Genetic analysis of one family with congenital limb malformations / 中华医学遗传学杂志

Objective@#To detect potential mutation in a Chinese pedigree affected with congenital limb malformations.@*Methods@#Clinical data was collected. Genomic DNA was extracted from peripheral blood samples of family members. The zone of polarizing activity regulatory sequence (ZRS) were amplified by PCR and subjected to direct sequencing.@*Results@#Among the 13 individuals in this pedigree, there were 4 PPD patients, who were characterized by varying degrees of deformity. The female patients suffered triphalangeal thumb and preaxial polydactyly, while the male patients only had preaxial polydactyly. Only one patient had foot involvement. TA heterogeneous mutations was discovered in the ZRS (105C>G) in all patients, the same mutation was not detected in 2 healthy family members.@*Conclusion@#The inheritance pattern of PPD was autosomal dominant inheritance. There was a significant variability of symptoms among family patients. The heterozygous mutation of the ZRS (105C>G) probably underlie the disease.

Genetic analysis of one family with congenital limb malformations / 中华医学遗传学杂志

OBJECTIVE@#To detect potential mutation in a Chinese pedigree affected with congenital limb malformations.@*METHODS@#Clinical data was collected. Genomic DNA was extracted from peripheral blood samples of family members. The zone of polarizing activity regulatory sequence (ZRS) were amplified by PCR and subjected to direct sequencing.@*RESULTS@#Among the 13 individuals in this pedigree, there were 4 PPD patients, who were characterized by varying degrees of deformity. The female patients suffered triphalangeal thumb and preaxial polydactyly, while the male patients only had preaxial polydactyly. Only one patient had foot involvement. TA heterogeneous mutations was discovered in the ZRS (105C>G) in all patients, the same mutation was not detected in 2 healthy family members.@*CONCLUSION@#The inheritance pattern of PPD was autosomal dominant inheritance. There was a significant variability of symptoms among family patients. The heterozygous mutation of the ZRS (105C>G) probably underlie the disease.

Clinical research on Cyclophosphamide drug metabolism in children with lupus nephritis / 中华实用儿科临床杂志

Objective To study the pharmacokinetic status of Cyclophosphamide (CYC) in children with lupus nephritis (LN),as well as the relationship between the pharmacokinetic results and clinical indicators,adverse reactions,curative effect evaluation.Methods Thirty patients hospitalized at Tianjin Children's Hospital from January 2014 to December 2016 were treated with glucocorticoid (GC) combined with CYC.Blood samples were collected in 6 point-in-time after intravenous CYC,a high performance liquid chromatography (HPLC) method was used to detect the blood drug concentration,and the pharmacokinetic results were calculated.All patients were followed up for 24 weeks,and the levels of serum albumin (ALB),24 hours urinary protein,serum creatinine (Scr),complement 3 (C3),therapeutic effect and systemic lupus erythematosus disease activity index scores were evaluated at the same time.Results Pharmacokinetic curve showed the second chamber model,the area under the curve (AUC) of time-effect relationship was (143.55 ±42.43) g/(L · h),peak concentration (Cmax) was (20.02 ± 3.55) g/L,and half-time period (T1/2) was(4.21 ± 0.96) h.Age and gender had no influence on AUC,Cmax and T1/2,and statistically significant correlation was found between serum ALB and T1/2,which was positively correlated (r =0.517,P ＜ 0.05).After 16 weeks of treatment,7 patients were partially responsive,22 cases had a complete remission,and the invalid case was only one.Followed up for 24 weeks,6 patients were partially responsive,24 cases had a complete remission.After 16 weeks of treatment,there were statistical differences in AUC among patients with complete response,partial response or no remission.And after 24 weeks,the patients between complete remission and partial remission had no statistically significant difference in the AUC.After 16 weeks and 24 weeks,T1/2 and Cmax had no statistical differences among those groups of patients.Adverse reactions included leukopenia (3 cases,10.00％),gastrointestinal symptoms (4 cases,13.33％) and respiratory tract infection (6 cases,20.00％).There was no statistical relationship between pharmacokinetic parameters and the occurrence of adverse reactions.Single factor analysis showed that there was a statistical significance between ALB,urine protein quantity and treatment effect,but multi-factor analysis showed that the relation between factors and therapeutic effect had no statistical significance.Conclusions HPLC method can be used for the detection of cyclophosphamide blood drug concentration.The cyclophosphamide pharmacokinetic status of children and adult is similar.ALB and T1/2 show a linear positive correlation.Single factor analysis shows a correlation between ALB and treatment effect.Therefore,the increasing level of plasma propagated before treatment can improve therapeutic effect possibly.Cyclophosphamide pharmacokinetic status has nothing to do with the occurrence of adverse drug reactions in the study.

