CatLet score and clinical CatLet score as predictors of long-term outcomes in patients with acute myocardial infarction presenting later than 12 hours from symptom onset.

BACKGROUND: Our recently developed Coronary Artery Tree description and Lesion EvaluaTion (CatLet) angiographic scoring system is unique in its description of the variability in the coronary anatomy, the degree of stenosis of a diseased coronary artery, and its subtended myocardial territory, and can be utilized to predict clinical outcomes for patients with acute myocardial infarction (AMI) presenting ≤12 h after symptom onset. The current study aimed to assess whether the Clinical CatLet score (CCS), as compared with CatLet score (CS), better predicted clinical outcomes for AMI patients presenting >12 h after symptom onset. METHODS: CS was calculated in 1018 consecutive AMI patients enrolled in a retrospective registry. CCS was calculated by multiplying CS by the ACEF I score (age, creatinine, and left ventricular ejection fraction). Primary endpoint was major adverse cardiac events (MACEs) at 4-year-follow-up, a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization. RESULTS: Over a 4-year follow-up period, both scores were independent predictors of clinical outcomes after adjustment for a broad spectrum of risk factors. Areas-under-the-curve (AUCs) for CS and CCS were 0.72(0.68-0.75) and 0.75(0.71-0.78) for MACEs; 0.68(0.63-0.73) and 0.78(0.74-0.83) for all-cause death; 0.73(0.68-0.79) and 0.83(0.79-0.88) for cardiac death; and 0.69(0.64-0.73) and 0.75(0.7-0.79) for myocardial infarction; and 0.66(0.61-0.7) and 0.63(0.58-0.68) for revascularization, respectively. CCS performed better than CS in terms of the above-mentioned outcome predictions, as confirmed by the net reclassification and integrated discrimination indices. CONCLUSIONS: CCS was better than CS to be able to risk-stratify long-term outcomes in AMI patients presenting >12 h after symptom onset. These findings have indicated that both anatomic and clinical variables should be considered in decision-making on management of patients with AMI presenting later.

Association between Abdominal Aortic Calcification and Coronary Heart Disease in Essential Hypertension: A Cross-Sectional Study from the 2013-2014 National Health and Nutrition Examination Survey.

BACKGROUND: This study aimed to investigate the association between abdominal aortic calcification (AAC) and coronary heart disease (CHD) in essential hypertension (EH). METHODS: This study included patients diagnosed with EH during the 2013-2014 NHANES survey cycle. The study cohort was categorized into the following four groups based on their AAC-24 score: no AAC (0); mild AAC (1-4); moderate AAC (5-15); and severe AAC (16-24). Logistic regression models were used to assess the association between AAC and CHD. Restricted cubic spline curves (RCS) were used to explore possible nonlinear relationships between AAC and CHD. RESULTS: The prevalence of CHD was found to be higher in the moderate AAC and severe AAC groups than in the group without AAC (40.1% versus 30.9%, 47.7% versus 30.9%). On a continuous scale, the fully adjusted model showed a 7% increase in the risk of CHD prevalence per score increase in AAC [OR (95% CI) = 1.07 (1.03-1.11)]. On a categorical scale, the fully adjusted model showed the risk of CHD prevalence in EH patients with moderate AAC and severe AAC was 2.06 (95%CI, 1.23-3.45) and 2.18 (1.09-5.25) times higher than that in patients without AAC, respectively. The RCS curve suggested a dose-response linear relationship between AAC and CHD. CONCLUSION: These findings highlight that in patients with EH, a higher severity of AAC is associated with a higher risk of CHD prevalence.

Coronary Artery Tree Description and Lesion Evaluation (CatLet) score for functional evaluation of coronary stenosis: a comparison study with pressure wire fractional flow reserve.

