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Zhe-Feng Zhao,1,* Bing-Bing Liu,1,* Jian-Nan Zhang,2,* Ni Shi,3,* Ping Zhang,1,* Gang-Zhi Yang,4 Yu-Fu Cao,4 Long-He Tian,4 Cheng-Cai Qiu,5 Yang Gao6,7 1Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 2Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 3Department of Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 4Department of Neurosurgery, People’s Hospital of Hegang City, Hegang, Heilongjiang, People’s Republic of China; 5Department of Neurosurgery, Traditional Chinese Medicine Hospital of Jixi City, Jixi, Heilongjiang, People’s Republic of China; 6Department of Critical Care Medicine, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 7Institute of Critical Care Medicine, The Sino Russian Medical Research Center of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhe-Feng Zhao, Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Email know810512@163.com Yang Gao, Department of Critical Care Medicine, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Email gaoyang0312@126.comObjective: In this study, we aimed to explore the demographic and clinical factors that could determine short- and long-term complete pain relief (CPR) in adult patients with primary trigeminal neuralgia (PTN) after microvascular decompression (MVD) to guide clinical practice.Methods: This single-center retrospective study included adult patients with PTN who underwent MVD as their initial neurosurgical procedure in the Department of Neurosurgery at the Second Affiliated Hospital of Harbin Medical University from January 2017 to December 2019 and completed a 3-year post-surgery follow-up. Demographic and clinical information was obtained from medical records. Pain relief of adult patients with PTN at various time points after sufficient decompression of trigeminal nerve (TN) during MVD was determined and classified by the patient’s subjective response and medications use. Pain relief of local patients was evaluated by outpatient follow-up at various time points, whereas that of local cases who could not return to outpatient or non-local cases was assessed through telephone or WeChat.Results: In univariate analysis, compression degree of TN and type of conflicting vessels constantly showed significant differences between the two groups at 3 months, 6 months, 1 year, 2 years, and 3 years after MVD. Compression degree of TN and type of conflicting vessels at various time points after MVD were always the related factors to CPR in logistic regression analysis, with the former having the greatest impact. The areas under the receiver operating characteristic (ROC) curve of CPR at various time points after MVD were 0.937, 0.874, 0.879, 0.864, and 0.869, respectively.Conclusion: In summary, compression degree of TN and type of conflicting vessels can determine short- and long-term CPR in adult patients with PTN after MVD.Keywords: compression degree of trigeminal nerve, type of conflicting vessels, microvascular decompression, sufficient decompression of trigeminal nerve, complete pain relief, primary trigeminal neuralgia

Objective: To observe the clinical characteristics and epidemic trends of human leptospirosis in Wenzhou, Zhejiang Province, China, from 2020 to 2022 and to provide a scientific basis for prevention and control in this area., Methods: Descriptive epidemiological methods were used in Wenzhou, China, from 2020 to 2022. Leptospira antibodies were detected by a microscopic agglutination test (MAT), and laboratory tests were conducted to analyse the prevalence of Leptospira in the population., Results: From 2020 to 2022, a total of 41 cases of human leptospirosis were reported in Wenzhou, China, with no deaths and an average annual incidence of 0.1428/100,000. The highest incidence was in 2021 (30 cases, incidence rate: 0.31/100,000), and the lowest incidence was in 2022 (three cases, incidence rate: 0.04/100,000). The high-incidence season was from August to October, in which a total of 36 cases were reported, accounting for 87.80% of total cases, most of which were males. The main occupation was farming, which accounted for 70.7% of the total number of cases. 90.2% of cases had fever symptoms, and the body temperature was between 36.5 ℃ and 40.1 ℃. A total of 32 positive samples were detected by MAT in six main groups, mainly the Autumnalis serogroup., Conclusions: The incidence of leptospirosis in Wenzhou, China, was at a moderate level from 2020 to 2022. Localities should actively strengthen the monitoring of leptospirosis host animals and populations, understand the infection rate and floral changes and prevent leptospirosis outbreaks., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 YueYing Zhou, XianMin Wang, HuiJuan Li, Zhengxing Wu, Ning Pan, HongYe Ning, SaiDuo Liu, XinChun Ye, Chao-Chao Qiu, KaiJia Wu, JiChan Shi.)

The study analyzes the risk factors associated with antituberculosis drug-induced liver injury (ATB-DILI), and the relationship between ATB-DILI and NAT2 gene polymorphisms. Out of the 324 included patients, 57 (17.59%) developed ATB-DILI. Age, history of liver disease, alcohol consumption and timing of antituberculosis (ATB) treatment were independent risk factors for ATB-DILI in the patients with tuberculosis (TB; p < 0.05). There was a significant difference in the distribution of NAT2 metabolic phenotypes between the study group and the control group (p < 0.05). The ATB drug treatment for pulmonary TB can cause a high incidence of ATB-DILI. Age, history of liver disease, alcohol consumption and timing of ATB treatment are independent risk factors for ATB-DILI in patients with TB.

Introduction: Chronic thyrotoxic myopathy (CTM) is a common, easily neglected complication of hyperthyroidism. There are currently no standard diagnostic criteria for CTM, and the ultrasonic characteristics of CTM-affected skeletal muscle remain unclear. Herein, we aimed to evaluate hyperthyroid patients for CTM by ultrasound and identify ultrasonic muscle parameter cutoffs for CTM diagnosis., Materials and Methods: Each participant underwent ultrasonography. The original (muscle thickness (MT), pennation angle (PA), and cross-sectional area (CSA)) and corrected (MT/height (HT), MT/body mass index (BMI), CSA/HT, and CSA/BMI) parameters of the vastus lateralis and vastus medialis (VM) were evaluated. The diagnostic effectiveness of ultrasound for predicting CTM was determined using receiver operating characteristic (ROC) curve analysis. Our study included 203 participants: 67 CTM patients (18 males, 49 females), 67 non-CTM patients (28 males, 39 females) and 69 healthy controls (20 males, 49 females)., Results: The CTM group had lower muscular ultrasonic and anthropometric parameters, higher thyroid hormone and thyroid-stimulating hormone receptor antibody (TRAb) levels, and a longer duration of hyperthyroidism than the non-CTM group (P < 0.05). The VM-PA, VM-CSA, VM-CSA/HT, and VM-CSA/BMI were lower in females than in males (P < 0.05). Free thyroxine (FT4) and TRAb both showed significant negative correlations with VM-MT, VM-MT/HT, VM-CSA, and VM-CSA/HT (P < 0.05). VM-MT/BMI and VM-CSA/HT, respectively, best predicted male and female CTM (AUC = 0.84, 0.85; cutoff ≤ 0.07, < 4.01)., Conclusion: Ultrasound measurement of muscular parameters, especially in the VM, is a valid and feasible way of diagnosing and characterizing possible CTM in hyperthyroidism.

Objective: To evaluate the value of ultrasound-based radiomics in the preoperative prediction of type I and type II epithelial ovarian cancer., Methods: A total of 154 patients with epithelial ovarian cancer were enrolled retrospectively. There were 102 unilateral lesions and 52 bilateral lesions among a total of 206 lesions. The data for the 206 lesions were randomly divided into a training set (53 type I + 71 type II) and a test set (36 type I + 46 type II) by random sampling. ITK-SNAP software was used to manually outline the boundary of the tumor, that is, the region of interest, and 4976 features were extracted. The quantitative expression values of the radiomics features were normalized by the Z-score method, and the 7 features with the most differences were screened by using the Lasso regression tenfold cross-validation method. The radiomics model was established by logistic regression. The training set was used to construct the model, and the test set was used to evaluate the predictive efficiency of the model. On the basis of multifactor logistic regression analysis, combined with the radiomics score of each patient, a comprehensive prediction model was established, the nomogram was drawn, and the prediction effect was evaluated by analyzing the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve., Results: The AUCs of the training set and test set in the radiomics model and comprehensive model were 0.817 and 0.731 and 0.982 and 0.886, respectively. The calibration curve showed that the two models were in good agreement. The clinical decision curve showed that both methods had good clinical practicability., Conclusion: The radiomics model based on ultrasound images has a good predictive effect for the preoperative differential diagnosis of type I and type II epithelial ovarian cancer. The comprehensive model has higher prediction efficiency., (© 2022. The Author(s).)

