RHC genotyping in Chinese Han population.

BACKGROUND: The Rh blood group system is characterized by its complexity and polymorphism, encompassing 56 different antigens. Accurately predicting the presence of the C antigen using genotyping methods has been challenging. The objective of this study was to evaluate the accuracy of various genotyping methods for predicting the Rh C and to identify a suitable method for the Chinese Han population. METHODS: In total, 317 donors, consisting 223 D+ (including 20 with the Del phenotype) and 94 D- were randomly selected. For RHC genotyping, 48C and 109bp insertion were detected on the Real-time PCR platform and -292 substitution was analyzed via restriction fragment length polymorphism (RFLP). Moreover, the promoter region of the RHCE gene was sequenced to search for other nucleotide substitutions between RHC and RHc. Agreement between prediction methods was evaluated using the Kappa statistic, and comparisons between methods were conducted via the χ2 test. RESULTS: The analysis revealed that the 48C allele, 109bp insertion, a specific pattern observed in RFLP results, and wild-type alleles of seven single nucleotide polymorphisms (SNPs) were in strong agreement with the Rh C, with Kappa coefficients exceeding 0.8. However, there were instances of false positives or false negatives (0.6% false negative rate for 109bp insertion and 5.4-8.2% false positive rates for other methods). The 109bp insertion method exhibited the highest accuracy in predicting the Rh C, at 99.4%, compared to other methods (P values≤0.001). Although no statistical differences were found among other methods for predicting Rh C (P values>0.05), the accuracies in descending order were 48C (94.6%) > rs586178 (92.7%) > rs4649082, rs2375313, rs2281179, rs2072933, rs2072932, and RFLP (92.4%) > rs2072931 (91.8%). CONCLUSIONS: None of the methods examined can independently and accurately predict the Rh C. However, the 109bp insertion test demonstrated the highest accuracy for predicting the Rh C in the Chinese Han population. Utilizing the 109bp insertion test in combination with other methods may enhance the accuracy of Rh C prediction.

Novel missense mutation c.797T>C (p.Met266Thr) gives rise to the rare B(A) phenotype in a Chinese family.

BACKGROUND AND OBJECTIVES: B(A) phenotype is usually formed by nucleotide mutations in the ABO*B.01 allele, with their products exhibiting glycosyltransferases (GTs) A and B overlapping functionality. We herein report a B(A) allele found in a Chinese family. MATERIALS AND METHODS: The entire ABO genes of the probands, including flanking regulatory regions, were sequenced through PacBio third-generation long-read single-molecule real-time sequencing. 3D molecular models of the wild-type and mutant GTB were generated using the DynaMut web server. The effect of the mutation on the enzyme function was predicted by PROVEAN and PolyPhen2. The predictions of stability changes were performed using DynaMut and SNPeffect. RESULTS: Based on serological and sequencing features, we concluded the two probands as possible cases of the B(A) phenotype. Crystallization analysis showed that Thr266 substitution does not disrupt the hydrogen bonds. However, some changes in interatomic contacts, such as loss of ionic interactions and hydrophobic contacts, and addition of weak hydrogen bonds, may have affected protein stability to some extent. This mutation was predicted to have a benign effect on enzyme function and slightly reduce protein stability. CONCLUSION: The probands had the same novel B(A) allele with a c.797T>C (p.Met266Thr) mutation on the ABO*B.01 backbone.

Polymorphisms in the promoter regions of RHD and RHCE genes in the Chinese Han population.

BACKGROUND AND OBJECTIVES: The Rh blood group system is the most polymorphic human blood group system. Previous studies have investigated variants in the RHD and RHCE promoter. The relevance of these variants to the Chinese Han population is further clarified in this study. MATERIALS AND METHODS: In total, 317 donors (223 Rh D-positive [D+], including 20 Del and 94 Rh D-negative [D-]) were randomly selected. The promoter regions and exon 1 of RHD and RHCE were amplified through polymerase chain reaction (PCR) whose products were directly sequenced using forward and reverse primers. RESULTS: Expected PCR products of the RHD promoter and exon 1 were amplified in 223 D+ individuals, including 20 Del individuals, and were absent in 81 of 94 D- individuals. Expected PCR products of RHCE were observed in all donors. Two single nucleotide variants (SNVs) were observed in the RHD promoter region. Moreover, 11 SNVs were observed in the promoter and exon 1 of RHCE. rs4649082, rs2375313, rs2281179, rs2072933, rs2072932, rs2072931 and rs586178 with strong linkage disequilibria were significantly different between the D+ and D- groups. [A;C] was the most common haplotype in the RHD promoter (NC_000001.11:g.[-1033A>G;-831C>T]). [G;T;T;A;T;A;C;G;A;C;G] was the most predominant haplotype in both total and D- groups. In D+ individuals, [A;C;T;G;C;G;C;G;C;C;C] was the most frequent haplotype in the RHCE promoter (NC_000001.11:g.[-1080A>G;-958C>T;-390T>C;-378G>A;-369C>T;-296G>A;-144C>G;-132G>A;-122C>A;28C>T;48C>G]). CONCLUSION: We speculate that the SNVs/haplotypes found in this article cannot significantly affect gene expression. The present study findings should help elucidate the molecular basis of the polymorphic expression of RHD and RHCE promoter regions.

