Reversible encephalitis-like episodes in fragile X-associated tremor/ataxia syndrome: a case report.

BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by CGG repeat expansion of FMR1 gene. Both FXTAS and neuronal intranuclear inclusion disease (NIID) belong to polyglycine diseases and present similar clinical, radiological, and pathological features, making it difficult to distinguish these diseases. Reversible encephalitis-like attacks are often observed in NIID. It is unclear whether they are presented in FXTAS and can be used for differential diagnosis of NIID and FXTAS. CASE PRESENTATION: A 63-year-old Chinese male with late-onset gait disturbance, cognitive decline, and reversible attacks of fever, consciousness impairment, dizziness, vomiting, and urinary incontinence underwent neurological assessment and examinations, including laboratory tests, electroencephalogram test, imaging, skin biopsy, and genetic test. Brain MRI showed T2 hyperintensities in middle cerebellar peduncle and cerebrum, in addition to cerebellar atrophy and DWI hyperintensities along the corticomedullary junction. Lesions in the brainstem were observed. Skin biopsy showed p62-positive intranuclear inclusions. The possibilities of hypoglycemia, lactic acidosis, epileptic seizures, and cerebrovascular attacks were excluded. Genetic analysis revealed CGG repeat expansion in FMR1 gene, and the number of repeats was 111. The patient was finally diagnosed as FXTAS. He received supportive treatment as well as symptomatic treatment during hospitalization. His encephalitic symptoms were completely relieved within one week. CONCLUSIONS: This is a detailed report of a case of FXTAS with reversible encephalitis-like episodes. This report provides new information for the possible and rare features of FXTAS, highlighting that encephalitis-like episodes are common in polyglycine diseases and unable to be used for differential diagnosis.

Heterozygous RELN missense variants associated with genetic generalized epilepsy.

PURPOSE: The RELN gene encodes the secreted glycoprotein Reelin and has important functions in both developing and adult brains. In this study, we aimed to explore the association between the RELN and genetic generalized epilepsy (GGE). METHODS: We performed whole-exome sequencing on a cohort of 92 patients with GGE. Based on amino acid sequence alignments, allele frequency, pedigree validation and computational modeling, the RELN variants were identified and clinical features of cases were summarized. Cell-based Reelin secretion assays were examined by Western blotting. Alterations of mutant Reelin transport through the secretion pathway were detected by immunofluorescence staining. RESULTS: Three novel pathogenic RELN variants (3.26%; c.2260C>T/p.R754W, c.2914C>G/p.P972A and c.3029G>A/p.R1010H) were identified. All probands showed adolescence-onset generalized seizures characterized by generalized epileptiform discharges with normal EEG backgrounds, no or mild cognitive impairment, and responded well to anti-seizure medications. All these variants were located in the central regions from 1B to 2A consecutive repeats, and protein modeling demonstrated structural alterations in Reelin. Moreover, we found that these heterozygous missense variants significantly decreased the secretion of mutant proteins in HEK-293T cells, and this impairment was due to the altered transport of mutant Reelin in the secretion pathway. CONCLUSION: These results suggest that RELN is potentially associated with GGE. The phenotype of GGE caused by RELN variants is relatively mild, and the pathogenic mechanism may involve a loss-of-function.

White matter integrity mediates the associations between white matter hyperintensities and cognitive function in patients with silent cerebrovascular diseases.

