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Background: The association between frailty and psychiatric disorders has been reported in observational studies. However, it is unclear whether frailty facilitates the appearance of psychiatric disorders or vice versa. Therefore, we conducted a bidirectional Mendelian randomization (MR) study to evaluate the causality., Methods: Independent genetic variants associated with frailty index (FI) and psychiatric disorders were obtained from large genome-wide association studies (GWAS). The inverse variance weighted method was utilized as the primary method to estimate causal effects, followed by various sensitivity analyses. Multivariable analyses were performed to further adjust for potential confounders., Results: The present MR study revealed that genetically predicted FI was significantly and positively associated with the risk of major depressive disorder (MDD) (odds ratio [OR] 1.79, 95 % confidence interval [CI] 1.48-2.15, P = 1.06 × 10 -9 ), anxiety disorder (OR 1.61, 95 % CI 1.19-2.18, P = 0.002) and neuroticism (OR 1.38, 95 % CI 1.18-1.61, P = 3.73 × 10 -5 ). In the reverse MR test, genetic liability to MDD (beta 0.232, 95 % CI 0.189-0.274, P = 1.00 × 10 -26 ) and neuroticism (beta 0.128, 95 % CI 0.081-0.175, P = 8.61 × 10 -8 ) were significantly associated with higher FI. Multivariable analyses results supported the causal association between FI and MDD and neuroticism., Limitations: Restriction to European populations, and sample selection bias., Conclusions: Our study suggested a bidirectional causal association between frailty and MDD neuroticism, and a positive correlation of genetically predicted frailty on the risk of anxiety disorder. Developing a deeper understanding of these associations is essential to effectively manage frailty and optimize mental health in older adults., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The spillover impact from disrupted healthcare services for non-COVID-infected diabetes mellitus (DM) patients caused by the reshuffling of the manpower during the pandemic remains understudied, especially in Hong Kong where healthcare resources were already strained before the pandemic., Aim: To evaluate the spill-over effect of the Pandemic on Hong Kong diabetes patients, we examined the change in all-cause mortality and the incidence of cardiovascular disease (CVD) from 2012 to 2021., Method: This retrospective cohort study analyzed data from Hong Kong Hospital Authority healthcare records covering all publicly provided care. Adults diagnosed with DM on/before December 31, 2010, without CVD before January 2012 were included. The 2016-2019 average all-cause mortality and the incidence of CVD after age-standardization represented the pre-pandemic levels. Subjects would leave the cohort after being infected with COVID-19., Results: A cohort of 159,693 patients with diabetes was identified and followed up for 10 years from January 2012 to December 2021. Compared to the pre-pandemic levels, 2020 saw a 12% increase in age-standardized mortality per 10,000 diabetic patients (incidence rate ratio [95% CI]: 1.12 [1.10 - 1.14]), but no significant change in age-standardized CVD incidence. However, in 2021, there were 11% (1.11[1.10 - 1.13]) and 13% (1.13 [1.11 - 1.15]) more new CVD cases and deaths, respectively, versus the pre-pandemic period., Conclusion: The COVID-19 outbreak in 2020 had negative spillover impacts on DM patients without COVID-19 in Hong Kong, with a higher mortality in 2020 and 2021 compared with the pre-pandemic level., (© British Journal of General Practice 2024.)

Background: Older adults with multimorbidity are at high risk of mortality following COVID-19 hospitalisation. However, the potential benefit of timely primary care follow-up on severe outcomes post-COVID-19 has not been well established., Aim: To examine the effectiveness of attending general outpatient within 30 days after discharge from COVID-19 on 1-year survival among older adults aged ≥85 years, with multimorbidity., Method: We emulated a target trial using a comprehensive public healthcare database in Hong Kong. The cloning-censoring-weighting technique was used to minimise immortal time bias and confounding bias by adjusting for demographics, hospitalisation duration and ICU admission, baseline chronic conditions, and medication history. The outcome included all-cause and cause-specific mortality., Results: Of 6183 eligible COVID-19 survivors, the all-cause mortality rate following COVID-19 hospitalisation was lower in general out-patient clinics (GOPC) group compared to non-GOPC group (17.1 versus 42.8 deaths per 100 person-year). After adjustment, primary care consultations within 30 days after discharge were associated with a significantly greater 1-year survival (difference in 1-year survival: 11.2%, 95% CI = 8.1% to 14.4%). We also observed better survival from respiratory diseases in the GOPC group. In a sensitivity analysis for different grace period lengths, we found that the earlier participants had a GOPC visit after COVID-19 discharge, the better the survival., Conclusion: Timely primary care consultations after discharge may improve survival following COVID-19 hospitalisation among older adults aged ≥85 years, with multimorbidity. Expanding primary care services and implementing follow-up mechanisms are crucial to support this vulnerable population's recovery and well-being., (© British Journal of General Practice 2024.)

Background: Recent studies had provided evidence that the gut microbiota is associated with sepsis. However, the potential causal relationship remained unclear., Methods: The present study aimed to explore the causal effects between gut microbiota and sepsis by performing Mendelian randomization (MR) analysis utilizing publicly accessible genome-wide association study (GWAS) summary-level data. Gut microbiota GWAS ( N = 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for sepsis were gained from the UK Biobank (sepsis, 10,154 cases; 452,764 controls). Two strategies were used to select genetic variants, i.e., single nucleotide polymorphisms (SNPs) below the locus-wide significance level (1 × 10 -5 ) and the genome-wide statistical significance threshold (5 × 10 -8 ) were chosen as instrumental variables (IVs). The inverse variance weighted (IVW) was used as the primary method for MR study, supplemented by a series of other methods. Additionally, a set of sensitivity analysis methods, including the MR-Egger intercept test, Mendelian randomized polymorphism residual and outlier (MR-PRESSO) test, Cochran's Q test, and leave-one-out test, were carried out to assess the robustness of our findings., Results: Our study suggested that increased abundance of Deltaproteobacteria, Desulfovibrionales, Catenibacterium , and Hungatella were negatively associated with sepsis risk, while Clostridiaceae1, Alloprevotella, LachnospiraceaeND3007group , and Terrisporobacter were positively correlated with the risk of sepsis. Sensitivity analysis revealed no evidence of heterogeneity and pleiotropy., Conclusion: This study firstly found suggestive evidence of beneficial or detrimental causal associations of gut microbiota on sepsis risk by applying MR approach, which may provide valuable insights into the pathogenesis of microbiota-mediated sepsis and strategies for sepsis prevention and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Zeng, Zhao, Tang, Lei, Wan, Deng and Liu.)

An increasing number of studies have shown that USP9X is closely related to cancer. However, its role in carcinogenesis and progression of laryngeal cancer has not yet been investigated. In this study, we found that USP9X was upregulated in laryngeal cancer tissues. The expression of USP9X was significantly correlated with degree of laryngeal cancer differentiation and lymphatic metastasis. USP9X knockdown led to a decrease in the ability of proliferation, migration, and invasion of FaDu cells. The proportion of FaDu apoptotic cells increased by interfering with the endogenous expression of USP9X. We speculated that inhibiting USP9X might induce apoptosis in FaDu cells by downregulating Mcl-1 and upregulating Bax protein expression. Our findings for the first time suggest the expression level and trend of USP9X in laryngeal cancer tissue and USP9X may plays an important role in promoting the occurrence and progression of laryngeal cancer. USP9X may be a potential target for intervention in treatment of laryngeal cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Losses of organic matter in agricultural watersheds result in eutrophication and land degra-dation, which not only threaten water quality and food security, but also lead to environmental problems such as the greenhouse gases emission. We used 13 C, 15 N and C/N as fingerprint markers to trace the sources of sedimentary organic matter at the outlet in the Nanyue small watershed. We analyzed the spatial distribution in watershed sedimentary organic matter and soils of typical land use types, including forest, paddy field, and vegetable fields. The Bayesian stable isotope mixing model was used to quantitatively estimate the contribution of different sources. The results showed that there was significant spatial variation of δ 13 C. The δ 13 C of sediment organic matter (-22.6‰±0.53‰) and forest soil (-23.13‰±1.71‰) was significantly higher than that of paddy soil (-25.24‰±1.4‰). The differences of δ 15 N among the sources were not significant, with sediment having the maximum (4.37±0.83)‰ and forest soil having the minimum (2.38±1.97)‰. Forest soil had the highest C/N of 16.66±7.18, while paddy soil had the lowest C/N of 11.95±0.92. The results of the Bayesian stable isotope mixture model showed that the contribution rates of forest land, paddy fields and vegetable fields to the organic matter deposited at the outlet in the watershed were 19.6%, 15.7%, and 64.7%, respectively. Paddy filed and vegetable field had a combined contribution rate of 80.4%. It was concluded that, soils of agricultural land were the main sources of organic matter deposited in the Nanyue small watershed, and that nutrient loss in the watershed would be effectively controlled by optimizing farmland management.

