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BackgroundWith the rapid industrialization, cadmium has become a primary heavy metal pollutant in cultivated land soil in China, which seriously affects human health. Previous studies have found that cadmium exposure associates with cognitive dysfunction in individuals, but there is a lack of research on the mechanism of cadmium exposure associated cognitive impairment in offspring in early life which is more vulnerable to various toxins and crucial for development of the neuro.ObjectiveTo explore the potential mechanism of brain-derived neurotrophic factor/tyrosine kinase receptor B (BDNF-TrkB) signaling pathway in cognitive dysfunction in mice after cadmium exposure in early-life.MethodsTwelve 8-week-old C57BL/6 pregnant mice were randomly divided into 2 groups, namely control group and cadmium exposure group, with 6 mice in each group. The exposure period was from pregnancy day 4.5 to lactation day 21 (E4.5-P21), during which distilled water or cadmium chloride solution (2.5 mg·kg−1·d−1) was given. After lactation, the offspring of the control group and the cadmium exposure group were given distilled water until 8 weeks of age. Then the toxicity effects of cadmium exposure on mice were evaluated by body weight and selected biochemical indicators. The cadmium content in brain was detected and the learning and memory ability was tested by Y maze and Morris water maze to evaluate cognitive function of offspring mice. Histopathological changes of the hippocampus were observed after Nissl staining and Golgi staining. The mRNA and protein expression levels of the BDNF-TrkB pathway and synapse were detected by real-time quantitative PCR (qPCR) and Western blot.ResultsCompared with the control group, no significant change was found in body weight, liver or kidney function in the cadmium exposure group (P> 0.05). However, compared with the control group, the cadmium content in brain was increased in the cadmium exposure group (P

Abstract Objectives To evaluate the usefulness of porta hepatis lymph nodes (PHLNs) on ultrasonography (US) scans in diagnosing biliary atresia (BA) and predicting the outcomes after Kasai portoenterostomy (KPE) surgery. Methods A total of 668 patients from one hospital were enrolled in the study (542 non-BA and 126 BA). The independent and combined diagnostic efficacy of PHLNs, triangular cord (TC) thickness, and gallbladder morphology were assessed by drawing the receiver operating characteristic (ROC) curves and counting the area under the ROC curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The US features, histopathological findings of PHLNs, and serum total bilirubin (TBIL) levels 3 months post-KPE were correlated. Results The AUC, sensitivity, specificity, PPV, and NPV of PHLNs with hyperechogenicity and a maximum length larger than 8.4 mm were 0.898, 81.8%, 97.8%, 89.6%, and 95.8%, respectively. The combination of PHLNs, TC thickness, and gallbladder morphology achieved the best overall diagnostic efficacy among all indicators with an AUC of 0.927 and a sensitivity of 99.2%. The germinal center number and bile particle number of PHLNs were positively correlated with pathological size and US echogenicity intensity of PHLNs, respectively (r = 0.591, 0.377, p = 0.001, 0.004). The pathological size of PHLNs in BA patients was negatively correlated with jaundice clearance status 3 months after KPE surgery (r = −0.385, p = 0.047). Conclusion PHLNs with hyperechogenicity and a maximum length > 8.4 mm are useful US indicators for BA diagnosis. Additionally, the enlargement of PHLNs might play a role in predicting outcomes of KPE surgery. Critical relevance statement The article proposed for the first time that PHLNs with hyperechogenicity and a maximum length > 8.4 mm are a useful US indicator for diagnosing BA. Key Points PHLNs may be helpful in diagnosing BA and predicting outcomes after surgery. Enlarged hyperechoic PHLNs are a useful diagnostic indicator for BA, and play a role in predicting surgical outcomes. These findings can assist clinicians in more accurately diagnosing BA, enabling more timely treatments. Graphical Abstract

