Objective:To summarize the clinical and genetic characteristics of pseudoachondroplasia and multiple epiphyseal dysplasia caused by COMP gene variants in pediatric patients.Methods:This retrospective study concluded 15 pediatric patients with COMP-related pseudoachondroplasia and multiple epiphyseal dysplasia at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine from July 2013 to August 2024. This paper analyzed clinical manifestations, laboratory findings and genetic testing.Results:This cohort comprised 15 pediatric patients (8 males and 7 females) with a diagnostic age of 5.3 (1.8,9.3) years. The major clinical presentations included abnormal gait (15/15), brachydactyly (11/15), genu varum (12/15), irregular metaphyseal changes (14/14) and epiphyseal dysplasia (14/14). Genetic analysis revealed 13 cases of pseudoachondroplasia and 2 multiple epiphyseal dysplasias cases associated with COMP gene variants. Fifteen variants were identified (8 pathogenic and 7 likely pathogenic), including 2 novel variants (c.1223A>G, c.1378G>C). Thirteen of these patients had variations clustered in exons 8-14 encoding the calmodulin-like domains, with c.1414_1419dupGACGAC emerging as a hotspot variant.Conclusions:COMP-related pseudoachondroplasia and multiple epiphyseal dysplasia predominantly manifest with gait abnormalities and skeletal deformities. COMP gene pathogenic variations were mainly located in calmodulin-like domains.

Objective:To summarize the clinical and genetic characteristics of pseudoachondroplasia and multiple epiphyseal dysplasia caused by COMP gene variants in pediatric patients.Methods:This retrospective study concluded 15 pediatric patients with COMP-related pseudoachondroplasia and multiple epiphyseal dysplasia at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine from July 2013 to August 2024. This paper analyzed clinical manifestations, laboratory findings and genetic testing.Results:This cohort comprised 15 pediatric patients (8 males and 7 females) with a diagnostic age of 5.3 (1.8,9.3) years. The major clinical presentations included abnormal gait (15/15), brachydactyly (11/15), genu varum (12/15), irregular metaphyseal changes (14/14) and epiphyseal dysplasia (14/14). Genetic analysis revealed 13 cases of pseudoachondroplasia and 2 multiple epiphyseal dysplasias cases associated with COMP gene variants. Fifteen variants were identified (8 pathogenic and 7 likely pathogenic), including 2 novel variants (c.1223A>G, c.1378G>C). Thirteen of these patients had variations clustered in exons 8-14 encoding the calmodulin-like domains, with c.1414_1419dupGACGAC emerging as a hotspot variant.Conclusions:COMP-related pseudoachondroplasia and multiple epiphyseal dysplasia predominantly manifest with gait abnormalities and skeletal deformities. COMP gene pathogenic variations were mainly located in calmodulin-like domains.

Objective To regard the implication of viruses particularly herpes in pemphigus vulgaris,and assess and compare the level of immunoglobulin G (IgG) antibodies against herpes simplex virus types 1 and 2 (HSV1 and HSV2),cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients with pemphigus vulgarisand healthy people.Methods In this study,23 patients with pemphigus vulgaris and 26 healthy individuals comprised the experimental and control groups,respectively.Serum samples were taken from both groups;the levels of IgG antibodies against HSV1,HSV2,CMV and EBV were measured using ELISA.Results Immunoglobulin G titer was higher for all four viruses in the patient group in comparison to the control group.This difference was significant for anti-EBV,anti-CMV and anti-HSV2 (t=2.16,P＜0.05;t =4.76,P＜ 0.01;t=3.75,P＜0.01),respectively,but not significant for anti-HSV1 (t=0.52,P＞0.05).Conclusion Viruses including EBV,CMV,and HSV2 probably play a role in the pathogenesis of pemphigus in addition to the effects of genetics,toxins and other predisposing factors.In this study,no statistically significant relationship was observed between HSV1 and pemphigus vulgaris.More studies must be done in this regard.

Objective This study was performed to investigate the levels of HSP70 in tissue in pemphigus as a possible new theoretical basis for further elucidate the pathogenesis of pemphigus.Methods The expression of HSP70 in 62 patients with pemphigus was determined by immunohistochemistry,and the normal skin was taken as control.Results The results showed that the positive cells of HSP70＞75 ％ in the blisters of pemphigus vulgaris and the positive cells of HSP70＞50％ in the inflammatory cells near the blisters,and the expression of HSP70 was significantly higher than that in normal skin,which was statistically significant(Z=5.42,4.73,P＜0.01).Conclusion The abnormal expression of HSP70 in inflammatory cells and psoriasis of pemphigus patients showed that HSP70 is involved in the pemphigus.

Objective To determine the intervention of mycophenolate mofetil (MMF) in glial scar formation and learning and memory function in a rat model of diffuse axonal injury (DAI).Methods Ninety-six SD rats were randomly divided into sham group, normal saline (NS) group and mycophenolate mofetil (MMF) group according to the random number table, with 32 rats per group.Immunohistochemistry was used to detect activated microglia cells, activated astrocytes and chondroitin sulphate proteoglycanns (CSPGs) in the hippocampus.Inage-Pro Plus software was used to quantitatively assess the changes of activated microglia cells, activated astrocytes and CSPGs.Morris water maze was applied for testing rat learning and memory function.Integrated absorbance (IA) of major constituents (microglia, astrosyte, chondroitin sulphate proteoglycan) of the glial scar was determined and analyzed for the correlation with the parameters of MWM.Results At 7, 14 and 28 days after injury, MMF group showed decreased IA of activated microglia in the hippocampus compared to sham and NS groups (P ＜ 0.05).At 7-11 days after injury, percent distance and percent time in the target quadrant of Morris water maze did not differ significantly among the three groups and were not related to the IA of glial scar.At 28-32 days after injury, percent distance and percent time in the target quadrant of Morris water maze lowered significantly in MMF group.At 28 days after injury, IA of the glial scar had a positive correlation with mean speed and mean escape latency, but negative correlation with percent distance and time in the target quadrant that measured in Morris water maze at 28-32 days after injury.Conclusion MMF significantly attenuates glial scar formation into the hippocampus and improves learning and memory function in rats during the recovery stage when administered in the early stage after DAI.

Objective To characterize the inheritance of erythropoietic protoporphyria (EPP) by detecting the mutations of ferroehelatase (FECH) gene in a Chinese family with EPP. Methods Peripheral blood samples were obtained from 4 patients and 3 unaffected individuals in a family with EPP, as well as from 50 unrelated healthy human controls. PCR was performed to amplify all the 11 exons and flanking sequence of FECH gene followed by direct sequencing. Results A splicing mutation,I.e., IVS3+1G→A, was identified in the proband as well as his symptomatic sister, cousin, grandfather and asymptomatic mother, but not in his asymptomatic father, grandmother, or unrelated healthy controls. The genotypes IVS1-23 T/C and IVS3-48 C/T were noted in the proband, his father, sister, cousin and grandfather, but absent in his mother or grandmother who carried IVS1-23 C/C and IVS3-48 T/T genotypes. Conclusions A novel splicing mutation is found in the FECH gene in a Chinese EPP family, which, together with two lowly expressed alleles IVS1-23T and IVS3-48C, is likely to be responsible for the clinical phenotype of EPP in this family.

OBJECTIVETo clone differentially expressed cDNA sequences involved in malignant transformation induced by benzo(a)pyrene metabolite dihydroxyepoxy benzo pyrene (BPDE).

METHODThe malignant transformation of human bronchial epithelial cell line 16HBE induced by BPDE in vitro was used as a model for comparing gene expression between the transformed cells and controls. cDNA representational difference analysis (cDNA-RDA) was performed to isolate differentially expressed cDNA fragment in transformed cells. The cDNA fragments were ligated to pGEM-T vector and transformed into JM109 bacteria. The plasmid DNA were sequenced and compared with data in GenBank by BLASTN.

RESULTSFive cDNA sequences were found to be novel ones and were registered in dbest database, which assigned accession numbers in GenBank are BG354691, BG354692, BG354693, BG354694 and BG354695, respectively. Eight of the remaining cDNA sequences showed sequence homology to those previously reported such as ribosomal protein S23, MLN137, ACTN4, transforming growth factor and G protein gene.

CONCLUSIONSThese 13 genes may be involved in BPDE-induced malignant transformation, but their biological characteristics and functions are left to further studies.

Benzopyrenes ; metabolism ; pharmacology ; Carcinogens ; pharmacology ; Cell Transformation, Neoplastic ; chemically induced ; genetics ; Cells, Cultured ; Cloning, Molecular ; DNA, Complementary ; analysis ; drug effects ; DNA, Neoplasm ; analysis ; Gene Expression ; drug effects ; Humans

Objective To explore the relationship between HLA sensitization and crossmatch and to assess its clinical value. Methods The subjects were divided into 3 groups :high sensitization group (PRA≥40％),low sensitization group (40％＞PRA≥10％) and non-sensitization group (PRA＜10％) according to the HLA antibody level detected by ELISA. The results of crossmatch were compared among the 3 groups. Results There was significant difference among the ratio of positive crossmatch in high sensitization group (39.4％),low sensitization group (10.5％)and non-sensitization group (2. 6％). Conclusion The sensitization level is positively correlated with the result of crossmatch. The improvement of matching precision can be made by using both of techniques mentioned above.

Objective To investigate the gene mutation in a pedigree with pachyonychia congenita typeⅡ(PC-Ⅱ)and to explore the relationship between the mutation and clinical manifestations.Methods The exon1of K17gene of genomic DNA from peripheral blood was amplified by PCR,and the PCR products were sequenced by automated sequencing system.Results In all the3patients of the pedigree with PC-Ⅱ(2patients presented as delayed-onset PC at4and15-16years of age respectively),the codon92(AAT)of K17gene was mutated as AGT,which caused missense mutation(N92S)in the1A domain of keratin17,but the2unaffected members of the pedigree and50unrelated controls had no such mutation.Conclusions Mutation of N92S in the1A domain of keratin17exists in this pedigree with PC-Ⅱ.Our results indicate that mutation in the1A domain of keratin17can present as delayed-onset pachyonychia congenita.Therefore,the site and type of keratin mutation are not the sole determinant of the age of onset for PC-Ⅱ,there may be other genetic and/or environmental factors that determine the age of onset of PC-Ⅱ.