Objective:To investigate the phenotypes of Rubinstein-Taybi syndrome (RSTS) caused by variants in the CREBBP or EP300 gene, and the correlation between genotype and phenotype.Methods:This case series study was performed on pediatric patients who were referred to the Children′s Hospital of Capital Institute of Pediatrics between January 2013 and July 2022. Both point variant and copy number deletion in CREBBP or EP300 gene were detected by whole exome sequencing, chromosomal microarray analysis, or copy number variation sequencing (CNV-seq). The variant categories were summarized and phenotype numbers were re-visited for RSTS patients. Based on variant types, the patients were divided into different groups (point variant or copy number deletion, EP300 or CREBBP point variant, and loss of function or missense variant). Phenotype counts between different groups were compared using the rank-sum test of two independent samples.Results:A total of 21 RSTS patients were recruited, including 12 males and 9 females, with ages ranging from 1 month to 14 years and 2 months. Among them, 67% (14/21) had point variants, and 33% (7/21) had copy number deletions. Out of these, 20 variants (95%) were de novo. Among 20 patients finishing phenotype count during re-visit, 95% (19/20) of the patients exhibited developmental delays before the age of 2 years. Additionally, 80% (16/20) of the patients had distinctive facial features. Considering phenotype count, no statistically significant difference was found between point variant (14 cases) and copy number deletion (6 cases) (5.0 (3.0, 7.0) vs. 5.0 (2.5, 5.3), Z=0.75, P=0.452), CREBBP (10 cases) and EP300 gene (4 cases) point variant (5.0 (3.8, 7.0) vs. 4.0 (2.0, 6.0), Z=1.14, P=0.253), and loss of function (9 cases) and missense (5 cases) variant (6.0 (4.5, 7.0) vs. 3.0 (2.5, 5.5), Z=1.54, P=0.121). Conclusions:Patients with RSTS primarily exhibit developmental delays in early childhood. Specific facial features serve as suggested signs of genetic testing. However, no significant genotype-phenotype correlation is found.

Objective To determine the infectiousness of the respiratory syncytial virus(RSV)18537 strain of subtype B in different host cell lines and evaluate its pathogenicity and pathological damage in various animal models.Methods The cytopathic features,viral plaque morphology,viral protein expression,and in vitro proliferation efficiency were assessed to determine the basic biological characteristics of such infections.Nasal drops were used to infect 10-month-old BALB/c mice and 6-week-old cotton mice.The viral load in lung tissue after infection was detected,and the pathological injury was analyzed to assess the pathogenicity.Results The RSV 18537 strain of subtype B strain induced polynuclear fusion in Hep-2 cells,and typical viral plaques were formed in BHK-21 cells.In addition,viral proteins could be detected in Hep-2 and A549 cells.In BALB/c and cotton mice infected with nasal drops,viral nucleic acids were detectable in lung tissue on day 5 post-infection.This dose caused mild thickening of alveolar walls with scattered lymphocytes and neutrophil infiltration.Conclusion The RSV 18537 strain of subtype B can be effectively proliferated in Hep-2 and A549 cells while infecting BALB/c mice and cotton mice,resulting in pathological injury to lung tissue.The 18537 strain of RSV subtype B is less contagious than the A2 strain of subtype A both in cells and animals.

Objective: Balb/c mice infected with respiratory syncytial virus(RSV) were used to investigate the metabolic changes in cecal luminal content. Methods: A total of 13 female Balb/c mice were randomly divided into Case group(n=7) and control(Ctrl) group(n=6). Animals in Case group were infected with RSV by using intranasal method, while mice in Ctrl group were treated with DMEM medium. Mice were anesthetized with intraperitoneal administration of 10% chloral hydrate and the cecal luminal contents were harvested under sterile conditions. Metabolite concentrations were measured by UPLC-QTOF/MS system. Univariate and multivariate statistical analysis were used to identify differential metabolites between Case and Ctrl groups. Results: The overall base peak chromatogram between Case and Ctrl groups had a clear disparity, and PCA and OPLS-DA analysis showed obviously discrepancy based overall metabolomic profile. L-serine, 2-ketobutyric acid, Oleic acid and Chenodeoxycholic acid glycine conjugate were enriched in Case group, whereas L-methionine, L-tyrosine and Nicotinic acid were depleted. Pathway analysis showed lysine degradation, Cysteine and methionine metabolism were enriched. Conclusion Lung injury induced by RSV infection may cause the endogenous metabolism disorder of cecal contents.

