Objective To investigate the effects of imatinib mesylate and sunitinib malate on the migration and invasion of gastroin-testinal stromal tumor(GIST)cells.Methods After identifying primary-cultured GIST cells,their morphology was characterized using atomic force microscopy(AFM).Changes in the expression of genes related to the PI3K/AKT signaling pathway were analyzed using quan-titative real-time PCR following drug treatments.Changes in the binding of related molecules were detected using AFM,and alterations in cell migration,invasive ability,and apoptosis were determined using scratch assay,Transwell assay,and flow cytometry,respectively.Results AFM imaging showed that pseudopods were flatly spread around the GIST cells,indicating characteristics consistent with easy metastasis.Administration of either imatinib or sunitinib significantly reduced the expression of genes related to the PI3K/AKT signaling pathway,the density of epidermal growth factor receptor(EGFR)on the surface of GIST cells,and molecular binding force with EGF.These changes were more pronounced with the combination treatment.Correspondingly,the invasive and migratory abilities of GIST cells were significantly reduced when either drug was administered alone and the inhibitory effect was more significant when the drugs were combined.Conclusion Both imatinib and sunitinib can significantly inhibit the expression of genes related to the PI3K/AKT signaling pathway,reduce the density of EGFR on the surface of GIST cells,and attenuate their molecular binding to EGF,thereby reducing the migration and invasion of GIST cells.However,the combination of these two drugs has a more significant effect.

Objective To investigate the effects of imatinib mesylate and sunitinib malate on the migration and invasion of gastroin-testinal stromal tumor(GIST)cells.Methods After identifying primary-cultured GIST cells,their morphology was characterized using atomic force microscopy(AFM).Changes in the expression of genes related to the PI3K/AKT signaling pathway were analyzed using quan-titative real-time PCR following drug treatments.Changes in the binding of related molecules were detected using AFM,and alterations in cell migration,invasive ability,and apoptosis were determined using scratch assay,Transwell assay,and flow cytometry,respectively.Results AFM imaging showed that pseudopods were flatly spread around the GIST cells,indicating characteristics consistent with easy metastasis.Administration of either imatinib or sunitinib significantly reduced the expression of genes related to the PI3K/AKT signaling pathway,the density of epidermal growth factor receptor(EGFR)on the surface of GIST cells,and molecular binding force with EGF.These changes were more pronounced with the combination treatment.Correspondingly,the invasive and migratory abilities of GIST cells were significantly reduced when either drug was administered alone and the inhibitory effect was more significant when the drugs were combined.Conclusion Both imatinib and sunitinib can significantly inhibit the expression of genes related to the PI3K/AKT signaling pathway,reduce the density of EGFR on the surface of GIST cells,and attenuate their molecular binding to EGF,thereby reducing the migration and invasion of GIST cells.However,the combination of these two drugs has a more significant effect.

Objective:To summarize the clinical features, electroencephalogram (EEG) and magnetoencephalogram (MEG) of patients with pure paroxysmal kinesigenic dyskinesia (PKD) and PKD with epilepsy, so as to better distinguish them and guide the treatments.Methods:The clinical data of 200 patients diagnosed with PKD in the Outpatient Department of Xuanwu Hospital, Capital Medical University from 2000 to 2023 were analyzed retrospectively. The patients were divided into 2 groups: pure PKD (174 cases) and PKD with epilepsy (26 cases) according to whether accompanied by epilepsy. The differences in clinical features, drug therapy, EEG and MEG were compared between the 2 groups.Results:The clinical features of the 2 groups were essentially similar, and the proportion of PKD dyskinesia induced by emotional stress in the pure PKD group (54/174, 31.03%) was higher than that in the PKD with epilepsy group (2/26, 7.69%; χ 2=5.010, P=0.025). In terms of pharmacological response, carbamazepine was the most commonly used medication in both groups, but patients with PKD with epilepsy may need a higher therapeutic dosages (0.2-0.4 g/d, and gradually increased to 0.8 g/d) to effectively manage both dyskinesia and seizures. Regarding the EEG and MEG, the proportion of EEG abnormalities was higher in PKD patients with epilepsy, mainly manifested as focal spikes [1/70(1.43%) vs 9/21(42.86%), χ 2=24.268, P<0.001], together with aberrant MEG discharge (4/18 vs 3/5, χ 2=1.155, P=0.282). The MEG dipoles were mainly distributed in the brain regions close to the frontal lobe and central region. Conclusions:The clinical manifestations of motor symptoms of pure PKD and PKD with epilepsy are similar, and carbamazepine remains the most effective treatment. PKD patients with epilepsy have a higher proportion of abnormal EEG, mainly manifested as focal spikes, and are more likely to show abnormal discharge of MEG, which could be used to distinguish them.

