Relationship between increased maternal serum free human chorionic gonadotropin levels in the second trimester and adverse pregnancy outcomes: a retrospective cohort study.

BACKGROUND: A retrospective cohort study was conducted to collect the data of pregnant women who received hospital delivery in Hangzhou Women's Hospital from January 2018 to December 2020, and who participated in the second trimester (15-20+6 weeks) of free beta human chorionic gonadotropin (free ß-hCG). And the study was conducted to explore the relationship between maternal serum free ß-hCG and adverse pregnancy outcomes (APO). METHODS: We retrospectively analyzed the clinical data of 1,978 women in the elevated maternal serum free ß-hCG group (free ß-hCG ≥ 2.50 multiples of the median, MoM) and 20,767 women in the normal group (0.25 MoM ≤ free ß-hCG < 2.50 MoM) from a total of 22,745 singleton pregnancies, and modified Poisson regression analysis was used to calculate risk ratios (RRs) and 95% confidence intervals (CI) of the two groups. RESULTS: The gravidity and parity in the elevated free ß-hCG group were lower, and the differences between the groups were statistically significant (all, P < 0.05). The risks of polyhydramnios, preeclampsia, and hyperlipidemia, were increased in women with elevated free ß-hCG levels (RRs: 1.996, 95% CI: 1.322-3.014; 1.469, 95% CI: 1.130-1.911 and 1.257, 95% CI: 1.029-1.535, respectively, all P < 0.05), intrauterine growth restriction (IUGR) and female infants were also likely to happen (RRs = 1.641, 95% CI: 1.103-2.443 and 1.101, 95% CI: 1.011-1.198, both P < 0.05). Additionally, there was an association between elevated AFP and free ß-hCG levels in second-trimester (RR = 1.211, 95% CI: 1.121-1.307, P < 0.001). CONCLUSIONS: APOs, such as polyhydramnios, preeclampsia, and hyperlipidemia, were increased risks of elevated free ß-hCG levels, IUGR and female infants were also likely to happen. Furthermore, there was an association between elevated AFP levels and elevated free ß-hCG levels in second-trimester. We recommend prenatal monitoring according to the elevated maternal serum free ß-hCG level and the occurrence of APO.

Fat-to-muscle ratio is associated with insulin resistance and cardiometabolic disorders in adults with type 1 diabetes mellitus.

AIMS: This study aimed to investigate the correlation of the fat-to-muscle ratio (FMR) with insulin resistance (IR) and cardiometabolic disorders (CMD) in patients with type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: We retrospectively recruited 420 adults with T1DM [52.6% men, median age 32.4 (24.5, 43.0) years]. Body composition was assessed by bioelectrical impedance analysis and FMR was calculated. The characteristics of the overall participants were compared between tertiles of FMR. Logistic regression analyses were performed to assess the association of FMR tertiles with IR and cardiometabolic risk factors. RESULTS: Median age and median haemoglobin A1c of all participants were 32.4 (24.5, 43.0) years and 7.4 (6.5, 8.7)%, respectively. The prevalence of IR and CMD was 18% and 38.6%. The FMR significantly differed between men and women [0.39 (0.31, 0.53) vs. 0.74 (0.63, 0.92), respectively, p < .001]. The proportion of IR and CMD gradually increased as the FMR increased. The multivariable-adjusted odd ratios for IR and CMD in FMR tertile 3 compared with tertile 1 were 4.8 [95% confidence interval (CI): (1.9, 12.1)] and 9.7 (95% CI: 4.2, 22.3), respectively, in men. For women, the corresponding odd ratios were 4.0 (95% CI: 1.2, 12.9) for IR and 5.8 (95% CI: 2.4, 13.6) for CMD. CONCLUSIONS: FMR is associated with IR and CMD in adults with T1DM and could be used as a promising parameter for targeting treatment in T1DM.

Exploiting the potential of commercial objectives to extend the field of view of two-photon microscopy by adaptive optics.

