AIM:To explore the protective effect of Xiaoxuming decoction(XXMD)on synaptic plasticity in the context of cerebral ischemia-reperfusion injury following ischemic stroke.METHODS:An oxygen-glucose depriva-tion/reoxygenation(OGD/R)model was employed in vitro using mouse hippocampal neurons(HT22 cells)to simulate ischemia-reperfusion injury.Cell viability was assessed using a CCK-8 assay to determine the optimal XXMD concentra-tion.The HT22 cells were divided into two groups:control and model(OGD/R).Cellular morphological changes were ob-served using an inverted microscope.The levels of IL-1β,IL-6 and TNF-α in the supernatant were quantified by ELISA.Ultrastructural changes were examined by transmission electron microscopy.Immunofluorescence staining was used to de-tect neuron markers NeuN and synaptic proteins NF200 and MAP2.The protein levels of NF200 and MAP2 were analyzed by Western blot.RESULTS:The highest cell survival rate occurred at an XXMD concentration of 100 mg/L(P<0.05).Compared with control group,the cells in model group exhibited round shape and shrinkage,mitochondrial swelling or vacuolization,and a marked decrease in survival rate.There were significant increases in IL-1β,IL-6 and TNF-α levels(P<0.05).Immunofluorescence intensity and protein levels of NeuN,NF200 and MAP2 were notably reduced(P<0.05).Treatment with XXMD improved cell morphology,ultrastructure and survival rate(P<0.05),and decreased in-flammatory factor levels(P<0.05).Compared with model group,the cells in OGD/R+XXMD group showed significantly increased immunofluorescence intensity and protein levels of NeuN,NF200 and MAP2(P<0.05).CONCLUSION:Xiaoxuming decoction may mitigate OGD/R-induced injury,potentially by inhibiting inflammatory responses and enhanc-ing synaptic plasticity.

BACKGROUND: Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys. METHODS: In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand-receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining. RESULTS: 15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47 , RASSF4 , EBAG9 , IER3 , SASH1 , SEPTIN7 , and NUB1 , which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL)-12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand-receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI. CONCLUSION Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell-cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.
Humans ; Mice ; Animals ; Transcriptome/genetics* ; Ligands ; Kidney/metabolism* ; Acute Kidney Injury/metabolism* ; Ischemia/metabolism* ; Reperfusion Injury/metabolism* ; Sequence Analysis, RNA ; Adaptor Proteins, Signal Transducing/metabolism* ; Tumor Suppressor Proteins/metabolism*

Objective:To analyze the role of perfusion index(PI)in assessing the severity of neonatal illnesses.Methods:A total of 502 newborns admitted to the Department of Neonatology within 24 hours of birth at Xinxiang Central Hospital from October 2018 to July 2019 were recruited.Neonatal critical illness score(NCIS)was graded within 24 hours of admission, and newborns were categorized into non-critical(NCIS>90 scores), critical(NCIS 70-90 scores)and extremely critical(NCIS<70 scores). PI was monitored in all newborns within 24 hours of birth in a resting state.A total of 502 PIs were recorded, including 341 cases of non-critical, 110 cases of critical and 51 cases of extremely critical.Results:The medium PI [ M( P25, P75)] of newborns in non-critical, critical and extremely critical groups were 1.80(1.40, 2.60), 0.96(0.74, 1.43)and 0.65(0.41, 1.10), respectively.PI values in extremely critical group was significantly lower than those in critical group and non-critical group( P<0.05). The medium PI [ M( P25, P75)] of full-term newborns, moderate/late preterm newborns and extremely/very preterm newborns were 1.70(1.20, 2.70), 1.60(1.10, 2.30) and 1.35(0.80, 2.30), respectively.PI in full-term newborns was significantly higher than those in moderate/late preterm newborns and extremely/very preterm newborns( P<0.05). PI was moderately positively correlated with NCIS in newborns( r=0.791, P<0.01). The area under the receiver operating characteristic curve of NCIS predicted by PI value was 0.846, and the prediction sensitivity and specificity were 85.0% and 70.8% when PI was 0.56. Conclusion:PI is correlated with NCIS in newborns, which is able to reflect the severity of neonatal illnesses.A low PI indicates severe conditions of neonatal illnesses.

