that can serve as a valuable tool for preoperative risk stratification and decision management.

Changes in the Mitochondria-Related Nuclear Gene Expression Profile during Human Oocyte Maturation by the IVM Technique.

To address which mitochondria-related nuclear differentially expressed genes (DEGs) and related pathways are altered during human oocyte maturation, single-cell analysis was performed in three oocyte states: in vivo matured (M-IVO), in vitro matured (M-IVT), and failed to mature in vitro (IM-IVT). There were 691 DEGs and 16 mitochondria-related DEGs in the comparison of M-IVT vs. IM-IVT oocytes, and 2281 DEGs and 160 mitochondria-related DEGs in the comparison of M-IVT vs. M-IVO oocytes, respectively. The GO and KEGG analyses showed that most of them were involved in pathways such as oxidative phosphorylation, pyruvate metabolism, peroxisome, and amino acid metabolism, i.e., valine, leucine, isoleucine, glycine, serine, and threonine metabolism or degradation. During the progress of oocyte maturation, the metabolic pathway, which derives the main source of ATP, shifted from glucose metabolism to pyruvate and fatty acid oxidation in order to maintain a low level of damaging reactive oxygen species (ROS) production. Although the immature oocytes could be cultured to a mature stage by an in vitro technique (IVM), there were still some differences in mitochondria-related regulations, which showed that the mitochondria were regulated by nuclear genes to compensate for their developmental needs. Meanwhile, the results indicated that the current IVM culture medium should be optimized to compensate for the special need for further development according to this disclosure, as it was a latent strategy to improve the effectiveness of the IVM procedure.

The impact of oral carbohydrate-rich supplement taken two hours before caesarean delivery on maternal and neonatal perioperative outcomes -- a randomized clinical trial.

BACKGROUND: To evaluate the impact of oral carbohydrate-rich (Ch-R) supplement taken 2 hours before an elective caesarean delivery (CD) on maternal and neonatal perioperative outcomes. METHODS: Ninety pregnant women undergoing elective CD were randomized into the Ch-R group, placebo group and fasting group equally. Participants' blood was drawn at three time points, before intervention, immediately after and 1 day after the surgery to measure maternal and neonatal biochemical indices. Meanwhile women's perioperative symptoms and signs were recorded. RESULTS: Eighty-eight pregnant women were finally included in the study. Women who had drunk Ch-R supplement had lower postoperative insulin level (ß = - 3.50, 95% CI - 5.45 to - 1.56), as well as postoperative HOMA-IR index (ß = - 0.74, 95% CI - 1.15 to - 0.34), compared with women who had fasted. Additionally, neonates of mothers who were allocated in the Ch-R group also had a higher glucose level, compared with neonates of mothers in the fasting group (ß = 0.40, CI 0.17 to 0.62). CONCLUSION: Oral Ch-R solution administered 2 hours before an elective CD may not only alleviate maternal postoperative insulin resistance, but also comfort women's preoperative thirst and hunger, compared to fasting. Additionally, it may increase neonatal glucose level as well. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000033163 . Data of Registration: 2020-5-22.

The effect of lysophosphatidic acid-supplemented culture medium on human immature oocytes matured in vitro.

BACKGROUND: Lysophosphatidic acid-supplemented culture medium significantly increases the oocyte maturation rate in vitro. However, potential targets and pathways involved remain unknown. METHODS: A total of 43 women, who underwent cesarean section and aged between 18 and 35 years with good health, were included in this study. Immature oocytes were obtained and cultured with 10 µM lysophosphatidic acid. After culture, oocyte maturation was assessed and oocytes and cumulus cells were collected for RNA sequencing. Hierarchical indexing for spliced alignment of transcripts 2 method was used to align clean reads to the human genome. The featureCounts and edgeR package were used to calculate gene expression and analyze differences between groups respectively. ClusterProfiler program was used to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. RESULTS: Oocyte maturation rate increased significantly following 48 h culture with lysophosphatidic acid. In cumulus cells, Gene Ontology analysis revealed the top 20 items enriched by upregulated genes and downregulated genes respectively; Kyoto Encyclopedia of Genes and Genomes analysis showed that upregulated genes in the treatment group were enriched in TNF signaling and insulin secretion pathways and downregulated genes were enriched in TNF signaling and cell adhesion molecules. In oocytes, Gene Ontology analysis revealed the top 20 items enriched by upregulated genes and downregulated genes respectively; Kyoto Encyclopedia of Genes and Genomes analysis showed that upregulated genes in the treatment group were enriched in MAPK signaling, gap junction, and cell cycle pathways and downregulated genes were enriched in MAPK signaling, estrogen signaling, RAP1 signaling, and gap junction pathways. CONCLUSIONS: Lysophosphatidic acid in culture medium enhances human oocyte maturation in vitro and the identified some potential pathways may associate with oocyte maturation.

