Integrated percutaneous sclerotherapy and surgical intervention for giant cutaneomucosal venous malformation from TIE2 mutation:A case report

Cutaneomucosal venous malformations(VMCMs)can manifest as sporadic or familial forms,following an autosomal dominant inheritance pattern.This report highlights the case of a 5-year-old girl presenting with a substantial congenital VMCM attributed to a TIE2 mutation,who underwent percutaneous sclerotherapy followed by surgery.The clinical,three-dimensional computed tomographic angiography(3D-CTA),as well as pathological and genetic findings concerning a patient with an extensive VMCM in the left pro-axillary region,are elucidated.The genetic analysis in this patient verified a missense mutation(c.2545T>C)in TIE2,confirming familial VMCMs.The combined strategy integrating percutaneous sclerotherapy and surgical excision is the most efficacious approach for managing large VMCMs and can successfully attain therapeutic goals.

Effective Development of Enterprise Emergency Management under the New Policy of Safety Production

In recent years,China has formed a more perfect emergency management system,and has achieved more significant results.The form of safety production has maintained a continuous good development trend,showing the characteristics of"two declines,one being basically flat,and one zero occurrence".In order to further strengthen the implementation of production safety responsibilities and resolutely prevent and contain extremely major accidents,the recent national production safety teleconference deployed 15 measures to pay close attention to the implementation,seriously pursue accountability,adhere to the red line,and immediately carry out in-depth and solid production safety inspections across the country.In such a high pressure situation,the ways to effectively carry out the security management of enterprises were briefly described in this paper.

DDX3X regulates cell survival and cell cycle during mouse early embryonic development

DDX3X is a highly conserved DEAD-box RNA helicase that participates in RNA transcription, RNA splicing, and mRNA transport, translation, and nucleo-cytoplasmic transport. It is highly expressed in metaphase II （MII） oocytes and is the predominant DDX3 variant in the ovary and embryo. However, whether it is important in mouse early embryo development remains unknown. In this study, we investigated the function of DDX3X in early embryogenesis by cytoplasmic microinjection with its siRNA in zygotes or single blastomeres of 2-cell embryos. Our results showed that knockdown of Ddx3x in zygote cytoplasm led to dramatically diminished blastocyst formarion, reduced cell numbers, and an increase in the number of apoptotic cells in blastocysts. Meanwhile, there was an accumulation of p53 in RNAi blastocysts. In addition, the ratio of cell cycle arrest during 2-cell to 4-cell transition increased following microinjection of Ddx3x siRNA into single blastomeres of 2-cell embryos compared with control. These results suggest that Ddx3x is an essential gene associated with cell survival and cell cycle control in mouse early embryos, and thus plays key roles in normal embryo development.

ON APPROXIMATION BY RECIPROCALS OF POLYNOMIALS WITH POSITIVE COEFFICIENTS IN ORLICZ SPACES

This paper discusses the approximation by reciprocals of polynomials with positive coefficients in Orlicz spaces and proved that if f（x） ∈ L^＊M[0, 1], changes its sign at most once in （0, 1）, then there exists x0 ∈ （0, 1） and a polynomial Pn∈ Fin（＋） such that ｜｜f（x）-x-x0/Pn（x）｜｜M≤Cω（f,n-1/2）M, where Пn（＋） indicates the set of all polynomials of degree n with positive coefficients

The role of ezrin-associated protein network in human sperm capacitation

Membrane modifications in sperm cells represent a key step in sperm capacitation; however, the molecular basis of these modifications is not fully understood. Ezrin is the best-studied member of the ezrin/radixin/merlin family. As a cross-linker between the cortical cytoskeleton and plasma membrane proteins, ezrin contributes to remodeling of the membrane surface structure. Furthermore, activated ezrin and the Rho dissociation inhibitor, RhoGDI, promote the formation of cortical cytoskeleton-polymerized actin through Rho activation. Thus, ezrin, actin, RhoGDI, Rho and plasma membrane proteins form a complicated network in vivo, which contributes to the assembly of the structure of the membrane surface. Previously, we showed that ezrin and RhoGDI1 are expressed in human testes. Thus, we sought to determine whether the ezrin-RhoGDIl-actin-membrane protein network has a role in human sperm capacitation. Our results by Western blot indicate that ezrin is activated by phosphorylation of the threonine567 residue during capacitation. Co-immunoprecipitation studies revealed that, during sperm capacitation, the interaction between ezrin and RhoGDI1 increases, and phosphostaining of two dimensional electrophoresis gels showed that RhoGDI 1 is phosphorylated, suggesting that RhoGDI 1 dissociates from RhoA and leads to actin polymerization on the sperm head. We speculate that activated ezrin interacts with polymerized actin and the glycosylated membrane protein cd44 after capacitation. Blocking sperm capacitation using ezrin- or actin-specific monoclonal antibodies decreases their acrosome reaction （AR） rate, but has no effect on the AR alone. Taken together, our results show that a network consisting of ezrin, RhoGDI1, RhoA, F-actin and membrane proteins functions to influence the modifications that occur on the membrane of the sperm head during human sperm capacitation.

