Causal relationship between gestational diabetes and preeclampsia: A bidirectional mendelian randomization analysis.

AIMS: The study aimed to explore the potential causal link between gestational diabetes mellitus (GDM) and preeclampsia (PE) using a bidirectional mendelian randomization (MR) analysis. MATERIALS: We conducted a bidirectional MR analysis to investigate the causal relationship between GDM and PE. Data from public genome-wide association studies (GWAS) for GDM and PE were obtained from the FinnGen consortium. Various MR methods were employed, including inverse-variance weighted (IVW), MR-Egger, and sensitivity analyses. Additionally, a knowledge-based approach identified genes underlying this potential connection. RESULTS: The IVW method revealed a lack of significant association between GDM and PE (OR: 1.04, 95 % CI: 0.96-1.14; p = 0.275). Conversely, IVW analysis indicated a causal connection from PE to GDM (OR: 1.14, 95 % CI: 1.06-1.23; p < 0.001). Molecular pathway analysis identified 20 key genes, including ASAP2, central to the PE-GDM relationship. Tissue enrichment analysis showed pertinent gene expression in significant tissues. Moreover, lower ASAP2 expression was detected in PE patients' placentas. CONCLUSIONS: Our bidirectional MR analysis offers evidence supporting a causal link between PE and GDM, elucidating their interconnected pathogenesis. Genetic and knowledge-based insights facilitate a deeper comprehension of these complex pregnancy complications.

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.

Causal relationship between iron status and preeclampsia-eclampsia: a Mendelian randomization analysis.

BACKGROUND: Preeclampsia/eclampsia is a severe pregnancy-related disorder associated with hypertension and organ damage. While observational studies have suggested a link between maternal iron status and preeclampsia/eclampsia, the causal relationship remains unclear. The aim of this study was to investigate the genetic causality between iron status and preeclampsia/eclampsia using large-scale genome-wide association study (GWAS) summary data and Mendelian randomization (MR) analysis. METHODS: Summary data for the GWAS on preeclampsia/eclampsia and genetic markers related to iron status were obtained from the FinnGen Consortium and the IEU genetic databases. The "TwoSampleMR" software package in R was employed to test the genetic causality between these markers and preeclampsia/eclampsia. The inverse variance weighted (IVW) method was primarily used for MR analysis. Heterogeneity, horizontal pleiotropy, and potential outliers were evaluated for the MR analysis results. RESULTS: The random-effects IVW results showed that ferritin (OR = 1.11, 95% CI: .89-1.38, p = .341), serum iron (OR = .90, 95% CI: .75-1.09, p = .275), TIBC (OR = .98, 95% CI: .89-1.07, p = .613), and TSAT (OR = .94, 95% CI: .83-1.07, p = .354) have no genetic causal relationship with preeclampsia/eclampsia. There was no evidence of heterogeneity, horizontal pleiotropy, or possible outliers in our MR analysis (p > .05). CONCLUSIONS: Our study did not detect a genetic causal relationship between iron status and preeclampsia/eclampsia. Nonetheless, this does not rule out a relationship between the two at other mechanistic levels.

Development and validation of a prediction model on spontaneous preterm birth in twin pregnancy: a retrospective cohort study.

BACKGROUND: This study was conducted to develop and validate an individualized prediction model for spontaneous preterm birth (sPTB) in twin pregnancies. METHODS: This a retrospective cohort study included 3845 patients who gave birth at the Chongqing Maternal and Child Health Hospital from January 2017 to December 2022. Both univariable and multivariable logistic regression analyses were performed to find factors associated with sPTB. The associations were estimated using the odds ratio (OR) and the 95% confidence interval (CI). Model performance was estimated using sensitivity, specificity, accuracy, area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). RESULTS: A total of 1313 and 564 cases were included in the training and testing sets, respectively. In the training set, univariate and multivariate logistic regression analysis indicated that age ≥ 35 years (OR, 2.28; 95% CI 1.67-3.13), pre-pregnancy underweight (OR, 2.36; 95% CI 1.60-3.47), pre-pregnancy overweight (OR, 1.67; 95% CI 1.09-2.56), and obesity (OR, 10.45; 95% CI, 3.91-27.87), nulliparity (OR, 0.58; 95% CI 0.41-0.82), pre-pregnancy diabetes (OR, 5.81; 95% CI 3.24-10.39), pre-pregnancy hypertension (OR, 2.79; 95% CI 1.44-5.41), and cervical incompetence (OR, 5.12; 95% CI 3.08-8.48) are independent risk factors for sPTB in twin pregnancies. The AUC of the training and validation set was 0.71 (95% CI 0.68-0.74) and 0.68 (95% CI 0.64-0.73), respectively. And then we integrated those risk factors to construct the nomogram. CONCLUSIONS: The nomogram developed for predicting the risk of sPTB in pregnant women with twins demonstrated good performance. The prediction nomogram serves as a practical tool by including all necessary predictors that are readily accessible to practitioners.

