tRNA-derived fragment 3'tRF-AlaAGC modulates cell chemoresistance and M2 macrophage polarization via binding to TRADD in breast cancer.

BACKGROUND: Drug resistance, including Adriamycin-based therapeutic resistance, remains a challenge in breast cancer (BC) treatment. Studies have revealed that macrophages could play a pivotal role in mediating the chemoresistance of cancer cells. Accumulating evidence suggests that tRNA-Derived small RNAs (tDRs) are associated the physiological and pathological processes in multiple cancers. However, the underlying mechanisms of tDRs on chemoresistance of BC in tumor-associated macrophages remain largely unknown. METHODS: The high-throughput sequencing technique was used to screen tDRs expression profile in BC cells. Gain- and loss-of-function experiments and xenograft models were performed to verify the biological function of 3'tRF-Ala-AGC in BC cells. The CIBERSORT algorithm was used to investigate immune cell infiltration in BC tissues. To explore the role of 3'tRF-Ala-AGC in macrophages, M2 macrophages transfected with 3'tRF-Ala-AGC mimic or inhibitor were co-cultured with BC cells. Effects on Nuclear factor-κb (NF-κb) pathway were investigated by NF-κb nuclear translocation assay and western blot analysis. RNA pull-down assay was performed to identify 3'tRF-Ala-AGC interacting proteins. RESULTS: A 3'tRF fragment of 3'tRF-AlaAGC was screened, which is significantly overexpressed in BC specimens and Adriamycin-resistant cells. 3'tRF-AlaAGC could promote cell malignant activity and facilitate M2 polarization of macrophages in vitro and in vivo. Higher expression of M2 macrophages were more likely to have lymph node metastasis and deeper invasion in BC patients. Mechanistically, 3'tRF-AlaAGC binds Type 1-associated death domain protein (TRADD) in BC cells, and suppression of TRADD partially abolished the enhanced effect of 3'tRF-AlaAGC mimic on phenotype of M2. The NF-κb signaling pathway was activated in BC cells co-cultured with M2 macrophages transfected with 3'tRF-AlaAGC mimic. CONCLUSIONS: 3'tRF-AlaAGC might modulate macrophage polarization via binding to TRADD and increase the effect of M2 on promoting the chemoresistance in BC cells through NF-κb signaling pathway.

Deciphering microbiome and fungi-bacteria interactions in chronic wound infections using metagenomic sequencing.

PURPOSE: Chronic wounds caused by infections impose a considerable global healthcare burden. The microbial features of these infections and possible correlations between bacteria and fungi may influence wound healing. However, metagenomic next-generation sequencing (mNGS) analyses of these features remain sparse. Therefore, we performed mNGS on chronic wound infection samples to investigate features and correlations between the bacteriome and mycobiome in 66 patients (28: chronic wounds; 38: non-chronic wounds). METHODS: Microbial community characteristics in patients with wound infections, microbiome-systemic inflammation associations, and bacteria-fungi correlations were analyzed. RESULTS: Infections constituted the primary cause of wounds in this study. Nontuberculous mycobacteria (23%) and Mycobacterium tuberculosis (13%) were the most common pathogens associated with chronic wounds, whereas Staphylococcus aureus (15%) was the most prevalent in non-chronic wound infections. Patients with chronic wound infections had a higher abundance of Pseudomonas aeruginosa than those without chronic wounds. Microbes with a high relative abundance in chronic wound infections were less significantly associated with plasma inflammatory factors than those in non-chronic wound infections. Additionally, a positive correlation between Candida glabrata and P. aeruginosa and an association between Malassezia restricta and anaerobic species were detected in patients with chronic wound infections. CONCLUSION: Our results further support the hypothesis that P. aeruginosa is a microbial biomarker of chronic wound infection regardless of the causative pathogens. Moreover, we propose a positive correlation between C. glabrata and P. aeruginosa in chronic wound infections, which advances the current understanding of fungi-bacteria correlations in patients with chronic wound infections.

Perinatal outcomes comparison between neuraxial and general anesthesia in pregnant women with placenta accreta spectrum: a multicenter retrospective study.

