Feifei Zhao

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.

Urbanization and the prevalence of schizophrenia in China between 1990 and 2010

Among the environmental risk factors for schizophrenia, evidence supports a role of urbanicity (1–3). In recent decades, urbanization has been occurring at a massive scale in low- and middle-income countries (4,5). It is therefore of global public health importance to explore how rapid urbanization might have affected the burden of schizophrenia in growing economies, with China being a prime example. Epidemiological evidence in China has improved over the past two decades and Chinese academic journals have become accessible in electronic databases (6). Moreover, China recently underwent urbanization and economic development at an unprecedented scale: 26.4% of its 1.1 billion inhabitants lived in urban areas in 1990, rising to 49.2-49.7% of 1.3 billion in 2010 (4,7). We may expect a significant increase of schizophrenia burden in China as a result. To explore this, we conducted a systematic review of the Chinese and English literature, through China National Knowledge Infrastructure, Wanfang and PubMed, for the years from 1990 to 2010. Only studies that had applied a case definition based on DSM-III or IV, ICD-9 or 10, or Chinese Classification of Mental Disorders (CCMD-2, 2R or 3) were retained. Based on pre-defined minimum quality criteria, 42 prevalence studies were selected. They were mostly large population-based studies, typically using a two-stage data collection design in which trained assessors performed an initial screening and psychiatrists followed up with a detailed evaluation. Direct contact was made with the corresponding authors of 13 studies to obtain any missing information. Geographically, the retained studies covered 21 of mainland China’s 31 provinces, municipalities and autonomous regions. Bayesian methods were applied to predict maximum likelihood for point prevalence and lifetime prevalence in urban and rural China in the years 1990, 2000 and 2010. The analyses of the 42 studies combined information from 2,284,957 people, 10,506 of whom were diagnosed with schizophrenia in their lifetime. In urban areas, the point prevalence (≥15 years) of the disorder was 0.32% (95% CI: 0.29-0.36) in 1990, 0.47% (95% CI: 0.44-0.50) in 2000, and 0.68% (95% CI: 0.57-0.81) in 2010. In contrast, in rural areas, the corresponding estimates were 0.37% (95% CI: 0.33-0.42), 0.36% (95% CI: 0.35-0.38), and 0.35% (95% CI: 0.33-0.38). Lifetime prevalence (≥15 years) in urban China was 0.39% (95% CI: 0.37-0.41) in 1990, 0.57% (95% CI: 0.55-0.59) in 2000, and 0.83% (95% CI: 0.75-0.91) in 2010. The corresponding estimates for rural areas were 0.37% (95% CI: 0.34-0.40), 0.43% (95% CI: 0.42-0.44), and 0.50% (95% CI: 0.47-0.53). Applying these prevalence estimates to the corresponding population of China, there were 3.09 (95% CI: 2.87-3.32) million persons affected during their lifetime in the year 1990. Twenty-seven percent of the cases were from urban areas, which corresponds to the overall proportion of urban residents in China in the same year (26.4%). By 2010, the number of persons affected with schizophrenia rose to 7.16 (95% CI: 6.57-7.75) million, a 132% increase, while the total population of China only increased by 18% during this period (4). Moreover, the contribution of expected cases from urban areas to the overall burden increased from 27% in 1990 to 62% in 2010, well above the proportion of urban residents in China in 2010 (49.2-49.7%). This study helps to establish the universality of urbanicity as a risk factor and the extent to which it affects the burden of schizophrenia in a large country that underwent rapid urbanization. As schizophrenia prevalence was found to be similar in rural and urban China at the beginning of industrialization (late 1980s) (8), our findings suggest that the mechanisms driving the risks of illness in urban areas are likely to be associated with modern urban lifestyles. The lower rates of schizophrenia found when China was less industrialized are consistent with studies that reported lower rates of the illness in low- and middle-income countries (3). This analysis has broad implications. Many populous parts of the world, particularly in low- and middle-income countries, are undergoing urbanization at a scale and rate that took Western countries centuries to achieve (9). Global urbanization may therefore result in an increased global prevalence of schizophrenia through mechanisms that need to be further explored.

Profiling plasma peptides for the identification of potential ageing biomarkers in Chinese Han adults

Advancing age is associated with cardiovascular disease, diabetes mellitus and cancer, and shows significant inter-individual variability. To identify ageing-related biomarkers we performed a proteomic analysis on 1890 Chinese Han individuals, 1136 males and 754 females, aged 18 to 82 years, using weak cation exchange magnetic bead based MALDI-TOF-MS analysis. The study identified 44 peptides which varied in concentration in different age groups. In particular, apolipoprotein A-I (ApoA1) concentration gradually increased between 18 to 50 years of age, the levels of fibrinogen alpha (FGA) decreased over the same age span, while albumin (ALB) was significantly degraded in middle-aged individuals. In addition, the plasma peptide profiles of FGA and four other unidentified proteins were found to be gender-dependent. Plasma proteins such as FGA, ALB and ApoA1 are significantly correlated with age in the Chinese Han population and could be employed as indicative ageing-related biomarkers.