Association of exosomal microRNAs in human ovarian follicular fluid with oocyte quality.

The postponement of childbearing by women has led to an increase in infertility. The reproductive aging process leads to a decrease in both the quantity and quality of oocytes. The aim of this study was to investigate exosomal microRNAs in human ovarian follicular fluid and explore their potential association with oocyte quality. We collected ovarian follicle fluid from 68 patients and assigned the patients to A (superior oocyte quality) or B (poor oocyte quality) group according to their oocyte quality. Exosomal miRNAs were extracted, library constructed and sequenced using the Illumina HiSeq platform. Subsequently, we analyzed exosomal miRNA expression, predicted the miRNA target genes, and enriched Gene Ontology terms using GOSeq. Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed using miRanda. A total of 47 miRNAs were found to be significantly differentially expressed between group A and group B (p < 0.05). Among nine differentially expressed miRNAs that were previously known, seven were upregulated in group B. In silico analysis indicated that several of these exosomal miRNAs were involved in pathways implicated in oocyte quality. Analysis of the expression of exosomal miRNAs in human ovarian follicular fluid showed that they were critical for maintaining oocyte quality. Our findings provide the basis for further investigations of the functions of exosomal miRNAs in the ovarian microenvironment and suggest that these exosomal miRNAs may be potential biomarkers for evaluating oocyte quality. The findings are potentially important to maintain oocyte quality in clinical settings.

The Integrated Analyses of Driver Genes Identify Key Biomarkers in Thyroid Cancer.

AIM: Thyroid cancer is the most common endocrine cancer, the incidence rate has continuously increased worldwide. However, there are still lack of effective molecular biomarkers for the diagnosis and treatment of the disease. The study was conducted to identify driver genes that may serve as potential biomarkers for the disease. METHODS: The computational tools oncodriveCLUST, oncodriveFM, icages and drgap were used to detect driver genes in thyroid cancer using somatic mutations from The Cancer Genome Atlas database. Integrated analyses were performed on the driver genes using multiomics data from the TCGA database. RESULTS: A set of 291 driver genes were identified in thyroid cancer. BRAF, NRAS, HRAS, OTUD4, EIF1AX were the top 5 frequently mutated genes in thyroid cancer. The weighted gene co-expression network analysis identified 4 coexpression modules. The modules 1-3 were significantly associated with patients' tumor size, residual tumor, cancer stage, distant metastasis and multifocality. SEC24B, MET and ITGAL were the hub genes in the modules 1-3 respectively. Hierarchical clustering analysis of the 20 driver genes with the most frequent copy number changes revealed 3 clusters of PRAD patients. Cluster 1 tumors exhibited significantly older age, tumor size, cancer stages, and poorer prognosis than cluster 2 and 3 tumors. 16 genes were significantly associated with number of lymph nodes, tumor size and pathologic stage, such as IL7 R, IRS1, PTK2B, MAP3K3 and FGFR2. CONCLUSIONS: The set of cancer genes and subgroups of patients shed insight on the tumorigenesis of thyroid cancer and open up avenues for developing prognostic biomarkers and driver gene-targeted therapies in thyroid cancer.

Single-cell multiomic analysis of in vivo and in vitro matured human oocytes.

