Integrative Proteomic Characterization of Human Lung Adenocarcinoma.

Genomic studies of lung adenocarcinoma (LUAD) have advanced our understanding of the disease's biology and accelerated targeted therapy. However, the proteomic characteristics of LUAD remain poorly understood. We carried out a comprehensive proteomics analysis of 103 cases of LUAD in Chinese patients. Integrative analysis of proteome, phosphoproteome, transcriptome, and whole-exome sequencing data revealed cancer-associated characteristics, such as tumor-associated protein variants, distinct proteomics features, and clinical outcomes in patients at an early stage or with EGFR and TP53 mutations. Proteome-based stratification of LUAD revealed three subtypes (S-I, S-II, and S-III) related to different clinical and molecular features. Further, we nominated potential drug targets and validated the plasma protein level of HSP 90ß as a potential prognostic biomarker for LUAD in an independent cohort. Our integrative proteomics analysis enables a more comprehensive understanding of the molecular landscape of LUAD and offers an opportunity for more precise diagnosis and treatment.

The association between circulating 25-hydroxyvitamin D and pancreatic cancer: a systematic review and meta-analysis of observational studies.

PURPOSE: The relationship between circulating 25-hydroxyvitamin D [25(OH)D] and pancreatic cancer has been well studied but remains unclear. The purpose of this study was to elucidate the association between circulating 25(OH)D and pancreatic cancer by using a meta-analytic approach. METHODS: PubMed, Embase, and Wed of Science databases were searched through October 15, 2022. A random or fixed-effects model was used to estimate the pooled odds ratio (OR), risk ratio (RR), hazard ratio (HR) and their 95% confidence intervals (CIs). RESULTS: A total of 16 studies including 529,917 participants met the inclusion criteria, of which 10 reported incidence and 6 reported mortality. For the highest versus lowest categories of circulating 25(OH)D, the pooled OR of pancreatic cancer incidence in case-control studies was 0.98 (95% CI 0.69-1.27), and the pooled HRs of pancreatic cancer mortality in cohort and case-control studies were 0.64 (95% CI 0.45-0.82) and 0.78 (95% CI 0.62-0.95), respectively. The leave-one-out sensitivity analyses found no outliers and Galbraith plots indicated no substantial heterogeneity. CONCLUSION: Evidence from this meta-analysis suggested that high circulating 25(OH)D levels may be associated with decreased mortality but not incidence of pancreatic cancer. Our findings may provide some clues for the treatment of pancreatic cancer and remind us to be cautious about widespread vitamin D supplementation for the prevention of pancreatic cancer.

ß-hydroxybutyrate and mitochondria mediate the association between medium-chain fatty acids, DHA and mild cognitive impairment: a nested case-control study.

BACKGROUND: Medium-chain fatty acids (MCFAs) and docosahexaenoic acid (DHA) could affect the occurrence of mild cognitive impairment (MCI). ß-hydroxybutyrate (BHB), mitochondrial DNA copy number (mtDNAcn) and mitochondrial DNA (mtDNA) deletions might be their potential mechanisms. This study aimed to explore the relationship between MCFAs, DHA and MCI, and potential mechanisms. METHODS: This study used data from Tianjin Elderly Nutrition and Cognition (TENC) cohort study, 120 individuals were identified with new onset MCI during follow-up, 120 individuals without MCI were selected by 1:1 matching sex, age, and education levels as the control group from TENC. Conditional logistic regression analysis and mediation effect analysis were used to explore their relationship. RESULTS: Higher serum octanoic acid levels (OR: 0.633, 95% CI: 0.520, 0.769), higher serum DHA levels (OR: 0.962, 95% CI: 0.942, 0.981), and more mtDNAcn (OR: 0.436, 95% CI: 0.240, 0.794) were associated with lower MCI risk, while more mtDNA deletions was associated with higher MCI risk (OR: 8.833, 95% CI: 3.909, 19.960). Mediation analysis suggested that BHB and mtDNAcn, in series, have mediation roles in the association between octanoic acid and MCI risk, and mtDNA deletions have mediation roles in the association between DHA and MCI risk. CONCLUSION: Higher serum octanoic acid and DHA levels were associated with lower MCI risk. Octanoic acid could affect the incidence of MCI through BHB, then mitochondria function, or through mitochondria function, or directly. Serum DHA level could affect the incidence of MCI through mitochondria function, or directly.

