Regulation of the activity of CYP450 has always been research focus of drug metabolism. The effect of compounds on the mRNA and protein expression level of CYP450 is the main purpose of most of the existing reports. In recent years, the protein modification in the posttranslation level has been found to participate in maintaining the proper function of CYP450, thus effect of posttranslational modification on the enzyme activity has been paid more and more attention. Posttranslational modifications including phosphorylation, nitration, and ubiquitination have been described to regulate the activity of CYP450. In this paper, recent developments in the effects of posttranslational modifications on the activity of CYP450 have been reviewed.

0.05) in both groups. In group B,cardiac output decreased by 13% at 15th min following deliberated hypotension (P0.05). It is suggested that PaCO_2 can be evaluated continuously and noninvasively by monitoring end-tidal CO_2 tension during SNP-induced hypotension.

Objective In order to know the operative key points of combined endoscopic nephroureterectomy. Methods Retrospective analyzed 16 patients with combined endoscopic nephroureterec-tomy, and then summarized perioperative nursing points. Results All the patients had successful operation without any complications. Conclusions Careful perioperative nursing are the guarantee for successful oper-ation, which can effective promote the rehabilitation for patients.

ObjectiveTo analyze the effect of temporal distance parameters on comfortable and maximal walking speed of hemiplegic stroke patients.MethodsThe comfortable and maximal walking speed of 85 hemiplegic stroke patients were tested by 10 m walking speed and temporal distance parameters of gait cycle were obtained. The effect of step length and walking rate on comfortable and maximal walking speed was analyzed.ResultsStep length and walking rate were significantly positive related to comfortable and maximal walking speed (r=0.849-0.915,P<0.001).The step regression analysis selected step length as a significant variable for comfortable and maximal walking speed (R2=0.835,R2=0.827,respectively). ConclusionThe important parameter that influences comfortable and maximal walking speed of hemiplegic stroke patients is step length.

Objective To observe effects and mechanisms of insulin on reperfusion injury after cerebral ischemia.Methods Sixty-six male Wistar rats were used in this study.All rats were divided into 3 groups as treated group(A),control group(B) and random sham-operated group(C).Four-vessel occlusion was used to establish global cerebral ischemia reperfusion model in study groups.The treated group were divided into 5 groups(A1-A5) and intraperineally injected with biosynthetic human insulin 2 IU/(kg?d) and 50%glucose 2 g/(kg?d) for 7 days,the blood glucose was monitored in preoperative and postoperative 3,6,12,24 h,and the blood glucose was maintained between 3.5-6.5 mmol/L.These animals of control group were given with saline 2 mL/(kg?d) for 7 days in abdominal cavity.All the rats were killed in the seventh day,brain homogenate was collected for detection of neuron specific enolase(NSE)and nitric oxide(NO).The hippocampus was separated for observation of electronic microscope.Results Concentration of NSE in brain tissue in group C was significantly higher than that of group A and group B,while the level in group A was higher than that of group B.Concentration of NO in group C was lower than that of group A and group B while the level of NO in group A was significantly lower than that of group B.Electron microscope showed that the ultrastructure of sham-operated group was nearly normal,damage degree of hippocampal neuron and gliacyte and capillary was gradually worse from group A1,A2 to A4,the damage degree of group B1,B2 and B4 was serious and there was no difference among them.Conclusion Insulin can really promote recovery of the cerebral injury after ischemia reperfusion.

OBJECTIVETo evaluate the effect of length of tibial stump on proprioceptive recovery after anterior cruciate ligament (ACL) reconstruction.

METHODSFrom March 2011 to December 2011,42 patients with ACL tear were performed with reconstruction. The patients were divided randomly into three groups: group A, the patients with remained length of tibial stump ranging from 15 to 20 mm, including 8 males and 6 females, with an average age of (28.2 ± 6.6) years old; group B, the patients with remained length of tibial stump ranging from 5 to 10 mm, including 9 males and 5 females, with an average age of (27.9 ± 6.4) years old; group C, the patients with remained length of tibial stump less than 2 mm, including 9 males and 5 females, with an average age of (28.6 ± 6.8) years, old. The stability of knee were assessed by Lanchman test and anterior drawer test. The function of knee was assessed by Lysholm score and Tegner activity rating. The proprioceptive recovery was evaluated by assessing the passive reproduction of the angles with limb movement into flexion and extension in no weight bearing position.

