Development Trend of Infectious Disease Hospitals in China 2002-2018: A Longitudinal Analysis of National Survey Data.

BACKGROUND: Infectious disease hospitals (IDHs) play very important roles in the battle against the infectious disease. The present study aims to systematically analyze the development trends and possible problems of IDHs in China. METHODS: Most of the data came from the China Health Statistics Yearbook 2003-2019. Joinpoint Regression Model was used to analyze the development trends of IDHs between 2002 and 2018. RESULTS: From 2002 to 2018, the number of IDHs in China increased from 126 to 167, with an average annual percent change (AAPC) of 1.82%. The ratio of nurses to beds increased from 0.38 to 0.46 with the AAPC of 0.88%, and average business housing area per bed increased with an AAPC of 1.97%. The percentage of liabilities to total assets increased year by year and the percentage of medical business costs to total expenditure decreased. The segmented trend of daily visits per physician from 2014 to 2018 was stable, and the segmented trend of daily inpatients per physician from 2012 to 2018 decreased significantly. In 2017, the rates of surgical inpatients leaving the hospital without the doctor's advice and surgical inpatients mortality were higher than 2016. CONCLUSION: Although the development of IDHs was generally good in China, the scale of IDHs was generally small, the ability to respond to major emergencies was weak, the problem of irrational resource allocation was still prominent, and the operation of IDHs was facing a dilemma.

Impact of CYP2R1, CYP27A1 and CYP27B1 genetic polymorphisms controlling vitamin D metabolism on susceptibility to hepatitis C virus infection in a high-risk Chinese population.

CYP27A1, CYP2R1 and CYP27B1 hydroxylases are involved in the synthesis of 1, 25-hydroxyvitamin D3, which plays a role in the immune regulation and pathogenesis of hepatitis C virus (HCV) infection. The aim of the present study was to investigate the relationships between polymorphisms in vitamin D pathway genes and HCV infection outcomes in a Chinese population. Nine single-nucleotide polymorphisms (SNPs) of CYP27A1, CYP2R1 and CYP27B1 were genotyped in a high-risk Chinese population. The distributions of these SNPs were compared among groups with different outcomes of HCV infection, including 863 cases of persistent HCV infection, 524 cases of spontaneous clearance, and 1079 uninfected controls. The results showed that the CYP2R1 rs12794714-G, rs10741657-A, rs1562902-C, and rs10766197-G alleles were significantly associated with increased susceptibility to HCV infection (all PFDR < 0.05, in additive/dominant models), and the combined effect of the four unfavorable alleles was related to an elevated risk of HCV infection in a locus-dosage manner (Ptrend = 0.008). Moreover, haplotype analysis suggested that, compared with the most frequent haplotype (Ars12794714Grs10741657Trs1562902Ars10766197), the haplotype containing four unfavorable alleles, GACG, was associated with a higher risk of HCV infection. The results of our study suggest that genetic variants in CYP2R1 may be biomarkers for predicting the susceptibility to HCV infection in the Chinese population.

Serum levels of trace elements in children born after assisted reproductive technology.

INTRODUCTION: The health and development of newborn children born via assisted reproductive technology (ART), as well as their health in adulthood, have raised great concern. This study was designed to investigate whether ART children have differences in the levels of trace elements compared with naturally conceived children. METHODS: This study included those ART children and controls aged 1 to 12 years assessed with a follow-up protocol. Serum levels of the trace elements zinc, copper, iron, calcium, magnesium and lead were determined and analyzed. RESULTS: There were no significant differences in age, gender or body weight between the ART and control groups. There were no significant differences in the rates of deficiency or excess of trace elements between the two groups. Serum lead levels in children born via ART were significantly higher than those in the controls, whereas the levels of zinc and iron were significantly decreased in the ART group, although these levels were still within the normal ranges. DISCUSSION: These results indicate the need to monitor the blood levels of zinc, iron and lead in ART children aged 1-6 years old. These findings contribute to our understanding on the long-term safety of ART and may facilitate screening for potential diseases related to trace elements.

Vitamin D binding protein polymorphisms influence susceptibility to hepatitis C virus infection in a high-risk Chinese population.

Vitamin D binding protein (VDBP) plays an important role in the immune modulation and pathogenesis of hepatitis C viral (HCV) infection by influencing serum vitamin D levels. The present study aims to evaluate the association of VDBP genetic polymorphisms with susceptibility to and chronicity of HCV infection in a high-risk Chinese population. Seven genetic variants in the VDBP gene were genotyped in a case-control study of 886 patients with HCV persistent infection, 539 subjects with spontaneous clearance, and 1081 uninfected controls. Logistic regression analysis was used to assess the effects of these variants on HCV infection outcomes. The results showed that two variants rs7041-G and rs3733359-T alleles were significantly associated with increased susceptibility of HCV infection, and the combined effect of the two unfavorable alleles was related to an elevated risk of HCV infection in a locus-dosage manner (Ptrend = 8.16 × 10-4). Interaction analysis manifested that rs7041-GT/GG and rs3733359-CT/TT jointly increased risk of HCV infection. Moreover, haplotype analysis suggested that compared with the most frequent TC haplotype, the haplotype carrying GT indicated a risk effect of HCV infection [odds ratio (OR) = 1.464]. However, no significant associations were observed for the other five variants. These findings implied that VDBP rs7041-G and rs3733359-T variants may contribute to increased susceptibility to HCV infection in a high-risk Chinese population.

