Objective To analyze the status of Leishmania infantum asymptomatic infection in human population of a Kala-azar endemic area in Wenxian County,Gansu Province,and to evaluate the tests used.Methods Blood samples were tested by PCR using two pairs of primers,RV1-RV2 and K13A-K13B,for detecting Leishmania-specific DNA.ELISA and rK39-dipstick were used to detect Leishmania-specific antibodies.Results The positive rate of PCR,ELISA and rK39-dipstick was 30.9%(83/269),24.2%(65/269) and 0(0/269) respectively.Conclusion The prevalence of asymptomatic infection of L.infantum in humans is high in the area.PCR test based on RV1-RV2 and K13A-K13B primer pairs is a sensitive and specific method for detecting the asymptomatic infection.

Objective To observe the image characteristics ofmultispectral scanning laser imaging (MSLI) and OCT in patients with pregnancy induced hypertension syndrome (PIHS).Methods A total of 112 patients (224 eyes) of PIHS patients diagnosed in Obstetrics Department of Tianjin First Central Hospital from May 2016 to May 2017 were included in this study.The average age of the patients was 27.00±2.14 years.The average course of the disease was 15.00 ±8.27 days.There were 174 eyes in 87 patients of blurred vision,dazzling and visual fatigue consciously.All patients performed BCVA,direct ophthalmoscope,B ultrasound,confocal scanning laser Ophthalmoscope (cSLO) and spectral-domain OCT (SD-OCT).SD-OCT was performed with Spectralis HRA+OCT from Heidelberg Company in Germany to acquire tomographic images.Using Herdelberg's colorful program (MultiColor) based on cSLO and operating in accordance with standard methods,one scan simultaneously obtained blue light reflection based on 488 nm,green light reflection based on 515 nm,and infrared reflection based on 820 nm,synthesis to MSLI.Fundus abnormalities were classified into arterial spasm (stage Ⅰ),arteriosclerosis (stage Ⅱ),and retinopathy (stage Ⅲ).OCT examination was divided into normal and abnormal cases according to the abnormality of retinal morphology and thickness.Results Of the 224 eyes,68 eyes (30.36％) showed normal fundus examination and 156 eyes (69.64％) showed abnormal fundus performance.Among them,28 eyes were stage Ⅰ (17.95％);40 eyes were stage Ⅱ (25.64％);88 eyes were stage Ⅲ (56.41％).Thirty-six eyes (16.07％) showed normal fundus and 188 eyes (83.93％) showed abnormal performance with OCT.Of the 188 eyes with abnormal fundus performance,86 eyes (45.74％) had retinal neuroepithelial serous detachment;56 eyes (29.79％) had RPE detachment;optic disc edema,bulge,and local reflexes in the retinal nerve fiber layer were enhanced and/or the thickness increased in 46 eyes (24.47％).In MSLI,48 eyes (21.43％) showed normal fundus;176 eyes (78.57％) showed abnormal performance.Retinal edema was showed in green on MSLI,serous retinal neuroepithelial layer detachment,RPE layer detachment,retinal nerve fiber layer thickening,accompanied by changes in local retinal structure.The higher the degree of bulge,the darker the color.Consistent with the range of retinal edema revealed by SD-OCT.Conclusions MSLI and SD-OCT images show highly consistent lesions in PIHS patients.MSLI can more clearly show superficial and deep retinal lesions.

Objective:To explore the mechanism of Fuyuan Xingnao Decoction in treatment of cerebral infarction based on network pharmacology and molecular docking.Methods:The active components and action targets of Fuyuan Xingnao Decoction were screened by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP),Traditional Chinese Medicine Integrated Database (TCMID),Bioactivity data of small organic molecules (PubChem),Universal Protein (Uniprot) and Swiss Target Prediction database platform. The databases of GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and Drug Bank and Pharmacogenomics Knowledgebase (PharmGKB) were used to screen targets of cerebral infarction. The drug target genes in Fuyuan Xingnao Decoction were intersected with those of cerebral infarction, the intersecting targets were introduced into Cytoscape 3.8.2 software to construct the component target network, and the PPI protein interaction network was constructed by using STRING analysis platform and Cytoscape 3.8.2 software to screen the core targets. Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) function enrichment analysis were carried out on the common target genes of Fuyuan Xingnao Decoction and cerebral infarction disease to obtain the relevant signal pathways. Finally, AutoDock and Pymol software were used for molecular docking between the predicted target and its corresponding components.Results:After screening, 80 effective components of Fuyuan Xingnao Decoction for treatment of cerebral infarction and 214 common targets of Fuyuan Xingnao Decoction and cerebral infarction were obtained. The core targets such as MAPK1, RELA, TP53, JUN, AKT1 and HSP90AA1 were related to the key targets of cerebral infarction, and they participated in the biological process of regulating the response to drugs, lipopolysaccharide and oxygen level, etc. The cell composition involved membrane raft, membrane micro region and nerve cell body, etc. Molecular functions mainly focused on nuclear receptor activity, ligand activated transcription factor activity, DNA binding transcription factor binding, etc.; it also involved in signal pathway of lipid and atherosclerosis, chemical carcinogen and receptor activation, fluid shear stress and atherosclerosis, etc. Molecular docking showed that good binding activities were seen between Quercetin and HSP90AA1 (-9.4 kJ/mol), between Kaempferol and HSP90AA1 (-9.4 kJ/mol), between Isorhamnetin and HSP90AA1 (-9.1 kJ/mol), and between Quercetin and JUN (-8.6 kJ/mol).Conclusion:Fuyuan Xingnao Decoction can prevent and treat cerebral infarction by regulating vascular endothelial function, promoting blood circulation, repairing and improving neural function, protecting blood-brain barrier, reducing cell apoptosis, and regulating immune and inflammatory response.

Hypoxia is a common feature of solid tumors. As transcription factors, hypoxia-inducible factors (HIFs) are the master regulators of the hypoxic microenvironment; their target genes function in tumorigenesis and tumor development. Intriguingly, both yes-associated protein (YAP) and its paralog transcriptional coactivator with a PDZ-binding motif (TAZ) play fundamental roles in the malignant progression of hypoxic tumors. As downstream effectors of the mammalian Hippo pathway, YAP and/or TAZ (YAP/TAZ) are phosphorylated and sequestered in the cytoplasm by the large tumor suppressor kinase 1/2 (LATS1/2)-MOB kinase activator 1 (MOB1) complex, which restricts the transcriptional activity of YAP/TAZ. However, dephosphorylated YAP/TAZ have the ability to translocate to the nucleus where they induce transcription of target genes, most of which are closely related to cancer. Herein we review the tumor-related signaling crosstalk between YAP/TAZ and hypoxia, describe current agents and therapeutic strategies targeting the hypoxia-YAP/TAZ axis, and highlight questions that might have a potential impact in the future.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia