Prenatal exposure to polycyclic aromatic hydrocarbons and phthalate acid esters and gestational diabetes mellitus: A prospective cohort study.

BACKGROUND: Polycyclic aromatic hydrocarbons and phthalate acid esters (PAHs & PAEs), known as endocrine disrupting chemicals (EDCs), widely exist in daily life and industrial production. Previous studies have suggested that PAHs & PAEs may modify the intrauterine homeostasis and have adverse effects on fetal development. However, epidemiological evidence on the associations between PAHs & PAEs and gestational diabetes mellitus (GDM) is still limited. OBJECTIVE: To investigate the effects of prenatal PAHs &PAEs exposure on the risk of GDM and hyperglycemia in pregnant women. METHODS: The study population was a total of 725 pregnant women from a prospective birth cohort study conducted from December 2019 to December 2021. Blood glucose levels were collected by the hospital information system. Urinary PAHs & PAEs concentrations were determined by gas chromatography tandem mass spectrometry. The Poisson regression in a generalized linear model (GLM), multiple linear regression, quantile-based g-computation method (qgcomp), and Bayesian kernel machine regression (BKMR) were applied to explore and verify the individual and overall effects of PAHs & PAEs on glucose homeostasis. Potential confounders were adjusted in all statistical models. RESULTS: A total of 179 (24.69%) women were diagnosed with GDM. The Poisson regression suggested that a ln-unit increment of 4-OHPHE (4-hydroxyphenanthrene) (adjusted Risk Ratio (aRR) = 1.13; 1.02-1.26) was associated with the increased GDM risk. Mixed-exposure models showed similar results. We additionally found that MBZP (mono-benzyl phthalate) (aRR = 1.19; 1.02-1.39) was positively related to GDM risk in qgcomp model. Although neither model demonstrated that 2-OHNAP (2-hydroxynaphthalene) and 9-OHFLU (9-hydroxyfluorene) increased the risk of GDM, 2-OHNAP and 9-OHFLU exposure significantly increased blood glucose levels. BKMR model further confirmed that overall effects of PAHs & PAEs were significantly associated with the gestational hyperglycemia and GDM risk. CONCLUSIONS: Our study presents that environmental exposure to PAHs & PAEs was positively associated with gestational glucose levels and the risks of developing GDM. In particular, 2-OHNAP, 9-OHFLU, 4-OHPHE and MBZP may serve as important surveillance markers to prevent the development of GDM.

The combination of deep learning and pseudo-MS image improves the applicability of metabolomics to congenital heart defect prenatal screening.

To investigate the metabolic alterations in maternal individuals with fetal congenital heart disease (FCHD), establish the FCHD diagnostic models, and assess the performance of these models, we recruited two batches of pregnant women. By metabolomics analysis using Ultra High-performance Liquid Chromatography-Mass/Mass (UPLC-MS/MS), a total of 36 significantly altered metabolites (VIP >1.0) were identified between FCHD and non-FCHD groups. Two logistic regression models and four support vector machine (SVM) models exhibited strong performance and clinical utility in the training set (area under the curve (AUC) = 1.00). The convolutional neural network (CNN) model also demonstrated commendable performance and clinical utility (AUC = 0.89 in the training set). Notably, in the validation set, the performance of the CNN model (AUC = 0.66, precision = 0.714) exhibited better robustness than the six models above (AUC≤0.50). In conclusion, the CNN model based on pseudo-MS images holds promise for real-world and clinical applications due to its better repeatability.

Comprehensive Analysis of Potential ceRNA Network and Different Degrees of Immune Cell Infiltration in Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a leading cause of death in critically ill patients due to hypoxemic respiratory failure. The specific pathogenesis underlying ARDS has not been fully elucidated. In this study, we constructed a triple regulatory network involving competing endogenous RNA (ceRNA) to investigate the potential mechanism of ARDS and evaluated the immune cell infiltration patterns in ARDS patients. Overall, we downloaded three microarray datasets that included 60 patients with sepsis-induced ARDS and 79 patients with sepsis alone from the public Gene Expression Omnibus (GEO) database and identified differentially expressed genes (DEGs, including 9 DElncRNAs, 9 DEmiRNAs, and 269 DEmRNAs) by R software. The DEGs were subjected to the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional enrichment analysis, and a protein-protein interaction (PPI) network was generated for uncovering interactive relationships among DEmRNAs. Then, a ceRNA network that contained 5 DElncRNAs, 7 DEmiRNAs, and 71 DEmRNAs was established according to the overlapping genes in both DEGs and predicted genes by public databases. Finally, we identified the TUG1/miR-140-5p/NFE2L2 pathway as the hub pathway in the whole network through Cytoscape. In addition, we evaluated the distribution of 22 subtypes of immune cells and recognized three differentially expressed immune cells in patients with sepsis-induced ARDS by "Cell Type Identification by Estimating Relative Subsets of Known RNA Transcripts (CIBERSORT)" algorithm, namely, naive B cells, regulatory T cells, and eosinophils. Correlations between differentially expressed immune cells and hub genes in the ceRNA network were also performed. In conclusion, we demonstrated a new potential regulatory mechanism underlying ARDS (the TUG1/miR-140-5p/NFE2L2 ceRNA regulatory pathway), which may help in further exploring the pathogenesis of ARDS.

