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Background: Known for its strong diuretic properties, the perennial herbaceous plant Orthosiphon stamineus Benth. is believed to preserve the kidney disease. This study compared the boiling water extract with powdered Orthosiphon stamineus Benth. and used a highly sensitive and high resolution UHPLC-Q-Exactive-Orbitrap-HRMS technology to evaluate its chemical composition., Results: Furthermore, by monitoring the absorption of prototype components in rat plasma following oral treatment, the beneficial ingredients of the Orthosiphon stamineus Benth. decoction was discovered. Approximately 92 substances underwent a preliminary identification utilizing relevant databases, relevant literature, and reference standards. As the compound differences between the powdered Orthosiphon stamineus Benth. and its water decoction were analyzed, it was found that boiling produced additional compounds, 48 of which were new. 45 blood absorption prototype components and 49 OS metabolites were discovered from rat serum, and a kidney tissue homogenate revealed an additional 28 prototype components. Early differences in the distribution of ferulic acid, cis 4 coumaric acid, and rosmarinic acid were shown using spatial metabolomics. It was elucidated that the renal cortex region is where rosmarinic acid largely acts, offering a theoretical foundation for further studies on the application of OS in the prevention and treatment of illness as well as the preservation of kidney function., Significance: In this study, UHPLC-Q Exactive Orbitrap-HRMS was employed to discern OS's chemical composition, and a rapid, sensitive, and broad-coverage AFADESI-MSI method was developed to visualize the spatial distribution of compounds in tissues., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ouyang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Sepsis is characterized by upregulated lipolysis in adipose tissue and a high blood triglyceride (TG) level. It is still debated whether serum TG level is related to mortality in septic patients. The aim of this study is to investigate the association between serum TG level and mortality in septic patients admitted to the intensive care unit (ICU)., Methods: Data from adult septic patients (≥18 years) admitted to the ICU for the first time were obtained from the Multiparameter Intelligent Monitoring in Intensive Care IV (MIMIC-IV) database. The patients' serum TG levels that were measured within the first week after ICU admission were extracted for statistical analysis. The endpoints were 28-day, ICU and in-hospital mortality., Results: A total of 2,782 septic patients were included. Univariate analysis indicated that the relationship between serum TG levels and the risk of mortality was significantly nonlinear. Both the Lowess smoothing technique and restricted cubic spline analyses revealed a U-shaped association between serum TG levels and mortality among septic patients. The lowest mortality rate was associated with a serum TG level of 300-500 mg/dL. Using 300∼500 mg/dL as the reference range, we found that both hypo-TG (<300 mg/dL) and hyper-TG (≥500 mg/dL) were associated with increased mortality. The result was further adjusted by Cox regression with and without the inclusion of some differential covariates., Conclusions: There was a U-shaped association between serum TG and mortality in septic ICU patients. The optimal concentration of serum TG levels in septic ICU patients is 300-500 mg/dL., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xiao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Human immunodeficiency virus-1 (HIV-1) exhibits high diversity and complexity in China, challenging the disease surveillance and antiretroviral therapy. Between July 1, 2014 and January 30, 2017, we investigated the profiles of HIV-1 infection stages, genotype distribution and drug resistance mutations (DRMs) using plasma samples from HIV Western blot (WB) confirmed blood donors from five Chinese blood centers (Chongqing, Guangxi, Luoyang, Mianyang, and Urumqi). HIV pol regions consisted of whole protease and partial reverse transcriptase were genotyped and analyzed for DRMs. Lag-Avidity testing was performed to identify the infection stages. Of the 356 HIV-1 WB positive samples tested by Lag-avidity assay, 19.1% (68/356) were recent infections. Genotyping on 356 amplified sequences presented the subtype distributions as following: CRF07&#95;BC (65.7%), CRF08&#95;BC (7.3%), CRF01&#95;AE (19.1%), B (4.2%), CRF55&#95;01B (3.1%), CRF59&#95;01B (0.3%) and CRF68&#95;01B (0.3%). No significant difference in genotype distribution was observed between recent and long-term infections. 48 DRMs were identified from 43 samples, indicating a drug resistance prevalence of 12.1% (43/356), which include seven protease inhibitors (PIs) accessory DRMs (Q58E, L23I and I84M), two PIs major DRMs (M46I, M46L), seven nucleoside RT inhibitors DRMs (D67N, K70Q, K219R and M184L), and 32 non-nucleoside RT inhibitors DRMs (K103N, V179E, K238N, V179D, E138G, G190E, A98G, Y188D and E138A). In addition, we had also identified CRFs from the 01B subtype including CRF55&#95;01B (3.1%), CRF59&#95;01B (0.3%) and CRF68&#95;01B (0.3%). As an important part of the continuous monitoring of HIV-1 circulating strains among blood donors, our findings were expected to contribute to the comprehensive AIDS control and development of proper diagnostics for HIV-1 in China., Competing Interests: The authors have declared that no competing interests exist.

Hepatitis C virus (HCV) genotype (GT) distribution in China shows significant geographical and demographic difference. As a routinely tested virus in Chinese blood bank systems, rare molecular epidemiology research in blood donors is reported. Our purpose is to investigate the HCV GT/subtypes distribution, phylogenetic analysis and population genetics in Chinese blood donors. Anti-HCV screen positive samples and donor demographics were collected. HCV Core and E1 gene fragments were amplified by RT-PCR, followed by sequencing and phylogenetic analysis to determine HCV GTs/subtypes using MEGA 7.0. The population genetics were performed using Arlequin v3.0 and Beast v1.10.4. SPSS Statistics 17.0 software was used to analyze the correlation between HCV GTs/subtypes distribution and demographic characteristics. 419 and 293 samples based on Core and E1 gene respectively were successfully amplified. HCV la, lb, 2a, 3a, 3b, 6a, 6e and 6n were found, and the corresponding proportions were 0.66% (3/455), 58.68% (267/455), 17.80% (81/455) and 5.05% (23/455), 3.52% (16/455), 12.31% (56/455), 0.88% (4/455) and 0.66% (3/455). Samples from Guangxi showed the most abundant genetic diversity with 8 subtypes were found. The number of haplotypes in HCV-1b is higher than 2a and 6a. The negative Tajima's D and Fu's Fs values of HCV-1b, 2a and 6a suggested the population expansion of those HCV subtypes. The distribution of HCV GT showed significant statistical difference by age and ethnicity. Conclusion: An abundance of HCV genetic diversity was found in Chinese blood donors with mainly 1b and then 2a subtype. There were significant geographical and demographic differences in HCV GTs/subtypes among Chinese blood donors. HCV subtype 1b has stronger viability and HCV subtype 6a has experienced significant expansion., Competing Interests: The authors have declared that no competing interests exist.

