Enabling Wasted A4 Papers as a Promising Carbon Source to Construct Partially Graphitic Hierarchical Porous Carbon for High-Performance Aqueous Zn-Ion Storage.

Considering the superiorities of abundance, easy collection, low cost, and nearly constant composition, the wasted A4 papers are deemed as a recyclable and scalable carbon source to fabricate functional carbon materials for Zn-ion hybrid supercapacitors (ZIHSCs), which integrate the supercapacitors' high-power output and batteries' high energy density. Herein, the wasted A4 papers are efficiently converted into an advanced carbon material owning a hierarchical porous structure with a high surface area and interconnected multiscale channels, a graphitic structure, and a good level of N/O codoping. By taking advantage of these features, an express electron/ion transfer pathway, a large accessible surface interface, and a robust architecture are achieved for swift kinetics, numerous active sites, and excellent steadiness to afford a charming Zn2+ storage capability for the aqueous coin-type ZIHSC device (a high capacity of 244 mAh g-1 at 0.1 A g-1 with a capacity conservation of 116.4 mAh g-1 even amplifying the current density by 200 times, a supreme energy density of 190.4 Wh kg-1, a supreme power output of 18 kW kg-1, and an eminent durability of 93.8% over 10,000 cycles at 10 A g-1). Excitingly, the quasi-solid ZIHSC device also bespeaks an enjoyable capacity of 211.7 mAh g-1, a high energy density of 159.3 Wh kg-1, good mechanical flexibility, and a low self-discharge rate. This work puts forward a simple and scalable strategy to enable the wasted A4 paper as a competitive carbon source to construct advanced cathode material for Zn2+ storage.

Unique genotype-phenotype correlations within LAMA2-related limb girdle muscular dystrophy in Chinese patients.

Background: LAMA2-related limb girdle muscular dystrophy (LGMD R23) is rare. The detailed clinical phenotypes and genetic information associated with LGMD R23 are unknown. Methods: We conducted a retrospective cross-sectional and longitudinal study on 19 LGMD R23 patients. Results: Normal early motor development was observed in 84.2% patients. Mild orthopedic complications were observed in 42.1% patients. 36.8% patients had seizures, which is unusually frequent in LGMD. Epilepsy was eventually diagnosed in 26.3% patients. 46.7% patients presented with motor neuropathy. Genetic analysis identified 29 pathogenic variants, with missense and frameshift variants being the most common. The mutant sites were mainly distributed in the N-terminal and G-like domains of laminin. The missense variants are distributed near the N-terminus (exons 3-11), whereas frameshift variants are distributed in exons 12-65. Five patients were diagnosed with epilepsy and all of them harbor at least one missense variants in exon 4. 71.4% variants of patients with motor neuropathy located in the LN domain. Conclusions: Missense variants in exon 4 maybe correlated with epilepsy and variants in the LN domain maybe correlated with motor neuropathy in Chinese patients. Our study expands the clinical and genetic spectrum caused by LAMA2 variations and provides novel genotype-phenotype correlations of LGMD R23.

Pan-genome analysis of the Burkholderia gladioli PV. Cocovenenans reveal the extent of variation in the toxigenic gene cluster.

Burkholderia gladioli has been reported as the pathogen responsible for cases of foodborne illness in many countries. The poisonous bongkrekic acid (BA) produced by B. gladioli was linked to a gene cluster absent in non-pathogenic strains. The whole genome sequence of eight bacteria strains, which were screened from the collected 175 raw food and environmental samples, were assembled and analyzed to detect a significant association of 19 protein-coding genes with the pathogenic status. Except for the common BA synthesis-related gene, several other genes, including the toxin-antitoxin genes, were also absent in the non-pathogenic strains. The bacteria strains with the BA gene cluster were found to form a single cluster in the analysis of all B. gladioli genome assemblies for the variants in the gene cluster. Divergence of this cluster was detected in the analysis for both the flanking sequences and those of the whole genome level, which indicates its complex origin. Genome recombination was found to cause a precise sequence deletion in the gene cluster region, which was found to be predominant in the non-pathogenic strains indicating the possible effect of horizontal gene transfer. Our study provided new information and resources for understanding the evolution and divergence of the B. gladioli species.

