OBJECTIVE: To investigate the clinical and genetic characteristics of a Chinese pedigree affected with Neurodevelopmental disorder with absent language and variable seizures (NEDALVS) due to variant of WASF1 gene, and to review the literature on NEDALVS associated with WASF1 gene variants. METHODS: A 4-year-and-8-month-old boy with NEDALVS diagnosed at Linyi People's Hospital in July 2024 due to "discovering language development delay for more than 2 years" and his family members were selected as the study subjects. Clinical data of the family members were collected. Peripheral venous blood samples were collected from family members. Whole-exome sequencing (WES) was performed, and candidate variants were verified, by Sanger sequencing. Pathogenicity of candidate variant was classified according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG). Using the MUpro website, SWISS-MODEL, PyMOL, Clustal X, PolyPhen-2, and Mutation Taster software, bioinformatics analysis of protein three-dimensional structure modeling for gene mutations, cross-species conservation of mutant amino acids, and pathogenicity prediction of mutation sites. Relevant literature was retrieved from databases such as CNKI, Wanfang Data Knowledge Service Platform, and PubMed, and the clinical phenotypes and genotypes of patients with WASF1 gene mutations reported in the literature were summarized and analyzed. This study was approved by the Medical Ethics Committee of Linyi People's Hospital (Ethics No.: YX200303). RESULTS: The proband, a 4-year and 8-month-old male, mainly presented with delayed language and motor development, accompanied by autistic behaviors; the proband's younger brother was 2 years and 7 months old at the time of consultation, mainly presented with delayed language and motor development, accompanied by short stature; the proband's mother mainly presents with limited language expression and poor interpersonal interaction; the proband's maternal grandmother mainly presents with soliloquizing?behavior. The results of WES showed that the proband carried a heterozygous mutation c.214C>T (p.Arg72Cys) in the WASF1 gene, and this site has not been recorded in the database. Sanger sequencing confirmed that the proband's younger brother, mother, and maternal grandmother had harbored the same variant. Based on the guidelines from the ACMG, this variant was rated as likely pathogenic (PM2_Supporting+PP1+PP3+PP4). Through SWISS-MODEL homology modeling and PyMOL structure visualization analysis, it was further confirmed that this variant can lead to a decrease in protein stability. Amino acid sequence conservation analysis of the WASF1 protein using Clustal X software suggested that the c.214C>T (p.Arg72Cys) variant has caused replacement of a highly conserved amino acid. According to the results of PolyPhen-2 and Mutation Taster, the p.Arg72Cys variant was predicted to be a hazardous. By following the retrieval strategy set in this study, a total of 5 research articles regarding to patients with NEDALVS caused by WASF1 gene mutations were retrieved, which involved 15 patients. Combining the proband and their family members discovered in this study, there were a total of 19 NEDALVS patients. The main clinical features included: motor developmental delay (100%, 17/17), language/intellectual developmental delay (100%, 17/17), epilepsy (64.7%, 11/17), autistic behavior (76.5%, 13/17), hypotonia (70.6%, 12/17), abnormal electroencephalogram (64.7%, 11/17), and short stature (17.6%, 3/17). All 19 patients had heterozygous mutations, with 8 mutation sites. Missense mutations were the most common, accounting for 84.2% (16/19). CONCLUSION A pathogenic variant of the WASF1 gene was identified in a pedigree affected with NEDALVS. Discovery of the novel variant has, expanded the mutational spectrum of the WASF1 gene.