Background: The National Essential Medicine Policy and the Zero Mark-up Policy was introduced to improve the rational use and affordability of medicine. This study analyzed the changes of medicine use at different Health Care Institutions in Hangzhou city after the implementation of National Essential Medicine Policy and the Zero Mark-up Policy., Methods: Facility based survey was conducted in 17 Health Care Institutions and 16406 outpatient prescriptions in 2011 and 2013 were collected. Average number of medicines, average number of antibiotics and average expenditure per prescription were analyzed. Comparisons between 2011 and 2013, among different levels of Health Care Institutions and age groups were conducted., Results: The average number of medicines per prescription, use of antibiotics, intramuscular (IM) injections and intravenous (IV) injections decreased while the use of hormones increased. No significant change of the average medicine expenditure per prescription was observed. Disparities among different levels of Health Care Institutions and different age groups existed., Conclusion: The problems of poly-pharmacy, overuse of antibiotics, intramuscular (IM) injections and intravenous (IV) injections and hormones still existed, however mitigated after the implementation of The National Essential Medicine Policy and the Zero Mark-up Policy., Competing Interests: The authors have declared that no competing interests exist.

Floral induction that initiates bolting and flowering is crucial for reproductive fitness in radishes. CONSTANS-like (CO-like, COL) genes play an important role in the circadian clock, which ensures regular development through complicated time-keeping mechanisms. However, the specific biological and functional roles of each COL transcription factor gene in the radish remain unknown. In this study, we performed a genome-wide identification of COL genes in the radish genome of three cultivars including 'Aokubi', 'kazusa' and 'WK10039', and we analyzed their exon-intron structure, gene phylogeny and synteny, and expression levels in different tissues. The bioinformatics analysis identified 20 COL transcription factors in the radish genome, which were divided into three subgroups (Group I to Group III). RsaCOL-09 and RsaCOL-12 might be tandem duplicated genes, whereas the others may have resulted from segmental duplication. The Ka/Ks ratio indicated that all the COL genes in radish, Arabidopsis, Brassica rapa, Brassica oleracea, Capsella rubella and rice were under purifying selection. We identified 6 orthologous and 19 co-orthologous COL gene pairs between the radish and Arabidopsis, and we constructed an interaction network among these gene pairs. The expression values for each COL gene during vegetable and flower development showed that the majority of Group I members had similar expression patterns. In general, the expression of radish COL genes in Groups I and III decreased during development, whereas the expression of radish COL genes in Group II first increased and then decreased. Substantial numbers of radish COL genes were differentially expressed after vernalization treatment. The expression levels of RsaCOL-02 and RsaCOL-04 were significantly increased during vernalization treatment, while the expression of RsaCOL-10 was significantly decreased. These outcomes provide insights for improving the genetic control of bolting and flowering in radish and other root vegetable crops, and they facilitate genetic improvements to radish yields and quality., Competing Interests: The authors have declared that no competing interests exist.

In this study, we present a fully-coupled fluid-structure interaction (FSI) framework that combines smoothed particle hydrodynamics (SPH) and nonlinear finite element (FE) method to investigate the coupled aortic and mitral valves structural response and the bulk intraventricular hemodynamics in a realistic left ventricle (LV) model during the entire cardiac cycle. The FSI model incorporates valve structures that consider native asymmetric leaflet geometries, anisotropic hyperelastic material models and human material properties. Comparison of FSI results with subject-specific echocardiography data demonstrates that the SPH-FE approach is able to quantitatively predict the opening and closing times of the valves, the mitral leaflet opening and closing angles, and the large-scale intraventricular flow phenomena with a reasonable agreement. Moreover, comparison of FSI results with a LV model without valves reveals substantial differences in the flow field. Peak systolic velocities obtained from the FSI model and the LV model without valves are 2.56 m/s and 1.16 m/s, respectively, compared to the Doppler echo data of 2.17 m/s. The proposed SPH-FE FSI framework represents a further step towards modeling patient-specific coupled LV-valve dynamics, and has the potential to improve our understanding of cardiovascular physiology and to support professionals in clinical decision-making.

The increasing complexity and diversity of the human immunodeficiency virus-1 (HIV-1) infections challenge the disease control and anti-retrovirus treatment in China. The infection stages and molecular characteristics of HIV-1 from infected Chinese blood donors were examined to shed light on the HIV genotype distribution and the status of drug resistance mutations (DRMs) in the changing HIV epidemic in China. Western blot (WB) confirmed HIV-1 positive plasma samples were collected from blood donors at five Chinese blood centers from April 16, 2012, through June 30, 2014. The HIV infection stages were determined using the Lag-avidity assay. HIV Pol regions including whole protease and partial reverse transcriptase (RT) were amplified and sequenced to establish the profile of genotype distribution and drug resistance mutations (DRMs). Viral loads were determined using the ROCHE COBAS system. Of the 259 HIV-1 positive samples tested by the Lag-avidity assay, 23.6% (61/259) were identified as recent infections. A total of 205 amplified sequences displayed the following genotype distributions: circulating recombinant form (CRF) 07&#95;BC (61.5%), CRF08&#95;BC (8.3%), CRF01&#95;AE (20%), B (6.3%), and 01B (3.9%). There was no significant difference in genotype distribution between recent and long-term infections. 31 DRMs were identified from 27 samples including four protease inhibitors (PIs) accessory DRMs, two PIs major DRMs (M46I), two nucleoside RT inhibitors DRMs (K219R and K70Q), and 23 nonnucleoside RT inhibitors DRMs. 27 samples had DRMs, yielding a drug resistance prevalence of 13.2% (27/205). Our findings provide important information for developing strategies for comprehensive HIV control and improving anti-retroviral treatment in China.

Cadmium, a toxic heavy metal, is widely present in food. It has been reported that chronic cadmium exposure is associated with kidney disease, osteoporosis, cardiovascular disease and cancer. The aim of this study was to assess the dietary cadmium exposure and potential health risk in different age-sex groups of the Chinese population (children aged 4-11 years, young people aged 12-17 years and adults aged over 18 years), and in the southern and northern population using a semi-probabilistic method. Cadmium was detected in 228,687 food samples from 32 food categrories by graphite furnace atomic absorption spectrometry. The dietary cadmium exposures were estimated by combining the cadmium concentration data with food consumption data derived from the China National Nutrient and Health Survey 2002, and evaluated against the Provisional Tolerable Monthly Intake (PTMI) of 25 μg/kg BW/month established by the Joint FAO/WHO expert committee on food additives (JECFA). The mean dietary cadmium exposure of the general Chinese population (15.3 μg/kg BW/month) was below the PTMI. The high consumer exposures (95th percentile, P95) for the general population and different sub-groups were higher than the PTMI. The dietary cadmium exposure of the southern population was apparently higher than that of the northern population. Rice was the most important contributor to cadmium exposure for Chinese people, especially those living in the southern areas of China. These findings indicated that the health risk from dietary cadmium exposure of the general Chinese people was low, but the health risk of cadmium exposure of certain sub-groups should be of concern.

