BackgroundObsessive-compulsive disorder （OCD） is a common neuropsychiatric illness and is listed as one of the top ten disabling conditions causing loss of income and reduced quality of life. Psychological distress is an important cause of anhedonia in OCD patients， and is closely related to psychosomatic symptoms. Therefore， exploring the role of anhedonia in the relationship between psychological distress and psychosomatic symptoms is of great significance for optimizing clinical psychological treatment protocols for OCD patients. ObjectiveTo explore the role of anhedonia in the relationship between psychological distress and psychosomatic symptoms in OCD patients， with the aim of providing references for managing psychosomatic symptoms in patients. MethodsA total of 90 patients who met the diagnostic criteria for OCD according to the International Classification of Diseases， tenth edition （ICD-10）， and who visited the Mental Health Center outpatient clinic of General Hospital of Ningxia Medical University from September 2023 to November 2024 were selected as the study objects. The instruments and techniques used for the evaluation were： Dimensional Anhedonia Rating Scale （DARS）， 10-item Kessler Psychological Distress Scale （K10） and Psychosomatic Symptom Scale （PSSS）. Model 4 of the Process for SPSS 26.0 was used to test the mediating role of anhedonia in the relationship between psychological distress and psychosomatic symptoms， with Bootstrapping used to assess the significance of mediating effect. ResultsA total of 84 patients （93.33%） completed the valid questionnaire. K10 score was positively correlated with PSSS total score， psychological symptom score and physical symptom score （r=0.559， 0.460， 0.551， P<0.01）. K10 score was negatively correlated with DARS total score （r=-0.527， P<0.01）. The total score of DARS was negatively correlated with PSSS total score （r=-0.497， P<0.01）. Anhedonia mediated the relationship between psychological distress and psychosomatic symptoms， with an indirect effect value was 0.148 （95% CI： 0.042~0.278）， accounting for 26.48% of the total effect. ConclusionPsychological distress can affect the psychosomatic symptoms in OCD patients both directly and indirectly via anhedonia.

Objective:To explore the clinical features and genetic etiology of a child with Baraitser-Winter syndrome (BWS).Methods:A BWS child who had sought medical attention at the Linyi People′s Hospital on April 8, 2022 was selected as the study subject. Clinical data of the child was collected, and peripheral blood samples were obtained from the child and his parents. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:The child, a 5-year-and-6-month-old male, had typical clinical features of BWS including congenital non-myogenic ptosis, arched eyebrows, wide philtrum, and pointed chin. Neurological symptoms included microcephaly, developmental delay, epilepsy, and deafness. Cranial MRI revealed enlarged frontal lobes, decreased white matter, and hydrocephalus. WES has identified a heterozygous c. 430G>A (p.Asn144Tyr) missense variant in the ACTG1 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP3_Moderate+ PP4). Conclusion:The heterozygous c. 430G>A (p.Asn144Tyr) missense variant of the ACTG1 gene probably underlay the pathogenesis of BWS in this child. Above finding has enriched the mutation spectrum of BWS-related genes and provided a basis for clinical diagnosis and genetic counseling.

Objective:To characterize and analyze the genetic variation of hemagglutinin (HA) of influenza A (H1N1) pdm09 subtype virus in Shandong Province, and explore the genetic variation patterns for providing reference for influenza monitoring, epidemic prevention and control, and vaccine strain selection.Methods:HA gene sequences of the recommended strains of influenza vaccine from 2009 to 2024 and the representative strains of each branch were downloaded from the GISAID Influenza Data Platform, and were phylogenetically analyzed and characterized in terms of amino acid site variation with the HA gene sequences of 298 influenza A (H1N1) virus strains isolated from Shandong Province. A phylogenetic tree was constructed using the maximum likelihood (ML) method of the IQ-TREE online tool, and the amino acid site variants were viewed using MegAlign software. The potential glycosylation sites of the HA gene were predicted using the NetNGlyc 1.0 online software.Results:The HA gene homology of the 298 influenza A (H1N1) viruses isolated in Shandong Province ranged from 91.2% to 100.0%. The evolutionary branches were gradually distantly related over time, but the direction of evolution was roughly the same as that in other provinces. Amino acid mutations in the HA occurred every year and most were found in the antigenic determinants.Conclusions:The HA genes of influenza viruses isolated in Shandong Province from 2009 to 2024 are still in the process of continuous evolution, and continuous monitoring of the epidemiological trends and the evolutionary directions of influenza viruses is essential for early warning of influenza virus pandemics.