Economic burden of public health care and hospitalisation associated with COVID-19 in China.

OBJECTIVES: This study aimed to evaluate the socio-economic burden imposed on the Chinese healthcare system during the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: A cross-sectional study was used to investigate how COVID-19 impacted health and medical costs in China. Data were derived from a subdivision of the Centers for Disease control and Prevention of China. METHODS: We prospectively collected information from the Centers for Disease Control and Prevention and the designated hospitals to determine the cost of public health care and hospitalisation due to COVID-19. We estimated the resource use and direct medical costs associated with public health. RESULTS: The average costs, per case, for specimen collection and nucleic acid testing (NAT [specifically, polymerase chain reaction {PCR}]) in low-risk populations were $29.49 and $53.44, respectively; however, the average cost of NAT in high-risk populations was $297.94 per capita. The average costs per 1000 population for epidemiological surveys, disinfectant, health education and centralised isolation were $49.54, $247.01, $90.22 and $543.72, respectively. A single hospitalisation for COVID-19 in China cost a median of $2158.06 ($1961.13-$2325.65) in direct medical costs incurred only during hospitalisation, whereas the total costs associated with hospitalisation of patients with COVID-19 were estimated to have reached nearly $373.20 million in China as of 20, May, 2020. The cost of public health care associated with COVID-19 as of 20, May, 2020 ($6.83 billion) was 18.31 times that of hospitalisation. CONCLUSIONS: This study highlights the magnitude of resources needed to treat patients with COVID-19 and control the COVID-19 pandemic. Public health measures implemented by the Chinese government have been valuable in reducing the infection rate and may be cost-effective ways to control emerging infectious diseases.

Is there a link between inorganic polyphosphate (polyP), mitochondria, and neurodegeneration?

Mitochondrial dysfunction - including increased apoptosis, calcium and protein dyshomeostasis within the organelle, and dysfunctional bioenergetics and oxidative status - is a common, early feature in all the major neurodegenerative diseases, including Alzheimer's Disease (AD) and Parkinson's Disease (PD). However, the exact molecular mechanisms that drive the organelle to dysfunction and ultimately to failure in these conditions are still not well described. Different authors have shown that inorganic polyphosphate (polyP), an ancient and well-conserved molecule, plays a key role in the regulation of mitochondrial physiology under basal conditions. PolyP, which is present in all studied organisms, is composed of chains of orthophosphates linked together by highly energetic phosphoanhydride bonds, similar to those found in ATP. This polymer shows a ubiquitous distribution, even if a high co-localization with mitochondria has been reported. It has been proposed that polyP might be an alternative to ATP for cellular energy storage in different organisms, as well as the implication of polyP in the regulation of many of the mitochondrial processes affected in AD and PD, including protein and calcium homeostasis. Here, we conduct a comprehensive review and discussion of the bibliography available regarding the role of polyP in the mitochondrial dysfunction present in AD and PD. Taking into account the data presented in this review, we postulate that polyP could be a valid, innovative and, plausible pharmacological target against mitochondrial dysfunction in AD and PD. However, further research should be conducted to better understand the exact role of polyP in neurodegeneration, as well as the metabolism of the polymer, and the effect of different lengths of polyP on cellular and mitochondrial physiology.

Defining the regulatory role of programmed cell death 4 in laryngeal squamous cell carcinoma.