Cancer cells prefer aerobic glycolysis, but little is known about the underlying mechanism. Recent studies showed that the rate-limiting glycolytic enzymes, pyruvate kinase M2 (PKM2) directly phosphorylates H3 at threonine 11 (H3T11) to regulate gene expression and cell proliferation, revealing its non-metabolic functions in connecting glycolysis and histone modifications. We have reported that the yeast homolog of PKM2, Pyk1 phosphorylates H3T11 to regulate gene expression and oxidative stress resistance. But how glycolysis regulates H3T11 phosphorylation remains unclear. Here, using a series of glycolytic enzyme mutants and commercial available metabolites, we investigated the role of glycolytic enzymes and metabolites on H3T11 phosphorylation. Mutation of glycolytic genes including phosphoglucose isomerase (PGI1), enolase (ENO2), triosephosphate isomerase (TPI1), or folate biosynthesis enzyme (FOL3) significantly reduced H3T11 phosphorylation. Further study demonstrated that glycolysis regulates H3T11 phosphorylation by fueling the substrate, phosphoenonylpyruvate and the coactivator, FBP to Pyk1. Thus, our results provide a comprehensive view of how glycolysis modulates H3T11 phosphorylation.

The most common ocular side effect of glucocorticoid (GC) therapy is GC-induced ocular hypertension (OHT) and GC-induced glaucoma (GIG). GC-induced OHT occurs in about 40% of the general population, while the other 60% are resistant. This study aims to determine the genes and pathways involved in differential GC responsiveness in the trabecular meshwork (TM). Using paired bovine eyes, one eye was perfusion-cultured with 100nM dexamethasone (DEX), while the fellow eye was used to establish a bovine TM (BTM) cell strain. Based on maximum IOP change in the perfused eye, the BTM cell strain was identified as a DEX-responder or non-responder strain. Three responder and three non-responder BTM cell strains were cultured, treated with 0.1% ethanol or 100nM DEX for 7 days. RNA and proteins were extracted for RNA sequencing (RNAseq), qPCR, and Western immunoblotting (WB), respectively. Data were analyzed using the human and bovine genome databases as well as Tophat2 software. Genes were grouped and compared using Student's t-test. We found that DEX induced fibronectin expression in responder BTM cells but not in non-responder cells using WB. RNAseq showed between 93 and 606 differentially expressed genes in different expression groups between responder and non-responder BTM cells. The data generated by RNAseq were validated using qPCR. Pathway analyses showed 35 pathways associated with differentially expressed genes. These genes and pathways may play important roles in GC-induced OHT and will help us to better understand differential ocular responsiveness to GCs., Competing Interests: The authors have declared that no competing interests exist.

Background: The decomposition of plant material in arid ecosystems is considered to be substantially controlled by water and N availability. The responses of litter decomposition to external N and water, however, remain controversial, and the interactive effects of supplementary N and water also have been largely unexamined., Methodology/principal Findings: A 3.5-year field experiment with supplementary nitrogen and water was conducted to assess the effects of N and water addition on mass loss and nitrogen release in leaves and fine roots of three dominant plant species (i.e., Artemisia halondendron, Setaria viridis, and Phragmites australis) with contrasting substrate chemistry (e.g. N concentration, lignin content in this study) in a desertified dune grassland of Inner Mongolia, China. The treatments included N addition, water addition, combination of N and water, and an untreated control. The decomposition rate in both leaves and roots was related to the initial litter N and lignin concentrations of the three species. However, litter quality did not explain the slower mass loss in roots than in leaves in the present study, and thus warrant further research. Nitrogen addition, either alone or in combination with water, significantly inhibited dry mass loss and N release in the leaves and roots of the three species, whereas water input had little effect on the decomposition of leaf litter and fine roots, suggesting that there was no interactive effect of supplementary N and water on litter decomposition in this system. Furthermore, our results clearly indicate that the inhibitory effects of external N on dry mass loss and nitrogen release are relatively strong in high-lignin litter compared with low-lignin litter., Conclusion/significance: These findings suggest that increasing precipitation hardly facilitates ecosystem carbon turnover but atmospheric N deposition can enhance carbon sequestration and nitrogen retention in desertified dune grasslands of northern China. Additionally, litter quality of plant species should be considered when modelling the carbon cycle and nutrient dynamics of this system., Competing Interests: The authors have declared that no competing interests exist.

In this study, we examined the influence of different nitrogen (N) application rates (0, 168, 240, 270 and 312 kg N ha(-1)) on soil properties, maize (Zea mays L.) yields and microbial communities of three types of soils (clay, alluvial and sandy soils). Phospholipid fatty acid analysis was used to characterize soil microbial communities. Results indicated that N fertilization significantly decreased microbial biomass in both clay and sandy soils regardless of application rate. These decreases were more likely a result of soil pH decreases induced by N fertilization, especially in the sandy soils. This is supported by structural equation modeling and redundancy analysis results. Nitrogen fertilization also led to significant changes in soil microbial community composition. However, the change differences were gradually dismissed with increase in N application rate. We also observed that N fertilization increased maize yields to the same level regardless of application rate. This suggests that farmers could apply N fertilizers at a lower rate (i.e. 168 kg N ha(-1)), which could achieve high maize yield on one hand while maintain soil microbial functions on the other hand.

Allogeneic hematopoietic stem cell transplantation is a widely used and effective therapy for hematopoietic malignant diseases and numerous other disorders. High-resolution human leukocyte antigen (HLA) haplotype frequency distributions not only facilitate individual donor searches but also determine the probability with which a particular patient can find HLA-matched donors in a registry. The frequencies of the HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes were estimated among 169,995 Chinese volunteers using the sequencing-based typing (SBT) method. Totals of 191 HLA-A, 244 HLA-B, 146 HLA-C, 143 HLA-DRB1 and 47 HLA-DQB1 alleles were observed, which accounted for 6.98%, 7.06%, 6.46%, 9.11% and 7.91%, respectively, of the alleles in each locus in the world (IMGT 3.16 Release, Apr. 2014). Among the 100 most common haplotypes from the 169,995 individuals, nine distinct haplotypes displayed significant regionally specific distributions. Among these, three were predominant in the South China region (i.e., the 20th, 31st, and 81sthaplotypes), another three were predominant in the Southwest China region (i.e., the 68th, 79th, and 95th haplotypes), one was predominant in the South and Southwest China regions (the 18th haplotype), one was relatively common in the Northeast and North China regions (the 94th haplotype), and one was common in the Northeast, North and Northwest China (the 40th haplotype). In conclusion, this is the first to analyze high-resolution HLA diversities across the entire country of China, based on a detailed and complete data set that covered 31 provinces, autonomous regions, and municipalities. Specifically, we also evaluated the HLA matching probabilities within and between geographic regions and analyzed the regional differences in the HLA diversities in China. We believe that the data presented in this study might be useful for unrelated HLA-matched donor searches, donor registry planning, population genetic studies, and anthropogenesis studies.