STUDY QUESTION: Are there any differences between in vivo (IVV) and in vitro (IVT) matured metaphase II (MII) oocytes at the molecular level? SUMMARY ANSWER: Between IVV and IVT oocytes, 507 differentially expressed genes (DEGs) were identified; the non-CpG methylomes were significantly different, but the CpG methylomes and genomic copy number variations (CNVs) were similar. WHAT IS KNOWN ALREADY: A previous study using microarray and single-cell RNA-seq analysis revealed that numerous genes were differentially expressed between IVV and IVT oocytes. Independent studies of DNA methylation profiling in human oocytes have revealed negative correlations between gene transcription and the DNA methylation level at gene promoter regions. No study has compared global CpG or non-CpG methylation between these two groups of oocytes. Although a high level of aneuploidy has been reported in MII oocytes, no direct comparison of IVV and IVT oocytes based on single-cell sequencing data has been performed. STUDY DESIGN, SIZE, DURATION: We collected eight IVV oocytes from six patients and seven IVT oocytes from seven patients and then analysed each oocyte using the previously established single-cell triple omics sequencing (scTrioseq) analysis to determine associations among the transcriptome, DNA methylome and chromosome ploidy in the oocytes. PARTICIPANTS/MATERIALS, SETTING, METHODS: All IVV oocytes were donated by patients who received 150 IU gonadotropin per day from the third day of their menstrual cycle, followed by GnRH antagonist after 5 days of gonadotropin stimulation. All IVT oocytes were from immature oocytes which were donated by volunteers undergoing delivery by caesarean section then cultured in oocyte maturation medium containing 75 mIU/ml hMG for 24 to 48 h. Every single oocyte was analysed using the previously established single-cell multiomic sequencing analysis. MAIN RESULTS AND THE ROLE OF CHANCE: There were 507 genes differentially expressed between the IVV (n = 8) and IVT (n = 7) oocytes, even though their global transcriptome profiles were similar. The enriched genes in IVV oocytes were related to the cell cycle process while those in IVT oocytes were related to mitochondrial respiration biogenesis. Although the global CpG methylation of the two groups of oocytes was similar, the non-CpG methylation level in IVV oocytes was higher than that in IVT oocytes. A high aneuploidy ratio was found in both groups, but the aneuploidy did not affect transcription according to the correlation analysis. LARGE-SCALE DATA: N/A. LIMITATIONS AND REASONS FOR CAUTION: Due to the difficulty in collecting MII oocytes, especially IVV matured oocytes, the sample size was limited. WIDER IMPLICATIONS OF THE FINDINGS: Our findings indicate that single-cell multiomic sequencing can be utilised to examine the similarity and differences between IVV and IVT matured MII oocytes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Ministry of Science and Technology of China, National Key R&D Program of China (No. 2017YFC1001601). The donated oocytes were collected by Shanghai Tenth People's Hospital. The authors declare no competing interests.

Aspirin modulates STOX1 expression and reverses STOX1-induced insufficient proliferation and migration of trophoblast cells.

BACKGROUND: A major cause of preeclampsia is the placental ischemia caused by insufficient trophoblast cells, invading into the spiral artery. Storkhead-box protein 1 (STOX1) is highly associated with preeclampsia. Meanwhile, low-dose aspirin for patients with preeclampsia is effective in reducing the incidence of preeclampsia. The aim of the present study was to explore the underlying mechanism, and the relationship between STOX1 and aspirin in preeclampsia. METHODS: The human choriocarcinoma cell line JEG-3 was employed to mimic trophoblast cells and establish a model for trophoblast cells overexpressing STOX1 and knockdown of JEG cell lines, which were treated with aspirin afterwards. Cell counting kit-8 (CCK-8) assay was utilized to estimate cell proliferation and optimal concentration of aspirin for further experiments. Meanwhile, transwell assay was used to detect migration, and flow cytometry was used to measure apoptosis. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting were applied to analyze the expression levels of STOX1 and related genes. RESULTS: Overexpression of STOX1 inhibited proliferation of JEG-3 cells through epidermal growth factor (EGF), vascular EGF (VEGF), and transforming growth factor beta 1 (TGF-ß1) proteins, while suppressed migration through MMP2, MMP9, and E-cadherin proteins. In contrast, apoptosis of JEG-3 cells was elevated by STOX1 through Bcl-2, Bax, and Cox-2 proteins. Furthermore, we found that aspirin modulated the expression level of STOX1 and reversed proliferation and migration of STOX1-induced insufficient trophoblast cells. CONCLUSION: The present study suggested that inhibition of the expression of STOX1 could promote the effects of aspirin in the treatment of preeclampsia.

The association between EGF A61G polymorphism and risk of colorectal cancer in a Chinese population: a case-control study.

Epidermal Growth factor (EGF) could induce colorectal cancer (CRC) cell to develop epithelial mesenchymal-transition and enhance their ability to invade and migrate. Several studies have thrown light on the association between EGF gene polymorphism and risk of CRC, but with conflicting results. Therefore, we determined EGF A61G polymorphism by using PCR-restriction fragment length polymorphism method in 341 CRC cases and 472 controls in a Chinese population. Our results showed that EGF A61G polymorphism increased the risk of CRC in a Chinese population (GG vs AA: adjusted OR: 1.92; 95% CI: 1.27-2.91; P=0.002; GG+AG vs AA: adjusted OR: 1.43; 95% CI: 1.05-1.94; P=0.022; GG vs AG+AA: adjusted OR: 1.65; 95% CI: 1.15-2.39, P=0.007; G vs A: OR: 1.39; 95% CI: 1.14-1.69, P=0.001). Stratified analyses revealed that the significant association was more evident in the females, smokers, drinkers, and old subjects (age ≥60 years). Furthermore, the GG and/or AG genotype carriers were more likely to have larger tumor size and lymph node metastasis. In conclusion, EGF A61G polymorphism is a genetic contributor to CRC in a Chinese Han population.