Comparative analysis of pressure ulcer development in stroke patients within and outside healthcare facilities: A systematic review and meta-analysis.

The risk of pressure ulcers in stroke patients is a significant concern, impacting their recovery and quality of life. This systematic review and meta-analysis investigate the prevalence and risk factors of pressure ulcers in stroke patients, comparing those in healthcare facilities with those in home-based or non-clinical environments. The study aims to elucidate how different care settings affect the development of pressure ulcers, serving as a crucial indicator of patient care quality and management across diverse healthcare contexts. Following PRISMA guidelines, a comprehensive search was conducted across PubMed, Embase, Web of Science and the Cochrane Library. Inclusion criteria encompassed studies on stroke patients in various settings, reporting on the incidence or prevalence of pressure ulcers. Exclusion criteria included non-stroke patients, non-original research and studies with incomplete data. The Newcastle-Ottawa scale was used for quality assessment, and statistical analyses involved both fixed-effect and random-effects models, depending on the heterogeneity observed. A total of 1542 articles were initially identified, with 11 studies meeting the inclusion criteria. The studies exhibited significant heterogeneity, necessitating the use of a random-effects model. The pooled prevalence of pressure injuries was 9.53% in patients without family medical services and 2.64% in patients with medical services. Sensitivity analysis confirmed the stability of these results, and no significant publication bias was detected through funnel plot analysis and Egger's linear regression test. The meta-analysis underscores the heightened risk of pressure injuries in stroke patients, especially post-discharge. It calls for concerted efforts among healthcare providers, policymakers and caregivers to implement targeted strategies tailored to the specific needs of different care environments. Future research should focus on developing and evaluating interventions to effectively integrate into routine care and reduce the incidence of pressure injuries in stroke patients.

Risk assessment and pathogen profile of surgical site infections in traumatic brain injury patients undergoing emergency craniotomy: A retrospective study.

Emergency craniotomy in patients with traumatic brain injury poses a significant risk for surgical site infections (SSIs). Understanding the risk factors and pathogenic characteristics of SSIs in this context is crucial for improving outcomes. This comprehensive retrospective analysis spanned from February 2020 to February 2023 at our institution. We included 25 patients with SSIs post-emergency craniotomy and a control group of 50 patients without SSIs. Data on various potential risk factors were collected, including demographic information, preoperative conditions, and intraoperative details. The BACT/ALERT3D Automated Bacterial Culture and Detection System was utilized for rapid bacterial pathogen identification. Statistical analyses included univariate and multivariate logistic regression to identify significant risk factors for SSIs. The study identified Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus as the most prevalent pathogens in SSIs. Significant risk factors for SSIs included the lack of preoperative antibiotic use, postoperative drainage tube placement, diabetes mellitus, and the incorporation of invasive procedures, all of which showed a significant association with SSIs in the univariate analysis. The multivariate analysis further highlighted the protective effect of preoperative antibiotics and the increased risks associated with anaemia, diabetes mellitus, postoperative drainage tube placement, and the incorporation of invasive procedures. Our research underscores the critical role of factors like insufficient preoperative antibiotics, postoperative drainage, invasive techniques, anaemia, and diabetes mellitus in elevating the risk of surgical site infections in traumatic brain injury patients undergoing emergency craniotomy. Enhanced focus on these areas is essential for improving surgical outcomes.

Causal relationships between birth weight, childhood obesity and age at menarche: A two-sample Mendelian randomization analysis.

