Association of single nucleotide polymorphisms of brain-derived neurotrophic factor gene and multidrug resistance 1 gene to refractory epilepsy in Chinese Han children

BACKGROUND： There are two hypotheses for the underlying cause of refractory epilepsy： ＂target＂ and ＂transport＂. Studies have shown that brain-derived neurotrophic factor （BDNF） is over-expressed in refractory epilepsy. Multidrug resistance 1 （MDR1） gene encodes for P-glycoprotein, the primary ATP-binding cassette transporter in the human body. Some single nucleotide polymorphisms of the MDR1 gene have been associated with refractory epilepsy. OBJECTIVE： To investigate the association between BDNF gene C270T polymorphism and MDR1 T-129C polymorphism with refractory epilepsy in Chinese Han children through the use of polymerase chain reaction （PCR）-restriction fragment length polymorphism analysis. DESIGN, TIME AND SETTING： A case-control, genetic association study was performed at the Central Laboratory, Third Xiangya Hospital of Central South University from June 2005 to November 2007. PARTICIPANTS： A total of 84 cases of unrelated children with epilepsy, including 41 cases of refractory epilepsy and 43 cases of drug-responsive epilepsy, were enrolled. An additional 30 healthy, Chinese Han children, whose ages and gender matched the refractory epilepsy patients, were selected as normal controls. METHODS： Venous blood was collected and genomic DNA was extracted from the blood specimens. C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene were genotyped using PCR-restriction fragment length polymorphism analysis. Association analysis using the Ftest and Chi-square test was statistically performed between C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene and refractory epilepsy. MAIN OUTCOME MEASURES： The distribution of genotypes and allele frequencies of C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene. RESULTS： The distribution of CC, CT, and TT genotypes, as well as C and T allele frequencies, in the BDNF gene was not significantly different between the refractory epilepsy group, drug-responsive epilepsy group, or the normal control group （P 〉 0.05）. The distribution of TT genotype and T allele frequencies of the MDR1 gene was significantly different in the refractory epilepsy group compared with the drug-responsive epilepsy and normal control groups （P 〈 0.05）. Comparison of haplotype combinations demonstrated that there were no significant differences in combinations of TT＋CC, -FI-＋CT, TC＋CC, and TC＋CT among the three groups （P 〉 0.05）. CONCLUSION： C270T polymorphism of the BDNF gene was not associated with refractory epilepsy in Chinese Han children, but T-129C polymorphism in the MDR1 gene was associated with refractory epilepsy in Chinese Han children. The TT genotype and T allele frequencies could serve as susceptibility loci for refractory epilepsy. Interactions between C270T in BDNF gene and T-129C in MDR1 gene were not observed in refractory epilepsy in Chinese Han children.

Atypical Presentation of Classical Bartter Syndrome as a Case of Chronic Diarrhea and Failure to Thrive

The classical Bartter syndrome is an uncommon tubular disorder of autosomal recessive inheritance, characterized by early childhood onset of polyuria, polydipsia, vomiting, dehydration, constipation and salt craving habit. The long-term outlook for patients with Bartter syndrome is not certain. If not properly treated, it may lead to failure to thrive and growth retardation. We herein report a case of 18-month-old girl child who presented chronic diarrhea and failure to thrive and then was diagnosed as a case of classical Bartter syndrome. She was successfully treated with potassium supplementation and ibuprofen therapy.

A Clinco-Bacteriological Study of Leprosy in Paediatric Age Group

Clinico-bacteriological study was done in 51 leprosy patients below 14 years of age. Majority of the patients were males in the age group of 11-14 years. Nearly 84% had not received any prior treatment because of lack of awareness and financial constraints. Only 11.76% had a positive contact history. Skin lesions were present in all cases and 84.3% had lesions mainly on the exposed areas of the body and their number was found to increase significantly with advancing age (p < 0.005). These lesions were hypo-pigmented patches in 88% cases. 88% of cases had hypo-anesthesia and nerve thickening was observed in 24% cases. The most common type of skin lesion was borderline tuberculoid (BT) in 53% cases. Positivity of the skin smears increased significantly as the number of the skin lesions per patient increased (p 0.001). Multibacillary cases were seen in 15.6% of cases and found only in the age group of 10-14 years of age. No statistically significant association between BCG vaccination and prevention of leprosy was seen.