OBJECTIVE: To evaluate the relationships between cognitive function and white matter hyperintensity volume (WMHV) in patients with silent cerebrovascular disease and to investigate whether white matter integrity or brain atrophy play a role in this association. METHODS: Automated Fiber Quantification and Voxel- based morphometry were used to track and identify the integrity of 20 well-defined white matter tracts and to measure the gray matter volume (GMV). A linear regression model was applied for examining the associations between cognitive function and WMHV and mediation analysis was used to identify the roles of white matter integrity or GMV in the influence of WMHV on cognitive function. RESULTS: Two hundred and thirty-six individuals were included for analysis. Executive function was linearly associated with fractional anisotropy (FA) of the right interior frontal occipital fasciculus (IFOF) (ß = 0.193; 95% CI, 0.126 to 1.218) and with WMHV (ß = -0.188; 95% CI, -0.372 to -0.037). Information processing speed was linearly associated with WMHV (ß = -0.357; 95% CI, -0.643 to -0.245), FA of the right anterior thalamic radiation (ATR) (ß = 0.207; 95% CI, 0.116 to 0.920), and FA of the left superior longitudinal fasciculus (SLF) (ß = 0.177; 95% CI, 0.103 to 1.315). The relationship between WMHV and executive function was mediated by FA of the right IFOF (effect size = -0.045, 95% CI, -0.015 to -0.092). Parallel mediation analysis showed that the association between WMHV and information processing speed was mediated by FA of the right ATR (effect size = -0.099, 95% CI, -0.198 to -0.038) and FA of the left SLF (effect size = -0.038, 95% CI, -0.080 to -0.003). CONCLUSION: These findings suggest a mechanism by which WMH affects executive function and information processing speed by impairing white matter integrity. This may be helpful in providing a theoretical basis for rehabilitation strategies of cognitive function in patients with silent cerebrovascular diseases.

Integration analysis identifies the role of metallothionein in the progression from hepatic steatosis to steatohepatitis.

Background: Non-alcoholic fatty liver disease (NAFLD), a metabolic disorder that develops from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), has become an epidemic of chronic liver dysfunction worldwide. However, mechanisms that govern the transition from NAFL to NASH have not been fully elucidated. Methods: Gene expression profile data of NAFLD liver tissues were obtained from Gene Expression Omnibus (GEO), including three microarray datasets with 60 NAFL and 44 NASH patients. Integrative differentially expressed genes (DEGs) between NAFL and NASH patients were identified using robust rank aggregation (RRA) analysis. Hub genes were identified combined with gene ontology functional annotation and protein-protein interaction network construction and validated using a sequencing dataset. Huh-7 cells with palmitate-induced lipid overload and NAFLD-diet mouse model of different stages were used to verify our findings. Results: RRA analysis determined 70 robust DEGs between NAFL and NASH. The most robustly upregulated genes were SPP1, AKR1B10, CHST9, and ANXA2, while the most robustly downregulated DEGs were SNORD94, SCARNA10, SNORA20, and MT1M. Cellular response to zinc ion (GO: 0071294) ranked first in GO analysis of downregulated genes, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment showed that mineral absorption (hsa04978) was significantly enriched. The involvement of the metallothionein pathway was further validated by the decrease of Mt1 expression during NAFL to NASH progression in NAFLD mice and the protection from lipotoxicity in liver cells by overexpressing MT1M. Conclusions: Our integrated analysis identified novel gene signatures and provided comprehensive molecular mechanisms underlying the transition from NAFL to NASH. Metallothionein might be a potential intervention target for NAFLD progression.

Upstream open reading frame with NOTCH2NLC GGC expansion generates polyglycine aggregates and disrupts nucleocytoplasmic transport: implications for polyglycine diseases.

Neuronal intranuclear inclusion disease (NIID) is neurodegenerative disease characterized by widespread inclusions. Despite the identification of GGC repeat expansion in 5'UTR of NOTCH2NLC gene in adult-onset NIIDs, its pathogenic mechanism remains unclear. Gain-of-function poly-amino-acid proteins generated by unconventional translation have been revealed in nucleotide repeat expansion disorders, inspiring us to explore the possibility of unconventional translation in NIID. Here we demonstrated that NOTCH2NLC 5'UTR triggers the translation of a polyglycine (polyG)-containing protein, N2NLCpolyG. N2NLCpolyG accumulates in p62-positive inclusions in cultured cells, mouse models, and NIID patient tissues with NOTCH2NLC GGC expansion. Translation of N2NLCpolyG is initiated by an upstream open reading frame (uORF) embedding the GGC repeats. N2NLCpolyG tends to aggregate with the increase of GGC repeat units, and displays phase separation properties. N2NLCpolyG aggregation impairs nuclear lamina and nucleocytoplasmic transport but does not necessarily cause acute death on neuronal cells. Our study suggests a similarity of pathogenic mechanisms between NIID and another GGC-repeat disease, fragile X-associated tremor ataxia syndrome. These findings expand our knowledge of protein gain-of-function in NIID, and further highlight evidence for a novel spectrum of diseases caused by aberrant polyG protein aggregation, namely the polyG diseases.

