OBJECTIVE: To explore the genetic etiology for a Chinese pedigree affected with X-linked cardiac valve dysplasia (CVDPX) and congenital chronic pseudo intestinal obstruction (CIIPX). METHODS: A pedigree presented at the First Hospital of Lanzhou University for CVDPX combined with CIIX was selected as the study subject. Whole exome sequencing (Trio-WES) was carried out, and the candidate variant was verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the First Hospital of Lanzhou University (Ethics No. LDYYSZLLKH2024-15). RESULTS: Both the proband and his affected younger brother were found to harbor a hemizygous c.443A>G (p.Tyr148Cys) variant of the FLNA gene, for which their mother was heterozygous and their father was not a carrier, suggesting an X-linked recessive inheritance pattern. The variant was not recorded in the OMIM and ClinVar databases, and was determined to be likely pathogenic (PM2+PS4+PP2+PP3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The patients had presented with typical CVDPX/CIIPX phenotype, including multiple valve dysplasia and chronic pseudo intestinal obstruction, in addition with gallbladder wall edema and thickening. Bioinformatic analysis showed that the variant site is highly conserved, and multiple algorithms had predicted its pathogenicity. CONCLUSION This study confirmed the diagnosis of CVDPX/CIIX in a Chinese pedigree, expanded the phenotype spectrum of FLNA gene variants, and provided a basis for genetic counseling and prenatal diagnosis for the pedigree.
Adult ; Female ; Humans ; Male ; Exome Sequencing ; Filamins/genetics* ; Genetic Diseases, X-Linked/genetics* ; Heart Defects, Congenital/genetics* ; Heart Valve Diseases/genetics* ; Pedigree ; East Asian People/genetics*

OBJECTIVE: To explore the mechanism and clinical manifestations of a case with complex structural variations involving chromosomes 5, 7, and 14, and assess the value of Chromosome conformation-based karyotyping (C-MoKa) for its diagnosis. METHODS: Two half-sibs by the same father presented at the First Hospital of Lanzhou University in December 2024 for severe multi-system abnormalities were selected as study subjects. Peripheral blood samples from the their parents were subjected to conventional chromosomal karyotyping analysis. The father was further analyzed using C-MoKa, while both siblings underwent copy number variation sequencing (CNV-seq). This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: LDYYSZLLKH2025-05). RESULTS: Conventional karyotype analysis indicated that the father has a karyotype of 46,XY,add(5)(p15.3). CNV-seq identified multiple chromosomal abnormalities in both siblings, including duplications and deletions of chromosomes 14 and 5. C-MoKa analysis further revealed a complex chromosomal structural variation involving chromosomes 5, 7, and 14 in the father. These variations were closely associated with the severe phenotypes noted in both children. CONCLUSION Complex chromosomal structural variations can lead to multi-system abnormalities and significantly impact reproductive health. Compared to conventional karyotyping, the C-MoKa technique has shown significant advantage in identifying such complex rearrangements. The combined application of multiple techniques can improve the accuracy of diagnosis, enabling genetic counseling for carriers to reduce their risk for producing further affected offspring.
Female ; Humans ; Male ; China ; Chromosome Aberrations ; DNA Copy Number Variations/genetics* ; Karyotyping ; Pedigree ; East Asian People/genetics*

