Fabry disease, a rare genetic disorder affecting multiple organs, has understudied correlations among enzyme activity, genotype, and clinical manifestations in patients of different sexes with classical and late-onset phenotypes. In this study, clinical data, α-Gal A activity, and GLA gene test results of 311 patients, who were categorized by classical and late-onset phenotypes, ⩽5% and > 5% of the normal mean value of enzyme activity, and truncated and nontruncated mutation groups, were collected. The common clinical manifestations of Fabry disease included acroparesthesia, hypohidrosis/anhidrosis, neuropsychiatric system, and renal and cardiovascular involvement. Multiorgan involvement was higher in males and classical phenotype patients. In both sexes, classical patients commonly presented with acroparesthesia and multiorgan involvement, whereas late-onset patients showed renal, neuropsychiatric, and cardiovascular involvement. Male and classical patients had lower enzyme activity than female and late-onset patients, respectively. Classical males with enzyme activity of ⩽5% of the normal mean level showed higher multiorgan involvement frequency than those with enzyme activity of > 5%, whereas no significant difference was observed among females. Ninety-five gene mutation sites were detected, with significant phenotype heterogeneity in patients with the same mutation. No significant difference in enzyme activity or clinical manifestations was observed between truncated and nontruncated mutations. Overall, male patients with Fabry disease, regardless of classical or late-onset phenotype, have a higher frequency of multiple-organ involvement and lower α-Gal A activity than female patients. α-Gal A activity was closely correlated with clinical symptoms in males but weakly correlated with clinical manifestations in females. The clinical manifestations of patients with the same mutation are heterogeneous, and the correlation between gene mutation and enzyme activity or clinical manifestation is weak.
Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Age of Onset ; alpha-Galactosidase/metabolism* ; China ; Fabry Disease/enzymology* ; Genotype ; Mutation ; Phenotype ; Sex Factors ; East Asian People/genetics*

Objective·To investigate the regulatory effects and underlying mechanisms of mouse mandibular osteoblasts on B cell differentiation and development.Methods·Single-cell suspensions from mouse mandibular bone were prepared using an optimized enzymatic digestion method and induced to differentiate into osteoblasts in vitro.Osteogenic potential was validated by real-time quantitative PCR(RT-qPCR),alkaline phosphatase(ALP)staining,and alizarin red S(ARS)staining.The spatial localization relationship between osteoblasts and B cells in mandibular tissues was examined via immunofluorescence staining.High-purity hematopoietic progenitor cells were isolated using fluorescence-activated cell sorting.A Transwell co-culture system was established to assess the regulatory effects of different osteoblast concentrations(5×104,2.5×105,and 5×105 cells/well)on B cell differentiation(5×104 cells/well).Flow cytometry and RT-qPCR were employed to evaluate B cell viability and differentiation.Additionally,RT-qPCR was used to analyze the expression of osteoblast-secreted factors associated with B cell development during osteogenic differentiation.Results·Mandibular osteoblasts exhibited robust osteogenic potential,as confirmed by ALP/ARS staining and high expression of osteogenic markers(Runx2,Osx,Ocn,and Alp)via RT-qPCR.Immunofluorescence revealed close spatial proximity between osteoblasts and B cells in mandibular tissues.In the co-culture system,osteoblasts promoted B cell differentiation in a concentration-dependent manner.RT-qPCR and immunofluorescence demonstrated that osteoblasts significantly upregulated key genes involved in B cell development(Ebf1,Rag1,Il7r,and Pax5;all P<0.001).Furthermore,osteoblast-derived factors(Il7,Baff,and Flt3l)were markedly elevated during osteogenic differentiation(all P<0.05).Conclusion·Mandibular osteoblasts enhance B cell differentiation and development in a concentration-dependent manner,likely through secreting growth factors that upregulate critical B cell differentiation genes.

Objective·To investigate the regulatory effects and underlying mechanisms of mouse mandibular osteoblasts on B cell differentiation and development.Methods·Single-cell suspensions from mouse mandibular bone were prepared using an optimized enzymatic digestion method and induced to differentiate into osteoblasts in vitro.Osteogenic potential was validated by real-time quantitative PCR(RT-qPCR),alkaline phosphatase(ALP)staining,and alizarin red S(ARS)staining.The spatial localization relationship between osteoblasts and B cells in mandibular tissues was examined via immunofluorescence staining.High-purity hematopoietic progenitor cells were isolated using fluorescence-activated cell sorting.A Transwell co-culture system was established to assess the regulatory effects of different osteoblast concentrations(5×104,2.5×105,and 5×105 cells/well)on B cell differentiation(5×104 cells/well).Flow cytometry and RT-qPCR were employed to evaluate B cell viability and differentiation.Additionally,RT-qPCR was used to analyze the expression of osteoblast-secreted factors associated with B cell development during osteogenic differentiation.Results·Mandibular osteoblasts exhibited robust osteogenic potential,as confirmed by ALP/ARS staining and high expression of osteogenic markers(Runx2,Osx,Ocn,and Alp)via RT-qPCR.Immunofluorescence revealed close spatial proximity between osteoblasts and B cells in mandibular tissues.In the co-culture system,osteoblasts promoted B cell differentiation in a concentration-dependent manner.RT-qPCR and immunofluorescence demonstrated that osteoblasts significantly upregulated key genes involved in B cell development(Ebf1,Rag1,Il7r,and Pax5;all P<0.001).Furthermore,osteoblast-derived factors(Il7,Baff,and Flt3l)were markedly elevated during osteogenic differentiation(all P<0.05).Conclusion·Mandibular osteoblasts enhance B cell differentiation and development in a concentration-dependent manner,likely through secreting growth factors that upregulate critical B cell differentiation genes.

OBJECTIVETo anatomically reconstruct the oculomotor nerve, trochlear nerve, and abducent nerve by skull base surgery.

METHODSSeventeen cranial nerves (three oculomotor nerves, eight trochlear nerves and six abducent nerves) were injured and anatomically reconstructed in thirteen skull base operations during a period from 1994 to 2000. Repair techniques included end-to-end neurosuture or fibrin glue adhesion, graft neurosuture or fibrin glue adhesion. The relationships between repair techniques and functional recovery and the related factors were analyzed.

RESULTSFunctional recovery began from 3 to 8 months after surgery. During a follow-up period of 4 months to 6 years, complete recovery of function was observed in 6 trochlear nerves (75%) and 4 abducent nerves (67%), while partial functional recovery was observed in the other cranial nerves including 2 trochlear nerves, 2 abducent nerves, and 3 oculomotor nerves.

CONCLUSIONSComplete or partial functional recovery could be expected after anatomical neurotization of an injured oculomotor, trochlear or abducent nerve. Our study demonstrated that, in terms of functional recovery, trochlear and abducent nerves are more responsive than oculomotor nerves, and that end-to-end reconstruction is more efficient than graft reconstruction. These results encourage us to perform reconstruction for a separated cranial nerve as often as possible during skull base surgery.

Abducens Nerve ; surgery ; Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; Nerve Regeneration ; Nerve Transfer ; methods ; Oculomotor Nerve ; surgery ; Oculomotor Nerve Injuries ; Skull Base Neoplasms ; surgery ; Trochlear Nerve ; surgery ; Trochlear Nerve Injuries