Study on semi-dynamic leaching and microstructure characteristics of MSWI fly ash solidified sediment.

municipal solid waste incineration (MSWI) fly ash partially replaces cement to solidify sediment, and then can be used as intermediate cover materials in landfill as one of the resources utilization ways of MSWI fly ash and sediment. The strength and the semi-dynamic leaching characteristics of MSWI fly ash solidified sediment under hydrochloric acid attack at different pH were studied by means of unconfined compressive strength (UCS), semi-dynamic leaching, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA). Results revealed that the UCS strength increased as the curing age and cement content increased. When the curing content is 50% and the replacement ratio of MSWI fly ash is 75% and 80%, the UCS of 7 d can be greater than 50 kPa. The primary contribution to the strength development was from silicic acid gels such as calcium silicate hydrate (C-S-H) and carbonates. Notably, the leaching behavior of Zn and Cu within the solidified sediment underwent substantial alterations. The leaching amount of heavy metals in a strong acidic environment (pH = 2) is significantly greater than that in a weak acidic (pH = 4) and neutral (pH = 7) environment. Conversely, minimal disparities were observed in the leaching characteristics of Zn and Cu between the weakly acidic and neutral environments. Ca(OH)2, C-S-H and carbonate exhibits a remarkable acid-resistant buffering capacity in the solidified sediment. The obvious diffusion coefficient (Dobs) was less than 10-9 m2/s in semi-dynamic leaching tests. Moreover, the mobility of Zn and Cu surpassing 12.5, coupled with a leaching index exceeding 8, further attests to the favorable S/S outcome achieved. Based on these findings, the solidified material is confidently recommended to be used as suitable landfill middle soil cover material.

Effect of acidic erosion on properties of solidified sewage sludge.

Solidified sludge can be regarded as a new type of earth cover material for domestic waste landfill. But the acidic environment result from the leachate in landfill is a potential threat to cement-based material. In order to evaluate the deterioration risk of solidified sludge in acidic environment, the leaching process of solidified sludge components under different pH conditions was investigated by taking Ni and Cr as the indexes of semi-dynamic leaching test. Under strongly acid environment (pH = 2), the leaching rate of Cr is significantly higher than that in the weakly acid environment or nearly neutral environment, and the diffusion coefficient increased by an order of magnitudes. The leaching and diffusion coefficients of Ni undergo a small influence from the adding amount of cement and pH value. Both Ni and Cr have relatively low migration ratio.

Clinical outcomes of automated versus continuous ambulatory peritoneal dialysis for end-stage kidney disease: protocol of a systematic review and meta-analysis.

INTRODUCTION: An increasing number of studies comparing automated peritoneal dialysis (APD) with continuous ambulatory peritoneal dialysis (CAPD) in clinical outcomes have been published since the publication of a systematic review and meta-analysis including three randomised controlled trials in 2007. We will conduct a systematic review and meta-analysis to explore more clinical outcomes of APD versus CAPD for end-stage kidney disease. METHODS AND ANALYSIS: The protocol is conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Three databases-PubMed, EMBASE and the Cochrane Library-will be searched comprehensively from inception to 16 June 2022, without language restriction. Studies reporting clinical outcomes comparing APD with CAPD will be included. Two independent reviewers will screen the titles and abstracts and then obtain and assess full texts of potential relevant articles for eligibility following the inclusion and exclusion criteria. The methodological quality of included observational studies will be assessed by using the Newcastle-Ottawa Scale. The risk of bias of included randomised controlled studies will be assessed by using the Cochrane Risk of Bias tool. Relative risk for dichotomous outcomes and standard mean difference for continuous outcomes with corresponding 95% CIs will be pooled for summary effects. Cochrane Q test and I 2 values will be used to assess heterogeneity between studies. To assess and explore the source of heterogeneity, subgroup analyses and sensitivity analyses will be conducted, and meta-regression, funnel plot and Egger's test will be performed if there are no less than 10 studies. Analyses will be performed using STATA software, V.13.0 (STATA Corporation, College Station, Texas, USA). ETHICS AND DISSEMINATION: Ethics approval is not applicable as no personal information is collected from patients. The results will be published in a peer-reviewed journal or disseminated in relevant academic conferences. PROSPERO REGISTRATION NUMBER: CRD42022311401.