Objective: Acute myocardial infarction (AMI) is a common acute cardiovascular crisis. Although the diagnosis and treatment of AMI are constantly improving, the mortality of AMI is still very high, and its pathogenesis is still unclear. This article focuses on the role of microRNA-431 (miR-431) in regulating myocardial apoptosis after myocardial infarction (MI) and its potential molecular mechanism., Materials and Methods: We constructed cell models and animal models of MI. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) was used to detect miR-431 expression in myocardium after MI. Western blot, cell counting kit-8 (CCK-8) assay, flow cytometry and terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling (TUNEL) staining were performed to detect myocardial apoptosis; pathological sections of myocardium, serum lactate dehydrogenase (LDH) levels and Caspase-3 activity in myocardium were employed to evaluate myocardial injury of MI rats; echocardiography was utilized to assess cardiac function of rats., Results: We revealed that miR-431 expression was decreased in H2O2-treated H9c2 cells and myocardium of MI rats. The expression of Cleaved Caspase-3 (C-Caspase-3) in H9c2 cells treated with H2O2 was significantly increased, the cell viability was dramatically decreased, the apoptosis rate and the percentage of TUNEL positive cells were notably increased, but up-regulation of miR-431 could reverse these effects. At the same time, compared with the sham group, serum LDH levels were observably increased, myocardial Caspase-3 activity was also increased, and cardiac function was greatly reduced, while overexpression of miR-431 could reduce myocardial injury and improve cardiac function of MI rats. Through the Luciferase reporter gene experiment, we found that miR-431 could directly target HIPK3., Conclusions: In summary, overexpression of miR-431 can inhibit apoptosis after myocardial infarction via targeting HIPK3, thereby reducing myocardial injury and improving cardiac function in MI rats.

Effects of elevated atmospheric CO 2 concentration and temperature on rice dry matter accumulation vary in planting regions and cropping systems. It remains unclear how dry matter productivity responds to factorial combination of elevated CO 2 and temperature in the double rice cropping system of China. Field experiments were conducted using open-top chambers (OTC) to simulate different scenarios of elevated CO 2 and/or temperature for three rotations of double rice in Jingzhou, Hubei Province. Liangyou 287 and Xiangfengyou 9 were used as rice cultivar for early rice and late rice, respectively. There were five treatments: UC, paddy field without OTC covering; CK, OTC with the similar temperature and CO 2 concentration to field environment; ET, OTC with 2 ℃ temperature elevation; EC, OTC with 60 μmol·mol -1 CO 2 elevation; ETEC, OTC with simu-ltaneous 2 ℃ temperature elevation and 60 μmol·mol -1 CO 2 elevation. We measured aboveground biomass, leaf area index (LAI) and net assimilation rate (NAR) of dry matter under different treatments. Our results showed that elevated CO 2 and/or temperature had no significant effects on NAR from transplanting to jointing, increased NAR from jointing to heading, but decreased NAR from heading to maturity (except for EC treatment in early rice). Elevated CO 2 and/or temperature promoted leaf area development at all growth stages, with ETEC showing the highest increase in LAI except at maturity. Warming and CO 2 enrichment jointly promoted dry matter accumulation at heading, with ETEC increasing aboveground biomass by 10.3%-39.8% and 23.6%-34.4% compared with CK in early rice and late rice, respectively. At maturity of early rice, elevated temperature partly offset the positive effects of elevated CO 2 on aboveground biomass, as shown by a reduction of 3.2%-14.1% under ETEC compared with EC. Contrarily at maturity of late rice, co-elevation of CO 2 and temperature further increased aboveground biomass, showing a synergistic interaction. Results from regression analysis showed that warming and CO 2 enrichment had positive effects on NAR at vegetative stages of double rice, while warming showed negative effects on NAR at reproductive stages. Considering the dissimilarities in growth characteristics, growing periods and ambient temperature, elevated CO 2 and temperature might increase dry matter production in the Chinese double rice cropping system.

Background: Liver cancer has a high mortality and morbidity rate throughout the world. In clinical practice, the prognosis of liver cancer patients is poor, and the complex reasons contribute to treatment failures, including fibrosis, hepatitis viral infection, drug resistance and metastasis. Thus, screening novel prognostic biomarkers is of great importance for guiding liver cancer therapy. Orosomucoid genes ( ORMs ) encode acute phase plasma proteins, including orosomucoid 1 (ORM1) and ORM2. Previous studies showed their upregulation upon inflammation, but the specific function of ORMs has not yet been determined, especially in the development of liver cancer., Aim: To determine the expression of ORMs and their potential function in liver cancer., Methods: Analysis of the expression of ORMs in different human tissues was performed on data from the HPA RNA-seq normal tissues project. The expression ratio of ORMs was determined using the HCCDB database, including the ratio between liver cancer and other cancers, normal liver and other normal tissues, liver cancer and adjacent normal liver tissues. Analysis of ORM expression in different cancer types was performed using The Cancer Genome Atlas and TIMER database. The expression of ORMs in liver tumor tissues and adjacent normal tissues were further confirmed using Gene Expression Omnibus data, including GSE36376 and GSE14520. The 10-year overall survival (OS), progression-free survival (PFS) and relapse-free survival (RFS) rates between high and low ORM expression groups in liver cancer patients were determined using the Kaplan-Meier plotter tool. Gene Set Enrichment Analysis (GSEA) was employed to explore the ORM2-associated signaling network. Correlations between ORM2 expression and tumor purity or the infiltration level of macrophages in liver tumor tissues were determined using the TIMER database. The correlation between ORM2 gene levels, tumor-associated macrophage (TAM) markers (including CD68 and TGFβ1) and T cell immunosuppression (including CTLA4 and PD-1) in liver tumor tissues and liver GTEx was determined using the GEPIA database., Results: ORM1 and ORM2 were highly expressed in normal liver and liver tumor tissues. ORM1 and ORM2 expression was significantly decreased in liver tumor tissues compared with adjacent normal tissues, and similar results were also noted in cholangiocarcinoma, esophageal carcinoma, and lung squamous cell carcinoma. Further analysis of the Gene Expression Omnibus Database also confirmed the downregulation of ORM1 and ORM2 in liver tumors. Survival analysis showed that the high ORM2 group had better survival rates in OS, PFS and RFS. ORM1 only represented better performance in PFS, but not in OS or RFS. GSEA analysis of ORM2 from The Cancer Genome Atlas liver cancer data identified that ORM2 positively associated with the G2/M checkpoint, E2F target signaling, as well as Wnt/β-catenin and Hedgehog signaling. Moreover, apoptosis, IFN-α responses, IFN-γ responses and humoral immune responses were upregulated in the ORM2 high group. ORM2 expression was negatively correlated with the macrophage infiltration level, CD68, TGFβ1, CTLA4 and PD-1 levels., Conclusion: The results showed that ORM1 and ORM2 were highly expressed specifically in liver tissues, whereas ORM1 and ORM2 were downregulated in liver tumor tissues. ORM2 is a better prognostic factor for liver cancer. Furthermore, ORM2 is closely associated with cancer-promoting pathways., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Triploid and pentaploid breeding is of great importance in agricultural production, but it is not always easy to obtain double ploidy parents. However, in fishes, chromosome ploidy is diversiform, which may provide natural parental resources for triploid and pentaploid breeding. Both tetraploid and hexaploid exist in Schizothorax fishes, which were thought to belong to different subfamilies with tetraploid Percocypris fishes in morphology, but they are sister genera in molecule. Fortunately, the pentaploid hybrid fishes have been successfully obtained by hybridization of Schizothorax wangchiachii (♀, 2n = 6X = 148) × Percocypris pingi (♂, 2n = 4X = 98). To understand the genetic and morphological difference among the hybrid fishes and their parents, four methods were used in this study: morphology, karyotype, red blood cell (RBC) DNA content determination and inter-simple sequence repeat (ISSR). In morphology, the hybrid fishes were steady, and between their parents with no obvious preference. The chromosome numbers of P. pingi have been reported as 2n = 4X = 98. In this study, the karyotype of S. wangchiachii was 2n = 6X = 148 = 36m + 34sm + 12st + 66t, while that the hybrid fishes was 2n = 5X = 123 = 39m + 28sm + 5st + 51t. Similarly, the RBC DNA content of the hybrid fishes was intermediate among their parents. In ISSR, the within-group genetic diversity of hybrid fishes was higher than that of their parents. Moreover, the genetic distance of hybrid fishes between P. pingi and S.wangchiachii was closely related to that of their parental ploidy, suggesting that parental genetic material stably coexisted in the hybrid fishes. This is the first report to show a stable pentaploid F1 hybrids produced by hybridization of a hexaploid and a tetraploid in aquaculture.

