Methylmalonic acidemia(MMA) is one of the most common diseases of autosomal recessive inherited organic acid metabolic disorder,which can cause multiple organ involvement.It can be found in infants or even in the neonatal period and be manifested as feeding difficulty,repeated vomiting,convulsions,abnormal muscle tension,mental retardation,hemolytic uremic syndrome(HUS),etc.In which HUS caused by MMA is better and better known by pediatricians when treating renal diseases while the diagnosis rate is increasing year by year.This article reviews the epidemiology,etiology,pathogenesis,clinical manifestations and treatment of HUS associated with MMA.

Hereditary glomerular disease is an important part of kidney diseases .In recent years , hereditary glomerular disea-ses had a high incidence and poor prognosis .Thus, the studies involving hereditary glomerular diseases such as Alport syndrome , he-reditary nephritis syndrome and thin basement membrane disease , etc.have significant implications .This review mainly focuses on the pathogenesis , clinical features , diagnosis and treatment of Alport syndrome and hereditary nephritis syndrome .

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at the post-transcriptional lev-el and then affect important physiological and pathological processes. Many microRNAs are tissue or organ-speciifc which make it possible for them to become potential biomarkers. Similarly, microRNAs are important for physiological functions of kidney and they are involved in various renal disorders. The review summarizes current information about microRNA effect on various kidney diseases, in order to provide references for the diagnosis and treatment of kidney disease in the future.

Objective To investigate the effect of butylphthalide and sodium chloride injection postconditioning on focal cerebral ischemia-reperfusion (I/R) injury and endoplasmic reticulum stress in rats.Methods Thirty-six male SPF Sprague-Dawley rats,aged 2-3 months,weighing 260-280 g,were randomly divided into 3 groups (n =12 each):sham operation group (group S),focal cerebral I/R group (group I/R) and butylphthalide and sodium chloride injection postconditioning group (group Buty).The animals were anesthetized with intraperitoneal 10 ％ chloral hydrate 300 mg/kg.Focal cerebral I/R was induced by occluding right middle cerebral artery for 2 h followed by 24 h reperfusion in I/R and Buty groups.Butylphthalide and sodium chloride injection 2.5 mg/kg was injected via the tail vein immediately after onset of reperfusion in Buty group,while the equal volume of normal saline was injected in I/R group.Neurological deficits were assessed and scored at 24 h of reperfusion,and then the brain was isolated for detection of neuronal apoptosis (by TUNEL) and the expression of glucose-regulated protein 78 (GRP78) and caspase-12 in ischemic cerebral cortex (by immunohistochemistry) in brain tissues.Apoptosis index was calculated.Results Compared with group S,the neurological deficit scores and apoptosis index were significantly increased,and the expression of GRP78 and caspase-12 was up-regulated in I/R and Buty groups (P ＜ 0.05 or 0.01).Compared with group I/R,the neurological deficit scores and apoptosis index were significantly decreased,the expression of GRP78 was up-regulated,and the expression of caspase-12 was down-regulated in group Buty (P ＜ 0.05).Conclusion Butylphthalide and sodium chloride injection postconditioning can reduce focal cerebral I/R injury in rats,and inhibition of endoplasmic reticulum stressmediated cell apoptosis is involved in the mechanism.