PURPOSE: We investigated the impact of anesthesia mode on perinatal outcomes in patients with placenta accreta spectrum (PAS) undergoing cesarean delivery and identified factors associated with adverse perinatal events. METHODS: The multicenter retrospective analysis was conducted in patients with PAS who delivered at three medical centers. Patients were classified according to whether they received general anesthesia (GA) or neuraxial anesthesia (NA). We compared the basic clinical characteristics of patients in the pre-propensity score matching (PSM) and post-PSM cohorts and identified factors associated with a high risk of adverse maternal outcomes. RESULTS: This study included a total of 425 patients, with 307 (72.2%) in the GA group and 118 (27.8%) in the NA group. After PSM, 162 patients were identified for analysis. In the post-matched cohort, the NA group exhibited shorter total operation time (P = 0.030) and postoperative length of hospital stay (P = 0.037). Additionally, the NA group experienced lower intraoperative blood loss (P < 0.001) and received fewer units of transfused packed red blood cells (PRBC) (P < 0.001). Multivariate logistic regression analysis indicated that GA (P < 0.001), emergency cesarean delivery (P = 0.010), vascular lacunae within the placenta (P < 0.001), hypervascularity of uterine-placental margin (P = 0.002), hypervascularity of the cervix (P = 0.014), and balloon placement in the abdominal aorta (P < 0.001) were associated with a high risk of adverse maternal events. CONCLUSION: In comparison to GA, cesarean delivery with NA in PAS patients appears to be associated with reduced intraoperative blood loss, PRBC transfusion, operating duration, and postoperative hospital stay.

Establishment of a risk classifier to predict the in-hospital death risk of nosocomial fungal infections in cancer patients.

BACKGROUND: Patients with malignancy are at a higher risk of developing nosocomial infections. However, limited studies investigated the clinical features and prognostic factors of nosocomial infections due to fungi in cancer patients. Herein, this study aims to investigate the clinical characteristics of in-hospital fungal infections and develop a nomogram to predict the risk of in-hospital death during fungal infection of hospitalized cancer patients. METHODS: This retrospective observational study enrolled cancer patients who experienced in-hospital fungal infections between September 2013 and September 2021. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of in-hospital mortality. Variables demonstrating significant statistical differences in the multivariate analysis were utilized to construct a nomogram for personalized prediction of in-hospital death risk associated with nosocomial fungal infections. The predictive performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. RESULTS: A total of 216 participants were included in the study, of which 57 experienced in-hospital death. C.albicans was identified as the most prevalent fungal species (68.0%). Respiratory infection accounted for the highest proportion of fungal infections (59.0%), followed by intra-abdominal infection (8.8%). The multivariate regression analysis revealed that Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 3-4 (odds ratio [OR] = 6.08, 95% confidence interval [CI]: 2.04-18.12), pulmonary metastases (OR = 2.76, 95%CI: 1.11-6.85), thrombocytopenia (OR = 2.58, 95%CI: 1.21-5.47), hypoalbuminemia (OR = 2.44, 95%CI: 1.22-4.90), and mechanical ventilation (OR = 2.64, 95%CI: 1.03-6.73) were independent risk factors of in-hospital death. A nomogram based on the identified risk factors was developed to predict the individual probability of in-hospital mortality. The nomogram demonstrated satisfactory performance in terms of classification ability (area under the curve [AUC]: 0.759), calibration ability, and net clinical benefit. CONCLUSIONS: Fungi-related nosocomial infections are prevalent among cancer patients and are associated with poor prognosis. The constructed nomogram provides an invaluable tool for oncologists, enabling them to make timely and informed clinical decisions that offer substantial net clinical benefit to patients.

Delayed interval delivery in a quadruplet pregnancy: a case report and literature review.

