The functions and mechanisms of long non-coding RNA in colorectal cancer.

CRC poses a significant challenge in the global health domain, with a high number of deaths attributed to this disease annually. If CRC is detected only in its advanced stages, the difficulty of treatment increases significantly. Therefore, biomarkers for the early detection of CRC play a crucial role in improving patient outcomes and increasing survival rates. The development of a reliable biomarker for early detection of CRC is particularly important for timely diagnosis and treatment. However, current methods for CRC detection, such as endoscopic examination, blood, and stool tests, have certain limitations and often only detect cases in the late stages. To overcome these constraints, researchers have turned their attention to molecular biomarkers, which are considered a promising approach to improving CRC detection. Non-invasive methods using biomarkers such as mRNA, circulating cell-free DNA, microRNA, LncRNA, and proteins can provide more reliable diagnostic information. These biomarkers can be found in blood, tissue, stool, and volatile organic compounds. Identifying molecular biomarkers with high sensitivity and specificity for the early and safe, economic, and easily measurable detection of CRC remains a significant challenge for researchers.

Optimizing Geriatric Venipuncture: A DRG-Compatible Team-Based Reengineering Strategy.

Objective: This study evaluates a reengineered intervention aimed at improving the clinical management of intravenous indwelling needles in geriatric patients, focusing on cost-efficiency within the Diagnosis-Related Group (DRG) payment framework. Methods: The intervention was assessed through a comparative study involving 387 elderly patients in the Geriatric Department of Xuanwu Hospital, between June 2021 and March 2022. The study contrasted outcomes between patients treated before and after implementing a new team-based management protocol in November 2021. Results: Findings indicate enhanced first-attempt venipuncture success, reduced consumable costs, and decreased complication rates in the post-intervention group (P < 0.001), compared to controls. Conclusion: The intervention demonstrates significant benefits in venipuncture efficiency, cost reduction, and patient safety, suggesting its potential for broader adoption in geriatric care.

A novel AllGlo probe-quantitative PCR method for detecting single nucleotide polymorphism in CYP2C19 to evaluate the antiplatelet activity of clopidogrel.

CYP2C19 gene has multiple single nucleotide polymorphism (SNP), which is the major determinant for clopidogrel treatment responses. Therefore, CYP2C19 SNP detection is essential for predicting clopidogrel efficacy. Currently, there is still no quick and effective method for routine detection of common CYP2C19 SNPs in clinical laboratories, which is critically needed prior to clopidogrel treatment. AllGlo™ based quantitative PCR was used to develop a novel genotyping method for CYP2C19 SNP detection, termed CyPAllGlo. The performance of CyPAllGlo was compared with that of the commonly used fluorescence in situ hybridization (FISH) method, and the data was verified by DNA sequencing. CyPallGlo was used to identify CYP2C19 polymorphisms in 363 patients with coronary heart disease. The univariate analysis was used to access the antiplatelet efficacy of clopidogrel in patients. The associations between CYP2C19 polymorphisms and clopidogrel efficacy were analyzed. Using CyPAllGlo to detect CYP2C19*2 and CYP2C19*3 alleles was highly specific and fast. The detection limit was approximately 0.07 µg/µl and 0.7 µg/µl for CYP2C19*2 and CYP2C19*3, respectively. The consistency between FISH and CyPAllGlo were 98.07% for CYP2C19*2 and 99.17% for CYP2C19*3. DNA sequencing showed that the accuracy of CyPAllGlo was 100%. The analysis time for the whole CyPAllGlo procedure was approximately 60 min. Univariate analysis showed that the anticoagulation efficacy of clopidogrel was related to patient age, CYP2C19 genotype, metabolic phenotype, and LDL level. The logistic regression analysis showed that the genotype of CYP2C19 and metabolic phenotype was the two risk factors for clopidogrel antiplatelet ineffectiveness. This novel CyPAllGlo is a rapid and accurate method for detection of CYP2C19 SNP. The specificity and consistency of CyPAllGlo are comparable with that of widely used DNA sequencing. These findings provide valuable rapid method for predicting clopidogrel efficacy, which can be quickly translated to improve personalized precision medicine for coronary heart disease treatment.