Objcctive To investigate the predictive value of the 40 Hz auditory steady-state response (ASSR) in patients with the malignant process of middle cerebral artery territory infarction.Methods The40 Hz ASSR and brainstem auditory evoked potential (BAEP) were performed within 72 hours after patients with middle cerebral artery terrtory infarction admitted in the neuro-intensive care unite (NICU).At the same time,the National Institutes of Health Stroke Scale (NIHSS) scores were assessed.Multivariable logistic regression analysis was used to deterrmine the influencing factors of the malignant process.The relevant indicators of the malignant process were analyzed by the receiver operating characteristic(ROC) curve in order to clear the predictive value of 40 Hz ASSR in the malignant process of middle cerebral artery territory infarction.Results A total of 104 patients with supratentorial middle cerebral artery territory infarction were included.They were divided into the malignant process group (n=59) or the non-malignant process group (n=45).There were significant differences in the baseline NIHSS scores (17.25 ± 7.23 vs.20.40 ± 8.09; t =- 2.055,P =0.043),infarct volume (105.85 ± 73.37 mm3 us.179.15 ± 144.38 mm3; t =-3.011,P =0.004),leukocyte count ([ 10.26 ±3.14] × 109/L vs.[ 13.45 ±5.42] × 109/L; t =-3.336,P =0.001),40 Hz ASSR (Z =-3.237,P =0.001),and short-latency somatosensory evoked potentials (Z =-3.130,P =0.002) grade between the malignant process group and the non-malignant process group.Multivariate logistic regression analysis showed that the40 Hz ASSR (odds ratio [OR] 3.347,95％ confidence interval [CI] 1.630 -6.872; P=0.014),infarct volume (OR 1.006,95％ CI 1.001 - 1.012,P=0.003),and leukocyte count (OR 1.277,95％ CI 1.074 - 1.402; P =0.001) were the independent predictors in patients with the malignant process of middle cerebral artery territory infarction.When the 40 Hz ASSR was grade 3,the sensitivity and specificity of predicting malignant process were 39.5％ and 94.4％.Conclusions The 40 Hz ASSR has an important predictive value in patients with the malignant process of middle cerebral artery territory infarction.

Objective To study the prevention effects of AduoLa Fuzhenglin(ADL)Oll the brain injury induced by microwave radiation in rats.Methods A total of 140 male Wismr rats were divided randomly into 5 groups,including control group,microwave exposed group,low dosage(0.75 g·kg-1·d-1)group.middle dosage(1.5 g·kg-1·d-1)group and high dosage(3 g·kg-1·d-1)group.Rats in three ADL groups were lavaged with ADL per day for 2 weeks before radiation.After administration,rats were exposed to microwave at 30 mW/cm2 for 15 min.The abilities of learning and memory were detected by Morris water maze,and the contents of amino acids neurotransmitter of hippocampus were detected by HPLC, then the histology and uhrastrncture of hippocampus were observed with light and electron microscope at 6 h,7 and 14 d after exposure.Results The abilities of learning and memory were declined(F=0.000-0.043,P<0.05)from 6 h to 7 d after exposure,and the contents of four kinds of amino acid neurotransmitter in hippocampus were decreased,of which GLU,GLY and GABA were decreased significantly(F=0.000-0.007,P<0.01)at 6h after exposure,then tissue edema,neuronal degeneration,neuron mitoehondria swelling and cavitation,endocytoplasmie rotieulum broaden,synaptic cleft blurred,and perivascular space widen were found in the hippocampus at 6 h and 7 d after exposure.The changes in low dosage group were similar to those of the radiation group.However,in middle and high dosage groups,the abilities of learning and memory were normal to some extent with the significant differences compared to the radiation group from 6 h to 7 d after exposure(F=0.015-0.028.P<0.05).The contents of four kinds of amino acid neurotransmitter were not decreased,especially GLU contents close tO normal level.There were significant differences between middle and high dosage groups and radiation group at 6 h after exposure(F=0.000-0.042,P<0.05).Moreover,no obvious injury in the hippocampus was observed in middle and high dosage groups at 6 h and 7 d after exposure.Conclusions Exposure to 30 mW/cm2 microwave radiation could decrease the abilities of learning and memory,induce amino acid neurotransmitter turbulence,and injure the histology and uhrastructure of hippocampus.ADL at the dosages of 1.5 and 3 g·kg-1·d-1 would have preventive effects on the injury induced by microwave exposure.The concentration of 1.5 g·kg-1 ·d-1 of ADL might be the effective dosage to prevent the brain damage after microwave exposure.

