[Research progress on role of traditional Chinese medicine in hepatic fibrosis based on miRNA-mediated activation of NLRP3 inflammasome].

In recent years, liver fibrosis has become a hotspot in the field of liver diseases. MicroRNA(miRNA)-mediated Nod-like receptor pyrin domain containing 3(NLRP3) inflammasome activation is pivotal in the pathogenesis of liver fibrosis. The present study mainly discussed the role of miRNA-mediated NLRP3 inflammasome activation in the pathogenesis of liver fibrosis. Different miRNA molecules regulated liver fibrosis by mediating NLRP3 inflammasome activation, including miRNA-350-3 p(miR-350-3 p)/interleukin-6(IL-6)-mediated signal transducer and activator of transcription 3(STAT3)/c-myc signaling pathway, miR-148 a-induced autophagy and apoptosis of hepatic stellate cells via hedgehog signaling pathway, miR-155-mediated NLRP3 inflammasome by the negative feedback of the suppressor of cytokine signaling-1(SOCS-1), miR-181 a-mediated downstream NLRP3 inflammatory pathway activation through mitogen-activated protein kinase kinase(MEK)/extracellular signal-regulated kinase(ERK)/nuclear transcription factor κB(NF-κB) inflammatory pathway, miR-21-promoted expression of NF-κB and NLRP3 of RAW264.7 cells in mice by inhibiting tumor necrosis factor-α inducible protein 3(A20), and miR-20 b-promoted expression of IL-1ß and IL-18 by activating NLRP3 signaling pathway. Additionally, the anti-liver fibrosis mechanism of different active components in Chinese medicines(such as Curcumae Rhizoma, Glycyrrhizae Radix et Rhizoma, Aurantii Fructus, Polygoni Cuspidati Rhizoma et Radix, Moutan Cortex, Paeoniae Radix Alba, Epimedii Folium, and Cinnamomi Cortex) was also explored based on the anti-liver fibrosis effect of miRNA-mediated NLRP3 inflammasome activation.

Gestational diabetes mellitus aggravates adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy.

PURPOSE: To evaluate the effect of intrahepatic cholestasis of pregnancy (ICP) with gestational diabetes mellitus (GDM) on perinatal outcomes and establish a prediction model of adverse perinatal outcomes in women with ICP. METHODS: This multicenter retrospective cohort study included the clinical data of 2,178 pregnant women with ICP, including 1,788 women with ICP and 390 co-occurrence ICP and GDM. The data of all subjects were collected from hospital electronic medical records. Univariate and multivariate logistic regression analysis were used to compare the incidence of perinatal outcomes between ICP with GDM group and ICP alone group. RESULTS: Baseline characteristics of the population revealed that maternal age (p < 0.001), pregestational weight (p = 0.01), pre-pregnancy BMI (p < 0.001), gestational weight gain (p < 0.001), assisted reproductive technology (ART) (p < 0.001), and total bile acid concentration (p = 0.024) may be risk factors for ICP with GDM. Furthermore, ICP with GDM demonstrated a higher association with both polyhydramnios (OR 2.66) and preterm labor (OR 1.67) compared to ICP alone. Further subgroup analysis based on the severity of ICP showed that elevated total bile acid concentrations were closely associated with an increased risk of preterm labour, meconium-stained amniotic fluid, and low birth weight in both ICP alone and ICP with GDM groups. ICP with GDM further worsened these outcomes, especially in women with severe ICP. The nomogram prediction model effectively predicted the occurrence of preterm labour in the ICP population. CONCLUSIONS: ICP with GDM may result in more adverse pregnancy outcomes, which are associated with bile acid concentrations.

Rational use of drugs to alleviate adverse outcomes caused by COVID-19 quarantine in women with intrahepatic cholestasis of pregnancy.

Purpose: This study aimed to investigate the impacts of home quarantine on pregnancy outcomes of women with intrahepatic cholestasis of pregnancy (ICP) during the COVID-19 outbreak and whether the rational use of drugs will change these impacts. Methods: This multi-center study was conducted to compare the pregnancy outcomes in women with ICP between the home quarantine group and the non-home quarantine group in southwest China. Propensity score matching was performed to confirm the pregnancy outcomes of the medication group and the non-medication group in women with ICP during the epidemic period. Results: A total of 3,161 women with ICP were enrolled in this study, including 816 in the home quarantine group and 2,345 in the non-home quarantine group. Women with ICP in the home quarantine group had worse pregnancy outcomes, such as a growing risk of gestational diabetes mellitus A1, fetal growth restriction, pre-eclampsia, preterm delivery, and even stillbirth. Drug therapy could alleviate some adverse pregnancy outcomes caused by home quarantine, including pre-eclampsia, preterm delivery, and meconium-stained amniotic fluid. Conclusion: COVID-19 quarantine would increase the incidence of ICP and lead to adverse pregnancy outcomes in women with ICP. The rational use of drugs reduced some obstetrical complications and improved partial pregnancy outcomes. Our findings suggested that the government and hospitals should enhance their management and life guidance for women with ICP and speed up developing home quarantine guidelines.