Two-photon microscopy (TPM) has provided critical in situ and in vivo information in biomedical studies due to its high resolution, intrinsic optical sectioning, and deep penetration. However, its relatively small field of view (FOV), which is usually determined by objectives, restricts its wide application. In this paper, we propose a segment-scanning sensorless adaptive optics method to extend the FOV and achieve high-resolution and large-FOV two-photon imaging. We demonstrated the proposed method by imaging fluorescent beads, cerebral nerve cells of mouse brain slices, and cerebral vasculature and microglia of live mice. The method extended the FOV of a commercial objective from 1.8 to 3.46 mm while maintaining a lateral resolution of 840 nm and high signal-to-noise ratio. Our technology is compatible with a standard TPM and can be used for large-scale biological exploration.

A facile solvothermal syntheses of NiFe layered double hydroxide-Bi2MoO6 heterostructure/reduced graphene oxide with efficient photodegradation for tetracycline.

A heterojunction of NiFe layered double hydroxide (NiFe LDH)-Bi2MoO6 (BMO) loaded on reduced graphene oxide (RGO) sheets was synthesized via an eco-friendly solvothermal reaction. The structural characterization shows that NiFe LDH-BMO heterojunctions are well-distributed on the surface of silk-like transparent RGO sheets. The modification of BMO by NiFe LDH and RGO greatly enhances the photocatalytic performance of BMO for degradation of tetracycline (TC) under visible light. The photocatalyst prepared with 3 wt% RGO shows the highest activity and cycle stability. TC can be completely removed in 80 min, which is about 8.7 times that pure BMO, and showing excellent reusability even after five cycles. The excellent enhancement of photocatalytic performance of NiFe LDH-BMO/RGO composite is attributed to the unique sheet-on-sheet hierarchical heterostructure combined with RGO sheets, facilitating the visible light absorption and photogenerated charge carriers separation.

Increased gene copy number of DEFA1/DEFA3 worsens sepsis by inducing endothelial pyroptosis.

Sepsis claims an estimated 30 million episodes and 6 million deaths per year, and treatment options are rather limited. Human neutrophil peptides 1-3 (HNP1-3) are the most abundant neutrophil granule proteins but their neutrophil content varies because of unusually extensive gene copy number polymorphism. A genetic association study found that increased copy number of the HNP-encoding gene DEFA1/DEFA3 is a risk factor for organ dysfunction during sepsis development. However, direct experimental evidence demonstrating that these risk alleles are pathogenic for sepsis is lacking because the genes are present only in some primates and humans. Here, we generate DEFA1/DEFA3 transgenic mice with neutrophil-specific expression of the peptides. We show that mice with high copy number of DEFA1/DEFA3 genes have more severe sepsis-related vital organ damage and mortality than mice with low copy number of DEFA1/DEFA3 or wild-type mice, resulting from more severe endothelial barrier dysfunction and endothelial cell pyroptosis after sepsis challenge. Mechanistically, HNP-1 induces endothelial cell pyroptosis via P2X7 receptor-mediating canonical caspase-1 activation in a NLRP3 inflammasome-dependent manner. Based on these findings, we engineered a monoclonal antibody against HNP-1 to block the interaction with P2X7 and found that the blocking antibody protected mice carrying high copy number of DEFA1/DEFA3 from lethal sepsis. We thus demonstrate that DEFA1/DEFA3 copy number variation strongly modulates sepsis development in vivo and explore a paradigm for the precision treatment of sepsis tailored by individual genetic information.

The Assembly and Jamming of Nanoparticle Surfactants at Liquid-Liquid Interfaces.

