BACKGROUND: 3-nitropropionic acid(3-NP) can inhibit the process of oxidative phosphorylation and injure the energy metabolism of the cell and thereby induce cell injury. However, small dose of 3-NP can excite intrinsic cellular protective factor to protect neurons and increase the tolerance of neurons to ischemic hypoxia through mild inhibiting the process of oxidative phosphorylation. It is unclear whether it also has the similar effect on dopaminergic neurons.OBJECTIVE: To investigate whether 3-NP preconditioning could enhance the tolerance of dopaminergic neurons to MPP+(1-methyl-4-phenylpyridine)toxicity.DESIGN: A randomized controlled exploring research based on neuroblastoma SH-SYSY cell that could secrete dopamine.SETTING: Department of neurology of a university hospital.MATERIALS: The study was conducted in the Laboratory of Pathophysiology of Tongji Medical College between March 2003 and November 2003. SH-SYSY cell was obtained from the Cell Center of Peking Union Medical University.INTERVENTIONS: Cells were randomly divided into 6 groups. MPP+ was added into the cultured dopaminergic neuron SH-SY5Y cells for the establishment of the cell model for Parkinson disease. Before the admission of MPP+ (0.25 mmol/L), 3-NP(0. 2 mmol/L) was added once or repetitive times to form preconditioning. Microculture tetrozolium(MTT) was used to detect cell survival rate, and[3H] DA uptake rate was used to test the anterior synaptic function of dopaminergic neurons.MAIN OUTCOME MEASURES: Major consequence: Cell survival rate;Minor consequence: [3H] DA uptake rate.RESULTS: Cell survival rate of MPP+ group was 54.3%, which was significantly lower than that of blank control group( P ＜ 0.01) . After 3-NP preconditioning, cell survival rate significantly elevated, which was 71.8%(single) or 85.2% (repetitive) . There was significant difference between single preconditioning and repetitive preconditioning( P ＜ 0.05 ). The results of[3H] DA uptake rate were similar to that of cell survival rate. [3H] DA uptake rate was 65.8% (single) or 80. 3% (repetitive), which was significantly higher than 50. 1% of MPP+ group. And moreover, repetitive preconditioning had more favorable effect than single preconditioning. Simple admission of 3-NP had no impact on cells.CONCLUSION: 3-NP preconditioning can significantly enhance the tolerance of dopaminergic neuron to MPP+ toxicity, which has significant protective effects on dopaminergic neuron. Repetitive preconditioning have more significant protective effects.

Blood samples were detected by 24 blood-glucose meters using glucose oxidase and another 18 glucose meters using glucose dehydrogenase. The plasma glucose was detected by the auto-chemistry analyzer as control. According to ISO1 5197 and EF9-A2, the bias of results from both glucose meters 100% fall in the range of ±0. 56 mmol/L( ＜4. 2 mmol/L) and ≥99. 7% in the range of ±20% ( ≥4. 2 mmol/L), predicted bias were all less than the true bias(Bc). As κ＞0. 6, the results from both glucose meters were in accordance with the results from autochemistry analyzer in judging hyperglycemia ( ＞6. 11 mmol/L) and hypoglycemia ( ＜ 3.89 mmol/L). Between the results from the two blood-glucose meters, κ＜0. 6. The accuracy of both glucose-meters are accepted for the purpose of clinical diagnosis and treatment.