Cyclin-dependent kinase 5 (CDK5) is a cytoplasmic serine/ threonine kinase. Knockdown of CDK5 enhances paclitaxel sensitivity in human ovarian cancer cells. This study explores the mechanisms by which CDK5 regulates paclitaxel sensitivity in human ovarian cancers. Multiple ovarian cancer cell lines and xenografts were treated with CDK5 small interfering RNA (siRNA) with or without paclitaxel to examine the effect on cancer cell viability, cell cycle arrest and tumor growth. CDK5 protein was measured by immunohistochemical staining of an ovarian cancer tissue microarray to correlate CDK5 expression with overall patient survival. Knockdown of CDK5 with siRNAs inhibits activation of AKT which significantly correlates with decreased cell growth and enhanced paclitaxel sensitivity in ovarian cancer cell lines. In addition, CDK5 knockdown alone and in combination with paclitaxel induced G1 cell cycle arrest and caspase 3 dependent apoptotic cell death associated with post-translational upregulation and nuclear translocation of TP53 and p27(Kip1) as well as TP53-dependent transcriptional induction of p21(Cip1) in wild type TP53 cancer cells. Treatment of HEYA8 and A2780 wild type TP53 xenografts in nu/nu mice with CDK5 siRNA and paclitaxel produced significantly greater growth inhibition than either treatment alone. Increased expression of CDK5 in human ovarian cancers correlates inversely with overall survival. CDK5 modulates paclitaxel sensitivity by regulating AKT activation, the cell cycle and caspase-dependent apoptosis. CDK5 inhibition can potentiate paclitaxel activity in human ovarian cancer cells.

Background: Esophageal squamous cell carcinoma (ESCC) is very common in China and is also one of the most common cancers worldwide. The purpose of this study was to examine the associations between genetic variants of various cancer-related genes and the risk of ESCC., Methods: In this study, we first examined the association between 18 potentially disruptive genetic variants of 17 genes, including alcohol dehydrogenase 4 (ADH4) and checkpoint kinase 2 (CHEK2), and ESCC risk in a Hangzhou population of 617 patients matched with 534 controls. Among the 18 single nucleotide polymorphisms (SNPs), two were validated in a Jinan population of 540 patients matched with 550 controls., Results: Sixteen SNPs in 15 genes, including CHEK2, did not have significantly different allele frequency distributions between ESCC patients and control subjects. A significantly increased risk of developing ESCC was revealed in subjects with the AA genotype of rs3805322 (ADH4) compared with those with the AG or GG genotype by unconditional univariate logistic regression analysis. Using a dominant model, the CC genotype of rs4822983 (CHEK2) had a marginally significant protective effect compared to the CT and TT genotypes. The association of ESCC risk with these two SNPs (rs3805322 and rs4822983) was further validated in a Jinan case-control set. Individuals with the ADH4 rs3805322 AA or AG genotype had ORs of 1.10 (95% CI = 0.81-1.49, P < 0.001) or 1.86 (95% CI = 1.33-2.59, P = 0.559), respectively, for developing ESCC compared with individuals with the GG genotype. CHEK2 rs4822983 CC carriers showed a marginally significantly decreased ESCC risk compared with those carrying the CT and TT genotypes in the validation set (95% CI = 0.61-1.01, P = 0.064). However, no evidence of interaction existed between the two SNPs and smoking or drinking in the Jinan case-control set., Conclusions: In conclusion, this current study provides substantial evidence that genetic polymorphisms of rs3805322 in the ADH4 gene may be associated with an increased risk of developing ESCC in two Chinese Han populations. Future studies to address the biological function of this polymorphism in the development of ESCC are warranted.

Nomogram has demonstrated its capability in individualized estimates of survival in diverse cancers. Here we retrospectively investigated 1195 patients with esophageal squamous-cell carcinoma (ESCC) who underwent radical esophagectomy at Zhejiang Cancer Hospital in Hangzhou, China. We randomly assigned two-thirds of the patients to a training cohort (n = 797) and one-third to a validation cohort (n = 398). Cox proportional hazards regression analyses were performed using the training cohort, and a nomogram was developed for predicting 3-year and 5-year overall survival rates. Multivariate analysis identified tumor length, surgical approach, number of examined lymph node, number of positive lymph node, extent of positive lymph node, grade, and depth of invasion as independent risk factors for survival. The discriminative ability of the nomogram was externally determined using the validation cohort, showing that the nomogram exhibited a sufficient level of discrimination according to the C-index (0.715, 95% CI 0.671-0.759). The C-index of the nomogram was significantly higher than that of the sixth edition (0.664, P-value < 0.0001) and the seventh edition (0.696, P-value < 0.0003) of the TNM classification. This study developed the first nomogram for ESCC, which can be applied in daily clinical practice for individualized survival prediction.

Alterations in histone lysine methylation and epigenetic regulators of gene expression could play a role in the neurobiology and treatment of patients diagnosed with mood spectrum disorder, including depression and anxiety. Mutations and altered expression of various lysine methyltransferases (KMTs) and demethylases (KDMs) have been linked to changes in motivational and emotional behaviors in preclinical model systems. However, it is not known whether regulators operating downstream of histone lysine methylation could affect mood-related behavior. Malignant Brain Tumor (MBT) domain 'chromatin reader' proteins bind to methylated histone lysine residues and associate with chromatin remodeling complexes to facilitate or repress gene expression. MBT proteins, including the founding member, L3mbtl1, maintain high levels of expression in neurons of the mature brain. Here, we exposed L3mbtl1 null mutant mice to a wide range of tests exploring cognition and mood-relevant behaviors at baseline and in the context of social isolation, as a stressor to elicit depression-related behavior in susceptible mice. L3mbtl1 loss-of-function was associated with significant decreases in depression and and anxiety in some of the behavioral paradigms. This was not associated with a more generalized neurological dysfunction because cognition and memory remained unaltered in comparison to controls. These findings warrant further investigations on the role of MBT chromatin reader proteins in the context of emotional and affective behaviors.