Objective To analyze and assess the postoperative motor function in children with spastic cerebral palsy (SCP) by surface electromyography (sEMG) and joint angle. Methods Sixteen children with SCP were involved in this study. The sEMG of rectus femoris, biceps femoris, semitendinosus, tibialis anterior, lateral gastrocnemius and medial gastrocnemius muscles and joint angles of the hip, knee and ankle during straight walking were collected preoperatively and postoperatively. In every gait phase, the mean values of joint angles, root mean square and integrated electromyography of sEMG were calculated, to evaluate muscle strength and muscular tension quantitatively. Results The muscle tension of lower limbs was significantly decreased (P<0.05). The muscle strength of rectus femoris and biceps femoris was decreased in the swing phase. At the midswing and terminal swing phase, the strength of tibialis anterior increased significantly (P<0.05). The flexion angle of hip and knee decreased significantly (P<0.05). The dorsiflexion angle of ankle increased significantly (P<0.05), and the varus angle decreased significantly (P<0.05). Conclusions After operation, the crouching gait and clubfoot were improved positively. Therefore, the motor function of children was improved. Combining sEMG and joint angle can evaluate the muscle function of patients quantitatively, and it also can provide references for clinical diagnosis.

OBJECTIVE: To explore the genetic variation of a Chinese family affected with congenital insensitivity to pain with anhidrosis and albinism. METHODS: Whole exome sequencing (WES) was carried out to screen potential variants within genomic DNA extracted from the proband and his parents. Whole genome sequencing (WGS) was applied when variants were not found completely. Suspected variants were validated by Sanger sequencing. RESULTS: WES has identified a heterozygous c.1729G>C (p.G577R) variant of NTRK1 gene and two heterozygous variants of OCA2 gene, namely c.1363A>G (p.R455G) and c.1182+1G>A. WGS has identified two additional heterozygous variants c.(851-798C>T; 851-794C>G) in deep intronic regions of the NTRK1 gene. CONCLUSION The compound heterozygous variants of the NTRK1 gene probably underlay the congenital insensitivity to pain with anhidrosis. And the compound heterozygous variants of the OCA2 gene probably underlay the albinism in the proband. In the case where no variant is detected by WES in the coding region, WGS should be considered to screen potential variants in the whole genome.
Albinism ; Child ; DNA Mutational Analysis ; Hereditary Sensory and Autonomic Neuropathies/genetics* ; Heterozygote ; Humans ; Membrane Transport Proteins ; Mutation ; Pedigree

OBJECTIVE: To explore the genetic etiology of two patients with Perrault syndrome (PRLTS) in a family. METHODS: Whole exome sequencing (WES) was carried out to screen potential variants within genomic DNA extracted from the proband. Suspected variants were validated by clinical data and results of Sanger sequencing. RESULTS: WES has identified two heterozygous variants of TWNK gene, namely c.1172G>A (p.Arg391His) and c.1844G>C (p.Gly615Ala). Sanger sequencing confirmed that the c.1172G>A (p.Arg391His), a known pathogenic variant, was derived from her father, while the c.1844G>C (p.Gly615Ala), a novel variant, was derived from her mother. Her brother, who was similarly affected, has carried the same compound heterozygous variants. CONCLUSION The compound heterozygous variants c.1172G>A (p.Arg391His) and c.1844G>C (p.Gly615Ala) of the TWNK gene probably underlie PRLTS in the sib pair. The above results have facilitated genetic counseling and prenatal diagnosis for the affected family.

Objective:To explore the effects of sandplay combined with sensory integration therapy on cognitive function in children with attention deficit hyperactivity disorder (ADHD).Methods:60 children with ADHD diagnosed in Baoji Maternal and Child Health Hospital from June 2018 to June 2019 were randomly divided into study group and control group.The children in the control group were treated by sandplay, while the patients in the study group were treated by sandplay combined with sensory integration.Results:There was no significant difference in Parent Symptom Questionnaire (PSQ) score, Combined Raven Test (CRT) results and attention test results between the two groups before treatment ( P>0.05), and there was no significant difference in PSQ score of control group after treatment ( P>0.05); The behavioral problems (0.92±0.23), anxiety (0.51±0.26), impulse/hyperactivity (1.06±0.31) and hyperactivity index (0.88±0.14) in the study group were significantly lower than those in the control group [behavioral problems (1.12±0.21), anxiety (0.79±0.45), impulse/hyperactivity (1.42±0.34) and hyperactivity index (1.16±0.17) ( P<0.05)]. There was no significant difference in the scores of mental disorders and learning problems between the two groups [(0.42±0.20), (1.28±0.44) vs (0.52±0.28), (1.37±0.48)] ( P>0.05). The results of CRT in the study group were (6.6±0.3, 7.3±0.2, 9.1±0.1, 5.5±0.2, 2.7±0.1, 117.3±4.4), which were higher than those in the control group (6.2± 0.1, 6.7±0.1, 8.7±0.1, 5.0±0.1, 2.2±0.1, 110.0±3.8) ( P<0.05). The slip time (52.4±0.1), error number (55.9±0.2) and missed report number (60.2 ±0.1) of the study group were significantly lower than those of the control group [slip time (56.1±0.2), error number (60.3±0.1) and missed report number (70.8±0.3)] ( P<0.05). Conclusions:Combination of sandplay and sensory integration can significantly improve the cognitive and behavioral abilities of children with attention deficit hyperactivity disorder, and improve the balance function of children, which is conducive to clinical application.