Objective:To analyze the gene sequence of varicella-zoster virus (VZV) in Liaoning Province, and determine the prevailing dominant genotypes and nucleotide and amino acid variations.Methods:The open reading frames (ORFs) of 31 VZV strains from 2017 to 2020 in Liaoning Province were analyzed by PCR, including 1, 6, 12, 16, 17, 21, 22, 35, 37, 38, 50, 54, 55, 56, 60 and 66. The amplified products were sequenced, combined with single nucleotide polymorphism (SNP) and phylogenetic tree to determine the virus genotype, and the variation of nucleotides and amino acids at different sites was analyzed.Results:All 31 VZV strains in Liaoning Province were Clade 2 genotype. Compared with Clade 2 genotype reference strains, the 31 strains had nucleotide and amino acid homology of 99.6%-100.0% and 98.7%-100.0%, respectively, and the genetic distance was 0-0.002. Compared with V-Oka vaccine strain, the 31 strains all had site mutation, which led to amino acid changes, including one strain with ACCTCCCAA deletion at 541-549 sites of ORF1 and two strains with inserted CGG at the 780-781 site of ORF1; the 31 VZV strains had point mutations at 24 sites, including 15 synonymous mutations, 9 missense mutations, 20 mutations in the coding region, 4 mutations outside the coding region, 13 synonymous mutations in the coding region and 7 missense mutations in the coding region. The missense mutations in the coding region included a base mutation of C→T at site 731, a base mutation of C→T at site 790, a base mutation of C→T at site 791, a base mutation of A→G at site 17829, a base mutation of G→A at site 24567, a base mutation of T→C at site 98261, a base mutation of A→C at site 101579, which leaded to the amino acid changes of Arginine→Lysine, Arginine→Glutamine, Arginine→Glutamine, Histidine→Arginine, Arginine→Glutamine, Tyrosine→Histidine, Leucine→Arginine.Conclusions:Clade 2 genotype is the dominant genotype of VZV in Liaoning Province in recent years, and the gene sequences of VZV strains in Liaoning Province is highly conserved. Studying the characteristics of VZV gene is of great significance for studying the molecular epidemiology of VZV in Liaoning Province, and provides important scientific basis for varicella control and vaccination plan.

OBJECTIVE To provide evidence for the safe clinical application of Trastuzumab for injection. METHODS Reports of adverse drug reaction （ADR） related to Trastuzumab for injection submitted in Beijing from June 2018 to May 2023 were collected. Statistical analyses were performed using SPSS 25.0 software. The gender and age of patients with ADRs， outcome， types of cancer， and the time of onset， severity， affected organs/systems of ADRs were included for analyses. The univariate Logistic regression analysis was conducted on patient fever and ADR prognosis. RESULTS A total of 195 patients with 318 instances of ADRs were included in the study. Women （87.69%） and patients aged 60-69 （33.85%） were more likely to experience ADRs. Breast cancer dominated （86.67%） in terms of cancer types； in terms of outcomes， most patients （67.69%） showed improvement， and some patients （27.69%） achieved full recovery. Overall， 68.72% of ADRs mainly occurred on the day of medication， and 95.38% of ADRs were of “moderate” severity. The most affected organs/systems were general diseases and various reactions at the administration site （40.57%）， with chills （18.87%） and fever （18.24%） being the most common. Univariate Logistic regression analysis showed that fever mostly occurred within 1 day of medication （OR＝5.63， 95%CI was 2.26-14.02， P＜ 0.001）. The time of onset of ADR greater than 1 day was a risk factor for poor ADR prognosis （OR＝20.08， 95%CI was 2.45- 164.43， P＝0.005）， mainly manifesting as bone marrow suppression and liver function abnormalities. Neutrophilia， cardiorespiratory arrest， and mixed liver damage were new ADRs not recorded in the drug’s instructions. CONCLUSION Women and patients aged ≥60 are high-risk groups for ADRs of Trastuzumab for injection. Chills and fever remain the most common ADRs of this drug， and these symptoms mostly occur within 1 day of medication， which have better prognoses. Close attention should be paid to the patient’s temperature changes on the day of drug infusion， with timely intervention. Regular monitoring of the patient’s hematological indicators is necessary to detect any bone marrow suppression and liver function abnormalities after medication.