Rapamycin mitigates inflammation-mediated disc matrix homeostatic imbalance by inhibiting mTORC1 and inducing autophagy through Akt activation.

Background: Low back pain is a global health problem that originated mainly from intervertebral disc degeneration (IDD). Autophagy, negatively regulated by the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway, prevents metabolic and degenerative diseases by removing and recycling damaged cellular components. Despite growing evidence that autophagy occurs in the intervertebral disc, the regulation of disc cellular autophagy is still poorly understood. Methods: Annulus fibrosus (rAF) cell cultures derived from healthy female rabbit discs were used to test the effect of autophagy inhibition or activation on disc cell fate and matrix homeostasis. Specifically, different chemical inhibitors including rapamycin, 3-methyladenine, MK-2206, and PP242 were used to modulate activities of different proteins in the PI3K/Akt/mTOR signaling pathway to assess IL-1ß-induced cellular senescence, apoptosis, and matrix homeostasis in rAF cells grown under nutrient-poor culture condition. Results: Rapamycin, an inhibitor of mTOR complex 1 (mTORC1), reduced the phosphorylation of mTOR and its effector p70/S6K in rAF cell cultures. Rapamycin also induced autophagic flux as measured by increased expression of key autophagy markers, including LC3 puncta number, LC3-II expression, and cytoplasmic HMGB1 intensity and decreased p62/SQSTM1 expression. As expected, IL-1ß stimulation promoted rAF cellular senescence, apoptosis, and matrix homeostatic imbalance with enhanced aggrecanolysis and MMP-3 and MMP-13 expression. Rapamycin treatment effectively mitigated IL-1ß-mediated inflammatory stress changes, but these alleviating effects of rapamycin were abrogated by chemical inhibition of Akt and mTOR complex 2 (mTORC2). Conclusions: These findings suggest that rapamycin blunts adverse effects of inflammation on disc cells by inhibiting mTORC1 to induce autophagy through the PI3K/Akt/mTOR pathway that is dependent on Akt and mTORC2 activities. Hence, our findings identify autophagy, rapamycin, and PI3K/Akt/mTOR signaling as potential therapeutic targets for IDD treatment.

NDUFA4L2 is a novel biomarker for colorectal cancer through bioinformatics analysis.

Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide. NDUFAL42 is an important mitochondrial respiratory chain subunit that plays a critical role in cellular energy metabolism. However, the role of NDUFA4L2 in CRC remains unclear. Therefore, we used the data obtained from The Cancer Genome Atlas (TCGA) database to prove the relationship between NDUFA4L2 and CRC. The expression levels of NDUFA4L2 in CRC tissues were analyzed by immunohistochemical staining of NDUFA4L2 from the HPA database. Wilcoxon rank sum test, Chi-square test, Fisher exact test and logistic regression were used to evaluate relationships between clinical-pathologic features and NDUFA4L2 expression. Receiver operating characteristic (ROC) curves were used to describe binary classifier value of NDUFA4L2 using area under curve (AUC) score. Kaplan-Meier method and Cox regression analysis were used to evaluate factors contributing to prognosis. Gene oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to predict the function of differentially expressed genes associated with NDUFA4L2. Gene set enrichment analysis (GSEA) was used to predict canonical pathways associated with NDUFA4L2.Immune infiltration analysis was performed to identify the significantly involved functions of NDUFA4L2. Protein-protein interaction (PPI) networks were established and 20 hub genes identified with Cytoscape software. Increased NDUFA4L2 expression in CRC was associated with T stage (P = .019), N stage (P < .001), Pathologic stage (P = .020), Residual tumor (P = .023), Perineural invasion (P = .039), Lymphatic invasion (P = .007), Histological type(P < .001), PFI event (P = .007) and DSS event (P = .004).ROC curve suggested the significant diagnostic and prognostic ability of NDUFA4L2 (AUC = 0.878). High NDUFA4L2 expression predicted a poorer Overall-survival (P = .021), poorer progression-free interval (P = .001), and poorer Disease Specific Survival (P = .002). GO, KEGG, GSEA and immune infiltration analysis showed that NDUFA4L2 expression was correlated with regulating the function of DNA and some types of immune infiltrating cells. NDUFA4L2 expression was significantly correlated with poor survival and immune infiltrations in CRC, and it may be a promising prognostic biomarker in CRC.