Clinicopathological features of granulomatous lobular mastitis and mammary duct ectasia.

Granulomatous lobular mastitis (GLM) and mammary duct ectasia (MDE) are inflammatory diseases. However, only a limited number of studies have focused on characterizing their clinicopathological features. The aim of the present study was to investigate the etiology, clinicopathological characteristics and diagnosis of GLM and MDE. The clinical information and treatment of 118 female patients with pathologically-proven GLM or MDE were retrospectively analyzed in the present study. A total of 29 cases had GLM, 77 had MDE and 12 had GLM accompanied by MDE. GLM tends to occur in patients who have had their last birth within 5 years and are usually <40 years of age. GLM masses were usually larger than MDE masses and suppurated or ulcerated more easily. Histopathologically, GLM was characterized by a significant granulomatous inflammatory reaction centered on lobules. Compared with MDE, GLM had a higher incidence of granuloma and microabscess formation within the lobules and surrounding tissue. More multinucleated giant cells within granuloma were observed in patients with GLM than in those with MDE, while MDE was characterized by significant dilatation of the duct terminals and inflammatory changes in the duct wall and periductal tissues. When compared with patients with GLM, foam cells within the duct epithelium or surrounding stroma were more common in patients with MDE. The present study demonstrated that GLM and MDE had distinct clinicopathological characteristics. Further research is required in order to identify more appropriate treatment strategies for these specific types of breast inflammation.

[Effect of continuous renal replacement therapy during percutaneous drainage in severe acute pancreatitis patients: a retrospective cohort study].

OBJECTIVE: To evaluate the clinical efficacy and safety of continuous renal replacement therapy (CRRT) in patients with severe acute pancreatitis (SAP) receiving percutaneous drainage (PCD). METHODS: Clinical data of SAP patients receiving PCD admitted to department of hepatobiliary surgery of the First Affiliated Hospital of Xi'an Jiaotong University from November 11th 2015 to May 13th 2018 were retrospectively analyzed. The patients were divided into CRRT group and control group according to whether or not receiving CRRT. Demographic data, relevant variables before and after PCD, complication and outcome were all compared. RESULTS: A total of 75 patients were included in the study, 30 were treated with application of CRRT and 45 without CRRT. (1) There was no significant difference in gender, age, body mass index (BMI), medical history (smoking, drinking), complications (cardiovascular disease, chronic lung disease, diabetes, chronic renal insufficiency), etiology (gallstone, alcohol abuse, hyperlipidemia and others), or white blood cell count (WBC), C-reactive protein (CRP), serum procalcitonin (PCT), fluid resuscitation, mechanical ventilation, vasoactive agent or intra-abdominal pressure within 48 hours after admission between the two groups. However, acute physiology and chronic health evaluation II (APACHE II) score within 48 hours after admission of CRRT group was significantly higher than that of control group (18.3±4.5 vs. 12.8±6.2, P < 0.05). (2) There was no significant difference in WBC, PCT, APACHE II score or computed tomography severity index (CTSI) before PCD between the two groups. There was no significant difference in the position or times of PCD procedure between the two groups, but the time interval of PCD in the CRRT group was significantly longer than that in the control group (days: 19.4±5.4 vs. 12.8±2.2, P < 0.05). Meanwhile, there was no significant difference in drainage of fluid properties, incidence of abdominal bleeding, infection, gastrointestinal fistula, endoscopic removal of necrotic tissue, laparotomy for removal of necrotic tissue or the time from PCD to endoscopy or laparotomy between two groups. However, the length of intensive care unit (ICU) stay and the length of hospital stay in the CRRT group were significantly longer than those in the control group (days: 23.2±8.5 vs. 15.3±12.1, 51.2±21.2 vs. 31.2±14.0, both P < 0.01). (3) Kaplan-Meier survival analysis showed that there was no significant differences in 1-year or 3-year cumulative survival rates between the two groups (χ21 = 0.097, P1 = 0.755; χ22 = 0.013, P2 = 0.908). CONCLUSIONS: CRRT is safe and feasible in the treatment of SAP patients receiving PCD procedure. It does not increase the risk of bleeding and may delay the time interval of PCD intervention. However, it may prolong the length of ICU stay and the length of hospital stay. It should be worthy of much attention for clinicians.