ObjectiveThis study aims to analyze the value of prenatal ultrasound in the screening, diagnosis, and treatment of double aortic arch (DAA) malformations.MethodsA retrospective analysis was conducted on 31 fetal cases with double aortic arch anomalies over a 12-year period from June 1, 2011 to June 1, 2023. The assessment included combined measurements of fetal tracheal internal diameter Z-score and DAA pinch angle, along with ultrasonographic findings, associated anomalies, genetic abnormalities, postnatal CTA images, and long-term postnatal outcomes.ResultsOf the 31 fetal double aortic arch cases, 15 were right aortic arch dominant, 2 were left aortic arch dominant, and 14 had a balanced double arch. Genetic testing was performed on 19 cases, revealing abnormalities in 2 cases, including one Turner syndrome, and one carrier of ichthyosis gene with heterozygous deletion. Out of the total cases, 29 were delivered, and 2 cases were terminated. Prenatal diagnosis accurately identified 29 cases (29/31, 93.5%), which was confirmed by postnatal pathological anatomy, echocardiography, surgery or CTA. Fetal tracheal internal diameter Z-scores were significantly smaller in the symptomatic group than in the asymptomatic group (−1.27 ± 0.49 vs −0.68 ± 0.60, P = 0.018). The area under the curve was 0.776 (95% confidence interval, 0.593–0.960) using a tracheal internal diameter z-score cutoff of −0.73 with a sensitivity of 90% and specificity of 64.7%. The double arch pinch angle was significantly smaller in the symptomatic group than in the asymptomatic group [52.50° (38.25° to 59.00°) vs 60.00° (53.50° to 70.50°), P = 0.035]. The area under the curve was 0.744 (95% confidence interval, 0.554–0.935), and the sensitivity for determining the presence or absence of symptoms was 90% when the cutoff value was 62.5°, with a specificity of 47.1%. Fifteen cases opted for surgery with favorable surgical outcome.ConclusionPrenatal echocardiography demonstrates good diagnostic efficacy for fetal double aortic arch. It is also essential to detect the presence of other underlying intra- and extracardiac malformations and genetic abnormalities. There is a significant difference in prenatal tracheal internal diameter Z-scores and double arch pinch angle between asymptomatic and symptomatic DAA infants. Symptomatic infants require early surgery, while asymptomatic infants should be monitored.

ObjectiveThis study aimed to assess the diagnostic value of prenatal echocardiography for identifying transposition of the great arteries (TGA) during pregnancy and evaluating the associated outcomes.MethodsWe conducted a retrospective analysis of 121 prenatally diagnosed patients with TGA at our hospital between January 2012 and September 2022. This analysis included prenatal ultrasound, prenatal screening, clinical management and follow-up procedures.ResultsAmong the 103 fetuses considered in the study, 90 (87.4%) were diagnosed with complete transposition of the great arteries (D-TGA), while 13 (12.6%) exhibited corrected transposition of the great arteries (CC-TGA). Diagnoses were distributed across the trimester, with 8 D-TGA and 2 CC-TGA patients identified in the first trimester, 68 D-TGA patients and 9 CC-TGA patients in the second trimester, and 14 D-TGA and 2 CC-TGA patients referred for diagnosis in the third trimester. Induction of labour was pursued for 76 D-TGA patients (84.4%) and 11 CC-TGA patients (84.6%), and 14 D-TGA patients (15.6%) and 2 CC-TGA patients (15.4%) continued pregnancy until delivery. Among the D-TGA patients, 9 fetuses (10.0%) underwent surgery, two of which were inadvertent fatality, while the remaining seven experienced positive outcomes. Additionally, seven TGA patients received palliative care, leading to four fatalities among D-TGA patients (5.2%), whereas 1 D-TGA patients and 2 CC-TGA patients survived.ConclusionThis study underscores the feasibility of achieving an accurate prenatal diagnosis of TGA during early pregnancy. The utility of prenatal ultrasound in the development of personalized perinatal plans and the application of multidisciplinary treatment during delivery are conducive.