Mechanical tension promotes skin nerve regeneration by upregulating nerve growth factor expression

This study aimed to explore the role of mechanical tension in hypertrophic scars and the change in nerve density using hematoxylin-eosin staining and S100 immunohistochemistry, and to observe the expression of nerve growth factor by western blot analysis. The results demonstrated that mechanical tension contributed to the formation of a hyperplastic scar in the back skin of rats, in conjunction with increases in both nerve density and nerve growth factor expression in the scar tissue. These experimental findings indicate that the cutaneous nervous system plays a role in hypertrophic scar formation caused by mechanical tension.

Association of atherosclerotic plaque features with collateral circulation status in elderly patients with chronic carotid stenosis

Objective To determine the association of carotid plaque features with collateral circulation status in elderly patients with moderate to severe carotid stenosis.Methods Elderly patients(>60 years)with moderate to severe carotid stenosis were recruited and categorized into good and poor collateral circulation groups,and underwent magnetic resonance imaging and computed tomography imaging.The carotid plaque features including lipid-rich necrotic core,intraplaque hemorrhage,calcification,and fibrous cap rupture(FCR)were evaluated,and maximum wall thickness,normalized wall index(NWI),and luminal stenosis were measured.The association between these variables and collateral circulation status was analyzed.Results Of the 97 patients(78 males,mean age:69.0±6.1 years),19(19.6%)had poor collaterals.The poor collateral group had a significantly higher NWI(93.7%±5.0%vs.89.0%±7.9%,P=0.011),a greater extent of stenosis(80.0%±11.4%vs.75.3%±9.4%,P=0.036)and FCR(84.2%vs.55.1%,P=0.020)compared with good collateral group.Carotid NWI(OR=3.83,95%CI:1.36–10.82,P=0.011)and more FCR(OR=6.77,95%CI:1.35–33.85,P=0.020)were associated with poor collateral circulation after adjustment for the confounding factors.The combination of NWI,FCR,systolic blood pressure,and triglycerides had the highest area-under-the-curve(AUC=0.85)for detection of poor collaterals.Conclusions Carotid plaque features,specifically NWI and FCR,are independently associated with poor collateral circulation,and the combination of carotid plaque features and traditional risk factors has a stronger predictive value for poor collateral circulation than plaque features alone.

Inflammation and cutaneous nervous system involvement in hypertrophic scarring

This study aimed to use a mouse model of hypertrophic scarring by mechanical loading on the dorsum of mice to determine whether the nervous system of the skin and inflammation participates in hypertrophic scarring. Results of hematoxylin-eosin and immunohistochemical staining demonstrated that inflammation contributed to the formation of a hypertrophic scar and increased the nerve density in scar tissue.Western blot assay verified that interleukin-13 expression was increased in scar tissue. These findings suggest that inflammation and the cutaneous nervous system play a role in hypertrophic scar formation.

Somatic GJA4 mutation in intracranial extra-axial cavernous hemangiomas

Objective Extra-axial cavernous hemangiomas(ECHs)are sporadic and rare intracranial occupational lesions that usually occur within the cavernous sinus.The aetiology of ECHs remains unknown.Methods Whole-exome sequencing was performed on ECH lesions from 12 patients(discovery cohort)and droplet digital polymerase-chain reaction(ddPCR)was used to confirm the identified mutation in 46 additional cases(validation cohort).Laser capture microdissection(LCM)was carried out to capture and characterise subgroups of tissue cells.Mechanistic and functional investigations were carried out in human umbilical vein endothelial cells and a newly established mouse model.Results We detected somatic GJA4 mutation(c.121G>T,p.G41C)in 5/12 patients with ECH in the discovery cohort and confirmed the finding in the validation cohort(16/46).LCM followed by ddPCR revealed that the mutation was enriched in lesional endothelium.In vitro experiments in endothelial cells demonstrated that the GJA4 mutation activated SGK-1 signalling that in turn upregulated key genes involved in cell hyperproliferation and the loss of arterial specification.Compared with wild-type littermates,mice overexpressing the GJA4 mutation developed ECH-like pathological morphological characteristics(dilated venous lumen and elevated vascular density)in the retinal superficial vascular plexus at the postnatal 3 weeks,which were reversed by an SGK1 inhibitor,EMD638683.Conclusions We identified a somatic GJA4 mutation that presents in over one-third of ECH lesions and proposed that ECHs are vascular malformations due to GJA4-induced activation of the SGK1 signalling pathway in brain endothelial cells.