Frailty in relation to the risk of carotid atherosclerosis and cardiovascular events in Chinese community-dwelling older adults: A five-year prospective cohort study.

OBJECTIVE: To investigate the frailty, as estimated by accumulated health deficits, in association with the symptomatic carotid atherosclerosis and in relation to five-year cardiovascular (CVD) outcomes. METHODS: This is a five-year prospective cohort study. Secondary analysis of data from the Beijing Longitudinal Study on Aging. Community-dwelling people aged 55+ years (n = 1257) have been followed between 2009 and 2014, and having carotid ultrasonography examinations with no CVD events at baseline. Frailty was quantified using the deficit accumulation-based frailty index (FI), constructed from 37 health deficits assessed at baseline. The association between the degree of frailty and carotid atherosclerosis was examined using odds ratios (OR) with multivariate logistic regression analyses. Effects of frailty on the probability of five-year cardiovascular events and mortality were evaluated using Cox proportional hazard ratios (HR). The analyses were adjusted for demographics, baseline carotid atherosclerosis status, and CVD risk factors. RESULTS: The FI showed characteristic properties and was independently associated with the major carotid atherosclerosis symptoms, including carotid artery intima-media thickening (the most frail vs. the least frail: OR = 4.39: 1.98-7.82), carotid plaque (OR = 3.41: 1.28-6.54), and carotid plaque stability (OR = 1.19, 95 % CI: 1.01-3.59). Compared with the least frail, the most frail individuals were more likely to develop a cardiovascular event in five years, including myocardial infarction (HR = 3.38, 95 % CI = 1.84-6.19), stroke (HR = 1.26, 95 % CI = 1.00-5.87), CVD death (HR = 6.33, 95 % CI = 1.69-11.02), and all-cause death (HR = 5.95, 95 % CI = 2.74-8.95). CONCLUSION: Deficit accumulation was closely associated with carotid atherosclerosis risks and strongly predicted five-year CVD events. The frailty index can be used to help identify older adults at high risks of CVD for improved preventive healthcare.

Preoperative Base Excess as a Predictor of Perioperative Complications in Patients with Nonidiopathic Scoliosis who Have High Risk Associated with General Anesthesia.

Introduction: Patients with nonidiopathic scoliosis often have a high risk associated with general anesthesia because of cardiac or pulmonary dysfunction secondary to underlying diseases. Base excess has been reported as a predictor in the management of trauma and cancer, although not yet in scoliosis. This study was performed to clarify the surgical outcomes and the association of perioperative complications with base excess in patients with nonidiopathic scoliosis who have a high risk associated with general anesthesia. Methods: Patients with nonidiopathic scoliosis who were referred to our institution from 2009 to 2020 because of their high risk associated with general anesthesia were retrospectively enrolled. High-risk factors for anesthesia were determined by a senior anesthesiologist and categorized into circulatory or pulmonary dysfunction. Perioperative complications were analyzed using the Clavien-Dindo classification; severe complications were defined as grade ≥III. We investigated high-risk factors for anesthesia, underlying diseases, preoperative and postoperative Cobb angle, surgery-related factors, base excess, and postoperative management. These variables were statistically compared between patients with and without complications. Results: Thirty-six patients (mean age, 17.9 years old; range, 11-40 years old) were enrolled (two patients declined surgery). High-risk factors were circulatory dysfunction in 16 patients and pulmonary dysfunction in 20 patients. The mean Cobb angle improved from 85.1° (36°-128°) preoperatively to 43.6° (9°-83°) postoperatively. Three intraoperative complications and 23 postoperative complications occurred in 20 (55.6%) patients. Severe complications occurred in 10 (27.8%) patients. All patients underwent postoperative intensive care unit management after posterior all-screw construction. A large preoperative Cobb angle (p=0.021) and base excess outliers (>3 or <-3 mEq/L) (p=0.005) were significant risk factors for complications. Conclusions: Patients with nonidiopathic scoliosis who have a high risk associated with general anesthesia have a higher complication rate. Preoperative large deformity and base excess (>3 or <-3 mEq/L) could be predictors of complications.