Reduced Arterial Compliance Associated with Metabolic Syndrome in Chinese Children and Adolescents

Objective To explore the metabolic syndrome and its association with arterial compliance in Chinese children and adolescents. Methods 337 participants aged 6 to 18 years with males accounted for 55.8% were grouped according to their traits of metablic syndrome. Anthropometry, blood pressure, fasting plasma glucose, insulin and serum lipid profile were measured. Homeostasis model was assessed and insulin resistance （HOMA-IR） index was measured and calculated for estimating individual insulin resistance. Arterial compliance was also measured using digital pulse wave analyzing method （Micro medical, London）, and stiffness index was calculated. Results The stiffness index in participants with metablic syndrome was significant higher than that in participants with no riskof metablic syndrome [（7.69±1.63） vs （6.25±0.86） m/s, P〈0.01] and stiffness index and HOMA-IR were progressively increased with the increase of traits of metablic syndrom （P for linear trend 〈0.001）. After gender, age, and pubertal development were adjusted, both traits of metablic syndrome and HOMA-IR were correlated positively with stiffness index （both P〈0.05）. Conclusion The clustering of metablic syndrome was closely associated with risk at increased arterial stiffness in Chinese children and adolescents. It was suggested that arterial compliance assessment of children and adolescents might be an important measure for prevention of cardiovascular diseases.

流感给健康儿童及其家庭带来的负担

目的:进行一个前瞻性、多中心的研究,来评估实验室证实的流感对健康儿童及其家庭产生的负担。方法:由5名初级医疗的儿科医师(PCPs)每周抽出两天时间登记来自意大利不同大城市的4个急诊科(EDs)在2001年11月1日至2002年4月30日期间所治疗的患儿。3771名14岁以下没有慢性疾病的儿童参与了该研究,这些儿童是研究期间在EDs或PCP门诊诊断为呼吸道感染的患儿。搜集患儿的鼻咽部拭子进行流感病毒分离及其RNA检测。

粪弹性蛋白酶-1检验对囊性纤维化病胰腺外分泌功能的评估作用优于粪脂肪酶检验

研究背景和目的:胰腺外分泌功能的直接测定法, 具有高敏感度和高特异性。然而,在实际中,尤其对于儿童患者,直接测定法并不实用。囊性纤维化病(CF)的间接检测法中,粪弹性蛋白酶-1 测定已被证实具有高度特异性和敏感度,粪脂肪酶检测的价值尚不明确。本研究分别采用粪弹性蛋白酶-1检测和脂肪酶检测,间接测评CF患儿胰腺外分泌功能。

Blood lead levels among children aged 0 to 6 years in 16 cities of China, 2004-2008

Background The adverse health effects of lead for children under 6 years are well known.Studies to assess the lead exposure among children in China are small in sample size and lack of national representative data.The aim of this study therefore was to describe blood lead levels and identify risk factors for lead exposure among children aged 0 to 6 years living in 16 cities in China.Methods We analyzed data from blood lead levels surveillance in China carried out in 16 large cities between 2004 and 2008.A stratified clustered random sampling strategy was used.A total of 69 968 children aged 0 to 6 years were included.We conducted multiple Logistic regression analyses to explore risk factors to high blood lead level.Results The geometric mean blood lead level of the children was 4.50 μg/dl （median：4.90 μg/dl; IQR：3.20-7.00 μg/dl）.Overall prevalence of blood lead level ≥10.00 μg/dl among 0-to 6-year-old children was 7.57%.But the proportion of blood lead level ≥5.00 but 〈10.00 μg/dl was 42.12%.Blood lead levels were significantly higher in boys （4.63 μg/dl） than in girls （4.35 μg/dl） （P 〈0.0001）.The geometric mean blood lead levels and prevalence of blood lead level ≥10.00 μg/dl increased with age （P 〈0.0001 for the two trends）.After controlling for sociodemographic,dietary and behavior factors,multivariable analysis indicated that lower maternal education,male gender,younger age,often biting pencil or/and toys,walking or playing for long time on the street,not washing hands before eating are major risk factors for higher lead levels.Conclusions The blood lead levels among Chinese children in urban areas are lower than previous studies but close to those of developed countries.However,children with low lead exposure account for almost half and the sociodemographic factors （age,male sex,and low mother education level） continue to be associated with higher blood lead levels.