Background: Pressure wire fractional flow reserve (FFR) and its derivatives, such as quantitative flow ratio (QFR), computational pressure flow-derived FFR (caFFR), coronary angiography-derived FFR (FFRangio), and computed tomography-derived FFR (FFRCT), have been validated for identifying functionally significant stenosis and guiding revascularization strategy. The limitations of using these methods include the side effects of hyperemia-induced agents, additional costs, and vulnerability to microvascular resistance. FFR is related both to the degree of a stenotic coronary artery and to its subtended myocardial territory. Coronary Artery Tree Description and Lesion Evaluation (CatLet) score (also known as Hexu) is a product of the degree of a stenosis and the weighting of the affected coronary artery (myocardial territory). Hence, we hypothesized that the CatLet score could predict hemodynamically significant coronary stenosis. Methods: We retrospectively enrolled consecutive patients with stable coronary artery disease. They attended Sichuan Science City Hospital with at least one lesion of 50-90% diameter stenosis in a coronary artery of 2 mm or larger. FFR measurement was obtained during invasive coronary angiography. The CatLet score was obtained by multiplying a fixed value of 2.0 (for non-occlusive lesions) and the weight of the affected coronary artery. The primary endpoint was the CatLet score's diagnostic accuracy in identifying hemodynamically significant coronary stenosis, with a pressure wire FFR of ≤0.80 being used as reference. Results: We analyzed the FFR and CatLet scores from 206 vessels in 175 patients with stable coronary disease and intermediate coronary lesions. The per-vessel analysis revealed an overall good correlation between the CatLet score and the FFR [r=-0.61; 95% confidence interval (95% CI): -0.69 to -0.52; P<0.01]. We also noted a significant CatLet score-FFR correlation for each of the left anterior descending artery (LAD), left circumflex (LCX), and right coronary artery (RCA). With a CatLet score ≥10 as a predictor of FFR ≤0.80, the overall diagnostic accuracy included a sensitivity of 78.80% (95% CI: 67.00-87.90%), a specificity of 85.00% (95% CI: 78.00-90.50%), a positive likelihood ratio of 5.25, a negative likelihood ratio of 0.25, and an area under the curve of 0.90 (95% CI: 0.85-0.94). Equivalent vessel-specific results were also achieved for each of the LAD, LCX, and RCA. Conclusions: The CatLet score, solely based on visual estimation of the results of coronary angiography, demonstrated good diagnostic performance with respect to myocardial ischemia. Its clinical values in guiding revascularization warrant further investigation.

The effect and mechanism of volatile oil emulsion from leaves of Clausena lansium (Lour.) Skeels on Staphylococcus aureus in vitro.

This study aimed to develop a suitable dosage form of volatile oil from wampee leaves and to explore its antibacterial mechanism in vitro. The chemical composition of the volatile oil from wampee leaves was determined by gas chromatography-mass spectrometry (GC-MS). Different microemulsion ratios were tested and their stabilities were investigated to determine the optimal ratio. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the wampee leaves volatile oil emulsion (WVOE) against Salmonella typhimurium (S. typhimurium) and Staphylococcus aureus (S. aureus) were determined using double-dilution and plate-counting methods, respectively. Morphological changes in these two bacteria were observed using scanning electron microscopy. Death, ultrastructural morphology, and biofilm formation were also assessed for S. aureus. Finally, we established an S. aureus-infected Lewis lung carcinoma (LLC) cell model to evaluate the protective effects of the volatile oil emulsion and the associated mechanisms. The volatile oil extracted from wampee leaves contained 37 compounds, of which 96.49% were aromatic hydrocarbons, terpenoids, and their oxygen-containing derivatives. The emulsion was most stable at 1:1 in the oil phase and 1:9 in the water phase. WVOE had poor antibacterial activity against S. typhimurium, but the MIC and MBC against S. aureus were 312.5 and 2,500 µg/mL, respectively. S. aureus survival rates were 84.6%, 14.5%, and 12.8% in the 1/2, 1, and 4 × MIC groups, respectively, compared with 97.2% in the control group. S. typhimurium survival was not affected by WVOE treatment. WVOE administration induced cavity formation and abnormal binary fission, and significantly inhibited biofilm formation in S. aureus cells. The WVOE notably reduced the number of S. aureus and inhibited TLR4, NLRP3, NF-κB, IL-6, IL-18, and TNF-α gene expression in S. aureus-infected LLC cells. The WVOE had a significant inhibitory effect on S. aureus and altered its cell membrane permeability. Moreover, it alleviated inflammation by inhibiting the NF-κB-NLRP3 pathway in S. aureus-infected LLC cells.

Three different routes of EHEC O157:H7 infection were used to establish EHEC broiler model.