OBJECTIVES: Observational studies suggest birth weight and childhood obesity are closely associated with age at menarche. However, the relationships between them are currently inconsistent and it remains elusive whether such associations are causal. Therefore, the aim of the study was to investigate whether there existed causal relationships between birth weight, childhood obesity and age at menarche. DESIGN, PATIENTS AND MEASUREMENTS: A two-sample Mendelian randomization (MR) study. The standard inverse variance weighted MR analyses were adopted to evaluate the causal effects of birth weight (n = 143,677), childhood body mass index (BMI) (n = 39,620) on age at menarche (n = 182,416) with summary statistics from large-scale genome-wide association studies (GWASs). Meanwhile, we validated our MR results with some sensitivity analyses including maximum likelihood, weighted-median and MR pleiotropy residual sum and outlier methods. RESULTS: The present study showed that each one standard deviation (1-SD) lower birth weight was predicted to result in a 0.1479 years earlier of age at menarche (ß = .1479, 95% confidence interval [CI] = 0.0422-0.2535; p = 0.0061). We also found that genetically predicted 1-SD increase in childhood BMI was causally associated with early age at menarche (ß = -.3966, 95% CI = -0.5294 to -0.2639; p = 4.73E-09). CONCLUSIONS: Our MR study suggests the causal effect of lower birth weight and higher childhood BMI on the increased risk of earlier menarche. It may be the opportune time to carry out weight control intervention in prenatal and early childhood development periods to prevent early menarche onset, thus decreasing the future adverse consequences.

Integrative analysis of multi-omics data to detect the underlying molecular mechanisms for obesity in vivo in humans.

BACKGROUND: Obesity is a complex, multifactorial condition in which genetic play an important role. Most of the systematic studies currently focuses on individual omics aspect and provide insightful yet limited knowledge about the comprehensive and complex crosstalk between various omics levels. SUBJECTS AND METHODS: Therefore, we performed a most comprehensive trans-omics study with various omics data from 104 subjects, to identify interactions/networks and particularly causal regulatory relationships within and especially those between omic molecules with the purpose to discover molecular genetic mechanisms underlying obesity etiology in vivo in humans. RESULTS: By applying differentially analysis, we identified 8 differentially expressed hub genes (DEHGs), 14 differentially methylated regions (DMRs) and 12 differentially accumulated metabolites (DAMs) for obesity individually. By integrating those multi-omics biomarkers using Mendelian Randomization (MR) and network MR analyses, we identified 18 causal pathways with mediation effect. For the 20 biomarkers involved in those 18 pairs, 17 biomarkers were implicated in the pathophysiology of obesity or related diseases. CONCLUSIONS: The integration of trans-omics and MR analyses may provide us a holistic understanding of the underlying functional mechanisms, molecular regulatory information flow and the interactive molecular systems among different omic molecules for obesity risk and other complex diseases/traits.

The effects of capsaicin intake on weight loss among overweight and obese subjects: a systematic review and meta-analysis of randomised controlled trials.

Animal studies have shown that capsaicin plays a positive role in weight management. However, the results in human research are controversial. Therefore, the present systematic review and meta-analysis aimed to evaluate the effect of capsaicin on weight loss in adults. We searched PubMed, Embase, China Biomedical Literature Database (CBM), Cochrane library and clinical registration centre, identifying all randomised controlled trials (RCT) published in English and Chinese to 3 May 2022. A random-effect model was used to calculate the weighted mean difference (WMD) and 95 % CI. Heterogeneity between studies was assessed by the Cochran Q statistic and I-squared tests (I 2 ). Statistical analyses were performed using STATA version 15.1. P-values < 0·05 were considered as statistically significant. From 2377 retrieved studies, fifteen studies were finally included in the meta-analyses. Fifteen RCT with 762 individuals were included in our meta-analysis. Compared with the control group, the supplementation of capsaicin resulted in significant reduction on BMI (WMD: -0·25 kg/m2, 95 % CI = -0·35, -0·15 kg/m2, P < 0·05), body weight (BW) (WMD: -0·51 kg, 95 % CI = -0·86, -0·15 kg, P < 0·05) and waist circumference (WC) (WMD: -1·12 cm, 95 % CI = -2·00, -0·24 cm, P < 0·05). We found no detrimental effect of capsaicin on waist-to-hip ratio (WMD: -0·05, 95 % CI = -0·17, 0·06, P > 0·05). The current meta-analysis suggests that capsaicin supplementation may have rather modest effects in reducing BMI, BW and WC for overweight or obese individuals.

The interaction effect of transfusion history and previous stroke history on the risk of venous thromboembolism in stroke patients: a prospective cohort study.