Anti-Inflammatory Effects of Adiponectin Receptor Agonist AdipoRon against Intervertebral Disc Degeneration.

Adiponectin, a hormone secreted by adipocytes, has anti-inflammatory effects and is involved in various physiological and pathological processes such as obesity, inflammatory diseases, and cartilage diseases. However, the function of adiponectin in intervertebral disc (IVD) degeneration is not well understood. This study aimed to elucidate the effects of AdipoRon, an agonist of adiponectin receptor, on human IVD nucleus pulposus (NP) cells, using a three-dimensional in vitro culturing system. This study also aimed to elucidate the effects of AdipoRon on rat tail IVD tissues using an in vivo puncture-induced IVD degeneration model. Analysis using quantitative polymerase chain reaction demonstrated the downregulation of gene expression of proinflammatory and catabolic factors by interleukin (IL)-1ß (10 ng/mL) in human IVD NP cells treated with AdipoRon (2 µM). Furthermore, western blotting showed AdipoRon-induced suppression of p65 phosphorylation (p < 0.01) under IL-1ß stimulation in the adenosine monophosphate-activated protein kinase (AMPK) pathway. Intradiscal administration of AdipoRon was effective in alleviating the radiologic height loss induced by annular puncture of rat tail IVD, histomorphological degeneration, production of extracellular matrix catabolic factors, and expression of proinflammatory cytokines. Therefore, AdipoRon could be a new therapeutic candidate for alleviating the early stage of IVD degeneration.

Prevalence and factors associated with insomnia among medical students in China during the COVID-19 pandemic: characterization and associated factors.

BACKGROUND: Insomnia has become an important issue in recent years. Insomnia is affected by many factors. Previous research has shown that during the COVID-19 pandemic, there would be a long-term negative effect on the mental health of medical college students. The state of medical college students' insomnia directly determines the results of medical education and the career development prospects of the medical students themselves. Therefore, it is very important to understand the insomnia situation of medical students in the post-epidemic era. METHODS: This study was conducted 2 years after the global COVID-19 pandemic (April 1-April 23, 2022). The study used an online questionnaire, administered through a web-based survey platform. The Athens Insomnia Scale (AIS), Fear of COVID-19 Scale (FCV-19S), GAD-2, PHQ-2, and socio-demographic information were surveyed by the Questionnaire Star platform. RESULTS: The prevalence of insomnia was 27.80% (636/2289). Grade(P < 0.05), age(P < 0.001), loneliness(P < 0.001), depression(P < 0.001), anxiety(P < 0.001), fear of COVID-19 was highly correlated with insomnia (P < 0.001). Adapting to online class(P < 0.001) was a protective factor of smartphone addiction. CONCLUSIONS: This survey shows that Insomnia was highly prevalent among the Chinese medical college students during the COVID-19 pandemic. Governments and schools should through psychological interventions to address the current situation of insomnia among medical students, and formulate targeted programs and strategies to reduce their psychological problems.

LncRNA DIRC1 is a novel prognostic biomarker and correlated with immune infiltrates in stomach adenocarcinoma.

