Insertion/Deletion (I/D) Polymorphism of Angiotensin-Converting Enzyme Gene in Steroid-Resistant Nephrotic Syndrome for Children: A Genetic Association Study and Meta-analysis

Abstract

An assessment of the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with steroid-resistant nephrotic syndrome (SRNS) risk in children is still controversial. A meta-analysis was performed to evaluate the relation between ACE gene polymorphisms and SRNS susceptibility. The relevant studies were screened from electronic database and eligible investigations were synthesized using meta-analysis methods. Seven investigations were identified for the analysis of association between ACE I/D gene polymorphism and SRNS risk in children, including five in Asians, one in Caucasians, and one in Africans. There was not a markedly positive association between D allele or DD genotype and SRNS susceptibility in Asians (OR = 1.60, p = 0.26; OR = 1.90, p = 0.38) and for Caucasian population (OR = 0.92, p = 0.86; OR = 0.27, p = 0.22). However, an association of D allele with SRNS susceptibility was observed (OR = 4.67, p = 0.003) in Africans, but not for DD genotype (OR = 6.00, p = 0.05). Interestingly, II genotype seemed to play a positive role against SRNS onset for Asians and African children (OR = 0.51, p = 0.02; OR = 0.07, p = 0.02), but not for Caucasians (OR = 0.33, p = 0.30). In conclusion, our results indicate that D allele or DD homozygous might not be a significant genetic molecular marker for the development of SRNS in Asians and Caucasian children. However, D allele seemed be associated with SRNS risk for Africans but DD genotype did not.     

高能 X射线治疗脑功能性疾病的剂量及照射方式探索

目的探索高能X射线使小白鼠脑组织产生坏死和凋亡的致死剂量和照射方式.方法应用100Gy、150Gy高能X射线一次与分二次照射小鼠全脑.制作光镜、电镜标本.结果光镜下显示神经元细胞核固缩,星形细胞水肿.电镜下表现为神经元染色质凝聚、核固缩,星形细胞水肿等.胶质细胞和神经元出现凋亡变化.分二次照射(2次间隔24h)组,星形细胞水肿较轻.结论100Gy、150Gy高能X射线可使小鼠脑神经元细胞产生坏死和凋亡;分二次(2次间隔24h)照射,星形细胞水肿轻于一次照射组.     

癌症疼痛X—刀治疗的初步分析

应用单个等中心，５ｍｍ准直仪，以血脑的腹后外核ＶＰＬ或腹后内核ＶＰＭ为损毁靶点，１００％等剂量线敷盖靶区，以１２０Ｇｙ剂量进行投照，对１５例癌症疼痛患者进行治疗，总有效率为７３．３％。经随访４￣１１月，无疼痛复发，也无明显并发症发生。本文总结了我们成功的经验，并认为立体定向放射神经外科可能成为治疗癌症疼痛的方法之一。     

Primary coenzyme Q10 Deficiency-6 (COQ10D6): Two siblings with variable expressivity of the renal phenotype

Primary coenzyme Q10 deficiency-6 (COQ10D6) is a rare autosomal recessive disorder caused by COQ6 mutations. The main clinical manifestations are infantile progressive nephrotic syndrome (NS) leading to end-stage renal disease and sensorineural deafness. A 7-year-old girl was diagnosed with steroid-resistant NS (SRNS) and an audiological work-up revealed bilateral sensorineural deafness. A renal biopsy demonstrated focal segmental glomerulosclerosis. Despite immunosuppressive therapy, her serum levels of creatinine increased and haemodialysis was indicated within 1 year after the diagnosis. Living-donor kidney transplantation was performed in the eighth month of haemodialysis. A diagnostic custom-designed panel-gene test including 30 genes for NS revealed homozygous c.1058C > A [rs397514479] in exon nine of COQ6. Her older brother, who had sensorineural hearing loss with no renal or neurological involvement, had the same mutation in homozygous form. COQ6 mutations should be considered not only in patients with SRNS with sensorineural hearing loss but also in patients with isolated sensorineural hearing loss with a family history of NS. The reported p.His174 variant of COQ8B was suggested to be a risk factor for secondary CoQ deficiency, while p.Arg174 appeared to improve the condition in a yeast model. Family segregation and the co-occurrence of biallelic p.Arg174 of COQ8B in a brother with hearing loss implied that the interaction of the altered COQ8B with the mutant COQ6 alleviated the symptoms in this family. CoQ10 replacement therapy should be initiated for these patients, as primary CoQ10 deficiency is considered the only known treatable mitochondrial disease.     

