Objective:To investigate the clinical and gene variant characteristics of PCDH19 gene related epilepsy, and improve the ability of clinicians in early disease identification. Methods:The clinical data of 3 PCDH19 gene related epilepsy patients admitted to Children′s Hospital Affiliated to Zhengzhou University from October 2018 to August 2023 diagnosed by gene detection were reviewed and analyzed. Results:All the patients are female, and the onset age of seizure ranged in their infancy. Seizures in clusters and fever sensitivity were observed in all patients, and were very hard to control by single-drug treatment. Proband 1 was seizure-free after 2 kinds of anti-epileptic drug treatment, but with mild degree of intellectual disability. Proband 2 had refractory epilepsy with severe degree of intellectual disability. Proband 3 was seizure-free after 2 kinds of anti-epileptic drug treatment and without intellectual disability. In the first family, the proband carried heterozygous c.369C>G variant in the PCDH19 gene which was identified as de novo after parental validation. In the second family, the proband carried c.1652T>A variant inherited from her mother. In the third family, the proband carried c.278G>A variant inherited from her father. The 3 mutations had not been reported in the Human Gene Mutation Database. Conclusions:PCDH19 gene related epilepsy is one special kind of X-linked inherited epilepsy syndrome characterized by seizures in clusters and sensitivity to fever. And gene detection can help with early diagnosis and make rational clinical strategies in time. The variants c.369C>G, c.1652T>A and c.278G>A have enriched the gene variant spectrum of PCDH19.

Objective To investigate the predictive efficiency of combined uterine artery hemodynamic parameters and oxidative stress indicators in early pregnancy on hypertensive diseases in pregnancy (HDP). Methods A total of 90 HDP patients (case group) and 30 healthy pregnant women (control group) as research subjects. The case group included 30 patients with pregnancy-induced hypertension, 30 patients with preeclampsia, and 30 patients with severe preeclampsia, respectively, and were divided into pregnancy-induced hypertension group, preeclampsia group, and severe preeclampsia group. Serum levels of reactive oxygen species (ROS), superoxide dismutase (SOD), heme oxygenase-1 (HO-1), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), and uterine artery hemodynamic parameters were compared between the two groups in early pregnancy (8 weeks to 13 weeks plus 6 days). The receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency of relevant indicators for HDP. Results The serum levels of SOD and GSH-PX were lower in the case group than that in the control group, and the serum level of MDA and the uterine artery pulsatility index (PI) were higher in the case group than that in the control group (P < 0.05). The serum levels of SOD and GSH-PX gradually decreased, and the serum levels of MDA and PI gradually increased in the pregnancy-induced hypertension group, the preeclampsia group, and the severe preeclampsia group (P < 0.05). The ROC curve showed that the combination of SOD, GSH-PX, MDA, and PI in early pregnancy had a higher predictive efficiency for HDP, with an area under the curve of 0.824, a sensitivity of 81.1%, and a specificity of 76.7%. Conclusion Patients with HDP have changes in oxidative stress indicators and uterine artery hemodynamic parameters in early pregnancy, and there are differences among patients with different disease severities. The combined detection of SOD, GSH-PX, MDA, and PI in early pregnancy can help predict HDP.

Objective:To investigate the clinical phenotype and genotypic characteristics of Legius syndrome.Methods:The clinical data of a child with precocious puberty and scattered café-au-lait macules admitted to Department of Neurology of the Children′s Hospital Affiliated to Zhengzhou University in July 2021 were retrospectively analyzed. Trio-whole exome sequencing (trio-WES) was used for genetic analysis to confirm the molecular diagnosis of the family. The relevant literature was reviewed to summarize the clinical characteristics of the disease.Results:The proband was a 10-year and 9-month-old girl, presenting with more than 5 café-au-lait macules with diameter>5 mm on the face and trunk, freckles in the axillary, without Lisch tubercles of iris and tumor signs of neurofibromatosis type 1, diagnosed as central precocious puberty at the age of 8. trio-WES results of the family revealed a spontaneous heterozygous nonsense mutation c.751(exon7) C>T in SPRED1 gene, causing a nonsense mutation in the amino acid sequence p.Arg251Ter (p. Ter251 *). Literature review showed a total of 88 pathogenic mutations were reported in SPRED1 gene, including frameshift mutations (41/88), nonsense mutations (31/88), splice mutations (7/88), missense mutations (6/88), and others (3/88), and no mutational hotspots were found. Clinical phenotype was as follows:>5 café-au-lait macules accounted for 92.8% (168/181), armpit and inguinal freckles 43.5% (73/168), macrocephaly 21.4% (31/145), learning disability 18.0% (30/166), psychomotor retardation 13.8% (22/159), lipoma (adult) 13.7% (21/153), Noonan facial sign 12.1% (21/173), and tumor phenotype of neurofibromatosis type 1 was not reported. Conclusions:The central precocious puberty phenotype of Legius syndrome was not reported in China. The clinical phenotype of Legius syndrome was mild, with a large variation, but without neurofibromatosis type 1 tumor phenotype. Genetic testing can be beneficial for early diagnosis of Legius syndrome.