In order to study the prevention and control EHEC disease measures in poultry, the infection process and development of this disease and the pathological changes of various organs were to be observed. In this study, chickens were infected with different doses of enterohemorrhagic Escherichia coli (EHEC) O157:H7 using different routes of administration to establish EHEC broiler model. A total of 195 14-day-old broilers were randomly divided into 13 groups: including control group, Enema-drip groups (1010, 1011, 1012, 1013 CFUs E. coli O157:H7), gavage groups (P.O) (1011, 1012, 1013, 1014 CFUs E. coli O157:H7), and intraperitoneal injection group (I.P.) (108, 109, 1010, 1011 CFUs E. coli O157:H7). Escherichia coli (E. coli) was given using enema-drip, gavage or intraperitoneal infection. Then the feed intake, weight changes, stool and clinical symptoms of the chicks were recorded during the experiment. 7 d after E. coli infection, blood was collected from the jugular vein and serological tests were carried out. The liver, spleen, and colon of the chicks were extracted to get the organ index, bacteria load, and their histopathological changes. After infection with E. coli, some chicks feces were green or red watery stool, sometimes accompanied by foam, and the material to weight ratio of broilers in I.P. group increased significantly (P < 0.05), the 108 CFUs group were 1.3 times as large as control group. Three modeling methods can result in abnormal serum lipid metabolism and liver function indexes (increase of AST, TBA, T-Bil and TC level; decrease of ALB, TG, and TP level). Infection of chicks with O157:H7 by all 3 methods resulted in its detection in the liver, spleen, and colon. Three modeling methods significantly decreased liver index, and inflammatory cell infiltration and hyperemia were observed in liver. The spleen index in E. coli broilers by gavage and enema-drip was significantly decreased, splenic hyperemia and periarteriolar hyalinosis were observed. The spleen was enlarged with purplish-black spheroids in I.P. group broilers, and the spleen histological changes was more serious. The colon villi of broilers in gavage and enema-drip groups were thinner, more prone to rupture, intestinal lamina propria hyperemia, and inflammatory cell infiltration. Moreover, the number of goblet cells in the mucosal epithelium increased. E. coli O157:H7 can induce liver, spleen and intestinal damage and reduce growth performance of chicks. By comparing these 3 methods, we found that chicks infected with O157:H7 by gavage had more severe liver and intestinal damage, the enema-drip method caused most serious intestinal damage, and I.P. method significantly damaged the liver and spleen of chickens.

Developing and Validating a Simple Risk Score for Patients with Acute Myocardial Infarction.

INTRODUCTION: Mortality from acute myocardial infarction (AMI) remains substantial. The current study is aimed at developing a novel simple risk score for AMI. METHODS: The Coronary Artery Tree description and Lesion EvaluaTion (CatLet) extended validation trial (ChiCTR2000033730) and the CatLet validation trial (ChiCTR-POC-17013536), both being registered with chictr.org, served as the derivation and validation datasets, respectively. Both datasets included 1,018 and 308 patients, respectively. They all suffered from AMI and underwent percutaneous intervention (PCI). The endpoint was 4-year all-cause death. Lasso regression analysis was used for covariate selection and coefficient estimation. RESULTS: Of 26 candidate predictor variables, the four strongest predictors for 4-year mortality were included in this novel risk score with an acronym of BACEF (serum alBumin, Age, serum Creatinine, and LVEF). This score was well calibrated and yielded an AUC (95% CI) statistics of 0.84 (0.80-0.87) in internal validation, 0.89 (0.83-0.95) in internal-external (temporal) validation, and 0.83 (0.77-0.89) in external validation. Notably, it outperformed the ACEF, ACEF II, GRACE scores with respect to 4-year mortality prediction. CONCLUSION: A simple risk score for 4-year mortality risk stratification was developed, extensively validated, and calibrated in patients with AMI. This novel BACEF score may be a useful risk stratification tool for patients with AMI.

Serum Copper Concentrations, Effect Modifiers and Blood Pressure: Insights from NHANES 2011-2014.

(1) Background: Epidemiological studies on the relationship between serum copper and hypertension are contradictory. We assessed the relationship between serum copper and blood pressure among adults in the United States. (2) Methods: We divided hypertension into two categories: treated hypertension and untreated hypertension. Linear or logistic regression analysis was applied to investigate the association between serum copper concentrations and blood pressure levels. (3) Results: As compared to quartile 1, the odds ratios (ORs) for untreated hypertension in quartiles 2, 3, and 4 were 1.02 (0.74-1.42), 1.23 (0.88-1.72), and 1.08 (0.74-1.58), respectively, in multivariable analysis (all p > 0.05). In non-hypertension, as compared with quartile 1, the ß (95% CI) of systolic blood pressure for quartiles 2, 3, and 4 was -0.92 (-2.07-0.23), -0.05 (-1.30-1.20), and -0.48 (-1.83-0.88), respectively, in multivariable analysis (all p > 0.05). As compared to quartile 1, the ORs for treated hypertension in quartiles 2, 3, and 4 were 1.36 (0.88-2.10), 1.35 (0.87-2.09), and 1.56 (0.98-2.47), respectively, upon multivariable analysis including antihypertensive medication use as a covariate (all p > 0.05). Furthermore, 1SD increase in serum copper was non-significantly associated with 1.16 (0.97-1.37)-fold increased risk of hypertension in multivariable analysis (p = 0.096). (4) Conclusion: In the present study, we discovered that the serum copper concentration was not related with hypertension or blood pressure levels. Antihypertensive drug use may distort the correlation between copper and blood pressure levels. Information on antihypertensive drug use may be taken into account when identifying new risk factors for hypertension.