The pollution of micro/nanoplastics in the natural environment is becoming increasingly serious, but the potential effects of nanoplastics on crops remain unclear. In the present study, the effects of polystyrene nanoplastics (PS-NPs) with a particle size of 80 nm on the chlorophyll content, antioxidant enzyme activity, and nutritional quality of Allium sativum L. were explored via hydroponic culture. The results showed that the chlorophyll contents in leaves of A. sativum treated with PS-NPs were significantly lower than those in the control, indicating that the synthesis of chlorophyll was inhibited. The superoxide dismutase (SOD), ascorbate peroxidase (APX) activities, and proline contents in leaves of A. sativum initially increased but then decreased with the increase in ρ (PS-NPs). The activity of guaiacol peroxidase (POD) increased with the increase in ρ (PS-NPs) for 10 days of treatment; however, it was inhibited for 20 days of treatment. The malondialdehyde (MDA) content increased with the rise in ρ (PS-NPs). When ρ (PS-NPs) increased to 100 mg·L -1 , the MDA content in leaves of A. sativum increased by 43.24% and 89.70% for 10 and 20-day treatments, respectively, compared with those in the control. Meanwhile, the contents of soluble protein, soluble sugar, and vitamin C were higher than those in the control for 10-day treatments; however, the vitamin C content decreased by 26.53% after 20 days of treatment. These results indicated that PS-NPs had a significant oxidative stress on A. sativum , and a high concentration of PS-NPs stress would have deleterious effects on the nutritional quality of A. sativum .

Objective: This study is aimed at identifying stemness-related genes in pancreatic ductal adenocarcinoma (PDAC)., Methods: The RNA-seq data of PADC patients were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The mRNA expression-based stemness index (mRNAsi) and epigenetically regulated mRNAsi (EREG-mRNAsi) of PADC patients were evaluated. The mRNAsi-related gene sets in PADC were identified by weighted gene coexpression network analysis (WGCNA). The key genes were further analyzed using functional enrichment analysis. The Kaplan-Meier survival analysis and the Cox proportional hazards model were used to evaluate the prognostic value of the key genes. Prognostic hub genes were used to establish nomograms. The receiver operating characteristic (ROC) curves, concordance index ( C -index), and calibration curves were used to assess the discrimination and accuracy of the nomogram. Finally, these results were validated in the Gene Expression Omnibus (GEO) database., Results: A total of 36 key genes related to mRNAsi were identified by WGCNA. A prognostic gene signature compromising seven genes (TPX2, ZWINT, UBE2C, CCNB2, CDK1, BUB1, and BIRC5) was established to predict the overall survival (OS) of PADC patients. The Cox regression analysis revealed that the risk score was an independent prognostic factor for PADC. Patients were then divided into the high-risk and low-risk groups. The ROC curves, C -index, and calibration curves indicated good performance of the prognostic signature in the TCGA and GEO datasets. Moreover, the nomogram incorporating clinical parameters showed better sensitivity and specificity for predicting the OS of PADC patients., Conclusion: The stemness-related prognostic model successfully predicted the OS of PADC patients and could be used for the treatment of PADC., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Xiao-Yan Huang et al.)

STAT2 is a central component of the ISGF3 transcriptional complex downstream of type I interferon (IFN-I) signaling. The significance of in vivo IFN-I/STAT1 signals in cDCs is well-established in the generation of antitumor cytotoxic T cell (CTL) responses. However, the role of STAT2 has remained elusive. Here, we report a clinical correlation between cDC markers and STAT2 associated with better survival in human metastatic melanoma. In a murine tumor transplantation model, targeted Stat2 deletion in CD11c+cDCs enhanced tumor growth unaffected by IFNβ therapy. Furthermore, STAT2 was essential for both, the activation of CD8a+cDCs and CD11b+cDCs and antigen cross-presentation in vivo for the generation of robust T cell killing response. In contrast, STAT2 in CD11c+cDCs was dispensable for stimulating an antigen-specific humoral response, which was impaired in global Stat2 deficient mice. Thus, our studies indicate that STAT2 in cDCs is critical in host IFN-I signals by sculpting CTL responses against tumors., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)

To gain a better understanding of the day-night variation characteristics of water-soluble ions, PM 2.5 samples were continuously collected for two months in the Nanjing Jiangbei New Area during winter. The diurnal variation and sources of water-soluble ions were studied. Results showed that the mass concentration of water-soluble ions ranged from 17.07 μg·m -3 to 168.43 μg·m -3 with a mean value of (59.01±30.75) μg·m -3 . The average mass concentration of water-soluble ions in daytime was higher than that in the nighttime. The concentration ratio of NO 3 - and NH 4 + to total ion concentrations was higher at night, while SO 4 2- and Cl - were higher during daytime. SO 4 2- , NO 3 - , and NH 4 + (SNA) were the dominant species of water-soluble ions in PM 2.5 in Nanjing. The mass concentration of SNA on polluted days was higher than that on clean days. The ratio of the anion-cation balance (AE/CE) was larger than 1, indicating that the PM 2.5 was acidic. There was a significant linear correlation between NH 4 + with NO 3 - and SO 4 2- , indicating that it occurred mainly in the form of NH 4 NO 3 and (NH 4 ) 2 SO 4 in PM 2.5 . The PMF source apportionment indicated that water-soluble ions of PM 2.5 were mainly derived from motor vehicle emissions, fossil fuel combustion, biomass burning, and dust in the Nanjing Jiangbei New Area.

Objective: The aim of this study is to explore the potential pathogenesis of juvenile dermatomyositis by bioinformatics analysis of gene chips, which would screen the hub genes, identify potential biomarkers, and reveal the development mechanism of juvenile dermatomyositis., Material and Methods: We retrieved juvenile dermatomyositis's original expression microarray data of message RNAs (mRNAs) and microRNAs (miRNAs) from NCBI's Gene Expression Omnibus database (GEO, http://www.ncbi.nlm.nih.gov/geo/); through the R package of limma in Bioconductor, we can screen the differentially expressed miRNAs and mRNAs, and then we further analyzed the predicted target genes by the methods such as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and miRNA-mRNA regulatory network construction and protein-protein interaction (PPI) network using Cytoscape 3.6.1., Results: Compared with normal juvenile skin tissues, 6 upregulated microRNAs and 5 downregulated microRNAs were identified from 166 downregulated microRNAs and 58 upregulated microRNAs in juvenile dermatomyositis tissues. The enrichment pathways of differentially expressed microRNAs include cell adhesion molecules (CAMs), autoimmune thyroid disease, Type I diabetes mellitus, antigen and presentation, viral myocardium, graft-versus-host disease, and Kaposi sarcoma-associated herpes virus infection. By screening of microRNA-messenger RNA regulatory network and construction of PPI network map, three target miRNAs were identified, namely, miR-193b, miR-199b-5p, and miR-665., Conclusion: We identified mir-193b, mir-199b-5p, and mir-6653 target miRNAs by exploring the miRNA-mRNA regulation network mechanism related to the pathogenesis of juvenile dermatomyositis, which will be of great significance for further study on the pathogenesis and targeted therapy of juvenile dermatomyositis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Cheng-Cheng Qiu et al.)