Using the interactions between nanoparticles (NPs) and polymeric ligands to generate nanoparticle surfactants (NPSs) at the liquid-liquid interface, the binding energy of the NP to the interface can be significantly increased, irreversibly binding the NPSs to the interface. By designing a simplified NPS model, where the NP size can be precisely controlled and the characteristic fluorescence of the NPs be used as a direct probe of their spatial distribution, we provide new insights into the attachment mechanism of NPSs at the liquid-liquid interface. We find that the binding energy of NPSs to the interface can be reduced by competitive ligands, resulting in the dissociation and disassembly of NPSs at the interface, and allowing the construction of responsive, reconfigurable all-liquid systems. Smaller NPSs that are loosely packed (unjammed) and irreversibly bound to the interface can be displaced by larger NPSs, giving rise to a size-dependent assembly of NPSs at the interface. However, when the smaller size NPSs are densely packed and jam at the interface, the size-dependent assembly of NPSs at the interface can be completely suppressed.

Adaptive optics via pupil ring segmentation improves spherical aberration correction for two-photon imaging of optically cleared tissues.

Optical clearing methods reduce the optical scattering of biological samples and thereby extend optical imaging penetration depth. However, refractive index mismatch between the immersion media of objectives and clearing reagents induces spherical aberration (SA), causing significant degradation of fluorescence intensity and spatial resolution. We present an adaptive optics method based on pupil ring segmentation to correct SA in optically cleared samples. Our method demonstrates superior SA correction over a modal-based adaptive optics method and restores the fluorescence intensity and resolution at high imaging depth. Moreover, the method can derive an SA correction map for the whole imaging volume based on three representative measurements. It facilitates SA correction during image acquisition without intermittent SA measurements. We applied this method in mouse brain tissues treated with different optical clearing methods. The results illustrate that the synaptic structures of neurons within 900 µm depth can be clearly resolved after SA correction.

Functional coupling of Tmem74 and HCN1 channels regulates anxiety-like behavior in BLA neurons.

Anxiety disorders are the most prevalent psychiatric disorders, but their pathogenic mechanism remains poorly understood. Here, we report that transmembrane protein 74 (TMEM74), which contains two putative transmembrane domains and exhibits high levels of mRNA in the brain, is closely associated with the pathogenesis of anxiety disorders. TMEM74 was decreased in the serum of patients with anxiety and the basolateral amygdaloid nucleus (BLA) in chronic stress mice. Furthermore, genetic deletion of Tmem74 or selective knockdown of Tmem74 in BLA pyramidal neurons resulted in anxiety-like behaviors in mice. Whole-cell recordings in BLA pyramidal neurons revealed lower hyperpolarization-activated cation current (Ih) and greater input resistance and excitability in Tmem74-/- neurons than in wild-type neurons. Accordingly, surface expression of hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels was also lower in the BLA of Tmem74-/- mice. The Ih current blocker ZD7288 mimicked these effects in BLA pyramidal neurons in wild-type mice but not in Tmem74-/- mice. Consistent with the improvement in anxiety-like behaviors, Tmem74 overexpression restored HCN1 channel trafficking and pyramidal neuron excitability in the BLA of Tmem74-/- and chronic stress mice. Mechanistically, we demonstrate that interactions between Tmem74 and HCN1 are physiologically relevant and that transmembrane domain 1 (TM1) is essential for the cellular membrane localization of Tmem74 to enhance Ih. Together, our findings suggest that Tmem74 coupling with HCN1 acts as a critical component in the pathophysiology of anxiety and is a potential target for new treatments of anxiety disorders.

[Noninvasive prenatal screening for twin pregnancy: an analysis of 2057 cases].