GABAergic Interneuron and Neurotransmission Are mTOR-Dependently Disturbed in Experimental Focal Cortical Dysplasia.

Focal cortical dysplasia (FCD) is a major cause for drug-resistant epilepsies. The molecular and cellular mechanisms of epileptogenesis in FCD are still poorly understood. Some studies have suggested that deficiencies of γ-aminobutyric acid (GABA) system may play an important role in type II FCD, but it remains controversial. In order to examine whether and how GABAergic interneurons and synaptic function are affected, we generated a somatic mTOR hyperactivation-based mouse model of type II FCD by in utero electroporation, quantified densities of interneurons in the malformed cortices, and recorded miniature inhibitory postsynaptic currents in dysmorphic neurons. We detected 20-25% reduction of GABAergic interneurons within malformed cortices, independent of cortical regions and cell subtypes but proportionate to the decrease of global neuron counts. GABAergic synaptic transmission from interneurons to mTOR hyperactivated dysmorphic neurons was dramatically disrupted, outweighing the decrease of interneuron counts. Postnatal mTOR inhibition partially rescued these alterations of GABAergic system. We also quantified the expression of GABAA receptor, GABA transporter, and chloridion transporter encoding genes and found that their expression was relatively intact within the malformed cortices. Taken together, these results confirmed that GABAergic interneuron and synapse transmission are disturbed profoundly in an mTOR-dependent manner in type II FCD. Our study suggests that postsynaptic mechanisms independent of interneuron reduction or altered expression of GABA synapse genes might be accountable for the impaired GABAergic neurotransmission in type II FCD as well as other mTOR-related epilepsies.

Bioinformatic analysis identifies key transcriptome signatures in temporal lobe epilepsy.

AIMS: To identify transcriptome signatures underlying epileptogenesis in temporal lobe epilepsy (TLE). METHODS: Robust rank aggregation analysis was used to integrate multiple microarrays in rodent models of TLE and determine differentially expressed genes (DEGs) in acute, latent, and chronic stages. Functional annotation and protein-protein interaction analysis were performed to explore the potential functions of the DEGs and identify hub genes with the highest intramodular connectivity. The association between hub genes and hippocampal sclerosis/seizure frequency was analyzed using publicly available RNA-sequencing datasets from TLE patients. We subsequently established a pilocarpine-induced status epilepticus (SE) model in rats and validated mRNA expression of hub genes by quantitative reverse transcription PCR (qRT-PCR). RESULTS: The DEGs in the acute, latent, and chronic phases of TLE in animal models were prominently enriched in inflammatory response. Hub genes identified in the acute phase mainly participated in biological processes including inflammation, blood-brain barrier damage, and cell adhesion. The hub genes in the latent phase were related to microglia/macrophage activation (Emr1 and Aif1) and phagocytosis (Cd68, Tyrobp, and Lyz). In the chronic phase, the hub genes were associated with activation of complements and microglia/macrophages. We further found that some hub genes identified in human TLE, such as Tlr2, Lgals3, and Stat3, were positively correlated with seizure frequency. Other hub genes, including Lgals3 and Serpine1, were associated with hippocampus sclerosis. qRT-PCR analysis confirmed that the mRNA levels of hub genes in rat hippocampus were significantly up-regulated after SE induction. CONCLUSIONS: Our integrated analysis identified hub genes in different stages of epilepsy. The functional annotations suggest that the activation and phagocytic activities of microglia/macrophages may play critical roles in epileptogenesis of TLE.

The Rodent Models of Dyskinesia and Their Behavioral Assessment.