BACKGROUND: As the rate of multiple pregnancies increases, delayed interval delivery (DID) is increasingly being implemented to improve perinatal outcomes. But there are no international guidelines for DID in multiple pregnancies. We report a case of DID in a quadruplet pregnancy and review the relevant literature to summarize the management of DID in multiple pregnancies. CASE PRESENTATION: A 22-year-old woman, 22 2/7 weeks' gestation, with quadruplets, was admitted to the hospital for a first cervical cerclage due to cervical dilation. Twenty-five days later, it was found that the cervix was dilated again, so after removing the cervical cerclage, the first quadruplet was delivered vaginally (25 6/7 weeks), and a second cervical cerclage was performed. Four days later, due to re-dilation of the cervix, after removal of the cervical cerclage, the second quadruplet was delivered vaginally (26 3/7 weeks), followed by a third cervical cerclage. Six days later, the pregnancy was terminated by cesarean section due to fetal distress, and the third and fourth quadruplets were delivered (27 2/7 weeks). The patient had no postoperative complications, and all four infants were treated in the neonatal intensive care unit and discharged successfully. CONCLUSION: This case emphasizes that comprehensive management of delayed interval delivery can improve perinatal outcomes in multiple pregnancies, including anti-infection, tocolytic therapy, practice to promote fetal lung, and cervical cerclage.

Bioinformatics methods in biomarkers of preeclampsia and associated potential drug applications.

BACKGROUND: Preeclampsia is a pregnancy-related condition that causes high blood pressure and proteinuria after 20 weeks of pregnancy. It is linked to increased maternal mortality, organ malfunction, and foetal development limitation. In this view, there is a need critical to identify biomarkers for the early detection of preeclampsia. The objective of this study is to discover critical genes and explore medications for preeclampsia treatment that may influence these genes. METHODS: Four datasets, including GSE10588, GSE25906, GSE48424 and GSE60438 were retrieved from the Gene Expression Omnibus database. The GSE10588, GSE25906, and GSE48424 datasets were then removed the batch effect using the "sva" R package and merged into a complete dataset. The differentially expressed genes (DEGs) were identified using the "limma" R package. The potential small-molecule agents for the treatment of PE was further screened using the Connective Map (CMAP) drug database based on the DEGs. Further, Weight gene Co-expression network (WGNCA) analysis was performed to identified gene module associated with preeclampsia, hub genes were then identified using the logistic regression analysis. Finally, the immune cell infiltration level of genes was evaluated through the single sample gene set enrichment analysis (ssGSEA). RESULTS: A total of 681 DEGs (376 down-regulated and 305 up-regulated genes) were identified between normal and preeclampsia samples. Then, Dexamethasone, Prednisone, Rimexolone, Piretanide, Trazodone, Buflomedil, Scoulerin, Irinotecan, and Camptothecin drugs were screened based on these DEGs through the CMAP database. Two modules including yellow and brown modules were the most associated with disease through the WGCNA analysis. KEGG analysis revealed that the chemokine signaling pathway, Th1 and Th2 cell differentiation, B cell receptor signalling pathway and oxytocin signalling pathway were significantly enriched in these modules. Moreover, two key genes, PLEK and LEP were evaluated using the univariate and multivariate logistic regression analysis from the hub modules. These two genes were further validated in the external validation cohort GSE60438 and qRT-PCR experiment. Finally, we evaluated the relationship between immune cell and two genes. CONCLUSION: In conclusion, the present study investigated key genes associated with PE pathogenesis that may contribute to identifying potential biomarkers, therapeutic agents and developing personalized treatment for PE.

Evaluation of respiratory samples in etiology diagnosis and microbiome characterization by metagenomic sequencing.

BACKGROUND: The application of clinical mNGS for diagnosing respiratory infections improves etiology diagnosis, however at the same time, it brings new challenges as an unbiased sequencing method informing all identified microbiomes in the specimen. METHODS: Strategy evaluation and metagenomic analysis were performed for the mNGS data generated between March 2017 and October 2019. Diagnostic strengths of four specimen types were assessed to pinpoint the more appropriate type for mNGS diagnosis of respiratory infections. Microbiome complexity was revealed between patient cohorts and infection types. A bioinformatic pipeline resembling diagnosis results was built based upon multiple bioinformatic parameters. RESULTS: The positive predictive values (PPVs) for mNGS diagnosing of non-mycobacterium, Nontuberculous Mycobacteria (NTM), and Aspergillus were obviously higher in bronchoalveolar lavage fluid (BALF) demonstrating the potency of BALF in mNGS diagnosis. Lung tissues and sputum were acceptable for diagnosis of the Mycobacterium tuberculosis (MTB) infections. Interestingly, significant taxonomy differences were identified in sufficient BALF specimens, and unique bacteriome and virome compositions were found in the BALF specimens of tumor patients. Our pipeline showed comparative diagnostic strength with the clinical microbiological diagnosis. CONCLUSIONS: To achieve reliable mNGS diagnosis result, BALF specimens for suspicious common infections, and lung tissues and sputum for doubtful MTB infections are recommended to avoid the false results given by the complexed respiratory microbiomes. Our developed bioinformatic pipeline successful helps mNGS data interpretation and reduces manual corrections for etiology diagnosis.