Programmed cell death 4 (PDCD4) is decreased in many different kinds of malignant tumors. EMT endows tumor cells invasive and metastatic properties. However, few studies have determined the role of PDCD4 in the regulation of EMT in the context of laryngeal carcinoma. We examined the relationship between PDCD4 and EMT-associated proteins E-cadherin and N-cadherin using laryngeal carcinoma tissues. Gene manipulation was used to define the regulatory capacity of PDCD4. We report that PDCD4 and E-cadherin/N-cadherin expression were significantly changed in the carcinoma tissues, and their expression was associated with pathological grade, metastatic state, and clinical stage. The suppression of PDCD4 (and consequently, E-cadherin) was concomitant with increased proliferation and G2-phase arrest, decreased apoptosis, and increased cell invasion. PDCD4 upregulation reversed the above-mentioned results. In nude mice, PDCD4 knockdown increased tumor growth and pathological features, confirming the tumorigenic role of PDCD4. Finally, PDCD4 silencing was associated with dysregulation of the carcinogenic Wnt-ß-catenin and the STAT3-miR-21 signaling pathways. This study revealed a dynamic regulatory relationship between PDCD4 and critical factors for EMT, establishing a broad, functional role for PDCD4 in laryngeal carcinoma, which may be propagated by the STAT3-miR-21 pathway. These findings provide new information on an EMT-associated target that may lead to a novel therapy.

Association between the polymorphism of HLA and ESRD in Dalian Han population located in north of China.

BACKGROUND: End-stage renal disease (ESRD), the last stage of chronic renal failure, is a global health problem. The number of ESRD patients worldwide is increasing faster than the number of kidneys available per year for renal transplantation. Most of the ESRD patients are awaiting renal transplantation. The immune response to the transplanted kidney is directed mainly against mismatched human leukocyte antigen (HLA) glycoproteins expressed on donor tissues. Thus, the analysis of HLA allele and haplotype polymorphisms is valuable not only for identifying ESRD susceptibility factors but also to improve graft survival. METHODS: In this study, 163 Han ESRD patients were recruited to participate. The blood samples were genotyped by sequence-specific oligonucleotide method. A group of 14,529 healthy Chinese Han individuals registered at the Dalian Blood Center as bone marrow donors, living in the same region and of the same ethnicity, were used as controls. RESULTS: We found that only one allele, HLA-DRB1*12, showed a positive association with ESRD (p = 0.004, pc = 0.028, odds ratio = 1.530, 95% confidence interval = 1.147-2.041); A*02-B*40-DRB1*09, A*02-B*40-DRB1*12, A*24-B*15-DRB1*12, and B*40-DRB1*12 were significantly more frequent in ESRD patients after Bonferroni correction (pc < 0.05). CONCLUSION: They were potentially valuable predictors for evaluating the risk of ESRD in the Dalian Han population.

Effect of vitamin A supplementation on gut microbiota in children with autism spectrum disorders - a pilot study.

BACKGROUND: Dysbiosis of gut microbiota are commonly reported in autism spectrum disorder (ASD) and may contribute to behavioral impairment. Vitamin A (VA) plays a role in regulation of gut microbiota. This study was performed to investigate the role of VA in the changes of gut microbiota and changes of autism functions in children with ASD. RESULTS: Sixty four, aged 1 to 8 years old children with ASD completed a 6-month follow-up study with VA intervention. High-performance liquid chromatography was used to assess plasma retinol levels. The Autism Behaviour Checklist (ABC), Childhood Autism Rating Scale (CARS) and Social Responsiveness Scale (SRS) were used to assess autism symptoms. CD38 and acid-related orphan receptor alpha (RORA) mRNA levels were used to assess autism-related biochemical indicators' changes. Evaluations of plasma retinol, ABC, CARS, SRS, CD38 and RORA mRNA levels were performed before and after 6 months of intervention in the 64 children. Illumina MiSeq for 16S rRNA genes was used to compare the differences in gut microbiota before and after 6 months of treatment in the subset 20 of the 64 children. After 6 months of intervention, plasma retinol, CD38 and RORA mRNA levels significantly increased (all P < 0.05); the scores of ABC, CARS and SRS scales showed no significant differences (all P > 0.05) in the 64 children. Meanwhile, the proportion of Bacteroidetes/Bacteroidales significantly increased and the proportion of Bifidobacterium significantly decreased in the subgroup of 20 (all false discovery rate (FDR) q < 0.05). CONCLUSIONS: Bacteroidetes/Bacteroidales were the key taxa related to VA. Moreover, VA played a role in the changes in autism biomarkers. It remains unclear whether the VA concentration is associated with autism symptoms. TRIAL REGISTRATION: The study protocol was peer reviewed and approved by the institutional review board of Children's Hospital, Chongqing Medical University in 2013 and retrospectively registered in Chinese Clinical Trial Registry (ChiCTR) on November 6, 2014 (TRN: ChiCTR-ROC-14005442 ).