Stargardt disease (STGD) is one of the most prevalent inherited macular dystrophy, and most often occurs in child or adolescence. Irreversible vision loss is observed in almost all cases. Type 1 (STGD1) is one of the most common type. It is an autosomal recessive condition, caused by mutations in the Abca4 gene. In recent years, encouraging progress has been made in the treatment of STGD1. C20-D3-retinyl acetate (ALK- 001), fenretinide and ICR-14967 (A1120) as visual cycle modulators, StarGen as gene supplementation therapies, and the stem cell transplantation of human embryonic stem cell-derived retinal pigment epithelium cells are the most promising therapies. With the development of studies and clinical trials, the clinical application of various treatments of STGD1 are expected in the near feature, which are expected to save the vision of most patients.

Objective:To summarize the experiences in the construction of Clinical Research Unite (CRU) at a hospital level, provide reference for CRU construction in the Chinese hospitals.Methods:The CRU construction should take clinical research project management as working priority, strengthen clinical research team building, improve process management, as well as improve project performance and output.Results:During the CRU construction period, the number and level of clinical research projects have been improved in various disciplines. The sample database and disease specific data have been accumulated. The CRU mode helps the high-quality development of clinical researches in hospital.Conclusions:The way our hospital take in the construction of CRU was a good example, and it may truly improve the quality and capacity of clinical researches.

Objective To investigate whether the population pharmacokinetics (PPK)models can optimize the initial dosage of individualized Valproic acid (VPA)in children with epilepsy. Methods The epileptic children without taking VPA previously were recruited from October 2015 to May 2017 at the Department of Pediatrics,Peking University First Hospital,and they were divided into the PPK model group and the traditional empirical method group by randomized method. The initial VPA dosages for the PPK model group were calculated by PPK model,whereas those of the traditional empirical method group were dosed at 20-25 mg/(kg·d)regularly. The steady-state serum trough concentrations of VPA were extracted,and then the number and percentage of the patients whose serum trough concen-trations of VPA were 50-100 mg/L in the 2 groups were analyzed and compared with prospectively randomized me-thod. Results Totally 65 epileptic children were recruited and they were randomly divided into the traditional empirical method group (32 cases)and the PPK model group (33 cases). Twenty-seven children in the traditional empirical method group were observed,and 12 children had local epilepsy attack and 15 had generalized seizures;whereas among 29 cases in the PPK model group,there were 12 local attack of epilepsy and 17 had generalized seizures. VPA add-on therapy was administrated in 9 cases and 15 cases in the traditional empirical method group and the PPK model group, respectively. There were 5 cases,21 cases and 1 case with VPA serum concentrations of ＜50 mg/L,50-100 mg/L and＞100 mg/L in the traditional empirical group;while there were 9 cases,20 cases and 0 case in the PPK model group. The VPA serum concentrations of 21 cases (77. 8%,21/27 cases)in the traditional empirical method group and 20 ca-ses (69. 0%,20/29 cases)in the PPK model group were 50-100 mg/L,respectively,and the difference was not sta-tistically significant(P＞0. 05). Conclusion Although the study doesn't suggest that the established PPK model of VPA in Chinese epileptic children is superior to the traditional empirical method,the PPK model might be potentially valuable for optimized individualized dosage adjustment for those with serum trough concentrations not in the reasonable range by the traditional empirical method and with clinical seizure or brain firing activities.

Objective To explore the value of cMRI and MRS in diagnosis and differential diagnosis of single brain metastases and localized high grade gliomas.Methods The cMRI (T1WI,T2WI and contrast-enhanced MRI)and MRS data of 23 cases with single brain metastases and in 28 cases with high grade gliomas confirmed by pathology were collected and analyzed retrospectively.Results cMRI:①There were no significant differences of T1WI,T2WI and constrast-enhanced MRI between single brain metastases and high-grade gliomas.②Enhanced images of single brain metastases and localized high-grade gliomas showed that there was a significant difference in the peritumoral edema area:the nodular or ring enhancement were found in single brain metastases,the outer outline of ring enhancement was smooth,and there was no enhancement at the peripheral edema area;Irregular patchy or ring enhancement were found in localized high-grade glioma tumor,both of the outer and inner edges of the ring enhancement rough,a little patchy enhancement at the peripheral edema area were found in 1 6 patients,and there was no enhancement of the edema area in the other 1 2 patients.MRS:①There were no significant differences of the tumor parenchyma in the peaks of NAA,Cr,Cho and central Lac between single brain metastases and localized high grade gliomas.②A significant difference of the peripheral edema area were observed between them.The peaks of NAA,Cr,Cho at the edema area in all single brain metastases patients were normal.But in all high-grade glioma patients,the NAA and Cr peaks were decreased,while the Cho peaks were increased.Conclusion The morphological manifestations of single brain metastases are similar to localized high grade gliomas.An obvious difference of cMRI and MRS lines exists in the peritumoral edema area between them,which could be used for differential diagnosis.

