Objective:To investigate the clinical and genetic characteristics of KDM6B gene variation associated neurological developmental disorder in a child. Methods:Clinical data were collected from a child of KDM6B gene variation associated neurological developmental disorder admitted to Children′s Hospital Affiliated to Zhengzhou University in July 2021. His clinical manifestations and genetic variation profiles were retrospectively analyzed and literature review was conducted. Results:The patient was a one-year-six-month old male, with protruding forehead, joint laxity, distal skeletal abnormalities, and behavioral, cognitive, language, intellectual, and psychomotor development disorder. The whole-exome sequencing and Sanger sequencing confirmed that there was a de novo heterozygous frameshift variation c.1718delC(p.Pro573Hisfs *9) in exon 11 of the KDM6B gene. This variation was classified as pathogenic (PVS1+PS2+PM2_supporting) according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines, with no prior reports. By literature review, no relevant Chinese literature was retrieved, whereas 4 English literatures were found, reporting 98 patients, totally 99 patients (including this case) with nervous system development disorder due to KDM6B gene variation. The main manifestations were neurodevelopmental disorders such as speech, motor, and behavioral abnormalities, mental retardation, as well as facial deformities, hypotonia, infantile feeding difficulties/gastroesophageal reflux, joint/ligament laxity, and abnormalities of the hands and toes/palms. A total of 83 variation sites were found, including 37 frameshift variations, 18 missense variations, 21 nonsense variations, and 7 splicing variations, all of which were heterozygous variations. Conclusions:The KDM6B gene variation can lead to neurodevelopmental disorder, craniofacial developmental and skeletal abnormalities. The de novo heterozygous variation in the KDM6B gene is considered to be the genetic etiology of this child. This study extends the spectrum of KDM6B gene variant.

Objective:To investigate the clinical and genetic characteristics of KDM6B gene variation associated neurological developmental disorder in a child. Methods:Clinical data were collected from a child of KDM6B gene variation associated neurological developmental disorder admitted to Children′s Hospital Affiliated to Zhengzhou University in July 2021. His clinical manifestations and genetic variation profiles were retrospectively analyzed and literature review was conducted. Results:The patient was a one-year-six-month old male, with protruding forehead, joint laxity, distal skeletal abnormalities, and behavioral, cognitive, language, intellectual, and psychomotor development disorder. The whole-exome sequencing and Sanger sequencing confirmed that there was a de novo heterozygous frameshift variation c.1718delC(p.Pro573Hisfs *9) in exon 11 of the KDM6B gene. This variation was classified as pathogenic (PVS1+PS2+PM2_supporting) according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines, with no prior reports. By literature review, no relevant Chinese literature was retrieved, whereas 4 English literatures were found, reporting 98 patients, totally 99 patients (including this case) with nervous system development disorder due to KDM6B gene variation. The main manifestations were neurodevelopmental disorders such as speech, motor, and behavioral abnormalities, mental retardation, as well as facial deformities, hypotonia, infantile feeding difficulties/gastroesophageal reflux, joint/ligament laxity, and abnormalities of the hands and toes/palms. A total of 83 variation sites were found, including 37 frameshift variations, 18 missense variations, 21 nonsense variations, and 7 splicing variations, all of which were heterozygous variations. Conclusions:The KDM6B gene variation can lead to neurodevelopmental disorder, craniofacial developmental and skeletal abnormalities. The de novo heterozygous variation in the KDM6B gene is considered to be the genetic etiology of this child. This study extends the spectrum of KDM6B gene variant.

Objective This study aimed to estimate the therapeutic effects of preformed metal crown(PMC)and pre-fabricated zirconia crowns(ZC)on decayed primary morals in children,as well as to analyze the possible influencing fac-tors.Methods A retrospective cohort study was performed on the data of 192 patients(aged 3 to 8)in the Stomatologi-cal Department of Shenzhen Children's Hospital from October 2021 to December 2021.The decayed mandibular first molars were selected and restored by vital-pulp therapy followed by PMC and ZC,including 96 cases(96 caries)in the PMC group and 96 cases(96 caries)in the ZC group.Oral clinical examination was performed at 3 months,1 year,and 2 years after treatment,overwiewing the clinical therapeu-tic effects and periodontal status of PMC and ZC groups,as well as recording the crown integrity,gingival index(GI),probing bleeding index(BI),plaque index(PLI)and various prosthetic indices.Results No significance differences existed in the periodontal status of PMC and ZC groups at 3 months,1 year,and 2 years after treatment(P>0.05).However,the GI,BI,and PLI in the PMC group were higher than those in the ZC group at 3 months,1 year,and 2 years after treatment,and the difference was dramatically signifi-cant(P<0.05).No significances difference existed in various prosthetic indices(P>0.05),as well as in the GI,BI,and PLI,between the two groups(P>0.05).No significant differences existed in various prosthetic indices between genders after PMC restoration(P>0.05).The scores of girls in various prosthetic indices after ZC restoration were higher than those of boys(P<0.05).Pearson correlation analysis indicated an inverse correlation between age in the PMC group and the GI,BI,PLI,and FDI indices(P<0.01),rather than in the ZC group(P>0.05).Conclusion PMC and ZC can be ap-plied to restore deciduous molar caries.The periodontal status of deciduous teeth in ZC group was superior to that in the PMC group.The periodontal status of deciduous teeth in PMC group may be stable with increased age.