Infections are considered important environmental triggers of autoimmunity and can contribute to autoimmune disease onset and severity. Nucleic acids and the complexes that they form with proteins-including chromatin and ribonucleoproteins-are the main autoantigens in the autoimmune disease systemic lupus erythematosus (SLE). How these nuclear molecules become available to the immune system for recognition, presentation, and targeting is an area of research where complexities remain to be disentangled. In this review, we discuss how bacterial infections participate in the exposure of nuclear autoantigens to the immune system in SLE. Infections can instigate pro-inflammatory cell death programs including pyroptosis and NETosis, induce extracellular release of host nuclear autoantigens, and promote their recognition in an immunogenic context by activating the innate and adaptive immune systems. Moreover, bacterial infections can release bacterial DNA associated with other bacterial molecules, complexes that can elicit autoimmunity by acting as innate stimuli of pattern recognition receptors and activating autoreactive B cells through molecular mimicry. Recent studies have highlighted SLE disease activity-associated alterations of the gut commensals and the expansion of pathobionts that can contribute to chronic exposure to extracellular nuclear autoantigens. A novel field in the study of autoimmunity is the contribution of bacterial biofilms to the pathogenesis of autoimmunity. Biofilms are multicellular communities of bacteria that promote colonization during chronic infections. We review the very recent literature highlighting a role for bacterial biofilms, and their major components, amyloid/DNA complexes, in the generation of anti-nuclear autoantibodies and their ability to stimulate the autoreactive immune response. The best studied bacterial amyloid is curli, produced by enteric bacteria that commonly cause infections in SLE patients, including Escherichia coli and Salmonella spps . Evidence suggests that curli/DNA complexes can trigger autoimmunity by acting as danger signals, molecular mimickers, and microbial chaperones of nucleic acids., (Copyright © 2019 Qiu, Caricchio and Gallucci.)

Gradations in skin color are a consequence of differing amounts of melanin and their varying distribution. Although many darkly pigmented skin lesions are melanocytic and can be attributed to melanin content, the color of a black lesion can also be due to blood, necrotic tissue, or exogenous pigment. The source, pattern, and distribution of the color in black lesions usually offer important insight into its etiology. This contribution reviews conditions that can take on a black color, discussing the cause of the hue and any additional impact sun exposure may have., (Copyright © 2019 Elsevier Inc. All rights reserved.)

White diseases are a heterogenous group characterized by hypopigmentation or depigmentation. Skin and eye color are determined by the number and size of melanosomes present. Melanin is produced by melanosomes in the melanocytes present within the epidermis of the skin, uvea, and retinal pigmented epithelium (RPE). Conditions altering the number of melanocytes or concentration of melanin result in a lack of pigmentation, appearing as "white diseases" ranging from the well-known albinism and vitiligo to more esoteric white hand syndrome and Degos disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Uncoupling proteins (UCPs) belong to the family of mitochondrial transporter proteins and mediate regulated proton leak across the inner mitochondrial membrane. The UCPs play an important role in energy homeostasis and reactive oxygen species (ROS) release, and have been established as candidate genes for obesity, diabetes and hypertension. This study examined the possible association between the single nucleotide polymorphisms (SNPs) of UCP1-3 genes and essential hypertension (EH) in a northeastern Han Chinese population. A total of 2207 Chinese Han subjects were enrolled, including 1045 normotensives and 1162 hypertensives. Genotyping of UCP1 rs1800592, UCP1 rs12502572, UCP2 rs659366, UCP2 rs660339, and UCP3 rs3781907 was detected using Sequenom MassArray System. SHEsis was used to analyze linkage disequilibrium and haplotype. No evident association was observed between the genotype distributions and allele frequencies of individual SNPs and EH. Haplotype analysis showed the haplotype GAATA (rs1800592-rs12502572-rs659366-rs660339-rs3781907) was significantly associated with lower EH risk (p = 0.001, χ 2  = 10.861, OR = 0.634, 95% CI = 0.483-0.833), and AGATG was associated with increased EH risk (p = 0.012, χ 2  = 6.287, OR = 1.265, 95% CI = 1.052-1.521). These findings suggest haplotypes of UCP1-3 genes are linked to EH risk in a northeastern Han Chinese population. Further investigation with larger sample size in multiethnic population is needed to confirm our results.

Background: Chronic pruritus is defined as itch lasting for greater than six weeks. Pruritus is a burdensome manifestation of several internal and external disease states with a significant impact on quality of life. Dupilumab has shown promise in treating a number of conditions including atopic dermatitis (AD) and asthma. Its success in reducing pruritus in AD has generated interest regarding its potential application in other pruritic conditions, such as chronic pruritus of unknown origin, uremic pruritus, and pruigo nodularis., Methods: In this retrospective analysis, we present a series of 20 recalcitrant pruritus patients seen at a tertiary center treated with off-label dupilumab at standard AD dosing., Results: Dupilumab was successful at reducing itch in all treated patients, leading to complete resolution in 12/20 patients and an overall mean NRSi reduction of 7.55. Dupilumab was well tolerated with no significant adverse effects., Conclusions: Our case series suggests dupilumab may be a safe and efficacious therapeutic option in several pruritic conditions and demonstrates the need for further studies to better ascertain its place in the pruritus treatment armamentarium., Competing Interests: Lisa L. Zhai, Kevin T. Savage, Connie C. Qiu, Annie Jin and Rodrigo Valdes-Rodriguez have no conflicts. Nicholas K. Mollanazar reports serving as an investigator in trials sponsored by Sanofi and Regeneron Pharmaceuticals. No other disclosures are reported.

Objective: Dendritic cells (DCs) are important players in immunity against pathogens, but overactive DCs have been implicated in autoimmune diseases, like lupus, in which a paucity of targeted therapies remains. Recent research shows that DCs upregulate their immunometabolism when activating. We explored whether modulating fatty acid (FA) metabolism needed for oxidative phosphorylation can affect the activation of two main DC subsets. Material and methods: Sorted murine plasmacytoid DCs (pDCs) and conventional DCs (cDCs), generated in FLT3-L medium, were treated with etomoxir, an inhibitor of FA oxidation, or TOFA, an inhibitor of FA synthesis, then stimulated with TLR9 agonist CpGA. Surface activation markers and viability were analyzed by flow cytometry, cytokine, and chemokine production and were measured by ELISA. Results: Modulation of FA metabolism suppressed the upregulation of costimulatory molecules and the production of proinflammatory cytokine IL-6 and type I Interferon-dependent chemokine CXCL10 by both subsets of DCs, without affecting DC viability, neither of resting DCs or upon activation. Etomoxir inhibited pDCs at lower doses than cDCs, suggesting that pDCs may be more susceptible to FA metabolic modulation. Conclusions: Both cDCs, the primary antigen presenting cell, and pDCs, the primary type I IFN producer, exhibit a suppressed ability to activate but normal viability when their FA metabolism is inhibited by etomoxir or TOFA. Our findings indicate that FA metabolism plays an important role in the activation of both pDCs and cDCs and suggest that its modulation is an exploitable therapeutic target to suppress DC activation in inflammation or autoimmunity.