OBJECTIVE: To explore the clinical features and genetic etiology of a child with Multiple congenital malformations-hypotonia-epilepsy syndrome type 3 (MCAHS3) and provide prenatal diagnosis for her parents. METHODS: A female child who had presented at Linyi People's Hospital on 27 July 2022 for recurrent convulsions for over 4 years was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples were taken from the child and her parents and subjected for whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out on amniotic fluid sample at 18 weeks' gestation. Bioinformatic software was used to analyze the pathogenicity of the protein model for the variant loci. RESULTS: The child was a 4-year-old female with frequent seizures, peculiar facial appearance, hypotonia and severe developmental delay. Genetic analysis revealed that she has harbored compound heterozygous variants of the PIGT gene, namely c.1126del (p.H376Tfs*56) and c.1285G>C (p.E429Q), which were respectively inherited from her mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.1126del (p.H376Tfs*56) variant was predicted to be pathogenic (PVS1+PM2_Supporting+PM4), and c.1285G>C (p.E429Q) variant was predicted to be likely pathogenic (PM2_Supporting+PM3+PM4). Prenatal diagnosis suggested that the fetus also harbored the same compound heterozygous variants, and the pregnancy was terminated with induced labor. CONCLUSION The c.1126del (p.H376Tfs*56) and c.1285G>C (p.E429Q) compound heterozygous variants of the PIGT gene probably underlay the MCAHS3 in this patient, and prenatal diagnosis has prevented birth of further affected child in this family.
Humans ; Female ; Child ; Pregnancy ; Child, Preschool ; Muscle Hypotonia/genetics* ; Prenatal Diagnosis ; Computational Biology ; Epileptic Syndromes ; Facies

Objective:To analyze the clinical characteristics of a child with developmental epileptic encephalopathy caused by NR4A2 gene mutation, and to summarize the clinical phenotypes and genotypes to improve the clinician′s understanding of this disease. Methods:The clinical data of a child with developmental epileptic encephalopathy admitted to Linyi People′s Hospital in August 2022 were collected, video electroencephalogram, craniocerebral magnetic resonance imaging and family whole exon sequencing were improved, and the suspected mutation sites were verified by Sanger sequencing. Relevant literature was consulted to summarize the clinical phenotypes and genetic characteristics of nervous system diseases caused by NR4A2 gene. Results:It was found that there was a heterozygous missense mutation at the locus c.866G>A (p.A289H) of NR4A2 gene in the child, which was a de novo mutation, and both parents were wild type. According to the American Society of Medical Genetics and Genomics variation classification, it was assessed as a suspected pathogenic variation. Through literature review, there were 16 related cases reported internationally, with clinical phenotypes including mental retardation/mental retardation, language disorders, seizures, muscle tone changes and different psychological and behavioral problems. Conclusions:The NR4A2 gene is not only associated with dopa responsive disorders, but also with neurological development, intellectual impairment, language development delay, and epilepsy. The mutation of NR42A gene c.866G>A (p.A289H) is the genetic cause of the patient, and the detection of this locus expands the NR4A2 gene spectrum. NR4A2 gene is one of the pathogenic genes of developmental epileptic encephalopathy.

Objective:To study the infection of human rhinovirus, respiratory syncytial virus and human adenovirus in Jinan from April 2018 to March 2019, and analyze epidemiological characteristics of human adenovirus.Methods:All of 1969 nasopharyngeal swabs were collected from hospitalized patients with acute respiratory tract infections in The Fourth People’s Hospital of Jinan, Qilu Children′s Hospital of Shandong University, Peoples Hospital of Zhangqiu District from April 2018 to March 2019, fluorescence quantitative PCR was used to detect the positive rate of human rhinovirus, respiratory syncytial virus and human adenovirus. Seven adenovirus positive samples were isolated and examined by sequencing, then we determined adenovirus type, constructed gene phylogenetic trees for analysis.Results:Of the 1969 samples, 242 were positive, the total positive rate was 12.30% (242/1969), the positive rate was 3.00% (59/1969) for rhinovirus, 6.30% (124/1969) for respiratory syncytial virus (RSV), and 3.86% (76/1969) for adenovirus. There was no significant difference in the detective rate of rhinovirus in different age groups (Fisher′s exact test value =8.376, P=0.720), the positive rates of RSV and adenovirus in different age groups was statistically significant ( χ2=19.28, 12.16; P=0.001, 0.016). There was a statistically significant difference in the positive rate of adenovirus between different sexes ( χ2=14.33, P<0.001), and there was no statistically significant difference in the positive rate of rhinovirus and RSV between males and females ( χ2=0.30, 2.90, P=0.862, 0.089). Comparing the positive rates of viral nucleic acid in different months, we found that the positive rate of rhinovirus, RSV and adenovirus separately reached the highest in October, December and November (8.61%, 26.50% and 8.84%). We constructed a gene phylogenetic tree after seven positive samples of adenoviruses were sequenced, by the molecular typing method we detected that seven adenovirus-positive samples were all HAdV-2 type. Conclusions:By comparing the epidemiological trends of human rhinovirus, RSV and human adenovirus in Jinan from April 2018 to March 2019 in different ages, genders, and months, providing reference basis for the early prevention and clinical treatment of acute respiratory tract infection.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with genetic epilepsy with febrile seizures plus (GEFS+). METHODS: Clinical data of the proband and his family members were collected. Following extraction of genomic DNA, the proband was subjected to high-throughput sequencing. Candidate variant was verified by Sanger sequencing of the proband and other family members. RESULTS: The pedigree, including 6 patients with febrile seizures from 3 generations, was diagnosed with typical GEFS+. Among them, 2 had febrile seizures (FS), 1 had febrile seizures plus (FS+), and 3 had febrile seizures with focal seizures. High-throughput sequencing revealed that the proband has carried a heterozygous missense variant of c.4522T>A (p.Tyr1508Asn) of the SCN1A gene. Sanger sequencing confirmed that other five patients and one normal member from the pedigree have also carried the same variant, which yielded a penetrance of 85.7%. CONCLUSION The c.4522T>A (p.Tyr1508Asn) of the SCN1A gene probably underlay the disease in this pedigree. The pattern of inheritance was consistent with autosomal dominant inheritance with incomplete penetrance. Above finding has enriched the variant spectrum of the SCN1A gene.
Epilepsy/genetics* ; Humans ; NAV1.1 Voltage-Gated Sodium Channel/genetics* ; Pedigree ; Phenotype ; Seizures, Febrile/genetics*