It has been shown that non-coding RNAs (ncRNAs) play an important regulatory role in pathophysiological processes involving inflammation. The vascular endothelial growth factor A ( VEGFA ) gene also participates in the inflammatory process. However, the relationships between ncRNAs and VEGFA are currently unclear. Here, this study was designed to determine the relationship between long non-coding RNA (lncRNA) H19, mircoRNA29b (miR-29b), and VEGFA in the development of diabetes mellitus (DM). We demonstrate that H19 is upregulated and miR-29b downregulated in individuals with DM and directly binds miR-29b. VEGFA is the target of miR-29b in the vascular endothelium of individuals with DM. We found that positive modulation of miR29b and inhibition of H19 and VEGFA significantly attenuates high glucose-induced endothelial inflammation and oxidative stress. We also found that the protein kinase B/endothelial nitric oxide synthase (AKT/eNOS) signal pathway in endothelial cells is activated through regulation of miR29b and H19 endogenous RNAs. We conclude that H19 suppression protects the endothelium against high glucose-induced inflammation and oxidative stress in endothelial cells by upregulation of miR-29b and downregulation of VEGFA through AKT/eNOS signal pathway activation. These results suggest a novel link between dysregulated ncRNA expression, inflammation, and the signaling pathway in the vascular endothelium of individuals with DM, indicating a promising strategy for preventing cardiovascular disease in such individuals., (Copyright © 2019 Cheng, Chen, Wan, Zhou, Wang and Zhu.)

In this work, we constructed a novel electrochemiluminescent (ECL) strategy based on sandwich immunoassay-induced target transformation assisted with catalyzed hairpin assembly (CHA) amplification for ultrasensitive bioassay with cysteine-rich protein 61 (CCN1) as a model. First, the target CCN1 could be equally transformed into the specific oligonucleotide (initiator I) labeled on the detection antibody based on the specific sandwich immunoassay. In addition, the initiator I triggered an efficient nonenzymatic CHA amplification in the presence of ferrocene-labeled hairpin 1 (Fc-H1) and hairpin 2 (H2) to produce massive hybrids (Fc-H1-H2) containing a sticky end labeled with ferrocene. Finally, Fc-H1-H2 could be immobilized on the capture probe single-stranded DNA (ssDNA)-modified electrode through the hybridization between the sticky end of Fc-H1-H2 and ssDNA, and a significantly quenched ECL signal could be obtained due to the efficient quench effect between ferrocene and the ECL indicator, ruthenium(II) tris(4,4'-dicarboxylicacid-2,2'-bipyridyl) [Ru(dcbpy) 3 2+ ], immobilized on the surface of the electrode, which was related to the concentration of target CCN1. As expected, the proposed ECL biosensor exhibited a relatively low detection limit of 3.9 fg/mL in a linear range from 10 fg/mL to 100 ng/mL. This ECL strategy inspired the clinical examination of the biomarker CCN1, providing potential application in early diagnosis and malignant monitoring of cancer.

Rotator cuff tear is a common disease that causes shoulder pain and limitation of activity. Rotator cuff repair with arthroscope has become the mainstream method with advance in surgical techniques. In spite of this, the highly rate of retear after surgery mainly because the tendon to bone interface form scar tissue rather than native tissue. Biomechanical of the interface is so poor to retear because of the change of Histological. In recent years, more and more researchers are devoted to the study of biology and biomechanical for improving the process of tendon to bone healing and restoring the original structure at the interface, This article reviews the research progress with four factors(inflammation, slow or limited bone ingrowth into the tendon graft, Mechanical stimulation, scant stem cell) and physiotherapy that affect tendon to bone healing., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.)

The nitrogen (N) pollution of water is a common global problem. To understand the key production process of N 2 O and identify the dominant N sources, Tuojia River, a typical agricultural watershed in a subtropical area, was investigated. To analyze the characteristics of dual nitrate isotopes (δ 15 N-NO 3 - ,δ 18 O-NO 3 - ) in water, and N isotope (δ 15 N org ) and carbon-nitrogen ratio (C/N) in sediment organic matter from four reaches(S1-S4), the stable isotopes method was used. The results showed that the sources of nitrate varied significantly among river segments and were affected by agricultural production and human habitation on the land surface. The average δ 15 N-NO 3 - in reaches S1, S2, S3, and S4 were 1.72‰, 2.62‰, 4.10‰, and -1.28‰, respectively, while the average δ 18 O-NO 3 - were 2.60‰,-0.06‰, 0.85‰, and -0.62‰. The N in terrestrial soil made a large contribution to nitrate sources in reach S1, while soil N, ammonium N fertilizer, and manure played a main role in reaches S2 and S3. Most of the nitrate came from ammonium N fertilizer in reach S4. We also found that δ 15 N org in sediment organic matter ranged from -0.69‰ to 11.21‰, and C/N was between 7.30 and 12.02. The mean δ 15 N org in reaches S1-S4 were 1.91‰, 2.96‰, 4.72‰, and 3.23‰, respectively, and the mean C/N values were 10.62, 8.63, 9.05, and 9.22, respectively. Although there were some differences in δ 15 N org among reaches S2-S4, the dominant N source was sewage in those reaches. However, soil organic matter was the main N source in the sediments of reach S1. The mean δ 18 O-NO 3 - in reaches S1-S4 were -7.01‰,-0.17‰,-0.28‰, and -0.60‰, respectively, indicating that nitrification was the key N 2 O production process in these reaches. The ratios of δ 15 N-NO 3 - and δ 18 O-NO 3 - were 0.66,-41.01,-30.23, and 9.39 in reaches S1-S4, respectively. Finally, we found that there was a positive correlation between NO 3 - -N and δ 15 N-NO 3 - . To summarize, the N transformation and N 2 O production could be dominated by the nitrification process in Tuojia River.

It was demonstrated in previous studies that cysteine-rich angiogenic inducer 61 (Cyr61) plays vital roles in hematological disorders, and we have already reported that the Cyr61 protein is a tumor promoter in acute myeloid leukemia (AML). Here, we investigated the association between CYR61 gene polymorphisms and susceptibility to AML.We genotyped 2 single-nucleotide polymorphisms (rs2297141 and rs6576776) in the region of the CYR61 gene by improved multiplex ligase detection reaction genotyping assays in a total of 275 samples, including samples from 137 AML patients and 138 healthy controls. Chi-squared tests and logistic regression analysis were performed to compare the different distributions of the genotypes and alleles between patients and healthy controls.The rs2297141 A allele was associated with lower risk of AML compared with the G allele (odds ratio [OR] = 0.704, 95% confidence interval [CI] = 0.503-0.985, P = .04) in both the dominant (OR = 0.447, 95% CI = 0.22-0.909, P = .025, AA vs GG) and recessive inheritance models (OR = 0.419, 95% CI = 0.23-0.763, P = .004, AA vs GA + GG). Although the distribution of the rs6576776 alleles was not different between patients with AML and normal controls, the CC genotype significantly increased the risk of AML in the dominant inheritance model (OR = 6.064, 95% CI = 1.303-28.216, P = .01, CC vs GG) and the recessive inheritance model (OR = 5.937, 95% CI = 1.291-27.306, P = .01, CC vs GC + GG). Additionally, it was shown that the rs2297141 and rs6576776 genotypes were associated with AML-M5 and AML-M2, respectively.Our findings indicated that genetic polymorphisms in the CYR61 gene may be considered potential AML risk factors in the Han Chinese population.