Dyskinesia, a major motor complication resulting from dopamine replacement treatment, manifests as involuntary hyperkinetic or dystonic movements. This condition poses a challenge to the treatment of Parkinson's disease. So far, several behavioral models based on rodent with dyskinesia have been established. These models have provided an important platform for evaluating the curative effect of drugs at the preclinical research level over the past two decades. However, there are differences in the modeling and behavioral testing procedures among various laboratories that adversely affect the rat and mouse models as credible experimental tools in this field. This article systematically reviews the history, the pros and cons, and the controversies surrounding rodent models of dyskinesia as well as their behavioral assessment protocols. A summary of factors that influence the behavioral assessment in the rodent dyskinesia models is also presented, including the degree of dopamine denervation, stereotaxic lesion sites, drug regimen, monitoring styles, priming effect, and individual and strain differences. Besides, recent breakthroughs like the genetic mouse models and the bilateral intoxication models for dyskinesia are also discussed.

[Prenatal diagnosis of a novel SOX10 mutation in a patient with syndromic hearing loss].

OBJECTIVE: To explore the genetic basis for a patient with syndromic hearing loss. METHODS: Genomic DNA of the patient was extracted, for which 127 deafness-related genes were enriched with a chip. Following next generation sequencing, pathogenic loci in exonic regions were analyzed through comparison against the databases. Genotype of her fetus for the suspected site was determined by testing the amniotic fluid sample. qPCR method was applied to verify the deletion of a large fragment. RESULTS: The proband was diagnosed with Waardenburg syndrome type 2, and had harbored a novel heterozygous deletion of the exons 3 and 4 of the SOX10 gene. Her fetus was found to carry the same deletion and presented with blue eyes and deafness after birth. CONCLUSION: Waardenburg syndrome type 2 due to SOX10 gene deletion may feature autosomal dominant inheritance with incomplete penetrance. The deletion of exons 3 and 4 of the SOX10 gene probably underlies the disease in this family.

Effects of fiber alignment on stem cells-fibrous scaffold interactions.

Considerable research has been focused on the utilization of electrospun ultrafine fibers to construct biomimetic scaffolds for tissue engineering applications. However, there is still a limited understanding of the effects of fiber alignment on stem cells-fibrous scaffold interactions and their role in deciding the fate of stem cells and scaffolds. Here, we tracked the real-time interactions between mesenchymal stem cells (MSCs) and aligned/non-aligned electrospun PCL-gelatin ultrafine fibers using time-lapse microscopy, and investigated the effects of fiber alignment on the behaviour of cell spreading, migration and differentiation, and scaffold remodeling. Cells were found to spread and migrate with increased velocity in the direction of aligned fibers as compared to non-aligned ones. Moreover, enhanced interactions between cells and aligned fibers were found to facilitate the infiltration of cells into the interior of fibrous constructs, which further led to enhanced micro-integration and scaffold remodeling as well as increased gene expression of late osteogenic markers as compared to non-aligned fibrous constructs. This study advances our understanding of the effects of fiber alignment on stem cells-fibrous scaffold interactions, and will facilitate the design of fibrous scaffolds with enhanced cell-matrix interactions for tissue engineering applications.

Effect of ultrasound on cyprid footprint and juvenile barnacle adhesion on a fouling release material.

In our earlier studies, we have demonstrated that low and high intensity ultrasound can prevent barnacle cyprid settlement. In this study, we found that ultrasound treatment reduced the adhesion of newly metamorphosed barnacles up to 2 days' old. This was observed in the reduction of adhesion strength of the newly settled barnacles from ultrasound treated cyprids on silicone substrate compared to the adhesion strength of barnacles metamorphosed from cyprids not exposed to ultrasound. Atomic force microscopy (AFM) was used to analyze the effect of ultrasound on barnacle cyprid footprints (FPs), which are protein adhesives secreted when the larvae explore surfaces. The ultrasound treated cyprids were found to secrete less FPs, which appeared to spread a larger area than those generated by untreated cyprids. The evidence from this study suggests that ultrasound treatment results in a reduced cyprid settlement and footprint secretion, and may affect the subsequent recruitment of barnacles onto fouling release surfaces by reducing the ability of early settlement stage of barnacles (up to 2 days' old) from firmly adhering to the substrates. Ultrasound therefore can be used in combination with fouling release coatings to offer a more efficient antifouling strategy.