Attenuating the innate immunity activation could ameliorate inflammation and disease in settings such as transplant rejection or autoimmunity. Recently, a pivotal role for metabolic re-programming in TLR-induced dendritic cell (DC) activation has emerged. Ethyl pyruvate (EP), a pyruvate derivative, possesses anti-inflammatory properties in vitro and in animal models of disease. However, its effects on DCs remain elusive. We found that EP attenuated LPS-induced activation of murine GM-CSF bone marrow-derived dendritic cells (DCs) in vitro , reducing pro-inflammatory cytokine and IL-10 production, costimulatory molecule and MHC expression, the type I Interferon (IFN-I) response, the LPS-induced cell death, and the ability of DCs to stimulate allogeneic T cells. DC activation induced by TLR7 and TLR9 ligands was also suppressed by EP in vitro . Finally, EP decreased TLR-induced activation stimulated in vivo in conventional DCs and inflammatory monocytes. Investigating EP mechanisms, we found that EP decreased glycolysis and mitochondrial respiration, upon and in absence of TLR stimulation, by reducing ERK, AKT, and nitric oxide (NO) activation. These results indicate that EP inhibits most of the DC biological responses to TLR triggering, altering the metabolic reprogramming necessary for DC activation.

Objective: To discuss the whole genome-wide screening of the longevity-related gene of Uyghur population in Hotan, Xinjiang. Methods: The whole gene scanning using genome-wide association study (GWAS) based on the pooling DNA and the SNP-Map strategy in the longevity group (≥90 years old) and control group (persons who died before 70 years old) was carried out. Then, through detecting varieties of SNP locus, the frequencies of genotype and allele were calculated by sequencing and PCR- restriction fragment length polymorphism (RFLP) method. Results: There was no significant difference of rs6450874, rs6800573 and rs6741735 genotypes and alleles frequency distributions between the two groups, however, there were statistical differences of rs1718307, rs4449651, rs11217987 and rs2907092 genotypes and alleles frequency distributions between the two groups. The TT genotype of rs11217987 ( OR =1.462, P =0.034) and the GG genotype of rs2907092 ( OR =3.000, P =0.018) were positively correlated to the longevity. And the T allele of rs11217987 ( OR =1.382, 95% CI: 1.075-1.776) and the G allele of rs2907092 ( OR =1.672, 95% CI: 1.267-2.205) had strong potential function to prolong life. The TT genotype of rs4449651 ( OR =6.892, P =0.009) and rs1718307 ( OR =4.036, P <0.001) were positively correlated to the longevity. Moreover, the T allele of both SNPs ( OR =1.793, 95% CI: 1.298-2.477; OR =1.830, 95% CI: 1.391-2.407) had strong potential function to prolong life. Conclusions: The GWAS test can effectively and extensively analyze human longevity-related genes. And rs1718307, rs4449651, rs11217987 and rs2907092 are related to the longevity of Uyghur population in Hotan, Xinjiang.

Background: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the most common cause of severe perinatal thrombocytopenia, arising from the transplacental passage of maternal antibodies directed at paternally inherited antigens on fetal platelets., Aim: To review the occurrence, management and perinatal outcomes of pregnancies complicated by FNAIT from a single tertiary obstetric hospital in Western Australia., Materials and Methods: The study was conducted as a retrospective review of cases with prenatally recognised FNAIT between 2001 and 2011, with the treatment modalities and outcomes analysed., Results: Over the 10-year period, 20 cases of clinically significant FNAIT in 13 women were managed at our centre. Three cases were complicated by antenatal intracranial haemorrhage (15%), and in all 3, this was the presenting feature leading to diagnosis. In 17/20 (85%) cases, anti-HPA 1a was the responsible antibody, with the remainder being anti-HPA 5b. In 16/17 cases with pre-pregnancy recognition, intravenous gammaglobulin (IVGG) was administered antenatally (gestation at commencement ranging from 13 to 26 weeks) with adjuvant prednisolone in three cases. Postnatal treatment (IVGG or platelet transfusion) was provided in 4/16 cases. There was no intracranial haemorrhage or demise in any case receiving prenatal therapy., Conclusions: FNAIT is a rare and serious condition. In our small single-centre study, there was variability in the therapeutic strategies, although IVGG was central to all prenatally managed pregnancies. None of the treated pregnancies was complicated by intracranial haemorrhage or fetal death. There is a need for ongoing refinement of FNAIT management protocols, both in the prenatal and in the postnatal period., (© 2012 The Authors ANZJOG © 2012 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

This study was designed to determine the significance of DNA methyltransferases (DNMTs) in DNA hypermethylation in esophageal squamous cell carcinoma (ESCC) and to identify DNA methylation markers in serum for the early diagnosis of ESCC. A promoter methylation profile of 12 tumor-related genes was assessed using methylation-specific PCR in ESCC and paired non-tumor tissue samples from 47 patients. Expression levels of DNMTs were examined by real-time reverse transcription-PCR and immunohistochemistry. Using MethyLight, the methylation status of 5 genes was analyzed in serum samples from 45 patients and 15 healthy individuals. A total of 46 (97.9%) of 47 ESCC samples showed methylation in at least one of the examined genes, and methylation was most frequent for RAR-β (46.8%), DAPK (46.8%), p16 (44.7%), and CDH1 (42.6%). Methylation of RASSF1A was significantly correlated with the poorly differentiated tumors and the early pathologic tumor classification (P=0.035 and P=0.046, respectively). Tumoral DNMT3b mRNA up-regulation was significantly correlated with hypermethylation of multiple tumor-related genes (P=0.021). In addition, hypermethylation of cell-free serum DNA was common in ESCC patients, and diagnostic accuracy was increased when methylation of multiple genes (RAR-β, DAPK, CDH1, p16 and RASSF1A) were analyzed in combination (ROC AUC 0.911, 82.2% sensitivity and 100% specificity). The present study suggests that hypermethylation of multiple tumor-related genes may be involved in the pathogenesis of ESCC and mediated by the increase of DNMT3b expression. A cluster of multiple methylated genes in serum DNA has the potential as a novel biomarker for ESCC diagnosis.

Objective: To investigate the association between the NINJ2 gene rs11833579 polymorphism and stroke in Han Chinese population., Methods: This study was a population-based cross-sectional case-control study. Polymerase chain reaction-restriction fragment length polymorphism (RFLP) and sequencing were used for the detection of NINJ2 genotypes in 790 patients with stroke (679 ischemic stroke) which were Han Chinese population from Fangshan First Hospital and 811 controls which were healthy Han Chinese population without family history of stroke in Fangshan district rural area., Results: In rs11833579 locus of the NINJ2 gene, the frequencies of GG genotype and allele G were higher in ischemic stroke patients than that in controls (P<0.001). The frequency of allele G of the NINJ2 gene was higher in cerebral hemorrhage patients than that in controls (P=0.005). Genotype had little effect on the glucose, total cholesterol and triglyceride., Conclusion: There is significant association between rs11833579 site polymorphism of the NINJ2 gene and risk for stroke in Han Chinese population from Fangshan district.

Objective: To explore the relationship between the -344T/C polymorphism of aldosterone synthase (CYP11B2) gene and essential hypertension in Chinese Mongolian population., Methods: By cluster-sampling method, a total of 1575 Mongolian people in Tongliao city of Inner Mongolia were included in this study. And 417 subjects were normotension, 596 subjects were prehypertension and 562 subjects were essential hypertension. A survey was conducted to collect data by personal interview using a standard questionnaire, meanwhile fasting blood samples were drawn. Height, weight, waist circumference, blood pressure, blood-fat indexes and fasting plasma glucose were measured. The variant genotypes of CYP11B2 were identified by PCR assays. The relationship between the -344T/C polymorphism of CYP11B2 gene and essential hypertension were analyzed by multinomial logistic regression model., Results: Crude prevalence of prehypertension among Mongolian people was 37.84% (596/1575) and hypertension was 35.68% (562/1575). The age-standardized prevalence of prehypertension was 38.57% and hypertension was 31.53%. The frequency of the T and C allele was 0.66 (481/728) and 0.34 (247/728) for normotension group, 0.69 (696/1042) and 0.33 (346/1042) for prehypertension group, 0.71 (706/998) and 0.29 (292/998) for hypertension group. The multiple logistic models showed CYP11B2 variant genotypes were associated with prehypertension (TT/CC, OR = 1.33, 95%CI: 0.87 - 2.01; TC/CC, OR = 1.74, 95%CI: 1.13 - 2.67; TC + TT/CC, OR = 1.49, 95%CI: 1.01 - 2.22); CYP11B2 variant genotypes were associated with hypertension (TT/CC, OR = 1.70, 95%CI: 1.07 - 2.70; TC/CC, OR = 1.59, 95%CI: 0.98 - 2.50; TC + TT/CC, OR = 1.66, 95%CI: 1.06 - 2.58)., Conclusion: CYP11B2 gene -344T/C polymorphism were associated with essential hypertension in Chinese Mongolian population.