The aim of this study was to investigate in vitro effects of fenitrothion (FNT) on mouse splenic lymphocytes. Here, naïve mice had their spleens harvested and splenocytes isolated. After exposure to FNT for 48 hr: splenocyte viability was measured using a tetrazolium dye assay; cell phenotypes, i.e., B-cells (CD19 + ), T-cells (CD3 + ), and T-cell subsets (CD4 + and CD8 + ), were quantified by flow cytometry; and, production of cytokines/granzyme-B was assessed via enzyme-linked immunosorbent assay. The ability for FNT to induce oxidative stress in the cells was evaluated by measuring hydroxyl radical (·OH) and malondialdehyde (MDA) production and changes in glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activity. The results showed that FNT significantly inhibited splenocyte proliferation, and decreased production of interleukin (IL)-2, interferon gamma, IL-4, and granzyme B, but had no impact on IL-6 production. FNT also selectively decreased splenic T-cell levels but did not induce changes in CD19 + B-cells. Further, within the T-cell populations, percentages of CD3 + , CD4 + , and CD8 + T-cells (particularly CD8 + T-cells) were reduced. Lastly, FNT selectively increased MDA and ·OH production and inhibited SOD and GSH-Px activities in the splenic lymphocytes. These findings suggest that, due to oxidative damage, FNT selectively inhibits splenic T-lymphocyte survival and cytokine/granzyme production in vitro.

This study aimed at exploring the key pathway of methane production and clarifying the composition and distribution of carbon (C) isotopes in the Tuojia River waterbody in Hunan Pro-vince. We estimated CH 4 concentrations and fluxes of four reaches (S 1 , S 2 , S 3 and S 4 ) by a two-layer diffusion model and gas chromatography. The spatial and temporal distribution of CH 4 flux and its relationship with environmental factors were examined. The key pathway of CH 4 production was investigated by stable C isotope method to analyze the distribution characteristics of 13 C isotope (δ 13 C) of water dissolved CH 4 and seston/benthic organic matter. There was significant seasonal variability in water pH, with mean value of (7.27±0.03). The concentration of dissolved oxygen (DO) showed strong seasonal and spatial variations, with the range of 0.43-13.99 mg·L -1 . The maximum value of DO occurred in S 1 and differed significantly in summer and autumin. In addition, DO differed significantly in winter and other seasons in S 2 , S 3 and S 4 . The concentration of dissolved organic carbon (DOC) showed a gradual increasing trend from source to estuary. The highest concentration of DOC (8.32 mg·L -1 ) was found in S 2 , while the lowest was observed in S 1 (0.34 mg·L -1 ). The electrical conductivity (EC) and oxidation-reduction potential (ORP) of water ranged from 17 to 436 μS·cm -1 and from -52.30 to 674.10 mV, respectively, which were significantly different among the four reaches (P＜0.05). Water ammonium nitrogen (NH 4 + -N) and nitrate nitrogen (NO 3 - -N) concentrations were in the ranges of 0.30-1.35 (averaged 0.90±0.10) mg·L -1 and 0.82-2.45 (averaged 1.62±0.16) mg·L -1 , respectively. The dissolved concentration and diffusion flux of CH 4 ranged from 0 to 5.28 μmol·L -1 and from -0.34 to 619.72 μg C·m -2 ·h -1 , respectively, with significant temporal and spatial variations. They showed a similar trend among reaches. Their values were highest in spring, followed by in winter and lowest in summer and autumn. Spatially, the CH 4 concentration and flux followed the order of S 2 >S 3 >S 4 >S 1 . The correlation analysis showed that CH 4 flux was positively correlated with NH 4 + -N and DOC. The pathway of CH 4 production of all reaches was dominated by acetic acid fermentation, while there were obvious differences among the four reaches. The contribution of CH 4 from acetic acid fermentation was greatest (87%) in S 1 , followed by S 4 (81%), S 2 (78%) and S 3 (76%). The mean value of the δ 13 C for dissolved CH 4 , seston organic matter and benthic organic matter was -41.64‰±1.91‰, -14.07‰±1.06‰ and -26.20‰±1.02‰, respectively. There was a positive correlation between the δ 13 C of dissolved CH 4 and benthic organic matter, whereas the δ 13 C value of dissolved CH 4 was negatively correlated with CH 4 flux.

The increased atmospheric temperatures resulting from the increased concentration of atmospheric carbon dioxide (CO2) have had a profound influence on global rice production. China serves as an important area for producing and consuming rice. Therefore, exploring the effects of the simultaneously rising levels of atmospheric CO2 and temperatures on rice growth and quality in the future is very important. The present study was designed to measure the most important aspects of variation for rice-related physiological, ecological and quality indices in different growing periods under a simultaneous increase of CO2 and temperature, through simulation experiments in climate-controlled growth chambers, with southern rice as the study object. The results indicated that the ecological indices, rice phenology, and leaf area would decrease under a simultaneous increase of CO2 and temperature. For the physiological indices, Malondialdehyde (MDA) levels increased significantly in the seedling period. However, it showed the trend of increase and subsequent decrease in the heading and filling periods. In addition, the decomposition of soluble protein (SP) and soluble sugar (SS) accelerated in filling period. The rice quality index of the Head Rice Rate showed the decreasing trend and subsequent increase, but the Chalky Rice Rate and Protein Content indices gradually decreased while the Gel Consistency gradually increased.

Endothelial dysfunction and apoptosis have key roles in the initiation and progression of atherosclerosis (AS). AS has been demonstrated to be associated with a high‑fat diet, which may increase endothelial permeability and apoptosis; however, the exact mechanisms underlying the development of AS remain poorly understood. MicroRNAs (miRNAs) are vital for the regulation of cardiovascular disease, and dysregulated miRNAs have been implicated in AS. The present study investigated whether miRNA (miR)‑126 regulates high‑fat diet‑induced endothelial permeability and apoptosis by targeting transforming growth factor β (TGFβ), a secreted protein that controls cellular proliferation and apoptosis. In the present study, apolipoprotein E (apoE)‑/‑ mice were fed a high‑fat diet in order to establish a model of AS. Mice were subcutaneously injected with a miR‑126 mimic, a miR‑126 antagomir or control miRNA. Reverse transcription‑quantitative polymerase chain reaction was used to assess miR‑126 expression, and a fluorometric assay was used to evaluate caspase‑3 activity. The effects of miR‑126 on the endothelial permeability of the aortic intima were also explored. Western blotting and immunohistochemical analysis were used to investigate the effects of miR‑126 on B‑cell lymphoma‑2 (Bcl‑2) and transforming growth factor (TGF) β protein expression levels. Furthermore, a luciferase assay was performed to verify whether TGFβ may be a direct target gene of miR‑126. In apolipoprotein E‑knockout mice, a high‑fat diet reduced miR‑126 expression and induced apoptosis as determined by the upregulation of caspase‑3 activity. A miR‑126 antagomir increased endothelial permeability and apoptosis in mice fed a high‑fat diet. By contrast, an miR‑126 mimic attenuated endothelial permeability and apoptosis. The reduction in miR‑126 was associated with a reduction in protein expression levels of Bcl‑2 and an increase of TGFβ in mice fed a high‑fat diet. In addition, the present study demonstrated that miR‑126 reduced TGFβ expression following binding to the 3'‑untranslated region of TGFβ mRNA. The current study demonstrated a role for miR‑126 in AS and identified TGFβ as a direct target of miR‑126. Furthermore, the present study demonstrated that miR‑126 contributed to endothelial permeability and apoptosis, and suggested that the downregulation of TGFβ may be involved in the molecular mechanisms underlying the actions of miR‑126. miR‑126 may therefore have potential as a novel therapeutic target for the treatment of AS.

Valproic acid (VPA) has been suggested to be a histone deacetylase inhibitor (HDACI). Our present study revealed that VPA at 1 mm, which had no effect on cell proliferation, can significantly increase the sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin (DDP). VPA treatment markedly decreased the mRNA and protein levels of ABCA1, while had no significant effect on ABCA3, ABCA7 or ABCB10. Luciferase reporter assays showed that VPA can decrease the ABCA1 promoter activity in both A549 and H358 cells. VPA treatment also decreased the phosphorylation of SP1, which can bind to -100 and -166 bp in the promoter of ABCA1. While the phosphorylation of c-Fos and c-Jun were not changed in VPA treated NSCLC cells. Over expression of HDAC2 attenuated VPA induced down regulation of ABCA1 mRNA expression and promoter activities. Over expression of HDAC2 also attenuated VPA induced DDP sensitivity of NSCLC cells. These data revealed that VPA can increase the DDP sensitivity of NSCLC cells via down regulation of ABCA1 through HDAC2/SP1 signals. It suggested that combination of VPA and anticancer drugs such as DDP might be great helpful for treatment of NSCLC patients.