Incidence and cost of haemolytic uraemic syndrome in urban China: a national population-based analysis.

BACKGROUND: Haemolytic uraemic syndrome (HUS) is a severe syndrome that causes a substantial burden for patients and their families and is the leading cause of acute kidney injury in children. However, data on the epidemiology and disease burden of HUS in Asia, including China, are limited. We aimed to estimate the incidence and cost of HUS in China.  METHODS: Data about HUS from 2012 to 2016 were extracted from the Urban Employee Basic Medical Insurance (UEBMI) and Urban Resident Basic Medical Insurance (URBMI) databases. All cases were identified by ICD code and Chinese diagnostic terms. The 2016 national incidence rates were estimated and stratified by sex, age and season. The associated medical costs were also calculated. RESULTS: The crude incidence of HUS was 0.66 per 100,000 person-years (95% CI: 0.35 to 1.06), and the standardized incidence was 0.57 (0.19 to 1.18). The incidence of HUS in males was slightly higher than that in females. The age group with the highest incidence of HUS was patients < 1 year old (5.08, 95% CI: 0.23 to 24.87), and the season with the highest incidence was autumn, followed by winter. The average cost of HUS was 2.15 thousand US dollars per patient, which was higher than the national average cost for all inpatients in the same period. CONCLUSIONS: This is the first population-based study on the incidence of HUS in urban China. The age and seasonal distributions of HUS in urban China are different from those in most developed countries, suggesting a difference in aetiology.

Artificial Intelligence-Assisted Bone Age Assessment to Improve the Accuracy and Consistency of Physicians With Different Levels of Experience.

Background: The accuracy and consistency of bone age assessments (BAA) using standard methods can vary with physicians' level of experience. Methods: To assess the impact of information from an artificial intelligence (AI) deep learning convolutional neural network (CNN) model on BAA, specialists with different levels of experience (junior, mid-level, and senior) assessed radiographs from 316 children aged 4-18 years that had been randomly divided into two equal sets-group A and group B. Bone age (BA) was assessed independently by each specialist without additional information (group A) and with information from the model (group B). With the mean assessment of four experts as the reference standard, mean absolute error (MAE), and intraclass correlation coefficient (ICC) were calculated to evaluate accuracy and consistency. Individual assessments of 13 bones (radius, ulna, and short bones) were also compared between group A and group B with the rank-sum test. Results: The accuracies of senior, mid-level, and junior physicians were significantly better (all P < 0.001) with AI assistance (MAEs 0.325, 0.344, and 0.370, respectively) than without AI assistance (MAEs 0.403, 0.469, and 0.755, respectively). Moreover, for senior, mid-level, and junior physicians, consistency was significantly higher (all P < 0.001) with AI assistance (ICCs 0.996, 0.996, and 0.992, respectively) than without AI assistance (ICCs 0.987, 0.989, and 0.941, respectively). For all levels of experience, accuracy with AI assistance was significantly better than accuracy without AI assistance for assessments of the first and fifth proximal phalanges. Conclusions: Information from an AI model improves both the accuracy and the consistency of bone age assessments for physicians of all levels of experience. The first and fifth proximal phalanges are difficult to assess, and they should be paid more attention.

Risk factors and prediction nomogram model for psychosocial and behavioural problems among children and adolescents during the COVID-19 pandemic: A national multicentre study: Risk Factors of Childhood Psychosocial Problems.