The potential application value of Long non-coding RNA disrupted in renal carcinoma 1 (DIRC1) has not yet been explored, the purpose of this study was to explore the relationship between DIRC1 and stomach adenocarcinoma (STAD) based on the cancer genome atlas database. Wilcoxon rank sum test, Chi-square test, Fisher test and logistic regression were used to evaluate relationships between clinical-pathologic features and DIRC1 expression. Receiver operating characteristic (ROC) curves were used to describe binary classifier value of DIRC1 using area under curve (AUC) score. Kaplan-Meier method was used to assess the impact of DIRC1 on prognosis and the impact of DIRC1-related hub genes on prognosis. Gene oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to predict the function of differentially expressed genes associated with DIRC1. Gene set enrichment analysis (GSEA) was used to predict biological states or processes associated with DIRC1. Immune infiltration analysis was performed to identify the significantly involved functions of DIRC1. Protein-protein interaction (PPI) networks were established and 10 hub genes identified with Cytoscape software. Real time-polymerase chain reaction (RT-PCR) was used to detect the expression of DIRC1 in Gastric Cancer patients and healthy people. Increased DIRC1 expression in STAD was associated with T stage (P = .004), race (P = .045), histologic grade (P = .029) and anatomic neoplasm subdivision (P = .034). ROC curve suggested the significant diagnostic ability of DIRC1 (AUC = 0.779). High DIRC1 expression predicted a poorer Overall survival (P = .004, hazard ratio: 1.63; 95% confidence interval: 1.17-2.27; P = .034). GO and KEGG analysis demonstrated that DIRC1 is related to epidermis, collagen-containing extracellular matrix, receptor-ligand activity, protein digestion and absorption, etc. GSEA demonstrated that E2F target, G2M checkpoint, Myc target, interferon γ reaction were differentially enriched in the high DIRC1 expression phenotype. SsGSEA and Spearman correlation revealed the relationships between DIRC1 and macrophages, dendritic cells, and Th1 cells were the strongest. Coregulatory proteins were included in the PPI network, higher expressions of 4 hub genes were associated with worse prognosis in STAD. RT-PCR showed that the expression of DIRC1 in the serum of Gastric Cancer patients was higher than healthy people (P = .027). DIRC1 expression was significantly correlated with poor survival and immune infiltrations in STAD, and it may be a promising prognostic biomarker in STAD.

Survival Rate after Palliative Surgery Alone for Symptomatic Spinal Metastases: A Prospective Cohort Study.

The effect of spine surgery for symptomatic spinal metastases (SSM) on patient prognosis remains unclear. This study aimed to reveal the prognosis of patients with SSM after spine surgery. One hundred twenty-two patients with SSM were enrolled in this prospective cohort study. The patients who received chemotherapy after enrollment were excluded. The decision of surgery depended on patient's willingness; the final cohort comprised 31 and 24 patients in the surgery and non-surgery groups, respectively. The patients were evaluated by their performance status (PS), activities of daily living (ADL) and ambulatory status. Survival was evaluated by the Kaplan-Meier method. The PS, ADL and ambulation were significantly improved in the surgery group compared to non-surgery group. The median survival was significantly longer in the surgery group (5.17 months, 95% confidence interval (CI) 3.27 to 7.07) than in the non-surgery group (2.23 months, 95% CI 2.03 to 2.43; p = 0.003). Furthermore, the patients with a better PS, ADL and ambulatory status had a significantly longer survival. Surgery improved the PS, ADL, ambulation and survival of patients with SSM. In the management of SSM, spine surgery is not only palliative but may also prolong survival.

LncRNA ALMS1-IT1 is a novel prognostic biomarker and correlated with immune infiltrates in colon adenocarcinoma.

Colon adenocarcinoma (COAD) is one of the most serious cancers. It is important to accurately predict prognosis and provide individualized treatment. Evidence suggests that clinicopathological features and immune status of the body are related to the occurrence and development of cancer. Expression of long non-coding RNA (LncRNA) ALMS1 intronic transcript 1 (ALMS1-IT1) is observed in some cancer types, and we believe that it may have the potential to serve as a marker of COAD. Therefore, we used the data obtained from the cancer genome atlas (TCGA) database to prove the relationship between ALMS1-IT1 and COAD. Wilcoxon rank sum test, Chi-square test, Fisher exact test and logistic regression were used to evaluate relationships between clinical-pathologic features and ALMS1-IT1 expression. Receiver operating characteristic curves were used to describe binary classifier value of ALMS1-IT1 using area under curve score. Kaplan-Meier method and Cox regression analysis were used to evaluate factors contributing to prognosis. Gene oncology (GO) and (Kyoto Encyclopedia of Genes and Genomes) KEGG enrichment analysis were used to predict the function of differentially expressed genes associated with ALMS1-IT1. Gene set enrichment analysis (GSEA) was used to predict canonical pathways associated with ALMS1-IT1.Immune infiltration analysis was performed to identify the significantly involved functions of ALMS1-IT1. Starbase database was used to predict miRNAs and RNA binding proteins (RBPs) that may interact with ALMS1-IT1. Increased ALMS1-IT1 expression in COAD was associated with N stage (P < .001), M stage (P = .003), Pathologic stage (P = .002), and Primary therapy outcome (P = .009). Receiver operating characteristic curve suggested the significant diagnostic and prognostic ability of ALMS1-IT1 (area under curve = 0.857). High ALMS1-IT1 expression predicted a poorer overall-survival (P = .005) and poorer progression-free interval (PFI) (P = .012), and ALMS1-IT1 expression was independently correlated with PFI in COAD patients (hazard ratio (HR) :1.468; 95% CI: 1.029-2.093; P =.034) (HR: 1.468; 95% CI: 1.029-2.093; P = .034). GO, KEGG, GSEA, and immune infiltration analysis showed that ALMS1-IT1 expression was correlated with regulating the function of DNA and some types of immune infiltrating cells. ALMS1-IT1 expression was significantly correlated with poor survival and immune infiltrations in COAD, and it may be a promising prognostic biomarker in COAD.