ObjectiveThe study aims to assess the ultrasonic features of fetal cardiac rhabdomyoma (CR), track the perinatal outcome and postnatal disease progression, investigate the clinical utility of ultrasound, MRI and tuberous sclerosis complex (TSC) gene analysis in CR evaluation, and offer evidence for determing of fetal CR prognosis.MethodsWe conducted a retrospective analysis of prenatal ultrasound-diagnosed fetal CR cases in our hospital from June 2011 to June 2022, tracked the perinatal outcomes, regularly followed live infants to analyze cardiac lesion changes and disease progression, and compared the sensitivities of ultrasound, MRI and their combination in the detecting of intracranial sclerosing nodules.ResultsOur study included 54 fetuses with CR: 32 pregnancies were terminated, 22 were delivered, 35 were diagnosed with TSC, 13 had simple CR without TSC, and in 6 cases, remained unclear whether TSC accompanied the CR due to insufficient evidence. 45 fetuses (83.3%) had multiple lesions, while 9 fetuses (16.7%) presented with a single lesion. Twelve cases had intracardiac complications, all associated with multiple lesions, and these cases exhibited larger maximum tumor diameters than the non-complicated group. Multiple intracardiac lesions were more prevalent in the TSC group than in the simple CR group. However, there was no significant difference in maximum tumor diameter between the two groups. Among 30 fetuses who underwent fetal brain MRI, 23 were eventually diagnosed with TSC, with 11 fetuses showing intracranial sclerosis nodules by ultrasound and 15 by MRI, and the diagnostic consistency was moderate (k = 0.60). Twenty-two fetuses were born and followed up for 6–36 months. CR lesions diminished or disappeared in 18 infants (81.8%), while they remained unchanged in 4 infants (18.2%). Ten out of 12 (83.3%) surviving children diagnosed with TSC developed epilepsy, and 7 (58.3%) had neurodevelopmental dysfunction.ConclusionsThe majority of CR cases involve multiple lesions, which are a primary risk factor for TSC. Through prenatal ultrasound examination is crucial for assessing fetal CR prognosis. Although ultrasound combined with MRI can detect intracranial sclerosis nodules in TSC fetuses, its sensitivity is limited. TSC gene sequencing is an essential diagnostic method. Simple CR cases without TSC generally have a favorable prognosis.

ObjectiveThe objective of the study is to explore the value of the four-section approach in detecting fetal heart defects in the first trimester (11–13+6 weeks), analyze the reasons for the inconsistency between the results of ultrasound examination in the first trimester and subsequent verification, and describe the most common abnormal flow patterns of four sections.Materials and methodsBetween June 2019 and June 2021, a prenatal four-section approach (upper abdominal transverse section, four-chamber section, three vessel–trachea section, and bilateral subclavian artery section) with verification results in early pregnancy was analyzed.ResultsIn total, 9,533 fetuses were included. Finally, 176 fetuses with congenital heart disease (CHD), containing 34 types, were identified. The total detection rate of cardiac abnormalities was 1.85%. 102 cases were accurately diagnosed by ultrasonography during early pregnancy. A total of 74 fetuses who had inconsistent results between fetal cardiac ultrasound and verification in early pregnancy were reported, of which the cases of 22 fetuses were inconsistent due to disease evolution and progression and the cases of 52 fetuses were inconsistent due to missed diagnosis and misdiagnosis. The sensitivity, specificity, positive predictive value, and negative predictive value of the four-section approach were 67.05%, 99.96%, 96.58%, and 99.33%, respectively. In this study, a total of 30 abnormal ultrasonic imaging patterns in four sections were summarized.ConclusionWe confirmed that the four-section approach in early pregnancy has a good diagnostic efficacy for fetal CHD. Intrauterine evolution of the fetal heart, missed diagnosis, and misdiagnosis are the reasons for the inconsistency between the results of early pregnancy ultrasound and subsequent verification. This study also presents the abnormal imaging patterns of four scan sections of CHD in early pregnancy, which are instructive for the rapid identification and diagnosis of CHD in the first trimester.

ObjectivesThis study aims to investigate the efficacy of prenatal ultrasonography in diagnosing the anomalous origin of the fetal pulmonary artery (AOFPA).MethodsA total of 26 AOFPA cases were retrospectively analyzed from January 2014 to January 2023. The features of the AOFPA were characterized by comparing the prenatal ultrasonic data with the results of anatomical casting after pregnancy termination or postnatal imaging and surgical intervention. Missed diagnoses and misdiagnoses were expounded.ResultsOf the 26 AOFPA cases, there were 13 cases of pulmonary artery sling, 8 cases of anomalous origin of the unilateral pulmonary artery, and five cases of unilateral absence of the pulmonary artery; 17 cases received pathological anatomy and casting after pregnancy termination, and nine cases were confirmed by postnatal imaging and surgery. Nineteen cases were accurately prenatally diagnosed (19/26, 73.1%), and seven cases were missed or misdiagnosed (7/26, 26.9%).ConclusionsPrenatal ultrasonography has a favorable diagnostic efficacy for anomalous origin of the fetal pulmonary artery. The absence of either the left or right pulmonary artery from the image of pulmonary artery bifurcation may indicate origin abnormalities of the pulmonary artery in fetuses, which signifies the necessity to detect the abnormal origin of the pulmonary artery on the affected side and other potential intracardiac malformation complications.