BACKGROUND: We aimed to explore the risk profiles attributable to psychosocial and behavioural problems during the coronavirus disease 2019 pandemic. To this end, we created a risk-prediction nomogram model. METHODS: A national multicentre study was conducted through an online questionnaire involving 12,186 children (6-11 years old) and adolescents (12-16 years old). Respondents' psychosocial and behavioural functioning were assessed using the Achenbach Child Behaviour Checklist (CBCL). Data were analysed using STATA software and R-language. RESULTS: The positive detection rate of psychological problems within Wuhan was greater than that outside Wuhan for schizoid (P = 0.005), and depression (P = 0.030) in children, and for somatic complaints (P = 0.048), immaturity (P = 0.023), and delinquent behaviour (P = 0.046) in adolescents. After graded multivariable adjustment, seven factors associated with psychological problems in children and adolescents outside Wuhan were parent-child conflict (odds ratio (OR): 4.94, 95% confidence interval (95% CI): 4.27-5.72), sleep problems (OR: 4.05, 95% CI: 3.77-4.36), online study time (OR: 0.41, 95% CI: 0.37-0.47), physical activity time (OR: 0.510, 95% CI: 0.44-0.59), number of close friends (OR: 0.51, 95% CI: 0.44-0.6), time spent playing videogames (OR: 2.26, 95% CI: 1.90-2.69) and eating disorders (OR: 2.71, 95% CI: 2.35-3.11) (all P < 0.001). Contrastingly, within Wuhan, only the first four factors, namely, parent-child conflict (5.95, 2.82-12.57), sleep problems (4.47, 3.06-6.54), online study time (0.37, 0.22-0.64), and physical activity time (0.42, 0.22-0.80) were identified (all P < 0.01). Accordingly, nomogram models were created with significant attributes and had decent prediction performance with C-indexes over 80%. LIMITATION: A cross-sectional study and self-reported measures. CONCLUSIONS: Besides the four significant risk factors within and outside Wuhan, the three additional factors outside Wuhan deserve special attention. The prediction nomogram models constructed in this study have important clinical and public health implications for psychosocial and behavioural assessment.

Psychosocial and behavioral problems of children and adolescents in the early stage of reopening schools after the COVID-19 pandemic: a national cross-sectional study in China.

This study aims to explore the psychosocial and behavioral problems of children and adolescents in the early stage of reopening schools. In this national cross-sectional study, a total of 11072 students from China were naturally divided into two groups based on their schooling status: reopened schools (RS) and home schooling (HS) group. The psychosocial and behavioral functioning were measured by Achenbach Child Behaviour Checklist (CBCL) and compared in these two groups. Multivariable logistic regression analyses were conducted to explore the independent predictors associated with the psychosocial and behavioral problems. Our results showed that the students in the RS group had more adverse behaviors than that of HS group. The RS group had the higher rates of parent-offspring conflict, prolonged homework time, increased sedentary time and sleep problems (all p < 0.001). When separate analyses were conducted in boys and girls, the RS group had the higher scores for (1) overall behavioral problems (p = 0.02 and p = 0.01), internalizing (p = 0.02 and p = 0.02) and externalizing (p = 0.02 and p = 0.004) behaviors in the 6-11 age group; (2) externalizing (p = 0.049 and p = 0.006) behaviors in the 12-16 age group. Multivariable regression showed parent-offspring conflict and increased sedentary time were the most common risk factors, while physical activity and number of close friends were protective factors for behavior problems in RS students (p < 0.01 or 0.05). The present study revealed that students' psychosocial and behavioral problems increased in the early stage of schools reopened unexpectedly. These findings suggest that close attention must be paid and holistic strategies employed in the school reopening process of post-COVID-19 period.

Analysis of chronic kidney disease among national hospitalization data with 14 million children.