OBJECTIVE: To analyze the results of noninvasive prenatal screening (NIPS) for fetal chromosome aneuploidy in twin pregnancy. METHODS: A total of 2057 women with twin-pregnancy between 12-26+6 weeks were recruited from Women's Hospital, Zhejiang University School of Medicine, Hangzhou Municipal Women's Hospital and Jiaxing Maternal and Child Health Hospital during February 2015 to August 2018. The cell-free DNA was extracted from the peripheral blood sample for DNA library, and non-invasive prenatal testing (NIPT) was performed by high-throughput sequencing technique. The fetal karyotype analysis or neonatal karyotype analysis was performed in pregnant women with fetal chromosome aneuploidy, and all subjects were followed up. The efficiency of NIPS testing for twin aneuploidy was calculated. RESULTS: NIPS revealed chromosome abnormalities in 11 out of 2057 twin pregnant women, 9 cases were confirmed chromosome abnormalities, 2 cases were normal and no false negative cases. In this screening, the detection rate, sensitivity, specificity, positive predictive value, false positive rate of NIPS were 100.00%, 100.00%, 99.90%, 81.82%, 0.10%. Those were 100.00%, 100.00%, 99.95%, 87.50% and 0.05% for trisomy 21, 100.00%, 100.00%, 100.00%, 100.00%, 0.00% for trisomy18, and the specificity and false positive rate for trisomy13 were 99.95% and 0.05%, respectively. CONCLUSIONS: NIPS can detect fetal chromosomal aneuploidy rapidly and accurately in twin pregnancies,and it is of value in clinical application.

Spontaneous Ectopic Tubal Pregnancy After Partial Salpingectomy.

Objective: To report a rare case of spontaneous ectopic pregnancy (EP) after partial salpingectomy treated by laparoscopy. Case Report: A 30-year-old gravida 1 para 0 woman with a history of left adnexectomy, due to left ovarian torsion 13 years ago, was referred to our hospital. She had experienced lower abdominal pain for 1 day and amenorrhea for 1 week. Transvaginal ultrasonography did not reveal an intrauterine pregnancy, but showed a suspected extrauterine gestational sac on the left adnexal area. The patient was diagnosed with ectopic pregnancy, and laparoscopy was performed. During the operation, we found a gestational sac on the left fallopian tube stump. Conclusion: The most significant risk factors for ectopic pregnancy (EP) are previous procedures and conditions that cause tubal injury. Therefore, it is necessary to be alert to the occurrence of the disease even if there is a history of tubal resection and ensure no part of the fallopian tube is left behind during removal.

Bacillus amyloliquefaciens A-1 inhibiting fungal spoilage in agricultural products is improved by metabolic engineering of enhancing surfactin yield.

Fungi and subsequent mycotoxins contamination in agricultural products have caused enormous losses and great harm to human and animal health. Biological control has attracted the attention of researchers due to its advantages, including mild conditions, low cost, high efficiency and low nutrient loss. In this study, a newly isolated strain Bacillus amyloliquefaciens A-1 (A-1), was screened for its ability to inhibit the growth and Aflatoxin B1 (AFB1) production of Aspergillus flavus NRRL 3357. Electron microscopy results revealed that mycelium and conidia of A. flavus were destroyed by A-1, affecting hyphae, cell walls, cell membranes and organelles. RNA-seq analysis indicated disturbance in gene expression profiles of A. flavus, including amino acid degradation and starch and sucrose metabolism pathways. Importantly, the biosynthesis of AFB1 was significantly inhibited by the down-regulation of key regulatory genes, aflR and aflS, and the simultaneous down-regulation of most structural genes. Genome analysis predicted six secondary metabolites biosynthetic gene clusters. Then, four surfactin synthesized by cluster C were identified as the main active substance of A-1 using HPLC-Q-TOF-MS. The addition of alanine, threonine, Fe2+ increased surfactin production. Notably, the overexpression of comX also improved surfactin production. The vivo test results indicated that A-1 could significantly inhibit the decay of pear by Aspergillus westerdijkiae, and the mildew of maize and peanuts. Especially, the overexpression of comX in A-1 could enhance the inhibitory activity. In conclusion, the inhibition mechanism of A-1 was revealed, and comX was found can improve the production of surfactin and subsequent activities, which provides the scientific basis for the development of biocontrol agents to reduce spoilage in agricultural products.