Imbalance of calcium homeostasis and abnormal autophagy are important pathogenesis mechanisms for neurodegenerative diseases, as PD, AD, and amyotrophic lateral sclerosis (ALS); and correlation is noted between imbalance of calcium homeostasis and abnormal autophagy. A number of studies have reported that different calcium storage compartments of cells can affect autophagy via calcium channels or Ca 2+-related signal proteins, such as cytoplasm calcium release-activated calcium modulator 1 (Orai1) and transient receptor potential canonical channel (TRPC), endoplasmic reticulum calcium channel inositol 1,4,5-triphosphate receptor (IP3R), mitochondrial calcium uniporter (MCU) related to Ca 2+ uptake, lysosomal calcium channel transient receptor potential channel mucolipin 1(TRPML1) and two-pore channels, cytoplasmic Ca 2+/calmodulin-dependent kinase kinase β (CaMKKβ)/AMP-activated protein kinase(AMPK) pathway. This review summarizes the research progress on autophagy regulated by Ca 2+ in intracellular calcium storage compartments and cytoplasm in neurodegenerative diseases, with a view to further understand the pathogenesis of these diseases.

Parkinson's disease is the second most common neurodegeneration, and its pathogenesis is related to mitochondrial dysfunction, oxidative stress and calcium homeostasis imbalance. In recent years, the relationship between Parkinson's disease and Ca 2+ has become a research hotspot. Calcium homeostasis disorders can lead to Parkinson's disease in different ways. The level of intracellular calcium ion depends on store-operated calcium entry (SOCE), calcium release-activated calcium modulator1 (Orai1), stromal interaction molecule 1 (STIM1) and transient receptor potential channel 1 (TRPC1) can form a functional complex to regulate it. PD neurotoxins can selectively damage dopaminergic neurons by reducing the function of Orai1-STIM1-TRPC1 complex and damaging SOCE and its downstream signal pathways. And the complex may affect the development of Parkinson's disease by acting on microglia and endoplasmic reticulum stress, and then regulate neuroinflammation and autophagy. Therefore, restoring the expression and function of Orai1-STIM1-TRPC1 function complex and maintaining calcium homeostasis may be the therapeutic targets of Parkinson's disease.

Objective:To understand the agglutination characteristics of different subtypes of avian influenza viruses, we selected erythrocytes from different sources to find suitable erythrocytes for influenza environmental sample detection.Methods:Different subtypes of avian influenza viruses, which were isolated from environmental sample between 2009 and 2016 in China, were selected to do hemagglutination assay using 5 animal erythrocytes (chicken, turkey, guinea pig, horse, and sheep). Flow cytometry was used to detect expression level and type of sialic acid receptors of different erythrocytes, and the characteristics of the receptor binding domain (RBD) of the viral hemagglutinin protein were analyzed by amino acid sequence.Results:In this study, a total of 28 strains of avian influenza virus including 14 subtypes were detected. The result showed that all viruses could agglutinate with turkey and guinea pig erythrocytes and the rest three erythrocytes were unable to produce agglutination with some viruses; among them, one H9N2 virus (A/environment/Anhui/43762/2015) did not agglutinate with chicken erythrocytes, one H1N1 virus (A/environment/Shandong/76972/2014) and two H9N2 viruses (A/environment/Chongqing/79449/2014 and A/environment/Anhui/43762/2015) did not agglutinate with horse erythrocytes, two viruses of H9N2 (A/environment/Chongqing/79449/2014 and A/environment/Anhui/43762/2015) and two viruses of H13N8 (A/environment/Qinghai Lake/166/2012 and A/environment/Qinghai Lake/13/2012) did not agglutinate with sheep erythrocytes. The result of flow cytometry showed that two sialic acid receptors, α-2, 3 and α-2, 6, were detected on the surface of erythrocytes of turkey, chicken and guinea pig, but the expression ratios of the two receptors were different. Only the expression of α-2, 3 sialic acid receptors was detected in horse and sheep erythrocytes. Sequence analysis suggested that amino acid substitution in key regions of viral hemagglutinin protein RBD may be an important factor affecting the binding properties of different erythrocytes.Conclusions:Our result suggested that turkey and guinea pig erythrocytes are the most sensitive in the hemagglutination test. Receptor expression and type of erythrocytes from different sources can significantly affect the agglutination reaction of different subtypes of avian influenza virus, and the amino acid changes in key regions of RBD can also affect the result of agglutination reaction.