A randomized controlled trial of low-dose aspirin for the prevention of preeclampsia in women at high risk in China.

BACKGROUND: Low-dose aspirin has been the most widely studied preventive drug for preeclampsia. However, guidelines differ considerably from country to country regarding the prophylactic use of aspirin for preeclampsia. There is limited evidence from large trials to determine the effect of 100 mg of aspirin for preeclampsia screening in women with high-risk pregnancies, based on maternal risk factors, and to guide the use of low-dose aspirin in preeclampsia prevention in China. OBJECTIVE: The Low-Dose Aspirin in the Prevention of Preeclampsia in China study was designed to evaluate the effect of 100 mg of aspirin in preventing preeclampsia among high-risk pregnant women screened with maternal risk factors in China, where preeclampsia is highly prevalent, and the status of low-dose aspirin supply is commonly suboptimal. STUDY DESIGN: We conducted a multicenter randomized controlled trial at 13 tertiary hospitals from 11 provinces in China between 2016 and 2019. We assumed that the relative reduction in the incidence of preeclampsia was at least 20%, from 20% in the control group to 16% in the aspirin group. Therefore, the targeted recruitment number was 1000 participants. Women were randomly assigned to the aspirin or control group in a 1:1 allocation ratio. Statistical analyses were performed according to an intention-to-treat basis. The primary outcome was the incidence of preeclampsia, diagnosed along with a systolic blood pressure of ≥140 mm Hg or a diastolic blood pressure of ≥90 mm Hg after 20 weeks of gestation, with a previously normal blood pressure (systolic blood pressure of <140 mm Hg and diastolic blood pressure of <90 mm Hg), and complicated by proteinuria. The secondary outcomes included maternal and neonatal outcomes. Logistic regression analysis was used to determine the significance of difference of preeclampsia incidence between the groups for both the primary and secondary outcomes. Interaction analysis was also performed. RESULTS: A total of 1000 eligible women were recruited between December 2016 and March 2019, of which the final 898 patients were analyzed (464 participants in the aspirin group, 434 participants in the control group) on an intention-to-treat basis. No significant difference was found in preeclampsia incidence between the aspirin group (16.8% [78/464]) and the control group (17.1% [74/434]; relative risk, 0.986; 95% confidence interval, 0.738-1.317; P=.924). Likewise, adverse maternal and neonatal outcomes did not differ significantly between the 2 groups. Meanwhile, the incidence of postpartum hemorrhage between the 2 groups was similar (6.5% [30/464] in the aspirin group and 5.3% [23/434] in the control group; relative risk, 1.220; 95% confidence interval, 0.720-2.066; P=.459). We did not find any significant differences in preeclampsia incidence between the 2 groups in the subgroup analysis of the different risk factors. CONCLUSION: A dosage of 100 mg of aspirin per day, initiated from 12 to 20 gestational weeks until 34 weeks of gestation, did not reduce the incidence of preeclampsia in pregnant women with high-risk factors in China.

The role of p53-MDM2 signaling in missed abortion and possible pathogenesis.

