Prenatal ultrasound diagnosis and quality control of fetal nuchal translucency. / èƒŽå„¿é¢ˆé¡¹é€æ˜Žå±‚äº§å‰è¶ å£°è¯Šæ–­åŠè´¨é‡æŽ§åˆ¶.

OBJECTIVES: In clinical ultrasound examinations, it is challenging to perform quality control on the images of each fetal nuchal translucency (NT) and crown-rump length (CRL). However, small measurement differences can increase the probability of false-positive or false-negative diagnosis. Therefore, it is necessary to establish a quality control system for fetal NT examination. This study aims to control the quality of fetal NT and CRL measurements, evaluate the accuracy of ultrasound physicians in early pregnancy NT measurements, and analyze the impact of increased fetal structure screening on the detection rate of chromosomal abnormalities. METHODS: Data were collected from cases before and after 12 months of NT examination quality control, with 2 214 before quality control and 2 538 cases after quality control. Three quality control data metrics were analyzed: NT multiple of median (NT-MoM), standard deviation (SD) of log10MoM [(SD) log10MoM], and the slope of NT on CRL (SNC). The performance of NT measurements was monitored through the individual CRL NT-MoM within the 0.9-1.1 MoM range of the normal median curve, while grouped based on different years of experience (<3 years, 3-6 years, >6 years), and NT-MoM values among these groups were compared. Data on NT thickening, structural anomalies, and chromosomal abnormalities were retrospectively analyzed during the quality control period. RESULTS: According to the curve equation of the American NTQR project group, the NT-MoM value before quality control was 0.921 7 MoM, the (SD) log10MoM value was 0.091 92, and the SNC value was 12.20%. After quality control, the NT-MoM value was 0.948 3 MoM, the (SD) log10MoM value was 0.094 81, and the SNC value was 11.43%. The comparison of NT-MoM values before and after quality control showed a statistically significant difference (P<0.000 1). The comparison of NT-MoM values measured by ultrasound physicians with different years of experience before and after quality control also showed statistically significant differences (P<0.000 1). The NT-MoM values for the 3-6 years and >6 years groups were higher after quality control (P<0.05), while the <3 years group showed no significant difference before and after quality control (P>0.05). After quality control, cases of NT thickening without significant structural abnormalities accounted for 19.05%, NT thickening with structural abnormalities accounted for 47.62%, and NT normal with structural abnormalities accounted for 33.33%. There were 36 cases of fetal heart abnormalities, accounting for 20.34% of the total abnormality rate, with a positive rate of 36% in chromosome tests. CONCLUSIONS: After quality control, ultrasound physicians measure NT more accurately, but differences among measurements remain. Measurements by experienced ultrasound physicians are closer to expected values, usually lower than expected. Monitoring fetal NT and CRL measurements helps improve measurement accuracy. Increasing structural screening during NT examinations, especially for the fetal heart, enhances the detection rate of chromosomal abnormalities.

Molecular genetic mechanism analysis and pedigree investigation of rare Bweak subgroup.

OBJECTIVE: To analyze the molecular mechanism of rare Bweak subgroup in the ABO blood group system and conduct pedigree investigations. METHODS: The blood group was detected by conventional serological method, and ABO gene of proband and her family was amplified and sequenced by polymerase chain reaction method. RESULTS: The study showed that the proband was a Bweak phenotype by conventional serological method. Her family's serological results were as follows, her father and eldest brother were Bweak subgroup while her mother and second eldest brother were O group. The proband's ABO gene sequencing result was ABO*BW.27/ABO*O.01.02. Her father, mother and two elder brothers were ABO*BW.27/ABO*O.01.01, ABO*O.01.01/ABO*O.01.02, ABO*BW.27/ABO*O.01.02, ABO*O.01.01/ABO*O.01.02. CONCLUSION: Conventional blood group serology combined with molecular diagnostic technology can accurately identify the Bweak subgroup, and the pedigree investigation analysis showed that the proband's allelic mutation came from her father. She has gained a point mutation of c.905A>G on the basis of ABO*B.01.

