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.

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.

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 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.

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.

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.

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.

Effects of policies and containment measures on control of COVID-19 epidemic in Chongqing.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging, rapidly evolving disease that spreads through the respiratory system and is highly contagious. In March 2020, the World Health Organization declared the COVID-19 outbreak a pandemic. In China, the pandemic was controlled after 2 mo through effective policies and containment measures. Describing the detailed policies and containment measures used to control the epidemic in Chongqing will provide a reference for the prevention and control of COVID-19 in other areas of the world. AIM: To explore the effects of different policies and containment measures on the control of the COVID-19 epidemic in Chongqing. METHODS: Epidemiological data on COVID-19 in Chongqing were prospectively collected from January 21 to March 15, 2020. The policies and prevention measures implemented by the government during the epidemic period were also collected. Trend analysis was performed to explore the impact of the main policy measures on the effectiveness of the control of COVID-19 in Chongqing. RESULTS: As of March 15, the cumulative incidence of COVID-19 in Chongqing was 1.84/100000 (576 cases) and the infection fatality rate was 1.04% (6/576). The spread of COVID-19 was controlled by effective policies that involved establishing a group for directing the COVID-19 epidemic control effort; strengthening guidance and supervision; ensuring the supply of daily necessities and medical supplies and equipment to residents; setting up designated hospitals; implementing legal measures; and enhancing health education. Medical techniques were implemented to improve the recovery rate and control the epidemic. Policies such as "the lockdown of Wuhan", "initiating a first-level response to major public health emergencies", and "implementing the closed management of residential communities" significantly curbed the spread of COVID-19. Optimizing the diagnosis process, shortening the diagnosis time, and constructing teams of clinical experts facilitated the provision of "one team of medical experts for each patient" treatment for severe patients, which significantly improved the recovery rate and reduced the infection fatality rate. CONCLUSION: The prevention policies and containment measures implemented by the government and medical institutions are highly effective in controlling the spread of the epidemic and increasing the recovery rate of COVID-19 patients.

DNA-Scaffolded Proximity Assembly and Confinement of Multienzyme Reactions.

Cellular functions rely on a series of organized and regulated multienzyme cascade reactions. The catalytic efficiencies of these cascades depend on the precise spatial organization of the constituent enzymes, which is optimized to facilitate substrate transport and regulate activities. Mimicry of this organization in a non-living, artificial system would be very useful in a broad range of applications-with impacts on both the scientific community and society at large. Self-assembled DNA nanostructures are promising applications to organize biomolecular components into prescribed, multidimensional patterns. In this review, we focus on recent progress in the field of DNA-scaffolded assembly and confinement of multienzyme reactions. DNA self-assembly is exploited to build spatially organized multienzyme cascades with control over their relative distance, substrate diffusion paths, compartmentalization and activity actuation. The combination of addressable DNA assembly and multienzyme cascades can deliver breakthroughs toward the engineering of novel synthetic and biomimetic reactors.

Colorimetric determination of xanthine in urine based on peroxidase-like activity of WO3 nanosheets.

Two-dimensional WO3 nanosheets were prepared by ultrasonic exfoliation of bulk WO3·2H2O in water and characterized by transmission electron microscopy, atomic force microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, Raman, dynamic light scattering. The nanosheets were discovered to possess the peroxidase-like catalytic activity, which can catalyze the oxidation of 3, 3', 5, 5'-tetramethylbenzidine by H2O2. The catalytic mechanism was also investigated by the scavenger experiments. Taking advantage of the peroxidase-like activity of WO3 nanosheets, a facile colorimetric method for xanthine was developed by combining the oxidation reaction of xanthine catalyzed by xanthine oxidase. The linear range for xanthine was ranged from 25 to 200 µmol L-1. The limit of detection for xanthine was 1.24 µmol L-1. The colorimetric method was applied to determine xanthine in urine samples.

ING5 inhibits lung cancer invasion and epithelial-mesenchymal transition by inhibiting the WNT/ß-catenin pathway.