Objective:To analyze the gene sequence of varicella-zoster virus (VZV) in Liaoning Province, and determine the prevailing dominant genotypes and nucleotide and amino acid variations.Methods:The open reading frames (ORFs) of 31 VZV strains from 2017 to 2020 in Liaoning Province were analyzed by PCR, including 1, 6, 12, 16, 17, 21, 22, 35, 37, 38, 50, 54, 55, 56, 60 and 66. The amplified products were sequenced, combined with single nucleotide polymorphism (SNP) and phylogenetic tree to determine the virus genotype, and the variation of nucleotides and amino acids at different sites was analyzed.Results:All 31 VZV strains in Liaoning Province were Clade 2 genotype. Compared with Clade 2 genotype reference strains, the 31 strains had nucleotide and amino acid homology of 99.6%-100.0% and 98.7%-100.0%, respectively, and the genetic distance was 0-0.002. Compared with V-Oka vaccine strain, the 31 strains all had site mutation, which led to amino acid changes, including one strain with ACCTCCCAA deletion at 541-549 sites of ORF1 and two strains with inserted CGG at the 780-781 site of ORF1; the 31 VZV strains had point mutations at 24 sites, including 15 synonymous mutations, 9 missense mutations, 20 mutations in the coding region, 4 mutations outside the coding region, 13 synonymous mutations in the coding region and 7 missense mutations in the coding region. The missense mutations in the coding region included a base mutation of C→T at site 731, a base mutation of C→T at site 790, a base mutation of C→T at site 791, a base mutation of A→G at site 17829, a base mutation of G→A at site 24567, a base mutation of T→C at site 98261, a base mutation of A→C at site 101579, which leaded to the amino acid changes of Arginine→Lysine, Arginine→Glutamine, Arginine→Glutamine, Histidine→Arginine, Arginine→Glutamine, Tyrosine→Histidine, Leucine→Arginine.Conclusions:Clade 2 genotype is the dominant genotype of VZV in Liaoning Province in recent years, and the gene sequences of VZV strains in Liaoning Province is highly conserved. Studying the characteristics of VZV gene is of great significance for studying the molecular epidemiology of VZV in Liaoning Province, and provides important scientific basis for varicella control and vaccination plan.

OBJECTIVE: To explore the clinical phenotype and genetic variant in a child with Verheij syndrome (VRJS). METHODS: A child who had presented at the Soochow University Affiliated Children's Hospital and Wujiang District Children's Hospital in July 2022 for "elevated scapula since early childhood" was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child had manifested elevated scapulae, torticollis, neck asymmetry, facial dysmorphism, dispersed café-au-lait spots, limited mobility of upper limbs and shoulder joints, and intellectual disability. Sequencing revealed that he has harbored a de novo heterozygous c.405dupT (p.Ile136Tyrfs*4) variant of the PUF60 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PVS1+PS2_moderate+PM2_supporting). Combined his clinical features and result of genetic testing, the child was diagnosed with VRJS due to variant of the PUF60 gene. CONCLUSION The clinical manifestations of VRJS include facial dysmorphism, intellectual disability, elevated scapulae, vertebral fusion, other skeletal malformations, without significant abnormalities of the heart, kidney, and eyes, which need to be distinguished from Klippel-Feil syndrome. Above finding has expended the mutation spectrum of the PUF60 gene and provided a reference for delineation of the genotype-phenotype correlation of the VRJS.
Child ; Child, Preschool ; Humans ; Male ; Cafe-au-Lait Spots ; Computational Biology ; Genetic Testing ; Genomics ; Intellectual Disability/genetics* ; Mutation