Retinitis pigmentosa (RP) is a group of hereditary blinding fundus diseases caused by abnormalities in photoreceptors of the retina.RP is highly heterogeneous in hereditary and cdinical phenotypes.It can be divided into simple type RP and syndrome type RP.The main inheritance patterns are autosomal dominant,autosomal recessive inheritance and X-linked inheritance.With the popularization and clinical application of gene sequencing technology,more and more disease-causing genes have been discovered,and these genes are mainly expressed in photoreceptor cells and retinal pigment epithelial cell.ln-depth understanding of RP pathogenic genes not only provides a theoretical basis for RP diagnosis and genetic counseling,but also provides guidance for RP gene therapy.

Objective To investigate serum total IgE levels of healthy population in two hospitals in Yantai and Weihai areas,to investigate the influencing factors of the levels of serum total IgE,which can provide information for the clinical diagnosis of allergic diseases.Methods The total serum IgE level was measured with chemiluminescence method in 1 200 cases of healthy people and 600 cases of smoking group in different age groups.Results The total IgE level of ≤6 years was (28.53±20.71)IU/mL,7-12 years was (29.74±25.94)IU/mL,13-18 years was (32±22.32)IU/mL,19-44 years was (45.2±36.27)IU/mL,45-60 years was (35.47±27.23)IU/mL,>60 years was (31.2±25.03)IU/mL.There was no effect of serum total IgE in different age groups:≤6 years,7-12 years,13-18 years,45-60 years,>60 years(t=0.610,1.508,0.777,0.160,1.518,all P>0.05),19-44 years was significantly different from other age groups(t=0.075,P<0.01).There was no gender difference of serum total IgE in different age groups (P>0.05).The total IgE level of the smoking group:19-44 years was (55.22±39.16)IU/mL,45-60 years was (42.63±28.46)IU/mL,>60 years was (39.32±26.73)IU/mL.The level of serum IgE in the smoking group was significantly higher than that in the same age group (t=0.142,0.174,0.235,all P<0.05).Conclusion No significant difference existed in healthy people of serum total IgE levels from birth to adulthood.However,the total IgE level rose when reached to 19-44 years,which then slightly declined as the growth of the age.There was no significant difference between male and female of the IgE levels in different age groups.But after the age of 19,smoking can lead to the increase of the total IgE level.

OBJECTIVEDesign a convenient and stable eye refractometer based on the theory of blur circle.

METHODSAnalyze the retinal blur circle in both Emsly reduced eye model and Liou & Brennan 1997 eye model by ZEMAX. Design the coefficients including PD (pupil diameter) and NO' (length between node point and fovea) with the purpose of improving the accuracy. At last, compare the clinical optometry data from this refractor with the data obtained from optometry hospital in Wenzhou.

RESULTSThe blur circle diameters are nearly the same in both reduced eye model and the Liou & Brennan 1997 eye model. With the PD = 4 mm and NO' = 20 mm, the refractor shows a fine accuracy in optometry. The paired t test shows that the myopia group and the astigmatism axial direction group have no statistical difference between the data from the blur circle refractor and the hospital (P > 0.05), while the astigmatism degree group has the result of P = 0.41 which may be caused by the poor cooperation of pediatric patients. 80% of the astigmatism degree data differ from the data from the hospital in less than 0.75D.

CONCLUSIONThe blur circle refractor, with the features of convenience and fine accuracy, is promised to be a new style of refractometer in the future.

Astigmatism ; Equipment Design ; Fovea Centralis ; Humans ; Models, Statistical ; Myopia ; Ophthalmoscopes ; Ophthalmoscopy ; Refraction, Ocular ; Visual Acuity