Background: Recent studies have verified that long noncoding RNAs (lncRNAs) involved in many biological functions and play crucial roles in human cancers progression, the study aimed to detect the association between long non-coding RNA HOXA11-AS and epithelial-mesenchymal transition (EMT) process in non-small cell lung cancer (NSCLC)., Methods: The lncRNA HOXA11-AS expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) assays in 78 paired of tumor tissue and adjacent normal tissue samples in NSCLC patients. Kaplan-Meier survival curves and log-rank test was used to examine the association between lncRNA HOXA11-AS expression and the over survival time in NSCLC patients. Transwell invasion assay was performed to detect the cell invasion ability. QRT-PCR and western-blot analysis detected the mRNA and protein expression of EMT related transcription factors ZEB1/ZEB2, Snail1/2 and EMT marker E-cadherin and N-cadherin in NSCLC cells. RIP and Chromatin immunoprecipitation assays were performed to analyze the association between lncRNA HOXA11-AS and miR-200b expression in NSCLC cells., Results: The lncRNA HOXA11-AS expression levels were significantly higher in NSCLC tissues compared with adjacent normal tissues and higher HOXA11-AS expression levels had a poor prognosis in NSCLC patients. Furthermore, knockdown of lncRNA HOXA11-AS in A549 and H1299 cells dramatically inhibited cell invasive abilities. Besides, the transcription levels and protein levels of EMT related transcription factors ZEB1/ZEB2, Snail1/2, and EMT maker N-cadherin were down-regulated after lncRNA HOXA11-AS was knocked down, but the mRNA and protein expression levels of EMT maker E-cadherin was increasing in A549 and H1299 cells. The mechanistic findings showed demonstrated that HOXA11-AS interacted with EZH2 and DNMT1 and recruited them to the miR-200b promoter regions to repress miR-200b expression in NSCLC cells, which promoted cell EMT in NSCLC., Conclusions: Our results showed that up-regulation of lncRNA HOXA11-AS predicted a poor prognosis and lncRNA HOXA11-AS promoted cell epithelial-mesenchymal transition (EMT) by inhibiting miR-200b expression in NSCLC.

Aim: To evaluate the effectiveness of the multidisciplinary Risk Assessment and Management Program for Patients with Diabetes Mellitus (RAMP-DM) in reducing the risks of microvascular complications., Methods: This prospective cohort study was conducted with 29,670 propensity-score-matched RAMP-DM participants and diabetes patients under the usual primary care (14,835 in each group). Study endpoints were the first occurrence of any diabetic microvascular complications, non-proliferative diabetic retinopathy/preproliferative diabetic retinopathy (NPDR/prePDR), sight-threatening diabetic retinopathy (STDR) or blindness, nephropathy, end-stage renal disease (ESRD), neuropathy and lower-limb ulcers or amputation. Log-rank tests and multivariable Cox proportional-hazards regressions were employed to estimate between-group differences in incidences of study endpoints., Results: After a median follow-up of 36 months with>41,000 person-years in each group, RAMP-DM participants had a lower incidence of microvascular complications (760 vs 935; adjusted hazard ratio [HR]: 0.73; 95% confidence interval [CI]: 0.66-0.81; P<0.001) and lower incidences of all specific microvascular complications except neuropathy (adjusted HR: 0.94; 95% CI: 0.61-1.45; P=0.778). Adjusted HRs for the RAMP-DM vs control group for ESRD, STDR or blindness, and lower-limb ulcers or amputation were 0.40 (95% CI: 0.24-0.69; P<0.001), 0.55 (95% CI: 0.39-0.78; P=0.001) and 0.49 (95% CI: 0.30-0.80; P=0.005), respectively., Conclusion: The RAMP-DM intervention was associated with lower incidences of all microvascular complications except neuropathy over a 3-year follow-up. These encouraging results constitute evidence that structured risk assessment and risk-stratified management provided by a multidisciplinary team is effective for reducing microvascular complications in diabetes patients., Clinical Trial Registry: NCT02034695, www.ClinicalTrials.gov., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Obesity worsens asthma control partly through enhanced airway neutrophilia, altered lung mechanics and comorbidities, including obstructive sleep apnea syndrome, gastroesophageal reflux disease and depression. Although controversial, obesity may also cause poorer outcomes in acute asthma. IL-17 is associated with neutrophilic inflammation, steroid resistance and severe asthma, but its importance in the association between asthma and obesity is unknown., Objective: To investigate the role of IL-17 in obese asthma in both acute and stable settings., Methods: Both stable (n = 177) and acute (n = 78) asthmatics were recruited and categorized into lean (n = 77 and 39 respectively), overweight (n = 41 and 17 respectively) and obese (n = 59 and 22 respectively) groups and compared for clinical characteristics, including sputum and plasma IL-17 protein concentrations, sputum cellularity, spirometry and comorbidities. Correlations of IL-17 expression with other measures were explored., Results: In stable subjects, airway neutrophilia and IL-17 concentrations were most prominent in the obese, and correlated positively with each other. Significant increase in plasma IL-17 levels was also noted and associated with elevated depressive symptoms in obesity. In acute asthma, IL-17 expression, like most other clinical measures, was similar among lean, overweight and obese groups, but was higher in acute versus stable asthma subjects, with sputum IL-17 correlating positively with sputum neutrophils and negatively with FEV 1 and plasma IL-17 showing a positive connection to airway eosinophilia during exacerbation., Conclusions: IL-17 contributes to worse disease control in obese asthma through enhancing airway neutrophilia and depression, and may implicate in asthma exacerbations. Effects of adiposity on acute asthma remain uncertain., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aim: To assess whether a structured diabetes education programme, the Patient Empowerment Programme, was associated with a lower rate of all-cause hospitalization and emergency department visits in a population-based cohort of patients with Type 2 diabetes mellitus in primary care., Methods: A cohort of 24 250 patients was evaluated using a linked administrative database during 2009-2013. We selected 12 125 patients with Type 2 diabetes who had at least one Patient Empowerment Programme session attendance. Patients who did not participate in the Patient Empowerment Programme were matched one-to-one with patients who did, using the propensity score method. Hospitalization events and emergency department visits were the events of interest. Cox proportional hazard and negative binomial regressions were performed to estimate the hazard ratios for the initial event, and incidence rate ratios for the number of events., Results: During a median 30.5 months of follow-up, participants in the Patient Empowerment Programme had a lower incidence of an initial hospitalization event (22.1 vs 25.2%; hazard ratio 0.879; P < 0.001) and emergency department visit (40.5 vs 44%; hazard ratio 0.901; P < 0.001) than those who did not participate in the Patient Empowerment Programme. Participation in the Patient Empowerment Programme was associated with a significantly lower number of emergency department visits (incidence rate ratio 0.903; P < 0.001): 40.4 visits per 100 patients annually in those who did not participate in the Patient Empowerment Programme vs. 36.2 per 100 patients annually in those who did. There were significantly fewer hospitalization episodes (incidence rate ratio 0.854; P < 0.001): 20.0 hospitalizations per 100 patients annually in those who did not participate in the Patient Empowerment Programme vs. 16.9 hospitalizations per 100 patients annually in those who did., Conclusions: Among patients with Type 2 diabetes, the Patient Empowerment Programme was shown to be effective in delaying the initial hospitalization event and in reducing their frequency., (© 2015 Diabetes UK.)

Present study examined the influence of different types of slow/controlled release urea on rice yield and annual greenhouse gas emissions in a paddy field, and assessed the greenhouse gas intensity (GHGI, equivalent to global warming potential GWP/rice yield). The results indicated that the optimized fertilization (OPT) treatment recorded the similar yield with reduced nitrogen fertilizer (21.4%) supply compared with the farmers' fertilizer practice (FFP) treatment, and decreased the annual emissions of CH 4 (12.6%) and N 2 O (12.5%) during the rice season, and N 2 O emission (33.3%) during the fallow period. Application of controlled release urea (CRU) reduced CH 4 emission by 28.9% during the rice-growing season with respect to OPT treatment, and showed negligible CH 4 emission during the fallow season. However, nitrification inhibitor (DMPP) treatment was found to reduce the CH 4 emissions by 41.6% and 76.9%, and N 2 O emissions by 85.7% and 6.5%, during the rice growing season and fallow season, respectively, compared with OPT treatment. In the fallow season, the N 2 O emissions accounted for 76.8%-94.9% of annual N 2 O emissions, which was clearly a key point for evaluation of greenhouse gas emissions in paddy. The average values of GHGI in OPT, CRU and DMPP treatments were 0.50, 0.41 and 0.33 kg·kg -1 , respectively. Considering the benefits of higher rice yield and lower annual greenhouse gas emissions, combined application of urea and nitrification inhibitor could be the best combination in paddy fields.