BACKGROUND: Blood transfusion and previous stroke history are two independent risk factors of venous thromboembolism (VTE) in stroke patients. Whether the potential interaction of transfusion history and previous stroke history is associated with a greater risk of VTE remains unclear. This study aims to explore whether the combination of transfusion history and previous stroke history increases the risk of VTE among Chinese stroke patients. METHODS: A total of 1525 participants from the prospective Stroke Cohort of Henan Province were enrolled in our study. Multivariate logistic regression models were used to explore the associations among transfusion history, previous stroke history and VTE. The interaction was evaluated on both multiplicative and additive scales. The odds ratio (95% CI), relative excess risk of interaction (RERI), attributable proportion (AP), and synergy index (S) of interaction terms were used to examine multiplicative and additive interactions. Finally, we divided our population into two subgroups by National Institutes of Health Stroke Scale (NIHSS) score and re-evaluated the interaction effect in both scales. RESULTS: A total of 281 (18.4%) participants of 1525 complicated with VTE. Transfusion and previous stroke history were associated with an increased risk of VTE in our cohort. In the multiplicative scale, the combination of transfusion and previous stroke history was statistically significant on VTE in both unadjusted and adjusted models (P<0.05). For the additive scale, the RERI shrank to 7.016 (95% CI: 1.489 ~ 18.165), with the AP of 0.650 (95% CI: 0.204 ~ 0.797) and the S of 3.529 (95% CI: 1.415 ~ 8.579) after adjusting for covariates, indicating a supra-additive effect. In subgroups, the interaction effect between transfusion history and previous stroke history was pronouncedly associated with the increased risk of VTE in patients with NIHSS score > 5 points (P<0.05). CONCLUSIONS: Our results suggest that there may be a potential synergistic interaction between transfusion history and previous stroke history on the risk of VTE. Besides, the percentage of VTE incidence explained by interaction increased with the severity of stroke. Our findings will provide valuable evidence for thromboprophylaxis in Chinese stroke patients.

Association of dietary inflammatory index and leukocyte telomere length with mild cognitive impairment in Chinese older adults.

BACKGROUND: There are minimal data on the relationship between DII and MCI in an elderly Chinese population and no research has assessed the potential effect of LTL. OBJECTIVE: We investigated the association between DII and MCI while taking into account the potential effect of LTL. METHODS: This cross-sectional study included 3,386 participants aged ≥ 60 years of age from the Tianjin Elderly Nutrition and Cognition Cohort study. DII score was constructed based on a validated self-administered food frequency questionnaire was calculated based on the method developed by Shivappa et al. LTL was measured by quantitative real-time polymerase chain reaction. Multivariable logistic regression analysis was used to analyze the association between DII, LTL and MCI. Moreover, mediation analysis was employed to test the mediation effect of LTL on the total effect of DII on MCI. RESULTS: Compared with the participants in the lowest tertiles of LTL and DII score, the odds ratios (ORs) of MCI in the highest tertiles were 0.386(95% CI: 0.281-0.529) and 1.650 (95% CI: 1.232-2.209), respectively. The significant association between DII score and MCI persisted after further adjusting for LTL (OR: 1.595; 95% CI: 1.189-2.140). The link between DII score and MCI was mediated partially by LTL (ßindirect effect= -0.008, P<0.05). CONCLUSION: High DII score was positively associated with MCI prevalence in an elderly Chinese population and the link between DII scores and MCI seemed to be mediated partially by LTL.

Telomere and mitochondria mediated the association between dietary inflammatory index and mild cognitive impairment: A prospective cohort study.

BACKGROUND: Diet and chronic inflammation might play a major role in the pathogenesis of mild cognitive impairment (MCI). In addition, peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) might mediate the relationship between inflammation and MCI risk. The purpose of the present study is to evaluate whether inflammatory potential of diet assessed by dietary inflammatory index (DII), chronic inflammation, peripheral blood LTL, and mtDNAcn were associated with the risk of MCI. RESULTS: A population-based cohort study was conducted with a total of 2944 participants. During a median follow-up of 2 years, 438 (14.90%) individuals were new-onset MCI. After adjustment, a higher score of DII (hazard ratio [HR]: 1.056, 95% CI: 1.005, 1.109), a higher log systemic immune inflammation index (SII) (HR: 1.333, 95% CI: 1.089, 1.633) and log system inflammation response index (SIRI) (HR: 1.487, 95% CI: 1.024, 2.161) predicted elevated risk of MCI. An increased mtDNAcn (HR: 0.843, 95% CI: 0.712, 0.997), but not LTL, predicted a decreased risk of MCI. Negative associations of log SII with LTL (ß:-0.359, 95% CI: -0.445, -0.273) and mtDNAcn (ß:-0.048, 95% CI: -0.090, -0.006) were found. Additionally, negative associations of log SIRI with LTL (ß: -0.035, 95% CI: -0.052, -0.017) and mtDNAcn (ß:-0.136, 95% CI: -0.216, -0.056) were also found. Path analysis suggested that SIRI, LTL, and mtDNAcn, in series, have mediation roles in the association between DII score and MCI risk. CONCLUSIONS: Higher DII, SII, and SIRI might predict a greater risk of MCI, while a longer LTL and an increased mtDNAcn were linked to a reduced risk of MCI among the older population. LTL and mtDNAcn could play mediation roles in the association between DII and MCI risk.