BACKGROUND: Missed abortion is one of the common obstetrical and gynecological complications, angiogenesis is the most important factor in fetal and placental development. However, the definite etiology and pathogenesis are not fully understood. METHODS: The mRNA levels of p53, MDM2, VEGF, and HIF-lα were detected in 60 villous samples of missed abortion patients and 64 healthy controls by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Immunohistochemistry was used to explore the expression and correlation of p53, MDM2, VEGF, and HIF-lα in villous tissues. Furthermore, we upregulated MDM2 expression in JEG-3 and BeWo cells under hypoxia, combined with Nutlin3, the cell cycle was determined using flow cytometry and the expressions of p53, MDM2, VEGF, and HIF-1α were determined by qRT-PCR and western blot. RESULTS: qRT-PCR demonstrated that the expressions of p53, MDM2, and HIF-1α were significantly increased and VEGF was decreased in missed abortion group compared with normal pregnancies. Correlation analysis found that p53 was positively correlated with MDM2 and HIF-1α, and negatively correlated with VEGF in missed abortion group. After administration of Nutlin3, overexpression of MDM2 could arrest cell cycle in G1 phase and reduce the proportion of S phase. The expression of p53 and MDM2 of JEG-3 cells and BeWo cells which transfected with pcDNA3.1-MDM2 plasmid were markedly increased after Nutlin3 addition under hypoxic conditions, while the expression of VEGF and HIF-1α decreased. CONCLUSION: Our data indicated that during the development of villi in early pregnancy, p53-MDM2 signaling regulate cell cycle and angiogenesis through interaction with HIF-1α and VEGF, which may be a crucial factor affecting pregnancy outcomes.

Assessment of the Clinical Utility of Circulating Tumor Cells at Different Time Points in Predicting Prognosis of Patients With Small Cell Lung Cancer: A Meta-Analysis.

OBJECTIVES: Numerous studies have elucidated that circulating tumor cells (CTCs) have significant prognostic value in various solid tumors. However, the prognostic value of CTCs in small cell lung cancer (SCLC) remains controversial. The current study was performed to investigate the prognostic significance of different time points of CTCs in SCLC. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library databases were retrieved for eligible studies. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to investigate the association between CTCs level and overall survival (OS) and progression-free survival (PFS) in SCLC. Furthermore, subgroup analyses, sensitivity analysis, Begg's and Egger's tests were also conducted. RESULTS: Sixteen cohort studies with 1103 participants were eligible for this meta-analysis. Our results revealed that higher pretreatment CTCs level was significantly correlated with worse OS in SCLC no matter CellSearch (HR, 2.95; 95%CI, 1.56-5.58; P = .001) or other methods (HR, 2.37; 95%CI, 1.13-4.99; P = .023) was used to detect CTCs. Higher pretreatment CTCs status detected by CellSearch was associated with shorter PFS (HR, 3.75; 95%CI, 2.52-5.57; P < .001), while there was no significant association when other methods were adopted to CTC detection (HR, 2.04; 95%CI, .73-5.68; P = .172). Likewise, we observed that higher post-therapy CTCs level detected by both CellSearch (HR, 2.99; 95%CI, 1.51-5.93; P = .002) and other methods (HR, 4.79; 95%CI, 2.03-11.32; P < .001) was significantly correlated with decreased OS in SCLC. However, higher post-therapy CTCs count detected by CellSearch was not correlated with worse PFS (HR, 1.80; 95%CI, .83-3.90; P = .135). Sensitivity analysis demonstrated that the pooled data were still stable after eliminating studies one by one. However, significant publication bias was observed between pretreatment CTCs level detected by CellSearch and OS of SCLC. CONCLUSION: Dynamic monitoring of CTCs level could be a non-invasive and effective tool to predict the disease progression and prognosis in patients with SCLC.

Association of ß-arrestin1 and p53-Mdm2 signaling in the development of missed abortion.

BACKGROUND: Missed abortion is a peculiar form of spontaneous abortion before 20 weeks' gestation. The definite etiology and pathogenesis are not fully understood. Recent studies have demonstrated that p53/Mdm2-mediated ubiquitination of the IGF-1R may be closely related to G-protein-coupled receptor kinases (GRK)/ß-arrestin1 system. Our previous studies have confirmed that the elevated expression of p53 and Mdm2 may be responsible for apoptosis during missed abortion. However, there was no information surrounding ß-arrestin1 in missed abortion. METHODS: The mRNA levels of ß-arrestin1 in villous samples of 30 missed abortion patients and 31 healthy controls were determined by real-time quantitative polymerase chain reaction (PCR). Immunohistochemistry was used to explore the expression and location of ß-arrestin1, p53, Mdm2, VEGF and HIF-lα in trophoblasts. Transwell assays were performed to examine the influences of ß-arrestin1 expression on cell invasion. Furthermore, we tested the effect of ß-arrestin1 on the expression of p53, Mdm2, ERK, AKT and NF-κB. RESULTS: The expression of ß-arrestin1 in the villous samples of missed abortion group was dramatically lower than control group by quantitative real-time-PCR and immunohistochemistry. Furthermore, the patients with missed abortion showed significantly higher levels of p53, Mdm2, HIF-lα and lower level of VEGF than healthy controls by immunohistochemistry. Functional studies showed that suppression of ß-arrestin1 in HTR-8 cells inhibited cell invasion. The protein expressions of ERK and AKT in HTR-8 cells were significantly downregulated by reducing the expression of ß-arrestin1, while the expressions of p53, Mdm2, NF-κB were enhanced. Overexpression of ß-arrestin1 exhibited the adverse effect. CONCLUSION: Our data indicated that ß-arrestin1 play an important role in maintaining the maternal-fetal tolerance, the decreased expression of ß-arrestin1 in the villous samples may be related with the development of missed abortion.