Combination of NGAL and Cystatin C for Prediction of Preeclampsia at 10-14 Weeks of Gestation.

BACKGROUND: Preeclampsia (PE) is a severe pregnancy complication and is an important cause for maternal and child death, premature delivery, and limited intrauterine growth and development. The aim of this study was to investigate the role of NGAL and cystatin C, alone and in combination, for early prediction of PE at 10 - 14 weeks of gestation. METHODS: Serum levels of NGAL and cystatin C were assessed in women at 10 - 14 weeks of gestation who subsequently developed PE (n = 128) and normal pregnancy outcome (n = 183). Comparison of clinical characteristics, NGAL, and cystatin C levels between normal pregnancy and PE groups were analyzed using Mann-Whitney test. The receiver operating characteristic curve (ROC curve) was used to analyze the value of serum NGAL and cystatin C levels in predicting PE. RESULTS: The levels of cystatin C and NGAL in the serum were significantly higher in the PE group [0.64 mg/L (0.52 - 0.78)] and [34.9 ng/mL (24.4 - 55.2), respectively] than in the normal pregnancy group [0.56 mg/L (0.49 - 0.65)] and [20.2 ng/mL (13.8 - 26.9), respectively]. ROC curve analysis showed that serum NGAL levels predicted the area under the curve in the PE period 0.739 (95% CI: 0.618 to 0.860). Serum cystatin C levels predicted the area under the curve in the PE period 0.722 (95% CI: 0.592 to 0.853). The combination of serum NGAL and cystatin C levels predicted the area under the curve in the PE period 0.877 (95% CI: 0.811 to 0.943). CONCLUSIONS: NGAL and cystatin C levels in serum appear to be ideal biomarkers for PE prediction at 10 - 14 weeks. The combination of NGAL and cystatin C will also be more valuable in discriminating patients at risk of developing PE from other pregnancy complications early in gestation.

MicroRNA-652-3p promotes the proliferation and invasion of the trophoblast HTR-8/SVneo cell line by targeting homeobox A9 to modulate the expression of ephrin receptor B4.

MicroRNAs (miRNAs) are emerging as novel modulators in the pathogenesis of preeclampsia (PE). Multiple miRNAs have been shown to regulate the proliferation and invasion of trophoblast cells, which play a critical role in successful pregnancies. miR-652-3p has been identified as a novel disease-associated miRNA that is dysregulated in various pathological processes. However, whether miR-652-3p is dysregulated in PE and regulates the cellular function of trophoblast cells remains unknown. In the present study, we aimed to investigate the expression pattern of miR-652-3p in PE and explore its potential function in trophoblast cells. Herein, we found that miR-652-3p expression was significantly decreased in the placental tissues of pregnant women with PE. Cellular function experiments showed that overexpression of miR-652-3p promoted the viability, proliferation, and invasion of trophoblast cells in vitro. By contrast, inhibition of miR-652-3p had the opposite effect. Bioinformatics analysis predicted that homeobox A9 (HOXA9), a crucial regulator of trophoblast cell function, was a potential target gene of miR-652-3p. A luciferase reporter assay confirmed that miR-652-3p directly interacted with the 3'-untranslated region of HOXA9. Moreover, miR-652-3p was shown to negatively regulate the expression of HOXA9 and ephrin receptor B4 (EphB4) in trophoblast cells. Notably, overexpression of HOXA9 or EphB4 significantly reversed the regulatory effect of miR-652-3p on proliferation and invasion of trophoblast cells. Taken together, our findings demonstrate that miR-652-3p regulates the proliferation and invasion of trophoblast cells, possibly through targeting HOXA9 and modulating EphB4 expression.

Progesterone maintains the status of granulosa cells and slows follicle development partly through PGRMC1.