Resveratrol suppresses the invasion and migration of human gastric cancer cells via inhibition of MALAT1-mediated epithelial-to-mesenchymal transition.

Resveratrol, a natural polyphenolic phytoalexin, was reported to exert multiple anticancer effects as a traditional Chinese medicine. However, research regarding the anticancer mechanism of resveratrol for the treatment and prevention of gastric cancer has reported conflicting results. In the present study, it was determined that resveratrol inhibited cell viability in a dose-dependent manner in the human gastric cancer cell line BGC823. Cell migration and invasion were suppressed significantly following treatment with 200 µM resveratrol. Additionally, resveratrol inhibited metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression, which was overexpressed in gastric cancer cells. Further experiments revealed that MALAT1 knockdown suppressed cell viability, migration, invasion and epithelial-to-mesenchymal transition in BGC823 cells. The present study indicated that resveratrol inhibited migration and invasion in human gastric cancer cells via suppressing MALAT1-mediated epithelial-to-mesenchymal transition, providing novel evidence for understanding the anticancer mechanism of resveratrol.

Correlations of PD-L1 gene polymorphisms with susceptibility and prognosis in hepatocellular carcinoma in a Chinese Han population.

AIMS: This study was performed to investigate the effect of PD-L1 polymorphisms on the susceptibility and prognosis of hepatocellular carcinoma (HCC) in a Chinese Han population. METHODS: Four single nucleotide polymorphisms (SNPs) of the PD-L1 gene, including rs2297136 (C > T), rs4143815 (C > G), rs2890658 (A > C) and rs17718883 (C > G) were examined in 225 HCC patients and 200 healthy controls using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Data revealed that the rs2297136 (C > T) SNP TT (p = 0.03) and rs4143815 (C > G) SNP GG genotypes (p < 0.001) were associated with significantly increased risks of HCC. No association was found between rs2890658 (A > C) SNP and HCC risk and this risk was significantly decreased in individuals with the rs17718883 SNP CG + GG genotype (p < 0.001). The rs2297136 (C > T) SNP CC + CT genotypes, the rs4143815 (C > G) CC genotype and the rs2890658 (A > C) AA genotype were associated with increased overall survival compared to their counterpart allelic genotypes (p < 0.001). The rs2890658 (A > C) SNP had no impact on the risk and prognosis of HCC (p > 0.05). CONCLUSIONS: Our results indicated that three functional polymorphisms (rs2297136, rs4143815 and rs17718883) of the PD-L1 gene were associated with HCC risk and prognosis, suggesting that genetic variants of PD-L1 polymorphisms might be a possible prognostic marker for the prediction of HCC risk and development. Validation by a larger prospective study from a more diverse ethnic population is needed to confirm these findings.

Multiple imaging techniques in the diagnosis of ampullary carcinoma.

BACKGROUND: Ampullary carcinoma is a neoplasia with a good prognosis compared to pancreatic cancer. But it is difficult to early diagnose because it lacks clear clinical symptoms. This study aimed to evaluate the efficacy of abdominal ultrasonography (US), enhanced computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) in detecting ampullary carcinoma. METHODS: Forty-one patients with ampullary carcinoma who had been confirmed pathologically among the inpatients at the First Affiliated Hospital of Zhejiang University School of Medicine from February 2003 to March 2007 were analyzed retrospectively. The accuracy of US, CT, MRCP and ERCP were compared in the diagnosis of ampullary carcinoma. RESULTS: The accurate rate for detection of ampullary carcinoma with US was 26.83%. The accuracy of CT and ERCP in detection of ampullary tumors was 84.62% and 100%, respectively, which were significantly higher than that of US (P<0.05). The accuracy of MRCP in detection of ampullary tumors was similar to that of US in spite of visualization of obstruction and dilatation of the pancreaticobiliary duct with MRCP. CONCLUSIONS: Because of the obscure and late onset of symptoms, ampullary carcinoma is difficult to diagnose early. Multiple imaging techniques should be carried out appropriately in order to early diagnose the disease and improve the prognosis.