Objective To analyze plasma vitamin E and CoQ10 levels in patients with autosomal recessive cerebellar ataxia for finding the evidence of the related pathogenesis research and therapeutic strategies.Methods The plasma vitamin E and CoQ10 levels were detected by high performance liquid chromatography (HPLC) with diode array detector in 123 probands of autosomal recessive cerebellar ataxia pedigrees.Quantitation was performed using vitamin E and CoQ10 external standard and two 5-point calibration curve;clinical manifestations were analyzed simuhaneously.Results Vitamin E and CoQ10 levels of healthy subjects in the plasma were (8.77 ± 2.28) μg/ml and (1.31 ± 0.38) μg/ml,respectively;the plasma vitamin E and CoQ10 levels of patients were (5.61 ± 2.04) μg/ml and (0.79 ± 0.26) μg/ml,respectively,which were significantly lower than those in healthy controls (t =11.87,13.15;all P＜ 0.01).Clinical manifestations were characterized by cerebellar symptoms,and gait instability was usually the first recognized abnormality.Most of early onset occurred before the age of 25 years (111/123);dysarthria and abnormal eye movement were observed,with cerebellar atrophy on MRI;concomitant symptoms were also present.Conclusions HPLC analysis shows that the plasma vitamin E and CoQ10 levels of patients with autosomal recessive cerebellar ataxia are generally lower than those in the healthy controls.Several patients with significant reductions in these two levels have genetic defects.The combination of clinical phenotypes,biochemical indexes and genetic analyses will be helpful for the establishment of diagnosis and specific treatment.

Objective To investigate the clinical features and genetic mutations of spinocerebellar ataxia type 17 (SCA17).Methods The pathological CAG triplet repeat expansions of the SCA3,SCA1,SCA2,SCA6,SCA7,SCA8,SCA12,SCA17 and dentatorubral pallidoluysian atrophy genes were analyzed in 708 probands of autosomal dominant familial SCA and 1 19 sporadic SCA cases.The CAG repeats of TATA-binding protein (TBP) gene were amplified by means of polymerase chain reaction and agarose gel electrophoresis.For the samples with two alleles,fragment analysis based on CEQ8000 sequencer was applied to analyze the CAG repeat numbers.Furthermore,the correlation between clinical features and CAG repeat in the TBP gene was studied carefully.Results The expanded CAG repeats in the TBP gene was detected in 5 cases with 37/50,36/45,38/52,38/53,36/54 separately.And the main clinical manifestations were ataxia and memory impairment.Conclusion These findings indicate that SCA17 might be a rare subtype of SCA in the Chinese population and the clinical features of SCA17 cover a wider spectrum than previously reviewed.

Objective Mitochondrial transfer RNA for leucine 1(MTTL1)is one of the most important causative genes of oxidative phosphorylation disorders.To understand the clinical,pathological and molecular genetics features of the disordel's caused by MTTL1 mutation.18 patients with a causative mutation in MTTL1 were analyzed.Methods The clinical features,the findings of tlleir biochemistry tests.the neuroimagings,the pathology of biopsied muscles and hereditary characteristics were retrospectively summarized.Results The mutations mt3243A>G and mt3271A>T within MTTL1 gene led to variant syndrome,encephalomyopathies with lactic acidosis and stroke like episodes,diabetes mellitus,progressive external ophthalmoplegia,leish syndrome and complex mitochondrial syndrome were reported.Usually,most patients were sporadic but maternal transmission was the common inherited model.Conclusion The disorders caused by the MTTL1 mutation are hishly phenotypic vailable.There is no association between phenotype and heteroplasmy in muscle.

Objective To summarize the experience in diagnosis and therapy of familial adenomatous polyposis with desmoid tumour. Methods Clinical data of 6 patients with familial adenomatous polyposis and desmoid tumour from Jan 1989 to Jan 2005 were retrospectively analyzed. Results Five patients received proctocolectomy and 1 abdominoperineal resection. The most common symptom was progressive painless mass in abdomen. All patients were confirmed by image examination. Four received surgery, 2 were treated by medicine postoperatively and 1 got watchful therapy. Postoperative recurrence developed in two cases and one suffered from short bowel syndrome. All patients were alive at the follow-up. Conclusions FAP with desmoid tumour is not a rare condition and we should pay attention to diagnosis and manage this disease entity. A reasonable remedy was selected according to general state of health and location of desmoid tumour which can improve prognosis and quality of life.