Renin is a rate-limiting enzyme of the renin-angiotensin system and plays a crucial role in the regulation of blood pressure (BP). Angiotensinogen (AGT) is the precursor of potent vasoactive hormone angiotensin II and the AGT gene has been incriminated as a marker for genetic predisposition to essential hypertension (EH) in some ethnic groups. The purpose of the study is to explore the association of a new genetic marker of renin gene, and AGT gene M235T, A-6G, and A-20C polymorphisms and their haplotypes with EH in the Mongolian population. On the basis of the prevalence survey, 243 hypertensives and 258 normotensives who had no blood relationship with each other were selected as subjects. All the subjects were interviewed with questionnaires and their blood specimens were collected. Renin gene insertion/ deletion (I/D) polymorphism was genotyped by PCR-polyacrylamide gel electrophoresis. AGT gene M235T, A-6G, and A-20C polymorphisms were genotyped by a PCR-restriction fragment length polymorphism and single-strand conformation polymorphism. The frequencies of renin genotype DD and allele D in hypertensives (36.21%, 63.79%, respectively) were significantly higher than those in normotensives (29.84%, 57.17%, respectively, P < 0.05). The odds ratios (OR) of renin genotype ID, DD to renin genotype II on hypertension were 1.98 (OR 95% CI 1.08-3.72) and 2.51 (OR 95% CI 1.33-4.88), respectively. There were no significant differences in the distributions of genotypes and alleles for AGT gene M235T, A-6G, and A-20C polymorphisms and all different haplotypes between the two groups. Renin gene I/D polymorphism is associated with EH, whereas AGT gene M235T, A-6G, and A-20C polymorphisms and the haplotypes are not associated with EH in the Mongolian population.

Objective: To explore the interaction between C (-344) T polymorphism of CYP11B2 and drinking index (DI) as well as their impact on the risk of hypertension in Chinese Mongolian population., Methods: A total of 1575 Mongolian people aged 20 and older including 562 hypertensive and 1013 normal-tensive from agricultural and pastoral areas in Tongliao city of Inner Mongolia, were included in this study. A cross-sectional survey was conducted to collect data by personal interview with local residents, using a standard questionnaire. Fasting blood samples were drawn and height, weight and blood pressure were measured. The variant genotypes of CYP11B2, ACE and eNOS were identified by PCR assays. Gene-environment interactions were analyzed, using multifactor dimensionality reduction (MDR) model. Based on the result of the best MDR model, a multiple logistic regression model was constructed as the final cause-effect interpretative model., Results: The interaction between CYP11B2 variant genotype and drinking index appeared the best MDR model with statistical significance (chi(2) = 66.35, P < 0.01). Testing balance accuracy of the model was 0.604. The cross-validation consistency was 10/10. Data from the final multiple logistic regression based on the MDR model showed that the main effects of both CYP11B2 variant genotype and the DI were not significantly different but the interaction between the genotype (TC) and the DI (90-) was, with regard to hypertension (OR, 10.25; 95%CI, 2.23 - 47.18; P = 0.003). The combined effects between CYP11B2 variant genotype and the DI showed that following indices as: genotype TT or TC combining non-zero drinking index, including genotype (TT) combining the drinking index (> or = 168), the genotype (TT) combining the drinking index (> or = 40), the genotype (TT) combining the drinking index (> or = 1) and the genotype (TC) combining the drinking index (> or = 90), were all risk factors of hypertension when comparing with genotype (CC) combining the drinking index (0), and the ORs (95%CI) appeared to be 2.07 (1.15 - 3.70), 2.35 (1.22 - 4.56), 2.05 (1.07 - 3.94) and 5.56 (2.54 - 12.18) respectively., Conclusion: Essential hypertension might positively be affected by the interaction of the C (-344) T polymorphism of CYP11B2 and the drinking index in Chinese Mongolian population.

Objective: To investigate the distribution of HLA-DRB alleles among the asthmatic children and find the alleles with a correlation with susceptibility or resistance to childhood asthma., Methods: The sequence-specific polymerase chain reaction (SSP-PCR) was used to analyze the HLA-DRB genotype in 117 asthmatic children and 120 healthy children in Beijing. Then the frequency of each type, odds ratio (OR) and the 95% confidence interval (CI) of OR were calculated., Results: The frequency of DR2 (15) in the asthmatic children was 12.0% (28/234) vs 5.4% (13/240) in the healthy children. The frequency was significantly higher than that of nonasthmatic children (OR = 2.590, 95% CI = 1.266-5.298, Chi(2) = 6.431, P < 0.05). Conversely, the frequencies of DR4, DR6 (1402), DR9 and DR53 in asthmatic children [9.4% (22/234), 0.9% (2/234),17.1% (40/234), 29.5% (69/234)] were significantly lower than that of the healthy children [16.3% (39/240), 5.0% (12/240), 31.3% (75/240), 44.2% (106/ 240)], P = 0.026, 0.008, 0.000, 0.001, OR = 0.481, 0.157, 0.312, 0.190. Multi-variate logistic regression demonstrated that the 95% CI of OR for each allele was 1.010-2.245, 0.757-1.116, 0.603-1.054, 0.855-1.014, 0.971-1.010, respectively., Conclusion: The allele HLA-DR2 (15) is correlated with the susceptibility to childhood asthma whereas it is not related with the severity of asthma.

Background: High-altitude pulmonary edema (HAPE) is thought of as an independent clinical disorder with a constitutional or genetic component in its etiology. We focused on 5 common polymorphisms within HSPA1A (rs1043618 and rs1008438), HSPA1B (rs1061581 and rs539689) and HSPA1L (rs2227956) of Hsp70 family to explore their potential interaction upon susceptibility to HAPE in Chinese., Methods: A total of 148 HAPE patients and 483 matched controls were recruited during the construction of Qinghai-Tibet railway from 2001 to 2006. Genotyping was performed using PCR-RFLP, PCR-SSCP and PCR-direct-sequencing techniques. Promoter activity was evaluated by luciferase reporter assays. Gene-gene interaction was conducted by MDR v.2.0, and haplotype-diplotype analysis by Haplo.stats v.1.4.0., Results: Significant differences were observed in the genotype (P=0.0136) and allele (P=0.0299) distributions of rs1008438, and in rs1061581 allele distribution (P=0.0421) between HAPE patients and controls. Interaction analysis indicated that 3 polymorphisms (rs1061581, rs1043618 and rs1008438) shared strong synergism with a testing accuracy of 0.792 and cross-validation consistency 10 out of 10 (P=0.001). Haplotypes Hap4 (G-C-A, in order of rs1061581, rs1043618 and rs1008438) and Hap5 (G-G-A) had an 86% reduced risk (P=0.0009) against and Hap7 (A-C-C) had a 2.43-fold increased risk for HAPE. When considered as diplotypes, significance was noted for Dip5 (Hap1-Hap7) (OR=3.39; 95% CI: 1.28-9.17; P=0.0140). Functional assessment supported the involvement of rs1008438 in the pathogenesis of HAPE., Conclusion: We demonstrated strong interaction of rs1061581, rs1043618 and rs1008438 polymorphisms within Hsp70 family upon susceptibility to HAPE in Chinese. Moreover, polymorphism rs1008438 might cause the development of HAPE via a change in HSPA1A promoter activity.