BACKGROUND: The main purpose was to determine basic epidemiological data on CKD among hospitalized pediatric patients in China. METHODS: Data from pediatric inpatients with CKD hospitalized from June 1, 2013 to May 31, 2017 were extracted from the electronic records of HQMS database, which includes over 14 million inpatients. Codes from the 10th revision of the International Classification of Diseases (ICD-10) were used to search the database. RESULTS: A total of 524 primary diseases of CKD were included in this study. In all, there were 278 231 pediatric inpatients with CKD, which accounted for 1.95 % of the 14 250 594 pediatric inpatients registered in the HQMS database. The number of pediatric inpatients with CKD was 67 498 in 2013, 76 810 in 2014, 81 665 in 2015 and 82 649 in 2016, which accounted for 1.93 %, 1.93 %, 1.99 and 2.09 %, respectively, of the total population of pediatric inpatients. The etiology of CKD was secondary nephrosis in 37.95 % of cases, which ranked first and followed by CAKUT with a percentage of 24.61 %. Glomerular diseases and cystic kidney disease accounted for 21.18 and 5.07 %, respectively. Among all 278 231 patients, 6 581 (2.37 %) had a primary discharge diagnosis of CKD. The renal pathology findings of CKD showed that IgA accounted for 51.17 %. CONCLUSIONS: This study provides a descriptive analysis of the hospitalized population of pediatric CKD patients. Our study provides important, fundamental data for policy making and legislation, registry implementation and the diagnosis, treatment and prevention of CKD in China.

[Efficacy and safety of steroid combined with immunosuppressants in the treatment of primary IgA nephropathy in children: a Meta analysis].

OBJECTIVE: To systematically evaluate the efficacy and safety of steroid combined with immunosuppressants in the treatment of primary IgA nephropathy in children. METHODS: English and Chinese electronic databases were searched to include the studies on the efficacy and safety of steroid combined with immunosuppressants versus steroid alone in the treatment of primary IgA nephropathy in children. Outcome measures included proteinuria remission rate, urinary protein quantification, incidence of adverse events, estimated glomerular filtration rate, and incidence of renal dysfunction. Review Manager 5.3 software was used for data analysis. RESULTS: A total of 7 studies with 381 children were included. The children had moderate to severe proteinuria. The Meta analysis showed that compared with the steroid alone group, the steroid combined with immunosuppressants group achieved a significantly higher rate of proteinuria remission (RR=1.36, 95%CI: 1.19-1.55, P<0.001) and significantly lower urinary protein quantification (SMD=-0.82, 95%CI: -1.23 to -0.41, P<0.001). There was no significant difference in the incidence rate of adverse events between the two groups (RR=1.28, 95%CI: 0.92-1.77, P=0.14). CONCLUSIONS: The current evidence shows that for children with primary IgA nephropathy who have moderate to severe proteinuria, steroid combined with immunosuppressants has a better effect than steroid alone and does not increase the incidence rate of adverse events.

Rare diseases in China: analysis of 2014-2015 hospitalization summary reports for 281 rare diseases from 96 tertiary hospitals.

BACKGROUND: There are many public health issues to resolve regarding rare diseases, including a lack of data from large-scale studies. The objective of this study was to explore fundamental data for a list of rare diseases in China, based on a hospitalization summary reports (HSRs) database. The Target Rare Diseases List (TRDL) 2017 was generated using an expert consensus method in which experts listed diseases according to research priorities. Using codes of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) and key search terms of rare diseases in English and Chinese, data were obtained from HSRs of 96 hospitals, covering a population of over 15 million in China from 2014 to 2015. We extracted and analyzed information on demographics, hospitalizations, and readmissions. RESULTS: A total 281 rare diseases were included in the TRDL 2017. Altogether, 106,746 hospitalizations for a rare disease were captured from 1 January 2014 to 31 December 2015, accounting for 0.69% of inpatients during the same period. The top 10 rare diseases with most cases on the TRDL 2017 were thalassemia, idiopathic pulmonary arterial hypertension, pulmonary Langerhans cell histiocytosis, moyamoya disease, motor neuron disease, idiopathic pulmonary fibrosis, systemic sclerosis, hepatolenticular degeneration, coarctation of the aorta, and transposition of the great arteries. Among the 24 cities in the database, the five cities with the most types of the rare disease were Beijing, Changsha, Guangzhou, Shanghai, and Chengdu, with 191, 162, 143, 141, and 133 types, respectively. The five cities with most cases of the 281 rare diseases were Beijing, Guangzhou, Shanghai, Nanning, and Chengdu. The age distribution of rare diseases was 52% for the age group 25-64 years, and 27% of cases in the age group of 0-14 years were among children. The 10 highest readmission rates ranged from 35 to 65%. CONCLUSIONS: This study provided the TRDL 2017 and descriptive analysis of 281 rare diseases in a hospitalized population. Our study reveals important fundamental information that will be useful in national policy making and legislation; registry implementation; and diagnosis, treatment, and prevention of rare diseases in China.