Partial Variable Stability for a Class of Nonlinear Systems with Time Delay

This article first gives a new class of integral inequalities. Then, as an application, the nonlinear neutral differential system with multiple delays is considered, and the trivial solution of the nonlinear neutral system with multiple delays is obtained. Uniform asymptotic Lipschitz stability. Obviously, the above system is a generalization of the traditional differential system. The purpose of this paper is to study the dual stability of neutral differential equations with delays, including equal asymptotically Lipschitz stability and uniformly asymptotic Lipschitz stability. The author uses the method of integral inequality to establish a double stability criterion. As a result, the local stability of differential equations is widely used in theory and practice, such as dynamic systems and control systems.

Innovations of Agricultural Scientific Research Institutions in Management of Special Materials

In recent years,the Ministry of Agriculture has increased input in agricultural scientific research projects.As a result,the procurement amount and quantity of special materials are increasing gradually,and the management of special materials becomes more standardized.In order to do well in management of special materials,the authors made exploration and thinking about further strengthening management of special materials in combination with actual conditions,including establishing regulations and systems,enhancing procurement process,strengthening requisition and safekeeping,and reinforcing general ledger management of special materials.

Double Lipschitz Stability for Nonlinearly Perturbed Differential Systems with Multiple Delay

In this paper, firstly a new class of time-delay differential inequality is proved. Then as an application, the nonlinearly perturbed differential systems with multiple delay are considered and it is obtained that the trivial solution of the nonlinear systems with multiple delay has uniform stability and uniform exponential Lipschitz asymptotic stability with respect to partial variables. It is obvious that the above system is a generalization of the traditional differential systems. The aim of this paper is to investigate the double stability of time-delay differential equations, including Uniform stability and Uniform Lipschitz stability. The author uses the method of differential inequalities with time-delay and integral inequalities to establish double stability criteria. As a result, the partial stability of differential equations is widely used both in theory and in practice such as dynamic systems and control systems.

Enlightenment on Classification of Environmental Pollution Events of Oil Spills at Sea

At present, China continues to increase domestic oil and gas exploration and development efforts, vigorously increases investment in scientific research, and unswervingly promotes the increase of oil and gas reserves and production, which will also bring new challenges to marine ecological environmental protection and pollution incidents. It is particularly important to thoroughly implement China’s Marine Environmental Protection Law, establish and improve the emergency response mechanism for oil spill pollution environmental incidents, and scientifically and reasonably delineate the level of oil spill pollution incidents. In response to this problem, the standard of the minimum pollution incident was analyzed and explained in this paper.

Viral-mediated gene therapy in pediatric neurological disorders

Background Due to the broad application of next-generation sequencing,the molecular diagnosis of genetic disorders in pediatric neurology is no longer an unachievable goal.However,treatments for neurological genetic disorders in children remain primarily symptomatic.On the other hand,with the continuous evolution of therapeutic viral vectors,gene therapy is becoming a clinical reality.From this perspective,we wrote this review to illustrate the current state regarding viral-mediated gene therapy in childhood neurological disorders.Data sources We searched databases,including PubMed and Google Scholar,using the keywords"adenovirus vector,""lentivirus vector,"and"AAv"for gene therapy,and"immunoreaction induced by gene therapy vectors,""administration routes of gene therapy vectors,"and"gene therapy"with"NCL,""SMA,""DMD,""congenital myopathy,""MPS""leukodystrophy,"or"pediatric metabolic disorders".We also screened the database of ClinicalTrials.gov using the keywords"gene therapy for children"and then filtered the results with the ones aimed at neurological disorders.The time range of the search procedure was from the inception of the databases to the present.Results We presented the characteristics of commonly used viral vectors for gene therapy for pediatric neurological disorders and summarized their merits and drawbacks,the administration routes of each vector,the research progress,and the clinical application status of viral-mediated gene therapy on pediatric neurological disorders.Conclusions Viral-mediated gene therapy is on the brink of broad clinical application.Viral-mediated gene therapy will dramatically change the treatment pattern of childhood neurological disorders,and many children with incurable diseases will meet the dawn of a cure.Nevertheless,the vectors must be optimized for better safety and efficacy.