Objective:To isolate and identify the virus from stool samples of children with hand, foot and mouth disease (HFMD) in Linyi City, Shandong Province in 2017, and analyze its genetic characteristics.Methods:Nucleic acid was detected in fecal specimens of children with hand, foot and mouth disease. Human rhabdomyosarcoma cells were used for virus isolation. The whole genome of the virus was sequenced, and the phylogenetic analysis and gene recombination analysis of the isolates were carried out by comparing with human enterovirus.Results:A coxsackievirus A group 2 type(CoV-A2), named SD17-430, was successfully isolated from fecal specimens of children with severe HFMD. Phylogenetic analysis further confirmed that the coxsackievirus genotype belonged to D2 genotype. The coding region of SD17-430 capsid protein had high homology with CoV-A2 international original strain, while the coding region of non-structural protein had high homology with CoV-A4 (MH086949) and CoV-A14 (KP036482).Conclusions:Compared with the original strain, CoV-A2 SD17-430 strain has a greater degree of genetic variation, and may have genetic recombination with multiple enteroviruses during its evolution. We should continue to strengthen the overall monitoring of HFMD pathogens in order to further understand the changes of pathogen spectrum and provide data reference for formulating more effective strategies for HFMD prevention and control.

Objective:To construct and rescue enhanced green fluorescent protein(EGFP)-labeled EGFP-EV-A71 recombinant virus.Methods:pMD19T-SDLY107 full-length plasmid was used as a template, and 2A protease recognition sequence was added to the 5′end of the structural protein VP4. EGFP gene was amplified using the pEGFP-N1 plasmid as a template and inserted into the above-mentioned recombinant plasmid. RD cells were transfected to rescue the recombinant virus EGFP-EV-A71 after enzymatic digestion and in vitro transcription. The cell culture infectious dose 50% endpoint (CCID 50) was determined. Real-time fluorescent quantitative PCR (qRT-PCR) was used to detect the virus replication level at different time points, and the virus replication curve was drawn to compare the replication ability of the recombinant virus and the parent virus. Lactate dehydrogenase (LDH) and cell proliferation (CCK-8) experiments were used to determine the cell injury rate and survival rate of infected cells, respectively. Results:Recombinant EV-A71 infectious cDNA clones containing specific restriction sites and EGFP were successfully constructed. Typical cytopathic effect and green fluorescence was observed. The qRT-PCR replication curve showed that the recombinant virus had similar replication kinetics to the parent virus.Conclusions:EGFP-labeled enterovirus type 71 recombinant virus EGFP-EV-A71 was successfully rescued.

Objective:To investigate the clinical effect of botulinum toxin type A injection in the prevention and treatment of frontal traumatic scars immediately after operation.Methods:From January 2016 to January 2018, among the 152 patients with frontal trauma admitted to the Department of Plastic Surgery, Daping Hospital, Army Military Medical University, patients with wounds almost perpendicular to the Langer line were selected. Immediately after debridement and suture, botulinum toxin type A was injected with a concentration of 2 U botulinum toxin per 0.10 ml of solution, 0.05 to 0.10 ml (1 to 2 U) per 1 cm was injected into the frontal muscle according to frontal muscle strength.With reference to the observer scar assessment scale and Vancouver scar scale, the color, width, texture, thickness, pain, and itching of the postoperative scar of the frontal wound were evaluated at follow-up.Results:A total of 44 patients were included, 22 males and 22 females, aged (31.5 ± 8.4) years old, with a wound length of 1-12 cm(average, 3.5 cm) and a Botox injection volume around wounds of 0.10-0.90 ml (2-18 U) . The patients were followed up for 6 to 24 months. One patient had mild to moderate ptosis, which completely disappeared within one month. Within 6 weeks after operation, the scars in 44 patients were pink and hard. 3-6 months later, the scars gradually became soft, narrow and flat with similiar skin color, no pain and itching left in 42 patients. The satisfaction rate was 95.5% (42/44). Two patients were dissatisfied because of scar pigmentation and width.Conclusions:Immediate injection of botulinum toxin type A after debridement and suture of the frontal trauma wound can effectively prevent and improve scar appearance with a high rate of satisfaction.