Generation of an induced pluripotent stem cell line (TRNDi012-B) from Fibrodysplasia Ossificans Progressiva (FOP) patient carrying a heterozygous mutation c. 617G > A in the ACVR1 gene.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of progressive ossification of skeletal muscle, fascia, tendons, and ligaments. Most FOP cases are caused by a heterozygous c. 617G > A mutation in the ACVR1 gene which encodes a gain-of-function of bone morphogenetic protein type I receptor. A human induced pluripotent stem cell (iPSC) line was generated from the dermal skin fibroblasts of a FOP patient who carries the c. 617G > A mutation in the ACVR1 gene. This iPSC line provides an attractive resource for FOP disease modeling.

Saracatinib is an efficacious clinical candidate for fibrodysplasia ossificans progressiva.

Currently, no effective therapies exist for fibrodysplasia ossificans progressiva (FOP), a rare congenital syndrome in which heterotopic bone is formed in soft tissues owing to dysregulated activity of the bone morphogenetic protein (BMP) receptor kinase ALK2 (also known as ACVR1). From a screen of known biologically active compounds, we identified saracatinib as a potent ALK2 kinase inhibitor. In enzymatic and cell-based assays, saracatinib preferentially inhibited ALK2, compared with other receptors of the BMP/TGF-ß signaling pathway, and induced dorsalization in zebrafish embryos consistent with BMP antagonism. We further tested the efficacy of saracatinib using an inducible ACVR1Q207D-transgenic mouse line, which provides a model of heterotopic ossification (HO), as well as an inducible ACVR1R206H-knockin mouse, which serves as a genetically and physiologically faithful FOP model. In both models, saracatinib was well tolerated and potently inhibited the development of HO, even when administered transiently following soft tissue injury. Together, these data suggest that saracatinib is an efficacious clinical candidate for repositioning in FOP treatment, offering an accelerated path to clinical proof-of-efficacy studies and potentially significant benefits to individuals with this devastating condition.

Torin 2 Derivative, NCATS-SM3710, Has Potent Multistage Antimalarial Activity through Inhibition of P. falciparum Phosphatidylinositol 4-Kinase (Pf PI4KIIIß).

Drug resistance is a constant threat to malaria control efforts making it important to maintain a good pipeline of new drug candidates. Of particular need are compounds that also block transmission by targeting sexual stage parasites. Mature sexual stages are relatively resistant to all currently used antimalarials except the 8-aminoquinolines that are not commonly used due to potential side effects. Here, we synthesized a new Torin 2 derivative, NCATS-SM3710 with increased aqueous solubility and specificity for Plasmodium and demonstrate potent in vivo activity against all P. berghei life cycle stages. NCATS-SM3710 also has low nanomolar EC50s against in vitro cultured asexual P. falciparum parasites (0.38 ± 0.04 nM) and late stage gametocytes (5.77 ± 1 nM). Two independent NCATS-SM3710/Torin 2 resistant P. falciparum parasite lines produced by growth in sublethal Torin 2 concentrations both had genetic changes in PF3D7_0509800, annotated as a phosphatidylinositol 4 kinase (Pf PI4KIIIß). One line had a point mutation in the putative active site (V1357G), and the other line had a duplication of a locus containing Pf PI4KIIIß. Both lines were also resistant to other Pf PI4K inhibitors. In addition NCATS-SM3710 inhibited purified Pf PI4KIIIß with an IC50 of 2.0 ± 0.30 nM. Together the results demonstrate that Pf PI4KIIIß is the target of Torin 2 and NCATS-SM3710 and provide new options for potent multistage drug development.

Bone Morphogenetic Protein 9 Is a Mechanistic Biomarker of Portopulmonary Hypertension.