BACKGROUND: Mainly pathological changes of Parkinson disease (PD)are related to irreversible degeneration and reduction of dopamine neurons of substantia nigra in midbrain; however, oxidative stress reaction plays an important role in onset of PD. 3-nitropropionie acid (3-NP) is an inhibitor of mitochondria compound I, and it can inhibit oxidative phosphorylation so as to restrain energy metabolism. However, professor Riepe from Germany found that small dose of 3-NP can increase the tolerance of neurons to ischemic hypoxia. It is unclear whether it can also strengthen the tolerance of dopamine neurons to neurotoxin.OBJECTIVE: To investigate the possible mechanism and prevention of repetitively preconditioning 3-NP for treating PD.DESIGN: Controlled observational animal study. SETTING: Department of Neurology, Union Hospital affiliated to TongjiMedical College, Huazhong University of Science and Technology. MATERIALS: The experiment was carried out at the Neurological Lab oratory, Union Hospital affiliated to Tongji Medical College, Huazhong U niversity of Science and Technology from March to July 2004. A total of48 C57BL mice, weighing 18-20 g, aged 2-3 months, of both genders, were randomly divided into 6 groups with 8 in each group. ① Blank con trol group: Mice were not medicated. ② 3-NP single administrationgroup: Mice were intraperitoneally injected with 3-NP once. ③ 3-NPrepetitively administrations group: Mice were intraperitoneally injectedwith 3-NP every 5 days for 5 times in total. ④ Neurotoxin group: Micewere intraperitoneally injected with neurotoxin once every day for 5 timesin total. ⑤ 3-NP single preconditioning group: Mice were intraperitoneal ly injected with 3-NP once, and 3 days later, they were intraperitoneallyinjected with neurotoxin once every day for 5 times in total. ⑥ 3-NPrepetitively preconditionings group: Mice were intraperitoneally injectedwith 3-NP and repetitively every 5 days for 5 times in total; 3 days later, mice were intraperitoneally injected with neurotoxin once every day for5 times in total. Dosages of 3-NP and neurotoxin were 20 mg/kg and30 mg/kg, respectively. METHODS: Motor coordination of mice was scored with pole test andtraction test before experiment and at 3 days after the last injection ofneurotoxin. Three days after complete injection, mice were sacrificed rapid ly to measure the contents of malondialdehyde (MDA) and reduced glu tathione (GSH) in the substantia nigra of midbrain. MAIN OUTCOME MEASURES: ① Motor and behavior scores; ② con tent of MDA; ③ content of GSH.~ULTS: All 48 mice were involved in the final analysis. ① Scores of pole test and traction test were decreased in neurotoxin group as compared with those in control group (P＜0.01); but the scores were increased after 3-NP single/repetitively preconditionings, and there were significant difference (P＜0.05, P＜0.01). Meanwhile, there was also significant differencebetween 3-NP repetitively preconditionings group and 3-NP single preconditioning group (P＜0.05). ② Content of MDA was increased in neurotoxin group as compared with that in control group, and there was significant difference (P＜0.01); content of MDA was decreased after 3-NP single preconditioning as compared with that in neurotoxin group, and there was significant difference (P＜0.05); content of MDA was remarkably decreased after 3-NP repetitively preconditionings as compared with that in neurotoxin group, and there was greatly significant difference (P＜0.01); meanwhile, there was also significant difference between 3-NP repetitively preconditionings group and 3-NP single preconditioning group (P＜0.05). ③As compared with that in blank control group, content GSH in 3-NP single administration group was not changed; content of GSH in 3-NP repetitively administrations group was increased (P＜0.05); content of GSH in neurotoxin group was decreased as compared with that in blank control group (P＜0.01); content of GSH in 3-NP single preconditioning group was not changed as compared with that in neurotoxin group (P＞0.05); content of GSH was increased after 3-NP repetitively preconditionings, and there was significant difference (P＜0.05); meanwhile, there was significant difference between 3-NP repetitively preconditionings group and 3-NP single preconditioning group (P＜0.05).CONCLUSION: 3-NP repetitively preconditionings can activate synthesis of GSH, protect dopamine neurons through decreasing production of MDA.