Flood variability in the upper Yangtze River over the last millennium——Insights from a comparison of climate-hydrological model simulated and reconstruction

Understanding hydrological responses to rising levels of greenhouse gases are essential for climate and impact research.It is,however,often limited by a lack of long record of observational data to provide a basis for understanding the longterm behavior of the climate system.Integrating reconstructed data and(global climate and hydrological)model simulations will help us to better understand the variability of climate and hydrology over timescales ranging from decades to centuries.In this study,we proposed an integrated approach to study flood variability in the upper reach of the Yangtze River over the last millennium to the end of the 21st century.To accomplish this,we first drove hydrological models using the precipitation and temperature from four Global Climate Models(GCM),BCC-CSM1.1,MIROC,MRI-CGCM3,and CCSM4,to simulate daily discharge for the upper reach of the Yangtze River during the period of the last millennium(850–1849),historical period(1850–2005),and a future period(2006–2099).Then,we evaluated whether the modeled precipitation,temperature,and extreme discharge had statistical properties similar to those shown in the documented dry-wet periods,temperature anomalies,and paleoflood records.Finally,we explored the extreme discharge variability using model simulations.The results indicate that:(1)The MIROC-ESM model,differing from the other three GCM models,revealed positive temperature changes from the warm period(Medieval Climate Anomaly;MCA)to the cold period(Little Ice Age;LIA),while the temperature variability of the other models was similar to the records.(2)The BCC-CSM1.1 model performed better than the others regarding correlations between modeled precipitation and documented dry-wet periods.(3)Over most of the subbasins in the upper Yangtze River,the magnitude of extreme discharge in the BCC-CSM1.1 model results showed that there was a decrease from the MCA to the LIA period and an increase in the historical period relative to the cold period,while a future increase was projected by the four GCMs under the influence of climate change.

KRAS mutation-induced EndMT of brain arteriovenous malformation is mediated through the TGF-β/BMP-SMAD4 pathway

Objective Somatic KRAS mutations have been identified in the majority of brain arteriovenous malformations(bAVMs),and subsequent in vivo experiments have confirmed that KRAS mutation in endothelial cells(ECs)causes AVMs in mouse and zebrafish models.Our previous study demonstrated that the KRASG12D mutant independently induced the endothelial-mesenchymal transition(EndMT),which was reversed by treatment with the lipid-lowering drug lovastatin.However,the underlying mechanisms of action were unclear.Methods We used human umbilical vein ECs(HUVECs)overexpressing the KRASG12D mutant for Western blotting,quantitative real-time PCR,and immunofluorescence and wound healing assays to evaluate the EndMT and determine the activation of downstream pathways.Knockdown of SMAD4 by RNA interference was performed to explore the role of SMAD4 in regulating the EndMT.BAVM ECs expressing the KRASG12D mutant were obtained to verify the SMAD4 function.Finally,we performed a coimmunoprecipitation assay to probe the mechanism by which lovastatin affects SMAD4.Results HUVECs infected with KRASG12D adenovirus underwent the EndMT.Transforming growth factor beta(TGF-β)and bone morphogenetic protein(BMP)signalling pathways were activated in the KRASG12D-mutant HUVECs and ECs in bAVM tissue.Knocking down SMAD4 expression in both KRASG12D-mutant HUVECs and ECs in bAVM tissues inhibited the EndMT.Lovastatin attenuated the EndMT by downregulating p-SMAD2/3,p-SMAD1/5 and acetylated SMAD4 expression in KRASG12D-mutant HUVECs.Conclusions Our findings suggest that the KRASG12D mutant induces the EndMT by activating the ERK-TGF-β/BMP-SMAD4 signalling pathway and that lovastatin inhibits the EndMT by suppressing TGF-β/BMP pathway activation and SMAD4 acetylation.

Sky Blue and Yellow Cluster Light-Emitting Diodes Based on Asymmetric Cu_(4)l_(4) Nanocubes

