Objective: To investigate the interaction between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and sleeping duration on risk of stroke in a Chinese Han ethnic population. Methods: In the case-control study and epidemiological investigation, the self-reported sleep duration and MTHFR C677T polymorphism of 245 patients with cerebral infarction, 222 patients with cerebral hemorrhage and 282 controls were collected. Multiple logistic regression was performed to analyze the interaction between MTHFR C677T polymorphism and sleeping duration on risk of stroke. Results: After adjustment for major confounding variables, multiple logistic regression analysis showed that: (1) There was significant association between long sleep duration (>8 hours of sleep per night) and cerebral infarction (OR=3.90; 95% CI:2.43-6.26), but not for cerebral hemorrhage (OR=1.16, 95% CI: 0.71-1.92). On the other hand, insomnia (sleep duration less than 6 hours) was neither associated with cerebral infarction nor hemorrhage. (2) MTHFR TT genotype increased the risk of cerebral infarction significantly (OR=2.01; 95% CI:1.12-3.61), but not for cerebral hemorrhage (OR=1.16,95% CI:0.71-1.92). (3) There was a significant synergistic effect of interaction between MTHFR TT677 genotype and long sleep duration on risk of cerebral infarction (OR=6.22; 95% CI:2.44-15.83). Conclusion: MTHFR TT677 genotype and long sleep duration increase the risk of cerebral infarction independent of confounding factors, respectively. Furthermore, there is a significant synergistic effect between MTHFR TT677 genotype and long sleep duration on risk of cerebral infarction in the Chinese Han ethnic population.

Objective: To determine the relationships between apoptosis induced by transforming growth factor beta 1 (TGF-β1) and Smad in human hepatoma cell lines. Methods: Three human hepatic carcinoma cell lines, involving different status of the p53 gene respectively, were used in this study.TGF-β1-induced apoptosis in hepatic carcinoma cell lines was quantitated using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. For identification of the mechanism of apoptosis induced by TGF-β1, these cell lines were transfected with a TGF-β1-inducible luciferase reporter plasmid containing Smad binding elements (SBE) and luciferase gene using LF2000, then were treated with TGF-β1. Relative luciferase activity was assayed respectively. Results: Among three cell lines studied with TUNEL assay, addition of TGF-β1 induced apoptosis only in HepG2 cells (wild type p53). In contrast, Huh-7 ( mutant p53) and Hep3B ( deleted p53) cell lines lacked apoptosis. The detection of luciferase activity indicated that HepG2 cells dramatically increased the response to TGF-β1 induction, Huh-7 and Hep3B cell lines significantly lowered luciferase expression. Conclusion: HepG2cells were highly susceptible to TGF-β1-induced apoptosis compared with Hep3B and Huh-7 cell lines.Smad4 may be a central mediator of the TGF-β1 signaling transdution pathway.

Objective: To investigate the protective factors and risk factors of nosocomial infection of severe acute respiratory syndrome (SARS) among health care workers (HCWs) , and thus provide the scientific basis for prevention and control of nosocomial infection. Methods: With the case-control study,a standardized questionnaire was used for data collection in three general hospitals where nosocomial infection had occurred. Univariate analysis was done at first. All concerned factors about SARS infection were scanned by using Chi-square test and Fisher' s exact test one by one, and determined as to whether they were risk factors or protective factors according to odd ratio (OR) score. Then, multivariate unconditional logistic regression analysis was used to re-analyze the picked-out factors for finding out which factors played independent roles. Results: Twenty-two factors (nineteen protective factors and three risk factors), among the total fifty-six factors, were significantly associated with SARS infection. Multivariate unconditional logistic regression revealed that factors such as double exposure suits ( OR = 0.053 ), education ( OR =0.072), gloves ( OR =0.102), hands sterilized by iodine ( OR =0.231 ), room air ventilation (OR = 0.32), were significantly protective; conversely, tracheal intubation ( OR = 30.793 ) was a significant risk factor. Conclusion: Strict defense and antisepsis measures were pivotal in preventing SARS infection among high-risk medical personnel. Education about associated knowledge and effective air ventilation were also important factors.

Objective: To investigate the expression of voltage-dependent potassium channel 1.3(Kv1.3) mRNA and protein during human monocyte-derived macrophage differentiation into foam cells and its function in foam cell formation. Methods: Human peripheral blood monocytes were isolated from healthy male volunteers by density gradient centrifugation and then by adherent method. The obtained monocytes were cultured for 5 days to differentiate into macrophages. Based on establishment of the human macrophage-derived foam cell model, the expression of Kv1.3 channel was investigated by immunocytochemical staining, reverse transcription-polymerase chain raction (RT-PCR) and Western blot. Furthermore, the effects of rMargatoxin, a Kv 1.3 channel-specific inhibitor, on cholesterol metabolism in macrophages incepting oxidized low density lipoprotein (OxLDL) were studied. Results: After the macrophages co-incubated with 30 mg/L OxLDL at 37 ℃ for 60 hours, the cellular volume obviously enlarged and many red lipid granules were deposited in cytoplasm. The total amount of cholesterol (TC),free cholesterol ( FC ) and cholesterol ester ( CE ) in cells markedly increased and the ratio of CE/TC rose from ( 14.4±6.8) % to (57.9±3.5) % (n=7,P＜0.05). However, the expression of Kv1.3 channel had no significant change. r Margatoxin (0.1 nmol/L and 10 nmol/L) markedly reduced the contents of TC, FC and CE in macrophages and the ratios of CE/TC decreased to (42.8±11.6) % and (22.6±8.0)% , respectively (n=7, P＜0.05). Meanwhile, the red lipid granules deposited in the cytoplasm of macrophages also decreased. Conclusion: These data clearly show that the expression of Ky1.3 channel does not change obviously during human monocyte-derived macrophage differentiation into foam cells and the blocking of it would prevent foam cell formation.