BackgroundTo explore the diagnostic clues and abnormality spectrum of heterotaxy syndrome by prenatal ultrasonography and postnatal verification.MethodsThe prenatal ultrasonic data of 88 heterotaxy syndrome fetuses were analyzed retrospectively as left isomerism (LI) and right isomerism (RI). Prenatal ultrasound compared with the anatomical casting of the fetal body after labor induction, and the confirmatory postnatal diagnosis after delivery.ResultsFetal LI showed typical malformations of gastric vesicles on different sides from the heart, absence of hepatic segment of the inferior vena cava (IVC), abdominal aorta (AO) parallel with the azygos vein (AV), bilateral left bronchus, bilateral left atrial appendages, and polysplenia; intracardiac malformations of AV septal defects (AVSD), single atrium (SA), left ventricular outflow tract obstruction (LVOTO), and double-outlet right ventricle (DORV); and cardiac conduction abnormalities of sinus bradycardia and AV blockage. Fetal RI reported typical malformations of gastric vesicles on different sides from the heart, juxtaposition of the IVC with AO, anomalous pulmonary venous connection (APVC), asplenia, and bilateral right atrial appendages; intracardiac malformations of AVSD, SA, single ventricle, pulmonary atresia and stenosis, and DORV. The postnatal verification revealed 3 malformations misdiagnoses and 4 malformations missed diagnoses in LI fetuses and 10 misdiagnoses and 8 missed diagnoses in RI fetuses.ConclusionsThe proposed five-step prenatal ultrasonography has an important diagnostic value for the identification and classification of heterotaxy syndrome. The different sides of gastric vesicles and cardiac apex are important diagnostic clues for heterotaxy syndrome, featuring disconnected or hypoplastic IVC, typical complex cardiac malformation, and atrioventricular block in fetal LI, and shown APVC, juxtaposition of IVC and AO, and intracardiac malformations such as AVSD, DORV, and LVOTO in fetal RI.

ObjectiveTo systematically verify the accuracy of a four-step prenatal ultrasonography in diagnosing fetal total anomalous pulmonary venous connection (TAPVC).MethodsA total of 62 TAPVC fetuses received prenatal ultrasonography and were confirmed by postnatal echocardiography, surgery, or postabortion autopsy. The suspected TAPVC fetuses were further screened by a four-step prenatal ultrasonography for TAPVC classification, pulmonary venous obstruction, and the associated malformations, and followed postpartum. The sonographic features, clinical data, and prognosis of the TAPVC fetuses were retrospectively analyzed.ResultsOf the 62 TAPVC fetuses, supracardiac TAPVC was found in 20 cases, intracardiac TAPVC in 12, infracardiac TAPVC in 21, and mixed TAPVC in 9. A total of 30 cases with right atrium isomerism were correctly diagnosed. Of the 11 cases with other intracardiac and extracardiac malformations, 1 case was missed to be diagnosed. Of the 21 isolated TAPVC cases, 6 were missed prenatally and 1 case was prenatally diagnosed as intracardiac and postnatally proved to be mixed (intracardiac type + supracardiac type) by echocardiography. Of the 13 TAPVC live births, 4 infants died in the neonatal period without operation. Of the nine infants undergoing the operation, five recuperated and survived; one survived but had complications with superior vena cava obstruction and collateral circulation formation, and three died postoperatively.ConclusionThe four-step prenatal ultrasound procedure can comprehensively and systematically evaluate fetal TAPVC, detailing the classification, potential obstruction, and associated malformations. It provides substantial support for subsequent prenatal counseling and neonatal assessment. The retrospective analysis also reveals that isolated TAPVC is more prone to be missed in diagnosis.