Cytochrome c injection induced embryo loss.

Cytochrome c has been used as first-aid in the clinic for organs which are lacking oxygen. But recent report show cytochrome c injection destroys dendritic cells (DCs) which play a pivotal role in feto-maternal tolerance. However, it is not clear whether cytochrome c injection causes abortion. The cytochrome c was injected by tail vein of mice at the Day 5.5 of pregnancy (E5.5) after mating with male BALB/c mice. The total number of implantations and resorption sites was recorded at the E12.5 in pregnant mice. Expression of interferon-γ, tumor necrosis-α interleukin (IL)-4, IL-10, IL-12 and transforming growth factor-ß in the mouse endometrium was measured by ELISA. Injection of cytochrome c via tail vein at the E5.5 induced fetal resorption at E12.5, and evoked an immune imbalance at the maternal-fetal interface. Notably, injection of mouse bone marrow-derived DCs (BM-DCs) rescued the cytochrome c-evoked embryo resorption. The present study suggests cytochrome c injection causes embryo resorption in mice, hinting caution regarding the use of cytochrome c in pregnant women. In addition, it may provide an easy and novel way to establish a mouse model of abortion.HighlightsCytochrome c injection induced fetal rejection.Cytochrome c injection leads to a T helper 1/T helper 2 imbalance at the maternal-fetal interface.A mouse model of abortion was established by injecting tail vein with cytochrome c.

[Effect of the reactive oxygen species-induced by bisphenol A on liver lipid metabolism disorder].

OBJECTIVE: To explore the toxic effect of bisphenol A on the liver, as well as the influence effect on lipid metabolism. METHODS: The toxic effects of bisphenols on human health were studied by using in vivo experiments of bisphenol A exposure in rats and in vitro experiments of human liver cell line HL-7702. Male SD rats were divided into control group(Ctrl), 1 mg/(kg·d) group(low), 5 mg/(kg·d) group(medium) and 25 mg/(kg·d) group(high) for 14 days subacute exposure of bisphenol A, to evaluate the toxic effect of bisphenol A on the liver in terms of body weight, liver organ index, liver pathological tissue sections, serum biochemical indicators. Then HL-7702 was divided into four groups: control group(Ctrl), low concentration treatment group(0. 16 µmol/L), medium concentration treatment group(4 µmol/L) and high concentration treatment group(100 µmol/L). After 24 hours of exposure to bisphenol A, the contents of triglyceride(TG) and total cholesterol(TC) in cells, reactive oxygen species(ROS) levels were detected, and the transcription levels of genes related to lipid metabolism and oxidative stress were detected by fluorescent quantitative PCR. RESULTS: The 14-day subacute exposure had no significant effect on rat body weight and liver body weight ratio, but liver pathological sections clearly showed that bisphenol A exposure can damage liver tissue structure. Serum biochemical indicator of total bile acid(TBA) was significantly reduced in the high-dose group, which was(4. 75±0. 33)µmol/L, creatinine(Cr) was significantly increased in the medium and high-dose group, which were(18. 00±0. 76)µmol/L and(18. 83±0. 75)µmol/L, respectively. TC, high-density lipoprotein(HDL-C) and low-density lipoprotein(LDL-C) were significantly reduced in the middle-and high-dose groups(P<0. 05), which were(1. 44±0. 10), (1. 14±0. 10)mmol/L;(0. 84±0. 04), (0. 63±0. 07)mmol/L and(0. 21±0. 04), (0. 16±0. 05)mmol/L, respectively. Bisphenol A exposure could significantly reduce the content of TC in hepatocytes(P<0. 05). BPA treatment could significantly increase ROS levels in HL-7702 cells. The transcription level of PPARα was significantly increased in the high concentration group, FABP1 was significantly increased in the high concentration group, SOD1 was significantly decreased in the medium and high concentration group(P<0. 05). CONCLUSION: Bisphenol A may cause oxidative stress by inducing excessive ROS production in liver cells, leading to liver damage and disorder of lipid metabolism in the body, thereby showing liver toxicity.