Ginsenoside Rh4 inhibits inflammation-related hepatocellular carcinoma progression by targeting HDAC4/IL-6/STAT3 signaling.

This study aimed to investigate the effects of Ginsenoside Rh4 (Rh4) on inflammation-related hepatocellular carcinoma (HCC) progression and the underlying mechanism. HCC cells (HUH7 and LM3) were induced by lipopolysaccharide (LPS) to establish an inflammatory environment in the absence or presence of Rh4. CCK-8, wound healing and transwell assays were employed to analyze the viability, migration and invasion of HCC cells. Ki67 expression was detected by immunofluorescence method. Besides, the levels of glucose and lactic acid were tested by kits. The expression of proteins related to migration, glycolysis and histone deacetylase 4 (HDAC4)/IL-6/STAT3 signaling was measured with western blot. The transplantation tumor model of HCC in mice was established to observe the impacts of Rh4 on the tumor growth. Results indicated that Rh4 restricted the viability and Ki67 expression in HCC cells exposed to LPS. The elevated migration and invasion of HCC cells triggered by LPS were reduced by Rh4. Additionally, Rh4 treatment remarkably decreased the contents of glucose and lactic acid and downregulated LDHA and GLUT1 expression. The database predicated that Rh4 could target HDAC4, and our results revealed that Rh4 downregulated HDAC4, IL-6 and p-STAT3 expression. Furthermore, the enforced HDAC4 expression alleviated the effects of Rh4 on the proliferation, migration, invasion and glycolysis of HCC cells stimulated by LPS. Taken together, Rh4 could suppress inflammation-related HCC progression by targeting HDAC4/IL-6/STAT3 signaling. These findings clarify a new anti-cancer mechanism of Rh4 on HCC and provide a promising agent to limit HCC development.

Associations between velamentous or marginal cord insertion and risk of adverse perinatal outcomes in twin pregnancies: a retrospective cohort study.

BACKGROUND: Velamentous cord insertion (VCI) and marginal cord insertion (MCI) are well-known risk factors for adverse perinatal outcomes in singleton pregnancies. However, the potential links between VCI or MCI and perinatal outcomes in twin pregnancies have yet to be systematically evaluated. This study aimed to investigate the relationships between VCI or MCI and perinatal outcomes in twin pregnancies. METHODS: This retrospective single-center cohort study included women with twin pregnancies who gave birth in a tertiary hospital in Southwest, China between January 2017 and December 2022. VCI and MCI were identified by abdominal ultrasound and confirmed after placental delivery. Logistic regression, multinomial logit regression and generalized estimation equation models were used to evaluate the association between VCI or MCI and perinatal outcomes. RESULTS: A total of 3682 twin pregnancies were included, including 100 (2.7%) pregnancies with VCI and 149 (4.0%) pregnancies with MCI. Compared to pregnancies with normal cord insertion, both monochorionic and dichorionic pregnancies with VCI were associated with an increased risk of preterm delivery 32-34 weeks (aRRR 2.94, 95% CI 1.03-8.39; aRRR 2.55, 95% CI 1.19-5.46, respectively), while pregnancies with MCI were not associated with preterm delivery. VCI was associated with a higher incidence of placental previa (aOR 6.36, 95% CI 1.92-21.04) in monochorionic pregnancies and placental accreta (aOR 1.85, 95% CI 1.06-3.23) in dichorionic pregnancies. MCI was associated with an increased risk of preeclampsia (aOR 3.07, 95% CI 1.49-6.32), intertwin birthweight discordance ≥ 20% (aOR 2.40, 95% CI 1.08-5.60) and selective fetal growth restriction (aOR 2.46, 95% CI 1.08-5.60) in monochorionic pregnancies and small-for-gestational age neonates (aOR 1.97, 95% CI 1.24-3.14) in dichorionic pregnancies. CONCLUSIONS: VCI was associated with an increased risk of preterm delivery in twin pregnancies irrespective of chorionicity, whereas MCI was associated with an increased preeclampsia risk, significant intertwin birthweight discordance in monochorionic pregnancies and small-for-gestational age neonates in dichorionic pregnancies.

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.

p14ARF ameliorates inflammation and airway remodeling in nitric acid aerosol inhalation-induced bronchiolitis obliterans.