[Usage of oXiris hemofilter for septic shock patients: a single-center experience].

OBJECTIVE: To evaluate the efficacy and safety of oXiris hemofilter for septic shock patients. METHODS: Clinical data of septic shock patients receiving continuous renal replacement therapy (CRRT) with oXiris hemofilter in department of surgical intensive care unit (SICU) of the First Affiliated Hospital of Xi'an Jiaotong University from March 1st, 2018 to July 20th, 2019 were retrospectively analyzed. The heart rate (HR), mean arterial pressure (MAP), oxygenation index (PaO2/FiO2), lactate (Lac), platelet count (PLT), serum procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP), noradrenaline (NE) dosage, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure score (SOFA) were compared before and after oXiris treatment and the prognosis were also analyzed. RESULTS: Six patients with septic shock were included [5 males, the average age was (56.3±11.8) years old]. A total of 13 oXiris hemofilter sets were performed during treatment. Compared with before treatment, the HR, IL-6 and CRP levels were significantly decreased after treatment [HR (bpm): 93.8±9.7 vs. 133.5±18.3, IL-6 (ng/L): 509.2±169.6 vs. 3 739.8±618.2, CRP (mg/L): 169.1±148.3 vs. 277.8±68.7, all P < 0.05], MAP, PaO2/FiO2 and PLT were significantly increased [MAP (mmHg, 1 mmHg = 0.133 kPa): 73.3±2.2 vs. 63.3±1.6, PaO2/FiO2 (mmHg): 166.8±40.4 vs. 95.1±56.2, PLT (×109/L): 73.3±27.5 vs. 41.2±21.4, all P < 0.05]; meanwhile, NE dosage, APACHE II and SOFA scores were significantly decreased [NE (µg×kg-1×min-1): 0.4±0.3 vs. 1.2±0.7, APACHE II: 18.8±6.9 vs. 30.0±7.3, SOFA: 11.7±4.2 vs. 17.3±2.1, all P < 0.05]. Although Lac and PCT decreased after treatment, there was no significant difference [Lac (mmol/L): 3.5±2.1 vs. 6.1±3.2, PCT (µg/L): 37.7±48.3 vs. 85.1±32.8, both P > 0.05]. At the end, 3 of the 6 patients survived and the others were discharged again medical advice. The length of SICU stay was 3 to 23 days, with an average of (13.0±8.5) days. No adverse events occurred during the treatment. CONCLUSIONS: oXiris hemofilter can effectively remove inflammatory mediators in circulation, significantly improve hemodynamic status and severity, and may be considered as a safe and reliable treatment modality for septic shock patients.

Thymoquinone inhibits metastatic phenotype and epithelial­mesenchymal transition in renal cell carcinoma by regulating the LKB1/AMPK signaling pathway.

Thymoquinone, isolated from the seeds of Nigella sativa, has exhibited antitumor properties in a variety of cancer types. However, few studies have investigated the effect of thymoquinone (TQ) on migration and invasion in renal cell carcinoma (RCC). In the present study, our results confirmed that TQ significantly inhibited the migration and invasion of the human RCC 769­P and 786­O cell lines, as demonstrated by wound healing and Transwell assays. Additionally, TQ upregulated the expression of E­cadherin and downregulated the expression of Snail, ZEB1 and vimentin at the mRNA and protein levels in a concentration­dependent manner. Subsequently, the phosphorylation levels of liver kinase B1 (LKB1) and AMP­activated protein kinase (AMPK) were increased upon TQ treatment. To further validate the role of LKB1/AMPK signaling, we revealed that TQ­mediated increase of E­cadherin level and reduction of Snail level could be further enhanced by LKB1 overexpression. Furthermore, co­treatment with the AMPK inhibitor Compound C attenuated the anti­metastatic effect of TQ on RCC and partially abrogated the high expression of E­cadherin and the low expression of Snail mediated by TQ. In contrast, the AMPK activator AICAR demonstrated the opposite effect. Collectively, the present study revealed that TQ could markedly suppress the metastatic phenotype and reverse the epithelial­mesenchymal transition in RCC by regulating the LKB1/AMPK signaling pathway, indicating that TQ may be a potential therapeutic candidate against RCC.