Adhesion of B. subtilis spores and vegetative cells onto stainless steel--DLVO theories and AFM spectroscopy.

Interactions between the bacterium Bacillus subtilis (either as vegetative cells or as spores) and stainless steel 316 (SS-316) surfaces were quantified using the classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory and extended DLVO (xDLVO) approach in conjunction with live force spectroscopy using an Atomic Force Microscope (AFM). The xDLVO approach accounts for acid-base (polar) interactions that are not considered in the classical DLVO theory. AFM results revealed that spores manifested stronger attraction interactions to stainless steel compared to their vegetative cells counterparts due to lower energy barrier as predicted by both the theoretical approaches as well as the higher hydrophobicity on the spore surfaces. Both DLVO and xDLVO theories predict that vegetative cells manifest weaker attachment on the surfaces compared to spores. Results of AFM force measurement corroborate these findings; spores recorded significantly higher adhesion force (2.92±0.4 nN) compared to vegetative cells (0.65±0.2 nN). The adhesion of spores presents greater challenges in biofilm control owing to its stronger attachment and persistence when the spores are formed under adverse environmental conditions.

Controlled biomineralization of electrospun poly(ε-caprolactone) fibers to enhance their mechanical properties.

Electrospun polymeric fibers have been investigated as scaffolding materials for bone tissue engineering. However, their mechanical properties, and in particular stiffness and ultimate tensile strength, cannot match those of natural bones. The objective of the study was to develop novel composite nanofiber scaffolds by attaching minerals to polymeric fibers using an adhesive material - the mussel-inspired protein polydopamine - as a "superglue". Herein, we report for the first time the use of dopamine to regulate mineralization of electrospun poly(ε-caprolactone) (PCL) fibers to enhance their mechanical properties. We examined the mineralization of the PCL fibers by adjusting the concentration of HCO(3)(-) and dopamine in the mineralized solution, the reaction time and the surface composition of the fibers. We also examined mineralization on the surface of polydopamine-coated PCL fibers. We demonstrated the control of morphology, grain size and thickness of minerals deposited on the surface of electrospun fibers. The obtained mineral coatings render electrospun fibers with much higher stiffness, ultimate tensile strength and toughness, which could be closer to the mechanical properties of natural bone. Such great enhancement of mechanical properties for electrospun fibers through mussel protein-mediated mineralization has not been seen previously. This study could also be extended to the fabrication of other composite materials to better bridge the interfaces between organic and inorganic phases.

TPPP acts downstream of RhoA-ROCK-LIMK2 to regulate astral microtubule organization and spindle orientation.

The actin cytoskeleton in eukaryotic cells undergoes drastic rearrangement during mitosis. The changes to the actin cytoskeleton are most obvious in the adherent cells, where the actin stress fibres are disassembled, and the cortical actin network becomes more prominent with concomitant increase in cell rigidity as cells round up and enter mitosis. Although the regulatory connections between the actin cytoskeleton and the early mitotic events are apparent, the mechanisms that govern these links are not well understood. Here, we report that LIMK1 and LIMK2, the downstream effectors of RhoA and ROCK, regulate centrosome integrity and astral microtubule organization, respectively. Surprisingly, LIMK1 and cofilin are not involved downstream of RhoA and ROCK in the regulation of astral microtubule organization. Instead, we find that LIMK2 acts through TPPP in the regulation of astral microtubule organization, whereas both LIMK1 and LIMK2 affect centrosome focusing. Both phenotypes are tightly coupled to spindle orientation in the mitotic cells. Thus, our results reveal a new regulatory link between the actin cytoskeleton and the mitotic spindle during the early stages of mitosis.

Mussel inspired protein-mediated surface modification to electrospun fibers and their potential biomedical applications.

