OBJECTIVE: To investigate the results of preimplantation genetic testing for monogenic diseases (PGT-M) in a Chinese pedigree affected with Primary carnitine deficiency (PCD). METHODS: A pedigree affected with PCD who visited Hainan Women and Children's Medical Center in April 2023 due to "SLC22A5 gene mutation found in offspring genetic testing and preparing for a second child" was selected as the study subject. Pathogenicity of the proband's variant sites was determined by referring to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG). Sanger sequencing was used to verify the variant sites of SLC22A5 gene in the proband and her parents, and the single nucleotide polymorphism (SNP) haplotype of the family was constructed by SNP microarray (SNP array) method to determine the carrier status of pathogenic genes. After fertilization via assisted reproductive technology, whole genome amplification (WGA) was performed on the biopsied trophoblastic cells. Sanger sequencing, next-generation sequencing (NGS), and SNP array techniques were then used to detect the variants in the SLC22A5 gene and chromosome copy number variation (CNV) in the embryos. Embryos without the variants were selected for transferring. After the successful pregnancy of the proband's mother, amniocentesis was not performed for prenatal diagnosis due to repeated vaginal bleeding. After delivery, neonatal peripheral blood sample was collected to verify the results of PGT-M, and follow-up was conducted. This study was reviewed and approved by the Medical Ethics Committee of Hainan Women and Children's Medical Center (Ethics No. HNWCMC-2022-178). RESULTS: In this study, the c.338G>A and c.760C>T variants in SLC22A5 gene were evaluated as pathogenic variants. Sanger sequencing results of this family showed that the c.338G>A and c.760C>T variants of the proband were inherited from his father and mother, respectively. Haplotypes of c.338G>A and c.760C>T variants of SLC22A5 gene were successfully constructed. PGT-M results showed that 2 of the 8 blastulas biopsied failed WGA, and the CNV detection results of the remaining 6 blastocysts were all euploid: 2 had no mutations in the SLC22A5 gene, 3 were single heterozygous carriers of paternal or maternal origin, and 1 was compound heterozygous carriers of paternal and maternal origin. Combined with the embryo morphology score, an intrauterine singleton pregnancy was achieved after the successful transfer of an optimal embryo with no CNV abnormalities and no paternal or maternal SLC22A5 gene mutations, resulting in the birth of a healthy female baby at 38⁺³ weeks of gestation. The results of peripheral blood chromosomal karyotyping analysis, CNV detection and SLC22A5 gene c.338G>A and c.760C>T site variant detection of the infant were consistent with those of PGT-M, and no abnormality was found. CONCLUSION PGT-M had helped the couple carrying SLC22A5 gene variant to have a healthy offspring and effectively blocked the transmission of PCD in this family.
Adult ; Female ; Humans ; Male ; Pregnancy ; Cardiomyopathies ; China ; East Asian People/genetics* ; Genetic Testing/methods* ; High-Throughput Nucleotide Sequencing ; Hyperammonemia/genetics* ; Mutation ; Pedigree ; Polymorphism, Single Nucleotide ; Preimplantation Diagnosis/methods* ; Solute Carrier Family 22 Member 5/genetics* ; Carnitine/deficiency* ; Muscular Diseases

To explore the anti-tumor effect of immunotherapy with recombinant protein vaccine based on FGFR-1 of chicken (cFR-1) in a mouse Meth A fibrosarcoma model, tumor volume and survival rate of the mice were observed at a 3-day interval. Microvessel density (MVD) was detected by immunohistochemistry. Auto-antibodies against self-FGFR-1 were detected by Western blotting and ELISA, respectively. The anti-FGFR-1 antibody-producing B cells (APBCs) were detected by enzyme-linked immunospot (ELISPOT) assay. Eighteen days after inoculation of tumor cells, the tumor volume was significantly smaller in cFR-1-immunized group than in mouse FGFR-1 (mFR-1) immunized group and normal saline (NS) control group (P<0.05), and the survival time was significantly longer in cFR-1-immunized group than in the control groups (P<0.01). MVD was significantly lower in cFR-1-immunized group than in mFR-1-immunized group and NS group (16.8+/-5.6 vs 64.6+/-1.8 and 59.6+/-8.7, P<0.01). Antibodies against self-FGFR-1 were found in mFR-1-immunized group, the major antibody subclasses were IgG1 and IgG2b. Compared with the two control groups, the numbers of APBCs in cFR-1-immunized group were significantly increased (P<0.01) These results demonstrated that the cFR-1-related anti-angiogenesis protein vaccine could induce the production of auto-antibodies against self-FGFR-1, which futher inhibit angiogenesis and growth of solid tumor.