X刀分次治疗帕金森病的临床应用

目的 探讨帕金森病(PD)的X刀分次治疗方法，为PD找出一条可行的无创治疗途径。方法 16例难治性PD病人，采用X刀140Gy分2次损毁丘脑腹外侧核中间部(VIM)治疗；8例病人采用165Gy分3次损毁VIM核治疗；每次间隔24h。结果 X刀治疗后3-24个月随访，24例病人消除或改善了震颤症状；僵直或运动减少症状不同程度的缓解；无并发症发生。神经生理学检查无显著改善。结论 X刀分次损毁VIM核，可安全、无创治疗PD；震颤症状改善显著。     

X—刀治疗癌症疼痛的初步分析

应用单个等中心，5mm准直仪，以VPL或VPM为损毁靶点，100％等剂量线敷盖靶区，以120Gy剂量进行投照，对15例癌症疼痛患者进行治疗。有效率为73．33％，该方法对疼痛部位偏高者疗效较好。经随访1～8个月，无疼痛复发，也无明显并发症。本文总结了成功经验，认为立体定向放射神经外科可能成为治疗癌症疼痛的理想方法之一。     

Genetic spectrum of renal disease for 1001 Chinese children based on a multicenter registration system

To explore the approaches and diagnostic yield of genetic testing for renal disease in children, we describe the genotype and phenotype of the national cohort of children with renal disease from 13 different regions of China recruited from 2014 to 2018 by building up the multicenter registration system (Chinese Children Genetic Kidney Disease Database, CCGKDD). Genetic diagnosis was confirmed in 42.1% of our cohort of 1001 pediatric patients with clinical suspicion of a genetic renal disease. Of the 106 distinct monogenetic disorders detected, 15 accounted for 60.7% of genetic diagnoses. The diagnostic yield was 29.1% in steroid resistant nephritic syndrome (SRNS), 61.4% in cystic renal disease, 17.0% in congenital anomalies of the kidney and urinary tract (CAKUT), 62.3% in renal tubular disease/renal calcinosis, and 23.9% for chronic kidney disease (CKD) 3 to 5 stage with unknown origin. Genetic approaches of target gene sequence (TGS), singleton whole-exome sequencing (WES) and trio-WES were performed with diagnostic rates of 44.8%, 36.2%, and 42.6%, respectively. The early use of trio-WES could improve the diagnostic rate especially in renal tubular disease and calcinosis. We report the genetic spectrum of Chinese children with renal disease. Establishment of the CCGKDD will improve the genetic work on renal disease.     

Association of macrophage migration inhibitory factor −173C allele polymorphism with steroid resistance in children with nephrotic syndrome

The potential effects of macrophage migration inhibitory factor (MIF) on the natural immune response are due to the inhibition of immune cell activation, which is regulated by glucocorticoids. In this study, we investigated MIF –173G/C genotype and C allele frequency in 214 patients with idiopathic nephrotic syndrome (INS) and 103 healthy volunteers. We found significant increases in GC genotype (OR=3, p=0.0009) and C allele frequency (OR=2.5, p=0.0007) in INS. Upon classifying patients as steroid responsive (n=137) or resistant (n=77), a 20-fold over-expression of the CC-genotype was found in the steroid-resistant group (OR=20, p=0.0002). Moreover, a significant increase in C allele frequency in patients with focal segmental glomerulosclerosis (FSGS) has also been noted when compared with other histopathological groups (OR=3.2, p=0.0017). Furthermore, significant increases in the CC genotype (15.6% vs 3.3%) and C allele (75% vs 32%) frequencies have been found in patients with permanent renal function failure (p=0.013 and p=0.0002, respectively). Patients with the CC genotype were found to be at considerably increased risk of permanent renal failure (OR=5.43, p=0.013) and end-stage renal disease (OR=5.53, p=0.020). Additionally, there was a correlation between age of detection of proteinuria and CC genotype. We found an earlier age of onset of proteinuria in patients with the CC genotype (1.9±1.7 years) than in patients who were GC-heterozygous (3.7±3.1 years) and GG-homozygous (3.6±2.9 years, p=0.88). In summary, our results indicate that the MIF –173 C allele confers an increased risk of susceptibility to INS and plays a crucial role in glucocorticoid responsiveness.