Mussel inspired proteins have been demonstrated to serve as a versatile biologic adhesive with numerous applications. The present study illustrates the use of such Mussel inspired proteins (polydopamine) in the fabrication of functionalized bio-inspired nanomaterials capable of both improving cell response and sustained delivery of model probes. X-ray photoelectron spectroscopy analysis confirmed the ability of dopamine to polymerize on the surface of plasma-treated, electrospun poly(ε-caprolactone) (PCL) fiber mats to form polydopamine coating. Transmission electron microscopy images demonstrated that self-polymerization of dopamine was induced by pH shift and that the thickness of polydopamine coating was readily modulated by adjusting the concentration of dopamine and reaction time. Polydopamine coatings were noted to affect the mechanical properties of underlying fiber mats, as mechanical testing demonstrated a decrease in elasticity and increase in stiffness of polydopamine-coated fiber mats. Polydopamine coatings were also utilized to effectively immobilize extracellular matrix proteins (i.e., fibronectin) on the surface of polydopamine-coated, electrospun fibers, resulting in enhancement of NIH3T3 cell attachment, spreading, and cytoskeletal development. Comparison of release rates of rhodamine 6G encapsulated in coated and uncoated PCL fibers also confirmed that polydopamine coatings modulate the release rate of loaded payloads. The authors further demonstrate the significant difference of rhodamine 6G adsorption kinetics in water between PCL fibers and polydopamine-coated PCL fibers. Taken together, polydopamine-mediated surface modification to electrospun fibers may be an effective means of fabricating a wide range of bio-inspired nanomaterials with unique properties for use in tissue engineering, drug delivery, and advanced biomedical applications.

Fabrication of large pores in electrospun nanofibrous scaffolds for cellular infiltration: a review.

In the past decade, considerable effort has been made to construct biomimetic scaffolds from electrospun nanofibers for engineering different tissues. However, one of the major concerns with electrospun nanofibrous scaffolds is that the densely arranged architecture of fibers and small pores or voids between fibers hinder efficient cellular infiltration or prevent three dimensional (3D) cellular integration with host tissue in vivo after implantation. To overcome this problem, many concepts or strategies applicable during the electrospinning or post-electrospinning procedures have been proposed to enlarge pore size of electrospun scaffolds. This article addresses the issues of pore geometry and cellular infiltration of electrospun scaffolds, and first reviews the fabrication solutions/approaches applied to achieve larger micropores in electrospun mats. The evidence and potential for fostering cellular infiltration using these improved porous scaffolds are then discussed. Finally, it is hoped that this will enable us to better exploit viable technologies or develop new ones for constructing ideal nanofibrous architecture for fulfilling specific tissue engineering needs.

[In vivo and in vitro research study of the influence on placenta angiogenesis by gene silencing of netrin-1].

OBJECTIVE: To study influence on angiogenesis of placenta by gene silencing of netrin-1. METHODS: Netrin-1 gene in human umbilical vein endothelial cells (HUVEC) and placenta of pregnant rats were silenced by RNA interference. The following methods were used in this study, including the phenytetrazoliumromide (MTT) for viability, clone formation for proliferation, transwell for migration, and tube formation for angiogenesis in vitro. The change of fetal growth was recorded. Placental microvessel density in pregnant rats was measured by immunohistochemical CD(34) staining in vivo. RESULTS: (1) HUVEC: viability and proliferation of HUVEC were remarkably inhibited by gene silencing of netrin-1, which number of clone formation, migration cell, tube formation were from (69 ± 6)%, 86 ± 17, 37 ± 9 decreased to (46 ± 5)%, 46 ± 13 and 17 ± 5 (P < 0.05) respectively. (2) Placenta of pregnant rats: after netrin-1 gene silenced, fetal weight were decreased from (2.39 ± 0.17) g to (2.12 ± 0.10) g (P < 0.05). Placental microvessel density was decreased from (258 ± 38)/mm(2) to (197 ± 32)/mm(2) in vivo (P < 0.05). CONCLUSIONS: Gene silencing of netrin-1 could inhibit viability, proliferation, migration, tubal formation of HUVEC and angiogenesis of placenta. Netrin-1 plays an important role in regulating angiogenesis in placenta.