Objective:To summarize the clinical phenotype and genotypic characteristics of children with truncation variation in SMC1A gene. Methods:The clinical data of a child with late-onset cluster seizures caused by truncation variation in SMC1A gene diagnosed in February 2021 in Children′s Hospital Affiliated to Zhengzhou University were collected. The relevant literature was reviewed to summarize the clinical characteristics. Results:The proband was a 5-year-old girl, presenting with first seizure at the age of 5 and cluster seizures. She had poor response to multiple antiepileptic drugs, and had normal neurodevelopment before seizures. Whole exome sequencing results revealed a spontaneous heterozygous nonsense variation c.55C>T in SMC1A gene, causing a nonsense variant in the amino acid sequence p.Gln19Ter(p.Gln19 *), which has not been reported. There were a total of 14 relevant literatures, and there were in total 32 cases with truncation variation in SMC1A gene including this case. All children were female and 30 children had early-onset intractable epilepsy, and first seizure median age was 5 months (range: 4 weeks to 40 months); 78.1% (25/32) of them had cluster seizures; 93.8% (30/32) had mental retardation; Cornelia de Lange syndrome clinical score in 68.8% (22/32) of them was≥4. The truncation variations in SMC1A gene of 31 children were de novo, and there were 16 children with frameshift variation (16/32), 12 children with nonsense variation [12/32; 3 children (9.4%, 3/32) with c.2923C>T], 4 children with splice variation (4/32). Conclusions:This study further expands the clinical phenotype and genotype of cases with truncation variation in SMC1A gene. Case presenting with female late-onset cluster seizures has not been reported in China, and genetic testing can be beneficial for early diagnosis of hereditary epilepsy and precision treatment.

Objective:To investigate the clinical phenotypes, therapy and genetic features of aldehyde dehydrogenase 7 family member A1 (ALDH7A1) gene mutations in five cases of pyridoxine dependent epilepsy (PDE) with diagnosis confirmed by next generation sequencing.Methods:Retrospective analysis was carried out on clinical data of five cases of PDE children with early epilepsy onset who were treated in the Department of Neurology of Children′s Hospital Affiliated to Zhengzhou University from February 2018 to November 2019. Next generation sequencing approach was used for genetic sequencing of proband ALDH7A1 gene and the first generation Sanger was used for validation of family members. And the characteristics of gene mutations were analyzed.Results:Among the five children diagnosed with PDE, the male to female ratio was 4 ∶ 1 and ages at clinic visit ranged from two months to 10 months old. In clinical phenotypes, all five cases experienced onset in neonatal period, with repeated seizures, manifested as myoclonus, spasms or focal paroxysm. The administration of antiepileptic drugs performed poorly in seizure control while long term oral intake of large dose pyridoxine showed better efficacy. All the five cases of children came from compound heterozygous mutations of father and mother, i.e. slicing homozygous mutation c.247-2(IVS2)A>T, missense mutation c.584A>G (p.N195S) and nonsense mutation c.1003C>T(p.R335 *), missense mutation c.1553G>C(p.R518T) and c.1547A>G(p.Y516C), missense mutation c.1547A>G(p.Y516C) and frameshift mutation c.1566_1568delTAC, missense mutation c.1061A>G(p.Y354C) and nonsense mutation c.841C>T(p.Q281X, 259), among which c.247-2(IVS2)A>T was novel splicing site mutation not reported before. Conclusions:PDE is induced by ALDH7A gene mutation. Early clinical manifestations are mostly onset of refractory epilepsy in neonatal period. Antiepileptic drugs perform poorly in terms of efficacy while pyridoxine can control seizure effectively. Gene analysis should be conducted on such patients for confirmed diagnosis.