Child, Preschool ; Female ; Humans ; Infant ; Male ; China ; Exome Sequencing ; Mutation ; Neurodevelopmental Disorders/genetics* ; Pedigree ; Seizures/genetics* ; East Asian People/genetics*

OBJECTIVE: To investigate the clinical and genetic characteristics of a family with Vissers-Bodmer Syndrome (VIBOS) and to review the relevant literature on VIBOS caused by CNOT1 gene variants. METHODS: A child diagnosed with VIBOS due to "growth retardation for over 6 years" at the Linyi People's Hospital on March 1, 2024 and her family members were selected as the study subjects. Clinical data of the family were collected. Peripheral venous blood samples were collected from the family members. Whole-exome sequencing (WES) was performed on the proband's peripheral blood, and Sanger sequencing was used for verification of the candidate variant in the family. Pathogenicity of the candidate variant was classified according to the "Standards and Guidelines for the Interpretation of Sequence Variants" established by the American College of Medical Genetics and Genomics American College of Medical Genetics (ACMG). Bioinformatics analysis, including pathogenicity prediction using Mutation Taster, three-dimensional protein structure modeling using SWISS-MODEL, and functional impact assessment using PyMOL, was performed. Relevant literature on VIBOS patients due to variants of the CNOT1 gene was retrieved from databases such as CNKI, Wanfang Data, and PubMed. The clinical phenotypes and genotypes of the patients were summarized. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: YX200303). RESULTS: The proband, a 6-year-and-7-month-old female, presented with short stature, distinctive facial features (esotropia, hypertelorism, prominent nasolabial folds), webbed neck, clinodactyly, and intellectual disability. WES revealed that she has carried a heterozygous c.736delG (p.V246*) variant of the CNOT1 gene, which was unreported previously. The proband's father exhibited borderline intellectual function but no short stature or distinctive facial features. Sanger sequencing confirmed that he has carried the same heterozygous variant. According to the ACMG guidelines, this genetic variant was predicted as "likely pathogenic" (PVS1+PM2_Supporting). The c.736delG (p.V246*) variant was predicted to have a deleterious effect by Mutation Taster. Subsequent homology modeling using SWISS-MODEL, coupled with structural visualization and comparison using PyMOL, confirmed that it may cause premature termination of translation and produce a truncated protein. Literature search has retrieved five articles on VIBOS due to CNOT1 gene variants, which included 45 cases. Together with the proband and her father, the common clinical features among these 47 patients included distinctive facial features (83.0%, 39/47), speech delay (70.2%, 33/47), motor delay (70.2%, 33/47), intellectual disability (59.6%, 28/47), and short stature (48.9%, 23/47). In terms of the types of the variants, missense variants were the most common (47.4%, 18/38), followed by frameshift variants (21.0%, 8/38). The variant sites have mainly located in exons 7, 25, and 31. No significant genotype-phenotype correlation was noted. CONCLUSION The c.736delG (p.V246*) frameshift variant of the CNOT1 gene is likely the genetic etiology of VIBOS in this proband. The clinical manifestations of the proband were more severe than in her fathers, which suggested phenotypic variability associated with this variant. This study has provided new evidence for the understanding of the genetic basis of VIBOS.
Child ; Female ; Humans ; Male ; Exome Sequencing ; Intellectual Disability/genetics* ; Mutation ; Pedigree ; Transcription Factors/genetics* ; East Asian People/genetics*

Objective To investigate the effect of type 2 diabetes mellitus(T2DM)on the expression of human leukocyte antigen-DR(HLA-DR)on the peripheral blood monocytes in patients with sepsis.Methods From March 2021 to February 2022,65 cases of sepsis with T2DM(sepsis with T2DM group),67 cases of sepsis without T2DM(sepsis group),and 60 cases of T2DM patients(T2DM group)admitted to Beijing Chaoyang Hospital of Capital Medical University were selected as the research objects.A total of 45 healthy volunteers who underwent physical examination during the same period were enrolled as the healthy control group.Gender,age,past medical history,glycated hemoglobin(HbA1c),blood glucose at admission,white blood cell count(WBC),lymphocyte count(LYM),hypersensitivity C-reactive protein(hs-CRP)and major infection sites were collected,sequential organ failure assessment(SOFA)score was performed within 24 hours after admission.The levels of HLA-DR+CD14+ in peripheral blood were detected by flow cytometry,expressed as a percentage and mean fluorescence intensity(MFI).The patients were followed up for 28 days.The effect of T2DM on the prognosis of sepsis patients at 28 days was observed,and the difference