Antifungal potential of lipopeptides produced by the Bacillus siamensis Sh420 strain against Fusarium graminearum.

Biological control is a more sustainable and environmentally friendly alternative to chemical fungicides for controlling Fusarium spp. infestations. In this work, Bacillus siamensis Sh420 isolated from wheat rhizosphere showed a high antifungal activity against Fusarium graminearum as a secure substitute for fungicides. Sh420 was identified as B. siamensis using phenotypic evaluation and 16S rDNA gene sequence analysis. An in vitro antagonistic study showed that Sh420's lipopeptide (LP) extract exhibited strong antifungal properties and effectively combated F. graminearum. Meanwhile, lipopeptides have the ability to decrease ergosterol content, which has an impact on the overall structure and stability of the plasma membrane. The PCR-based screening revealed the presence of antifungal LP biosynthetic genes in this strain's genomic DNA. In the crude LP extract of Sh420, we were able to discover several LPs such as bacillomycin, iturins, fengycin, and surfactins using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Microscopic investigations (fluorescent/transmission electron microscopy) revealed deformities and alterations in the morphology of the phytopathogen upon interaction with LPs. Sh420 LPs have been shown in grape tests to be effective against F. graminearum infection and to stimulate antioxidant activity in fruits by avoiding rust and gray lesions. The overall findings of this study highlight the potential of Sh420 lipopeptides as an effective biological control agent against F. graminearum infestations.IMPORTANCEThis study addresses the potential of lipopeptide (LP) extracts obtained from the strain identified as Bacillus siamensis Sh420. This Sh420 isolate acts as a crucial player in providing a sustainable and environmentally friendly alternative to chemical fungicides for suppressing Fusarium graminearum phytopathogen. Moreover, these LPs can reduce ergosterol content in the phytopathogen influencing the overall structure and stability of its plasma membrane. PCR screening provided confirmation regarding the existence of genes responsible for biosynthesizing antifungal LPs in the genomic DNA of Sh420. Several antibiotic lipopeptide compounds were identified from this bacterial crude extract using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Microscopic investigations revealed deformities and alterations in the morphology of F. graminearum upon interaction with LPs. Furthermore, studies on fruit demonstrated the efficacy of Sh420 LPs in mitigating F. graminearum infection and stimulating antioxidant activity in fruits, preventing rust and gray lesions.

Performance of noninvasive prenatal screening for fetal sex chromosome aneuploidies in a cohort of 116,862 pregnancies.

BACKGROUND: Noninvasive prenatal screening (NIPS) has shown good performance in screening common aneuploidies. However, its performance in detecting fetal sex chromosome aneuploidies (SCAs) needs to be evaluated in a large cohort. RESEARCH DESIGN AND METHODS: In this retrospective observation, a total of 116,862 women underwent NIPS based on DNA nanoball sequencing from 2015 to 2022. SCAs were diagnosed based on karyotyping or chromosomal microarray analysis (CMA). Among them, 2,084 singleton pregnancies received karyotyping and/or CMA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of NIPS for fetal SCAs were evaluated. RESULTS: The sensitivity was 97.7% (95%CI, 87.7-99.9), 87.3% (95% CI, 76.5-94.4), 96.1% (95%CI, 86.5-99.5), and 95.7% (95% CI, 78.1-99.9), the PPV was 25.8% (95%CI, 19.2-33.2), 80.9% (95%CI, 69.5-89.4), 79.0% (95%CI, 66.8-88.3), and 53.7% (95%CI, 37.4-69.3) for 45,X, 47,XXY, 47,XXX, and 47,XYY, respectively. The specificity was 94.1% (95%CI, 93.0-95.1) for 45,X, and more than 99.0% for sex chromosome trisomy (SCT). The NPV was over 99.0% for all. CONCLUSIONS: NIPS screening for fetal SCAs has high sensitivity, specificity and NPV. The PPV of SCAs was moderate, but that of 45,X was lower than that of SCTs. Invasive prenatal diagnosis should be recommended for high-risk patients.