ObjectiveTo establish a nomogram to predict the outcome of biliary atresia (BA) infants 3-months post- Kasai portoenterostomy (KPE).MethodsBA Infants who underwent KPE from two hospitals were included in the training (n = 161) and validation cohorts (n = 64). A logistic regression equation (Equation A) for predicting the serum total bilirubin (TBIL) level 3-month post-KPE was established in the training cohort. Then, a nomogram was developed based on Equation A in the training cohort and validated in the validation cohort. Moreover, a new equation (Equation B) was generated based on the nomogram and the size of the enlarged hilar lymph nodes (LNs) in the validation cohort. The predictive performance of the nomogram was evaluated by the receiver operating characteristic (ROC) curve and by calculating the area under the ROC curve (AUC), sensitivity, specificity, and positive (PPV) and negative (NPV) prediction values.ResultsA nomogram based on gallbladder morphology and serum levels of TBIL and total protein (TP) was established with AUC (95%CI) of 0.673 (0.595, 0.745) and 0.647 (0.518, 0.763), sensitivity (95%CI) of 71.4% (62.1%,79.6%) and 81.8% (59.7%,94.8%), specificity (95%CI) of 63.3% (48.3%,76.6%) and 47.6% (32.0%,63.6%), PPV (95%CI) of 81.6% (72.5%,88.9%) and 45.0% (29.3%,61.5%), and NPV (95%CI) 49.2% (36.4%,62.1%) and 83.3% (62.6%,95.3%), respectively, in the training and validation cohorts. Furthermore, in the validation cohort, the AUC (95%CI) of Equation B was 0.798 (95%CI: 0.679, 0.888), which was significantly higher than that of the nomogram (P = 0.042).ConclusionA nomogram based on the pre-KPE gallbladder morphology, TBIL, and TP to predict the outcome of BA 3-months post-KPE is established. Moreover, the addition of the size of the enlarged hilar LNs into the nomogram further improves its predictive value.

An accurate understanding of soil heavy metal (HM) pollution characteristics and source apportionment, and a recognition of the major factors influencing ecological and human health risks (HHRs) are essential for soil HM pollution control and remediation. In this study, 212 surface soils (0–20 cm) and 15 profile soils (0–100 cm) were collected from cropland soils around an e-waste dismantling site in Taizhou city, Zhejiang Province, China. Spatial analysis was used to evaluate the pollution characteristics of HMs (Cd, Cu, Pb, Zn, Cr and Ni). Principal component analysis (PCA) and positive matrix factorization (PMF) were also conducted to quantify their source contributions. A modified source-oriented HHR assessment integrated source-oriented ecological risk and source-oriented HHR assessment was developed to describe the major factors that influenced HHR. Results showed that 94.81 %, 88.21 %, 36.79 % and 47.17 % of Cd, Cu, Pb and Zn, respectively, in surface soils exceeded their screening values in the soil environmental quality standard for agricultural soils (GB 15618–2018). Spatial analysis indicated that high values of Cd, Cu, Pb and Zn were distributed near the e-waste dismantling site. The results of PCA and PMF showed that the primary sources of HMs in the study area are e-waste dismantling activities, natural sources and atmospheric deposition, which contribute 27 %, 46 % and 27 % of HM pollutants, respectively. The results of source-oriented ecological risk and HHR assessment indicated that e-waste dismantling activities and natural sources were primary sources for ecological risk and HHR. However, source-oriented HHR assessment may underestimate the contribution of e-waste dismantling activities by ignoring HM pollution levels. The modified source-oriented HHR assessment highlights that e-waste dismantling activities were major factor that affect noncarcinogenic risk. This study could provide important data support for subsequent environmental remediation of soil HM pollution in cropland soils around e-waste dismantling sites.

Abstract Background Growing evidence has indicated the vital parts of long non-coding RNAs (lncRNAs) in modulating the progression of assorted human cancers, including cervical cancer (CC). Nevertheless, the role and mechanism of aspartyl-tRNA synthetase antisense RNA 1 (DARS-AS1) have been not comprehensively illustrated in CC yet. Methods Real-time quantitative polymerase chain reaction (RT-qPCR) was exploited for assessing RNA expression while western blot for protein expression in CC cells. The cell counting kit-8 (CCK-8), colony formation and TdT-mediated dUTP Nick-End Labeling (TUNEL) assays, as well as flow cytometry analysis, were employed to evaluate the modulation of DARS-AS1 on the proliferation and apoptosis of CC cells. In addition, RNA immunoprecipitation (RIP), RNA pull down assay and luciferase reporter assay confirmed the interactivity among DARS-AS1, miR-628-5p and jagged canonical Notch ligand 1 (JAG1). RBP-JK luciferase reporter assay determined the activity of Notch pathway. Results DARS-AS1 level was significantly increased in CC cells. Moreover, down-regulation of DARS-AS1 hampered cell the proliferation and accelerated the apoptosis of CC cells. Importantly, DARS-AS1 was a competing endogenous RNA (ceRNA) to elevate JAG1 level through sequestering miR-628-5p, leading to activated Notch pathway to aggravate CC tumorigenesis. Conclusions DARS-AS1/miR-628-5p/JAG1/Notch signaling accelerates CC progression, indicating DARS-AS1 as a novel therapeutic target for patients with CC.