Histological changes of gastric mucosa after Helicobacter pylori eradication: a systematic review and meta-analysis.

AIM: To systematically review pathological changes of gastric mucosa in gastric atrophy (GA) and intestinal metaplasia (IM) after Helicobacter pylori (H. pylori) eradication. METHODS: A systematic search was made of PubMed, Web of Science, EMBASE, ClinicalTrials.gov, OVID and the Cochran Library databases for articles published before March 2013 pertaining to H. pylori and gastric premalignant lesions. Relevant outcomes from articles included in the meta-analysis were combined using Review Manager 5.2 software. A Begg's test was applied to test for publication bias using STATA 11 software. χ(2) and I(2) analyses were used to assess heterogeneity. Analysis of data with no heterogeneity (P > 0.1, I (2) < 25%) was carried out with a fixed effects model, otherwise the causes of heterogeneity were first analyzed and then a random effects model was applied. RESULTS: The results of the meta-analysis showed that the pooled weighted mean difference (WMD) with 95%CI was 0.23 (0.18-0.29) between eradication and non-eradication of H. pylori infection in antral IM with a significant overall effect (Z = 8.19; P <0.00001) and no significant heterogeneity (χ(2) = 27.54, I(2) = 16%). The pooled WMD with 95%CI was -0.01 (-0.04-0.02) for IM in the corpus with no overall effect (Z = 0.66) or heterogeneity (χ(2) = 14.87, I(2) =0%) (fixed effects model). In antral GA, the pooled WMD with 95% CI was 0.25 (0.15-0.35) with a significant overall effect (Z = 4.78; P < 0.00001) and significant heterogeneity (χ(2) = 86.12, I(2) = 71%; P < 0.00001). The pooled WMD with 95% CI for GA of the corpus was 0.14 (0.04-0.24) with a significant overall effect (Z = 2.67; P = 0.008) and significant heterogeneity (χ(2) = 44.79, I(2) = 62%; P = 0.0003) (random effects model). CONCLUSION: H. pylori eradication strongly correlates with improvement in IM in the antrum and GA in the corpus and antrum of the stomach.

[Application of gene-based logistic kernel-machine regression model on studies related to the genome-wide association].

To explore the gene-based logistic kernel-machine regression model and its application in genome-wide association study(GWAS). Using the simulated genome-wide single-nucleotide polymorphism(SNPs)genotypes data, we proposed a practical statistical analysis strategy-named 'the logistic kernel-machine regression model', based on the gene levels to assess the association between genetic variations and complex diseases. The results from simulation showed that the P value of genes in related diseases was the smallest among all the genes. The results of simulation indicated that not only it could borrow information from different SNPs that were grouped in genes and reducing the degree of freedom through hypothesis testing, but could also incorporate the covariate effects and the complex SNPs interactions. The gene-based logistic kernel-machine regression model seemed to have certain statistical power for testing the association between genetic genes and diseases in GWAS.

Effects of uncoupling protein 2 -866G/A polymorphism on platelet reactivity and prognosis in Chinese patients with type 2 diabetes and ischemic stroke.

The purpose of this study was to assess the effects of -866G>A polymorphism of mitochondrial uncoupling protein 2 (UCP-2) on platelet reactivity and prognosis in patients with type 2 diabetes and ischemic stroke (IS). A total of 405 Chinese patients with type 2 diabetes and stroke were assessed in a 4-year follow-up case-control study. Patient response to antiplatelet therapy was measured with the Platelet Function Analyzer-100 by means of collagen/adenosine diphosphate (CADP) and collagen/epinephrine (CEPI) cartridges. The primary end point was a composite of stroke and TIA (transient ischemic attack), the secondary end point was death. The -866G>A polymorphism in UCP-2 was genotyped by TaqMan MGB probe method. The -866G>A SNP in UCP-2 was not significantly associated with recurrence of diabetic ischemical stroke (p = 0.57). A significant trend toward nonfull response to antiplatelet therapy was seen in patients carrying A allel in comparison with those carrying GG genotype, as shown by the CADP and CEPI tests (p < 0.0001). Our 4-year follow-up study shows no association between -866G>A variant of UCP-2 in type 2 diabetes and the risk of developing stroke. But in conclusion, the A allel is associated with clopidogrel resistance.

[Gene-based principal component logistic regression model and its application on genome-wide association study].

To explore the gene-based principal component logistic regression model and its application in genome-wide association study. Using the simulated genome-wide single nucleotide polymorphism (SNPs) genotypes data, we proposed a practical statistical analysis strategy-'the principal component logistic regression model', based on the gene levels to assess the association between genetic variations and complex diseases. The simulation results showed that the P value of genes in related diseases was the smallest among the results from all the genes. The results of simulation indicated that not only it could reduce the degree of freedom through hypothesis testing but could also better understand the correlations between SNPs. The gene-based principal component logistic regression model seemed to have certain statistical power for testing the association between genetic genes and diseases in the genome-wide association studies.