BACKGROUND: To investigate the protective effect of p14ARF in a nitric acid (NA) aerosol inhalation-induced bronchiolitis obliterans (BO) mouse model and its potential regulatory mechanism. METHODS: A BO mouse model was established by NA aerosol inhalation. The expressions of p14ARF, phosphatidylinositol-3-kinase (PI3K), and protein kinase B (AKT) were detected by quantitative reverse transcription PCR (qRT-PCR) and western blot (WB). Hematoxylin (HE) staining, Masson staining, and periodic acid-Schiff (PAS) staining observed pulmonary histological changes. TdT-mediated dUTP nick end labeling (TUNEL) staining detected pulmonary cell apoptosis, and enzyme-linked immunosorbent assay (ELISA) measured matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), interleukon-6 (IL-6), and transforminh growth factor-ß (TGF-ß) levels in lung tissue and bronchoalveolar lavage fluid (BALF). RESULTS: The expressions of p14ARF, PI3K, and AKT showed a time gradient change, with a decrease trend (*P < 0.05 and **P < 0.01). Severe inflammatory infiltration and tracheal fibrosis were found in lung tissue in the modeling group (BO group) compared with the control group (Con group). The pH, PaO2, and PaO2/FiO2 values significantly reduced, while the PaCO2 value and the number of TUNEL-positive cells increased in BO group (P < 0.05). In addition, MMP-2, MMP-9, IL-6, and TGF-ß levels remarkably increased, with an increase in the number of white blood cells, neutrophils, and lymphocytes in BO group (P < 0.05). Furthermore, p14ARF up-regulation reversed the trend of the aforementioned indexes in BO mice. CONCLUSIONS: p14ARF ameliorated the inflammatory response and airway remodeling in a BO mouse model via the PI3K/AKT pathway.

Influence factors for upper respiratory tract infection in Chinese rural children: A cross-sectional study.

Aim: The prevalence rate of upper respiratory tract infection (URTI) is high in children. Influencing factors for URTI have been reported in Chinese urban children, but those have not been explored in rural children. In China, children in the rural areas are a disadvantaged group. Therefore, this study aims to explore influencing factors for URTI in Chinese rural children. Methods: This is a cross-sectional study based on the 1991-2015 China Health and Nutrition Survey (CHNS). In total, 5,289 children were eligible for the analysis, including 3,684 rural children and 1,605 urban children. The generalized estimating equation was used to determine the influencing factors, and results were expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: The results showed that rural children aged 7-12 and 13-17 years had lower odds of URTI than those aged 0-1 year, with OR value of 0.17 (95% CI, 0.11-0.27) and 0.12 (95% CI, 0.08-0.19), respectively. Compared with uneducated mothers, those with education level of primary school (OR: 0.59, 95% CI, 0.42-0.84), lower middle school (OR: 0.53, 95% CI, 0.38-0.73), and upper middle school and technical school (OR: 0.62, 95% CI, 0.40-0.95) were associated with the lower odds of URTI in rural children. Children, whose mothers were office workers, had 46% lower odds of URTI than those with farmer mothers (OR: 0.54, 95% CI, 0.34-0.84). Conclusions: This study found that mother's education level, children's age, and mother's occupation were significant influencing factors for URTI, which suggested the importance to improve mother's health-related knowledge and working conditions in Chinese rural areas.

[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.

Corepressors SsnF and RcoA Regulate Development and Aflatoxin B1 Biosynthesis in Aspergillus flavus NRRL 3357.

Aspergillus flavus is a saprophytic fungus that can be found across the entire world. It can produce aflatoxin B1 (AFB1), which threatens human health. CreA, as the central factor in carbon catabolite repression (CCR), regulates carbon catabolism and AFB1 biosynthesis in A. flavus. Additionally, SsnF-RcoA are recognized as the corepressors of CreA in CCR. In this study, ssnF and rcoA not only regulated the expressions of CCR factors and hydrolase genes, but also positively affected mycelia growth, conidia production, sclerotia formation, and osmotic stress response in A. flavus. More importantly, SsnF and RcoA were identified as positive regulators for AFB1 biosynthesis, as they modulate the AF cluster genes and the relevant regulators at a transcriptional level. Additionally, the interactions of SsnF-CreA and RcoA-CreA were strong and moderate, respectively. However, the interaction of SsnF and RcoA was weak. The interaction models of CreA-SsnF, CreA-RcoA, and SsnF-RcoA were also simulated with a docking analysis. All things considered, SsnF and RcoA are not just the critical regulators of the CCR pathway, but the global regulators involving in morphological development and AFB1 biosynthesis in A. flavus.