Background: Irrational use of medicines has been an issue concerned all over the world and the outlooks in developing countries are more severe. This study aimed to assess the different patterns of irrational use of medicines and its influential factors in China and Vietnam., Methods: A systematic review was performed on both published and grey literatures in English, Chinese and Vietnamese languages between 1993 and 2013 based on the WHO framework. Quality assessment was conducted on the basis of the Critical Appraisal Skills Programme. Key indicators were analyzed to compare the irrational use of medicines in two countries., Results: A total of 67 published works about China and 29 about Vietnam were included, the majority of which were cross-sectional prescription studies in both China and Vietnam. Irrational use of medicines was found in both the countries but issues with polypharmacy as well as overuse of antibiotics were more severe in Vietnam while overuse of injections was unique to China. Various patterns of irrational use were also indicated between urban and rural areas, and among different levels of hospitals. Rarely does literature focus on the analysis of influential factors of irrational use of medicines. While lack of proper knowledge from both providers and patients were the most recognized influential factors in both countries, economic incentives from pharmaceutical companies in China, and weak control and regulation over prescriptions in Vietnam were the main factors attributed to this issue., Conclusion: Severe irrational use of medicines has been abundantly evidenced in both China and Vietnam, highlighting the importance of policy interventions on the issue. However, limited evidence on the appropriateness or its compliance (conformity) to guidelines of prescription has been found. In addition, convincing evidence on the underlying explanation of this issue is lacking, although economic incentives, health insurance coverage, and knowledge of service providers and users have been implied to be factors influencing irrational drug use.

Endostar, a novel modified recombinant human endostatin, is now widely studied for the treatment of diseases that are characterized or caused by pathological angiogenesis. However, its molecular mechanism remains unclear. In this study, we investigated the effects of Endostar on the Wnt/β-catenin signaling pathway, which has emerged as an important aspect of angiogenesis. We showed that Endostar significantly inhibited the proliferation, migration, invasion, and capillary-like tube formation of human umbilical vascular endothelial cells in a dose-dependent manner. Using a luciferase reporter assay, we also demonstrated that Endostar suppressed β-catenin-dependent T cell factor transcriptional activity in increasing doses. Moreover, we found that Endostar treatment also restricted the stabilized mutant β-catenin-mediated increase in transcriptional activity, suggesting that Endostar exerts its inhibitory influence on Wnt/β-catenin signaling by targeting β-catenin or its downstream molecules. Western blot and immunofluorescence results revealed that Endostar significantly decreased nuclear and total β-catenin levels. Finally, we discovered that Endostar down-regulated cyclin D1 and VEGF, two proteins that are known as the downstream targets of Wnt/β-catenin signaling and that also play important roles in angiogenesis. Our findings suggested that Endostar inhibits angiogenesis and that the downregulation of the Wnt/β-catenin signaling pathway may be involved in the inhibition of angiogenesis by Endostar. These results support the use of Endostar in further clinical applications.

Promoter methylation of the O(6)-methylguanine-DNA-methyltransferase (MGMT) gene has been considered a prognostic marker and has become more important in the treatment of glioblastoma. However, reports on the correlation between MGMT and clinical outcomes in Chinese glioblastoma patients are very scarce. In this study, quantitative methylation data were obtained by the pyrosequencing of tumor tissues from 128 GBM patients. The median overall survival (OS) was 13.1 months, with a 1-year survival of 45.3%. The pyrosequencing data were reproducible based on archived samples yielding data for all glioblastomas. MGMT promoter methylation was detected in 75/128 cases (58.6%), whereas 53/128 (41.4%) cases were unmethylated. Further survival analysis also revealed that methylation was an independent prognostic factor associated with prolonged OS but not with progression-free survival (PFS) (p = 0.029 and p = 0.112, respectively); the hazard radios were 0.63 (95% CI: 0.42-0.96) and 0.72 (95% CI: 0.48-1.09), respectively. These data indicated that MGMT methylation has prognostic significance in patients with newly diagnosed high-grade glioblastoma undergoing alkylating agent-based chemotherapy after surgical resection.

Background: Sedentary behavior is ubiquitous in modern adults' daily lives and it has been suggested to be associated with incident cancer. However, the results have been inconsistent. In this study, we performed a systematic review and meta-analysis of prospective cohort studies to clarify the association between sedentary behavior and incident cancer., Method: PubMed and Embase databases were searched up to March 2014. All prospective cohort studies on the association between sedentary behavior and incident cancer were included. The summary relative risks (RRs) with 95% confidence intervals (CIs) were estimated using random effect model., Results: A total of 17 prospective studies from 14 articles, including a total of 857,581 participants and 18,553 cases, were included in the analysis for sedentary behavior and risk of incident cancer. The overall meta-analysis suggested that sedentary behavior increased risk of cancer (RR = 1.20, 95%CI = 1.12-1.28), with no evidence of heterogeneity between studies (I(2) = 7.3%, P = 0.368). Subgroup analyses demonstrated that there were statistical associations between sedentary behavior and some cancer types (endometrial cancer: RR = 1.28, 95% CI = 1.08-1.53; colorectal cancer: RR = 1.30, 95%CI = 1.12-1.49; breast cancer: RR = 1.17, 95%CI = 1.03-1.33; lung cancer: RR = 1.27, 95%CI = 1.06-1.52). However, there was no association of sedentary behavior with ovarian cancer (RR = 1.26, 95%CI = 0.87-1.82), renal cell carcinoma (RR = 1.11, 95%CI = 0.87-1.41) or non-Hodgkin lymphoid neoplasms (RR = 1.09, 95%CI = 0.82-1.43)., Conclusion: The present meta-analysis suggested that prolonged sedentary behavior was independently associated with an increased risk of incident endometrial, colorectal, breast, and lung cancers, but not with ovarian cancer, renal cell carcinoma or non-Hodgkin lymphoid neoplasms.