Controllably optimizing excited-state characteristics is crucial for luminescent nanoclusters but remains a formidable challenge.Herein,we report an effective"ligand-induced asymmetrization"strategy for constructing thermally activated delayed fluorescence-featured cubic Cu4l4 nanoclusters with asymmetric configurations,named[tBCzDBFDP]_(2)Cu_(4)l_(4) and[PTZDBFDP]_(2)Cu_(4)l_(4).Through changing 3,6-di-tert-butyl-carbazole(tBCz)to phenothiazine(PTZ)with a stronger electron-donating effect,emission color is tuned from greenish blue of[tBCzDBFDP]_(2)Cu_(4)l_(4) to yellow of[PTZDBFDP]_(2)Cu_(4)l_(4),as well as the triplet locally excited state of the former to the triplet charge transfer state of the latter.Temperature-correlated spectroscopic investigation indicates that in terms of triplet quenching suppression,[tBCzDBFDP]_(2)Cu_(4)l_(4) is superior to[PTZDBFDP]_(2)Cu_(4)l_(4),in accord with the stabilities of their triplet locally excited state and triplet charge transfer state.As a consequence,these asymmetric Cu4l4 nanocubes endowed their cluster light-emitting diodes with the external quantum efficiencies beyond 12%for sky blue and 8%for yellow.These results suggest the significance and effectiveness of ligand engineering for optoelectronic nanoclusters.

A brain structural connectivity biomarker for autism spectrum disorder diagnosis in early childhood

Background:Autism spectrum disorder(ASD)is associated with altered brain development,but it is unclear which specific structural changes may serve as potential diagnostic markers,particularly in young children at the age when symptoms become fully estab-lished.Furthermore,such brain markers need to meet the requirements of precision medicine and be accurate in aiding diagnosis at an individual rather than only a group level.Objective:This study aimed to identify and model brain-wide differences in structural connectivity using diffusion tensor imaging(DTI)in young ASD and typically developing(TD)children.Methods:A discovery cohort including 93 ASD and 26 TD children and two independent validation cohorts including 12 ASD and 9 TD children from three different cities in China were included.Brain-wide(294 regions)structural connectivity was measured using DTI(fractional anisotropy,FA)together with symptom severity and cognitive development.A connection matrix was constructed for each child for comparisons between ASD and TD groups.Pattern classification was performed on the discovery dataset and the resulting model was tested on the two independent validation datasets.Results:Thirty-three structural connections showed increased FA in ASD compared to TD children and associated with both autistic symptom severity and impaired general cognitive development.The majority(29/33)involved the frontal lobe and comprised five different networks with functional relevance to default mode,motor control,social recognition,language and reward.Overall,clas-sification achieved very high accuracy of 96.77%in the discovery dataset,and 91.67%and 88.89%in the two independent validation datasets.Conclusions:Identified structural connectivity differences primarily involving the frontal cortex can very accurately distinguish novel individual ASD from TD children and may therefore represent a robust early brain biomarker which can address the requirements of precision medicine.

Responses of Primary Afferent Fibers to Acupuncture-Like Peripheral Stimulation at Different Frequencies:Characterization by Single-Unit Recording in Rats

The pain-relieving effect of acupuncture is known to involve primary afferent nerves(PANs) via their roles in signal transmission to the CNS.Using single-unit recording in rats,we characterized the generation and transmission of electrical signals in Aβ and Aδ fibers induced by acupuncture-like stimuli.Acupuncture-like signals were elicited in PANs using three techniques:manual acupuncture(MAc),emulated acupuncture(EAc),and electro-acupuncture(EA)-like peripheral electrical stimulation(PES).The discharges evoked by MAc and EAc were mostly in a burst pattern with average intra-burst and inter-burst firing rates of 90 Hz and 2 Hz,respectively.The frequency of discharges in PANs was correlated with the frequency of PES.The highest discharge frequency was 246 Hz in Aβ fibers and 180 Hz in Aδ fibers.Therefore,EA in a dense-disperse mode(at alternating frequency between 2 Hz and 15 Hz or between 2 Hz and 100 Hz) best mimics MAc.Frequencies of EA output>250 Hz appear to be obsolete for pain relief.

Involvement of Opioid Peptides in the Analgesic Effect of Spinal Cord Stimulation in a Rat Model of Neuropathic Pain

Spinal cord stimulation(SCS)-induced analgesia was characterized,and its underlying mechanisms were examined in a spared nerve injury model of neuropathic pain in rats.The analgesic effect of SCS with moderate mechanical hypersensitivity was increased with increasing stimulation intensity between the 20%and 80%motor thresholds.Various frequencies(2,15,50,100,10000 Hz,and 2/100 Hz dense-dispersed)of SCS were similarly effective.SCS-induced analgesia was maintained without tolerance within 24 h of continuous stimulation.SCS at 2 Hz significantly increased methionine enkephalin content in the cerebrospinal fluid.The analgesic effect of 2 Hz was abolished byμorκopioid receptor antagonist.The effect of 100 Hz was prevented by aκantagonist,and that of 10 kHz was blocked by any of theμ,δ,orκreceptor antagonists,suggesting that the analgesic effect of SCS at different frequencies is mediated by different endorphins and opioid receptors.