RATIONALE: BMP9 (bone morphogenetic protein 9) is a circulating endothelial quiescence factor with protective effects in pulmonary arterial hypertension (PAH). Loss-of-function mutations in BMP9, its receptors, and downstream effectors have been reported in heritable PAH. OBJECTIVES: To determine how an acquired deficiency of BMP9 signaling might contribute to PAH. METHODS: Plasma levels of BMP9 and antagonist soluble endoglin were measured in group 1 PAH, group 2 and 3 pulmonary hypertension (PH), and in patients with severe liver disease without PAH. MEASUREMENTS AND MAIN RESULTS: BMP9 levels were markedly lower in portopulmonary hypertension (PoPH) versus healthy control subjects, or other etiologies of PAH or PH; distinguished PoPH from patients with liver disease without PAH; and were an independent predictor of transplant-free survival. BMP9 levels were decreased in mice with PH associated with CCl4-induced portal hypertension and liver cirrhosis, but were normal in other rodent models of PH. Administration of ALK1-Fc, a BMP9 ligand trap consisting of the activin receptor-like kinase-1 extracellular domain, exacerbated PH and pulmonary vascular remodeling in mice treated with hypoxia versus hypoxia alone. CONCLUSIONS: BMP9 is a sensitive and specific biomarker of PoPH, predicting transplant-free survival and the presence of PAH in liver disease. In rodent models, acquired deficiency of BMP9 signaling can predispose to or exacerbate PH, providing a possible mechanistic link between PoPH and heritable PAH. These findings describe a novel experimental model of severe PH that provides insight into the synergy between pulmonary vascular injury and diminished BMP9 signaling in the pathogenesis of PAH.

Discovery of 3-(4-sulfamoylnaphthyl)pyrazolo[1,5-a]pyrimidines as potent and selective ALK2 inhibitors.

The pyrazolo[1,5-a]pyrimidine LDN-193189 is a potent inhibitor of activin receptor-like kinase 2 (ALK2) but is nonselective for highly homologous ALK3 and shows only modest kinome selectivity. Herein, we describe the discovery of a novel series of potent and selective ALK2 inhibitors by replacing the quinolinyl with a 4-(sulfamoyl)naphthyl, yielding ALK2 inhibitors that exhibit not only excellent discrimination versus ALK3 but also high kinome selectivity. In addition, the optimized compound 23 demonstrates good ADME and in vivo pharmacokinetic properties.

Efficient Synthesis of 1,9-Substituted Benzo[h][1,6]naphthyridin-2(1H)-ones and Evaluation of their Plasmodium falciparum Gametocytocidal Activities.

A novel three-component, two-step, one-pot nucleophilic aromatic substitution (SNAr)-intramolecular cyclization-Suzuki coupling reaction was developed for the synthesis of benzo[h][1,6]naphthyridin-2(1H)-ones (Torins). On the basis of the new efficiently convergent synthetic route, a library of Torin analogs was synthesized. The antimalarial activities of these compounds were evaluated against asexual parasites using a growth inhibition assay and gametocytes using a viability assay.

Novel lead structures with both Plasmodium falciparum gametocytocidal and asexual blood stage activity identified from high throughput compound screening.

BACKGROUND: Blocking malaria transmission is an important step in eradicating malaria. In the field, transmission requires the production of sexual stage Plasmodium parasites, called gametocytes, which are not effectively killed by the commonly used anti-malarials allowing individuals to remain infectious after clearance of asexual parasites. METHODS: To identify new gametocytocidal compounds, a library of 45,056 compounds with diverse structures was screened using a high throughput gametocyte viability assay. The characteristics of active hits were further evaluated against asexual stage parasites in a growth inhibition assay. Their cytotoxicity were tested against mammalian cells in a cytotoxicity assay. The chemical scaffold similarity of active hits were studied using scaffold cluster analysis. RESULTS: A set of 23 compounds were identified and further confirmed for their activity against gametocytes. All the 23 confirmed compounds possess dual-activities against both gametocytes responsible for human to mosquito transmission and asexual parasites that cause the clinical symptoms. Three of these compounds were fourfold more active against gametocytes than asexual parasites. Further cheminformatic analysis revealed three sets of novel scaffolds, including highly selective 4-1H-pyrazol-5-yl piperidine analogs. CONCLUSIONS: This study revealed important new structural scaffolds that can be used as starting points for dual activity anti-malarial drug development.