MiR-140 suppresses airway inflammation and inhibits bronchial epithelial cell apoptosis in asthma by targeting GSK3ß.

AIM OF THE STUDY: Asthma is a common and complex chronic inflammatory disease induced by genetic and environmental factors that affects the airways of the lungs. MicroRNAs (miRNAs) are key regulators of various cellular processes and have been shown to be critically involved in asthma progression. The objective of our study was to clarify the function and molecular mechanism of miR-140 in the progression of asthma. MATERIALS AND METHODS: MiR-140 expression was evaluated using RT-qPCR. Pathological changes in the lung tissue were confirmed using HE and PAS staining. The levels of IL-5, TGF-ß1, and IL-13 in the serum or bronchioalveolar lavage fluid were detected with an ELISA. Cellular apoptosis was measured using a TUNEL assay. The levels of Bax, Bcl-2, Cleaved caspase-3, and glycogen synthase kinase-3ß (GSK-3ß) were verified with a western blot. GSK3ß expression was also confirmed by immunohistochemistry. The binding ability between miR-140 and GSK3ß was confirmed using a luciferase reporter assay, RNA immunoprecipitation (RIP) assay and Pull-down assay. RESULTS: MiR-140 was markedly downregulated in asthmatic mice. Additionally, miR-140 weakened airway inflammation and bronchial epithelial cell apoptosis in asthmatic mice. Further experiments revealed that miR-140 negatively regulated GSK3ß expression and could bind to GSK3ß in asthma. Finally, rescue assays demonstrated that GSK3ß overexpression rescued the effects of miR-140 on asthma progression. CONCLUSION: MiR-140 targeted GSK3ß to suppress airway inflammation and inhibit bronchial epithelial cell apoptosis in asthma.

The inhibitory mechanism of methyl jasmonate on Aspergillus flavus growth and aflatoxin biosynthesis and two novel transcription factors are involved in this action.

As the most toxic and carcinogenic mycotoxin, aflatoxin B1 (AFB1) biosynthesis depends on a series of enzymatic reactions and a complicated regulatory system. Methyl jasmonate (MeJA) is one of stress associated phytohormones. In this study, MeJA could inhibit A. flavus growth and AFB1 production with a dose-dependent manner. SEM and TEM analysis indicated that morphological ultrastructure deteriorations were observed in A. flavus treated with MeJA. RNA-Seq indicated that the initial-steps aflatoxins (AFs) genes were no drastic difference, but the middle- and later- steps genes were significantly down-regulated, which might be due to the decreases of global regulators, especially AtfB. More importantly, two novel regulators (AFLA_085880 and AFLA_015850) were involved in the inhibition, and were recognized as the critically positive regulators for AFs productions. The two genes mutants also showed significantly decrease expressions of AFs cluster genes and AFs associated regulators, and subsequent AFB1 biosynthesis. This research partly clarified inhibitory mechanism of MeJA and made some contributions to the elimination of AFs contamination.

Sustained release of tulobuterol from graphene oxide laden hydrogel to manage asthma.

Bronchial asthma is a chronic disease which is currently treated using various inhalants. However, the medication adherence with the inhalants is poor due to complex procedure to use them along with frequent dosing. In this paper, we have developed tulobuterol loaded Pluronic® F127-reduced graphene oxide transdermal hydrogel to sustain the release of tulobuterol to manage asthma for days. The synthesis of Pluronic® F127-reduced graphene oxide was confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, and Raman spectroscopy. The transmission electron microscope showed wrinkled flat nano sheets. The hydrogel showed sufficient mechanical properties for topical application and was safe in the skin irritation study (rabbit model). The ex vivo release data demonstrated the ability of reduced graphene oxide to sustain the release of tulobuterol for 72 h, due to strong π-π interaction between drug and graphene oxide. The pharmacokinetic profile in Sprague-Dawley rat model confirmed the potential of tulobuterol-Pluronic® F127-reduced graphene oxide hydrogel to sustain the release of tulobuterol for effective management of asthma.

Proposal-Based Visual Tracking Using Spatial Cascaded Transformed Region Proposal Network.