Acute Coronary Syndrome May be Associated with Decreased Resolvin D1-to-Leukotriene B4 Ratio.

An imbalance between inflammation-resolving lipid mediators and proinflammatory leukotrienes with the instability of atherosclerotic plaques in experimental models has been reported. However, the contribution of the balance of Resolvin D1 (RvD1) to Leukotriene B4 (LTB4) in predicting acute coronary syndrome (ACS) remains unknown. This study investigated the association of RvD1-to-LTB4 ratio with ACS.Eighty-one patients with ACS and 90 stable coronary artery disease (SCAD) patients were included in this study. Plasma RvD1 and LTB4 levels were measured with commercial kits.Patients with ACS had higher LTB4 levels, lower RvD1 levels, and a lower RvD1-to-LTB4 ratio than patients with SCAD. History of diabetes mellitus, elevated Troponin I, LTB4, and decreased RvD1-to-LTB4 ratio (odds ratio [OR]: 1.025; 95% confidence interval [CI]: 1.014-1.040; P < 0.001) were independently correlated with ACS. Receiver operating characteristic curve analysis demonstrated that RvD1-to-LTB4 ratio was a potential biomarker for the risk of ACS.A circulating proinflammatory lipid profile, characterized by a low RvD1-to-LTB4 ratio may be associated with ACS in patients with ischemic heart disease.

Apolipoprotein E polymorphism ε4-stratified longitudinal association between daytime naps, sleep apnea and mild cognitive impairment: A prospective cohort study.

BACKGROUND AND PURPOSE: Sleep characteristics, including taking a nap and sleep apnea, have been proven to have effects on cognitive function, and apolipoprotein E polymorphism ε4 (APOEε4) has been confirmed to be a risk factor for mild cognitive impairment (MCI), but epidemiological studies linking sleep characteristics and APOEε4 are scarce. We aimed to explore the longitudinal association between sleep characteristics and MCI in an overall cohort, in APOEε4 carriers and in APOEε4 non-carriers. METHODS: We included 3053 older adults from the Tianjin Elderly Nutrition and Cognition Cohort (TENCC) study, recruited from March 2018 to June 2019, and followed up from March 2021 to June 2021. All participants underwent detailed neuropsychological evaluation that allowed psychometric MCI classification. Information on self-reported sleep characteristics was gathered via face-to-face interviews. Crude and multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression models. RESULTS: In the multivariable-adjusted models, taking a nap at noon was associated with decreased risk of MCI in all participants (yes vs. no: HR 0.723, 95% CI 0.592, 0.883) and in APOEε4 non-carriers (yes vs. no: HR 0.719, 95% CI 0.576, 0.897). Sleep apnea was associated with increased risk of MCI in all participants (vs. good: HR 2.213, 95% CI 1.171, 4.180) and in APOEε4 non-carriers (vs. good: HR 2.217, 95% CI 1.085, 4.529). CONCLUSIONS: This study suggests that taking a nap at noon might be a potential protective factor against development of MCI in APOEε4 non-carriers, and sleep apnea might be associated with increased incidence of MCI in APOEε4 non-carriers.

Circulating folate concentrations and the risk of mild cognitive impairment: A prospective study on the older Chinese population without folic acid fortification.