A case of autoimmune lymphoproliferactive syndrome and literature review / 中华儿科杂志

<p><b>OBJECTIVE</b>To summarize the clinical characteristics, diagnosis and treatment of a case with autoimmune lymphoproliferative syndrome (ALPS) .</p><p><b>METHOD</b>The patient was diagnosed as autoimmune lymphoproliferactive syndrome (ALPS) after being admitted to the Department of Rheumatism and Immunology of Tianjin Children's Hospital in February 20, 2014. The clinical characteristics, physical examination, laboratory tests, gene tests, and treatment process were analyzed and related literature was reviewed.</p><p><b>RESULT</b>The patient was a 16-month- old boy.Since the first month of life, he started to have repeatedly fever, diarrhea, shortness of breath, lymphadenopathy, hepatosplenomegaly, anemia (HGBmin 50 g/L) and thrombocytopenia (min 35 × 10⁹/L) . But multiple exams showed a normal peripheral blood leukocyte count, hypergammaglobulinemia (IgG 19 800 mg/L, IgA 1 710 mg/L, IgM 2 590 mg/L) and significantly increased serum vitamin B12. Flow cytometric measures showed that CD3⁺ CD4⁻ CD8⁻ T lymphocytes significantly increased ( > 10%) at four times. The count of CD3⁺ TCRαβ⁺ CD4⁻ CD8⁻T lymphocytes (double negative T cells; DNTs) >3% twice. The genetic test showed that 309th FAS gene area showed heterozygous mutations, the boy was diagnosed as ALPS. Added examinations of lymphocytes apoptosis induced by FAS was positive. He was treated with prednisone 15 mg once daily and immunomodulator 150 mg three times a day, while in maintaining period with normal levels of hemoglobin and platelet, the dose of prednisone was reduced gradually. Till now, the patient has been treated and observed for 8 months. We retrieved the reports of ALPS in the databases at home and abroad published in recent 10 years, more than 400 cases reported from foreign countries, but there were only 5 domestic cases. Among those, 4 had onset in infancy and 1 at 6-years of age. All the cases presented servere lymphadenopathy and hepatosplenomegaly with anemia (4 of them with hemolytic anemia) and thrombocytopenia. Three cases had a history of frequent infection, one of them had glomerulonephritis. All patient with significant high level of serum immunoglobulin ( > 1.5 times upper limit of normal range), in 3 of them serum vitamin B12 was > 1.5 pg/L (the other 2 cases missed the exam). In 5 cases CD3⁺ CD4⁻ CD8⁻T cells > 10%, and in 2 case DNTs were 8.9% and 15.7% respectively (the other 3 cases missed the exam). Three cases were clearly detected with FAS mutations. All patients were treated with corticosteroid, 2 of them were added with mycophenolate mofetil. The therapy presented effective result in early 1-3 months, but no long-term follow-up reports were available.</p><p><b>CONCLUSION</b>ALPS is a disorder of disrupted lymphocyte homeostasis caused by defective Fas-mediated apoptosis, and it is one of the primary immunodeficiency diseases. The onset of the disease occurs during infancy mainly. Clinical lymphoid hyperplasia and autoimmune phenomena are outstanding signs, which can be associated with frequent infections and allergies. The level of serum vitamin B12 > 1.5 pg/L and the count of CD3⁺ CD4⁻ CD8⁻ T cell show important significance. Exact diagnosis should depend on detecting DNTs and FAS gene.</p>

Effect of antioxidant on pulmonary surfactant in acute lung injury rats / 中国小儿急救医学

Objective To explore the changes of neutrophil elastase (NE) and surfactant protein A (SP-A) in acute lung injury(ALI) rats,and the effect of antioxidant. Methods Sixty healthy mature Wister rats were divided into 2 groups, the control group and treatment group. The rats in two groups all received peritoneal injection of E. coli to establish the ALI animal model. 30 minutes after injection of E. coli,the rats in treatment group were injected reduced glutathione from vena caudalis. The levels of NE in blood and expressions of SP-A in lung tissue were detected at 3,6 and 12 hours after injection of E. coli. Results ALI symptom appeared 3 hours after injection of E. coli in the control group, obvious after 6 hours, the rats vomi-ted pink secretion after 12 hours. Lung edema and bleeding were found by pathologic examination. No obvious symptom was found in treatment group after 3 hours, slight tachypnea after 6 hours, slight edema in pulmonary tissue after 12 hours. After administration of reduced glutathione,levels of NE at 3,6 and 12 hours in the treatment group were lower than those in the control group,and indicated statistical significance in 6 and 12 hours(P <0. 05) ;Levels of SP-A in 3,6 and 12 hours in the treatment group were higher than those in the control group, and indicated statistical significance in 3,6 and 12 hours (P < 0. 05). Conclusion Dysfunction of pulmonary surfactant is secondary in ALI, degradation of SP-A is the one of reasons, the application of reduced glutathione as antioxidant, could effectively suppress NE to decompose basosexine elastin of cells and destroy surface active protein, has protective effect on ALI.