Objective: To identify the genetic defects of the the adiponectin (APM1) gene that contribute to the development of type 2 diabetes (T2DM) and determine the functional single nucleotide polymorphisms (SNPs) in the APM1 gene associated with T2DM in Han nationality., Methods: The APM1 gene 5'-UTR was screened by direct sequencing to identify common polymorphisms. Identified SNPs were genotyped in 585 nondiabetic controls, 278 subjects with impaired glucose intolerance (IGT) and 212 patients with T2DM. The functions of SNPs in the regulatory region were assessed by reporter gene assay. Possible association between SNPs and plasma APMI levels or metabolic parameters was statistically assessed., Results: Three SNPs were identified in the APM1 gene 5'-UTR. A case-control study revealed that SNP -11377 G/C had significant differences in allele frequencies between T2DM patients and nondiabetic controls (G 0.314/C 0.686 vs. G 0.265/C 0.735, P=0.03). Haplotype analysis of three SNPs in the APM1 gene showed that no significant association of haplotypes with T2DM. IGT was detected in the present study. Reporter gene assay showed that SNP did not influence the transcription efficiency in the 3T3-L1 cell line., Conclusion: SNP -11377 G/C in the proximal promoter region of the APM1 gene contributes to the development of T2DM in Han nationality but may not be a functional SNP in the APM1 gene.

Objective: To investigate the association of ghrelin gene polymorphisms with metabolic syndrome in Han Nationality Chinese., Methods: A total of 240 patients with metabolic syndrome and 427 adults aged above forty years were recruited. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analysis., Results: The allelic frequency of the Leu72Met polymorphism was 17.3% in the patient group and 11.9% in the control group (chi2 = 7.36, P = 0.007). Metabolic syndrome was more prevalent among carriers of the Met72 variant (43.8 vs 33.1%, age- and sex-adjusted odds ratio = 1.57, P = 0.01). No Arg51Gln variants were found in our study subjects., Conclusion: Rather than being associated with its individual components, Leu72Met polymorphism is associated with metabolic syndrome in the Han Nationality Chinese. Arg51Gln polymorphism is rare in the Han Nationality Chinese.

Objective: To evaluate whether the clustering of risk factors, both environmental and genetic, increases the risk of essential hypertension (EH) and the accumulation of risk factors influences the blood pressure level in normotensives., Methods: On the basis of a prevalence survey, 501 subjects of Mongolian ethnicity (243 hypertensives and 258 normotensives) who were not related to each other were selected to conduct a case-control study. All subjects were interviewed with questionnaires and their blood specimens were collected. Renin gene insertion/deletion (I/D) polymorphism, a new genetic marker, was genotyped with PCR and polyacrylamide gel electrophoresis., Results: Overweight, alcohol consumption, and renin gene I/D polymorphism were significant risk factors of EH (P<0.05). The odds ratios (OR) for the number of risk factors were 2.39 (95%CI: 0.98-6.74) for one risk factor, 5.03 (95%CI: 2.06-14.18) for two, and 6.09 (95%CI: 1.85-22.38) for three respectively after adjusting for age and sex. In normotensives, age- and sex-adjusted mean blood pressures increased with more accumulation of risk factors. However, there were no significant differences among the different blood pressure levels according to the number of risk factors (P>0.05)., Conclusion: Overweight, alcohol consumption, and renin gene I/D polymorphism are risk factors of EH in the Mongolian ethnic population of China. The accumulation of the risk factors causes a sharp increase of the risk of EH.

Objective: To explore the relationship between genetic polymorphisms of C-344T in the promoter region and K173R in the exon 3 of aldosterone synthase gene (CYP11B2) and the incidence of essential hypertension in a northern Chinese Han population., Methods: We conducted a case-control study including 182 hypertensive patients and 189 healthy controls in Harbin newspaper office and assayed the genotypes of C-344T and K173R using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing technology., Results: The distributions of C-344T and K173R genotype frequencies in men and women were in accordance with the Hardy-Weinberg equilibrium. The differences of C-344T allele and genotype as well as K173R allele frequency distributions between hypertensive patients and healthy controls were not statistically significant in men and women and pooled population (P > or = 0.05). The difference of K173R genotype frequency distribution reached borderline significance (P = 0.0500) and was more pronounced in women (P = 0.0038) according to the dominant mode of inheritance. Moreover, the magnitude of this mode of inheritance was more remarkable after the confounding factors were adjusted. K173R statistically correlated with the systolic hypertension in women., Conclusion: The CYP11B2 K173R polymorphism correlates with the susceptibility of essential hypertension in the northern Chinese Han population.

Objective: To study the physiological characteristics and cardiac electrophysiology of the "desert people" in Taklimakan Desert, an isolated population of Uygurs., Methods: Two hundred and twenty-four out of the 1030 "desert people", 133 males aged 37.8 +/- 17.5 (15-99) and 91 females aged 34.1 +/- 12.1 (27-85), underwent measurement of height, body weight, waist circumference, and blood pressure. Twelve-lead resting electrocardiogram was obtained and Minnesota coding was conducted. 150 Kariya Uygurs, 76 males aged 50.7 +/- 15.6 (27-85) and 75 females aged 46.6 +/- 11.7 (24-69) were used as controls., Results: The abnormal Minnesota coding rate in the "desert people" as a whole was 46.0%, significantly higher than that of the controls (35.1%, P < 0.05). In the "desert people", the abnormal Minnesota coding rate was 54.9% in the males, significantly higher than that in the females (33.0%, P < 0.05). In the control group, the abnormal coding rate was 28.0% in the females and 42.1% in the males. The ECG high left R amplitude rate (code 3-1, 3-3) of the "desert people" as a whole was 32.6%, significantly higher than that of the controls (12.6%, P < 0.001). Within the "desert people" group, the ECG high left R amplitude rate of the females was 19.8%, significantly lower than that of the males (41.2%, P < 0.005). Within the control group, the ECG high left R amplitude rate of the females was 10.7%, not significantly different from that of the males (14.5%, P > 0.5). The hypertension rate of the "desert people" was 7.6%, significantly lower than that of the controls (36.4%, P < 0.005). The hypertension rate of the "desert people" coded as with left high R amplitude was 12.2%, significantly lower than that of the controls coded as with left high R amplitude (41.6%, P < 0.005). The overweight and obesity rate of the "desert people" was 9.6%, significantly lower than that of the controls (23%, P < 0.005). The arrhythmia (8-1 - 8-8) rate of the "desert people" was 8.92%, not significantly different from that of the controls (6.62%, P > 0.05). The incidence of conduction block (7-1 - 7-8) of the "desert people" was 3.12%, not significantly different from that of the controls (2.64%, P > 0.05)., Conclusion: The higher incidence of ECG high left R amplitudes and low prevalence of hypertension in the "desert people" suggest that the high left R amplitude in "Desert people" may be related to their thin chest wall, low BMI, and physiological left ventricular hypertrophy. The "desert people" have more physical work, and less stress and pollution. They have low incidence of congenital heart disease, rheumatic heart disease and hypertension. All these may be associated with a low incidence of arrhythmia.