[Association between development of hypertension and nutrition in school-age children in Fengdu County of Chongqing, China].

OBJECTIVE: To investigate the association between the development of hypertension and nutrition in school-age children in Fengdu County of Chongqing, China. METHODS: A total of 8 033 children from 2 public primary schools in Fengdu County of Chongqing, whose registered residence was in the subdistricts where the two schools were located, were selected as study subjects using cluster random sampling. Body height, body weight, and blood pressure were measured, and the semi-quantitative food frequency questionnaire was used for dietary survey. The association between body mass index (BMI), dietary nutrients, and the development of hypertension in children was analyzed. RESULTS: A total of 7 538 children were enrolled for analysis. The detection rates of obesity, overweight, and hypertension were 9.11%, 12.27%, and 11.83% respectively. In children with obesity and overweight, the detection rate of hypertension was 33.62% and 17.84% respectively, 4.02 and 2.13 times that in normal children. The multivariate logistic stepwise regression analysis revealed that increased intake of calcium and sodium increased the risk of hypertension (OR=1.003 and 1.002 respectively), while the increased iron intake and calcium intake per unit body weight reduced the risk of hypertension (OR=0.979 and 0.926 respectively). CONCLUSIONS: The prevalence of hypertension and obesity in school-age children in Fengdu County of Chongqing is high. BMI and dietary nutrients are closely associated with the development of hypertension in children. Active control of body weight, adjustment of dietary structure, and limitation of sodium intake should be adopted to reduce the development of hypertension in school-age children.

[Effect of dietary vitamin A intake on plasma vitamin A concentration in preschool children of Banan district, Chongqing, China].

OBJECTIVE: To study the relationship between dietary vitamin A intake and plasma vitamin A concentration, and establish the theoretical basis for dietary intake predicting vitamin A nutritional status. METHODS: By using cluster sampling, 492 children aged 2-7 years in kindergartens in Banan district of Chongqing were selected. A cross-sectional nutrition and health survey was conducted, including the clinical examination, anthropometry, laboratory test and dietary survey. RESULTS: Among the children surveyed, 229 were boys, and 263 girls, the mean age was (4.54 ± 0.87) years, height (107.50 ± 7.20) cm, and weight (18.42 ± 3.41) kg, the mean value of plasma vitamin A was (1.04 ± 0.30) µmol/L. The prevalence of marginal vitamin A deficiency (MVAD) was 43.5%. No cases of severe clinical vitamin A deficiency were found (plasma vitamin A ≤ 0.35 µmol/L). Clinical examination found no conjunctiva, corneaor skin abnormalities, and no Bitot's spots. Prevalence of the last two weeks colds were 27.4% (135/492), no diarrhea and other gastrointestinal or digestive diseases were found. The proportion of insufficient dietary vitamin A intake (<600 µg RE/d) was as high as 50.0%. By using correlation analysis, plasma retinol concentrations were related to dietary vitamin A intake (r=0.162, P<0.001), and to dietary energy intake (r=0.107, P=0.017). After adjustment for the effects of other non-dietary factors on vitamin A deficiency, the multivariate logistic regression showed that vitamin A-rich foods of liver intake=0 g/d (OR=1.95, 95% CI: 1.05-3.61, P=0.034), vitamin A-rich fruits intake=0 g/d (OR=1.55, 95% CI: 1.03-2.33, P=0.034), vitamin A-rich vegetables intake<200 g/d (OR=3.47, 95% CI: 1.37-8.75, P=0.009) were important risk factors of vitamin A deficiency. But we had not found the correlation between the intake of meat, eggs and milk and vitamin A deficiency. CONCLUSION: Dietary factors may be the major risk factor of vitamin A deficiency in the three kindergartens. The dietary vitamin A intakes are significantly related to plasma retinol concentrations, and the vitamin A-rich foods intakes can predict the body's vitamin A nutritional status.

[Current status and urban-rural comparison of clinical agency of detection, management, and health insurance for hypertensive patients in communities of five provinces in China in 2010].