Limited data are available with regard to the impact of daily lifestyle choices in patients with coronary heart disease (CHD) who have undergone stent placement. Thus, the aim of the present study was to investigate the impact of daily lifestyle factors in patients with CHD following stent implantation. Between March 2005 and March 2006, 129 consecutive patients with CHD were admitted to Cangzhou Central Hospital at Hebei Medical University (Cangzhou, China). The patients underwent coronary stenting and participated in a 7-year clinical follow-up that analyzed the impact of their daily lifestyle choices on CHD following the stent placement. Rates of dinner satiety [95% confidence interval (CI), 1.121-10.97, P=0.005], smoking (95% CI, 4.05-34.90, P=2.01×10 -7 ) and heavy alcohol use (95% CI, 1.32-11.05, P=0.006) were significantly higher in the repeated (re)-revascularization group when compared with the non-revascularization group. In addition, the exercise rate was significantly lower in the re-revascularization group when compared with the non-revascularization group (95% CI, 0.02-0.65, P=0.005). However, no statistically significant differences were observed between the groups with regard to sleeping patterns (95% CI, 0.03-0.71, P=0.270) or anxiety rates (P=0.289). A coronary angiography performed during re-revascularization revealed in-stent restenosis in 26% of the patients, stenoses at the entrance to or exit from the stent in 29% of the patients and new lesions in 19% of the patients. Furthermore, original lesions exhibited deterioration in 26% of the patients. The clinical endpoint was reached in 55% of the patients between 3 and 5 years of the follow-up period. In conclusion, poor daily lifestyle habits can increase the in-stent restenosis rate, accelerate the progression of the original lesion and promote the emergence of new lesions in patients with CHD following stent placement.

Background: Studies on the long-term effectiveness of multidisciplinary risk-stratification based management in Chinese population were rare. This study aimed to evaluate the effectiveness of a multidisciplinary risk assessment and management program for patients with diabetes mellitus (RAMP-DM) in reducing the risks of cardiovascular complications and all-cause mortality., Methods: A prospective cohort study was conducted in 18,188 propensity score matched RAMP-DM participants and subjects with diabetes under usual primary care (9,094 subjects in each group). The study endpoints were the first occurrence of coronary heart disease (CHD), stroke, heart failure (HF), total cardiovascular disease (CVD) and all-cause mortality. We constructed multivariable Cox proportional hazard regressions to estimate the association between the RAMP-DM intervention and the first occurrence of study endpoints., Results: The median follow-up period was 36 months. Three hundred and ninety-nine CVD events occurred in the RAMP-DM group, as compared with 608 in the control group [adjusted hazard ratio, 0.629; 95% confidence interval (CI) 0.554-0.715; P < 0.001]. The total number of all-cause deaths in RAMP-DM group was less than half that of control group (202 vs 552, adjusted hazard ratio, 0.363; 95% CI, 0.308-0.428; P < 0.001). The adjusted hazard ratios of the RAMP-DM group for CHD, stroke, and HF were 0.570 (95% CI, 0.470-0.691; P < 0.001), 0.652 (95% CI, 0.546-0.780; P < 0.001), and 0.598 (95%CI, 0.446-0.802; P = 0.001), respectively., Conclusions: The RAMP-DM intervention was associated with lower incidences of individual and total cardiovascular complications, as well as all-cause mortality over 3 years follow-up. The encouraging results provided evidence to support that the structured risk-stratification management leading by a multidisciplinary clinical team was an effective approach to reduce future cardiovascular complications in people with diabetes., Clinical Trial Registry: NCT02034695, http://www.ClinicalTrials.gov.

Aims: To assess whether a structured diabetes education programme, the Patient Empowerment Programme (PEP), was associated with a lower risk of first cardiovascular disease (CVD) event and all-cause mortality in a population-based cohort of patients with type 2 diabetes mellitus (T2DM) in primary care., Methods: A Chinese cohort of 27 278 patients with T2DM and without previous CVD events on or before the baseline study recruitment date was linked to the Hong Kong administrative database from 2008 to 2013. The PEP was provided to patients with T2DM treated at primary care outpatient clinics through community trained professional educators. PEP non-participants were matched one-to-one with the PEP participants using a propensity score method with respect to their baseline covariates. Cox proportional hazard regression was performed to estimate the associations of the PEP with the occurrence of first CVD event, coronary heart disease, stroke, heart failure and death from any cause, controlling for baseline characteristics., Results: During a median of 21.5 months follow-up, 795 (352 PEP participants and 443 PEP non-participants) patients experienced a first CVD event. After adjusting for confounding variables, PEP participants had a lower rate of all-cause mortality [hazard ratio (HR) 0.564, 95% confidence interval (CI) 0.445-0.715; p < 0.001], first CVD (HR 0.807, 95% CI 0.696-0.935; p = 0.004) and stroke (HR 0.702; 95% CI 0.569-0.867; p = 0.001) than those without PEP., Conclusions: Enrolment in the PEP was associated with lower all-cause mortality and a lower number of first CVD events among patients with T2DM. The CVD benefit of PEP might be attributable to improving metabolic control through empowerment of self-care and the enhancement of quality of diabetes care in primary care., (© 2014 John Wiley & Sons Ltd.)

Background: The objective of this observational study was to determine whether there is an association between extubation success and uric acid in chronic obstructive pulmonary disease patients with mechanical ventilation admitted to the intensive care units, and identify the risk markers for extubation success in COPD patients with mechanical ventilation., Methods: Consecutive COPD patients with intubation were screened at baseline. The study included patients on mechanical ventilation (MV) for over 12 hours and who, in the process of weaning, were subjected to low-level pressure support. Exclusion criteria were age under 18 years, ventilation via tracheotomy, and patients failing to cooperate for different reasons. The final study population consisted of 106 patients. Demographic, clinical, laboratory, and mechanical ventilation parameters were carefully recorded. Logistic regression was used for the multivariate analysis of independent risk factors., Results: Uric acid on admission, duration of mechanical ventilation, pressure support ventilation, and APACHE II score on admission were significantly higher in COPD patients with extubation failure than in those with extubation success (p < 0.05), but lower tidal volume before weaning was observed in COPD patients with extubation failure. Among these patients, multiple logistic analyses indicated the independent risk factors for extubation success in the COPD subjects included serum uric acid level, APACHE II score on admission, and duration of mechanical ventilation. The diagnosis analysis showed that higher uric acid level and APACHE II score on admission and longer duration of mechanical ventilation had a significant ability to reflect extubation success in the COPD patients with respiratory failure., Conclusions: The novel finding of this study is that the extubation failure in COPD patients with respiratory failure is strongly related to serum uric acid level, APACHE II score on admission, and duration of mechanical ventilation. These results might be helpful for selecting the best time to remove the tracheal intubation and improving extubation success rate in COPD patients with respiratory failure.

Introduction: The role of inflammation and immunity in COPD treatment is increasingly being recognized. The relationship between anti-inflammation/immunoregulation and emphysema in COPD lungs remains to be elucidated. The aim of this study was to investigate the effects of azithromycin (Azm) on the development of emphysema in smoking-induced COPD in rats., Methods: Sprague-Dawley rats (n = 50) were randomly assigned to normal, COPD, saline-treated, Azm-treated, and levofloxacin-treated (Lev) groups. The effects of treatment were assessed by measuring the levels of vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay and measuring the numbers of neutrophil and macrophage in bronchoalveolar lavage fluid, vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR2) protein expression by western blotting. Lung function measurements and histopathological evaluations (mean linear intercept and destructive index) were performed., Results: FEV0.3/FVC and peak expiratory flow were lower in the COPD group than in the normal group. Mean linear intercept and destructive index were lower in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. The numbers of neutrophil and macrophage in bronchoalveolar lavage fluid were lower in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. As confirmed by western blotting, the levels of VEGF in lung homogenates were higher in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. VEGFR2 protein expression was higher in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups., Conclusions: Azm attenuates pulmonary emphysema by partly reversing the decrease in the numbers of inflammatory cells (neutrophil and macrophage) and VEGF secretion and VEGFR2 protein expression in smoking-induced COPD in rats., (Copyright © 2015 by Daedalus Enterprises.)