BACKGROUND: The longitudinal association between serum folate concentrations and the risk of cognitive impairment remains unclear in populations with low folate levels. We examined the association between serum folate concentrations and mild cognitive impairment (MCI) in older adults in China, where mandatory fortification of foods with folic acid has not been implemented. We further explored if homocysteine (Hcy) and leukocyte telomere length (LTL) mediate the association between serum folate and MCI. METHODS: We performed a longitudinal analysis of 3974 participants aged ≥60 years from the Tianjin Elderly Nutrition and Cognition (TENC) cohort study. The associations between serum folate level and the risk of cognitive impairment overall and stratified by apolipoprotein E (APOE) ε4 genotypes were evaluated using multivariable Cox proportional hazards models. The mediating effects of Hcy and LTL on the folate-MCI association were explored via a path analysis approach. RESULTS: Within a 3-year follow-up, we documented 560 incident MCI cases. After multivariable adjustment, higher serum folate concentrations were associated with lower incidence of MCI, with hazard ratios (95% confidence interval) across quartiles of folate (from lowest to highest concentrations) of 1.00 (reference), 0.66 (0.52, 0.83), 0.57 (0.45, 0.73), 0.66 (0.52, 0.84), respectively (p for trend <0.001). In mediation analyses, the status of serum folate deficiency and MCI were correlated via two intermediary pathways, Hcy and Hcy-telomere (p < 0.05). CONCLUSIONS: Lower folate concentrations, independently of APOE genotype, were associated with increased risk of MCI among elderly Chinese people, a population with relatively low folate intake. Our data were compatible with the mediation hypothesis that the association between folate status and MCI was mediated by Hcy and LTL.

Association between methionine cycle metabolite-related diets and mild cognitive impairment in older Chinese adults: a population-based observational study.

BACKGROUND: Homocysteine (Hcy) and folate, involved in a common metabolic pathway supplying essential methyl groups for DNA and protein synthesis, have been found to be associated with cognitive function. Moreover, diet may influence methionine cycle metabolites (MCM) as well as mild cognitive impairment (MCI), but MCM-related dietary patterns are unclear in an older population. OBJECTIVE: The study aimed to identify MCM-related dietary patterns of older Chinese adults, and examine their association with the prevalence of MCI in a large population-based study. METHODS: This study included 4457 participants ≥ 60 years of age from the Tianjin Elderly Nutrition and Cognition Cohort study. Dietary data were collected using a valid self-administered food frequency questionnaire, and factor analysis was used to identify major dietary patterns in the population. MCM-based dietary patterns were derived using reduced rank regression (RRR) based on serum folate and Hcy as response variables. RESULTS: Compared with the participants in the lowest quartile of vegetarian pattern and processed foods pattern, the odds ratios (ORs) of MCI in the highest quartile were 0.72 (95% CI 0.53-0.98) and 1.39 (95% CI 1.03-1.88), respectively. In the MCM-based dietary patterns derived using RRR, the ORs for MCI for the highest quartile of MCM patterns I and II were 0.58 (95% CI 0.44-0.78) and 1.38 (95% CI 1.04-1.83), respectively, compared with participants in the lower quartile. CONCLUSIONS: Findings from this large population-based study suggested that adopting an MCM-related dietary pattern, especially avoiding processed foods, can decrease the occurrence of MCI.

Combined lifestyle factors on mortality among the elder population: evidence from a Chinese cohort study.

BACKGROUND: Numerous studies have suggested that lifestyle-related factors are associated with mortality, however limited evidence is available for the Chinese elder population. METHODS: The data of this study was obtained from the Chinese Longitudinal Health Survey (CLHLS) during 2008 - 2018, lifestyle-related factors including body mass index (BMI), smoking, drinking, consumption of vegetables and fruits, physical activity and sleep duration were included as dependent variables in the analysis. A lifestyle risk score was created using six unhealthy behaviors: smoking, drinking, unhealthy weight, physical inactivity, not eat vegetables or fruits and short or prolonged sleep. The Kaplan-Meier curves were used to illustrate the cumulative effect of lifestyle factors on mortality and cox regression models were conducted to estimate the combined effects of lifestyle-related factors on total mortality. RESULTS: The results illustrated that low BMI, smoking, no fruit eating, and no physical inactivity were risk factors for total mortality. KM curves showed significant cumulative effect of unhealthy lifestyle factors on mortality. Compared with participants without any unhealthy factors, the hazard ratio (HR) for participants with six unhealthy factors was 1.335 (1.015,1.757) for all-cause mortality. CONCLUSIONS: This study demonstrated poor adherence to a healthy lifestyle may increase all-cause mortality and specific combinations of lifestyle related factors have different effects on mortality among Chinese elderly population.