ObjectiveTo determine the clinical value of high-frequency ultrasonography (US) in the evaluation and diagnosis of pancreaticobiliary maljunction (PBM) among children.MethodsThe clinical subjects consisted of 31 pediatric patients who were diagnosed with PBM from January 2015 to May 2021 in Fujian Provincial Maternity and Children's Hospital. The primary outcomes included diagnosis accuracy, imaging characteristics of each type of PBM based on JSPBM, time length of operation, and cost of service. Secondary outcomes were the serum amylase and bilirubin levels.ResultsThe diagnostic accuracy of US was 90.3% and comparable to the other imaging methods—MRCP (82.6%), IOC (79.2%), and ERCP (100%), respectively. The time length of operation and direct cost were significantly lower than other imaging pathways. Stenotic type (A) is associated with a high internal diameter of CBD, and dilated channel type (C) presents increased internal diameter and length of CC as well as internal diameter of PD. There were higher levels of the serum bilirubin seen in type A and of serum amylase in type C compared with others.ConclusionHigh-frequency US is a safe, cost-effective, and non-invasive imaging tool for the diagnosis and evaluation of PBM in pediatrics.

Objective. Ovarian cancer (OvCa) is the most lethal gynaecological malignancy worldwide. We aimed to illustrate the potential function and molecular mechanism of exosomal microRNA-543 (miR-543) in the oncogenesis and development of OvCa. Methods. Differentially expressed microRNAs in exosomes derived from OvCa cell lines were identified by bioinformatic analysis and verified by RT-PCR. Cell proliferation ability was estimated by clonogenic and 5-ethynyl-2′-deoxyuridine assays in vitro and in vivo. Potential involved pathways and targets of exosomal miRNAs were analysed using DIANA and verified by pyrosequencing, glucose quantification, dual-luciferase reporter experiments, and functional rescue assays. Results. Bioinformatic analysis identified miR-543 and its potential target genes involved in the cancer-associated proteoglycan pathway. The expression of miR-543 was significantly decreased in exosomes derived from OvCa cell lines, patient serum, and OvCa tissues, while the mRNA levels of insulin-like growth factor 2 (IGF2) were increased. Furthermore, the overexpression of miR-543 resulted in the suppression of OvCa cell proliferation in vitro and in vivo. Moreover, miR-543 was significantly negatively correlated with IGF2 in OvCa tissues in comparison with paracarcinoma tissues. Notably, upregulation of miR-543 led to increased cell supernatant glucose levels and suppressed cell growth, which was rescued by overexpression of IGF2. Conclusions. Exosomal miR-543 participates in the proteoglycan pathway to suppress cell proliferation by targeting IGF2 in OvCa.

High proportions of placental lymphocytes expressing DX5+/CD25+/FOXP3+/CD45+/CD4+ are beneficial to maintain immune tolerance and improve pregnancy outcomes. This study aimed to compare and evaluate the therapeutic effects of aspirin, vitamin D3 (VitD3), and progesterone on the autoimmune recurrent spontaneous abortion (RSA) model. The autoimmune RSA mouse model was constructed, and the embryo loss rate was calculated for each group. Then, primary mouse placental lymphocytes were isolated, and the expression of DX5+/CD25+/FOXP3+/CD45+/CD4+ was detected through flow cytometry. The serum levels of anti-cardiolipin antibody (ACA), β2-GP1, CXCL6, IFN-γ, and IL-6 were measured by ELISA to evaluate the proportion of Th1 and Th2 cells. Autoimmune RSA significantly increased the embryo loss rate, which was improved by aspirin, VitD3, and progesterone treatment, and progesterone treatment had the best effect among the three treatments. The positive expression of DX5+/CD25+/FOXP3+/CD45+/CD4+ in the VitD3 and progesterone groups was significantly higher than that in the autoimmune RSA group, and the expression was highest in the progesterone treatment group. In the plasma of autoimmune RSA mice, the ACA, β2-GP1, CXCL6, and IFN-γ levels were significantly higher and the IL-6 level was lower than the levels in control mice. All these changes could be reversed by aspirin and progesterone treatment. In conclusion, aspirin, VitD3 and progesterone treatment improved pregnancy outcomes in autoimmune RSA mice by regulating the Th1/Th2 balance and cytokines, and progesterone had the best effect of the three treatments.

