Objective To investigate whether the vohage-gated chloride channel CLC-2 gene— CLCN2 is associated with idiopathic generalized tonie-clonic seizures(often called a grand mal seizure, GME)of Jinuo people and Han people from Yunnan province.Methods Three regions,including Intron 2, Exon 5 and Exon 19(Intron 18),of CLCN2 were selected to conduct sequence analysis.The case-control study design was used to detect association between gene polymorphism and idiopathic generalized tonic- clonic seizures of Jinuo people and Han people from Yunnan province.Results No previously reported susceptible mutations were found in Intron 2,Exon 5 and Exon 19 in Jinuo people and Han people from Yunnan province.However we found a single nucleotide polymorphism(SNP)at site 146 of Intron 18. Case-control study were carried out,using this SNP.Distribution of the 3 genotypes(TT,TC,CC)has a significant difference between the IGTCS patients of Han people and the normal controls of Han people(9, 3,29 cases and 22,9,26,respectively,x~2=16.079,P

OBJECTIVETo investigate the effect of curcumin (Cur) on histone deacetylase (HDAC1) and P21(WAF1/CIP1), a cyclin dependent kinase inhibitor, in HepG2 cells for exploring the mechanism of Cur in anti-cancer.

METHODThe HDAC1, P21(WAF1/CIP1) proteins and P21(WAF1/CIP1) mRNA were extracted from human hepatoma cells treated with or without Cur of different concentrations at different time points. Western blot analysis was performed to determine the levels of HDAC1 and P21(WAF1/CIP1) proteins, respectively. RT-PCR was performed to detect the level of P21(WAF1/CIP1) mRNA.

RESULTThe IC50 of concentration treated by Cur was 25 micromol x L(1) on HepG2 cell. The level of HDAC1 was obviously inhibited by Cur, and decreased at 4 hours at IC, and lasted for 48 h in a time-dependent manner. The inhibition of HDAC1 was significant at the Cur concentration of 12.5 micromol x L(-1) but there was no difference between 50 and 100 micromol x L(-1). The levels of P21(WAF1/CIP1) mRNA and protein were up-regulated by Cur in dose and time-dependent manner, and the change of mRNA and protein was detected at 8 hours and lasted for 48 hours.

CONCLUSIONCur can inhibit the level of HDAC1 and enhance the expression of P21(WAF1/CIP1) protein and mRNA, and the results suggest that inhibiting HDAC1 and increasing P21(WAF1/CIP1) may be one of the possible mechanisms of anti-cancer by Cur.

Blotting, Western ; Carcinoma, Hepatocellular ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Curcuma ; chemistry ; Curcumin ; administration & dosage ; isolation & purification ; pharmacology ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; metabolism ; Dose-Response Relationship, Drug ; Gene Expression Regulation, Neoplastic ; drug effects ; Histone Deacetylase Inhibitors ; Histone Deacetylases ; metabolism ; Humans ; Liver Neoplasms ; genetics ; metabolism ; pathology ; Plants, Medicinal ; chemistry ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors

Objective To investigate the prognostic sequelae in neontes with hypoxic-ischemic encephalopathy (HIE) and ven-tricnlar dilatation.Methods Seventy-six full term newborns infants with HIE were followed up at the age from 3 to 19 months after therapy. Twenty-five infants among them were followed up by telephone in the epidemic period of SARS.Results Among 76 infants of 88 newborn infants with HIE(84.6%), 73 infants were normal (96.1% ). 1 infant had cerebral palsy (1.3%), 2 infants died (2.6 %).Among 39 cases with mild HIE, none of them had cerebral sequelae; among moderate HIE. 1 infant had cerebral palsy (2.9%) 1 infant died (2. 9 %), interlenkin-4 among severe HIE 50 % died (P00.5 The poor outcome of HIE in those infants were related to intrauterine growth retardation,severe birth asphyxia;and inadequate treatment.Cranial ultra-sonography of 49 infants were done on follow-up,and 12 of them (24.5 % ) had ventricular dilatations, which appeared after birth with 6 infants. Others occurred on follow-up with 1 infant had cerobral palsy,all ventricular dilatations recovered to normal at 12- 19 months except the cerebral palsy.Conclusions The poor outcome of HIE depends on the infants with intranterine growth relarda-tion,severe birth asphyxia and inadequate treatment.The prognosis of transient ventrealar ddatation are good except cerebral palsy.J Appl Clin pediatr,2004,19(12) : 1045- 1047

OBJECTIVETo discuss the pathological characteristics of cervical spinal fracture complicating ankylosing spondylitis (AS) and the effect of combined anterior and posterior operation.