The Uyghur population and genetic susceptibility to type 2 diabetes: potential role for variants in CAPN10, APM1 and FUT6 genes

Genome‐wide association studies have successfully identified over 70 loci associated with the risk of type 2 diabetes mellitus (T2DM) in multiple populations of European ancestry. However, the risk attributable to an individual variant is modest and does not yet provide convincing evidence for clinical utility. Association between these established genetic variants and T2DM in general populations is hitherto understudied in the isolated populations, such as the Uyghurs, resident in Hetian, far southern Xinjiang Uyghur Autonomous Region, China. In this case–control study, we genotyped 13 single‐nucleotide polymorphisms (SNPs) at 10 genes associated with diabetes in 130 cases with T2DM and 135 healthy controls of Uyghur, a Chinese minority ethnic group. Three of the 13 SNPs demonstrated significant association with T2DM in the Uyghur population. There were significant differences between the T2DM patients and controls in the risk allele distributions of rs3792267 (CAPN10) (P = 0.002), rs1501299 (APM1) (P = 0.017), and rs3760776 (FUT6) (P = 0.031). Allelic carriers of rs3792267‐A, rs1501299‐T, and rs3760776‐T had a 2.24‐fold [OR (95% CI): 1.35–3.71], 0.59‐fold [OR (95% CI): 0.39–0.91], 0.57‐fold [OR (95% CI): 0.34–0.95] increased risk for T2DM respectively. We further confirmed that the cumulative risk allelic scores calculated from the 13 susceptibility loci for T2DM differed significantly between the T2DM patients and controls (P = 0.001), and the effect of obesity/overweight on T2DM was only observed in the subjects with a combined risk allelic score under a value of 17. This study observed that the SNPs rs3792267 in CAPN10, rs1501299 in APM1, and rs3760776 in FUT6 might serve as potential susceptible biomarkers for T2DM in Uyghurs. The cumulative risk allelic scores of multiple loci with modest individual effects are also significant risk factors in Uyghurs for T2DM, particularly among non‐obese individuals. This is the first investigation having observed/found genetic variations on genetic loci functionally linked with glycosylation associated with the risk of T2DM in a Uyghur population.

Abnormal Methylation of Imprinted Genes and Cigarette Smoking: Assessment of Their Association With the Risk of Male Infertility

Male infertility is a complicated disease with causes generally split into 2 broad categories: genetic factors and environmental factors. The present study was designed to investigate the association between the methylation patterns of H19 and SNRPN imprinting control region (ICR) and male infertility and to assess the gene–environment interactions between environmental factors and methylation patterns. A total of 205 DNA samples from 48 oligozoospermia (OZ), 52 asthenozoospermia (AZ), 55 teratozoospermia (TZ) patients, and 50 normozoospermia (NZ) men were analyzed. The mean methylation level of H19-ICR in OZ (80.40% ± 12.74%) and AZ patients (81.17% ± 13.18%) was significantly lower than methylation in men with NZ (88.51% ± 10.54%, P<.001, P<.001, respectively). The mean methylation level of SNRPN-ICR in AZ patients (7.74% ± 5.71%) and TZ patients (9.33% ± 5.48%) was significantly higher than in NZ men (6.32% ± 3.54%, P<.001, P<.001, respectively). Among environmental factors, smoking was correlated with OZ (odds ratio [OR] = 5.12, 95% CI: 2.05-12.83), AZ (OR = 5.65, 95% CI: 2.13-14.99), and TZ (OR = 5.54, 95% CI: 2.21-13.89). Gene–environment interaction analysis revealed that hypomethylation of H19-ICR in OZ patients and hypermethylation of SNRPN-ICR in AZ and TZ patients were significantly associated with an increased the risk of infertility in men who were smokers (OR = 15.30, 95% CI: 1.13-207.97; OR = 13.20, 95% CI: 1.21-143.57; OR = 10.59, 95% CI: 1.04-107.39, respectively). This study demonstrated that hypomethylation of H19-ICR and hypermethylation of SNRPN-ICR are associated with male infertility, and the risk is potentiated by smoking.