Association of Hypoxia-Inducible Factor-2 Alpha Gene Polymorphisms with the Risk of Hepatitis B Virus-Related Liver Disease in Guangxi Chinese: A Case-Control Study.

OBJECTIVE: Hypoxia-inducible factor-2 alpha (HIF-2a) plays a major role in the progression of disease, although the role of HIF-2α gene polymorphisms in hepatitis B virus (HBV)-related diseases remains elusive. The aim of this study is to determine whether HIF-2a rs13419896 and rs6715787 single-nucleotide polymorphisms (SNPs) are associated with susceptibility to chronic hepatitis B (CHB), liver cirrhosis (LC), or hepatocellular carcinoma (HCC). METHOD: A case-control study of 107 patients with CHB, 83 patients with LC, 234 patients with HCC, and 224 healthy control subjects was carried out, and the HIF-2a rs13419896 and rs6715787 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: No significant differences were observed in the genotype or allele frequency of two HIF-2a SNPs between the cases and controls (all p>0.05). However, in subgroup analysis by gender, the HIF-2a rs13419896 GA and AA genotypes were significantly associated with a risk of CHB (odds ratio [OR] = 3.565, 95% confidence interval [CI] = 1.123-11.314, p = 0.031 and OR = 12.506, 95% CI = 1.329-117.716, p = 0.027) in females, and the A allele of rs13419896 was associated with a risk of CHB (OR = 2.624, 95% CI = 1.244-5.537, p = 0.011) and LC (OR = 2.351, 95% CI = 1.002-5.518, p = 0.050) in females. The rs6715787 CG genotype polymorphism may contribute to a reduced risk of LC in the Guangxi Zhuang Chinese population (OR = 0.152, 95% CI = 0.028-0.807, p = 0.027), as determined via subgroup analysis by ethnicity. Moreover, binary logistic regression analyses that were adjusted by drinking status indicated that the AA genotype of rs13419896 may contribute to an increased risk of LC in the non-alcohol-drinking population (OR = 3.124, 95% CI = 1.091-8.947, p = 0.034). In haplotype analysis, GG haplotype was significantly associated with a reduced risk of LC (OR = 0.601, 95% CI = 0.419-0.862, p = 0.005). CONCLUSIONS: The HIF-2a rs13419896 polymorphism is associated with an increased risk of CHB and LC in the Guangxi Chinese population, especially in females and in the non-alcohol-drinking population, while the HIF-2a gene rs6715787 polymorphism is associated with a decreased risk of LC in the Guangxi Zhuang population.

In vitro evaluation of imidazo[4,5-c]quinolin-2-ones as gametocytocidal antimalarial agents.

Novel imidazo[4,5-c]quinolin-2-ones were synthesized and evaluated in asexual blood stage and late stage gametocyte assays of Plasmodium falciparum, a major causative agent of malaria. The design of these compounds is based on a recently identified lead compound from a high throughput screen. A concise synthesis was developed that allowed for generation of analogues with substitution around both the quinoline and imidazolidinone rings. Through structure-activity relationship studies, a number of potent compounds were identified that possessed excellent antimalarial activity against both the asexual and sexual stages with minimal cytotoxicity in mammalian cells. This is the first Letter describing SAR and gametocytocidal activity of imidazo[4,5-c]quinolin-2-ones, a new lead series for malaria treatment and prevention.

Role of IL-18 Gene Promoter Polymorphisms, Serum IL-18 Levels, and Risk of Hepatitis B Virus-related Liver Disease in the Guangxi Zhuang Population: a Retrospective Case-Control Study.