The Yellow Sea Large Marine Ecosystem (YSLME) is an important socioeconomic zone in Asia, but has been deteriorated by various environmental pollutants over the last half century. However, comprehensive coastal pollution assessments, particularly for heavy metals (HMs), have been limited from an international perspective. Here, we first evaluate coastal HM pollution in sediment and water from 119 riverine, estuarine, and marine locations along the BS and Yellow Sea to perform a comparative assessment between the two countries of China and South Korea. The occurrence, distribution, sources, multimedia fate, interactions, associated environmental factors, and potential ecological risks relating to the HM pollution are widely addressed. Eight typical HMs (As, Hg, Zn, Cu, Pb, Cd, Cr, and Ni) were targeted in both sediments and water, and in situ water properties (pH, dissolved oxygen, salinity, and temperature) and sediment properties (pH and organic matter (OM) content) were analyzed. The results indicated that As, Cd, Cr, Cu, Ni, and Pb concentrations in water were higher in the estuarine area than those in riverine and marine areas and that particularly severe HM pollution was evidenced in the BS. The dominant elements in pollution hot spots varied greatly among the countries and regions. According to the geo-accumulation index (Igeo) and pollution load index (PLI) values, the sediments exhibited high Hg and Pb pollution in the BS; high As, Hg, and Pb pollution in the Yellow Sea of China; and high Cd and Hg pollution in the Yellow Sea of South Korea. In general, the sediments were moderately contaminated by HMs based on the high PLI (>1.0) and risk index (RI) values (>160). Ni and Cr in the sediment mainly originated from geogenic sources, while the other elements (Zn, As, Cd, Cu, Hg, and Pb) were primarily linked to anthropogenic sources. Based on the partial redundancy analysis, we found that environmental factors, especially OM, contributed significantly to the concentrations of HMs in both the sediments and water. The sediment HMs significantly contributed to the waterborne HMs due to their release from the sediments to the water column. An overall assessment of the contamination status, spatial distribution, and potential sources of HMs suggested that the water-sediment interaction of HMs and the influence by environmental factors should be subsequently considered for a better understanding of the multimedia fate of HMs in the given dynamic YSLME system or similar environments elsewhere. Keywords: Coastal ecosystem, Multimedia fate, Heavy metals, Ecological risk assessment, Influencing factors, Transnational survey

Abstract Background Aneurysmal subarachnoid hemorrhage (aSAH) is the most common types of subarachnoid hemorrhage, which is a critical clinical problem with high morbidity, mortality, and economic impact. Recent studies have shown that APOE was a genetic risk factor of aSAH, however, the studies lack consistent conclusions and the evidence from Chinese Han population is rare. Objective To determine the relationship between APOE polymorphism and the incidence of aSAH in Chinese Fujian Han population and explore the possible mechanism of ApoE in the pathogenesis of aSAH. Methods A total of 131 patients newly diagnosed with aSAH were selected as aSAH group and 137 healthy subjects were selected as the control group. All the samples were analyzed for blood lipids and serum ApoE levels, and ApoE genotype was determined by a commercial chip and further confirmed with Sanger sequencing. An adjusted multivariate logistic regression analysis was carried out to estimate the effects of APOE polymorphism on the risk of aSAH. Results Compared with the controls, the serum TC, HDL-C and ApoA1 levels in aSAH were significantly lower: TC (4.52 ± 1.38 vs. 5.11 ± 0.86 mmol/L, P

ABCG2 and SLC2A9 encode the uric acid transporters ABCG2 and GLUT9. ABCG2 single nucleotide polymorphism (SNP) can reduce the expression and transport function of ABCG2 protein, and then cause intestinal uric acid excretion dysfunction, resulting in the increase of blood uric acid. The regulation of blood uric acid by SLC2A9 is complicated. Loss of function of SLC2A9 may lead to decreased renal tubule uric acid reabsorption, impaired intestinal uric acid excretion and impaired hepatic uric acid uptake. ABCG2 promotes gout attacks by causing hyperuricemia(HUA) and increasing inflammatory responses. On the contray, loss of function of SLC2A9 can instead reduce oxidation and inflammatory responses. In addition, ABCG2 has a close relationship with early-onset gout and its SNP is a risk factor for early onset gout.