Objective:To evaluate the effect of individualized blood pressure management on postoperative delirium in elderly hypertensive patients undergoing radical resection for gastrointestinal tumor.Methods:One hundred and sixty elderly hypertensive patients of both sexes, aged 60-80 yr, with body mass index of 19-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective radical resection for gastrointestinal tumor under general anesthesia, were divided into 2 groups ( n=80 each) using a random number table method: standardized blood pressure management group (group S) and individualized blood pressure management group (group I). Combined intravenous-inhalational anesthesia was performed, and BIS values were maintained at 40-60 and heart rate at 50-100 times/min during surgery in both groups. In group S, intraoperative systolic blood pressure was maintained above 90 mmHg with a decrease of less than 30% of the baseline value, while intraoperative fluctuation of systolic blood pressure was maintained less than 10% of the baseline value in group I. The use of vasoactive agents, numerical rating scale scores within 3 days after operation, and length of hospital stay were recorded. Postoperative delirium was evaluated by Confusion Assessment Method within 5 days after surgery. Results:Compared with group S, the intraoperative usage rate of norepinephrine was significantly increased, the incidence of postoperative delirium was reduced( P<0.05), and no significant change was found in the numerical rating scale scores and length of hospital stay in group I ( P>0.05). Conclusions:Individualized blood pressure management can reduce the development of postoperative delirium in elderly hypertensive patients undergoing radical resection for gastrointestinal tumor.

Objective To analyze the epidemiological characteristics of measles cases with immunization history of measles-containing vaccine (MCV), and to provide a basis for improving measles prevention and control measures. Methods Data were collected through the measles surveillance system and the immunization program information management system. Data were analyzed by descriptive epidemiological methods. Results A total of 9 164 cases of measles were reported in Liaoning Province during 2014-2021, of which the cases of measles with immunization history of 1 dose MCV accounted for 5.64%, and ≥ 2 doses accounted for 3.60%. There was a statistically significant difference in the immunization proportion among different years (χ²=184.534, P<0.001). The cumulative inoculation rate of measles cases was 23.85%, the immunization rates among different groups varied from 3.57% to 35.94%, and the differences were statistically significant (χ²=109.448, P<0.001). There was a statistically significant difference between 2-6 years old and 7-14 years old in the immunization rate of 1 dose and ≥ 2 doses (χ²=4.147, P<0.05). The onset time of most cases was over 2 weeks after the last dose of MCV vaccination, accounting for 82.06%. The incidence rates of fever, cough, catarrh symptoms, conjunctivitis, lymph node enlargement and articular pain were all significantly lower in the cases with immunization history than those in the patients without a history of MCV immunization (P<0.05). Conclusion The cases with immunization history account for a certain proportion in measles cases, mainly secondary vaccination failure. The incidence rate of fever, cough, catarrhal symptoms, conjunctivitis, Koch's patches, lymphadenopathy, joint pain, and other clinical symptoms in measles patients with a history of MCV immunization is lower than that in patients without immunization history. Inoculation of MCV is of great significance in relieving clinical symptoms. It is necessary to inoculate two doses of MCV in time for measles prevention and control.

Objective To understand the epidemiological characteristics of rubella in Liaoning Province in 2019,and analyze the epidemiological characteristics of rubella virus genotypes and gene subtypes at molecular level.Methods By collecting the incidence data of rubella in Liaoning Province in 2019 from the national notifiable infectious diseases reporting system,the epidemiological characteristics of rubella were analyzed.At the same time,the measles/rubella laboratory network of Liaoning Province was used to collect throat swab samples from suspected rubella outbreaks and sporadic cases.After three generations of blind transmission of positive samples,rubella virus isolates were obtained.Viral nucleic acid was extracted,amplified and the 739 bp nucleotide fragment sequence of E1 gene of positive rubella virus isolates was determined.The phylogenetic tree was constructed with the genotype reference strain sequences recommended by WHO and the published gene subtype reference strain sequences.The genotypes and subtypes were compared and the amino acid variation sites were analyzed.Results The reported incidence of rubella in Liaoning Province in 2019 was 0.927/100 000,which showed an obvious trend of recovery after a significant decrease in the incidence of rubella from 2017 to 2018,and the age of rubella patients was mainly 15 to 19 years old.A total of 55 rubella virus strains were isolated from 7 cities in Liaoning Province in 2019.Sequence phylogenetic analysis showed that all rubella isolates belonged to 1E-L2 gene subtype,which was also the dominant gene subtype of rubella epidemic in China.The nucleotide and amino acid homology among the strains were 99.051%～99.864% and 98.780%～100% respectively.Compared with the BRD-Ⅱ vaccine strain,the rubella isolates mainly showed A333T mutation and showed highly conserved amino acid sequence.Conclusion The 2019 rubella isolates in Liaoning Province were all 1E-L2 gene subtypes,which led to the resurgence of rubella epidemic.Therefore,molecular epidemiological surveillance of rubella virus should be further strengthened to provide a basis for the formulation and elimination of rubella prevention and control measures in Liaoning Province.