Objective:To explore the functional connections of the whole brain and the two hemispheres in patients with obsessive-compulsive disorder (OCD).Methods:Twenty-six patients with obsessive-compulsive disorder(patients group) and thirty-seven healthy controls matched in gender, age and education(control group) were enrolled.All the participants accepted the resting-state functional magnetic resonance (rs-fMRI) scan.Based on DPABI and REST software, degree centrality (DC) and voxel - mirrored homotopic connectivity (VMHC) approaches were used to explore the pattern of functional connection in OCD.Results:Compared with the control group, the DC values in the right posterior cerebellar lobe(MNI: x, y, z=45, -87, -12), left precentral gyrus(MNI: x, y, z=-54, 9, 39), left inferior parietal lobule(MNI: x, y, z=-48, -51, 42), right anterior cingulate cortex(MNI: x, y, z=3, 18, 48) were significantly higher( t values were 5.75, 5.26, 5.28 and 5.16, respectively), and the DC values in the left inferior frontal gyrus(MNI: x, y, z=-36, 9, 30) were significantly lower( t value was -6.65) in patients group.The VMHC values in bilateral posterior cerebellar lobe(MNI: x, y, z=±51, -69, -33), bilateral inferior parietal lobule(MNI: x, y, z=±48, -51, 54), bilateral anterior cingulate cortex(MNI: x, y, z=±3, 21, 45)in patients group were significantly higher that those in control group( t values were 5.19, 5.19, 5.02, 5.02, 5.15 and 5.15, respectively). The DC and VMHC values in patients group were not significantly correlated with clinical symptoms(-0.23< r<0.19, P>0.05). Conclusion:OCD patients have abnormal connections between key brain network nodes and relevant brain regions, and functional connections have increased among multiple cerebral hemispheres.

Overuse of antibiotics in aquaculture, husbandry and healthcare has led to antibiotics residues in the enviuronment and the generation of antibiotic resistant bacteria that can be transferred into the human gut through food chain. Based on literatures, we reviewed the influence of bacterial resistance on intestinal flora and related immune regulation. Taking the source of antibiotic resistance to human intestinal flora as an entry point, we addressed the structure of human intestinal flora and the composition of drug resistance genes after exposure to pollutants. Moreover, we discussed the relationship among changes of intestinal flora, antibiotic resistance genes and immunomodulation related diseases. Last, we also indicated future research needs.

OBJECTIVE:To establish a method for the simultaneous determination of curdione,germacrone and furanodiene of zedoray turmeric oil in Ruxiankang injection. METHODS:HPLC was performed on the column of Zorbax SB-C18 with mobile phase of acetonitrile-water (gradient elution) at a flow rate of 1.0 ml/min,detection wavelength was 216 nm,column temperature was 30℃,and the injection volume was 10 μl. RESULTS:The linear range was 60-480 μg/ml for curdione(r=0.999 0),40-320 μg/ml for germacrone(r=0.999 0)and 40-320 μg/ml(r=0.999 0);RSDs of precision,stability and reproducibility tests were lower than 2.0%;recoveries were 95.21%-99.89%(RSD=1.6%,n=6),102.33%-104.89%(RSD=1.0%,n=6)and 97.38%-99.06%(RSD=0.7%,n=6),respectively. CONCLUSIONS:The method is simple and accurate,and can be used for simultaneous contents deter-mination of curdione,germacrone and furanodiene of zedoray turmeric oil in Ruxiankang injection.

Objective To investigate the changing characteristics of myocardial movement in patients with dilated cardiomyopathy by three?di?mensional speckle tracking echocardiography(3D?STE). Methods The peak systolic global longitudinal train(GLS),global radial strain(GRS), global circumferential stain(GCS)and global area strain(GAS)of left ventricle were measured by 3D?STE technology in 69 patients with dilated cardiomyopathy. According to the left ventricular ejection fraction(LVEF),all patients were divided into group A(35%≤LVEF<50%)and group B (LVEF<35%). The differences of measurements were compared between two groups. The correlation between global myocardial strain in all direc?tions and left ventricular ejection fraction was analyzed. Results The GLS,GRS,GCS and GAS were significantly higher in group A than those in group B(P<0.01). The GLS,GRS,GCS and GAS were correlated with LVEF in group A(r=-0.871,0.610,-0.423,-0.797;P<0.05).The GCS,GRS and GAS were correlated with LVEF in group B(r=-0.517,0.368,-0.438;P<0.05). There was no significant correlation between GLS and LVEF in group B. Conclusion 3D?STE technology can be applied to evaluate the change of the myocardial movement. GLS is a promis?ing marker of the prognosis in patients with DCM.

Objective To develop the methods for identification and determination of scutellarin in compound Granule Tetrandra .Methods A TLC method was used to identify quality for scutellarin ,and a HPLC method was used to determine the content of scutellarin .Results The spot was clear in TLC identification without interference of negative control .The sam-ple size of scutellarin had a good linear relationship with peak area r=0 .9996(n=5)when ranged from 22 .4~156 .8 μg/ml , with the average recovery rate 97 .79% ( RSD=0 .32% ,n=6) .Conclusion The method is simple ,with good specificity and reproducibility ,which can be used as the quality control for this preparation .