TWIST1 Alleviates Hypoxia-induced Damage of Trophoblast Cells by inhibiting mitochondrial apoptosis pathway.

Preeclampsia (PE), especially severe and early-onset preeclampsia is one of the major causes of maternal and neonatal morbidity and mortality. However, the exact mechanism is not fully understood. In this study, we first demonstrated that the expression of TWIST1 was decreased in the placental tissues of patients with early-onset severe preeclampsia, compared with non-severe early onset preeclampsia. In hypoxia-treated HTR-8/SVneo cells, our study showed that TWIST1 expression was significantly decreased. Moreover, TWIST1 overexpression reduced apoptosis and enhanced invasion and tube formation of HTR-8/SVneo cells while TWIST1 knockdown showed the opposite results. Mechanistically, TWIST1 inhibited apoptosis by blocking the activation of mitochondrial apoptosis signaling Bax/Bcl-2/Caspase-9/Caspase-3, which was confirmed by the use of Caspase-9 activator and inhibitor. This was in line with the reduced ROS formation and the decreased mitochondrial transmembrane potential. On the other hand, TWIST1 increased the ability of migration and invasion of HTR-8/SVneo cells via enhancements of MMP-2/9 expression. Taken together, for the first time we show that TWIST1 plays an important role in the survival, invasion and tube formation of-HTR8/SVneo cells treated with hypoxia. This hypoxia-treated cell model partly mimics the in vivo condition of decreased placental perfusion induced by H/R. Thus, our study provides an important clue about TWIST1 molecular mechanism underlying the development of preeclampsia.

Microbiological Diagnostic Performance of Metagenomic Next-generation Sequencing When Applied to Clinical Practice.

Background: Metagenomic next-generation sequencing (mNGS) was suggested to potentially replace traditional microbiological methodology because of its comprehensiveness. However, clinical experience with application of the test is relatively limited. Methods: From April 2017 to December 2017, 511 specimens were collected, and their retrospective diagnoses were classified into infectious disease (347 [67.9%]), noninfectious disease (119 [23.3%]), and unknown cases (45 [8.8%]). The diagnostic performance of pathogens was compared between mNGS and culture. The effect of antibiotic exposure on detection rate was also assessed. Results: The sensitivity and specificity of mNGS for diagnosing infectious disease were 50.7% and 85.7%, respectively, and these values outperformed those of culture, especially for Mycobacterium tuberculosis (odds ratio [OR], 4 [95% confidence interval {CI}, 1.7-10.8]; P < .01), viruses (mNGS only; P < .01), anaerobes (OR, ∞ [95% CI, 1.71-∞]; P < .01) and fungi (OR, 4.0 [95% CI, 1.6-10.3]; P < .01). Importantly, for mNGS-positive cases where the conventional method was inconclusive, 43 (61%) cases led to diagnosis modification, and 41 (58%) cases were not covered by empirical antibiotics. For cases where viruses were identified, broad-spectrum antibiotics were commonly administered (14/27), and 10 of 27 of these cases were suspected to be inappropriate. Interestingly, the sensitivity of mNGS was superior to that of culture (52.5% vs 34.2%; P < .01) in cases with, but not without, antibiotic exposure. Conclusions: mNGS could yield a higher sensitivity for pathogen identification and is less affected by prior antibiotic exposure, thereby emerging as a promising technology for detecting infectious diseases.

Importation of Mumps Virus Genotype K to China from Vietnam.