Layer-by-Layer Engineered All-Liquid Microfluidic Chips for Enzyme Immobilization.

Enzyme immobilization in the confines of microfluidic chips, that promote enzyme activity and stability, has become a powerful strategy to enhance biocatalysis and biomass conversion. Here, based on a newly developed all-liquid microfluidic chip, fabricated by the interfacial assembly of nanoparticle surfactants (NPSs) in a biphasic system, a layer-by-layer assembly strategy to generate polysaccharide multilayers on the surface of a microchannel, greatly enhancing the mechanical properties of the microchannel and offering a biocompatible microenvironment for enzyme immobilization, is presented. Using horseradish peroxidase and glucose oxidase as model enzymes, all-liquid microfluidic enzymatic and cascade reactors have been constructed and the crucial role of polysaccharide multilayers on enhancing the enzyme loading and catalytic efficiency is demonstrated.

Hydrangea-like NiMoO4-Ag/rGO as Battery-type electrode for hybrid supercapacitors with superior stability.

It is a great challenge to design electrode materials with good stability and high specific capacitance for supercapacitors. Herein, a three-dimensional (3D) hydrangea-like NiMoO4 micro-architecture with Ag nanoparticles anchored on the surface has been designed by adding EDTA-2Na, which was assembled with reduced graphene oxide (rGO) and named as NiMoO4-Ag/rGO composite. Benefiting from the synergetic contributions of structural and componential properties, NiMoO4-Ag/rGO composite exhibits a high specific capacitance of 566.4 C g-1 at 1 A g-1, and great cycling performance with 90.5% capacitance retention after 1000 cycles at 10 A g-1. The NiMoO4-Ag/rGO electrode shows an enhanced cycling stability due to the two-dimensional towards two-dimensional (2D-2D) interface coupling between rGO and NiMoO4 nanosheets, and the stable 3D hydrangea-like micro-architecture. Moreover, NiMoO4-Ag/rGO with 5-15 nm pore structure and enhanced conductivity exhibits improved charge transfer and ions diffusion. Besides, NiMoO4-Ag/rGO//AC capacitor displays an outstanding energy density of 40.98 Wh kg-1 at 800 kW kg-1, and an excellent cycling performance with 73.3% capacitance retention at 10 A g-1 after 8000 cycles. The synthesis of NiMoO4-Ag/rGO composite can provide an effective strategy to solve the poor electrochemical stability and slow electron/ion transfer of NiMoO4 material as supercapacitors electrode.

Diagnostic value of maternal alpha-fetoprotein variants in second-trimester biochemical screening for trisomy 21 and 18.