RESULTSLanchman test and anterior drawer test of all patients were negative at 6 months postoperatively., and there was one case of positive outcome in each group at 12 month and 18 month postoperatively. Lysholm score and Tegner activity score of all patients at 18 month postoperatively were significantly better than that preoperatively, and there were no significant difference among three groups at 18 month postoperatively. There were no significant difference in the production of the angles at flexion to 20° and extention to 80° and 20° among these groups before and after operation. The reproduction of the angles of group A and B at flexion to 50° and extention to 50° at 6 month postoperatively were significantly better than that of group A and B preoperatively and that of group C at 6 month postoperatively, and there were no significant difference among three groups at 18 month postoperatively. The reproduction of the angles of group A and B at flexion to 80° at 12 month postoperatively were significantly better than that of group A and B preoperatively and that of group C at 12 month postoperatively, and there were no significant difference among three groups at 18 month postoperatively.

CONCLUSIONPreservation of tibial stump in ACL reconstruction has benefit in proprioceptive recovery at early stage postoperatively and the length of tibial stump should be reserved with a range from 5 to 10 mm.

Adult ; Anterior Cruciate Ligament ; physiopathology ; surgery ; Anterior Cruciate Ligament Injuries ; Anterior Cruciate Ligament Reconstruction ; Female ; Humans ; Knee Joint ; physiopathology ; surgery ; Male ; Proprioception ; Range of Motion, Articular ; Tibia ; chemistry ; physiopathology ; surgery ; Young Adult

Objective To investigate the association between levels of serum alanine aminotransferase (ALT) and the risks of metabolic syndrome in middle-aged and elderly Chinese. Methods After excluding subjects with known liver disease, excess alcohol consumption and serum ALT≥40 IU/L,1 664 subjects aged 40 years or older from Baoshan Community, Shanghai were recruited to undergo questionnaire interview, anthropometric measurements, and fasting blood sampling. Biochemical features were evaluated and the metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria with modification on waist circumference cutoff which is more appropriate for an Asian population. Results Increased ALT levels were associated with more unfavorable metabolic risk profiles. The prevalence rates of the metabolic syndrome in participants with increasing ALT quartiles were 29. 2% , 38. 0% , 44.9% , and 62. 9% , respectively (P for trend <0. 01 ). ALT concentrations were significantly elevated with increasing number of the metabolic syndrome components (P for trend<0.01). Serum ALT levels were significantly associated with the risks of metabolic syndrome and most of its components in a dose-response manner. As compared with participants in the first ALT quartile, the risks of metabolic syndrome were increased by 146% , central obesity by 204% , hypertension by 35% , high triglycerides by 133% , and hyperglycemia by 72% in participants of the fourth ALT quartile. Conclusions A high-normal serum ALT level was significantly associated with an increased risk of the metabolic syndrome in middle-aged and elderly Chinese.

Objectve To investigate the association between insertion/deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) gene and autosomal dominant polycystic kidney disease (ADPKD). Methods Polymorphism of ACE gene was analyzed by polymease chain reavtion (PCR) in 103 ADPKD patients and 16 ADPKD family constellations including 35 patients and 30 non-ill people. Clinical data were collected and age of onset, hepatocyst, hypertension, urinary tract infecton, urinary concretion, hematuria were used as the main parameters to analyze the association between ACE gene polymorphism and ADPKD. Results The age of onset in DD genotype was 7.2 years younger than that in DI genotype [(31.90±11.41) vs (39.10±10.08) years, P<0.05] and was 14.25 years younger than that in Ⅱ gene type [(31.90±11.41) vs(46.15±14.74) years, P<0.05]. The age of onset in I/D genotype was 7.05 years younger than that in Ⅱ genotype [(39.10±10.08) vs (46.15±14.74) years, P<0.05]. There were significance differences of main clinical symptoms (hypertension, hematuria and urinary tract infection) among three genotype groups. In 11 family constellations, ACE gene polymorphism presented genetic linkage, but without significant difference (P>0.05); the genotype distribution was not significantly different between ADPKD and non-ill people (P>0.05), as well as between man and woman (P>0.05); the DD genotype frequency was significantly higher in ADPKD patients with chronic renal failure (P<0.05). Conclusions The age of onset in DD gentype is the youngest among three groups. The incidence of hypertension and hematuria in DI genotype is the highest. The ACE gene polymorphism in ADPKD family constellation does not provide diagnosis information. The ACE gene I/D polymorphism may not contribute to ADPKD. The DD genotype of ACE may be a risk factor of renal failure in the ADPKD.

