Endometrial cancer intraoperative sentinel lymph node identification can effectively guide treatment.

OBJECTIVE: To explore the significance of intraoperative sentinel lymph node (SLN) identification in endometrial cancer. METHODS: We retrospectively analyzed the clinical data of 56 patients with intraoperative SLN recognition (group A) and 50 patients without intraoperative SLN recognition (group B). SLN and pelvic abdominal lymph node distribution, SLN recognition rate, SLN recognition effect, mortality, the incidence of adverse events, and cumulative survival rate were statistically analyzed. RESULTS: SLN were identified and removed in 41 of the 56 patients, with a recognition rate of 82.14% (46/56). The sensitivity of SLN was 83.72%, the specificity was 84.62%, and the negative predictive value was 61.11%. There were 15 patients with no SLN metastasis found in the pathological examination during the operation, among which two patients with poorly differentiated adenocarcinoma and clinical stage II patients underwent immunohistochemical staining, and three patients showed SLN micro-metastasis but no cancer tissue metastasis in the lymph node dissection. There was no significant difference in the incidence of total adverse events between group A and group B (P>0.05). The cumulative survival rate of group A was higher than that of group B (P=0.018). CONCLUSION: Intraoperative SLE identification can avoid false negative results, is safe and feasible, and can prolong the survival time of patients with endometrial cancer.

Effects of insulin aspart and metformin on gestational diabetes mellitus and inflammatory markers.

BACKGROUND: Gestational diabetes mellitus (GDM) refers to hyperglycemia caused by insulin resistance or insufficient insulin secretion during pregnancy. Patients with GDM have a high risk of pregnancy complications, which can adversely affect both maternal and fetal health. Therefore, early diagnosis, treatment and monitoring of GDM are essential. In recent years, a new treatment scheme represented by insulin aspart combined with metformin has received increasing attention. AIM: To explore the effects of insulin aspart combined with metformin on patients with GDM and inflammatory markers. METHODS: From April 2020 to September 2022, 124 patients with GDM in Sanya Women and Children's Hospital Managed by Shanghai Children's Medical Center were collected and analyzed retrospectively. The control group (CG) comprised 62 patients treated with insulin aspart alone, and 62 patients treated with insulin aspart and metformin formed the observation group (OG). Before and after treatment, improvement of blood-glucose-related indexes [fasting blood glucose (FBG), 2-h postprandial glucose (2h PG) and hemoglobin A1c (HbA1c)], serum related factor [serum homocysteine (Hcy)], serum inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-6 and C-reactive protein (CRP)] were compared between the two groups. The clinical efficacy, adverse pregnancy outcomes and incidence of pregnancy complications were compared between the two groups. RESULTS: After treatment, the levels of FBG, 2h PG, HbA1c, Hcy, TNF-α, IL-6 and CRP in both groups were significantly decreased (P < 0.05), and the levels of FBG, 2h PG, HbA1c, Hcy, TNF-α, IL-6 and CRP in the OG were lower than in the CG (P < 0.05). The total clinical effectiveness in the OG was higher than that in the CG (P < 0.05). The total incidence of adverse pregnancy outcomes and complications in the OG was significantly lower than in the CG (P < 0.05). CONCLUSION: Insulin aspart combined with metformin are effective for treatment of GDM, which can reduce blood-glucose-related indexes, Hcy and serum inflammatory cytokines, and risk of adverse pregnancy outcomes and complications.

Dissecting human placental cells heterogeneity in preeclampsia and gestational diabetes using single-cell sequencing.

