Trophoblast-derived miR-410-5p induces M2 macrophage polarization and mediates immunotolerance at the fetal-maternal interface by targeting the STAT1 signaling pathway.

BACKGROUND: Macrophages phenotypic deviation and immune imbalance play vital roles in pregnancy-associated diseases such as spontaneous miscarriage. Trophoblasts regulate phenotypic changes in macrophages, however, their underlying mechanism during pregnancy remains unclear. Therefore, this study aimed to elucidate the potential function of trophoblast-derived miRNAs (miR-410-5p) in macrophage polarization during pregnancy. METHODS: Patient decidual macrophage tissue samples in spontaneous abortion group and normal pregnancy group (those who had induced abortion for non-medical reasons) were collected at the Reproductive Medicine Center of Renmin Hospital of Wuhan University from April to December 2021. Furthermore, placental villi and decidua tissue samples were collected from patients who had experienced a spontaneous miscarriage and normal pregnant women for validation and subsequent experiments at the Shenzhen Zhongshan Obstetrics & Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital), from March 2021 to September 2022. As an animal model, 36 female mice were randomly divided into six groups as follows: naive-control, lipopolysaccharide-model, agomir-negative control prevention, agomir-410-5p prevention, agomir-negative control treatment, and agomir-410-5p treatment groups. We analyzed the miR-410-5p expression in abortion tissue and plasma samples; and supplemented miR-410-5p to evaluate embryonic absorption in vivo. The main source of miR-410-5p at the maternal-fetal interface was analyzed, and the possible target gene, signal transducer and activator of transcription (STAT) 1, of miR-410-5p was predicted. The effect of miR-410-5p and STAT1 regulation on macrophage phenotype, oxidative metabolism, and mitochondrial membrane potential was analyzed in vitro. RESULTS: MiR-410-5p levels were lower in the spontaneous abortion group compared with the normal pregnancy group, and plasma miR-410-5p levels could predict pregnancy and spontaneous abortion. Prophylactic supplementation of miR-410-5p in pregnant mice reduced lipopolysaccharide-mediated embryonic absorption and downregulated the decidual macrophage pro-inflammatory phenotype. MiR-410-5p were mainly distributed in villi, and trophoblasts secreted exosomes-miR-410-5p at the maternal-fetal interface. After macrophages captured exosomes, the cells shifted to the tolerance phenotype. STAT1 was a potential target gene of miR-410-5p. MiR-410-5p bound to STAT1 mRNA, and inhibited the expression of STAT1 protein. STAT1 can drive macrophages to mature to a pro-inflammatory phenotype. MiR-410-5p competitive silencing of STAT1 can avoid macrophage immune disorders. CONCLUSION: MiR-410-5p promotes M2 macrophage polarization by inhibiting STAT1, thus ensuring a healthy pregnancy. These findings are of great significance for diagnosing and preventing spontaneous miscarriage, providing a new perspective for further research in this field.

A novel index for staging hepatitis B related liver cirrhosis in patients with hepatocellular carcinoma.

Information on the stage of liver cirrhosis is essential for prognostication and decisions on surgical planning for hepatocellular carcinoma (HCC) patients. But a non-invasive liver cirrhosis staging model is still lacking. The aim of our study was to develop a non-invasive model based on routine clinical parameters to evaluate the severity of cirrhosis in hepatitis B related HCC patients. A total of 226 HCC patients with chronic hepatitis B virus (HBV) infection who had liver resection were analyzed in this retrospective study. We found that platelets, prothrombin activity, maximum oblique diameter of right hepatic lobe and spleen length were the independent predictors of liver cirrhosis in HCC patients. By cumulating the weight of risk scores of independent variables, we constructed the PPMS (PLT/PTA/maximum oblique diameter of right hepatic lob/spleen length) index. The areas under the receiver operating characteristic curves (AUROC) of PPMS index were 0.820, 0.667, and 0.650 in predicting ≥cirrhosis 1 (C1), ≥cirrhosis 2 (C2), and ≥cirrhosis 3 (C3), respectively. The optimal cut-off value of the PPMS index for predicting ≥C1, ≥C2, and ≥C3 was 4.392, 4.471, and 4.784, respectively. And the corresponding sensitivity was 63.1%, 63.2%, and 64.7%, the corresponding specificity was 89.4%, 64.3%, and 62.5%, respectively. Our study constructed a non-invasive liver cirrhosis index (PPMS) could distinguish patients from different stages of liver cirrhosis, which might add more preoperative information for HCC patients.

Risk factors to discriminate neoplastic polypoid lesions of gallbladder: A large-scale case-series study.