Objective To investigate the expression of JAM-1 after microwave irradiation and its correlation with blood-brain barrier integrity. Methods A total of 160 male Wistar rats were divided into a sham radiation group and a radiation group. The radiation group was subdivided into three sub-groups treated with micrewaves at average power densities of 10, 30 and 100 mW/cm2. Rats in each group were sacrificed and their brain tissue sampled at 6 hours and 1, 3, 7 and 14 days after the irradiation. Evans blue ( EB ) dye, laser confocal microscopy,Western blotting, RT-PCR and image analysis were used to test the permeability of the blood-brain barrier and the expression of JAM-1 in protein and at the gene level in the rats' hippocampus and cortex. Results There was an increase of EB in the hippocampus 3 to 14 days after 10 and 100 mW/cm2 microwave irradiation. The EB level increased progressively in the 10 and 30 mW/cm2 groups within 7 d after irradiation but recovered by the 14th day. It also increased progressively in the 100 mW/cm2 group within 14 d after irradiation. In the hippocampus, EB was observed only in the lumens of the blood vessels in the sham group, but EB had diffused out of the blood vessels in the irradiated groups by the 3rd day after irradiation. After 10 or 30 mW/cm2 microwave irradiation, JAM-1 protein in the hippocampus and cortex decreased significantly within 7 d after irradiation but recovered by the 14th day. It decreased progressively in the 100 mW/cm2 group within 14 d after irradiation. The expression of JAM-1 mRNA in the hippocampus decreased significantly at 6 h after irradiation at all power levels, but it recovered within 7 days in the 10 and 30 mW/cm2 groups. Conclusions Microwave radiation can decrease the expression of JAM-1 in the hippocampus and cortex. The degree of decrease is positively correlated with the microwave radiation power. The change might involve increasing the permeability of the blood-brain barrier.

Objective To explore the therapeutic effect of recombinant human interleukin(rhIL-11) and curcumin on jejunal damage in mice after neutron irradiation.Methods 140 male BALB/c mice were randomly divided into 4 groups:20 mice in healthy control group,60 mice in mere irradiation group,30 mice in IL-11 treatment group and 30 mice in curcumin treatment group.The mere irradiation group mice were wholly exposed to 3 Gy neutron irradiation.The treatment groups mice were intraperitoneally enterocoelia once a day for 5 d after irradiation.The mortality of the mice were observed.The mice in the control and mere irradiation groups were killed 6 h,1,3,and 6 d post-irradiation,respectively,and the mice of the 2 treatment groups were killed 3 and 6 d post-irradiation,respectively and the samples of jujunum were colleted.HE staining,argyrophilic of nucleaolar organizer regions staining,Feulgen staining,and image analysis were used to observe the pathology and levels of argyrophilic proteins and DNA.Results The mice in the mere irradiation group all died at 5 d post-irradiation,while 2 mice in the IL-11 treatment group and 3 in the curcumin group survived.Large area necrosis and exfoliation were found in the intestinal epithelial mucosa of the mere irradiated group mice since 6 h to 3 d after irradiation.Crypt cell regeneration was seen occasionally found 3 days later and much more 5 days later.Crypt cell regeneration was obviously found in the intestinal epithelial mucosa and lots of new villi were observed 5 d after irradiation in both treatment groups,however,the amounts of crypt cells and new villi of the curcumin treatment group were less than those of the IL-11 treatment group.The contents of AgNOR and DNA in the intestinal epithelial cells 5 days after irradiation of the 2 treatment groups were all significantly higher than those of the mere irradiation group (F = 0.015-0.035,all P ＜ 0.05) but without significant differences between them.Conclusions Jejunal damage in mice could be induced after 3 Gy neutron irradiation.rhIL-11 and curcumin might reduce the damage and promote the regeneration and repair of the intestinal epithelium.