Youxin Wang

Association of systemic lupus erythematosus with decreased immunosuppressive potential of the IgG glycome.

Glycans attached to the Fc portion of IgG are important modulators of IgG effector functions. Interindividual differences in IgG glycome composition are large and they associate strongly with different inflammatory and autoimmune diseases. IKZF1, HLA–DQ2A/B, and BACH2 genetic loci that affect IgG glycome composition show pleiotropy with systemic lupus erythematosus (SLE), indicating a potentially causative role of aberrant IgG glycosylation in SLE. We undertook this large multicenter case–control study to determine whether SLE is associated with altered IgG glycosylation.

Association between dopaminergic genes (SLC6A3 and DRD2) and stuttering among Han Chinese

Normal function of the dopaminergic system is necessary for speech fluency. There was evidence that the activities of dopamine transporter (DAT) and dopamine D2 receptor (DRD2) could be altered in people with speech disfluency. This study aims to ascertain the possible correlation between two dopaminergic genes (SLC6A3 and DRD2) and disorder of speech fluency, and to determine the allelic frequencies of the five single-nucleotide polymorphisms (SNPs) (rs2617604, rs28364997, rs28364998 in SLC6A3 and rs6275, rs6277 in DRD2) among Han Chinese patients with this disorder. A sample of 112 patients with speech disfluency and 112 gender-matched controls were included in this case–control study. The results show that the presence of C allele at rs6277 in DRD2 gene is associated with increased susceptibility to the disorder, whereas T allele is protective. Haplotype 939T/957T is also a protective factor.

A Quinine-Squaramide Catalyzed Enantioselective Aza-Friedel–Crafts Reaction of Cyclic Trifluoromethyl Ketimines with Naphthols and Electron-Rich Phenols

A highly enantioselective aza-Friedel-Crafts (aza-F-C) reaction of cyclic trifluoromethyl ketimines and naphthols/phenols was developed with fluorenyl-substituted quinine-squaramide as the catalyst. This protocol enables direct access to biologically important chiral trifluoromethyl dihydroquinazolinones with up to 99% yields and up to 99% ees.

Increasing Incidence of Thyroid Cancer in Shanghai, China, 1983-2007

Increasing incidence of thyroid cancer has been observed in some countries such as the United States, United Kingdom, France, and so on. Joinpoint regression was used to analyze the incidence of thyroid cancer in Shanghai, China, from 1983 to 2007. The results showed that there were 2 distinct slopes: in men, representing a significant annual percentage change (APC) of 2.6% from 1983 to 2000 (P < .001) followed by a sharp APC of 14.4% (P < .001), and in women, representing a significant APC of 4.9% from 1983 to 2003 (P < .001) followed by a sharp APC of 19.9% (P = .001). The sharp increase in thyroid cancer occurred 5 and 8 years after the iodine supplementation by salt, for men and women, respectively, suggesting that either the developed screening techniques or iodine supplementation might have contributed to the rapid increase in the incidence of thyroid cancer. The burden of thyroid cancer cases is expected to be substantial, based on predictions through 2020.

Screening Novel Biomarkers for Metabolic Syndrome by Profiling Human Plasma N-Glycans in Chinese Han and Croatian Populations

N-glycans play an essential role in biological process and are associated with age, gender, and body mass parameters in Caucasian populations, whereas no study has been reported in Chinese populations. To investigate the correlation between N-glycan structures and metabolic syndrome (MetS) components, we conducted a population-based study in 212 Chinese Han individuals. The replication study was performed on 520 unrelated individuals from a Croatian island Korčula. The most prominent observation was the consistent positive correlations between different forms of triantennary glycans and negative correlations between glycans containing core-fucose with MetS components including BMI, SBP, DBP, and fasting plasma glucose (FPG) simultaneously. Significant differences in a number of N-glycan traits were also detected between normal and abnormal groups of BMI, BP, and FPG, respectively. In the multivariate analysis, the level of monosialylated glycans (structure loadings = -0.776) was the most correlated with the MetS related risk factors, especially with SBP (structure loadings = 0.907). Results presented here are showing that variations in the composition of the N-glycome in human plasma could represent the alternations of human metabolism and could be potential biomarkers of MetS.

The Association Between Glycosylation of Immunoglobulin G and Hypertension: A Multiple Ethnic Cross-Sectional Study

AbstractMore than half of all known proteins, and almost all membrane and extra-cellular proteins have oligosaccharide structures or glycans attached to them. Defects in glycosylation pathways are directly involved in at least 30 severe human diseases.A multiple center cross-sectional study (China, Croatia, and Scotland) was carried out to investigate the possible association between hypertension and IgG glycosylation. A hydrophilic interaction chromatography of fluorescently labeled glycans was used to analyze N-glycans attached to IgG in plasma samples from a total of 4757 individuals of Chinese Han, Croatian, and Scottish ethnicity.Five glycans (IgG with digalactosylated glycans) significantly differed in participants with prehypertension or hypertension compared to those with normal blood pressure, while additional 17 glycan traits were only significantly differed in participants with hypertension compared to those of normal blood pressure. These glycans were also significant correlated with systolic blood pressure (SBP) or diastolic blood pressure (DBP).The present study demonstrated for the 1st time an association between hypertension and IgG glycome composition. These findings suggest that the individual variation in N-glycosylation of IgG contributes to pathogenesis of hypertension, presumably via its effect on pro- and/or anti-inflammatory pathways.