The uncoupling protein 2 -866G > a polymorphism is associated with the risk of ischemic stroke in Chinese type 2 diabetic patients.

AIMS: To determine genetic predispsitions for diabetic cerebral ischemia, we investigated the relationship between the -866G>A polymorphism of uncoupling protein (UCP) 2 and the risk of ischemic stroke in two cohorts of type 2 diabetic patients. METHODS: A total of 844 type 2 diabetic patients with 4-year prospective study were examined using a case-control methodology. And 404 cases with ischemical stroke, 440 cases without ischemical stroke. The -866G>A polymorphism in UCP2 was genotyped by TaqMan MGB probe method. RESULTS: The -866G>A SNP in UCP2 was significantly associated with diabetic ischemical stroke (odds ratio [OR]= 1.94; 95% confidence interval [CI]= 0.68 to1.31; P < 0.037). Similar results were observed for baseline cases of IS. Stratification by sex confirmed an allelic association with IS in women, whereas no association was observed in men. CONCLUSIONS: The A allele of the -866G>A variant of UCP2 was associated with increased risk of IS in Chinese diabetic women with type 2 diabetes in a 4-year prospective study. This association was independent of other common IS risk factors.

[Using two-stage case-control designs to study the genome-wide association].

Genome-wide association study is an important approach to identify common genetic variants that predispose to human disease. Because of the high cost of genotyping on hundreds of thousands of markers on thousands of subjects, a more cost-effective two-stage case-control design is applied by most genome-wide association studies. To describe the design and statistical methods of the two-stage case-control study, this paper introduces the principles of two-stage case-control design, its implementing steps in genome-wide association study and the features of its application. The method is illustrated with an example.

[Association between calpain-10 gene polymorphism and risk of type 2 diabetes mellitus: a meta analysis].

OBJECTIVE: The purpose of this study was to approach the relation of SNP43, SNP44 locus, main haplotypes and haplotype combinations with type 2 diabetes mellitus (T2DM). METHODS: According to the theory and principles of systematic review, data from case-control studies regarding the association between calpain-10 (CAPN10) gene and T2DM were derived through electronic search of PubMed and Chinese journals databases. To gain a more precise estimation of the relationship, a stratified Meta-analysis with four subgroups was performed according to the races. Publication bias was also assessed. RESULTS: The association with T2DM in different races was evaluated. In Mongoloid race, SNP43-G allele, G/G genotype and 111/221 haplotype combination showed notable association with T2DM with ORs (95%CI) as 1.368 (1.155 - 1.620), 1.437 (1.186 - 1.741) and 2.762 (1.287 - 5.927) respectively. In Caucasoid race, SNP44-C allele, 111/111 hapotype combination showed strong relationship with T2DM with ORs (95%CI) as 1.144 (1.023 - 1.278), 1.291(1.050 - 1.586) respectively. In Hybrid race, only one positive finding was obtained which was SNP44-C allele with OR (95%CI) as 1.653 (1.025 - 2.665). CONCLUSION: SNP43-G allele, G/G genotype, 111/221 were risk factors to Mongoloid race. And SNP-C allele, 111/111 haplotype combination were risk factors to Caucasoid race, and SNP44-C allele to Hybrid race.

[Introduction on "case-sibling control design"].

OBJECTIVE: To introduce the design and statistical methods of case-sibling control design and to analyze the published data. METHODS: Data from an association study between the coronary heart disease and methylenetetrahydrofolate reductase gene C677T polymorphism was analyzed by the sib transmission/disequibrium test (s-TDT) and the sibship disequilibrium (SDT) methods. RESULTS: Using s-TDT method, Z value was 0.27 with P > 0.05. The result of SDT method showed that chi-square was 0.31 with 1 df, P > 0.05. All results suggested that neither s-TDT nor SDT showed significant difference between the transmitted and untransmitted methylenetetrahydrofolate reductase gene C677T allele distributions. CONCLUSION: Case-sibling control design might avoid population stratification by using siblings as controls thus might be used to test association and linkage between genes and disease.

[Case-parental control study].

OBJECTIVE: To introduce the methodology on the design and statistical method as well as analysis of published data related to case-parental control study. METHODS: Data from a research on association between the human neural tube defects and the T allelic variant TIVS7-2 was analyzed by haplotype relative risk (HRR), genotype relative risk (GRR) and transmission/disequilibrium test (TDT) methods. RESULTS: Using the HRR method, HRR value was 1.33 (chi-square statistic is 1.4618 with P = 0.2266). The results of the GRR method showed that psi(1) value was 1.26 and psi(2) value was 0.98 (chi-square statistic is 3.1809 with 2 df, P = 0.2038). The transmission/disequilibrium test showed that TDT was 1.4516 with P = 0.2283. All results suggested that when a weak association of TIVS7-2 allele with neural tube defects was found, there was no evidence showing the statistical difference. CONCLUSION: The case-parental control design method avoids population stratification when parents used as controls. This method might be used to test the association between genes and disease, as well as to evaluate the gene environmental interaction.