Progesterone receptor membrane component 1 (PGRMC1) mediates antimitotic and antiapoptotic actions of progesterone in granulosa cells, which indicates that PGRMC1 may play a key role in maintaining the status of granulosa cells. The current study investigated the effects of progesterone on intracellular signaling involved in differentiation, follicle development, inflammatory responses, and antioxidation, and determined the role of PGRMC1 in these processes. Our results demonstrated that progesterone slowed follicle development and inhibited p-ERK1/2, p-p38, caspase-3, p-NF-κB, and p-IκB-α signals involved in differentiation, steroidogenesis, and inflammatory responses in granulosa cells. Progesterone inhibited the steroidogenic acute regulatory protein and the cholesterol side-chain cleavage enzyme and decreased pregnenolone production. A PGRMC1 inhibitor and a PGRMC1 small interfering RNA ablated these inhibitory effects of progesterone. Interfering with PGRMC1 functions also decreased cellular antioxidative effects induced by an oxidant. These results suggest that PGRMC1 might play a critical role in maintaining the status of granulosa cells and balancing follicle numbers.

BTB/POZ domain-containing protein 7: epithelial-mesenchymal transition promoter and prognostic biomarker of hepatocellular carcinoma.

UNLABELLED: Epithelial-mesenchymal transition (EMT) is a critical step in the metastasis of hepatocellular carcinoma (HCC). BTB/POZ domain-containing protein 7 (BTBD7) regulates EMT-associated proteins implicated in HCC progression. However, the role(s) of BTBD7 in HCC have not been identified. Using highly metastatic HCC HCCLM3 cells, immortalized L02 hepatocytes, metastatic HCC animal models, and three independent cohorts of HCC patient specimens, we aimed to determine the involvement of BTBD7 in HCC metastasis. We show that BTBD7 messenger RNA and protein was highly expressed in HCC cells and tumor tissues, with such expression being associated with: enhanced cell motility, venous invasion, and poor prognosis. BTBD7 promoted HCC angiogenesis and metastasis in vitro and in vivo, but did not influence cell proliferation or colony formation. BTBD7 enhancement of HCC invasion and EMT phenotype occurred through activation of a RhoC-Rock2-FAK-signaling pathway, resulting in matrix metalloproteinase-2/9 production and microvessel formation. Applying a predictive risk score model, Cox regression analysis revealed that high BTBD7 expression integrated with high microvessel density was a powerful independent predictive factor of HCC clinical outcome. CONCLUSION: The present study identifies BTBD7 as a novel candidate prognostic factor and a potential therapeutic target of HCC. (HEPATOLOGY 2013; 57:2326-2337).

Functional analysis of two mutation sites in the OCA2 gene.

To analyse the genetic aetiology of a child with oculocutaneous albinism and to explore the effects of two mutation sites on the function of the OCA2 protein at the mRNA and protein levels via the use of recombinant carriers in vitro. Whole-exome sequencing (WES) and Sanger sequencing were used to analyse the pathogenic genes of the child and validate the mutations in the parents. pEGFP and phage vectors carrying wild-type and mutant OCA2 were constructed using the coding DNA sequence (CDS) of the whole gene-synthesized OCA2 as a template and transfected into HEK293T cells, after which expression analysis was performed. The child in this study was born with white skin, hair, eyelashes, and eyebrows and exhibited nystagmus. Genetic analysis indicated that the child carried two heterozygous mutations: c.1079C > T (p.Ser360Phe) of maternal origin and c.1095_1103delAGCACTGGC (p.Ala366_Ala368del) of paternal origin, conforming to an autosomal recessive inheritance pattern. In vitro analysis showed that the expression of the c.1079C > T (p.Ser360Phe) mutant did not significantly change at the mRNA level but did increase at the protein level, suggesting that the mutation may lead to enhanced protein stability, and the c.1095_1103delAGCACTGGC (p.Ala366_Ala368del) mutation resulted in the loss of three amino acids in exon 10, producing a truncated protein. In vitro expression analysis also revealed that the expression of the mutant gene was significantly downregulated at both the mRNA and protein levels, suggesting that the mutation can simultaneously produce truncated proteins and lead to protein degradation. This case study enriches the phenotypic spectrum of OCA2 gene disease. In vitro expression analysis confirmed that both mutations affect protein expression, providing a theoretical basis for analysing the pathogenicity of these two mutations.