Immunoglobulin G N-Glycans as potential postgenomic biomarkers for hypertension in the Kazakh population

Next-generation (postgenomic) biomarkers from the nascent field of glycomics now offer fresh vistas for innovation in chronic disease biomarkers and system diagnostics in clinical medicine. Our previous work has shown an association between hypertension and immunoglobulin G (IgG) glycome composition, suggesting that individual variation in N-glycosylation of IgG might contribute to hypertension pathogenesis. The present study examined, for the first time to the best of our knowledge, the IgG N-glycans as potential biomarkers for hypertension in the Kazakh population. The profile of 60 N-glycopeptides of IgG subclass isolated from plasma samples of 150 Kazakh study participants was analyzed by nano ultra-performance liquid chromatography with mass spectrometry. Fourteen IgG subclass-specific Fc N-glycopeptide structures, along with one derived glycosylation trait in subclasses IgG2/3 and IgG4, were found to correlate with systolic blood pressure and/or diastolic blood pressure. For differentiation of hypertension and healthy status in the Kazakh population sample, the receiver operating characteristic curve analysis showed that the performance of the model, including nine IgG N-glycans, was greater than the traditional gender, age, and body mass index based model (p < 0.05). This study indicates that alteration in Fc N-glycopeptide profiles of plasma IgG subclasses is associated with blood pressure status in the Kazakh population. IgG N-glycosylation profiles may serve as potential biomarkers for hypertension in the Kazakhs, thus contributing to move toward personalized medicine. Further studies of postgenomic glycomic biomarkers in cardiovascular and chronic diseases are timely and called for.

The genetic associations and epistatic effects of the CCR5 promoter and CCR2-V64I polymorphisms on susceptibility to HIV-1 infection in a Northern Han Chinese population.

The outcome of human immunodeficiency virus (HIV)-1 infection and course to AIDS are variable among individuals. Both chemokine receptor 5 (CCR5) and CCR2 gene polymorphisms play essential roles in the susceptibility of HIV-1 infection. To investigate the main and epistatic effects of the CCR5 promoter and CCR2-V64I polymorphisms on HIV-1 infection in the Northern Han Chinese, subjects of 91 HIV-1-infected patients and 91 health controls were recruited. Single-nucleotide polymorphisms (SNPs) in the CCR5 promoter region and CCR2-V64I variants were genotyped. In the single-locus analysis, CCR5 58755-G and CCR5 59653-T alleles were significantly associated with HIV-1 infection (odds ratio [OR]=0.529, 95% confidence interval [CI]: 0.295-0.948; OR=1.710, 95% CI: 1.039-2.814). After adjustment with age and gender, subjects with the CCR5 59653-CT genotype showed the increased risk of HIV-1 infection compared with those with the wild-type CC genotype (adjusted OR=2.502; 95% CI: 1.332-4.698). No positive association was observed in other SNPs. Haplotype-based association analysis revealed that the haplotype TATGC was associated with the susceptibility to HIV-1 infection (p=0.003). Besides, we found the significant epistatic effects between the CCR5 58755-A/G and CCR5 59029-A/G polymorphisms associated with the lower risk of HIV-1 infection. In addition, we also identified the best three-factor interaction model, including the CCR5 58755-A/G, 59029-A/G, and CCR2-V64I polymorphisms, indicating that there were also strong gene-gene interactions between the CCR5 promoter and CCR2 polymorphisms on the susceptibility of HIV-1 infection. These findings contribute to understanding the genetic mechanism for the susceptibility of HIV-1 infection in Northern Han Chinese.

Screening for potential serum-based proteomic biomarkers for human type 2 diabetes mellitus using MALDI-TOF MS

Type 2 diabetes mellitus (T2DM) is a complex, pandemic disease contributing towards the global burden of health issues. To date, there are no simple clinical tests for the early detection of T2DM.

The Expected Number of Background Disease Events during Mass Immunization in China

It is critical to distinguish events that are temporarily associated with, but not caused by, vaccination from those caused by vaccination during mass immunization. We performed a literature search in China National Knowledge Infrastructure and Pubmed databases. The number of coincident events was calculated based on its incidence rate and periods after receipt of a dose of hypothesized vaccine. We included background incidences of Guillain-Barré syndrome, anaphylaxis, seizure, sudden adult death syndrome, sudden cardiac death, spontaneous abortion, and preterm labour or delivery. In a cohort of 10 million individuals, 7.71 cases of Guillain-Barré syndrome would be expected to occur within six weeks of vaccination as coincident background cases. Even for rare events, a large number of events can be expected in a short period because of the large population targeted for immunization. These findings may encourage health authorities to screen the safety of vaccines against unpredictable pathogens.