METHODSEighteen AS patients with traumatic cervical fracture-dislocation were treated operatively from January 2000 to January 2006. The symptom duration of AS was 14.5 years on average. Three cases had undergone osteotomy in lumbar spine. There were 4 cases of Grade A, 3 cases of Grade B, 9 cases of Grade C and 2 cases of Grade D according to Frankel's score. There were 15 cases of Grade III dislocation and 3 cases of Grade II. All patients underwent surgical procedures by combined anterior and posterior approach.

RESULTSThere were 4 anterior-posterior procedures, 8 anterior-posterior-anterior procedures and 6 posterior-anterior procedures. Seven patients had one stage operation and 11 cases underwent two stage surgeries. There was certain extent of neurological improvement in 14 incomplete paraplegic patients, but no improvement in 4 complete paraplegic patients. The follow-up period was 21.2 months on average and the time for bone fusion was 3.6 months. There were 4 complications during operation and a long-term complication in follow-up.

CONCLUSIONSThe study suggests that anterior combined with posterior approach makes the spine stable and relieves the pressure immediately. It is a reasonable surgical strategy for treatment of cervical spinal fracture-dislocation with AS.

Adult ; Cervical Vertebrae ; injuries ; Humans ; Joint Dislocations ; surgery ; Male ; Middle Aged ; Postoperative Complications ; etiology ; Retrospective Studies ; Spinal Fractures ; surgery ; Spondylitis, Ankylosing ; complications

OBJECTIVETo analyze clinical features of 4 families with hereditary hemorrhagic telangiectasia (HHT) and potential mutations of ENG, ACVRL1 and SMAD4 genes.

METHODSFour unrelated HHT patients and their affected family members were analyzed. All exons and flanking regions of ENG, ACVRL1 and SMAD4 genes were analyzed with PCR and direct sequencing and multiplex ligation-dependent probe amplification (MLPA) methods.

RESULTSEleven patients from the 4 families were enrolled in this study. Two ENG and 1 ACVRL1 mutations were identified, among which an ENG mutation (c.207G>A; p.L69L) and an ACVRL1 mutation (c.817C>T; p.L273L) have been previously reported. In addition, a novel ENG mutation (c.1004A>T; p.Q335L) has been found in 3 different families. Similar mutations were not detected in 200 healthy individuals. No mutations of ENG, ACVRL1 and SMAD4 were found in the fourth family.

CONCLUSIONA novel mutation c.1004A>T (p. Q335L) of ENG has been identified in patients with HHT. And there is significant phenotypic variability and genetic heterogeneity with the disease.

Activin Receptors, Type II ; genetics ; Adolescent ; Adult ; Amino Acid Sequence ; Antigens, CD ; genetics ; Endoglin ; Female ; Genetic Testing ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Receptors, Cell Surface ; genetics ; Smad4 Protein ; genetics ; Telangiectasia, Hereditary Hemorrhagic ; diagnosis ; genetics

OBJECTIVETo calculate heritabilities of personality disorders (PDs) in twin population.

METHODSBased on informed consent, we used Personality Diagnostic Questionnaire (fourth-version) as our screening tool to study the adult twins (aged 20 - 70 years) in Qingdao city. There were 324 twin pairs whose zygosity had been determined. Structural equation modeling was used to estimate the heritabilities by 242 same-sex twin pairs.

RESULTSThe best-fitting models yielded a heritability of 68.26% (60.26 - 74.78) of overall PDs, 59.00% (49.22 - 67.17) of cluster A, 64.99% (56.24 - 72.16) of cluster B, and 63.66% (54.72 - 71.02) of cluster C. There were significant genetic effects for schizotypal, narcissistic and dependent, explaining 49.96% (37.94 - 60.14), 52.89% (41.85 - 62.24) and 68.87% (60.80 - 75.40) of the variance respectively. No genetic effects were found on Histrionic, but common environmental effect accounted for 54.08% (44.50 - 62.43) of the total variances.

CONCLUSIONPD was mainly determined by genetic factor. These findings may provide evidence for future research on PD.

Adult ; Aged ; Analysis of Variance ; China ; Cluster Analysis ; Diseases in Twins ; genetics ; Environment ; Genetic Predisposition to Disease ; Humans ; Middle Aged ; Models, Genetic ; Personality Disorders ; genetics ; Personality Inventory ; Risk Factors ; Surveys and Questionnaires ; Young Adult

OBJECTIVETo observe the effects of Huganjiexian decoction on rat hepatic fibrosis and the creation of cytokines.