BACKGROUND: The aim of this study was to assess the relationship between IL-18 gene polymorphisms and HBV-related diseases and whether these polymorphisms influence its expression in the Guangxi Zhuang population. MATERIALS AND METHODS: We enrolled 129 chronic HBV infected (CHB) patients, 86 HBV-related liver cirrhosis (LC) patients and 160 healthy controls in our study. Polymerase chain reaction-restriction fragment length polymorphism methods were used to detect IL-18 gene -607C/A, -137G/C polymorphisms, and an ELISA kit was employed to determine serum IL-18 levels. RESULTS: No correlation was found between the -607C/A polymorphism and risk of HBV-related disease. For the -137G/C polymorphism, the GC genotype and C allele were associated with a significantly lower risk of CHB (95%CI: 0.32-0.95, p=0.034 and 95%CI: 0.35-0.91, p=0.018) and HBV-related LC (95%CI: 0.24-0.89, p=0.022 and 95%CI: 0.28-0.90, p=0.021). A similar decreased risk was also found with the A-607C-137 haplotype. With respect to IL-18 expression, it was significantly lower in both patient groups, but no association was noted between the two polymorphisms in the IL-18 gene and its expression. CONCLUSIONS: Our study indicated that the -137C allele in the IL-18 gene may be a protective factor for HBV-related disease, and serum IL-18 level may be inversely associated with CHB and HBV-related LC.

Association between IL-18 polymorphisms, serum levels, and HBV-related hepatocellular carcinoma in a Chinese population: a retrospective case-control study.

BACKGROUND: Interleukin (IL)-18 gene polymorphisms have been found to play multiple roles in various diseases. However, studies focused on its involvement in hepatocellular carcinoma (HCC) remains controversial, and no much study has taken IL-18 serum levels into consideration. This study investigates the association between IL-18 polymorphisms and risk of hepatitis B virus-related HCC and their impact on serum IL-18 serum levels. METHODS: A total of 153 patients and 165 healthy controls were enrolled in this study. Polymorphisms at positions -607C/A and -137G/C in the IL-18 gene were determined using the polymerase chain reaction-restriction fragment length polymorphism method. Serum IL-18 levels were determined with an ELISA kit. RESULTS: No relationship was found between the -607C/A polymorphism and an individual's susceptibility to HCC. For the -137G/C polymorphism, the GC genotype and C allele were found to be significantly associated with decreased HCC risk (OR 0.506, 95% CI 0.290-0.882, P = 0.016 and OR 0.520, 95% CI 0.332-0.814, P = 0.004, respectively). The A(-607)C(-137) haplotype was also associated with a significant decreased risk of HCC (OR 0.495, 95% CI 0.294-0.834, P = 0.007). Serum IL-18 levels were found to be significantly lower in HCC patients compared to the control group in both the overall population and subjects with the different SNPs. Further, no association was found between serum IL-18 levels and the different genotypes within the same SNP. CONCLUSION: These findings suggest that the -137G/C SNP in IL-18 may be a protective factor against HCC. Nevertheless, none of the studied SNPs was associated with the expression of IL-18.

Association between catalase gene polymorphisms and risk of chronic hepatitis B, hepatitis B virus-related liver cirrhosis and hepatocellular carcinoma in Guangxi population: a case-control study.

Reactive oxygen species (ROS) play critical roles in hepatocarcinogenesis. The catalase (CAT) enzyme is involved in the repair of ROS. Therefore, we investigate the association between CAT gene polymorphisms and the risk of hepatocellular carcinoma (HCC). A total of 715 subjects were divided into 4 groups: 111 chronic hepatitis B (CHB) patients, 90 hepatitis B virus (HBV)-related liver cirrhosis (LC) patients, 266 HBV-HCC patients, and 248 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect CAT gene rs1001179, rs769217, and rs7943316 polymorphisms. Binary logistic regression analyses adjusting for sex, age, ethnicity, smoking and alcohol consumption, and body mass index suggested that subjects carrying the rs769217 T allele were at marginally increased risk of CHB, LC, and HCC, with adjusted odds ratios (ORs) of 1.51 (95% confidence interval [CI] = 1.04-2.20, P = 0.029), 1.48 (95% CI = 1.03-2.14, P = 0.035), and 1.51 (95% CI = 1.14-1.98, P = 0.004), respectively. Similarly, those individuals carrying the rs769217 TT genotype had a moderately increased risk of CHB, LC, and HCC, with adjusted ORs of 2.11 (95% CI = 1.05-4.22, P = 0.035), 2.00 (95% CI, 1.01-3.95, P = 0.047), and 1.93 (95% CI = 1.14-3.28, P = 0.015), respectively. Moreover, subjects carrying the rs769217 CT genotype and at least 1 copy of the T allele (dominant model) were 1.78 times and 1.83 times more likely to develop HCC, respectively (OR = 1.78, 95% CI = 1.16-2.73, P = 0.009 and OR = 1.83, 95% CI = 1.23-2.71, P = 0.003). This association between CAT rs769217 T alleles and HCC risk is significantly strengthened among men, nonsmokers, nondrinkers, and among individuals <50 years of age. Furthermore, we found 1 high-risk haplotype GTA for CHB (OR = 1.45, 95% CI = 1.05-2.01) and 1 protective haplotype GCA for HCC risk (OR = 0.67, 95% CI = 0.52-0.87). We did not found any significant difference in CAT rs1001179 and rs7943316 polymorphisms between controls and cases. Our findings suggest that the CAT rs769217 T allele is associated with increased risk of CHB, HBV-LC, and HBV-HCC in Guangxi population.