Effect of Rongchang capsule (茸菖胶囊) on seizure behavior,cognitive impairment,and hippocampal DNA damage and inflammatory factors in epileptic rats

OBJECTIVE: To observe the behavioral changes and changes in DNA fragments and related inflammatory factors in the hippocampus of epileptic rats pretreated with Rongchang capsule(茸菖胶囊).METHODS: Eighty Sprague-Dawley rats were randomly divided into the normal group(NG), model group(MG), sodium valproate group(VG), and Rongchang capsule group(RG)(n = 20 in each group). Pentylentetrazol was administered to the MG, VG, and RG to induce epilepsy. The VG and RG were pretreated with 1/2 the therapeutic dose of sodium valproate and Rongchang capsule, respectively. Changes in convulsion behavior and water maze learning were observed. Single cell gel electrophoresis was used to detect changes in the DNA in the hippocampus. The tail length(TL) and Olive tail moment(OTM) of cells were analyzed by GASP software. The expression of interleukin-1β(IL-1β),high mobility group box 1(HMGB1), transforming growth factor-β(TGF-β), and CCL4 in the hippocampus was determined by Western blotting.RESULTS: Rongchang capsule had a weaker effect on convulsive latency than sodium valproate, but significantly reduced seizure susceptibility. The spatial learning ability of the RG was better than that of the VG(P ≤ 0.01). The TL and OTM were significantly higher in the MG than the NG(P < 0.01). The RG had a better TL and OTM than the VG(P < 0.01).Combined with the microscopy results, DNA damage was most pronounced in the MG. Drug intervention decreased the DNA damage in the VG and RG. The expressions of IL-1β, CCL4, and HMGB1 in the hippocampus were significantly greater in the MG than the NG(P < 0.01), and were significantly reduced in the RG and VG compared with the MG(P < 0.01);however, there was no intergroup difference in the expression of TGF-β. The average values for the expression of inflammatory factors in the hippocampus were higher in the RG than in the VG;thus, Rongchang capsule may have a weaker effect on reducing the expression of inflammatory factors in the hippocampus than sodium valproate.CONCLUSION: Pretreatment with Rongchang capsule prevents or delays cognitive impairment in rats with induced epilepsy, reduces hippocampal DNA damage, and decreases the hippocampal expressions of IL-1β, CCL4, and HMGB1.

CCR2 enhances CD25 expression by FoxP3^(+) regulatory T cells and regulates their abundance independently of chemotaxis and CCR2^(+) myeloid cells

A wide array of chemokine receptors,including CCR2,are known to control Treg migration.Here,we report that CCR2 regulates Tregs beyond chemotaxis.We found that CCR2 deficiency reduced CD25 expression by FoxP3^(+) Treg cells.Such a change was also consistently present in irradiation chimeras reconstituted with mixed bone marrow from wild-type(WT)and CCR2−/−strains.Thus,CCR2 deficiency resulted in profound loss of CD25 ^(hi) FoxP3^(+) Tregs in secondary lymphoid organs as well as in peripheral tissues.CCR2−/−Treg cells were also functionally inferior to WT cells.Interestingly,these changes to Treg cells did not depend on CCR2+monocytes/moDCs(the cells where CCR2 receptors are most abundant).Rather,we demonstrated that CCR2 was required for TLR-stimulated,but not TCR-or IL-2-stimulated,CD25 upregulation on Treg cells.Thus,we propose that CCR2 signaling can increase the fitness of FoxP3^(+) Treg cells and provide negative feedback to counter the proinflammatory effects of CCR2 on myeloid cells.

Causal relationship between 14 site-specific cancers and venous thromboembolism

Background:It has been observed that cancer and venous thromboembolism(VTE)are associated,but anticancer therapy may violate the causality.Therefore,this study aimed to elucidate the causal relationship of various cancers to VTE using Mendelian randomization(MR).Methods:Three MR methods were used to estimate causal effects:Inverse variance weighted(IVW),MR-Egger and weighted median.Sensitivity analyses included Cochran's Q-test,MR-Egger intercept test and MRPRESSO.Gene ontology enrichment analysis was performed to elucidate the underlying mechanisms of VTE development in cancer patients.Results:The primary IVW approach showed that non-Hodgkin's lymphoma(NHL)might increase the risk of VTE(odds ratio[OR]:1.20,95%confidence interval[95%CI]:1.00–1.44,p=0.045),while melanoma possibly reduced the risk of VTE(OR:0.89,95%CI:0.82–0.97,p=0.006),although there was no significance after adjustment for multiple testing.No association was observed between VTE risk and other site-specific cancers.Gene ontology enrichment analysis revealed that vitamin D played an important role in the development of VTE in cancer patients.Conclusions:Our findings suggested that genetically predicted NHL was associated with higher VTE risk,whereas melanoma had lower VTE risk compared with other site-specific cancers.Moreover,this study suggested that anticancer therapy and increased extensive examination might play a more important role in VTE development than the nature of cancer.