Niemann-Pick disease type C (NPC) is a fatal,neurovisceral lipid storage disease,neuropathologically characterized by cytoplasmic sequestration of glycolipids in neurons,progressive neuronal loss,neurofibrillary tangles (NFTs) formation,and axonal spheroids (AS).Cytoskeletal pathology including accumulation of hyperphosphorylated cytoskeletal proteins is a neuropathological hallmark of the mouse model of NPC (npc mice).With a goal of elucidating the mechanisms underlying the lesion formation,we investigated the temporal and spatial characteristics of cytoskeletal lesions and the roles of cdc2,cdk4,and cdk5 in lesion formation in young npc mice.Cytoskeletal lesions were detectable in npc mice at three weeks of age.Importantly,concomitant activation of cdc2/cyclin B 1 kinase and accumulation of a subsequently generated cohort of phospho-epitopes were detected.The activation of cdk4/cyclin D1 and cdk5/p25 kinases was observed during the fourth week of life in npc mice,and this activation contributed to the lesion formation.We concluded that the progression of cytoskeletal pathology in npc mice older than four weeks is accelerated by the cumulative effect of cdc2,cdk4,and cdk5 activation.Furthermore,cdc2/cyclin B1 may act as a key initial player one week earlier.Targeting cell cycle activation may be beneficial to slow down the NPC pathogenesis.

Objective To evaluate the synergistic effect of everolimus on cisplatin-mediated cytotoxicity against human cutaneous squamous cell carcinoma COLO-16 cells.Methods Cultured COLO-16 cells were divided into several groups to be treated with everolimus at different concentrations of 50,100 and 200 nmol/L or 25 μmol/L cisplatin for 12 and 24 hours.Acridine orange (AO)-labeled autophagic vesicles combined with lysomal enzyme inhibitors (E64d and pepstatin) were used to detect the levels of autophagy and autophagic flow.Western blot analysis was performed to track the conversion of the autophagosome marker microtubule-associated protein 1 light chain-3 (LC3)-Ⅰ to LC3-Ⅱ,as well as to detect cleavage levels of Caspase 3 and poly-ADP-ribose polymerase (PARP).Lactate dehydrogenase (LDH) assay was conducted to detect cell death,and Annexin V-EGFP staining to evaluate cell apoptosis.Results The LC3-Ⅱ / LC3-Ⅰ ratios (LC3-Ⅰ conversion to LC3-Ⅱ) after 12-and 24-hour treatment did not differ among the 50-,100-and 200-nmol/L everolimus groups (12 hours:3.52 ± 0.21 vs.4.03 ± 0.39 vs.5.05 ± 0.22,P ＞ 0.05;24 hours:3.38 ± 0.26 vs.3.29 ± 0.06 vs.6.57 ± 0.16,P ＞ 0.05),but were significantly higher in the three everolimus groups than in the control group receiving no treatment (12 hours:2.07 ± 0.05,P ＜ 0.05;24 hours:2.61 ± 0.16,P ＜ 0.05).After 12-hour treatment,no significant differences were observed in the ratio of LC3-Ⅱ to β-actin between the 50-nmol/L everolimus + E64d + pepstatin group (1.26 ± 0.40),100-nmol/L everolimus ± E64d + pepstatin group (1.16 ± 0.34),200-nmol/L everolimus + E64d + pepstatin group (1.21 ± 0.39) and E64d + pepstatin group (1.19 ± 0.27,P ＞ 0.05).Moreover,there was no significant difference in the percentages of autophagic vesicle-positive cells between the 100-nmol/L everolimus + E64d + pepstatin group and E64d + pepstatin group (2.06％ ± 0.61％ vs.1.68％ ± 0.62％,P ＞ 0.05).After 24-hour treatment,the everolimus + cisplatin group showed significantly increased rate of cell death compared with the cisplatin alone group (42.58％ ± 0.93％ vs.18.20％ ± 1.46％).However,no significant differences were observed in the cleavage levels of Caspase 3 and PARP,the number of annexin V-labelled cells and ratio of LC3-Ⅱ to β-actin between the everolimus + cisplatin group and the cisplatin-alone group (P ＞ 0.05).Conclusion Everolimus has a synergistic effect on the cisplatin-mediated COLO-16 cell death,and this effect does not depend on cell apoptosis or autophagy.