Adjuvant treatment with Yupingfeng formula for primary nephrotic syndrome in children: A PRISMA systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Yupingfeng formula (YPFF) has been prescribed as adjuvant treatment for pediatric patients with primary nephrotic syndrome (PNS) in China for years. However, the efficacy and adverse effects of these formulations are controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to evaluate the benefits and harms of YPFF in treating PNS in children. METHODS: The MEDLINE, EMBASE, Cochrane Library, CNKI, VIP, WanFang, and CBM databases were searched for RCTs comparing therapies with and without YPFF for PNS from inception to May 13, 2017. Relative risk (RR) and 95% confidence intervals (CI) were expressed for dichotomous outcomes, and weighted mean difference (WMD) with 95% CI for continuous outcomes. Cochrane collaboration tool was used to evaluate the risk of bias of methodologies. RESULTS: Eight studies with 538 participants were identified. Treatment with YPFF significantly increased serum levels of IgA (WMD, 0.48, 95% CI, 0.40-0.56, P < .001), IgG (WMD, 3.36, 95% CI, 2.61-4.12, P < .001), CD4 T-lymphocytes (WMD, 3.35, 95% CI, 2.26-4.43, P < .001), but decreased the level of CD8 T-lymphocytes (WMD, -3.38, 95% CI -5.48 to -1.28, P = .002). YPFF also increased the rates of complete remission (RR: 1.35, 95% CI, 1.09-1.67, P = .005), and decreased the rates of relapse (RR: 0.57, 95% CI, 0.45-0.71, P < .001), and infection (RR: 0.72, 95% CI 0.62-0.83, P < .001). There was no significant difference in the level of IgM between the groups (WMD, 0.12, 95% CI -0.11-0.35, P = .322). CONCLUSIONS: YPFF could improve total remission rate and decrease the frequency of relapse and infection rate. The beneficial influence of YPFF may be associated with its immunomodulatory effects. More high-quality studies with larger sample sizes are needed to further identify its efficacy and safety.

What is the impact of human leukocyte antigen mismatching on graft survival and mortality in renal transplantation? A meta-analysis of 23 cohort studies involving 486,608 recipients.

BACKGROUND: The magnitude effects of human leukocyte antigen (HLA) mismatching on post-transplant outcomes of kidney transplantation remain controversial. We aim to quantitatively assess the associations of HLA mismatching with graft survival and mortality in adult kidney transplantation. METHODS: We searched PubMed, EMBASE and the Cochrane Library from their inception to December, 2016. Priori clinical outcomes were overall graft failure, death-censored graft failure and all-cause mortality. RESULTS: A total of 23 cohort studies covering 486,608 recipients were selected. HLA per mismatch was significant associated with increased risks of overall graft failure (hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.05-1.07), death-censored graft failure (HR: 1.09; 95% CI 1.06-1.12) and all-cause mortality (HR: 1.04; 95% CI: 1.02-1.07). Besides, HLA-DR mismatches were significant associated with worse overall graft survival (HR: 1.12, 95% CI: 1.05-1.21). For HLA-A locus, the association was insignificant (HR: 1.06; 95% CI: 0.98-1.14). We observed no significant association between HLA-B locus and overall graft failure (HR: 1.01; 95% CI: 0.90-1.15). In subgroup analyses, we found recipient sample size and ethnicity maybe the potential sources of heterogeneity. CONCLUSIONS: HLA mismatching was still a critical prognostic factor that affects graft and recipient survival. HLA-DR mismatching has a substantial impact on recipient's graft survival. HLA-A mismatching has minor but insignificant impact on graft survival outcomes.

The impact of human leukocyte antigen mismatching on graft survival and mortality in adult renal transplantation: A protocol for a systematic review and meta-analysis.