A frailty index based on routine laboratory data predicts increased risk of mortality in Chinese community-dwelling adults aged over 55 years: a five-year prospective study.

BACKGROUND: Frailty can be operationalized based on the accumulation of deficits using a frailty index (FI) and is associated with an increased risk of adverse health outcomes. Here, we aim to compare validity of a FI from laboratory data with that of the common clinical FI for prediction of mortality in adults aged 55 + years, also examine whether combined FI could improve identification of adults aged 55 + years at increased risk of death. METHODS: Data for this analysis were obtained from the Beijing Longitudinal Study of Aging that involved 1,257 community-dwelling Chinese people, aged 55 + years at baseline. The main outcome measure was 5-year mortality. An FI-self-report based on 30 self-reported health-related data was constructed. An FI-lab was developed using laboratory data, in addition to pulse, systolic and diastolic blood pressure, pulse pressure, body mass index (BMI) and waist. A combined FI comprised all items from each FI. Kaplan-Meier survival curve and Cox proportional hazards models were performed to evaluate the risk of each FI on death. The area under receiver operating characteristic(ROC) curves were used to compare the discriminative performance of each FI. RESULTS: Of 1257 participants, 155 died and 156 lost at the end of the 5-year follow-up. The mean FI-self-report score was 0.11 ± 0.10, the FI-lab score was 0.33 ± 0.14 and FI-combined score was 0.19 ± 0.09. Higher frailty level defined by each FI was associated with higher risk of death. After adjustment for age and sex, Cox proportional hazards models showed that the higher scores of frailty were associated with a higher risk of mortality for each FI, the hazard ratios for the FI-self-report and FI-lab and FI-combined were 1.04 (1.03 to 1.05) and 1.02 (1.01 to 1.03) and 1.05 (1.04 to 1.07), respectively. The areas under the ROC curve were 0.79 (0.77-0.82) for the FI-self-report, 0.77(0.75-0.80) for the FI-lab and 0.81(0.78-0.82) for FI-combined. CONCLUSIONS: A FI from laboratory data can stratify older adults at increased risk of death alone and in combination with FI based on self-report data. Assessment in clinical settings of creating an FI using routine collected laboratory data needs to be further developed.

Discovering Innate Driver Variants for Risk Assessment of Early Colorectal Cancer Metastasis.

Metastasis is the main fatal cause of colorectal cancer (CRC). Although enormous efforts have been made to date to identify biomarkers associated with metastasis, there is still a huge gap to translate these efforts into effective clinical applications due to the poor consistency of biomarkers in dealing with the genetic heterogeneity of CRCs. In this study, a small cohort of eight CRC patients was recruited, from whom we collected cancer, paracancer, and normal tissues simultaneously and performed whole-exome sequencing. Given the exomes, a novel statistical parameter LIP was introduced to quantitatively measure the local invasion power for every somatic and germline mutation, whereby we affirmed that the innate germline mutations instead of somatic mutations might serve as the major driving force in promoting local invasion. Furthermore, via bioinformatic analyses of big data derived from the public zone, we identified ten potential driver variants that likely urged the local invasion of tumor cells into nearby tissue. Of them, six corresponding genes were new to CRC metastasis. In addition, a metastasis resister variant was also identified. Based on these eleven variants, we constructed a logistic regression model for rapid risk assessment of early metastasis, which was also deployed as an online server, AmetaRisk (http://www.bio-add.org/AmetaRisk). In summary, we made a valuable attempt in this study to exome-wide explore the genetic driving force to local invasion, which provides new insights into the mechanistic understanding of metastasis. Furthermore, the risk assessment model can assist in prioritizing therapeutic regimens in clinics and discovering new drug targets, and thus substantially increase the survival rate of CRC patients.