Region proposal network (RPN) based trackers employ the classification and regression block to generate the proposals, the proposal that contains the highest similarity score is formulated to be the groundtruth candidate of next frame. However, region proposal network based trackers cannot make the best of the features from different convolutional layers, and the original loss function cannot alleviate the data imbalance issue of the training procedure. We propose the Spatial Cascaded Transformed RPN to combine the RPN and STN (spatial transformer network) together, in order to successfully obtain the proposals of high quality, which can simultaneously improves the robustness. The STN can transfer the spatial transformed features though different stages, which extends the spatial representation capability of such networks handling complex scenarios such as scale variation and affine transformation. We break the restriction though an easy samples penalization loss (shrinkage loss) instead of smooth L1 function. Moreover, we perform the multi-cue proposals re-ranking to guarantee the accuracy of the proposed tracker. We extensively prove the effectiveness of our proposed method on the ablation studies of the tracking datasets, which include OTB-2015 (Object Tracking Benchmark 2015), VOT-2018 (Visual Object Tracking 2018), LaSOT (Large Scale Single Object Tracking), TrackingNet (A Large-Scale Dataset and Benchmark for Object Tracking in the Wild) and UAV123 (UAV Tracking Dataset).

Association between serum iron levels and the risk of cervical cancer in Chinese: a meta-analysis.

OBJECTIVES: To evaluate the association between serum iron levels and cervical cancer risk in Chinese populations. METHODS: A literature search was conducted using the PubMed, WanFang, and SinoMed databases up to April 30, 2019. Pooled standard mean differences (SMD) and 95% confidence intervals (CI) were analyzed using R software with a random-effects model. RESULTS: Data from nine studies comprising 454 cervical cancer patients and 880 controls were used in the analysis. Our results demonstrated that serum iron levels in cervical cancer patients were significantly lower than those in controls in Chinese populations (summary SMD = -1.24, 95%CI = -1.37 to -1.10; I2 = 93.4%). No publications bias was detected. Sensitivity analysis indicated that no single study had a significant effect on the overall SMD. CONCLUSIONS: Our findings show that serum iron levels are lower in patients with cervical cancer than in control individuals. However, further high-quality studies are necessary to clarify the role of serum iron levels in cervical cancer risk.

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.

Pulmonary Artery Sling Presenting as Pneumonia and Inhalation of a Foreign Body.

Pulmonary artery sling is a rare cause of respiratory distress created by compression of the lower trachea and right mainstem bronchus due to an aberrant origin of the left pulmonary artery. The condition is frequently associated with recurrent respiratory infections and other congenital malformations including tracheal rings. We present the case of an infant presenting with pulmonary distress and a history of recurrent respiratory infection. The infant underwent surgery to remove a foreign object; however, the symptoms did not resolve. Bronchoscopy revealed bronchus stenosis, and subsequent echocardiogram and CT scans revealed the presence of a pulmonary artery sling. We prescribed infection prophylaxis with the immunomodulator OM-85 to mitigate the risk of further infections prior to surgery. PAS and bronchus stenosis were corrected successfully by surgical intervention leading to resolution of symptoms of respiratory distress and a reduction in the incidence of respiratory infection.

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.

Snail Driving Alternative Splicing of CD44 by ESRP1 Enhances Invasion and Migration in Epithelial Ovarian Cancer.

BACKGROUND/AIMS: Our study aims to investigate the role, effect and mechanisms of ESRP1 (epithelial splicing regulatory protein 1) in epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer (EOC). METHODS: Microarray and immunohistochemical analysis of ESRP1 expression were performed in EOC cases. The correlations between ESRP1 expression and clinical factors on EOC were assessed. Lentivirus-mediated RNA interference and EGFP vector which contains ESRP1 gene were used to down-regulate and up-regulate ESRP1 expression in human EOC cell lines. Roles of ESRP1 in cell growth, migration and invasion of EOC cells were also measured by Cell Counting Kit-8 and Transwell systems in vitro and by a nude mice intraperitoneal transplantation model in vivo. RESULTS: By the analysis of Gene Expression Omnibus (GEO) (p<0.05) and our own microarray data (p<0.001), ESRP1 expression in EOC was significantly different from normal ovarian tissue. It was abundant in the nuclei of cancer cells and in malignant lesions. However, it was weakly expressed or negative in both normal and benign lesions. High ESRP1 expression in EOC was associated with poor clinical outcomes. Decreased ESRP1 expression significantly increased cell migration and invasion both in vivo and in vitro. Snail strongly repressed ESRP1 transcription through binding to the ESRP1 promoter in EOC cells. Furthermore, ESRP1 regulated the expression of CD44s. Down-regulated ESRP1 resulted in an isoform switching from CD44v to CD44s, which modulated epithelial-mesenchymal transition (EMT) program in EOC. Up-regulatin of ESRP1 was detected in mesenchymal to epithelial transition (MET) in vivo. CONCLUSIONS: ESRP1 regulates CD44 alternative splicing during the EMT process which plays an important role in EOC carcinogenesis. In addition, ESRP1 is associated with disease prognosis in EOC.