Tibetan annual wild barley is rich in genetic variation. This study was aimed at the exploitation of new SSRs for the genetic diversity and phylogenetic analysis of wild barley by data mining. We developed 49 novel EST-SSRs and confirmed 20 genomic SSRs for 80 Tibetan annual wild barley and 16 cultivated barley accessions. A total of 213 alleles were generated from 69 loci with an average of 3.14 alleles per locus. The trimeric repeats were the most abundant motifs (40.82%) among the EST-SSRs, while the majority of the genomic SSRs were di-nuleotide repeats. The polymorphic information content (PIC) ranged from 0.08 to 0.75 with a mean of 0.46. Besides this, the expected heterozygosity (He) ranged from 0.0854 to 0.7842 with an average of 0.5279. Overall, the polymorphism of genomic SSRs was higher than that of EST-SSRs. Furthermore, the number of alleles and the PIC of wild barley were both higher than that of cultivated barley, being 3.12 vs 2.59 and 0.44 vs 0.37. Indicating more polymorphism existed in the Tibetan wild barley than in cultivated barley. The 96 accessions were divided into eight subpopulations based on 69 SSR markers, and the cultivated genotypes can be clearly separated from wild barleys. A total of 47 SSR-containing EST unigenes showed significant similarities to the known genes. These EST-SSR markers have potential for application in germplasm appraisal, genetic diversity and population structure analysis, facilitating marker-assisted breeding and crop improvement in barley.

China was one of the countries with highest esophageal squamous cell carcinoma (ESCC) incidence and mortality worldwide. Alcohol drinking has been identified as a major environmental risk-factor related to ESCC. The alcohol dehydrogenase (ADH) family are major enzymes involved in the alcohol-metabolizing pathways, including alcohol dehydrogenase 1B (ADH1B) and ADH1C. Interestingly, ADH1B and ADH1C genes locate tandemly with ADH7 in a genomic segment as a gene cluster, and are all polymorphic. Several ESCC susceptibility single nucleotide polymorphisms (SNPs) of the ADH1B-ADH1C-ADH7 cluster have been identified previously through a genome-wide association study (GWAS). In the study, we examined the association between five ADH1B-ADH1C-ADH7 cluster SNPs (rs1042026, rs17033, rs1614972, rs1789903 and rs17028973) and risk of developing ESCC. Genotypes were determined in two independent case-control sets from two regions of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Our data demonstrated that these ADH1B-ADH1C-ADH7 cluster SNPs confer susceptibility to ESCC in these two case-control sets, which were consistent to results of the previous GWAS.

Shape string is structural sequence and is an extremely important structure representation of protein backbone conformations. Nuclear magnetic resonance chemical shifts give a strong correlation with the local protein structure, and are exploited to predict protein structures in conjunction with computational approaches. Here we demonstrate a novel approach, NMRDSP, which can accurately predict the protein shape string based on nuclear magnetic resonance chemical shifts and structural profiles obtained from sequence data. The NMRDSP uses six chemical shifts (HA, H, N, CA, CB and C) and eight elements of structure profiles as features, a non-redundant set (1,003 entries) as the training set, and a conditional random field as a classification algorithm. For an independent testing set (203 entries), we achieved an accuracy of 75.8% for S8 (the eight states accuracy) and 87.8% for S3 (the three states accuracy). This is higher than only using chemical shifts or sequence data, and confirms that the chemical shift and the structure profile are significant features for shape string prediction and their combination prominently improves the accuracy of the predictor. We have constructed the NMRDSP web server and believe it could be employed to provide a solid platform to predict other protein structures and functions. The NMRDSP web server is freely available at http://cal.tongji.edu.cn/NMRDSP/index.jsp.

Abnormal cell mechanical stiffness can point to the development of various diseases including cancers and infections. We report a new microfluidic technique for continuous cell separation utilizing variation in cell stiffness. We use a microfluidic channel decorated by periodic diagonal ridges that compress the flowing cells in rapid succession. The compression in combination with secondary flows in the ridged microfluidic channel translates each cell perpendicular to the channel axis in proportion to its stiffness. We demonstrate the physical principle of the cell sorting mechanism and show that our microfluidic approach can be effectively used to separate a variety of cell types which are similar in size but of different stiffnesses, spanning a range from 210 Pa to 23 kPa. Atomic force microscopy is used to directly measure the stiffness of the separated cells and we found that the trajectories in the microchannel correlated to stiffness. We have demonstrated that the current processing throughput is 250 cells per second. This microfluidic separation technique opens new ways for conducting rapid and low-cost cell analysis and disease diagnostics through biophysical markers.

Alpha-synuclein protein is strongly implicated in the pathogenesis Parkinson's disease. Increased expression of α-synuclein due to genetic multiplication or point mutations leads to early onset disease. While α-synuclein is known to modulate membrane vesicle dynamics, it is not clear if this activity is involved in the pathogenic process or if measurable physiological effects of α-synuclein over-expression or mutation exist in vivo. Macrophages and microglia isolated from BAC α-synuclein transgenic mice, which overexpress α-synuclein under regulation of its own promoter, express α-synuclein and exhibit impaired cytokine release and phagocytosis. These processes were affected in vivo as well, both in peritoneal macrophages and microglia in the CNS. Extending these findings to humans, we found similar results with monocytes and fibroblasts isolated from idiopathic or familial Parkinson's disease patients compared to age-matched controls. In summary, this paper provides 1) a new animal model to measure α-synuclein dysfunction; 2) a cellular system to measure synchronized mobilization of α-synuclein and its functional interactions; 3) observations regarding a potential role for innate immune cell function in the development and progression of Parkinson's disease and other human synucleinopathies; 4) putative peripheral biomarkers to study and track these processes in human subjects. While altered neuronal function is a primary issue in PD, the widespread consequence of abnormal α-synuclein expression in other cell types, including immune cells, could play an important role in the neurodegenerative progression of PD and other synucleinopathies. Moreover, increased α-synuclein and altered phagocytosis may provide a useful biomarker for human PD.

Focal and diffuse neuronal loss happened after traumatic brain injury (TBI). With little in the way of effective repair, recent interest has focused on endogenic neural progenitor cells (NPCs) as a potential method for regeneration. Whether endogenic neural regeneration happened in the cortex of adult rat after TBI remains to be determined. In this study, rats were divided into a sham group and a TBI group, and the rat model of medium TBI was induced by controlled cortical impact. Rats were injected with BrdU at 1 to 7 days post-injury (dpi) to allow identification of differentiated cells and sacrificed at 1, 3, 7, 14 and 28 dpi for immunofluorescence. Results showed nestin(+)/sox-2(+) NPCs and GFAP(+)/sox-2(+) radial glial (RG)-like cells emerged in peri-injured cortex at 1, 3, 7, 14 dpi and peaked at 3 dpi. The number of GFAP(+)/sox-2(+) cells was less than that of nestin(+)/sox-2(+) cells. Nestin(+)/sox-2(+) cells from posterior periventricle (pPV) immigrated into peri-injured cortex through corpus callosum (CC) were found. DCX(+)/BrdU(+) newborn immature neurons in peri-injured cortex were found only at 3, 7, 14 dpi. A few MAP-2(+)/BrdU(+) newborn neurons in peri-injured cortex were found only at 7 and 14 dpi. NeuN(+)/BrdU(+) mature neurons were not found in peri-injured cortex at 1, 3, 7, 14 and 28 dpi. While GFAP(+)/BrdU(+) astrocytes emerged in peri-injured cortex at 1, 3, 7, 14, 28 dpi and peaked at 7 dpi then kept in a stable state. In the corresponding time point, the percentage of GFAP(+)/BrdU(+) astrocytes in BrdU(+) cells was more than that of NPCs or newborn neurons. No CNP(+)/BrdU(+) oligodendrocytes were found in peri-injured cortex. These findings suggest that NPCs from pPV and reactive RG-like cells emerge in peri-injured cortex of adult rats after TBI. It can differentiate into immature neurons and astrocytes, but the former fail to grow up to mature neurons.