Objective To analyze the prognostic factors and causes of death of patients with systemic lupus erythematosus (SLE).Methods A database with 319 patients were developed.They were newly diagnosed SLE in the Department of Rheumatology and Immunology,Affiliated Drum Tower Hospital of Nanjing University Medical School from 1999 to 2009.Normal distribution of measurement data was presented using mean±standard deviation.The skewed distribution of data was described by median(interquartile range).Using the rate or proportions,the character of classification data was also stated.Survival rate of SLE patients over time was studied by the Kaplan-Meier method,and prognostic factors were analyzed by COX proportional hazards model.Results The 5 year and 10-year survival rates was 96.2%, 88.7%, respectively Prognostic factors affecting survival included duration from onset to diagnosis, anemia, white blood cells in urine, low serum albumin,low C4 level,abnormal ECG and ultrasound echocardiography, pulmonary arterial hypertension (PAH) and systemic lupus erythematosus disease activity index (SLEDAI). However, PAH,duration from onset to diagnosis, low serum albumin were the independent poor prognostic factors and the relative risk and 95% confidence interval were 2.419 (1.052-5.564), 1.162 (1.043-1.294), 0.924 (0.873-0.978), respectively. Renal failure, pulmonary hypertension and infection were the main causes of death,followed by multiple organ failure and lupus encephalopathy. Conclusion PAH, duration from onset to diagnosis, low serum albumin are the important factors predicting poor prognosis. Early diagnosis, timely treatment of SLE organ damages and preventing complications are the key factors to improve the prognosis of patients with SLE.

OBJECTIVE:To analyze the cost-effectiveness of3kinds of Chinese patent drugs in the treatment of insomnia outpatients.METHODS:78outpatients with insomnia were randomly divided into group A,group B and group C,and they were treated with shumian capsule,sweet dream capsule and compound semen ziziphi spinosae capsule,respectively,then,cost-effectiveness analysis was carried out with pharmacoeconomics.RESULTS:The per capita costs(C)for group A,B and C were288.20yuan,163.08yuan and139.22yuan respectively,the reduction in PSQI scores(E 1 )were5.15,8.88and11.84respectively,the effective rates(E 2 )were26%,46%,and64%respectively;The average cost-effect ratios C/E 1 were55.96,18.36,and11.76respectively;C/E 2 were11.08,3.55,and2.18respectively;The increment of the cost-effect ratios?C/?E 1 for group A and B were—22.27and—8.06respectively;?C/?E 2 were—3.92,—1.33respectively,as compared with group C.CONCLUSION:Compound semen ziziphi spinosae capsule is more economical in3drugs in treating insomnia outpatients.

Mutations in the parkin gene have recently been identified in familial and isolated patients with early-onset Parkinson disease (PD) and that subregions between exon 2 and 4 of the parkin gene are hot spots of deletive mutations. To study the distribution of deletions in the parkin gene among variant subset patients with PD in China, and to explore the role of parkin gene in the pathogenesis of PD, 63 patients were divided into early onset and later onset groups. Exons 1-12 were amplified by PCR, templated by the genomic DNA of patients, and then the deletion distribution detected by agarose electrophoresis. Four patients were found to be carrier of exon deletions in 63 patients with PD. The location of the deletion was on exon 2 (1 case), exon 3 (2 cases) and exon 4 (1 case). All patients were belong to the group of early onset PD. The results showed that parkin gene deletion on exon 2, exon 3 and exon 4 found in Chinese population contributes partly to early onset PD.
Exons/*genetics ; *Gene Deletion ; Parkinson Disease/*genetics ; Point Mutation ; Ubiquitin-Protein Ligases/*genetics

OBJECTIVETo study the effect of Kaixin San on the rate-limiting enzyme in biosynthesis of melatonin (MT) and pineal body in rat depression model.

METHODThe unpredictable chronic mild stress was used to establish the rat depression model for 21 days. The rats were divided into the normal control group, the model group, Kaixin San low, medium and high dose groups (KXS 65, 130, 260 mg x kg x d(-1)) and the trazodone group. All groups were administered at 30 min after modeling each day. Rats were sacrificed and the pineal glands were isolated immediately after acquisition tail venous blood at 2:00a. m on the 22nd day. The plasma was analyzed for melatonin content by using a rat metabolic panel Milliplex kit. The pineal glands were analyzed for AANAT and HIOMT mRNA levels by Real-time quantitative PCR and for AANAT and HIOMT activity by a radiometric assay simultaneously.

RESULTThe plasma MT concentration, expression of AANT and HIOMT mRNA, activity of AANAT in rat pineal glands of the model group were significantly lower than the control group (P < 0.05), but the activity of HIOMT showed not change. Compared with the model group, all of Kaixin San groups showed increase in MT concentration in plasma (P <0. 05) , with the medium dose group revealing the highest level. Besides, the medium dose group displayed significant increase in AANAT, HIOMT mRNA level and AANAT activity (P < 0.05), but no increase in HIOMT activity.