Associations of blood pressure components with risks of cardiovascular events and all-cause death in a Chinese population: A Prospective Study.

The associations of blood pressure components with cardiovascular risks and death remain unclear, and the definition of wide pulse pressure (PP) is still controversial. Using data from 1257 participants without a history of cardiovascular disease, who were followed for 4.84 years, we performed multivariable Cox regression analyses to assess how systolic blood pressure (SBP), diastolic blood pressure (DBP), and PP contribute to risks of cardiovascular events and all-cause death. Among all participants, SBP and PP were significantly associated with the risks of cardiovascular events and all-cause death (all p < .05). DBP was not significantly associated with the risk of all-cause death; rather, it was only associated with a marginally significant 1% increased risk for cardiovascular events (p = 0.051). In participants aged < 65 years, DBP was significantly associated with a 3% increased risk for cardiovascular events (hazard ratio [HR]: 1.03, 95% confidence interval [95% CI]: 1.01-1.06). The association between PP and cardiovascular events appeared to be J-shaped in comparison to participants with the lowest-risk PP (50-60 mmHg), with adjusted HRs of 1.71 (95% CI: 1.03-2.85), 1.63 (95% CI: 1.00-2.68), and 2.13 (95% CI: 1.32-3.43) in the <50, 60.0-72.5, and ≥72.5 mmHg subgroups, respectively. The optimal cutoff points of a wide PP for predicting the risks of cardiovascular events and all-cause death were 70.25 and 76.25 mmHg, respectively. SBP and PP had a greater effect on cardiovascular risk, whereas DBP independently influenced cardiovascular events in middle-aged participants. Considerable PP alterations should be avoided in antihypertensive treatment.

Protective Effects of Growth Differentiation Factor-6 on the Intervertebral Disc: An In Vitro and In Vivo Study.

Growth differentiation factors (GDFs) regulate homeostasis by amplifying extracellular matrix anabolism and inhibiting pro-inflammatory cytokine production in the intervertebral disc (IVD). The aim of this study was to elucidate the effects of GDF-6 on human IVD nucleus pulposus (NP) cells using a three-dimensional culturing system in vitro and on rat tail IVD tissues using a puncture model in vivo. In vitro, Western blotting showed decreased GDF-6 expression with age and degeneration severity in surgically collected human IVD tissues (n = 12). Then, in moderately degenerated human IVD NP cells treated with GDF-6 (100 ng/mL), immunofluorescence demonstrated an increased expression of matrix components including aggrecan and type II collagen. Quantitative polymerase chain reaction analysis also presented GDF-6-induced downregulation of pro-inflammatory tumor necrosis factor (TNF)-α (p = 0.014) and interleukin (IL)-6 (p = 0.016) gene expression stimulated by IL-1ß (10 ng/mL). Furthermore, in the mitogen-activated protein kinase pathway, Western blotting displayed GDF-6-induced suppression of p38 phosphorylation (p = 0.041) under IL-1ß stimulation. In vivo, intradiscal co-administration of GDF-6 and atelocollagen was effective in alleviating rat tail IVD annular puncture-induced radiologic height loss (p = 0.005), histomorphological degeneration (p < 0.001), matrix metabolism (aggrecan, p < 0.001; type II collagen, p = 0.001), and pro-inflammatory cytokine production (TNF-α, p < 0.001; IL-6, p < 0.001). Consequently, GDF-6 could be a therapeutic growth factor for degenerative IVD disease.

Combined homocysteine and apoE rs429358 and rs7412 polymorphism in association with serum lipid levels and cognition in Chinese community-dwelling older adults.