OBJECTIVE: To investigate the status of the clinical agency of detection, management, and health insurance for hypertensive patients in urban and rural communities of five provinces in China in 2010, in order to provide fundamental data for implementation and evaluation of community health management of hypertensive patients in basic public health service. METHODS: From Jiangsu, Shandong, Hebei, Sichuan and Gansu provinces, cities and districts (counties) were selected according to economic development level and 10 survey sites were finally determined. In each survey site, 3-4 communities or townships were selected by cluster sampling methods in 2010. A total of 8326 eligible hypertensive patients (4363 in urban and 3963 in rural) were included. The urban-rural difference of clinical agency and health insurance was compared for hypertensive patients. RESULTS: In urban areas, 43.74% (1867/4268) hypertensive patients were first diagnosed at hospitals of district level or above, 25.07% (1070/4268) at community health service centers (CHSC), and 20.20% (862/4268) at community health service stations (CHSS), respectively; 30.72% (1274/4147) and 31.11% (1290/4147) patients chose CHSC and CHSS for their follow-up visiting, respectively; 60.23% (3073/5102) antihypertensive medication was obtained from pharmacies. In rural areas, 54.58% (2133/3908) hypertensive patients were first diagnosed at village clinics, 22.36% (874/3908) at township hospitals, and 18.86% (737/3908) at hospitals of county level or above; 70.49% (2695/3823) patients chose village clinics for their follow-up visiting; 46.23% (2116/4577) antihypertensive medication was obtained from village clinics, and 36.29% (1661/4577) from pharmacies. The main reasons for choosing clinical agency for both urban and rural patients were convenience (45.79%, 6276/13 706) and low cost (11.78%, 1614/13 706). The proportions of reimbursements for hospitalization expenses and total medical expenses for hypertensive patients in urban in the past year were 66.67% and 34.78%, respectively, which were much higher than those in rural (35.71% and 9.50%) (Z value was -12.13 and -17.56, P < 0.01). CONCLUSION: Community-based hypertension detection and routine blood pressure measurement during clinical visiting should be further strengthened to improve early diagnosis of hypertension. The development of community-based clinical agency should be able to provide convenient and low cost health service for hypertensive patients to improve treatment, follow-up and control of hypertension.

[Near infrared distance sensing method for Chang'e-3 alpha particle X-ray spectrometer].

Alpha particle X-ray spectrometer (APXS) is one of the payloads of Chang'E-3 lunar rover, the scientific objective of which is in-situ observation and off-line analysis of lunar regolith and rock. Distance measurement is one of the important functions for APXS to perform effective detection on the moon. The present paper will first give a brief introduction to APXS, and then analyze the specific requirements and constraints to realize distance measurement, at last present a new near infrared distance sensing algorithm by using the inflection point of response curve. The theoretical analysis and the experiment results verify the feasibility of this algorithm. Although the theoretical analysis shows that this method is not sensitive to the operating temperature and reflectance of the lunar surface, the solar infrared radiant intensity may make photosensor saturation. The solutions are reducing the gain of device and avoiding direct exposure to sun light.

[Temperature effect correction for Chang'E-3 alpha particle X-ray spectrometer].

Alpha particle X-ray spectrometer (APXS) is one of the payloads of Chang'E-3 lunar rover of China's Lunar Exploration Project. The present paper introduces briefly the components of APXS, how it works and its working environment on the lunar surface. The environmental temperature effect has been studied with simulations and experiments, and the results show that the temperature of the APXS sensor will be varying during the measuring on the lunar surface. And another experiment reveals that the energy resolution becomes worse if the sensor's temperature is varying. In this paper, a correction method based on Pearson's chi-squared test is presented. The method can improve the energy resolution when the sensor's temperature is varying. We have tested the method with the spectra acquired by APXS in the temperature varying period of Temperature Cycling Test, and the results show that the method is efficient and reliable.

Amino Acid-Based Formula vs. Extensively Hydrolyzed Formula in the Treatment of Feeding Intolerance in Preterm Infants: Study Protocol for a Randomized Controlled Trial.