Iron oxides based nanozyme sensor arrays for the detection of active substances in licorice.

With the increasing applications of traditional Chinese medicines worldwide, authenticity identification and quality control are significant for them to go global. Licorice is a kind of medicinal material with various functions and wide applications. In this work, colorimetric sensor arrays based on iron oxide nanozymes were constructed to discriminate active indicators in licorice. Fe2O3, Fe3O4, and His-Fe3O4 nanoparticles were synthesized by a hydrothermal method, possessing excellent peroxidase-like activity that can catalyze the oxidation of 3,3',5,5' -tetramethylbenzidine (TMB) in the presence of H2O2 to produce a blue product. When licorice active substances were introduced in the reaction system, they showed competitive effect on peroxidase-mimicking activity of nanozymes, resulting in inhibitory effect on the oxidation of TMB. Based on this principle, four licorice active substances including glycyrrhizic acid, liquiritin, licochalcone A, and isolicoflavonol with the concentration ranging from 1 µM to 200 µM were successfully discriminated by the proposed sensor arrays. This work supplies a low cost, rapid and accurate method for multiplex discrimination of active substances to guarantee the authenticity and quality of licorice, which is also expected to be applied to distinguish other substances.

Arsenic induced progesterone production in a caspase-3-dependent manner and changed redox status in preovulatory granulosa cells.

Arsenic contamination is a principal environmental health threat throughout the world. However, little is known about the effect of arsenic on steroidogenesis in granulosa cells (GCs). We found that the treatment of preovulatory GCs with arsenite stimulated progesterone production. A significant increase in serum level of progesterone was observed in female Sprague-Dawley rats following arsenite treatment at a dose of 10 mg/L/rat/day for 7 days. Further experiments demonstrated that arsenite treatment did not change the level of intracellular cyclic AMP (cAMP) or phosphorylated ERK1/2 in preovulatory GCs; however, progesterone production was significantly decreased when cAMP-dependent protein kinase (PKA) or ERK1/2 pathway was inhibited. This implied that the effect of arsenite on progesterone production may require cAMP/PKA and ERK1/2 signaling but not depend on them. Furthermore, we found that arsenite decreased intracellular reactive oxygen species (ROS) but increased the antioxidant glutathione (GSH) levels and mitochondrial membrane potential (ΔΨm) in parallel to the changes in progesterone production. Progesterone antagonist blocked the arsenic-stimulated increase of GSH levels. Arsenite treatment induced caspase-3 activation, although no apoptosis was observed. Inhibition of caspase-3 activity significantly decreased progesterone production stimulated by arsenite or follicle-stimulating hormone (FSH). GSH depletion with buthionine sulfoximine led to cell apoptosis in response to arsenite treatment. Collectively, this study demonstrated for the first time that arsenite stimulates progesterone production through cleaved/active caspase-3-dependent pathway, and the increase of GSH level promoted by progesterone production may protect GCs against apoptosis and maintain the steroidogenesis of GCs in response to arsenite treatment.

Intrauterine infusion of clinically graded human umbilical cord-derived mesenchymal stem cells for the treatment of poor healing after uterine injury: a phase I clinical trial.