Preeclampsia (PE) and gestational diabetes mellitus (GDM) are pregnancy-specific complications, which affect maternal health and fetal outcomes. Currently, clinical and pathological studies have shown that placenta homeostasis is affected by these two maternal diseases. In this study, we aimed to gain insight into the heterogeneous changes in cell types in placental tissue-isolated from cesarean section by single-cell sequencing, including those patients diagnosed with PE (n = 5), GDM (n = 5) and healthy control (n = 5). A total of 96,048 cells (PE: 31,672; GDM: 25,294; control: 39,082) were identified in six cell types, dominated by trophoblast cells and immune cells. In addition, trophoblast cells were divided into four subtypes, including cytotrophoblast cells (CTBs), villous cytotrophoblasts (VCTs), syncytiotrophoblast (STB), and extravillous trophoblasts (EVTs). Immune cells are divided into lymphocytes and macrophages, of which macrophages have 3 subtypes (decidual macrophages, Hofbauer cells and macrophages), and lymphocytes have 4 subtypes (BloodNK, T cells, plasma cells, and decidual natural killer cells). Meanwhile, we also proved the orderly differentiation sequence of CTB into VCT, then STB and EVT. By pair-wise analysis of the expression and enrichment of differentially expressed genes in trophoblast cells between PE, GDM and control, it was found that these cells were involved in immune, nutrient transfer, hormone and oxidative stress pathways. In addition, T cells and macrophages play an immune defense role in both PE and GDM. The proportion of CTB and EVT cells in placental tissue was confirmed by flow cytometry. Taken together, our results suggested that the human placenta is a dynamic heterogenous organ dominated by trophoblast and immune cells, which perform their respective roles and interact with other cells in the environment to maintain normal placental function.

SP1-SYNE1-AS1-miR-525-5p feedback loop regulates Ang-II-induced cardiac hypertrophy.

Cardiac hypertrophy (CH) has become a huge threat to human health. Recent years, long noncoding RNAs (lncRNAs) have been studied in human diseases, including CH. According to bioinformatics analysis, 10 lncRNAs possibly involved in the progression of CH were screened out. Among which, lncRNA SYNE1 antisense RNA 1 (SYNE1-AS1) could be upregulated by Angiotensin II (Ang-II) in cardiomyocytes. Thus, we chose SYNE1-AS1 to do further study. To identify the biological function of SYNE1-AS1 in CH, SYNE1-AS1 was silenced in Ang-II-induced cardiomyocytes. Results of immunofluorescence staining demonstrated that increased cell surface area in Ang-II-induced cardiomyocytes was reduced by SYNE1-AS1 knockdown. Moreover, the hypertrophic responses were attenuated by SYNE1-AS1 knockdown. Mechanically, SYNE1-AS1 positively regulated Sp1 transcription factor (SP1) by sponging microRNA-525-5p (miR-525-5p). On the basis of previous reports, SP1 can transcriptionally activate lncRNAs. Therefore, we investigated the interaction between SP1 and SYNE1-AS1 promoter. Intriguingly, SYNE1-AS1 was activated by SP1. At last, rescue assays demonstrated the function of SP1-SYNE1-AS1 axis in CH. In conclusion, SP1-induced upregulation of lncRNA SYNE1-AS1 promoted CH via miR-525-5p/SP1 axis.

YcgC represents a new protein deacetylase family in prokaryotes.

Reversible lysine acetylation is one of the most important protein posttranslational modifications that plays essential roles in both prokaryotes and eukaryotes. However, only a few lysine deacetylases (KDACs) have been identified in prokaryotes, perhaps in part due to their limited sequence homology. Herein, we developed a 'clip-chip' strategy to enable unbiased, activity-based discovery of novel KDACs in the Escherichia coli proteome. In-depth biochemical characterization confirmed that YcgC is a serine hydrolase involving Ser200 as the catalytic nucleophile for lysine deacetylation and does not use NAD(+) or Zn(2+) like other established KDACs. Further, in vivo characterization demonstrated that YcgC regulates transcription by catalyzing deacetylation of Lys52 and Lys62 of a transcriptional repressor RutR. Importantly, YcgC targets a distinct set of substrates from the only known E. coli KDAC CobB. Analysis of YcgC's bacterial homologs confirmed that they also exhibit KDAC activity. YcgC thus represents a novel family of prokaryotic KDACs.