METHODSRat hepatic fibrosis was induced by intraperitoneally injection of carbon tetrachloride. At the same time, these rats were treated with different dosages of Huganjiexian decoction. Sho-saiko-to compound treating group and Fufangbiejiarangan Tablets treating group were used as positive controls. After twelve weeks, all rats were executed. Histopathologic changes were observed after H.E and Masson stainings. The expression of collagen type I, collagen type III, TGF-beta 1 and PDGF-BB in liver were detected by immunohistochemical staining.

RESULTSCompared with fibrotic group, hepatic fibrosis in decoction groups was significantly improved. In decoction groups, levels of collagen type I, collagen type III, TGFbeta1 and PDGF-BB were decreased, especially in the low-dose curcumin group. The TGF-beta 1 positive percentage were 7.56%+/-2.18%, 29.25%+/-7.84%, 13.54%+/-4.15%, 21.82%+/-6.64%, 20.06%+/-7.14%, 13.78%+/-4.35%, 12.75%+/-3.98% in liver tissues from normal group, model group, low, middle, high curcumin, Sho-saiko-to compound and Fufangbiejiarangan Tablets treating groups respectively (P less than 0.05); while the PDGF-BB positive percentage were 1.68%+/-0.41%, 11.70%+/-2.28%, 3.65%+/-0.76%, 5.24%+/-1.04%, 6.37%+/-1.12%, 4.16%+/-0.61%, 3.38%+/-0.56% in liver tissues from those groups respectively (P less than 0.05).

CONCLUSIONHuganjiexian decoction can improve rat hepatic fibrosis, possibly via inhibiting the expression of collagen type I, collagen type III, TGFbeta1 and PDGF-BB.

Animals ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Liver Cirrhosis ; drug therapy ; metabolism ; Male ; Medicine, Chinese Traditional ; Phytotherapy ; Platelet-Derived Growth Factor ; metabolism ; Proto-Oncogene Proteins c-sis ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism

Objective Development and application of a real time fluorescent quantitative PCR (FQ-PCR) assay for detecting WU polyomavirus in children with low respiratory tract infections.Methods The VP2 gene of WU polyomavirus was selected as the detection target,from which the real time primers and probes were designed.The standard curve was established by using recombinant plasmid as template.And the FQ-PCR assay for specific detection of WU polyomavirus was established.The speciflcity,sensitivity and reproducibility of the method were evaluated. Furthermore,the clinical specimens from children with respiratory tract infections collected in Wenling First People's Hospital were quantitatively detected using this method.Results In this study,the FQ-PCR method was established to detect a specific fragment in VP2gene of WU polyomavirus.The standard curve coefficient R2 was 0.998.And this method can detect as low as 50 copies recombinant plasmid.The clinical specimens of sputum and throat swab from children with respiratory tract infections were quantitatively detected using this method.7 sputum specimens were detected as WU polyomavirus positive in 700 sputum specimens,the positive ratio was 1.00％.No positive specimens were detected in 146 specimens of throat swabs and 846 blood samples from same patient population.Conclusion .The results indicated that the FQ-PCR assay method established in this study was specific,rapid and sensitive for detecting WU polyomavirus in children with lower respiratory tract infections.The sputum specimen is more suitable to be used for gene detection of WU polyomavirus than throat swab or blood.

Objective To evaluate the safety and efficacy of cefaze-done injection ( CZD) compared with cefazolin injection ( CZL) in the treatment of acute bacterial respiratory infections.Methods Eligible subjects were divided randomly to receive 2.0 g cefazedone injection or cefazolin injection twice a day for 7 to 14 days.Efficacy and safety evaluation were done in accordance with the clinical trial protocol.Results Two hundred and sixty patients in 11 hospitals were en-rolled, 126 in CZD group( trial) and 134 in CZL group( control).There were no statistical differences in basic conditions between two groups( P >0.05 ).Cure rates of CZD group and CZL group were 95.5% and 94.9% in PPS ( P>0.05 ).Bacteria clearance rates of CZD group and CZL group were100% and 91.7% in BPPS and the total cure rates of CZD group and CZL group were 94.4% and 91.7% in BPPS, respectively ( P>0.05).Ten out off 126 patients in CZD group and 14 out off 134 in CZL group developed adverse events( AE ).Six and eleven events in CZD group and CZL group
were evaluated to be related with study drugs.One case in CZL group developed severe AE , which was considered not related with study drug.Conclusion Cefazedone injection is safe and effective in the treatment of respiratory infections.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.