BACKGROUND: Human leukocyte antigen (HLA) was important biological barrier to a successful transplantation. Quantitative evaluations of the effect of HLA mismatching on heart, liver, umbilical cord blood, and hematopoietic stem cell transplantation, have previously been reported. In new era of immunosuppression, the reported magnitude effect of HLA mismatching on survival outcomes of kidney transplantation was controversial. In addition, the current kidney allocation guideline recommendations in different countries were inconsistent in term of HLA mismatching. We undertake this study to conduct a systematic review and meta-analysis to assess the magnitude effect of HLA mismatching in adult kidney transplantation, with a particular focus on graft survival and mortality. METHODS: The present systematic review and meta-analysis protocol was conducted following the Meta-analysis of Observational Studies in Epidemiology protocol (MOOSE-P) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocol (PRISMA-P). PubMed, EMBASE, Cochrane library Database will be searched without language restriction. Studies fulfill the following criteria will be eligible: included study cohorts comprising adult recipients; reported the association between HLA mismatching (per mismatches or HLA-A, -B, -DR mismatches) and posttransplant survival outcomes; provided effect estimates of hazard ratios (HRs) with 95% confidence interval (CIs). The incidence of measured outcomes was defined according to the European Renal Best Practice Transplantation Guidelines and Kidney Disease: Improving Global Outcomes Guidelines. RESULTS: This study will quantitatively assess the association of HLA per mismatches, DR-antigen mismatches, A-antigen mismatches, and B-antigen mismatches with survival outcomes of overall graft failure, death-censored graft failure, all-cause mortality, and mortality with a functioning graft. CONCLUSION: This study will determine the issues on what extent HLA compatibility influenced recipient and graft survival and which HLA antigen plays a more important role in kidney transplantation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017071894.

Effect of human leukocyte antigen mismatching on the outcomes of pediatric kidney transplantation: a systematic review and meta-analysis.

BACKGROUND: Kidney transplantation is regarded as the optimal treatment for pediatric patients with end-stage renal disease. Here, we address a controversial topic in pediatric kidney transplantation by performing a quantitative evaluation of the effect of human leukocyte antigen (HLA) mismatching on the outcomes of pediatric kidney transplantation. METHODS: We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 31 December 2016 for cohort studies assessing the risk ratio (RR) of HLA mismatching on pediatric kidney transplantation. Outcome measures included graft failure, rejection and all-cause mortality. RRs and 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models. RESULTS: Eighteen studies comprising a total of 26 018 pediatric recipients were included in the evaluation. Compared with 0-1 HLA-DR mismatch, 2 mismatches significantly increased the risk of graft failure at 1 year (RR: 1.41, 95% CI: 1.11-1.80), 3 years (RR: 1.28, 95% CI: 1.08-1.52), 5 years (RR: 1.21, 95% CI: 1.04-1.41) and 10 years (RR: 1.30, 95% CI: 1.02-1.67). For HLA-A + B, the 5-year graft failure risk was higher for 2-4 mismatches compared with 0-1 mismatch (RR: 3.17, 95% CI: 1.20-8.36), but not for 3-4 compared with 0-2 mismatches (RR: 1.49, 95% CI: 0.79-2.80). CONCLUSIONS: Based on pooled analysis, HLA-DR and HLA-A + B are important factors affecting post-transplant outcomes, especially graft failure, in pediatric recipients. Additional randomized controlled trials with higher quality evidence are needed for further investigation.

Clinical and genetic factors associated with warfarin maintenance dose in northern Chinese patients with mechanical heart valve replacement.