of HLA-DR+CD14+ levels between the survivor group and the non-survivor group was compared.Results The percentage and MFI of HLA-DR+CD14+ expressions in T2DM group were significantly lower than those in the healthy control group[the percentage of HLA-DR+CD14+ expression:87.72%(76.18%,93.64%)vs.94.86%(92.91%,95.70%),HLA-DR+CD14+ MFI:10.80(8.45,14.45)vs.12.40(1.45,15.28)],the sepsis with T2DM group and sepsis group were further reduced than those in healthy control group and T2DM group[the percentage of HLA-DR+CD14+ expression:70.78%(42.22%,84.73%),68.95%(44.95%,87.00%)vs.94.86%(92.91%,95.70%),87.72%(76.18%,93.64%),MFI of HLA-DR+CD14+:5.50(3.81,9.20),5.29(3.35,9.59)vs.12.40(1.45,15.28),10.80(8.45,14.45),all P<0.05].There was no significant difference in the percentage and MFI of HLA-DR+CD14+ expressions,SOFA score,and 28-day mortality between sepsis group and sepsis with T2DM group(P>0.05).The age of the non-survivor group of sepsis patients with and without T2DM was significantly higher than that of the survivor group[years:sepsis group was 68(60,74)vs.61(52,69),sepsis with T2DM group was 66(64,73)vs.60(53,68),both P<0.05],and SOFA score was significantly higher than that of the survivor group[sepsis group:14(11,16)vs.8(5,11),sepsis with T2DM group:12(9,16)vs.8(6,11),both P<0.05],the percentage of HLA-DR+CD14+ and HLA-DR+CD14+ MFI in the non-survivor group were significantly lower than those in the survivor group[the percentage of HLA-DR+CD14+was 44.94%(28.01%,64.45%)vs.77.14%(47.41%,88.35%)in sepsis group and 40.68%(34.83%,66.64%)vs.73.46%(58.44%,85.31%)in sepsis with T2DM group,the MFI of HLA-DR+CD14+ was 3.92(2.30,5.44)vs.7.07(3.39,10.55)in sepsis group and 3.90(3.34,6.04)vs.6.81(4.41,9.32)in sepsis with T2DM group,all P<0.05].Correlation analysis showed that the percentage of HLA-DR+CD14+ in T2DM group,sepsis group,and sepsis with T2DM group was negatively correlated with hs-CRP(r values were-0.448,-0.628 and-0.457,all P<0.001),MFI was also negatively associated with hs-CRP(rvalues were-0.289,-0.540,-0.323,all P<0.05).The percentage of HLA-DR+CD14+ in sepsis group and sepsis with T2DM group was negatively correlated with SOFA score(r values were-0.520 and-0.558,all P<0.001),and MFI was also negatively correlated with SOFA score(r values were-0.327 and-0.482,all P<0.01).Conclusion The levels of HLA-DR+CD14+ decreased in both T2DM and sepsis patients,however,there was no further decrease in those patients with sepsis who also had T2DM.

Objective: To isolate and identify the undescribed compounds from the fruits of Cinnamomum migao and evaluate its nitric oxide inhibition potential. Methods: The chromatographic techniques of silica gel, Sephadex, and HPLC were used for isolation and purification of the compounds, while HR-ESI-MS, 1D NMR, 2D NMR, ECD, and X-ray diffraction techniques were used to characterize and confirm the isolated compounds. Moreover, the anti-inflammatory activity of the isolated compounds was carried out to check inhibitory potential against the production of nitric oxide with RAW264.7 cells stimulated by LPS. Results: Camganoid A (1), a novel sesquiterpene possessing an unprecedented skeleton, and camganoid B (2), containing a unique eight-membered sesquiterpene moiety with a new carbon skeleton, were isolated and identified from the fruits of C. migao. The absolute configurations of 1 and 2 were confirmed by single crystal X-ray diffraction and electronic circular dichroism (ECD) calculations. Among these compounds, compound 1 exhibited potent inhibitory activity against the production of nitric oxide with IC

Objective To verify the feasibility of applying hydrothermal synthesis for preparing oyster hydroxyapatite(HA) and to develop a preparation method of oyster HA porous material for bone repair.Methods Hydrothermal synthesis was applied for preparing oyster HA,and the reaction condition was 220 ℃ for 6 h.Then,the prepared oyster HA was used as the raw material for porous scaffold preparation by sponge-soaking and sintering,successively.The porosity and compressive strength of the scaffold were adjusted by controlling the soaking time and absorbed HA slurry of the sponges.Results Hydrothermal synthesis was an effective method for preparing oyster HA.When the volume of the sponge cube was 1 cm3,the material absorbed by one to three times sponge-soaking were 0.184 8 g,0.318 1 g and 0.426 1 g,respectively,the corresponding porosity were 91.5％,82.9％ and 78.5％,and the compressive strength were 1.06 MPa,3.99 MPa and 8.49 MPa.Conclusion The oyster shell powder can be effectively converted into HA under the hydrothermal reaction condition of 220 ℃ for 6 h.The preparation of HA porous bone repair material by sponge-soaking method can obtain ideal porosity and mechanical strength.However,in this preparation process,the number of sponge-soaking and the weight of the absorbed HA slurry should be exactly controlled in order to obtain desired properties.