Application of TMS technology in newborn screening has resulted in major expansion of disorder panel for metabolic diseases in recent years. This automated, multiplex testing methodology detects multiple analytes from single analysis of one blood spot, which leads to detection of 30-35 disorders of amino acids, organic acids, and fatty acids metabolism. The early identification of persons affected with inborn errors of metabolism has led to unexpected discoveries related to the natural history of the disorder or options for therapy. This article summarized (1) the basic principles of this technology and methodology. (2) Current status of application of this methodology in the United States, European countries and in China. (3) The positive impacts on the public health and advances in medical genetics. Finally (4) Challenges, issues and possible solutions. The purpose of this article aimed at introducing new technology and exploring the possibilities of implementing into developing countries where medical genetics is not developed and foreseeing the possible problems and obstacles.

Autism is a neurodevelopmental disorder characterized by impairments in social skills, language, and behavior. It is now clear that autism is not a disease, but a syndrome characterized by phenotypic and genetic complexity. The etiology of autism is still poorly understood. Available evidence from a variety of sources strongly suggests that many genetic disorders are frequently associated with autism for their similar phenotypes. Based on this fact, this review begins by highlighting several principal genetic syndromes consistently associated with autism (fragile X, tuberous sclerosis, Angelman syndrome, Pader-Willi syndrome, Rett syndrome, Down syndrome and Turner syndrome). These genetic disorders include both chromosome disorders and single gene disorders. By comparing the similar phenotype, protein marker and candidate genes, we might make some breakthrough in the mechanism of autism and other genetic disorders.

Dystonia is a syndrome which is characterized by sustained muscle contractions, producing twisting, repetitive, and patterned movements, or abnormal postures. According to genetic basis, dystonia is classified into 13 subtypes. We mainly discussed two subtypes, DYT1 and DYT5, in this review. Early-onset primary dystonia is caused by the mutation of DYT1 gene, which leads to TORSINA abnormal. GTP cyclohydrolase 1 (GTPCH1)-deficient DRD(DYT5) is caused by the mutations of GCH1 gene. By genetic testing, we can confirm clinical diagnosis of each subtype and develop prenatal diagnosis for it.

Lysosomal storage disorders (LSDs) are genetic defects caused by lysosomal hydrolase deficiencies. These deficiencies lead to substrate accumulation affecting cells, tissues and organs. Detecting abnormal compound excretion and deficient enzymes assist diagnosis of these disorders for treatment and prevention. This mini review summarizes clinical presentations and diagnostic workup of LSDs and updates the new development in the area.

The Department of Pediatrics of Peking University First Hospital has a long term of outstanding history.It was established about 60 years ago.After the division of pediatric neurology(DPN) had been established in 1960s,it had been assigned to cover genetic disorders.During the recent 20 years,efforts have been put on three aspects:(1)Pediatric neurology clinical service and education;(2)research studies of childhood epilepsies and pediatric neurogenetic disorders;and (3) development of a strong DPN team to establish a comprehensive pediatric neurological program.In this paper,we reviewed the history of the pediatric neurology division in our department,our clinical and research work and achievements for neurogenetic diseases.

Objective:To compare the therapeutic and toxic profile of topotecan given intraperitoneally with intravenously in human ovarian cancer xenografted into athymic nude mice.Methods: Eighty female Balb-c/nu-nu mice were randomized assigned into eight groups (n=10). Xeneografts resulted from intramesentery injection of cultured human ovarian cancer cells SKOV3 in athymic mice. Onset of intraperitoneal treatment with either topotecan or cisplatin (7.5 mg/kg) was on day 7. Animals scheduled for topotecan i.p. received intraperitoneal application of topotecan (1.5 mg/kg×2, 3.0 mg/kg×2, 6.0 mg/kg×2 or 10.0 mg/kg×1). Animals scheduled for topotecan i.v. received intravenous administration of topotecan (6.0 mg/kg×2 or 10.0 mg/kg×1). Two weeks after drug application animals were killed. Tumor growth inhibition were assessed and compared with untreated mice and cisplatin intraperitoneally administered mice. Acute toxicity was determined by loss of body weight. Cell cycle division and apoptosis after drug administration was determined by flow cytometric analysis.Results: In a panel of ten tumour xenografts, intraperitoneal topotecan was significantly more effective than intravenous administration. The toxicity profile suggested a better tolerability in terms of weight loss after intraperitoneal administration than cisplatin control. Topotecan 10.0 mg/kg i.p. per day (1 day) schedule was an optimal treatment for ovarian cancer and well tolerated by mice with no signs of acute toxicity. Topotecan and cisplatin induce cells G0-G1 arrest and apparent apoptosis. No significant difference among mice treated with topotecan intraperitoneally or intravenously or cisplatin was observed in term of apoptosis and cell cycle perturbation.Conclusion:The results may have implications for the future design of clinical studies on intraperitoneal application of topotecan. It suggests that apoptosis and cell cycle perturbation play an limited role in the mechanism of topotecan administration.