Relationships between the Osteocalcin gene polymorphisms, serum osteocalcin levels, and hepatitis B virus-related hepatocellular carcinoma in a Chinese population.

BACKGROUND: Available evidence has demonstrated that osteocalcin may play a role in pathogenesis of cancer, and mutation of the osteocalcin gene may be involved in the cancer development. The aim of this study is to determine whether osteocalcin gene polymorphisms are associated with hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) among Chinese population. METHODS: A total of 515 subjects were divided into four groups: 129 patients with chronic hepatitis B (CHB), 62 patients with HBV-related liver cirrhosis (LC), 154 patients with HBV-related HCC, and 170 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect osteocalcin gene rs1800247 and rs1543297 polymorphisms. RESULTS: Compared with healthy controls, the rs1800247 HH and Hh genotypes were associated with a significantly increased susceptibility to HCC (HH versus hh: OR = 6.828, 95% CI 2.620-17.795, P < 0.001; Hh versus hh: OR = 6.306, 95% CI 3.480-11.423, P < 0.001, respectively). Similarly, the subjects bearing the H allele of rs1800247 had more than a 2.4-fold increased risk for development of HCC (OR = 2.484, 95% CI 1.747-3.532, P < 0.001) compared with those bearing the h allele. In addition, we found significant decreased serum osteocalcin levels in HBV-related HCC patients (11.73 ± 8.18 ng/mL) compared with healthy controls (15.3 ± 6.06 ng/mL). Furthermore, the serum osteocalcin levels were significantly lower in HCC patients than healthy controls among the individuals with heterozygous Hh genotype (P = 0.003) and CT genotype (P < 0.001). In contrast, there were no significant differences in the genotype and allele of rs1543297 polymorphisms between the groups of patients and healthy controls. CONCLUSIONS: These findings for the first time suggest that genetic variant in osteocalcin gene rs1800247 polymorphisms may be a risk factor for HBV-related HCC. We also find an inverse association of serum osteocalcin levels with HCC.

The CD4 C868T Polymorphism and Its Correlation with HIV-1 Infection in a Chinese Population.

Previous studies performed in Kenya have suggested that the C868T single nucleotide polymorphism (SNP) in CD4 increases the risk of HIV-1 acquisition; however, no relevant study has been conducted in China. To evaluate the influence of this SNP on risk of HIV-1 infection in a Chinese population, the CD4 genotype was determined by DNA sequencing in 101 HIV-1 patients and 102 healthy controls. No significant differences in the genotype and allele distributions of this polymorphism were observed among the patient and control groups. Additionally, binary logistic regression analyses adjusted by age and gender revealed that the C868T polymorphism was not associated with risk of HIV-1 infection. Furthermore, when analyses of genotype and allele frequencies were stratified by gender, similar nonsignificant results were found. Our study demonstrates a null association between the CD4 C868T polymorphism and an individual's susceptibility of HIV-1 acquisition in a Chinese population. Further studies are warranted to confirm these results.