During May-August 2016, mumps virus genotype K was detected in 12 Vietnam citizens who entered China at the Shuikou border crossing and 1 girl from China. We provide evidence that mumps genotype K is circulating in Vietnam and was imported to China from Vietnam.

Nestin is highly expressed in foetal spinal cord isolated from placenta previa patients and promotes inflammation by enhancing NF-κB activity.

PURPOSE: Nestin is expressed in various tissues of the embryo in patients with placenta previa, while the regulatory mechanism still unknown. MATERIALS AND METHODS: All participants terminated pregnancy. Among them, 75 patients with placenta previa were assigned to the case group and 80 healthy pregnant women with normal placenta were assigned to the control group. Expression of nestin and CDK5 in foetal spinal cord tissues was detected by Western blot and quantitative real-time RT-PCR methods. The enzyme-linked immunosorbent assay (ELISA) was used to determine the serum expression of some pro-inflammatory cytokines in placenta previa patients. The interaction between nestin and CDK5 was evaluated by immunoprecipitation and siRNA inhibition of nestin was performed to estimate its effect on NF-κB activity in foetal spinal cord tissues. RESULTS: Along with increased expression of nestin and CDK5 in foetal spinal cord tissues in the case group, IL-1ß, IL-6, TNF-α and IFN-γ were increased in the serum of placenta previa patients. siRNA inhibition analysis indicated that nestin interacted with CDK5 and regulated NF-κB activity in foetal spinal cord tissues. CONCLUSIONS: Nestin is highly expressed and the interaction between nestin and CDK5 might lead to the progress of placenta previa through its regulation on NF-κB.

Promoter Methylation Status of WNT2 in Placenta from Patients with Preeclampsia.

BACKGROUND Preeclampsia is a serious multisystem disorder of human gestation, affecting up to 10% of pregnant women worldwide, and results in maternal morbidity and mortality. The aim of this study was to determine the gene expression pattern and methylation status of the promoter of the WNT2 gene in placentas from patients with preeclampsia and to evaluate the potential role of the WNT2 pathway in the pathogenesis of preeclampsia. MATERIAL AND METHODS Real-time quantitative polymerase chain reaction (PT-PCR) was used to determine the WNT2 gene expression level. Western blot analysis was used to identify alterations in wnt2 protein expression. RESULTS The mRNA and protein expression levels of the WNT2 gene were reduced in placentas from patients with preeclampsia when compared with placentas from healthy women. The average methylation level of the promoter of the WNT2 gene was elevated in the placentas from patients with preeclampsia compared with the controls placentas from healthy women. CONCLUSIONS The findings of this study have shown that molecular mechanisms, including aberrant activation of the WNT2 gene signaling pathway, may be involved in the pathogenesis of preeclampsia. Promoter hypermethylation and reduced expression of the WNT2 gene requires further study to determine a potential role in the diagnosis and treatment of preeclampsia.

High prevalence and genetic diversity of noroviruses among children with sporadic acute gastroenteritis in Nanning City, China, 2010-2011.

A molecular epidemiological study of Norovirus (NoV) infections in children aged <5 years was conducted in the outpatient department of a hospital between January 2010 and December 2011 in Nanning City, Guangxi Zhuang Autonomous Region of China. Fecal samples were collected from 354 pediatric patients with acute gastroenteritis, and were screened for the presence of NoV with one-step real-time reverse-transcription polymerase chain reaction (RT-PCR). NoV genogroup II (GII) was detected in 28.5% (101/342) of samples, but no NoV GI was found. Eighty-four of the NoV GII strains were successfully sequenced, and they were clustered into seven genotypes: GII.4 (77.4%), GII.2 (8.3%), GII.14 (4.8%), GII.7 (3.6%), GII.3 (2.4%), GII.6 (2.4%), and GII.12 (1.2%). The predominant GII.4 variant in circulation was variant 2006b (92.3%). Importantly, the emergence of variant GII.4 2010 was detected. NoV was detected throughout the year, but mainly during the cold months. The highest prevalence of NoV was detected in young children aged <2 years. The NoV detection rates did not differ significantly in males and females. This is the first report to demonstrate the high prevalence and genetic diversity of NoVs in children with sporadic acute gastroenteritis in Nanning. Our study findings indicate the need for continual surveillance to monitor epidemiological changes and potential new variants of these viruses.