Objective: To investigate the association of polymorphisms in the apolipoprotein B gene (APOB) 3'variable number of tandem repeat with natural longevity in the Xinjiang Uighur nationality people., Methods: Totally 191 healthy individuals over 90 years and 53 individuals aged 65-70 years were recruited among Xinjiang Uighur population, the nationality, gender and living area were matched. Genotyping was performed using polymerase chain reaction-sequence specific primer(PCR-SSP) and PCR-sequencing., Results: Fourteen alleles were found in the Xinjiang Uighur nationality population. The frequency of HVE36 and HVE42 in the natural longevity group were significantly higher than that in the control group (both P<0.05) and HVE44, HVE46, HVE48 and HVE58 were only found in the natural longevity group. However, the frequency of HVE26, HVE30 and HVE34 were markedly lower in the natural longevity group compared to the control group. Logistic regression analyses revealed that allele L and the genotypes LL were positively associated with age, whereas the allele S and genotype SS were negatively associated with age (both P<0.05). Each allele consists of 15 bp tandem repeats with rich-AT by PCR-sequencing., Conclusion: These results indicate that the S allele, and SS genotype are frail factors in China Uighur natural longevity people, whereas allele L and genotypes LL are protective factors.

Objective: To investigate the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with type 2 diabetes mellitus (T2DM)., Methods: Two hundred and nine patients with T2DM diagnosed based on the criteria for diabetes mellitus in 1999 by WHO and 221 controls were recruited from general population of Dongcheng District in Beijing. All subjects were genotyped for the I/D polymorphism of ACE gene by PCR-fragment length polymorphism (FLP) assay. Blood pressure, levels of plasma glucose, lipids and serum insulin were determined. Body mass index (BMI), waist-hip ratio (WHR) and homeostasis model assessment-insulin resistance index (HOMA-IR) were calculated., Results: The genotype frequencies for ACE genes DD, ID, and II were 19.1%, 42.1%, and 38.8% in patients, respectively, and 9.6%, 49.4%, and 41.0% in controls, respectively. The ACE DD genotype frequency was significantly higher in patients than in controls (chi2 = 7.61, P = 0.022). Multivariate logistic regression analysis showed that the ACE DD genotype was a risk factor for T2DM, with the OR of 2.35 (95% CI 1.17-4.71) adjusted for age, sex, BMI, WHR, blood pressure, and serum cholesterol levels., Conclusion: The ACE DD genotype is associated with the increased susceptibility to type 2 diabetes mellitus.

Essential hypertension (EH) is a complex multifactorial disorder with genetic and environmental factors contributing to its prevalence. The genetic features have been revealed from the significant familial aggregation and the consistency among twins. Therefore, identification of EH susceptibility genes will be helpful to understand the pathophysiology of the disease, identify populations with potential risks of developing the disease, and select antihypertensive drugs. The present article introduces the search strategies of EH susceptibility genes and some genetic variants related to EH; meanwhile, it tries to analyze the difficulties and the role for samples in identifying susceptibility genes to EH.

Objective: To explore the distribution of polymorphisms of apolipoprotein E(apoE) gene and its relation to natural longevity in the Xinjiang Uighur people., Methods: Using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP), the authors obtained data from centenarians(n=42), 90-year-old people (n=102), 65-70-year-old people (n=70) and controls(n=53)., Results: The frequencies of apoE genotypes epsilon 3/4, epsilon 3/3 and epsilon 2/3 were 2.4%, 69.0% and 23.8% respectively in the centenarian group, and the frequencies of their epsilon 4, epsilon 3 and epsilon 2 alleles were 1.2%, 82.1% and 16.7%. The frequencies of genotype epsilon 3/4 and epsilon 4, epsilon 3 allele in the centenarian group were significantly lower than those in controls(P< 0.01), whereas the frequencies of genotype epsilon 2/3 and epsilon 2 allele in the centenarian group were significantly higher than those in controls(P< 0.01). Longevity was noted to be positively correlated with epsilon 2 and negatively correlated with epsilon 4., Conclusion: This relationship reflects a genetic influence on differential survival and may point to pleiotropic age-dependent effects on longevity.

Objective: To explore the distribution of I/D polymorphisms of angiotensin converting enzyme (ACE) gene and its relation to natural longevity in the Xinjiang Uygur people., Methods: Polymerize chain reaction, single strand conformation polymorphism, and direct sequencing technique were used to test the I/D polymorphisms of ACE gene in 42 centenarians, 102 people aged 90-99, 70 people aged 65-70, 53 cases of natural death aged 65-70 were used as controls., Results: The frequencies of ACE genotypes DD, DI, and II were 28.6%, 30.9%, and 40.5% respectively in the centenarian group, the frequency rates of D and I alleles were 0.44 and 0.56. The frequency rate of D/D genotype of the centenarian group was significantly higher than that of the group aged 65-70 (28.6% vs. 12.9%, chi2 = 4.25, P < 0.05), however, not significantly different from that of the group aged 90 (P > 0.05). The frequency rate of D allele of the group of centenarian was significantly higher than that of the group aged 65-70 (44.0% vs. 36.4%, chi2 = 4.47, P < 0.05). The frequency rates of genotype D/D and D alleles were significantly higher in the centenarian group than in the controls (both P < 0.01)., Conclusion: ACE gene polymorphism is closely correlated with life span of individuals. Longevity is the result of pleiotropic age-dependent influence of multiple factors.

Objective: To investigate whether the polymorphisms of beta2-adrenergic receptor (beta2-AR) at position 16, 27, 164 are associated with asthma in Northern Chinese subjects., Methods: Genomic DNA was collected from unrelated Northern Chinese population of Han ethnicity, including 125 unrelated asthmatic individuals and 96 healthy controls. Beta2-AR genes at position 16, 27, 164 were amplified by using restriction fragment length polymorphism (RFLP) and allelic specific polymerase chain reaction methods. All asthmatics had their serum IgE (total and specific) antibody or skin-prick test measured, bronchial reactivity to methacholine (Mch) and bronchial reversibility by beta2-agonist evaluated., Results: (1) The frequency of Gly 16 homozygous was significantly higher in the asthmatic group than that in healthy controls (22.4% vs. 8.3%, P < 0.05), OR was 2.9 with 95% CI 1.26-6.78. The proportion of Gly 16 allele was also higher in asthmatics than that in control (0.46 vs. 0.36, P < 0.05); Gly16 homozygous was not independently associated with asthma pathogenesis (P = 0.21, OR 0.42 with 95% CI 0.11-1.61). (2) Of 51 night attack patients, 18 carrying Gly16 homozygosity, if compared with 10 of 74 nonnocturnal asthmatics carrying this genotype, there was significant difference between these two groups (35.3% vs. 13.5%, P < 0.01). (3) The average dose of PD20-Mch was significantly lower in patients carrying Gln 27 homozygous than those carrying homozygous Glu 27 and Gln/Glu 27 heterozygous (0.2 +/- 0.3, 1.6 +/- 0.8, and 2.1 +/- 3.0 micromol/L, P < 0.05)., Conclusion: Beta2AR gene polymorphisms might confer susceptibility to asthma in Chinese Northern patients. Beta2-AR gene, coordinated with other candidate loci, plays a role in the development of asthma.