The MTHFR C677T polymorphism contributes to increased risk of Alzheimer's disease: evidence based on 40 case-control studies.

The association between methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and Alzheimer's Disease (AD) risk has been widely reported with inconsistent results. We performed an updated meta-analysis of all available studies to clarify this situation. We conducted a comprehensive literature search in PubMed Alzgene, Embase, and Chinese Biomedical Literature database (CBM) for the period up to June 2014. Finally, a total of 40 case-control studies with 4503 AD cases and 5767 controls were included. Overall, significant increased AD risk was found, when all studies were pooled into the meta-analysis. In subgroup analyses stratified by ethnicity, age of onset, and APOE ϵ4 status, significant increased AD risk was found in Asians, late-onset AD, and APOE ϵ4 carriers, but not in Caucasians, early-onset AD, and non-APOE ϵ4 carriers. The present meta-analysis suggested that the MTHFR is a candidate gene for AD susceptibility. The MTHFR C677T polymorphism may be a risk factor for AD in Asians, APOE ϵ4 carriers, and late-onset AD. Further, investigations taking the potential gene-gene and gene-environmental interactions into consideration for the MTHFR C677T polymorphism should be conducted.

Establishing reference values for blood urea nitrogen and serum creatinine in Chinese Han ethnic adult men.

BACKGROUND: The aim was to calculate the two-sided 95th percentile reference values for blood urea nitrogen (BUN) and serum creatinine (SCr) in Chinese Han ethnic adult men. METHODS: Serum samples were collected from Chinese Han ethnic adult men aged 20 - 69 years. After screening based on the inclusion and exclusion criteria, a total of 1575 individuals were enrolled in our study. BUN and SCr values were measured on an automatic analyzer (Dade Behring, USA). The data was analyzed and calculated using nonparametric statistical methods. RESULTS: BUN and SCr values were not normally distributed. The reference values were in the range 3.3 - 7.5 mmol/L for BUN and 64 - 113 micromol/L for SCr. BUN levels were significantly lower in the smoking group than the non-smoking group (Z = -4.52, p < 10(-5)). An increase with age was observed in BUN levels (r(s) = 0.172, p < 0(-5)) and lower SCr levels were weakly associated with the older subjects (r(s) = -0.071, p = 0.005). Moreover, it was found that higher Body Mass Index (BMI) tended toward higher levels of SCr (r(s) = 0.118, p < 10(-5)). CONCLUSIONS: The reference values established for BUN and SCr exhibit a slight deviation compared to those developed in previous studies. We propose reference values of BUN for smokers and non-smokers be constructed, and age- and BMI-specific reference values be applied in clinical laboratories.

Determination of reference intervals for serum complement C3 and C4 levels in Chinese Han ethnic males.

BACKGROUND: Clinical laboratory reference intervals (RIs) for serum complement C3 and C4 levels have been established in many countries but there is a lack of published data regarding normal RIs in Chinese population. We attempted to establish RIs for serum complement C3 and C4 levels in Chinese Han ethnic males. METHODS: A total of 1,234 healthy male subjects, aged 20 - 69 years, were collected from the Fangchenggang Area Male Health and Examination Survey (FAMHES). Serum complement C3 and C4 levels were measured by immunoturbidimetry. The two-sided 95-percentile RIs were calculated using parametric statistical methods. RESULTS: Serum C3 values showed normal distribution and C4 were log-normal distributed. The two-sided 95% RIs (mean +/- 2 SD) for serum C3 and C4 were 0.656 - 1.52 g/L and 0.181 - 0.561 g/L, respectively. Body Mass Index (BMI) had a significant positive association with C3 (r = 0.342) and C4 (r = 0.258), and age had a significant positive association with C4 (r = 0.117). No significant difference was found either between smoking groups or drinking groups. A significant increase with BMI was found both for C3 (p < 0.001) and C4 (p < 0.001). BMI-specific RIs were also calculated. CONCLUSIONS: The RIs for serum C3 and C4 show a slight deviation compared to previously reported reference levels. BMI-specific reference values should be implemented in clinical laboratories.