Background: Feeding intolerance is a common problem in preterm infants, which is associated with an increased risk of infections, prolonged hospitalization, and increased economic costs. When human milk is not available, formula feeding is required. Amino acid-based formula and extensively hydrolyzed formula could be considered for use for severe feeding intolerance. A recent Cochrane meta-analysis found that preterm infants fed extensively hydrolyzed formula compared with standard formula could not reduce the risk of feeding intolerance and necrotizing enterocolitis, and weight gain was slower. Some studies reported that preterm infants fed amino acid-based formula could reduce the gastric residual volume. We hypothesize that amino acid-based formula can improve feeding intolerance and establish full enteral feeding more rapidly in preterm infants compared with extensively hydrolyzed formula. Method: The randomized, prospective, controlled trial was conducted at the Children's Hospital of Chongqing Medical University (Chongqing, China). A total of 190 preterm infants with gestational age <32 weeks or birth weight <1,500 g and with a diagnosis of feeding intolerance were included. Patients were randomized to an amino acid-based formula-fed group and an extensively hydrolyzed formula-fed group. The primary outcome is the time (days) to reach full enteral feedings. Secondary outcomes include duration of vomiting and abdominal distension, gastric residual volume, body weight, length and head circumference during hospitalization, length of hospital stay (days), cost of hospitalization, time (days) of parenteral nutrition, change of abdomen circumference, main serum parameters, and incidence of adverse events. Discussion: The successful implementation of our study will provide robust evidence for formula alternatives in preterm infants with feeding intolerance. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT05347706.

The Determinants of Adolescent Glycolipid Metabolism Disorder: A Cohort Study.

Background: The increased prevalence of glycolipid metabolism disorders (GLMD) in childhood and adolescents has a well-established association with adult type 2 diabetes and cardiovascular diseases; therefore, determinants of GLMD need to be evaluated during this period. Objectives: To explore the prevalence of and risk factors for GLMD from the prenatal period through childhood and adolescence. Methods: A bidirectional cohort study which was established in 2014 and followed between March 1 and July 20, 2019, was used to illustrate the impact factors for GLMD. Stratified cluster sampling in urban-rural areas was used to include subjects from four communities in Chongqing. 2808 healthy children aged between 6 and 9 years in 2014 entered the cohort in 2014 and followed in 2019 with a follow-up rate of 70%. 2,136 samples (aged 11.68 ± 0.60 years) were included. Results: The prevalence rates of insulin resistance (IR), prediabetes/diabetes, and dyslipidemia were 21.02%, 7.19%, and 21.61%, respectively. Subjects with an urban residence, no pubertal development, dyslipidemia in 2014, higher family income, and higher parental education had significantly elevated fasting insulin (FI) or homeostasis model assessment of insulin resistance (HOMA-IR) levels; subjects with female sex, no pubertal development, dyslipidemia in 2014, obesity, gestational hypertension, maternal weight gain above Institute of Medicine guidelines, and single parents had increased triglyceride or triglyceride/high-density lipoprotein (HDL). Adolescents with rural residence had higher HbA1c level. Conclusion: We observed that the prevalence of GLMD was high in childhood and adolescents, and rural-urban areas, sex, pubertal development, dyslipidemia in a younger age, maternal obesity, and hypertension were associated with increased GLMD risk, suggesting that implementing the community-family intervention to improve the GLMD of children is essential.

Relationship between quality of life and adolescent glycolipid metabolism disorder: A cohort study.

BACKGROUND: The prevalence of glucolipid metabolic disorders (GLMDs) in children and adolescents has a recognized association with cardiovascular diseases and type 2 diabetes mellitus in adulthood. Therefore, it is important to enhance our under-standing of the risk factors for GLMD in childhood and adolescence. AIM: To explore the relationship between quality of life (QoL) and adolescent GLMD. METHODS: This study included 1956 samples in 2019 from a cohort study established in 2014. The QoL scale and glycolipid indexes were collected during follow-up; other covariates of perinatal factors, physical measures, and socioeconomic indicators were collected and adjusted. A generalized linear regression model and logistic regression model were used to analyse the correlation between QoL and GLMD. RESULTS: Higher scores of QoL activity opportunity, learning ability and attitude, attitude towards doing homework, and living convenience domains correlated negatively with insulin and homeostasis model assessment insulin resistance (IR) levels. Psychosocial factors, QoL satisfaction factors, and total QoL scores had significant protective effects on insulin and IR levels. Activity opportunity, learning ability and attitude, attitude towards doing homework domains of QoL, psychosocial factor, and total score of QoL correlated positively with high density lipoprotein. In addition, the attitude towards doing homework domain was a protective factor for dyslipidaemia, IR > 3, and increased fasting blood glucose; four factors, QoL and total QoL score correlated significantly negatively with IR > 3. In subgroup analyses of sex, more domains of QoL correlated with insulin and triglyceride levels, dyslipidaemia, and IR > 3 in females. Poor QoL was associated with an increased prevalence of GLMD, and the effect was more pronounced in males than in females. Measures to improve the QoL of adolescents are essential to reduce rates of GLMD. CONCLUSION: Our study revealed that QoL scores mainly correlate negatively with the prevalence of GLMD in adolescents of the healthy population. The independent relationship between QoL and GLMD can be illustrated by adjusting for multiple covariates that may be associated with glycaemic index. In addition, among females, more QoL domains are associated with glycaemic index.