Effect of different concentrations of neogenin on proliferation, apoptosis and related proliferative factors in human trophoblasts.

The underlying effect of different concentrations of neogenin on proliferation, apoptosis and the related proliferative factors in human trophoblasts was explored in order to understand the function of neogenin during placentation. TEV-1 cell line was cultured and the expression of netrin-1 was detected by using indirect cellular immunofluorescence. Exponentially growing TEV-1 cells were treated by different concentrations of neogenin (0, 1, 5, 10, 50 ng/mL) for 24 h. Cell viability was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. TEV-1 cell apoptosis was assessed by flow cytometry (FCM). The expression of netrin-1 mRNA and protein in TEV-1 cells was examined by using real-time PCR and Western blot, respectively. It was found that immunoreactivity for netrin-1 was observed in cytoplasm of the trophoblasts. Immediately after treatment with different concentrations of neogenin for 24 h, the netrin-1 expression began to increase. Real-time PCR revealed that the expression level of netrin-1 mRNA was 37.59+/-10.25 times higher than control group when TEV-1 cells were exposed to 50 ng/mL neogenin (P<0.01), and the same tendency was seen by using Western blot. MTT results showed that proliferation of TEV-1 cells was independent of neogenin. Meanwhile, apoptosis was significantly increased to (22.15+/-6.15)% at 50 ng/mL neogenin and (6.55+/-0.25)% without neogenin (P<0.01). It is suggested that neogenin regulates proliferation and apoptosis of TEV-1 cells. And it can enhance the ability of TEV-1 cells to express netrin-1 in a dose-dependent manner. Neogenin may play an important biological role in the normal human pregnancy and contribute to the physiological pregnancy process.

Evaluation of "J"-shaped uterine incision during caesarean section in patients with placenta previa: a retrospective study.

This study evaluated the efficacy and safety of "J"-shaped uterine incision for caesarean section for patients diagnosed with placenta previa. A total of 55 consecutive cases of placenta previa treated in Union Hospital were retrospectively analyzed over a period of two years and 10 months. The subjects were divided into two groups with respect to the uterine incision. Twenty-four pregnant women with placenta previa who were indicated for caesarean section underwent the procedure using a new "J"-shaped uterine incision and 31 pregnant women with placenta previa received caesarean section that used the traditional transverse incision. The two groups were compared in terms of operation time, estimated blood loss, infant expulsion time, exhaust time and postoperative recovery. Meanwhile, comparison was also made in neonatal clinical data between the two groups. Compared with the "J"-shaped incision group, the traditional incision group had a lower Apgar scores (P<0.05). However, there existed no statistically significant differences in the overall time of operation and postoperative period of breaking wind (P>0.05). It is concluded that, with caesarean section for placenta previa patients, the "J"-shaped uterine incision significantly decreases intraoperative blood loss and facilitates the fetal delivery.

Evaluation of"J"-shaped Uterine Incision during Caesarean Section in Patients with Placenta Previa: A Retrospective Study / 华中科技大学学报（医学）（英德文版）

This study evaluated the efficacy and safety of"J"-shaped uterine incision for caesarean section for patients diagnosed with placenta previa.A total of 55 consecutive cases of placenta previa treated in Union Hospital were retrospectively analyzed over a period of two years and 10 months.The subjects were divided into two groups with respect to the uterine incision.Twenty-four pregnant women with placenta previa who were indicated for caesarean.section underwent the procedure using a new"J"-shaped uterine incision and 31 pregnant women with placenta previa received caesarean section that used the traditional transverse incision.The two groups were compared in terms of operation time,estimated blood loss,infant expulsion time,exhaust time and postoperative recovery.Meanwhile,comparison was also made in neonatal clinical data between the two groups.Compared with the"J"-shaped incision group,the traditional incision group had a lower Apgar scores(P<0.05).However,there existed no statistically significant differences in the overall time of operation and postoperative period of breaking wind(P>0.05).It is concluded that,with caesarean section for placenta previa patients,the"J"-shaped uterine incision significantly decreases intraoperative blood loss and facilitates the fetal delivery.