Multifactorial impact on the outcome of interval debulking surgery in patients with advanced epithelial ovarian or peritoneal cancers.

OBJECTIVE: To evaluate the impact of multiple clinical features upon the outcome of interval cytoreductive surgery and thus upon the survival in patients with advanced ovarian cancer and primary peritoneal carcinoma. METHODS: A retrospective analysis of patients receiving NACT followed by IDS between 2009 and 2017. Patients were analyzed according to the pre-NACT CA125, pre-IDS CA125, pre-IDS CA125 decline, patients' pre-IDS BMI, multisite bowel involvement and different working years of surgeons, for their influence upon the IDS outcome (e.g. optimal vs suboptimal) and the survival. RESULTS: After interval debulking surgery following 1-6 cycles of NACT, all patients analyzed were identified as optimal (n = 113) and suboptimal (n = 47) based on patients' record. The PFS/OS were 21/68 months and 9/26 months in optimal and suboptimal groups, respectively (p = .000, p = .000). Although differential levels of pre-IDS CA125, pre-IDS CA125 decline, bowel involvement and surgeons' working years were found to be significantly different between the two groups, surgeons' working years and multisite bowel invasion were the independent factors for IDS outcome, and the latter one was also highly related to survival. CONCLUSIONS: Following NACT, the rate of optimal IDS might be improved for patients without multisite bowel involvement. For those with bowel involvement, management strategy made by well-experienced surgeons might be a key factor for the outcome of IDS.

Serum CA125 levels predict outcome of interval debulking surgery after neoadjuvant chemotherapy in patients with advanced ovarian cancer.

OBJECTIVE: To evaluate the correlation between the changes of serum CA125 level and the outcome of interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT) in patients with advanced epithelial ovarian cancer (EOC). METHODS: A retrospective review for 62 patients with FIGO stage III or IV EOC treated with NACT-IDS was conducted. Demographic data, clinical characters, pathological features and prognosis were collected. Continuous variables were evaluated by Student's t-test or Mann-Whitney U test. Categorical variables were evaluated by chi square test or Fisher's exact test as appropriate for category size. Standard univariate analyses and multivariable analysis with logistic regression were performed to identify independent predictor of optimal IDS. Kaplan-Meier method was used to analyze the prognosis. RESULTS: No statistical difference was found on serum CA125 levels between suboptimal (n = 34)IDS and optimal (n = 28) IDS either before NACT (median levels: 1552.2 U/mL and 1715.5 U/mL, p = 0.453) or before IDS (median levels: 27.25 U/mL and 26.4 U/mL, p = 0.713). Those with optimal IDS achieved longer progression free survival (PFS) and overall survival (OS) than those with suboptimal IDS (median PFS: 22 and 13.5 months, p < 0.001; median OS: 33.5 and 21 months, p = 0.005). Eighteen of 31 patients (58.1%) with serum CA125 declines ≥0.95828 achieved optimal IDS compared to 10 of the 31 patients (32.3%) with serum CA125 declines <0.95828 (p = 0.041). Standard univariate analyses and multivariable analysis showed that serum CA125 declines ≥0.95828 could be an independent predictor of optimal IDS. CONCLUSION: Patients who underwent optimal IDS have better prognosis compare to suboptimal IDS. The changes of serum CA125 after neoadjuvant chemotherapy might predict optimal interval debulking surgery in patients with advanced epithelial ovarian cancer.

The C3G/Rap1 pathway promotes secretion of MMP-2 and MMP-9 and is involved in serous ovarian cancer metastasis.

Complete resection is pivotal to improve survival to epithelial ovarian cancer (EOC). Crk SH3-domain-binding guanine nucleotide-releasing factor (C3G) is involved in multiple signaling pathways and it has opposite roles in different cancers. The present study aimed to identify C3G expression in ovarian tissue samples from patients with EOC and to explore its association with tumor grade. Eighty-seven archival paraffin-embedded, formalin-fixed, ovarian cancer tissues with serous histology were stained for C3G by immunohistochemistry. To evaluate the contribution of C3G to Rap1 activity, 36 patients with serous ovarian cancer (SOC) were investigated. Additionally, C3G was knocked down in SKOV3 and HEY cells. C3G regulated Rap1 activity and high Rap1 activity was correlated with poor differentiation, advanced FIGO stage, and unsuccessful cytoreductive surgery of SOC. Knockdown of C3G suppressed cell invasion, intravasation and extravasation, and reduced Rap1 activity and secretion of matrix metalloproteinase (MMP)-2 and MMP-9. C3G-mediated activation of Rap1 could direct the tumor pattern of human SOC by promoting the secretion of MMP-2 and MMP-9. These results suggest that C3G is involved in the metastatic spread of EOC.