The impact of obesity epidemic on type 2 diabetes in children and adolescents: A systematic review and meta-analysis.

AIM: To assess the impact of the obesity epidemic on type 2 diabetes (T2D), prediabetes and glycometabolic indices in children and adolescents. METHODS: We searched four electronic databases (PubMed, Embase, Cochrane and Web of Science). Cross-sectional or cohort studies that reported on obesity and the prevalence of T2D or prediabetes in children and adolescents were reviewed. The study design, sample size and clinical outcomes were extracted from each study. The prevalence of T2D and prediabetes from the studies were pooled using meta-analysis methods. RESULTS: Meta-analysis of 228184 participants showed that the prevalence of T2D was 1.3% (95% confidence interval (CI), 0.6-2.1%) in obese subjects, which was 13 times that in normal weight subjects (0.1%, 95% CI, 0.01-0.2%). The prevalence of prediabetes in obese subjects was 3 times that in normal subjects at 17.0% (13.0-22.0%) vs. 6.0% (0.01-11.0%). Moreover, BMI was positively correlated with the prevalence of T2D, prediabetes and glycometabolic indices in obese children and adolescents. CONCLUSION: The pooled results confirm that obesity in children and adolescents leads to statistically significant increases in the prevalence of T2D and prediabetes and in glycometabolic indicator levels.

Active demethylation upregulates CD147 expression promoting non-small cell lung cancer invasion and metastasis.

Non-small cell lung cancer (NSCLC) is a fatal disease, and its metastatic process is poorly understood. Although aberrant methylation is involved in tumor progression, the mechanisms underlying dynamic DNA methylation remain to be elucidated. It is significant to study the molecular mechanism of NSCLC metastasis and identify new biomarkers for NSCLC early diagnosis. Here, we performed MeDIP-seq and hMeDIP-seq analyses to detect the genes regulated by dynamic DNA methylation. Comparison of the 5mC and 5hmC sites revealed that the CD147 gene underwent active demethylation in NSCLC tissues compared with normal tissues, and this demethylation upregulated CD147 expression. Significantly high levels of CD147 expression and low levels of promoter methylation were observed in NSCLC tissues. Then, we identified the CD147 promoter as a target of KLF6, MeCP2, and DNMT3A. Treatment of cells with TGF-ß triggered active demethylation involving loss of KLF6/MeCP2/DNMT3A and recruitment of Sp1, Tet1, TDG, and SMAD2/3 transcription complexes. A dCas9-SunTag-DNMAT3A-sgCD147-targeted methylation system was constructed to reverse CD147 expression. The targeted methylation system downregulated CD147 expression and inhibited NSCLC proliferation and metastasis in vitro and in vivo. Accordingly, we used cfDNA to detect the levels of CD147 methylation in NSCLC tissues and found that the CD147 methylation levels exhibited an inverse relationship with tumor size, lymphatic metastasis, and TNM stage. In conclusion, this study clarified the mechanism of active demethylation of CD147 and suggested that the targeted methylation of CD147 could inhibit NSCLC invasion and metastasis, providing a highly promising therapeutic target for NSCLC.

[The analysis of drug cost and direct medical expense in community health management of hypertensive patients].