BACKGROUND: Intrauterine adhesion and cesarean scar diverticulum are the main complications of poor healing after uterine injury. Human umbilical cord MSCs transplantation has been regarded as the most potential treatment in the clinic, the safety and efficacy of which in the clinic, however, remains unclear. METHODS: In this study, ten patients were enrolled: six with intrauterine adhesion and four with cesarean scar diverticulum. All the patients were injected with human umbilical cord MSCs twice into the uterus. Beside the chest X-ray, ECG and abdominal ultrasound, many laboratory tests including blood routine, liver and renal function, ovarian function, tumor biomarkers, and immune function were used to estimate the safe after stem cell transplanted. In addition, the efficacy of stem cell transplanted was shown by the endometrial thickness, the volume of the uterus, and cesarean scar diverticulum based on 3D ultrasound imaging. RESULTS: We found that all results of these laboratory tests were normal in these enrolled patients before and after cell injection. Meanwhile, the results of the chest X-ray and ECG were also normal in the treatment process. The abdominal ultrasound showed that the size of the left and right kidneys was inconsistent in one patient after cell therapy, while those of other patients were normal. In addition, endometrial thickness, the volume of the uterus, and cesarean scar diverticulum showed an improving tendency, but no significant difference was noted. CONCLUSION: In summary, intrauterine injection of clinically graded human umbilical cord MSCs was safe for poor healing after uterus injury. Trial registration NCT03386708. Registered 27 December 2017, https://clinicaltrials.gov/ct2/show/NCT03386708?cond=CSD&cntry=CN&draw=2&rank=2.

LncRNA XIST serves as a diagnostic biomarker in gestational diabetes mellitus and its regulatory effect on trophoblast cell via miR-497-5p/FOXO1 axis.

BACKGROUND: Gestational diabetes mellitus (GDM) is increasingly common in pregnancy. This study's purpose was to identify the expression of XIST and manifest the potential mechanism of XIST in GDM. METHODS: Ninety-three patients with GDM and 93 normal pregnant women were included in this investigation. qRT-PCR was conducted to evaluate the expression of miR-497-5p and XIST and the relationship between XIST and fasting blood glucose (FBG) was explored by Pearson assay. The clinical diagnosis of XIST on GDM patients was validated by the receiver operator characteristic (ROC) curve. Cell counting kit-8 (CCK-8) was applied to elucidate cell viability. Luciferase reporter assay was performed to document the relationship among XIST, miR-497-5p, and FOXO1. RESULTS: The expression of XIST was increased in GDM patients and HTR-8/SVneo cell models caused by high glucose (HG). The expression of XIST was associated with the FBG levels and appeared to be a feasible indicator in discriminating GDM patients. The expression of miR-497-5p was prominently reduced in GDM patients and cell models. Inhibition of XIST might alleviate the adverse function of HG on cell viability via sponging miR-497-5p. FOXO1 was proved to be a downstream target gene of miR-497-5p. CONCLUSIONS: Overexpression of XIST and downregulation of miR-497-5p were indicated in this publication. XIST might serve as a promising diagnostic marker for GDM patients. XIST/miR-497-5p/FOXO1 axis played a critical role in the regulation of trophoblast cells.

Intracellular redox imbalance and extracellular amino acid metabolic abnormality contribute to arsenic-induced developmental retardation in mouse preimplantation embryos.

Inorganic arsenic, an environmental contaminant, is known to cause cancer, developmental retardation, and many other serious diseases. Previous researches have shown that arsenic exerts its toxicity partially through generating reactive oxygen species (ROS). However, it is still not well understood how ROS links arsenic exposure to developmental retardation of preimplantation embryo. Here we demonstrate that high-level arsenite induces severe redox imbalance by decreasing the levels of glutathione and increasing the levels of ROS through the oxidative stress adaptor p66Shc, which induces apoptosis by activating the cytochrome c-caspase. In addition, low-level arsenite seriously perturbs the metabolism of extracellular amino acid, especially that of the cytotoxic and antioxidative amino acids in preimplantation embryos, may also be the reason for developmental delay. Furthermore, an antioxidant, N-acetyl-L-cysteine, improves the development of arsenite-exposed embryos by reducing intracellular ROS and adjusting amino acid metabolism, suggesting that increasing the intracellular antioxidant level may have preventive or therapeutic effects on arsenic-induced embryonic toxicity. In conclusion, we suggest that p66Shc-linked redox imbalance and abnormal extracellular amino acid metabolism mediate arsenite-induced embryonic retardation.