Background: To assess whether the Multidisciplinary Risk Assessment and Management Program for Patients with Diabetes Mellitus (RAMP-DM) led to improvements in biomedical outcomes, observed cardiovascular events and predicted cardiovascular risks after 12-month intervention in the primary care setting., Methods: A random sample of 1,248 people with diabetes enrolled to RAMP-DM for at least 12 months was selected and 1,248 people with diabetes under the usual primary care were matched by age, sex, and HbA1c level at baseline as the usual care group. Biomedical and cardiovascular outcomes were measured at baseline and at 12-month after the enrollment. Difference-in-differences approach was employed to measure the effect of RAMP-DM on the changes in biomedical outcomes, proportion of subjects reaching treatment targets, observed and predicted cardiovascular risks., Results: Compared to the usual care group, RAMP-DM group had lower cardiovascular events incidence (1.21% vs 2.89%, P = 0.003), and net decrease in HbA1c (-0.20%, P < 0.01), SBP (-3.62 mmHg, P < 0.01) and 10-year cardiovascular disease (CVD) risks (total CVD risk, -2.06%, P < 0.01; coronary heart disease (CHD) risk, -1.43%, P < 0.01; stroke risk, -0.71%, P < 0.01). The RAMP-DM subjects witnessed significant rises in the proportion of reaching treatment targets of HbA1c, and SBP/DBP. After adjusting for confounding variables, the significance remained for HbA1c, predicted CHD and stroke risks., Conclusions: The RAMP-DM resulted in greater improvements in HbA1c and reduction in observed and predicted cardiovascular risks at 12 months follow-up, which indicated a risk-stratification multidisciplinary intervention was an effective strategy for managing Chinese people with diabetes in the primary care setting., Trial Registry: ClinicalTrials.gov, NCT02034695.

KIF22 is a microtubule-dependent molecular motor protein with DNA-binding capacity. It is well known that KIF22 plays a critical role in cell mitosis as a motor protein; however, the role of altered KIF22 expression and its transcriptional regulatory function in cancer development have not yet been defined. This study showed that KIF22 was overexpressed in human cancer tissues, and inhibition of KIF22 significantly led to accumulation of cells in the G2/M phases, resulting in suppression of cancer cell proliferation. The investigation of the molecular mechanisms demonstrated that cell division cycle 25C (CDC25C) is a direct transcriptional target of KIF22, and inhibition of KIF22 increased CDC25C expression and cyclin-dependent kinase 1 (CDK1) activity, resulting in delayed mitotic exit. Phosphorylation of KIF22 was required for its transcriptional regulatory function and the reduction of CDK1 activity. Thus, we conclude that inhibition of KIF22 suppresses cancer cell proliferation by delaying mitotic exit through the transcriptional upregulation of CDC25C., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The study aimed to examine the association between health-related quality of life (HRQOL) assessed with overall survival (OS) and recurrence after diagnosis of colorectal cancer (CRC)., Methods: Overall 160 patients with advanced stage CRC were recruited in an observational study and completed the generic and condition-specific HRQOL questionnaires at the colorectal specialist outpatient clinic in Hong Kong, between 10/2009 and 07/2010. Socio-demographic and clinical characteristics including duration since diagnosis, primary tumor location and treatment modality, were collected to serve as predictor variables in regression models. All-cause death or CRC recurrence was the event of interest. Association between HRQOL with OS was assessed using Cox regression. Association between HRQOL and CRC recurrence was further modeled by competing-risks regression adjusted for the competing-risks of death from any cause., Results: After a median follow-up of 23 months, there were 22 (16.1%) incidents of CRC recurrence and 15 (9.4%) deaths. Decreased physical functioning (hazard ratios, HR = 0.917, 95% CI:0.889-0.981) and general health of domains in SF-12 (HR = 0.846, 95% CI:0.746-0.958) or SF-6D scores (HR = 0.010, 95% CI:0.000-0.573) were associated with an increased risk of death, with adjustment of patients' characteristics. Increased vitality (HR = 1.151, 95% CI:1.027-1.289) and mental health (HR = 1.128, 95% CI:1.005-1.265) were associated with an increased likelihood of death. In models adjusted for competing-risk of death, those with worse HRQOL was not associated with increased risk of CRC recurrence., Conclusions: Although self-reported HRQOL was not a significant prognostic factor for CRC recurrence, the HRQOL provided independent prognostic value about mortality in patients with advanced stage of CRC.

Background: To evaluate the effects of a large population-based patient empowerment programme (PEP) on clinical outcomes and health service utilization rates in type 2 diabetes mellitus (T2DM) patients in the primary care setting., Research Design and Subjects: A stratified random sample of 1,141 patients with T2DM enrolled to PEP between March and September 2010 were selected from general outpatient clinics (GOPC) across Hong Kong and compared with an equal number of T2DM patients who had not participated in the PEP (non-PEP group) matched by age, sex and HbA1C level group., Measures: Clinical outcomes of HbA1c, SBP, DBP and LDL-C levels, and health service utilization rates including numbers of visits to GOPC, specialist outpatient clinics (SOPC), emergency department (ED) and inpatient admissions, were measured at baseline and at 12-month post-recruitment. The effects of PEP on clinical outcomes and health service utilization rates were assessed by the difference-in-difference estimation, using the generalized estimating equation models., Results: Compared with non-PEP group, PEP group achieved additional improvements in clinical outcomes over the 12-month period. A significantly greater percentage of patients in the PEP group attained HbA1C≤7% or LDL-C≤2.6 mmol/L at 12-month follow-up compared with the non-PEP group. PEP group had a mean 0.813 fewer GOPC visits in comparison with the non-PEP group., Conclusions: PEP was effective in improving the clinical outcomes and reduced the general outpatient clinic utilization rate over a 12-month period. Empowering T2DM patients on self-management of their disease can enhance the quality of diabetes care in primary care., Trial Registration: ClinicalTrials.gov NCT01935349.

Background and Aims: The objective of this observational study was to determine whether there is an association between atrial fibrillation (AF) and uric acid and to identify the risk markers for AF in obstructive sleep apnea (OSA)., Methods: Consecutive patients with newly diagnosed OSA were screened at baseline. The final study population consisted of 516 patients. One hundred and eight patients had AF. Demographic, clinical, laboratory, and echocardiographic characteristics were carefully recorded. Logistic regression was used for the multivariate analysis of independent risk factors., Results: Uric acid, triglyceride, high-density lipoprotein, C-reactive protein (CRP), left atrial diameter, interventricular septum thickness, apnea hypopnea index, and Epworth sleepiness scale were significantly higher in OSA patients with AF than in those without AF (p <0.05). Among these patients, multiple logistic analyses indicated the independent risk factors for AF occurrence in the OSA subjects included serum uric acid level, left atrial diameter, percentage of time with SaO2 <90%, CRP. The diagnosis analysis showed that higher uric acid, CRP, left atrial diameter and percentage of time with SaO2 <90% had a significant ability to reflect the presence of AF occurrence., Conclusions: The novel finding of this study is that the occurrence of AF in OSA patients is strongly related to serum uric acid level, left atrial diameter, percentage of time with SaO2 <90% and CRP level. These results may be helpful for monitoring AF occurrence in OSA patients., (Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the responsiveness of generic and mapped preference-based measures based on the anchor of global change in health condition of colorectal cancer (CRC) patients., Study Design and Setting: A baseline sample of 333 Chinese CRC patients was recruited between September 2009 and July 2010 and was surveyed prospectively at 6-month follow-up. Preference-based indices were derived from the generic SF-6D measure (SF-6DDirect), from the Short Form-12 (SF-6DSF-12), and mapped from the condition-specific Functional Assessment of Cancer Therapy-Colorectal (SF-6DFACT-C). Responsiveness of three measures was assessed using standardized effect size, standardized response mean, responsiveness statistic, and receiver operating characteristic (ROC) curve analysis., Results: The SF-6DSF-12 and SF-6DFACT-C indices were significantly more responsive to detect positive changes than the SF-6DDirect index in improved groups. In worsened group, the SF-6DDirect and SF-6DFACT-C indices showed significant decline from baseline to 6-month follow-up. The areas under the ROC curve for SF-6DDirect and SF-6DFACT-C indices were not statistically different from 0.7. The SF-6DFACT-C index was more responsive to changes in health status compared with other indices., Conclusion: Direct SF-6D measure was more responsive than mapped preference-based measures in improved group but the direction was reversed in worsened group. The use of a preference-based index mapped from a condition-specific measure captures both negative and positive important changes among CRC., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To investigate the expression of dual oxidase 2 (DUOX2) in psoriasis vulgaris lesions, atopic dermatitis (AD) lesions and normal skin and its role in cutaneous anti-inflammation., Methods: Tissue samples were harvested from psoriasis lesion area, psoriasis non-lesion area, AD lesion area and AD non-lesion area, as well as normal skin, the expression level of DUOX2 protein was detected by immunohistochemical staining. The mRNA level of DUOX2 was detected by reverse transcription polymerase chain reaction (RT-PCR) analysis., Results: The expression of DUOX2 protein was observed in all groups which mainly located in basal layer, spinous layer and dermal papilla layer. Compared with the psoriasis non-lesion group and normal skin group, the expression level of DUOX2 protein in psoriasis lesion group was significant higher (P<0. 01). The expression of DUOX2 protein in AD lesion group was stronger than that in AD non-lesion group and normal skin group (P<0. 01). In addition, the expression level of DUOX2 protein in AD lesion group was significant higher than that in psoriasis lesion group (P<0. 01). RT-PCR test revealed DUOX2 mRNA was expressed positively in psoriasis and AD lesions., Conclusion: The strong expression of DUOX2 in psoriasis vulgaris lesion and AD lesion suggested that DUOX2 may play an important role in the mechanisms of cutaneous anti-inflammation.