To evaluate the clinical predictive value of serum alpha-fetoprotein variants (AFP-L2, AFP-L3) in combination with maternal serum prenatal screening biomarkers in predicting fetal trisomy 21 and trisomy 18. We analyze the data of singleton pregnant women at 15-20+6 weeks of 731,922 gravidas from October 2007 to September 2019. The research objects were separated into the following groups: control (n = 569), trisomy 21 (n = 116), and trisomy 18 (n = 52). The cases were diagnosed by chromosomal karyotypic analysis of amniotic fluid cells. Level of AFP-L2 and AFP-L3 were detected in maternal serum among control women and patients. Receiver operator characteristic analysis, detection rate, false positive rate, false negative rate, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio, comprehensive discriminant improvement, net weight classification improvement, decision curve analysis and Hosmer-lemeshow (H-L) test were used to investigate the predictive value of free ß-hCG, AFP, AFP-L2 and AFP-L3 on the risk models of trisomy 21, 18. There was a statistically significant difference in maternal serum AFP-L2 and AFP-L3 multiple of the median (MoM) among the trisomy 21, trisomy 18, and control groups. The AUCs of AFP-L2 and AFP-L3 for the screening trisomy 21 and trisomy 18 fetus were 0.785, 0.758 and 0.775, 0.754. According to ROC, the optimal cut-off values of AFP-L2 and AFP-L3 for predicting trisomy 21 and trisomy 18 fetuses all were 1.09 MoM and 1.30 MoM, respectively. The risk-calculation model constructed by AFP-L2 + AFP-L3 MoM manifested better efficiency than the original single-value truncation method using AFP MoM alone. Compared with different modeling methods, the AUC of trisomy 21 fetuses predicted by AFP-L2 + AFP-L3 + free ß-hCG achieved an optimal value (0.938), while the AUC of trisomy 18 fetus predicted by AFP-L2 + free ß-hCG was the best (0.991). Compared with AFP, the IDI of AFP-L2 or AFP-L3 alone increased 9.56% and 12.34%; the NRI increased 26.50% and 26.70 in predicting trisomy 21. For trisomy 18, the IDI of AFP-L2 or AFP-L3 alone declined with 8.12% and 1.52%; the NRI declined with 13.84% and 8.54%. In the combined model, the model with best detection rate, false positive rate and positive likelihood ratio was AFP-L2 + AFP-L3 + free ß-hCG, followed by AFP-L2 + free ß-hCG and AFP-L3 + free ß-hCG, and finally AFP + free ß-hCG. Maternal serum AFP-L2 and AFP-L3 in the second trimester is a good marker for screening trisomy 21 and trisomy18 with high sensitivity and specificity. The combined screening results are better than the single marker, and the efficiency of AFP-L2 + AFP-L3 + free ß-hCG is the best.

Construction and predictive value of risk models of maternal serum alpha-fetoprotein variants and fetal open neural tube defects.

The correlation of maternal serum alpha-fetoprotein (AFP) variants (AFP-L2, AFP-L3), free beta-human chorionic gonadotropin (free ß-hCG), and open neural tube defects (ONTDs) during the second trimester, and the screening efficiency of different risk models remain indistinct. We conducted a retrospective case-control study, and studied 57 pregnant women with ONTD fetuses and 569 pregnant women with normal fetuses. The receiver operating characteristic curve method indicated the best cutoff value and area under the curve (AUC). The predictive value of ONTD risk models by free ß-hCG, AFP, AFP-L2, and AFP-L3 was investigated via integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA). Compared to the control group, AFP, AFP-L2, and AFP-L3 levels were significantly higher, while free ß-hCG level was significantly lower in the study group. The triple-index model of free ß-hCG + AFP-L2 + AFP-L3 and the dual-index model of AFP-L2 + AFP-L3 showed the best predictive values, respectively (AUC = 0.905; AUC = 0.885). The order of the single-index model AUCs was AFP-L3 > AFP-L2 > AFP > free ß-hCG. The negative predictive value, false positive rate, and negative likelihood ratio of AFP-L2, AFP-L3 alone, or combined with free ß- hCG were better than those of AFP alone; however, the positive likelihood ratio was the opposite. The replacement of AFP by AFP-L2 or AFP-L3 combined with free ß-hCG increased the IDI and NRI for predicting ONTD. The top five DCAs were AFP-L2 + free ß-hCG, free ß-hCG, AFP-L3, AFP + free ß-hCG, and AFP. Indicators of maternal serum free ß-hCG, AFP-L2, and AFP-L3 in the second trimester exhibited high sensitivity and specificity screening for ONTD fetuses. Risk models constructed using AFP-L2 + AFP-L3 and AFP-L2 + AFP-L3 + free ß-hCG demonstrated better screening efficiency.

miR-17-5p Promotes migration of human hepatocellular carcinoma cells through the p38 mitogen-activated protein kinase-heat shock protein 27 pathway.