Objective To investigate the effects of dexmedetomidine preconditioning on ischemia-reperfusion(I/R) injury to isolated rat hearts.Methods Twenty-four male Wistar rats weighing 230-260 g were anesthetized with intraperitoneal 10％ chloral hydrate 400 mg/kg and heparin 500 IU/kg.Their hearts were excised and perfnsed in a Langendorff apparatus with K-H solution saturated with 95％O2-5％CO2 at 37 ℃.Twenty-four isolated rat hearts were randomly divided into 3 groups after 10 min of equilibration(n =8 each):group I/R,dexmedetomidine 0.23,2.30 ng/ml preconditioning group (groups D I,D Ⅱ ).In group I/R,the hearts were perfused continuously for another 30 min.In groups D Ⅰ and D Ⅱ,the hearts were perfused with K-H solution containing dexmedetomidine 0.23,2.30 ng/ml for 20 min followed by 10 min washout before ischemia.All hearts were subjected to 30 min of global ischemia followed by 120 min of reperfusion with K-H solution.The activities of creatine kinase(CK) and lactate dehydrogenase(LDH) in coronary effluent were measured at the end of 10 min equilibration(balance),and at 5,30,60 and 120 min of reperfusion.Myocardial tissues were obtained at the end of reperfusion for determination of the activity of SOD and the content of MDA.Results Compared with group I/R,the CK and LDH activities in coronary effluent and MDA content in myocardium were significantly decreased,the SOD activity was significantly increased in groups D I and D Ⅱ ( P ＜ 0.05).Compared with group D Ⅰ,the CK and LDH activities in coronary effluent and MDA content in myocardium were significantly decreased,the SOD activity was significantly in group DⅡ ( P ＜ 0.05).Conclusion Dexmedetomidine preconditioning can attenuate myocardial I/R injury in a concentration-dependent manner in rats.

Objective The article was to analyze the features of gene mutation and clinical phenotype in Alport syndrome. Methods Next-generation sequencing was applied to capture the exons of COL4A3, COL4A4, COL4A5 genes in 30 cases of children with suspected or confirmed diagnosis of Alport syndrome and Sanger method was used to identify gene mutations of related family mem-bers.Provean database was applied in protein function prediction.We collected and analyzed clinical data of AS patients on the basis of gene mutation. Results All 30 children were diagnosed with AS by gene sequencing, among whom 4 boys were autosomal reces-sive inheritance, 16 boys and 10 girls were X-linked Alport syndrome.Next-generation sequencing detected 35 different gene mutations of COL4A3, COL4A4, COL4A5, including 19 missense mutations, 2 synonymous mutations, 4 splice-site mutations, 3 truncating mu-tations, 2 insertion mutations, 4 deletion mutations and 1 compound mutations.It was observed by Sanger sequencing that 20 mutations were inherited from the mother, 8 from the father, homozygous mutation in 1 propositus from the parents respectively, 8 novel mutations and 1 with unidentified source.All the 30 children had an onset of hematuria or proteinuria, 17 cases had a positive family history, 1 case had hearing loss, and no pathogenesis or renal insufficiency was found in the children.Renal biopsy was performed on 23 children, 13 minimal change disease ( MCD) and 10 mesangial proliferative glo-merulonephritis ( MsPNG) by light microscope.Extensive lamination and split of glomerular basement membrane dense layers were found in 9 children by electron microscope. Conclusion XLAS ac-counts for most AS patients and missense mutation is the main type in pathogenic mutations.Altogether, 31 mutations without disease notification were found.Most of children showed MCD in renal biopsy, with atypical electron microscope manifestations and rare extra renal manifestations.

Acute kidney injury is a clinical common disease,but it is a dangerous illness with higher o-verall mortality.Even mild renal insufficiency carries complications.Therefore,it is very important for the early diagnosis of acute kidney injury,which is based on high sensitivity,strong specificity of biomarkers.

Objective Alport syndrome is one of the diseases that may lead to the end-stage renal disease ( ESRD) in chil-dren, and the methods for its diagnosis and treatment remain quite limited.This study aimed to investigate the clinical and genetic di-agnosis of a Chinese family with hematuria companied by genetic nephritis. Methods We analyzed the renal pathology of 7 patients in a family, performed immunofluorescence staining of type-Ⅳcollagen in the nephridial and skin tissue, conducted gene sequencing i-dentification using the exon sequence method, and examined the blood and urine samples from the patients. Results Renal patholo-gy manifested mesenterium hyperplasia in the index patient, with IgM+under the light microscope, no thickening or thinning under the electromicroscope, and no absence of type-Ⅳcollagen on immunofluorescence analysis.Mutation of c.1365_1373del TCCAGGCCC (p.Pro456_Pro458del3) was observed in exon 21 of the COL4A5 gene.Only 1682 amino acids were found in the mutated protein as compared with 1685 in the wild type. Conclusion This is the first case of Alport syndrome induced by gene deletion mutation ever reported in China and abroad.There are many female patients in this family, all with a high risk of reproduction failure.Antepartal gene diagnosis or genetic diagnosis before embryo transfer may contribute to the prevention of the disease.