[Study on characteristic chromatogram and content determination of Wuzhuyu Decoction reference sample].

In this study, the critical quality attributes of Wuzhuyu Decoction reference sample were explored by using characteristic chromatogram, index component content and dry extract rate as indexes.The dissemination relationship of quantity value between medicinal materials-decoction pieces-reference sample was investigated to preliminarily formulate the quality standard of the reference sample.The characteristic chromatogram of 15 batches of Wuzhuyu Decoction was established by high performance liquid chromatography(HPLC) and the similarity analysis was conducted.Common peaks were demarcated and assigned to medicinal materials.Moreover, quantitative determination of limonin, evodiamine, rutaecarpine and ginsenoside Rb_1 of Wuzhuyu Decoction were performed.The dissemination of quantity value was explored combined with dry extract rate, similarity of characteristic chromatogram and transfer rate of index component content.A total of 18 common peaks were identified in the corresponding materials of Wuzhuyu Decoction reference sample, with the similarity of characteristic chromatogram greater than 0.9, and Fructus Evodiae, Radix Ginseng, Rhizoma Zingiberis Recens and Fructus Jujubae contributed 9, 5, 8 and 2 chromatographic peaks, respectively.The index component content of corresponding materials and the transfer rates of medicinal materials-decoction pieces and decoction pieces-reference sample of different batches of Wuzhuyu Decoction reference sample were as follows: the content of limonin was 0.16%-0.51%, and the transfer rates were 83.66%-115.60% and 38.54%-54.58%, respectively; the content of evodiamine was 0.01%-0.11%, the transfer rated were 80.80%-116.15% and 3.23%-12.93%, respectively; the content of rutaecarpine was 0.01%-0.05%, the transfer rates were 84.33%-134.53% and 5.72%-21.24%, respectively; the content of ginsenoside Rb_1 was 0.06%-0.11%, and the transfer rates were 90.00%-96.92% and 32.45%-67.24%, respectively.The dry extract rate of the whole prescription was 22.58%-29.89%.In this experiment, the dissemination of quantity value of Wuzhuyu Decoction reference sample was analyzed by the combination of characteristic chromatogram, index component content and dry extract rate.A scientific and stable quality evaluation method of the reference sample was preliminarily established, which provided basis for the subsequent development of Wuzhuyu Decoction and the quality control of related preparations.

Urinary protein biomarker panel predicts esophageal squamous carcinoma from control cases and other tumors.

PURPOSE: Discovery of noninvasive urinary biomarkers for the early diagnosis of esophageal squamous carcinoma (ESCC). METHODS: We conducted proteomic analyses of 499 human urine samples obtained from healthy individuals (n = 321) and ESCC (n = 83), bladder cancer (n = 17), breast cancer (n = 12), colorectal cancer (n = 16), lung cancer (n = 33) and thyroid cancer (n = 17) patients from multiple medical centers. Those samples were divided into a discovery set (n = 247) and an independent validation set (n = 157). RESULTS: Among urinary proteins identified in the comprehensive quantitative proteomics analysis, we selected a panel of three urinary biomarkers (ANXA1, S100A8, TMEM256), and established a logistic regression model in the discovery set that can correctly classify the majority of ESCC cases in the validation sets with the area under the curve (AUC) values of 0.825. This urinary biomarker panel not only discriminates ESCC patients from healthy individuals but also differentiates ESCC from other common tumors. Notably, the panel distinguishes stage I ESCC patients from healthy individuals with AUC values of 0.886. On the analysis of stage-specific biomarkers, another combination panel of protein (ANXA1, S100A8, SOD3, TMEM256) demonstrated a good AUC value of 0.792 for stage I ESCC. CONCLUSIONS: Urinary biomarker panel represents a promising auxiliary diagnostic tool for ESCC, including early-stage ESCC.