UNLABELLED: miR-17-5p is overexpressed in hepatocellular carcinoma (HCC), but the specific regulatory mechanisms of miR-17-5p in HCC remain unknown. We investigated the molecular basis of miR-17-5p as an oncogene in human HCC cell lines. Our in vivo and in vitro data indicate that miR-17-5p up-regulates the migration and proliferation of HCC cells. Interestingly, proteomic and western blotting assays revealed that miR-17-5p significantly activates the p38 mitogen-activated protein kinase MAPK pathway and increases the phosphorylation of heat shock protein 27 (HSP27). Our results also suggest that E2F1-dependent down-regulation of Wip1 regulates miR-17-5p-p38-HSP27 signaling. Furthermore, suppression of HSP27 expression by small interfering RNA or the p38 MAPK pathway-specific inhibitor SB203580 decreases the migration of HCC cells overexpressing miR-17-5p but does not reduce their proliferation. Finally, we show that miR-17-5p expression correlates well with HSP27 status in primary human HCC tissues with metastasis. CONCLUSION: Our findings suggest that the p38 MAPK pathway plays a crucial role in miR-17-5p-induced phosphorylation of HSP27 and, as a consequence, phosphorylated HSP27 enhances the migration of HCC cells. Our data highlight an important role of miR-17-5p in the proliferation and migration of HCC cells and support the potential application of miR-17-5p in HCC therapy.

Clinical Efficiency of Non-invasive Prenatal Screening for Common Trisomies in Low-Risk and Twin Pregnancies.

To evaluate the clinical efficiency of non-invasive prenatal screening (NIPS) for fetal aneuploidies in low-risk and twin pregnancies, patients who received NIPS in a tertiary university hospital were enrolled, and their clinical data, NIPS results and pregnancy outcomes were collected. Patients were divided into singleton and twin pregnancies, and then those with singleton pregnancies were divided into low- and high-risk pregnancies. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were estimated. Comparisons were made on the clinical efficiency of NIPS between singleton and twin pregnancies, as well as between low- and high-risk pregnancies. Of 66,172 patients enrolled, 59,962 were eligible for analysis. The sensitivity, specificity and NPV were ≥ 99% in singleton and twin pregnancies. The PPVs were 90.4, 56.6, and 13.0% in singleton pregnancies, while 100, 33.3, and 0% in twin pregnancies for trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13), respectively (P > 0.05 for all). The PPVs were 97.4 and 90.0% in high-risk pregnancies, while 78.6 and 16.7% in low-risk pregnancies for T21 and T18, respectively (P < 0.05 for all). In summary, the performance of NIPS in singleton pregnancies was similar to that in twin pregnancies. NIPS can be recommended for all pregnancies regardless of the risks.

An altered pattern of liver apolipoprotein A-I isoforms is implicated in male chronic hepatitis B progression.

Chronic hepatitis B (CHB) appears to progress more rapidly in males than in females, and CHB-related hepatic cirrhosis and hepatocellular carcinoma are predominately diseases that tend to occur in men and postmenopausal women. To obtain more insight into the underlying mechanisms of gender disparity of CHB progress, two-dimensional difference gel electrophoresis was employed to compare liver proteome of C57BL/6 and HBV transgenic (HBV-Tg) mice both in male and female groups. We identified 8 differently expressed proteins in male HBV-Tg mice and 12 in female HBV-Tg mice. Apolipoprotein A-I (Apo A-I) was found to be down-regulated in male and female HBV-Tg mouse liver. It is more interesting that the pattern of liver Apo A-I isoforms was altered in male HBV-Tg mice but not in female HBV-Tg mice. Our further results indicated that the basic Apo A-I isoform, based on pI positions from serum 2-dimensional Western blotting, increased in male CHB patient sera but not in female CHB patient sera. Finally, we identified that the oxidative modification Apo A-I mainly reside in basic isoform. This pattern of selectively modified Apo A-I isoforms may be considered as a pathological hallmark that may extend our knowledge of the molecular pathogenesis of CHB progression.