Fruit set of plants largely depends on the biosynthesis and crosstalk of phytohormones. To date the role of cytokinins (CKs) in the fruit development is less understood. Here, we showed that parthenocarpic fruit could be induced by 1-(2-chloro-4-pyridyl)-3-phenylurea (CPPU, an active CK) in tomato (Solanumlycopersicum cv. Micro-Tom). The fresh weight of CPPU-induced parthenocarpic fruits was comparable with that induced by GA3. Importantly, CPPU-induced parthenocarpy was found to be compromised by simultaneous application of paclobutrazol (a GA biosynthesis inhibitor), and this effect could be restored by exogenous GA3. Like pollination, CPPU-induced fruit showed enhanced accumulation of GA1+3 and indole-3-acetic (IAA), which were accompanied by elevated expression of GA biosynthesis genes like SlGPS, SlGA20ox1, SlGA20ox2 and SlGA3ox1, and IAA biosynthesis gene ToFZY. Elevated GAs level in CPPU-induced fruits was also associated with down-regulation of GA inactivation genes, namely SlGA2ox1,2,3,4,5 in comparison with untreated control. These results suggested that CKs may induce parthenocarpy in tomato partially through modulation of GA and IAA metabolisms.

Aim: To explore the association between genetic polymorphisms of the receptor for advanced glycation end-products (RAGE) and susceptibility, chemotherapy response rate and prognosis of non-small cell lung cancer (NSCLC)., Method: This is a prospective study in which 562 patients with NSCLC and 764 healthy controls were enrolled. Three RAGE genetic polymorphisms, namely, -429T/C, -374T/A and 82G/S were genotyped. Platinum-based chemotherapy was given to 432 subjects with advanced inoperable NSCLC and their responses to chemotherapy were evaluated., Results: All the polymorphic genotypes of RAGE polymorphisms were associated with susceptibility for NSCLC. Only the 82G/S polymorphisms denoted a significant difference between responders and non-responders to chemotherapy. The 82SS genotype and 82S allele distribution not only increased the NSCLC risk, but also was associated with a lower chemotherapy response rate and poor prognosis, indicated by overall survival and progression free survival., Conclusion: The 82G/S genetic polymorphism of RAGE gene might be used as a genetic marker to screen for patients sensitive to thermotherapy and to predict the prognosis of NSCLC.

Na(V)1.5 is a cardiac voltage-gated Na(+) channel αsubunit and is encoded by the SCN5a gene. The activity of this channel determines cardiac depolarization and electrical conduction. Channel defects, including mutations and decrease of channel protein levels, have been linked to the development of cardiac arrhythmias. The molecular mechanisms underlying the regulation of Na(V)1.5 expression are largely unknown. Forkhead box O (Foxo) proteins are transcriptional factors that bind the consensus DNA sequences in their target gene promoters and regulate the expression of these genes. Comparative analysis revealed conserved DNA sequences, 5'-CAAAACA-3' (insulin responsive element, IRE), in rat, mouse and human SCN5a promoters with the latter two containing two overlapping Foxo protein binding IREs, 5'-CAAAACAAAACA-3'. This finding led us to hypothesize that Foxo1 regulates Na(V)1.5 expression by directly binding the SCN5a promoter and affecting its transcriptional activity. In the present study, we determined whether Foxo1 regulates Na(V)1.5 expression at the transcriptional level and also defined the role of Foxo1 in hydrogen peroxide (H(2)O(2))-mediated Na(V)1.5 suppression in HL-1 cardiomyocytes using chromatin immunoprecipitation (ChIP), constitutively nuclear Foxo1 expression, and RNAi Foxo1 knockdown as well as whole cell voltage-clamp recordings. ChIP with anti-Foxo1 antibody and follow-up semi-quantitative PCR with primers flanking Foxo1 binding sites in the proximal SCN5a promoter region clearly demonstrated enrichment of DNA, confirming Foxo1 recruitment to this consensus sequence. Foxo1 mutant (T24A/S319A-GFP, Foxo1-AA-GFP) was retained in nuclei, leading to a decrease of Na(V)1.5 expression and Na(+) current, while silencing of Foxo1 expression by RNAi resulted in the augmentation of Na(V)1.5 expression. H(2)O(2) significantly reduced Na(V)1.5 expression by promoting Foxo1 nuclear localization and this reduction was prevented by RNAi silencing Foxo1 expression. These studies indicate that Foxo1 negatively regulates Na(V)1.5 expression in cardiomyocytes and reactive oxygen species suppress Na(V)1.5 expression through Foxo1.

Trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of the HER2 oncoprotein, can effectively target HER2-positive breast cancer through several mechanisms. Although the effects of trastuzumab on cancer cell proliferation, angiogenesis and apoptosis have been investigated in depth, the effect of trastuzumab on microRNA (miRNA) has not been extensively studied. We have performed miRNA microarray profiling before and after trastuzumab treatment in SKBr3 and BT474 human breast cancer cells that overexpress HER2. We found that trastuzumab treatment of SKBr3 cells significantly decreased five miRNAs and increased three others, whereas treatment of BT474 cells significantly decreased two miRNAs and increased nine. The only change in miRNA expression observed in both cell lines following trastuzumab treatment was upregulation of miRNA-194 (miR-194) that was further validated in vitro and in vivo. Forced expression of miR-194 in breast cancer cells that overexpress HER2 produced no effect on apoptosis, modest inhibition of proliferation, significant inhibition of cell migration/invasion in vitro and significant inhibition of xenograft growth in vivo. Conversely, knockdown of miR-194 promoted cell migration. Increased miR-194 expression markedly reduced levels of the cytoskeletal protein talin2 and specifically inhibited luciferase reporter activity of a talin2 wild-type 3'-untranslated region, but not that of a mutant reporter, indicating that talin2 is a direct downstream target of miR-194. Trastuzumab treatment inhibited breast cancer cell migration and reduced talin2 expression in vitro and in vivo. Knockdown of talin2 inhibited cell migration/invasion. Knockdown of trastuzumab-induced miR-194 expression with a miR-194 inhibitor compromised trastuzumab-inhibited cell migration in HER2-overexpressing breast cancer cells. Consequently, trastuzumab treatment upregulates miR-194 expression and may exert its cell migration-inhibitory effect through miR-194-mediated downregulation of cytoskeleton protein talin2 in HER2-overexpressing human breast cancer cells.