The effects of genetic variants on warfarin dosing vary among different ethnic groups, especially in the Chinese population. The objective of this study was to recruit patients through a rigorous experimental design and to perform a comprehensive screen to identify gene polymorphisms that may influence warfarin dosing in northern Han Chinese patients with mechanical heart valve replacement. Consenting patients (n = 183) with a stable warfarin dose were included in this study. Ninety-six single nucleotide polymorphisms (SNPs) in 30 genes involved in warfarin pharmacological pathways were genotyped using the Illumina SNP GoldenGate Assay, and their associations with warfarin dosing were assessed using univariate regression analysis with post hoc comparison using least significant difference analysis. Multiple linear regression was performed by incorporating patients' clinical and genetic data to create a new algorithm for warfarin dosing. From the 96 SNPs analyzed, VKORC1 rs9923231, CYP1A2 rs2069514, CYP3A4 rs28371759, and APOE rs7412 were associated with higher average warfarin maintenance doses, whereas CYP2C9 rs1057910, EPHX1 rs2260863, and CYP4F2 rs2189784 were associated with lower warfarin doses (P < 0.05). Multiple linear regression analysis could estimate 44.4% of warfarin dose variability consisting of, in decreasing order, VKORC1 rs9923231 (14.2%), CYP2C9*3 (9.6%), body surface area (6.7%), CYP1A2 rs2069514 (3.7%), age (2.7%), CYP3A4 rs28371759 (2.5%), CYP4F2 rs2108622 (1.9%), APOE rs7412 (1.7%), and VKORC1 rs2884737 (1.4%). In the dosing algorithm we developed, we confirmed the strongest effects of VKORC1, CYP2C9 on warfarin dosing. In the limited sample set, we also found that novel genetic predictors (CYP1A2, CYP3A4, APOE, EPHX1, CYP4F2, and VKORC1 rs2884737) may be associated with warfarin dosing. Further validation is needed to assess our results in larger independent northern Chinese samples.

Association of apolipoprotein E (APOE) polymorphisms with warfarin maintenance dose in a northern Han Chinese population.

BACKGROUND: Apolipoprotein E (apoE) induces the uptake of vitamin K-rich lipoproteins by the liver, which likely affects inter-individual variation of warfarin dosing requirements. Associations between APOE polymorphisms and warfarin dosing were previously reported inconsistently among different ethnic groups, so the present study investigated this association in northern Han Chinese patients with mechanical heart valve prosthesis. METHODS: A total of 186 patients who underwent mechanical heart valve replacement and attained a stable warfarin dose were included. APOE single nucleotide polymorphisms (SNPs) rs7412 and rs429358 were genotyped using Illumina SNP GoldenGate Assay. Genotyping results were confirmed by direct sequencing. PHASE v2.1 software was used to construct rs7412 and rs429358 haplotypes. The effects of different APOE genotypes on warfarin dose were analyzed statistically. RESULTS: The mean warfarin maintenance dose was 3.10 ± 0.96 mg/day, and the mean international normalized ratio (INR) was 2.09 ± 0.24. APOE E2, E3, and E4 allele frequencies were 11.6 %, 82.5 %, and 5.9 %, respectively. No E2/E2 or E4/E4 genotypes were detected in this population. E2/E3, E3/E3, E2/E4, and E3/E4 genotype frequencies were 21.0 %, 67.2 %, 2.2 %, and 9.7 %, respectively. Significant differences in warfarin dose requirements were observed among patients with E2/E3, E3/E3, and E3/E4 genotypes (p < 0.05). In post hoc comparison, daily warfarin maintenance doses were significantly higher in E2/E3 heterozygotes compared with E3/E3 homozygotes (p < 0.05), but no differences in dose requirements were found between E3/E4 and E3/E3, or E2/E3 and E3/E4 (p > 0.05). Patients were divided into low-intensity anticoagulant treatment group (1.6 ≤ INR <2.0) and relatively high-intensity anticoagulant treatment group (2.0 ≤ INR ≤ 2.5), and significantly higher warfarin dose requirements were observed in E2/E3 heterozygotes compared with E3/E3 homozygotes in both subgroups (p < 0.05). Multivariable analysis adjusting for other confounders showed that E2/E3 genotype was associated with a significantly higher warfarin dose compared with E3/E3 genotype (p < 0.05). CONCLUSIONS: APOE allele and genotype frequencies in the northern Han Chinese population appear to differ from other racial groups or populations living in other regions of China. The APOE E2 variant was associated with a significantly higher warfarin maintenance dose. Thus, APOE polymorphisms could be one of the predictors influencing warfarin doses in this population.