The diagnostic value of miRNA-141 in prostate cancer: A systematic review and PRISMA-compliant meta-analysis.

BACKGROUND: miR-141 has gradually demonstrated its value in the diagnosis of prostate cancer. However, the diagnostic parameters in previous studies differ. A systematic review was conducted to explore the diagnostic value of miR-141 in prostate cancer. METHODS: A comprehensive search of the literature in the PubMed, Medline, Cochrane Library, and Embase databases was performed. The included 7 studies assessed the diagnostic value of miR-141 in patients with prostate cancer up to October 31, 2019. We used meta-disc version 1.4 and STATA software version 12.0 to analyze the data. RESULTS: The pooled sensitivity and specificity were 0.70 (95% confidence interval [CI] 0.64-0.75) and 0.73 (95% CI 0.64-0.80), respectively. The positive likelihood ratio was 2.88 (95% CI 1.40-5.93), and the negative likelihood ratio was 0.38 (95% CI 0.20-0.71). Further, we note that the pooled diagnostic odds ratio of miR-141 for prostate cancer was 9.94 (95% CI: 2.55-38.80). The summary area under the receiver operating characteristic curve was 0.83 (95% CI: 0.79-0.86). The results of meta-regression suggested that heterogeneity was mainly derived from patient age. The results of the Fagan nomogram showed that it was increased significantly by testing miR-141 for diagnosing prostate cancer. CONCLUSION: This meta-analysis suggests that miR-141 has a high diagnostic value for prostate cancer. In the future, large-scale prospective studies are needed to verify and evaluate this result.

MicroRNA-454 contributes to sustaining the proliferation and invasion of trophoblast cells through inhibiting Nodal/ALK7 signaling in pre-eclampsia.

MicroRNAs (miRNAs) are emerging as important regulators in the pathogenesis of pre-eclampsia (PE). Recent evidence has reported that miR-454 plays an important role in regulating cell proliferation and invasion. The decreased proliferation and invasion of trophoblast cells contribute to the pathogenesis of PE. However, whether miR-454 is involved in the regulation of trophoblast cell proliferation and invasion remains unknown. In this study, we aimed to investigate the potential role and underlying mechanism of miR-454 in regulating trophoblast cell proliferation and invasion in vitro. We found that miR-454 expression was significantly decreased in placental tissues from PE patients compared to controls. Transfection of miR-454 mimics promoted the proliferation, reduced the apoptosis, and increased invasion of trophoblast cells, while transfection of miR-454 inhibitor showed opposite effects. Bioinformatics analysis showed that activin receptor-like kinase 7 (ALK7) was a potential target gene of miR-454. Dual-luciferase reporter assay showed miR-454 directly targeted the 3'-untranslated region of AKL7. Further experiments showed that miR-454 negatively regulated ALK7 expression. Interestingly, transfection of miR-454 mimics significantly abrogated the inhibitory effect of Nodal on trophoblast cell proliferation and invasion. Moreover, overexpression of ALK7 markedly reversed the promotion effect of miR-454 on trophoblast cell proliferation and invasion. Overall, our results suggest that miR-454 promotes the proliferation and invasion of trophoblast cells by downregulation of ALK7. Our study suggests that miR-454 may play critical roles in the pathogenesis of PE and serve as a potential therapeutic target for treatment of PE.

Seasonal variations and sources of atmospheric polycyclic aromatic hydrocarbons and organochlorine compounds in a high-altitude city: Evidence from four-year observations.