Background: Acinetobacter baumannii is characterized by strictly aerobic, gram-negative, nonmotile, nonlactose-fermenting, oxidase-negative, catalase-positive coccobacilli, and the combination of its environmental resilience and its rapid development of resistance to multiple classes of antimicrobials renders it a successful nosocomial pathogen., Objectives: The aim of this study was to identify specific risk factors and outcome of nosocomial pneumonia because of carbapenem-resistant Acinetobacter baumannii (CRAB)., Methods: The retrospective study, set in a 1,500-bed referral and tertiary care hospital, was conducted to analyze the clinical and microbiologic data of patients with nosocomial pneumonia because of Acinetobacter baumannii (A baumannii) from January 2006 to December 2011. Comparisons were made between patients with CRAB pneumonia and patients with carbapenem-susceptible A baumannii (CSAB) pneumonia. Only the first isolation of A baumannii was considered., Results: A total of 145 patients with CSAB pneumonia and 97 patients with CRAB pneumonia was included. Among these patients, the independent risk factors for acquiring CRAB pneumonia were Acute Physiology and Chronic Health Evaluation II (APACHE II) score (>20) at admission, systemic illnesses (chronic respiratory disease and cerebrovascular accident), presence of excess noninvasive or invasive devices (mechanical ventilation), and ever used antibiotics within 28 days (carbapenem and cefepime). The patients with CRAB pneumonia had higher mortality rate than CSAB pneumonia. Multivariate analysis showed that, among patients with A baumannii pneumonia, APACHE II score (>20) at pneumonia onset, infections with other microorganisms, and inappropriate therapy were independently associated with 28-day mortality., Conclusion: Patients with CRAB pneumonia have a higher mortality rate than those with CSAB pneumonia. The nosocomial occurrence of CRAB pneumonia is strongly related to systemic illnesses, APACHE II score, mechanical ventilation, and ever used antibiotics within 28 days., (Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Here we describe the morphologies of Au nanocrystals self-assembled in fcc 3D superlattices called supracrystals. The average size of the nanocrystals is either 5 or 7 nm with a very small size distribution (<7%). The coating agents used to stabilize the nanocrystals are dodecanethiol (C12H25-SH), tetradecanethiol (C14H29-SH), and hexadecanethiol (C16H33-SH). The influences of the evaporation time, the volume of the chamber used to evaporate the toluene solvent, and the substrate temperature are studied. For nanocrystals characterized by the same size and coating agent, the supracrystal morphologies markedly change on increasing the evaporation time from 8 to 9 to 25 h whereas a slight change takes place on increasing the chamber volume. The nanocrystals' ability to self-order in supracrystals decreases upon increasing the chain length of the coating agent from dodecanethiol (C12) to tetradecanethiol (C14) to hexadecanethiol (C16). Decreasing the evaporation rate (25 h) and/or increasing the substrate temperature (50 °C) improves the nanocrystal ordering in fcc supracrystals. A hierarchy in nanocrystal ordering has the following sequence disordered assemblies, supracrystal film sitting on a disordered nanocrystal film, supracrystal films grown layer-by-layer, and finally supracrystals grown in solution with various well-defined shapes.

Objective: To examine the responsiveness of generic and condition-specific instruments based on the anchor of self-reported level of global change in patients with colorectal cancer (CRC)., Study Design and Setting: Three hundred thirty-three patients with CRC were surveyed at two assessments at baseline and follow-up at 6 months from September 2009 to July 2010 using the Short Form-12 Health Survey version 2 (SF-12v2) and Functional Assessment of Cancer Therapy-Colorectal (FACT-C) measures. The responsiveness of the two measures was evaluated using standardized effect size, standardized response mean, responsiveness statistic, and receiver operating characteristic (ROC) curve analysis., Results: In worsened group, internal responsiveness of detecting negative changes was satisfactory for most subscales of FACT-C and SF-12v2. The FACT-C subscales were significantly more responsive to positive changes detection than the SF-12v2 subscales in improved group. Physical well-being subscale, Trial Outcome Index (TOI), and total score of FACT-C were more externally responsive to ROC curve analysis. The FACT-C measure was generally more responsive to changes in health status compared with SF-12v2 measure., Conclusion: TOI and total score of FACT-C were the most responsive among subscales of condition-specific measure, which were more responsive than all generic subscales with the exception of social domain. Complementary use of condition-specific and generic instruments to evaluate the health-related quality of life of CRC patients is encouraged., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: To develop a mapping model for estimating six-dimensional health state short form (SF-6D) utility scores from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (QLQ-C30 and QLQ-CR29) scores in patients with colorectal cancer (CRC), with and without adjustment for clinical and demographic characteristics., Methods: Ordinary least squares regression models were applied to a cross-sectional data set of 216 patients with CRC collected from a regional hospital in Hong Kong. Item responses or scale scores of cancer-specific (QLQ-C30) and colorectal-specific health-related quality-of-life (QLQ-CR38/CR29) data and selected demographic and clinical characteristics of patients were used to predict the SF-6D scores. Model goodness of fit was examined by using exploratory power (R(2) and adjusted R(2)), Akaike information criterion, and Bayesian information criterion, and predictive performance was evaluated by using root mean square error, mean absolute error, and Spearman's correlation coefficients between predicted and observed SF-6D scores. Models were validated by using an independent data set of 56 patients with CRC., Results: Both scale and item response models explained more than 67% of the variation in SF-6D scores. The best-performing model based on goodness of fit (R(2) = 75.02%), predictive ability in the estimation (root mean square error = 0.080, mean absolute error = 0.065), and validation data set prediction (root mean square error = 0.103, mean absolute error = 0.081) included variables of main and interaction effects of the QLQ-C30 supplemented by QLQ-CR29 subset scale responses and a demographic (sex) variable., Conclusions: SF-6D scores can be predicted from QLQ-C30 and QLQ-CR38/CR29 scores with satisfactory precision in patients with CRC. The mapping model can be applied to QLQ-C30 and QLQ-CR38/CR29 data sets to produce utility scores for the appraisal of clinical interventions targeting patients with CRC using economic evaluation., (Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objective: To identify the best transfect conditions for lentiviral vector to transfect CD34+ stem cells from human cord blood., Methods: CD34+ hematopoietic stem cells from human cord blood were transduced with pTRIPdU3-RNAiTALh-EF1a-GFP plasmid expressing GFP by the second generation and third generation lentiviral vector system. The transfect conditions such as the concentration of the virus, polybrene, transfect volume and media, multiplicity of infection (MOI) values, incubating time and centrifugation in 12-well plate at 200 x g were tested to obtain optimal transfect conditions. The number of CFU were counted and the types of CFU were identified by light microscope after the transfected cells (non-infected stem cells served as control) were cultured for 14 days at a 37 degrees C, 5% CO2 incubator., Results: The second-generation lentiviral vector plasmid had higher infect rate than the third-generation. The optimal transfect conditions were determined as: fresh sorting CD34+ cells, 10(7) TU virus concentration, Polybrene 2 microg/mL in opti-MEM medium, centrifuged at 200 x g for 1 h and then co-culture 8 h for cells and virus mixture in one well in flat-bottomed 12-well plate (repeated once). Both infected and non-infected CD34+ stem cells developed CFUs with similar numbers and types of colonies after being cultured for 14 days in the cytokine-containing 1:1 liquid medium/semi-solid medium., Conclusion: The identified optimal conditions can enable effective lentiviral vector transduction of CD34+ without interrupting the differentiation potential of the hematopoietic stem cells.