Objective To explore the in vivo killing effects of nanosecond pulsed electric fields on mouse breast cancer in tumor bearing BALB/c mice. Methods Twenty four BALB/c mice models with subcutaneous EMT-6 breast cancer were prepared and divided into experimental group and control group (n=12). In experimental group, the mice were treated by the pulsed electric fields with peak voltage of 700 V/cm, rise times of 57 ns, durations of 70μs and duty ratio of 50%on the tumor tissue with two parallel electrodes under anaesthesia. One hundred pulses were given and the energy was just 9.75 J with effective action period of 7 ms. Tumor volume, animal weight and histopathologic changes after 1, 3, 5 and 7 d were observed after irreversible electroporation. Results The tumor volume in experimental group increased more slowly than that in control group, especially at the 1-3 d after treatment with a standstill. Histopathological examination results showed that the tumor tissue had obvious coagulation necrosis and tissue edema after electrical stimulation treatment, and mass vacuole like structure appeared in tumor tissue from the third day after treatment and vascular injury occurred at the early stage. Conclusions In the given field conditions, steep pulsed electric field has inhibitory effect on tumor growth. In order to achieve more ideal tumor therapy effect, further studies on steep pulse dose are needed.

OBJECTIVETo summarize the clinical features, imaging characteristics, diagnosis and treatment of a case with central nervous system infection caused by Exophiala dermatitidis, as well as to review the related literature.

METHODAssociated literature and clinical data of an 8-year-old boy who was diagnosed as central nervous system infection caused by Exophiala dermatitidis in Beijing Children's Hospital Affiliated to Capital Medical University and hospitalized twice from 2012 to 2014 were analyzed retrospectively.

RESULTThe boy was 8 years old with the chief complaint of dizziness for 2 months, intermittent fever for 1 month accompanied with spasm twice. He was diagnosed as bile ducts space-occupying lesions 2 years ago, when the pathological diagnosis was fungal infection. The boy was treated with irregular anti-fungal therapy. Then the boy developed nervous symptoms, impaired consciousness and abnormal physical activity that developed gradually. After hospitalization the cerebral MRI of the boy showed space-occupying lesions accompanied with edema of surrounding area. Filamentous fungi was found by brain biopsy, which was culture positive for Exophiala dermatitidis. After diagnosis the boy was treated with amphotericin B (AMB), voriconazole and 5-Fu, as well as symptomatic treatment. The state of the boy was improved gradually. Two months later, the boy could communicate with others normally and move personally. The lesions and edema seen on the MRI was decreased moderately. Accordingly, the boy was treated with oral voriconazole maintenance treatment for about 1 year and 4 months after discharge. During this period, the state of him was stable without symptoms. The lesions shown by MRI did not disappear but decreased on regular examination. However, recently the disease of the boy progressed again, with dizziness, neck pain, headache and progressive nervous symptoms (intermittent spasm, inability to cough, and impaired consciousness). The boy died at last, even with the active treatment at the second hospitalization. Exophiala dermatitidis was culture-positive again in his CSF, and was confirmed by PCR successfully.

CONCLUSIONThe central nervous system infection caused by Exophiala dermatitidis is rare. Clinical features of this disease were similar to those of other fungal CNS infection, cerebral MRI of which could show the similar lumpy lesions. Diagnosis of the disease should be based on pathology and culture.

Amphotericin B ; administration & dosage ; Antifungal Agents ; administration & dosage ; Brain ; diagnostic imaging ; microbiology ; pathology ; Central Nervous System Infections ; diagnosis ; drug therapy ; microbiology ; Cerebrospinal Fluid ; microbiology ; Child ; Drug Therapy, Combination ; Exophiala ; isolation & purification ; Fatal Outcome ; Fluorouracil ; administration & dosage ; Humans ; Magnetic Resonance Imaging ; Male ; Mycoses ; diagnosis ; drug therapy ; microbiology ; Radiography ; Voriconazole ; administration & dosage

Objective To evaluate the role of serum CA125 level in diagnosing the epithelial ovarian tumor.Methods Serum CA125 level of seventy-two patients who were operated for epithelial ovarian tumor between Apr 2005 and Jun 2007 in PUMC hospital were recruited and analyzed retrospectively.Using microparticle enzyme immunoassay(MEIA) to determine the serum CA125 level,and evaluate the serum CA125 level in diagnosing epithelial ovarian cancer.Results The CA125 was higher than 35?/ml in 35/39 ovarian serous cystadenocarcinoma cases with 89.7% positive rate,CA125 was higher than 35?/ml in 9/12 ovarian borderline serous cystadenoma with 75% positive rate,and CA125 was higher than 35?/ml in 4/21 ovarian serous cystadenoma with 19% positive rate.Conclusion The serum CA125 level before operation can predict benign epithelial tumor or epithelial ovarian cancer.