Lijiang is a high-altitude city located on the eastern fringe of the Tibetan Plateau, with complex seasonal atmospheric circulations (i.e. westerly wind, Indian Monsoon, and East Asia Monsoon). Very few previous studies have focused on seasonal variations and sources of organic pollutants in Lijiang. In this study, a four-year air campaign from June 2009 to July 2013 was conducted to investigate the temporal trends and the sources of polycyclic aromatic hydrocarbons (PAHs) and organochlorine compounds [including organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs)]. The atmospheric PAH concentrations in winter are 2-3 times of those in summer, probably because of the combined result of enhanced local emission and long-range atmospheric transport (LRAT) during winter. Traffic pollution was the primary local source of PAHs, while biomass burning is the dominant LRAT source. OCPs and PCBs also mainly underwent LRAT to reach Lijiang. The peak concentrations of most of OCPs occurred in pre-monsoon season and winter, which were carried by air masses from Myanmar and India through westerly winds. As compared with other sites of the Tibetan Plateau, without the direct barrier of the Himalaya, Lijiang is easily contaminated by the incursion of polluted air masses.

Association between Allogeneic or Autologous Blood Transfusion and Survival in Patients after Radical Prostatectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: A number of studies have investigated the effect of perioperative blood transfusion (PBT) for patients after radical prostatectomy (RP), with some reporting conflicting results. A systematic review of the literature and a meta-analysis were conducted to explore the association between PBT (autologous or allogeneic) and biochemical recurrence-free survival (BRFS), overall survival (OS) and cancer-specific survival (CSS) in patients undergoing RP. METHODS: The PubMed, Medline, Cochrane Library, and Embase databases were searched for published controlled clinical studies on perioperative allogeneic or autologous blood transfusion (BT) and patient survival after RP. STATA software version 12.0 was used for data analysis. We used hazard ratios (HRs) and 95% confidence intervals (CIs) to test the correlation between BT and patient survival after RP. RESULTS: Data from a total of 26,698 patients in ten published studies were included in the meta-analysis. The meta-analysis results showed that autologous BT was not associated with BRFS (HR: 1.06; 95% CI: 0.96-1.18; Z = 1.17; P = 0.24), OS (HR: 0.86; 95% CI: 0.71-1.04; Z = 1.58; P = 0.11), or CSS (HR: 0.98; 95% CI: 0.49-1.96; Z = 0.05; P = 0.96). Allogeneic BT exhibited a significant association with worse BRFS (HR: 1.09; 95% CI: 1.01-1.16; Z = 2.37; P = 0.02), OS (HR: 1.43; 95% CI: 1.24-1.64; Z = 4.95; P<0.01) and CSS (HR: 1.74; 95% CI: 1.18-2.56; Z = 2.81; P = 0.005). CONCLUSION: Our data showed an association between allogeneic BT and reduced BRFS, OS and CSS in patients after RP. These findings indicate that perioperative blood conservation strategies are important for decreasing the allogeneic BT rate.

The influence of climate change on the accumulation of polycyclic aromatic hydrocarbons, black carbon and mercury in a shrinking remote lake of the southern Tibetan Plateau.

A sediment core from a remote lake, Pumoyum Co, located in the southern TP, was analyzed for polycyclic aromatic hydrocarbons (PAHs), black carbon (BC) and mercury. Concentrations ranged from 30 to 229ng/g for PAHs, 0.46 to 1.48mg/g for BC and 10 to 30ng/g for mercury. Significant correlations were found among the concentrations of PAHs, BC and mercury, suggesting the sources of these pollutants to be similar; mainly from combustion processes. Further diagnosis of the likely sources of BC and PAHs suggested that petroleum combustion has been one of the increasing sources in the last few decades, but biomass burning remains the dominant source of these pollutants. The historic trends of the three pollutants closely followed historic BC emission trends from Europe (before 1970) and southern Asia (after 2000). With economic development in southern Asia, concentrations of pollutants in the sediments of Pumoyum Co have increased during the past decade. However, the accumulation fluxes of the pollutants during that period remained stable, which may be due to the recent low precipitation and less catchment erosion of Pumoyum Co (experienced a drier climate and shrinking of lake area).

Progesterone amplifies oxidative stress signal and promotes NO production via H2O2 in mouse kidney arterial endothelial cells.