Objective To evaluate the effect of fentanyl on the efficacy of low-dose ropivacaine for spinal anesthesia in patients undergoing anorectal surgery.Methods Forty ASA Ⅰ or Ⅱ patients,aged 20-55 yr,with body mass index 18-28 kg/m2,scheduled for anorectal surgery,were randomly divided into 2 groups (n =20 each):0.5％ ropivacaine 7.5 mg group (group R) and 0.3％ ropivacaine 6.0 mg+ fentanyl 10 μg group (group RF).A catheter was implanted into the subarachnoid space (L3.4 interspace) and advanced caudally until lumbar region.Group R received hyperbaric 0.5％ ropivacaine 1.5 ml.Group RF received 2.0 ml mixture of hyperbaric 0.3％ ropivacaine 6.0 mg and fentanyl 10μg.The onset time of sensory and motor block,upper level of sensory block,and duration of sensory and motor block were recorded.Motor block was assessed by modified Bromage scale.Results Compared with group R,the duration of sensory and motor block was significantly shortened,and modified Bromage scores were significantly decreased in group RF (P ＜ 0.05 or 0.01),and no significant change was found in the onset time of sensory and motor block and upper level of sensory block between the two groups (P ＞ 0.05).Conclusion 0.3 ％ ropivacaine 6.0 mg combined with fentanyl 10 μg provides satisfactory spinal anesthesia for anorectal surgery,with lower degree and faster recovery of motor block.

Objective To explore the relationships between the expression of PECAM-1 and the degree of ALI in Paraquat induced lung injury model of rabbits. Method Thirty six adult New Zealand rabbits were randomly divided into three groups: 8 mg/kg (Group A), 16 mg/kg (Group B) and 32 mg/kg ( Group C) according to the dose of Paraquat which were infusion into stomach. After poisoned, the animals were monitored for seven days, and then sacrificed. The upper lobe of lung were removed for HE,Masson staining and immunohistochemisty. The ALl score, fibrosis of lung and expression of PECAM-1 were semiquantitative analyzed. Results Each group has 12 animals suffered from poisoning. The survival time of animals in Group C was (6. 47 ± 0. 99 ) days, shorter than (6. 09 + 1.04) days ( P = 0. 031 ) in Group B and (4. 77 + 2. 04) days ( P = 0. 0 07) in Group A. The ALI score were ( 8. 33 ± 1.03) points in Group A, superior to (9. 83 ± 1.17) points ( P = 0. 047 ) in Group B and ( 11.50 + 1.38) points ( P ＜ 0. 01 ) in group C, Group B vs Group C, P=-0.03o The fibrosis degree of lung was (31.09 +2.05)% in Group A,not severe as (34. 37 ±1.62)% (P=0. 002) in Group B and (36. 54 ±0. 44)% (P ＜0. 01 ) in Group C, Group B vs Group C, P = 0. 026. The Pearson correlation analysis showed the expression of PECAM-1 was negative correlated to ALI score (Coe = -0. 732, P =0. 001 ) and fibrosis degree of lung (Coe = -0. 779, P ＜ 0. 001 ) . Conclusions The expressions of PECAM-1 were significantly decreased in New Zealand after Paraquat poisoned, which were dose dependent, correlated to ALI scored and fibrosis degree of lung, so it may play an important role in the development of lung injured induced by Paraquat.