OBJECTIVE: To investigate the current situation of drug cost, hospitalization cost and direct medical expense in community health management of hypertensive patients, in order to lay foundation for evaluating whether the community health management in basic public health service has cost-effect in Health Economics. METHODS: A total of 8326 hypertensive patients from 10 survey pilots in 5 provinces were selected by cluster sampling methods, including 3967 patients who took part in community health management for over 1 year as management group and 4359 cases who have never taken part in community health management as control group. The essential information of research objects were collected by questionnaire; and the medical cost information in the last year (from November 2009 to November 2010) were collected retrospectively. The different annual medical treatment cost, hospitalization cost and direct medical expense in the two groups were compared and analyzed. RESULTS: The average annual drug cost in hypertension was (621.50 ± 1337.78) yuan per patient; while the cost was (616.13 ± 1248.40) yuan in management group and (626.44 ± 1414.30) yuan in control group respectively. The average annual drug cost of hypertensive patients who took medicine therapy was (702.05 ± 1401.79) yuan per person, while the cost in the management group ((688.50 ± 1300.70) yuan) was much lower than it in control group ((714.64 ± 1489.60) yuan). The annual average drug cost in urban was (731.88 ± 1403.31) yuan per person, which was higher than it in rural as (407.44 ± 1171.44) yuan per person. The average hospitalized rate was 12.2% (1014/8326), and the average annual cost among the hospitalized patients was (9264.47 ± 18 088.49) yuan per person; while the cost was (7583.70 ± 13 267.00) yuan in management group, which was lower than it in control group as (11 028.00 ± 21 919.00) yuan. The average annual hospitalized cost in hypertension was (1064.87 ± 6804.83) yuan per person; while the cost was (936.73 ± 5284.90) yuan in management group, which was lower than it in control group as (1181.50 ± 7937.90) yuan. The average annual direct medical expense in hypertension was (2275.08 ± 8225.66) yuan per person; while the expense was (2165.10 ± 6564.60) yuan in management group and (2375.20 ± 9487.60) yuan in control group. The average annual direct medical expense in urban ((2801.06 ± 9428.54) yuan per person) was higher than it in rural ((1254.70 ± 4990.27) yuan per person). CONCLUSION: The community health or standardized management of hypertensive patients can reduce the average annual drug cost and hospitalization cost (around 26 yuan and 245 yuan separately); and thereby save the annual direct medical expense per capita in hypertension (around 210 yuan). In the reform and development of national medical health system, we should enhance and promote the standardized community health management of hypertensive patients.

[Effects of deguelin on proliferation and apoptosis of MCF-7 breast cancer cells by phosphatidylinositol 3-kinase/Akt signaling pathway].

OBJECTIVE: To study the effects of deguelin on proliferation and apoptosis of human breast cancer cell line MCF-7 and on phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. METHODS: After treatment with 0, 1, 5, 10, 15 and 20 µmol/L of deguelin for 6, 24, 48 and 72 hours, the proliferation inhibition rate of MCF-7 cells was measured by cell counting kit-8 assay. Apoptosis rate of MCF-7 cells was detected with Annexin V-fluorescein isothiocyanate/propidium iodide double staining by flow cytometry and the apoptotic morphology was observed under a transmission electron microscope. After treatment with 0, 1 and 5 µmol/L of deguelin for 6 hours, 5 proteins involved in the PI3K/Akt signaling pathway were examined by Western blot analysis. RESULTS: Deguelin at doses of 5, 10, 15 and 20 µmol/L inhibited the proliferation of MCF-7 cells at 6, 24, 48 and 72 hours. There was a significant difference in each group compared with the control group (P<0.01). The inhibitory effect was more marked with increasing concentration and duration of treatment. There were statistical differences (P<0.05) among 5, 10, 15 and 20 µmol/L groups. However, 1 µmol/L of deguelin had no obvious effects on the proliferation of MCF-7 cells at 6, 24, 48 and 72 hours, showing no significant difference compared with control group (P>0.05). Deguelin at doses of 5, 10, 15 and 20 µmol/L induced apoptosis of MCF-7 cells at 6 hours. There were significant differences (P<0.01) in the early and late apoptosis rate between the treated groups and the control group. The typical apoptotic MCF-7 cells were observed under the transmission electron microscopy. However, 1 µmol/L of deguelin had no apparent effect in inducing apoptosis of MCF-7 cells at 6 hours. After treatment with 5 µmol/L of deguelin for 6 hours the expression of phosphorylated phosphatase and tensin homologue deleted on chromosome 10 (PTEN) (Ser380), phosphorylated 3-phosphoinositide-dependent protein kinase 1 (PDK1) (Ser241), phosphorylated Akt (Thr308) and phosphorylated glycogen synthase kinase-3ß (GSK-3ß) (Ser9) proteins were significantly reduced in MCF-7 cells, while there was no significant change in the expression of total Akt protein. However, after treatment with 1 µmol/L of deguelin for 6 hours, there was no apparent change in the expression of these 5 proteins. CONCLUSION: Deguelin can inhibit the phosphorylation of GSK-3ß (Ser9) via inhibition of the phosphorylation of PTEN (Ser380) and PDK1 (Ser241) pathway, thus inducing apoptosis and inhibiting proliferation of MCF-7 cells.