The role of progesterone on the cardiovascular system is controversial. Our present research is to specify the effect of progesterone on arterial endothelial cells in response to oxidative stress. Our result showed that H2O2 (150 µM and 300 µM) induced cellular antioxidant response. Glutathione (GSH) production and the activity of Glutathione peroxidase (GPx) were increased in H2O2-treated group. The expression of glutamate cysteine ligase catalytic subunit (GCLC) and modifier subunit (GCLM) was induced in response to H2O2. However, progesterone absolutely abolished the antioxidant response through increasing ROS level, inhibiting the activity of Glutathione peroxidase (GPx), decreasing GSH level and reducing expression of GClC and GCLM. In our study, H2O2 induced nitrogen monoxide (NO) production and endothelial nitric oxide synthase (eNOS) expression, and progesterone promoted H2O2-induced NO production. Progesterone increased H2O2-induced expression of hypoxia inducible factor-α (HIFα) which in turn regulated eNOS expression and NO synthesis. Further study demonstrated that progesterone increased H2O2 concentration of culture medium which may contribute to NO synthesis. Exogenous GSH decreased the content of H2O2 of culture medium pretreated by progesterone combined with H2O2 or progesterone alone. GSH also inhibited expression of HIFα and eNOS, and abolished NO synthesis. Collectively, our study demonstrated for the first time that progesterone inhibited cellular antioxidant effect and increased oxidative stress, promoted NO production of arterial endothelial cells, which may be due to the increasing H2O2 concentration and amplified oxidative stress signal.

BMP-4 induced proliferation and oriented differentiation of rat hepatic oval cells into hepatocytes.

OBJECTIVE: To explore the role of bone morphogenetic protein 4 (BMP-4) in hepatic progenitor cells (HPCs). METHODS: The effect of BMP-4 on rat hepatic oval cells was examined by using the WB-F344 rat hepatocytic epithelial stem-cell-like cell line. This hepatocytic cell line could exert various hepatocyte functions including the secretion of albumin and urea. Immunohistochemistry was used to examine the effects of BMP-4 and its antagonist, Noggin, on the proliferation and differentiation of these cells, cellular uptake and excretion of indocyanine green, the periodic acid-schiff (PAS) assay for glycogen storage and the expression of hepatic markers. RESULTS: Our results showed for the first time that BMP-4 may acted as a potential inducer of hepatic differentiation in rat hepatic oval cells. CONCLUSIONS: This cell source offers a much-needed attractive and expandable source for future investigations of drug screening, stem cell technologies and cellular transplantation, in a society with increasing levels of liver disease and damage.

miR-99b promotes metastasis of hepatocellular carcinoma through inhibition of claudin 11 expression and may serve as a prognostic marker.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, mainly due to its high rates of postoperative recurrence and metastasis. Moreover, there is no widely accepted prognostic marker of recurrence. Therefore, the aim of the present study was to determine whether such a marker could be provided by a microRNA (miRNA), since recent evidence indicates that miRNAs are important contributors to the metastatic phenotype. In the present study, we showed that miR-99b was expressed at high levels in tissues of patients with HCC and in cell lines derived from HCCs. Elevated levels of miR-99b predicted poor overall survival as well as disease-free survival of patients with HCC. Moreover, miR-99b expression levels correlated with capsule formation and microvascular invasion, which are required for postoperative recurrence. Overexpression or knockdown of miR-99b expression increased or inhibited, respectively, the metastasis of HCC cells in vitro. Furthermore, using a dual­luciferase assay, we demonstrated that miR-99b inhibited the expression of claudin 11 (CLDN11), a component of tight junction strands by directly targeting the 3'-untranslated region of CLDN11 mRNA. In addition, CLDN11 expression was increased or decreased when miR-99b expression was inhibited or elevated in the HCC cells, respectively. Moreover, the expression of miR-99b was inversely correlated with CLDN11 mRNA or CLDN11 levels in the HCC tissues. These findings suggest that a high level of miR-99b expression is an independent prognostic factor and correlates with poor survival of patients with HCC. Therefore, inhibition of miR-99b expression may serve as a therapeutic approach for inhibiting the metastatic phenotype of HCC.