Objective: To investigate the echocardiographic characteristics, pathological anatomy and genetic abnormality of congenital absent semilunar valves in first trimester. Methods: Eleven cases of congenital absent semilunar valve fetus diagnosed at 11-13^{+ 6} weeks of gestation in Guangxi Magernity & Child Healthcare Hospital from December 2014 to December 2018 were analyzed. The characteristics of echocardiography and the abnormal microanatomy of cardiac tissue after labor induction was compared. Results: The crown-lump length of the 11 fetus was 46-74(62.0±9.2)mm, and nuchal translucency thickness(NT) was 2.4-10.4 (6.4±2.6)mm. The NT of 10 cases were greater than 3.0 mm. Color Doppler flow imaging revealed that biphasic bidirectional flow in the aortic arch and/or pulmonary artery at the 3VT view( "to-and-fro" ) in those 11 cases, and pansystolic turbulence and pandiastolic reflux spectrum were showed on spectral Doppler. Among them, there were 10 cases of " stealing type" , including 2 cases of isolate absent aortic valves, 3 cases of absent pulmonary valves and 5 cases of absent both aortic and pulmonary valves; and all the 10 cases had secondary ultrasonic manifestations of fetal heart failure. Chromosome analysis and detection of genes showed that 4 cases with Trisomy 13 syndrome, 3 cases with Trisomy 18 syndrome, 1 case with 22q11.2 deletion, 1 case with 12q24.32q24.33 deletion and 1 case was normal. Pathological anatomy revealed enlarged heart in 8 cases, isolate absent aortic valves in 2 cases (1 case complicated with pulmonary atresia, absence of ductus arteriosus and thymus), absent pulmonary valves in 3 cases, absent both aortic and pulmonary valves in 3 cases, relics of semilunar valves in 3 cases. And 2 cases of absent pulmonary valves and 3 cases of absent both aortic and pulmonary valves with short and thick ductus arteriosus. Only 1 case was congenital absent semilunar valve in " non-stealing type" without secondary ultrasonic manifestations of fetal heart failure. Chromosome analysis and detection of genes showed 22q11.2 deletion, and there were relics of semilunar valves in the pathological anatomy. It also combined with tetralogy of Fallot and absence of ductus arteriosus. Conclusions In first trimester, congenital absent semilunar valves are more common as " stealing type" . The echocardiographic features of congenital absent semilunar valves are the " in-out sign" of aorta arch and/or pulmonary artery and biphasic spectrum in spectral Doppler. Trisomy 13 syndrome and trisomy 18 syndrome significantly increased the risk of congenital absent semilunar valves in " stealing type" in first trimester.

OBJECTIVE: To explore the genetic etiology of two pedigrees affected with congenital arthrogryposis. METHODS: Whole exome sequencing (WES) was used to screen potential variations in the proband. Suspected variations were analyzed with bioinformatics software and validated by Sanger sequencing. RESULTS: A heterozygous c.1123G>A (p.Glu375Lys) variation was detected in the proband and an affected fetus from pedigree 1, while a de novo heterozygous c.118 G>A (p.Val40Met) variation was detected in an affected fetus from pedigree 2. CONCLUSION The two heterozygous variations of the MYH3 gene probably underlie the disease in the pedigrees. Above results have facilitated genetic counseling and prenatal diagnosis.
Arthrogryposis ; Cytoskeletal Proteins ; genetics ; Female ; Heterozygote ; Humans ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Whole Exome Sequencing

OBJECTIVE: To carry out mutation analysis for a Chinese family affected with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). METHODS: Whole exome sequencing (WES) was used to screen potential mutations within genomic DNA extracted from the proband. Suspected mutation was validated by combining clinical data and results of Sanger sequencing. RESULTS: A homozygous deletional mutation c.3665_3675delGTGCTGTCTTA (p.S1222fs) was found in the proband, for which her parents were both heterozygous carriers. CONCLUSION WES is capable of detecting mutation underlying this disorder and facilitating genetic counseling and prenatal diagnosis for the affected family. A novel pathogenic mutation of the SACS gene was discovered.
Female ; Genes, Recessive ; Heat-Shock Proteins ; genetics ; Humans ; Muscle Spasticity ; Mutation ; Spinocerebellar Ataxias ; congenital