Objective: To evaluate the potential implications of the genetic variability of angiotensin converting enzyme, angiotensinogen and angiotensin II type 1 receptor gene for essential hypertension in Tibetan., Methods: A case-control study was conducted in 173 hypertensive individuals and 193 individuals with normal blood pressure. Multiple logistic regression analyses were used to estimate the risks of developing hypertension for different genotypes, and haplotype analyses of the angiotensinogen gene were used to determine the association between two-locus angiotensinogen gene polymorphisms and hypertension., Results: As to the risk to high blood pressure and high systolic pressure, women with MM genotype were 7.7 (95% CI: 1.3-20.5) and 8.7 (95% CI: 1.8-20.1) times higher than those with TT genotype after adjustment for age and body mass index. Haplotype frequencies for M235T and G-6A were significantly different between hypertensive individuals and controls, which indicated an association of angiotensinogen gene haplotypes with hypertension, and a significant association of 235T/-6A haplotype with hypotensive effect., Conclusion: Our results suggest that angiotensinogen gene 235MM is a predictor for hypertension development in Tibetan women but not in men, and may exert its hypertensive effect on linkage disequilibrum with a possible function locus of G-6A.

Objective: To investigate the association of specific functional gene ACE (I/D) variants of the renin-angiotensin system with essential hypertension (EH) and interaction between ACE (I/D) gene and risk factors for EH in a genetically homogenous Mongolia rural population of China., Methods: Individuals (n=1099) were recruited from general population of Kezuohouqi Banner in Inner Mongolian Autonomous Region., Results: The association was found between ACE genotype DD plus ID and EH, with an interaction between ACE genotype DD plus ID and cigarette smoking in an additive model. Cigarette smoking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 7.10 to 1.16. Interaction between ACE genotype DD plus ID and alcohol drinking on EH appeared an additive model. Alcohol drinking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 1.66 to 1.09. BMI and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 6.15 to 2.49. Interactions between ACE genotype and WHR on EH showed a multiplicative model. In a short,there was an interaction between ACE gene and cigarette smoking, alcohol drinking and BMI on EH, especially in a low dose-exposure effect, Conclusion: It is important for individuals who carry ACE D allele gene to prevent EH, and furthermore, to prevent and control coronary heart disease, in a view of population-based prevention.

Objective: To clarify whether A1166C polymorphism of the angiotensin II type 1 receptor (AT(1)R) gene is associated with susceptibility to essential hypertension in Han, Tibetan and Yi populations in China., Methods: This study involved 302 normotensive and 446 hypertensive subjects. The polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in genomic DNA. The data were analyzed by ANCOVA, chi-square test, and multiple logistic regression., Results: In normotensive controls, the A1166 allele frequencies were 0.979, 0.939 and 0.965 in Han, Tibetan and Yi participants, respectively. There was no significant intergroup variation in frequency of the allele in normotensives (chi-square=4.166, P=0.125). The frequency of the A1166 allele in Tibetan male hypertensives was significantly higher than that in normotensives (chi-square=11.46, P=0.001). There was no significant difference in A1166C genotype distribution and allele frequency between normotensives and hypertensives either in the Han (P=0.465) or Yi (P=0.357) populations. Body mass index in the Han and Yi populations (P=0.0001), age in the Tibetan and Yi populations (P=0.0001), and AA genotype in the Tibetan male population (P=0.0034) all were independent risk factors for hypertension. Diastolic blood pressure levels were significantly higher in Tibetan male subjects with the AA genotype than in those with the AC+CC genotype (P=0.0040)., Conclusion: The A1166 allele is very common in Han, Tibetan and Yi populations, approximately 1.35-fold more common than in Caucasians. The A1166 allele of the AT(1)R gene may be a predisposing factor for essential hypertension in Tibetan males. A1166C polymorphism of the AT(1)R gene is probably not involved in the pathogenesis of essential hypertension in Han and Yi populations.

Objective: To investigate whether beta 2-adrenergic receptor gene (beta 2AR) polymorphism at position 16, 27, 164 is in association with asthma susceptibility or asthmatic phenotype (including nocturnal asthma, serum IgE level, bronchial responsiveness, the status of asthmatics)., Methods: By using PCR-RFLP and allelic-specific PCR (ASP), the polymorphism of beta 2AR gene at position 16, 27, 164 in 125 Han origin asthmatics and 96 normal healthy controls with the same ethnic nearby Beijing region were genotyped. All patients had their serum total IgE (TIgE) measured by RAST, pulmonary ventilatory function assessed by FEV1% and FEV1/FVC, bronchial responsiveness challenged by methacholine (if FEV1% > 70%), and brocho-reversibity by inhaling beta 2-agonist., Results: There was higher prevalence of Gly16 homozygous of beta 2AR in asthmatics than that in normal healthy controls (22.4% vs 8.3%, P < 0.05), with odd ratio (OR) 2.918 (95% CI: 1.256-6.781); Also there was higher frequency of Gly16 homozygous of beta 2AR in nocturnal asthmatics than that in nonnocturnal asthmatics (35.3% vs 13.5%, P < 0.01), but Gly16 homozygous of beta 2AR was low an independent risk factor for the pathogenesis of asthma. The dose of methacholine was low in asthmatics carrying Gln27 homozygous beta 2AR than Glu27 homozygous beta 2AR and Gln/Glu27 heterozygous beta 2AR in brocho-challenge test [(0.205 +/- 0.275) vs (2.11 +/- 3.00) vs (1.575 +/- 0.828) mumol, P < 0.05]., Conclusions: Gly16 homozygous beta 2AR was associated with asthma susceptibility in Chinese patients with Han ethnic nearby Beijing region, and Gly16 homozygous beta 2AR was associated significantly with nocturnal asthma. Glu27 homozygous beta 2AR was related to hyper-bronchial reactivity of asthmatics.

Objective: To analyse IL-2, IL-2R mRNA gene expression and protein production before, during, and after rejection of heart transplantation in vitro model., Method: The in vitro system consists of peripheral PBMC of health donor as response cells and cardiomyocytes of patient suffering from acyanotic congenital heart disease as stimulating cells. Reverse transcription-polymerase chain reaction (RT-PCR) was used., Results: mRNA transcription and protein production of IL-2, IL-2R rose markedly after stimulation of alloantigen, and were different from those of the control (P < 0.05, P < 0.01). The summit of IL-2, IL-2R mRNA transcription was detected 24 hours after initiation of mixed culture, 48 hours earlier than the time (72 hours) at which damage of cardiomyocytes was detected electronmicroscopy and the peak of IL-2, IL-2R protein production detected., Conclusion: IL-2/IL-2R system plays an important role in the rejection of heart transplantation. Detection of IL-2, IL-2R mRNA transcription is significant for early diagnosis of rejection. RT-PCR makes analysis of mRNA rapid, and is sensitive and high specific.

Sixteen female, Sprague-Dawley rats were divided into four equal groups. Two groups served as controls receiving low or regular concentrations of fluoride (F); animals in the other two groups were given drinking water, containing 100 parts/10(6) F, for 3 weeks either during or immediately before pregnancy. Thirteen days after delivery, the pups and dams were killed and various tissues analysed for F content. Prenatal F supplementation increased F concentrations in plasma, mandibular incisors and femoral epiphyses of pups by 25, 36 and 38% respectively, when given during pregnancy. Only a slight increase of 9 and 11% in the respective F concentrations of incisors and epiphyses occurred when the supplement was given before pregnancy. The fluoride level of milk was consistently higher than that of the maternal plasma. These results suggest the need for further study of prenatal F supplementation.

Acetyltransferase was isolated by histone-Sepharose affinity chromatography from human cord blood red cells. The enzyme was detected only in very young red cells. The semipurified enzyme and [14C]acetyl-CoA were used to acetylate isolated Hb F tetramer and alpha and gamma subunits. The in vitro acetylated products were characterized by globin chain separation by CM-cellulose chromatography and tryptic peptide analysis by reverse-phase HPLC. Acetylation of both the gamma-chains and the alpha-chains could occur within the Hb F tetramer. Acetylation also could take place on intact subunits. It appears that some Hb FIC could be formed in the cells by utilizing Hb F or free gamma-chains as acetylation substrate.