Objective To evaluate the efficacy of hydromorphone for postoperative parent-controlled intravenous analgesia in pediatric patients.Methods Seventy-five pediatric patients of both sexes,aged 2-5 yr,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective surgery for treatment of developmental displasia of the hip,were divided into 2 groups using a random number table:sufentanil group (group S,n =38) and hydromorphone group (group H,n =37).Parent-controlled intravenous analgesia was carried out within 48 h after operation.Parent-controlled intravenous analgesia solution contained sufentanil 2 μg/kg (group S) or hydromorphone 200 μg/kg (group H) in 100 ml of normal saline.The analgesia pump was set up with a 0.5 ml bolus dose,a 15-min lockout interval and infusion at a rate of 0.5 ml/h.Ramsay sedation scores were recorded at 0.5,1,4,8,12,24 and 48 h after extubation (T1-7).At 1 h before operation (To),T3 and T6,blood samples were collected from the ulnar vein for determination of the concentration of substance P in serum.The total consumption of analgesics,the number of successfully delivered doses,the number of attempts and drug-related adverse reactions were recorded,and parents' satisfaction was scored.Results Compared with group S,Ramsay sedation scores were significantly decreased at T1-3,the number of attempts was increased (P＜0.05),and no significant change was found in the total consumption of analgesics,the number of successfully delivered doses,degree of parents' satisfaction,serum concentration of substance P or incidence of drug-related adverse reactions in group H (P＞0.05).Conclusion Hydromorphone can be safely and effectively used for postoperative parent-controlled intravenous analgesia in pediatric patients.

Background Mitochondrial dynamin-related protein 1 (DRP1) regulates mitochondrial division and plays an important role in maintaining hepatocyte function. However, the role of DRP1 in cadmium exposure-induced maternal liver damage in pregnant mice remains unclear. Objective To investigate the role and mechanism of DRP1 in maternal liver damage induced by cadmium exposure during pregnancy. Methods This study consisted of animal experiments and cell experiments. (1) Animal experiments. Mice at 14 days of gestation were randomly divided into three groups: a control group, a low-dose cadmium group (LCd group: 2.5 mg·kg⁻¹), and a high-dose cadmium group (HCd group: 5 mg·kg⁻¹). The pregnant mice were intraperitoneally injected with cadmium chloride (CdCl₂) for 6 and 24 h in the next morning. The weights of pregnant mice, uterus, maternal liver, and fetal mice were recorded after sacrifice. Serum and liver of pregnant mice were collected, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected, and liver tissues were stained with HE to observe changes in liver function and liver tissue structure. The expressions of oxidative phosphorylation-related proteins, hypoxia inducible factor-1α (HIF-1α) and DRP1 proteins in liver of pregnant mice were detected by Western blotting. (2) Cell experiments. AML12 cells were treated with CdCl₂ (10 μmol·L⁻¹) for 0, 2, 6, 12, and 24 h. The expressions of oxidative phosphorylation-related proteins, DRP1, and hypoxia inducible factor-1α (HIF-1α) proteins were detected. AML12 cells were pretreated with DRP1 inhibitor Mdivi-1 for 1 h and then CdCl₂ (10 μmol·L⁻¹) for 12 h to detect the expression of oxidative phosphorylation-related proteins and DRP1 protein. AML12 cells were treated with Hif-1α siRNA for 48 h and CdCl₂ (10 μmol·L⁻¹) for 6 h to detect the expression of HIF-1α and DRP1 proteins. Results The results of animal experiments showed that cadmium exposure in pregnant mice had no effects on maternal liver weight and liver coefficient. However, the histomorphological changes and necrosis in hepatocytes were observed. Compared with the control group, the serum ALT and AST levels of pregnant mice in the LCd group were significantly increased after 6 h (P＜0.05), and the levels in the HCd group were significantly increased after 6 and 24 h (P＜0.05). Cadmium exposure during pregnancy significantly up-regulated HIF-1α and DRP1 expressions and down-regulated the expressions of oxidative phosphorylation-related proteins in maternal livers. In vitro cell experiments showed that the expressions of oxidative phosphorylation-related proteins was significantly decreased and HIF-1α and DRP1 protein expressions were significantly increased in the AML12 cells treated with CdCl₂ for 6 h. Mdivi-1 pretreatment significantly antagonized the inhibitory effect of cadmium on the expressions of oxidative phosphorylation-related proteins in AML12 cells, while Hif-1α siRNA pretreatment significantly antagonized the up-regulative effect of cadmium on DRP1 expression in AML12 cells. Conclusion Cadmium exposure in pregnant mice may up-regulate DRP1 expression by activating HIF-1α signaling, then inhibit oxidative phosphorylation level of hepatic cells, and ultimately lead to maternal liver damage.