BACKGROUND: Polypoid lesion of gallbladder (PLG) size larger than 10 mm is considered to be one of the surgical indications, but the final pathological results are mostly non-neoplastic polyps. The aim of the study was to define the risk factors to discriminate neoplastic PLG and create more precise criteria for surgical indications. METHODS: A large scale, case-series study based on 2704 patients who underwent cholecystectomy for PLG was designed. Logistic regression analysis and receiver operating characteristic curve (ROC) was adopted to identify risk factors and the optimal size criteria for predicting neoplastic PLG. RESULTS: Patients in the neoplastic group were significantly older than those in the non-neoplastic group and the average PLG size is much larger in the neoplastic group (18.5 ± 4.7 mm vs 12.6 ± 3.6 mm). Neoplastic PLGs are prone to be single and non-neoplastic polyps are usually multiple. On Multivariate logistic regression analysis, PLG size larger than 15 mm and age older than 43 years were found to be the independent risk factors to discriminate neoplastic PLG （Odds ratio 3.546 and 2.77 respectively）. The ROC curve showed that 12 mm might be the more reasonable PLG size threshold for the surgical suggestion. CONCLUSIONS: Considering its moderate diagnostic accuracy, the size of gallbladder polyp larger than 10 mm is insufficient to indicate surgical therapy for PLG and 12 mm should be the more optimal polyp's size threshold. Patients older than 43 years have a higher risk of having neoplastic polyps.

Predicting the stages of liver fibrosis with multiphase CT radiomics based on volumetric features.

PURPOSES: To develop and externally validate a multiphase computed tomography (CT)-based machine learning (ML) model for staging liver fibrosis (LF) by using whole liver slices. MATERIALS AND METHODS: The development dataset comprised 232 patients with pathological analysis for LF, and the test dataset comprised 100 patients from an independent outside institution. Feature extraction was performed based on the precontrast (PCP), arterial (AP), portal vein (PVP) phase, and three-phase CT images. CatBoost was utilized for ML model investigation by using the features with good reproducibility. The diagnostic performance of ML models based on each single- and three-phase CT image was compared with that of radiologists' interpretations, the aminotransferase-to-platelet ratio index, and the fibrosis index based on four factors (FIB-4) by using the receiver operating characteristic curve with the area under the curve (AUC) value. RESULTS: Although the ML model based on three-phase CT image (AUC = 0.65-0.80) achieved higher AUC value than that based on PCP (AUC = 0.56-0.69) and PVP (AUC = 0.51-0.74) in predicting various stage of LF, significant difference was not found. The best CT-based ML model (AUC = 0.65-0.80) outperformed the FIB-4 in differentiating advanced LF and cirrhosis and radiologists' interpretation (AUC = 0.50-0.76) in the diagnosis of significant and advanced LF. CONCLUSION: All PCP, PVP, and three-phase CT-based ML models can be an acceptable in assessing LF, and the performance of the PCP-based ML model is comparable to that of the enhanced CT image-based ML model.

Combination of hepatocyte fraction and diffusion-weighted imaging as a predictor in quantitative hepatic fibrosis evaluation.

OBJECTIVE: To investigate the performance of the combined hepatocyte fraction (HepF) and apparent diffusion coefficient (ADC) values to stage hepatic fibrosis (HF) in patients with hepatitis B/C. MATERIALS AND METHODS: A total of 281 patients with hepatitis B/C prospectively underwent gadoxetate disodium-based T1 mapping and diffusion-weighted imaging. HepF was determined from pre and postcontrast T1 mapping with pharmacokinetics. The independent predictors of the HF stage (S0-4) were identified from HepF, ADC, conventional T1-based parameters, and age using a logistic regression analysis. The performances of independent and combined predictors in diagnosing various HF stages were compared by analyzing receiver operating characteristic curves. The intraclass correlation coefficient (ICC) was used to assess the interobserver reproducibility of each predictor. RESULTS: In total, 167 patients with various stages of HF were included. All measurements had excellent interobserver agreement (ICC ≥ 0.75). The hepatic relative enhancement, HepF ,and ADC values were significantly different among various HF stages (p < 0.05). The HepF and ADC were independent predictors of > S0, > S1, > S2 , and > S3 disease (p < 0.05). T1Liver, T1Spleen, and T1Liver/Spleen were independent predictors of S > 2 disease (p < 0.05). The performance of HepF combined with the ADC (area under the curve (AUC) = 0.84-0.95) was higher than HepF (AUC = 0.79-0.92) or ADC (AUC = 0.82-0.89) alone in diagnosing > S0, > S1, > S2 , and > S3 disease. CONCLUSION: The combined predictor of HepF and ADC shows acceptable performance for staging HF.