Modelling the transmission dynamics of meticillin-resistant Staphylococcus aureus in Beijing Tongren hospital

Semi-professional volunteers work in many tertiary care hospitals in China as healthcare assistants. Proper infection control measures are needed to reduce nosocomial transmission involving volunteers. A compartmental model was constructed to describe the transmission characteristics of meticillin-resistant Staphylococcus aureus (MRSA) in the emergency ward (EW) and respiratory intensive care unit (RICU) for volunteers in Beijing Tongren Hospital, Beijing, China. The model consists of components describing uncolonized and colonized patients, uncontaminated and contaminated healthcare workers (HCWs), and uncontaminated and contaminated volunteers. The basic reproduction number (R(0)) was calculated, and the dependence of R(0) on various model parameters was analysed. Moreover, simulations of the model were performed for comparision with the reported data on the numbers of colonized patients in the EW and RICU from 3 March 2009 to 28 February 2010, respectively. Sensitivity analysis of R(0) showed that increasing handwashing compliance among HCWs and volunteers would reduce the risk of transmission dramatically. As volunteers care for patients on a one-to-one basis, this study showed that the number of MRSA-positive patients would increase if volunteers were replaced by HCWs. Therefore, in addition to improving hand hygiene among HCWs, the employment of properly trained volunteers is an attractive alternative to decrease MRSA and other multi-drug resistant bacteria infections in the hospital setting.

The ecology of medical care in Beijing

Background We presented the pattern of health care consumption, and the utilization of available resources by describing the ecology of medical care in Beijing on a monthly basis and by describing the socio-demographic characteristics associated with receipt care in different settings. Methods A cohort of 6,592 adults, 15 years of age and older were sampled to estimate the number of urban-resident adults per 1,000 who visited a medical facility at least once in a month, by the method of three-stage stratified and cluster random sampling. Separate logistic regression analyses assessed the association between those receiving care in different types of setting and their socio-demographic characteristics. Results On average per 1,000 adults, 295 had at least one symptom, 217 considered seeking medical care, 173 consulted a physician, 129 visited western medical practitioners, 127 visited a hospital-based outpatient clinic, 78 visited traditional Chinese medical practitioners, 43 visited a primary care physician, 35 received care in an emergency department, 15 were hospitalized. Health care seeking behaviors varied with socio-demographic characteristics, such as gender, age, ethnicity, resident census register, marital status, education, income, and health insurance status. In term of primary care, the gate-keeping and referral roles of Community Health Centers have not yet been fully established in Beijing. Conclusions This study represents a first attempt to map the medical care ecology of Beijing urban population and provides timely baseline information for health care reform in China.

hCLP46 regulates U937 cell proliferation via Notch signaling pathway

Human CAP10-like protein 46 kDa (hCLP46) is the homolog of Rumi, which is the first identified protein O-glucosyltransferase that modifies Notch receptor in Drosophila. Dysregulation of hCLP46 occurs in many hematologic diseases, but the role of hCLP46 remains unclear. Knockdown of hCLP46 by RNA interference resulted in decreased protein levels of endogenous Notch1, Notch intracellular domain (NICD) and Notch target gene Hes-1, suggesting the impairment of the Notch signaling. However, neither cell surface Notch expression nor ligand binding activities were affected. In addition, down-regulated expression of hCLP46 inhibited the proliferation of U937 cells, which was correlated with increased cyclin-dependent kinase inhibitor (CDKI) CDKN1B (p27) and decreased phosphorylation of retinoblastoma (RB) protein. We showed that lack of hCLP46 results in impaired ligand induced Notch activation in mammalian cell, and hCLP46 regulates the proliferation of U937 cell through CDKI-RB signaling pathway, which may be important for the pathogenesis of leukemia.

Prevalence of metabolic syndrome and optimal waist circumference cut-off points for adults in Beijing

BACKGROUND In the modified ATP III definition for metabolic syndrome (MS), the cut-off values for central obesity were set to > or =90 cm for male and > or =80 cm for women. Recently, a new Chinese definition for central obesity was set to > or =90 cm for male and > or =85 cm for women according to the corresponding BMI value of 25 kg/m(2). OBJECTIVE The purpose of this study was to explore the optimal WC cut-off points to reflect the cluster of multiple risk factors for adults in Beijing. METHOD The data collected during the surveillance of risk factors for non-communicable diseases in Beijing 2005 were used, with a total of 16,711 adults studied. Subjects with two or more components from the modified ATP III definition other than central obesity were considered to have multiple risk factors. RESULTS The optimal WC cut-off points were 87 cm in men and 80 cm for women. When applied the WC advised definition for MS, the age-standardized prevalence was 38.0% for male and 32.3% for women, which is significantly higher than using the original one for men (34.7% vs 32.3%, P<0.001). CONCLUSION The present study indicated that optimal waist circumference cut-off points were lower than that proposed in the modified ATP III definition, especially for men.