BACKGROUND: ING5 is the last member of the Inhibitor of Growth (ING) candidate tumor suppressor family that has been implicated in multiple cellular functions, including cell cycle regulation, apoptosis, and chromatin remodeling. Our previous study showed that ING5 overexpression inhibits lung cancer aggressiveness and epithelial-mesenchymal transition (EMT), with unknown mechanisms. METHODS: Western blotting was used to detect total and phosphorylated levels of ß-catenin and EMT-related proteins. Immunofluorescent staining was used to observe E-cadherin expression. Proliferation and colony formation, wound healing, and Transwell migration and invasion assays were performed to study the proliferative and invasive abilities of cancer cells. RESULTS: ING5 overexpression promotes phosphorylation of ß-catenin at Ser33/37, leading to a decreased ß-catenin protein level. Small hairpin RNA-mediated ING5 knockdown significantly increased the ß-catenin level and inhibited phosphorylation of ß-catenin S33/37. Treatment with the WNT/ß-catenin inhibitor XAV939 inhibited ING5-knockdown promoted proliferation, colony formation, migration, and invasion of lung cancer A549 cells, with increased phosphorylation of ß-catenin S33/37 and a decreased ß-catenin level. XAV939 also impaired ING5-knockdown-induced EMT, as indicated by upregulated expression of the EMT marker E-cadherin, an epithelial marker; and decreased expression of N-cadherin, a mesenchymal marker, and EMT-related transcription factors, including Snail, Slug, Twist, and Smad3. Furthermore, XAV939 could inhibit the activation of both IL-6/STAT3 and PI3K/Akt signaling pathways. CONCLUSION: ING5 inhibits lung cancer invasion and EMT by inhibiting the WNT/ß-catenin pathway.

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 ).

WSTF promotes proliferation and invasion of lung cancer cells by inducing EMT via PI3K/Akt and IL-6/STAT3 signaling pathways.

Williams syndrome transcription factor (WSTF), which is encoded by the BAZ1B gene, was first identified as a hemizygously deleted gene in patients with Williams syndrome. WSTF protein has been reported to be involved in transcription, replication, chromatin remodeling and DNA damage response, and also functions as a tyrosine protein kinase. However, the function of WSTF in cancer is not known. Here, we show that WSTF overexpression promotes proliferation, colony formation, migration and invasion of lung cancer A549 and H1299 cells. WSTF overexpression also promotes tumor growth and invasive abilities of lung cancer cells in mouse xenograft models. cDNA microarray and subsequent qRT-PCR validation revealed that WSTF overexpression significantly upregulated the expression of EMT (epithelial to mesenchymal transition) marker fibronectin (FN1) and EMT-inducing genes Fos and CEACAM6. The changes of EMT markers including downregulated E-cadherin and upregulated N-cadherin and FN1 were further confirmed at both mRNA and protein levels upon WSTF overexpression, with typical morphological changes of EMT. Furthermore, WSTF activates both PI3K/Akt and IL-6/STAT3 oncogenic signaling pathways. Treatment with PI3K inhibitor ZSTK474 or STAT3 inhibitor niclosamide reversed the effects of WSTF overexpression by inhibiting cell proliferation, migration and invasion, with decreased level of p-Akt, p-STAT3 and IL-6. ZSTK474 and niclosamide also reversed EMT markers and EMT-inducing proteins including Snail, Slug, Twist and CEACAM6 in WSTF-overexpressing A549 cells. Taken together, these results demonstrate that WSTF may act as an oncoprotein in lung cancer to accelerate tumor aggressiveness by promoting EMT via activation of PI3K/Akt and IL-6/STAT3 pathways.

[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 Contrast on Visual Spatial Summation in Different Cell Categories in Cat Primary Visual Cortex.

Multiple cell classes have been found in the primary visual cortex, but the relationship between cell types and spatial summation has seldom been studied. Parvalbumin-expressing inhibitory interneurons can be distinguished from pyramidal neurons based on their briefer action potential durations. In this study, we classified V1 cells into fast-spiking units (FSUs) and regular-spiking units (RSUs) and then examined spatial summation at high and low contrast. Our results revealed that the excitatory classical receptive field and the suppressive non-classical receptive field expanded at low contrast for both FSUs and RSUs, but the expansion was more marked for the RSUs than for the FSUs. For most V1 neurons, surround suppression varied as the contrast changed from high to low. However, FSUs exhibited no significant difference in the strength of suppression between high and low contrast, although the overall suppression decreased significantly at low contrast for the RSUs. Our results suggest that the modulation of spatial summation by stimulus contrast differs across populations of neurons in the cat primary visual cortex.