Background: Honey bees are exposed to phytochemicals through the nectar, pollen and propolis consumed to sustain the colony. They may also encounter mycotoxins produced by Aspergillus fungi infesting pollen in beebread. Moreover, bees are exposed to agricultural pesticides, particularly in-hive acaricides used against the parasite Varroa destructor. They cope with these and other xenobiotics primarily through enzymatic detoxificative processes, but the regulation of detoxificative enzymes in honey bees remains largely unexplored., Methodology/principal Findings: We used several approaches to ascertain effects of dietary toxins on bee susceptibility to synthetic and natural xenobiotics, including the acaricide tau-fluvalinate, the agricultural pesticide imidacloprid, and the naturally occurring mycotoxin aflatoxin. We administered potential inducers of cytochrome P450 enzymes, the principal biochemical system for Phase 1 detoxification in insects, to investigate how detoxification is regulated. The drug phenobarbital induces P450s in many insects, yet feeding bees with phenobarbital had no effect on the toxicity of tau-fluvalinate, a pesticide known to be detoxified by bee P450s. Similarly, no P450 induction, as measured by tau-fluvalinate tolerance, occurred in bees fed xanthotoxin, salicylic acid, or indole-3-carbinol, all of which induce P450s in other insects. Only quercetin, a common pollen and honey constituent, reduced tau-fluvalinate toxicity. In microarray comparisons no change in detoxificative gene expression was detected in phenobarbital-treated bees. However, northern blot analyses of guts of bees fed extracts of honey, pollen and propolis showed elevated expression of three CYP6AS P450 genes. Diet did not influence tau-fluvalinate or imidacloprid toxicity in bioassays; however, aflatoxin toxicity was higher in bees consuming sucrose or high-fructose corn syrup than in bees consuming honey., Conclusions/significance: These results suggest that regulation of honey bee P450s is tuned to chemicals occurring naturally in the hive environment and that, in terms of toxicological capacity, a diet of sugar is not equivalent to a diet of honey.

Background: Red blood cell distribution width (RDW), an automated measure of red blood cell size heterogeneity (e.g., anisocytosis) that is largely overlooked, is a newly recognized risk marker in patients with cardiovascular diseases, but its role in persistent viral infection has not been well-defined. The present study was designed to investigate the association between RDW values and different disease states in hepatitis B virus (HBV)-infected patients. In addition, we analyzed whether RDW is associated with mortality in the HBV-infected patients., Methodology/principal Findings: One hundred and twenty-three patients, including 16 with acute hepatitis B (AHB), 61 with chronic hepatitis B (CHB), and 46 with chronic severe hepatitis B (CSHB), and 48 healthy controls were enrolled. In all subjects, a blood sample was collected at admission to examine liver function, renal function, international normalized ratio and routine hematological testing. All patients were followed up for at least 4 months. A total of 10 clinical chemistry, hematology, and biochemical variables were analyzed for possible association with outcomes by using Cox proportional hazards and multiple regression models. RDW values at admission in patients with CSHB (18.30±3.11%, P<0.001), CHB (16.37±2.43%, P<0.001) and AHB (14.38±1.72%, P<0.05) were significantly higher than those in healthy controls (13.03±1.33%). Increased RDW values were clinically associated with severe liver disease and increased 3-month mortality rate. Multivariate analysis demonstrated that RDW values and the model for end-stage liver disease score were independent predictors for mortality (both P<0.001)., Conclusion: RDW values are significantly increased in patients with hepatitis B and associated with its severity. Moreover, RDW values are an independent predicting factor for the 3-month mortality rate in patients with hepatitis B.

Chromosome 8q24 is commonly amplified in many types of cancer, particularly lung cancer. Polymorphisms in this region are associated with risk of different cancers. To investigate the relationship between three single nucleotide polymorphisms (SNPs) (rs1447295, rs16901979 and rs6983267) on 8q24 and lung cancer risk, we conducted an association study in two Han Chinese populations: one population was from Zhejiang Province (576 case patients and 576 control subjects), whereas the other was from Fujian Province (576 case patients and 576 control subjects). We found that rs6983267 was significantly associated with an increased risk of lung cancer in both populations. Compared with the TT genotype, the GG genotype was associated with a significant 1.555-fold increased risk of lung cancer [95% confidence interval (CI) 1.218-1.986, P = 4.0×10(-4)]. This effect was more pronounced in never-smokers [odds ratio (OR) = 2.366, 95% CI 1.605-3.488, P = 1.4×10(-5)]. Analyses stratified by histology revealed that rs6983267 GG genotype was most associated with patients with other histological types (OR = 3.012, 95% CI 1.675-5.417, P = 2.3×10(-4)). The AA genotype of rs1447295 was associated with increased risk for adenocarcinoma compared with the CC genotype (OR = 2.260, 95% CI 1.174-4.353, P = 0.015). Furthermore, the GG genotype of rs6983267 was associated with worse survival in the Zhejiang population (hazard ratio (HR) = 1.646, 95% CI 1.099-2.464, P = 0.016). No association was observed for rs16901979. These results suggest that genetic variations on 8q24 may play significant roles in the development and progression of lung cancer.

MicroRNAs (miRNAs) are endogenous small RNAs playing an important regulatory function in plant development and stress responses. Among them, some are evolutionally conserved in plant and others are only expressed in certain species, tissue or developmental stages. Cucumber is among the most important greenhouse species in the world, but only a limited number of miRNAs from cucumber have been identified and the experimental validation of the related miRNA targets is still lacking. In this study, two independent small RNA libraries from cucumber leaves and roots were constructed, respectively, and sequenced with the high-throughput Illumina Solexa system. Based on sequence similarity and hairpin structure prediction, a total of 29 known miRNA families and 2 novel miRNA families containing a total of 64 miRNA were identified. QRT-PCR analysis revealed that some of the cucumber miRNAs were preferentially expressed in certain tissues. With the recently developed 'high throughput degradome sequencing' approach, 21 target mRNAs of known miRNAs were identified for the first time in cucumber. These targets were associated with development, reactive oxygen species scavenging, signaling transduction and transcriptional regulation. Our study provides an overview of miRNA expression profile and interaction between miRNA and target, which will help further understanding of the important roles of miRNAs in cucumber plants.