Phospholipase A2 group IIA correlates with circulating high-density lipoprotein cholesterol and modulates cholesterol efflux possibly through regulation of PPAR-γ/LXR-α/ABCA1 in macrophages.

BACKGROUND: Secretory phospholipase A2 group IIA (sPLA2-IIA) is an independent risk factor for cardiovascular disease, but its role on high-density lipoprotein cholesterol (HDL-C) level has not been clarified. The aim of the present study was to explore the association between circulating sPLA2-IIA and HDL-C, and to evaluate if sPLA2-IIA enhances cholesterol efflux capacity through regulation of peroxisome proliferator-activated receptor γ (PPAR-γ), liver X receptor α (LXR-α), and ATP-binding cassette A1 (ABCA1). METHODS: 131 patients with coronary artery disease were enrolled. The plasma level of sPLA2-IIA was tested with enzyme-linked immunosorbent assay kit, and serum lipids were assessed by biochemical analyzer. Human monocyte-macrophage cell line THP-1 was co-incubated with sPLA2-IIA in the presence/absence of selective PPAR-γ antagonist GW9662 in vitro. Real-time PCR and Western-blot were employed to measure the mRNA and protein expressions of PPAR-γ, LXR-α, and ABCA1, respectively. The cholesterol efflux was evaluated by using an assay kit. RESULTS: In subjects, circulating level of sPLA2-IIA was positively related with that of HDL-C (r = 0.196, p = 0.024). The plasma level of sPLA2-IIA was significantly higher in the high HDL-C (≥ 1.04 mmol/L) group (7477.828 pg/mL) than that in low HDL-C (< 1.04 mmol/L) group (5836.92 pg/mL, p = 0.004). For each increase of 1 pg/µl in sPLA2-IIA level, the adjusted odds ratio for HDL-C ≥ 1.04 mmol/L was 1.143. Co-incubation of THP-1 cells with sPLA2-IIA resulted in increased expressions of PPAR-γ, LXR-α, and ABCA1, as well as enhanced cholesterol efflux capacity, that were all reversed by administration of GW9662. CONCLUSIONS: Circulating sPLA2-IIA was positively associated with HDL-C. PPAR-γ/LXR-α/ABCA1 might be responsible for sPLA2-IIA-regulated cholesterol efflux in macrophages.

Ezetimibe Improves Rosuvastatin Effects on Inflammation and Vascular Endothelial Function in Acute Coronary Syndrome Patients Undergoing PCI.

BACKGROUND: Little is known of the acute effects of ezetimibe in patients with acute coronary syndrome (ACS) undergoing PCI. We investigated whether ezetimibe improves inflammation and vascular endothelial function in patients with ACS undergoing PCI. METHODS: We randomized 171 patients with ACS undergoing PCI to receive ezetimibe 10 mg/day plus rosuvastatin 20 mg/day (combination group, n = 81) versus rosuvastatin 20 mg/day (rosuvastatin group, n = 90). Lipid profile, type II secretory phospholipase A2 (sPLA2-IIa), interleukin-1ß (IL-1ß), vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1) were measured at baseline and after 7 days. Three months after PCI, clinical outcomes were examined. RESULT: The levels of sPLA2-IIa and IL-1ß reduced significantly in both groups, but more when ezetimibe and rosuvastatin were coadministered (sPLA2-IIa: 6.16 ± 2.67 vs. 7.42 ± 3.53 ng/ml, p=0.01; IL-1ß: 37.39 ± 26.25 vs. 48.98 ± 32.26 pg/ml, p=0.01). A significant rise of VCAM-1 and ICAM-1 was observed on day 7 after PCI in the both groups, but was less in the combination group (VCAM-1: 918.28 ± 235.31 vs. 988.54 ± 194.41 ng/ml, p=0.03; ICAM-1: 213.01 ± 100.15 vs. 246.88 ± 105.71 ng/ml, p=0.03). Patients in the combination versus rosuvastatin group appeared to suffer from less major adverse events. Periprocedural therapy of ezetimibe improves rosuvastatin effects on proinflammatory responses and endothelial function associated with ACS patients undergoing PCI. This trial is registered with https://clinicaltrials.gov/ct2/show/ChiCTR-IPR-17012219 (Chinese Clinical Trial Registry, http://www.chictr.org.cn on 02/08/2017).