BACKGROUND: ApoE gene polymorphism and serum total homocysteine (tHcy) has been reportedly associated with cognition. In this study, we assessed the association of combined ApoE gene polymorphism and tHcy with cognition in Chinese elder adults. METHODS: A cross- sectional study was carried out by recruiting 1458 community-dwelling people aged 55+ and above in Beijing in 2009. All participants were interviewed using a standard questionnaire and underwent a physical examination. The mini-mental scale examination (MMSE) score was used in assessing cognitive function. Fasting venous blood samples were taken for ApoE rs429358, rs7412 genotyping, tHcy and other serum lipid measurements. RESULTS: Participants with high serum tHcy level showed a relatively lower orientation, attention abilities as well as the total MMSE score than the group with normal tHcy after adjusting confounding factors. ApoE rs429358 and rs7412 variants were observed to have the highest serum TC and TG level in the subjects with high serum tHcy level (p <  0.05). Cognition of the subjects was found to be significantly associated with high serum tHcy level and ApoE genetic polymorphism (p <  0.05). Independent of age, BMI, education levels, smoking and alcohol drinking, the worst cognitive ability were detected in the high serum tHcy level subjects with ApoE rs429358C/T and rs7412 C/T as compare with other groups, especially orientation function, memory and delayed recall ability and attention ability. CONCLUSION: High serum tHcy level in combination with ApoE rs429358 and rs7412 variants might be linked with serum lipid levels and cognition, particularly for orientation function and memory and delayed recall ability in old Chinese adults.

Self-healing Growth of LaNiO3 on a Mixed-Terminated Perovskite Surface.

Developing atomic-scale synthesis control is a prerequisite for understanding and engineering the exotic physics inherent to transition-metal oxide heterostructures. Thus, far, however, the number of materials systems explored has been extremely limited, particularly with regard to the crystalline substrate, which is routinely SrTiO3. Here, we investigate the growth of a rare-earth nickelate─LaNiO3─on (LaAlO3)(Sr2AlTaO6) (LSAT) (001) by oxide molecular beam epitaxy (MBE). Whereas the LSAT substrates are smooth, they do not exhibit the single surface termination usually assumed necessary for control over the interface structure. Performing both nonresonant and resonant anomalous in situ synchrotron surface X-ray scattering during MBE growth, we show that reproducible heterostructures can be achieved regardless of both the mixed surface termination and the layer-by-layer deposition sequence. The rearrangement of the layers occurs dynamically during growth, resulting in the fabrication of high-quality LaNiO3/LSAT heterostructures with a sharp and consistent interfacial structure. This is due to the thermodynamics of the deposition window as well as the nature of the chemical species at interfaces─here, the flexible charge state of nickel at the oxide surface. This has important implications regarding the use of a wider variety of substrates for fundamental studies on complex oxide synthesis.

Prevalence and Risk Factors Comparison of Anterior and Posterior Intracranial Arterial Stenosis.

The prevalence and risk factors of intracranial atherosclerotic stenosis (ICAS) located in the anterior circulation (AC) and posterior circulation (PC) has been scarcely noted in the general population. We aimed to determine ICAS prevalence and risk factor profile of AC and PC in a representative population. Data were from the China Hypertension Survey of Beijing. In total, 4800 people aged 35 years or older were enrolled in this subsurvey for ICAS, and 3954 participants were eligible for analysis. ICAS was assessed by transcranial Doppler. The prevalence of ICAS in AC was much greater than that in PC (11.9% vs. 4.2%), and subjects with ICAS in PC were 3.9 years older than those with ICAS in AC. Multivariable logistics regression showed that the odds of hypertension and diabetes increased by 79% (OR: 1.79, 95% CI: 1.40-2.27) and 35% (OR: 1.35, 95% CI: 1.04-1.75) in those with AC vascular lesions and by 3.35 times (OR: 3.35, 95% CI: 2.49-4.50) and 71% (OR: 1.71, 95% CI: 1.19-2.46) in those with PC vascular lesions compared with those without vascular lesions. Most modifiable vascular risk factors for ICAS appeared to exert similar magnitudes of risk for PC to AC lesions.