To explore the anti-tumor effect of immunotherapy with recombinant protein vaccine based on FGFR-1 of chicken (cFR-1) in a mouse Meth A fibrosarcoma model, tumor volume and survival rate of the mice were observed at a 3-day interval. Microvessel density (MVD) was detected by immunohistochemistry. Auto-antibodies against self-FGFR-l were detected by Western blotting and ELISA, respectively. The anti-FGFR-1 antibody-producing B cells (APBCs) were detected by enzyme-linked immunospot (ELISPOT) assay. Eighteen days after inoculation of tumor cells, the tumor volume was significantly smaller in cFR-l-immunized group than in mouse FGFR-1 (mFR-1) immunized group and normal saline (NS) control group (P＜0.05), and the survival time was significantly longer in cFR-l-immunized group than in the control groups (P＜0.01). MVD was significantly lower in cFR-l-immunized group than in mFR-l-immunized group and NS group (16.8 ±5.6 vs 64.6±1.8and 59.6±8.7, P＜0.01). Antibodies against self-FGFR-1 were found in mFR-l-immunized group, the major antibody subclasses were IgG1 and IgG2b. Compared with the two control groups, the numbers of APBCs in cFR-l-immunized group were significantly increased (P＜0.01) These results demonstrated that the cFR-1-related anti-angiogenesis protein vaccine could induce the production of auto-antibodies against self-FGFR-1, which futher inhibit angiogenesis and growth of solid tumor.

The possibility that a recombinant protein vaccine based on xenogeneic homologous FGFR-1 of chicken induces production of autoantibodies against self-FGFR-1 in BALB/c mice was examined by using ELISA, Western blot analysis and ELISPOT assay respectively. Autoantibodies against mouse FGFR-1 were identified by Western blot analysis and ELISA. Compared with the two control groups, the number of APBCs, which were detected by ELISPOT assay, was significantly increased in the spleens of mice immunized with cFR1 (P < 0.05). IgG1 and IgG2b, which were detected by ELISA, were the major subclasses and were substantially increased in response to chicken FGFR-1 when compared with control group. The recombinant chicken FGFR-1 protein used as a vaccine can induce autoantibodies against self-FGFR-1 in mice and provide a basis for the active immunotherapy of tumor angiogenesis.

The possibility that a recombinant protein vaccine based on xenogeneic homologous FGFR-1 of chicken induces production of autoantibodies against self-FGFR-1 in BALB/c mice was examined by using ELISA, Western blot analysis and ELISPOT assay respectively. Autoantibodies against mouse FGFR-1 were identified by Western blot analysis and ELISA. Compared with the two control groups, the number of APBCs, which were detected by ELISPOT assay, was significantly increased in the spleens of mice immunized with cFR1 (P＜0.05). IgG1 and IgG2b, which were detected by ELISA, were the major subclasses and were substantially increased in response to chicken FGFR-1 when compared with control group. The recombinant chicken FGFR-1 protein used as a vaccine can induce autoantibodies against self-FGFR-1 in mice and provide a basis for the active immunotherapy of tumor angiogenesis.

OBJECTIVEIn order to minimize lead pollution and to protect the identified individuals with high blood lead level from lead contamination, an epidemiological study was carried on children living around the village and township-owned lead industries in Tianying town.

METHODSEnvironmental monitoring: lead levels in air, soil, drinking water and crops were measured. Biological monitoring: 959 children aged 5 - 12 years were selected from villages where the lead smelters located near the residential areas and the battery disassembling was done in some families. The control children (207 pupils) were from other villages without lead exposure. Blood lead, ZnPP and teeth lead were determined. Height, weight and head circle of children and IQ scores were measured.

RESULTSThe environment was seriously polluted. The average lead concentrations in air and soils were 8.5 times and 10 times of the MACs (national health standard) respectively. Eighty-five per cent the air samples with lead concentrations higher than the national health standard. Local crops and wheat at farmers' home were also contaminated by lead dust, with. Lead content being 24 times higher than the standard. The mean blood lead and ZnPP levels of children lived in the polluted areas were 496 microgram/L and 9.41 microgram/g Hb respectively. The lead exposure caused adverse effects on children's IQ and physical development.

CONCLUSIONIt is necessary to remove and reduce currently active sources of lead pollution in the community and to increase public awareness of potential health effects of lead exposure.

Air Pollutants ; analysis ; Child ; Child Development ; drug effects ; Child, Preschool ; China ; Crops, Agricultural ; chemistry ; Environmental Monitoring ; methods ; Environmental Pollution ; adverse effects ; analysis ; Female ; Health Status ; Humans ; Industrial Waste ; adverse effects ; analysis ; Lead ; adverse effects ; blood ; Male ; Soil Pollutants ; analysis ; Suburban Health ; standards ; Urban Health ; standards