CONCLUSIONKaixin San can regulate AANAT activity of pineal bodyand regulate MT biosynthesis in rat depression model.

Acetylserotonin O-Methyltransferase ; genetics ; Animals ; Arylalkylamine N-Acetyltransferase ; genetics ; Depression ; blood ; genetics ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation, Enzymologic ; drug effects ; Male ; Melatonin ; biosynthesis ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar

BACKGROUNDMatrix metalloproteinase-9 (MMP-9) is one of significant extracellular matrix catabolic enzymes, which is known to relate to the initiation, progression and growth of the tumor. The aim of this study is to investigate the effects of MMP-9 antisense oligonucleotide (ASODN) on the apoptosis and metastasis of human lung adenocarcinoma A549 cell.

METHODSMTT was used to analyze the effect of MMP-9 ASODN transfection on A549 cell growth. Flow cytometry was used to analyze the cell cycle and apoptosis. MTT chromometry and scratch migration were used to observe the capability of adhesion and immigration of the A549 cell.

RESULTSMMP-9 ASODN inhibited the survival rate of the A549 cell and the action was concentration-and time-dependent. The peak concentration of MMP-9 ASODN was 600 nmol/L at 48 hours after transfection. After transfection of MMP-9 ASODN to A549 cell, the percentage of A549 apoptosis cell was significantly higher than that of control group (P < 0.01), but the adhesion and migration cut down predominantly (P < 0.01).

CONCLUSIONSMMP-9 ASODN can depress the adhesion and migration and inhibit proliferation of adenocarcinoma A549 cell effectively, and can promote apoptosis of the A549 cell.

To investigate the distribution of possible novel mutations from parkin gene in variant subset of patients with Parkinson's disease (PD) in China and explore whether parkin gene plays an important role in the pathogenesis of PD, 70 patients were divided into early-onset group and late-onset group; 70 healthy subjects were included as controls. Genomic DNA from 70 normal controls and from those of PD patients were extracted from peripheral blood leukocytes by using standard procedures. Mutations of parkin gene (exon 1-12) in all the subjects were screened by PCR-single strand conformation polymorphism (SSCP), and further sequencing was performed in the samples with abnormal SSCP results, in order to confirm the mutation and its location. A new missense mutation Gly284Arg in a patient and 3 abnormal bands in SSCP electrophoresis from samples of another 3 patients were found. All the DNA variants were sourced from the samples of the patients with early-onset PD. It was concluded that Parkin point mutation also partially contributes to the development of early-onset Parkinson's disease in Chinese.
DNA Mutational Analysis ; Exons ; Genotype ; Parkinson Disease/*genetics ; *Point Mutation ; Polymorphism, Single-Stranded Conformational ; Ubiquitin-Protein Ligases/biosynthesis ; Ubiquitin-Protein Ligases/*genetics

Mutations in the parkin gene have recently been identified in familial and isolated patients with early-onset Parkinson disease (PD) and that subregions between exon 2 and 4 of the parkin gene are hot spots of deletive mutations. To study the distribution of deletions in the parkin gene among variant subset patients with PD in China, and to explore the role of parkin gene in the pathogenesis of PD, 63 patients were divided into early onset and later onset groups. Exons 1-12 were amplified by PCR, templated by the genomic DNA of patients, and then the deletion distribution detected by agarose electrophoresis. Four patients were found to be carrier of exon deletions in 63 patients with PD. The location of the deletion was on exon 2 (1 case), exon 3 (2 cases) and exon 4 (1 case). All patients were belong to the group of early onset PD. The results showed that parkin gene deletion on exon 2, exon 3 and exon 4 found in Chinese population contributes partly to early onset PD.
Adult ; Aged ; Exons ; genetics ; Female ; Gene Deletion ; Humans ; Male ; Middle Aged ; Parkinson Disease ; genetics ; Point Mutation ; Ubiquitin-Protein Ligases ; genetics