Neutrophil-to-lymphocyte ratio in relation to trauma severity as prognosis factors in patients with multiple injuries complicated by multiple organ dysfunction syndrome: A retrospective analysis.

OBJECTIVE: This study aimed to explore potential risk factors for the occurrence of multiple organ dysfunction syndrome (MODS) in patients with multiple injuries by evaluating neutrophil-to-lymphocyte ratio (NLR)-associated trauma severity. METHODS: This retrospective case-control study included 95 patients with multiple injuries, who were admitted to our hospital (between January 2018 and December 2020). Clinical data including gender, age, underlying disease, number of injury sites (NIS), injury severity score (ISS), hemoglobin level within 24 h of admission (HL-24h), neutrophil count (NC), white blood cell count, platelet count (PC), NLR, d-dimer level, activated partial thromboplastin time (APTT), complicated shock within 24 h of admission (CS-24h), length of stay, as well as prognostic outcome was systematically analyzed. According to MODS occurrence, patients were divided into a MODS group (n = 27) and a non-MODS group (n = 68). The risk factors affecting patients with multiple injuries complicated by MODS were identified using univariate and multivariate logistic regression analyses. Candidate risk factors were further analyzed using receiver operating characteristic (ROC) curves. RESULTS: Univariate analysis revealed a significant difference between the MODS and non-MODA groups in terms of NIS, ISS, HL-24h, PC, APTT, d-dimer level, CS-24h, NLR, NC, prognostic outcome, and other indicators (p < .05). Multivariate logistic regression analysis showed that  d-dimer levels within 24 h of admission and ISS, NLR, and CS-24h were significantly associated with multiple injuries complicated by MODS. Compared with the non-MODS controls, the NLR in the MODS group showed a much higher level and tended to rise with the increase in ISS score, indicating a significant intergroup difference (p < .05). The ROC curve analysis results suggested that the NLR had good sensitivity and specificity for predicting the prognosis of patients with MODS with multiple injuries. CONCLUSION: d-dimer level, ISS, NLR, and CS-24h are important risk factors for MODS in patients with multiple injuries. Notably, NLR expression may be a good indicator of injury severity and predictor of the occurrence of MODS in patients with multiple injuries. Therefore, assessment of injury severity and coagulation function, active resuscitation, as well as prevention of infection should be emphasized during treatment of multiple injuries, to reduce and prevent the risk of MODS in patients with multiple injuries.

Revisit of the CatLet (Hexu) angiographic scoring system: a narrative review.

Background and Objective: We have recently developed the Coronary Artery Tree description and Lesion EvaluaTion (CatLet or Hexu, invented by He and Xu) angiographic scoring system, which, considering the coronary anatomy in its diversity, the stenosis degree of a coronary artery, and the myocardial territory subtended by the diseased coronary artery, can be utilized to predict clinical outcomes for patients with acute myocardial infarction (available at www.catletscore.com). Its values for clinical practice and coronary artery disease research are building upon. Over the past two years, the principles underlying this novel angiographic scoring system do not materially change although slight adjustments have really happened. Given these adjustments and the scoring experience gained in daily use, we think that it is necessary to elaborate on these points so that readers with interest are capable to better use this CatLet or Hexu angiographic scoring system both in clinical practice and in scientific research. Methods: The principles underlying this novel angiographic scoring system include the 17-myocardial segmental model, law of competitive blood supply, and law of flow conservation. Key Content and Findings: The adjustments made to this novel angiographic scoring system include: (I) the short axis of the left ventricle at the basal level is used to characterize the six types of right coronary artery size; (II) segments marked with 'X and 'S have a unified preset difference of one segment as adopted in the characterization of left anterior descending artery; (III) segments marked with '+ have been added to explain the rare variability in the obtuse marginal branches or in the posterolateral vessels in some cases. The CatLet or Hexu angiographic scoring system strictly follows the law of flow conservation in weighting assignment, and the lesion scoring correction has been additionally emphasized and detailed. Conclusions: The elaboration on these adjustments and scoring experience gained on the CatLet or Hexu angiographic scoring system will help to boost its use in cardiovascular field. The utilities of this novel angiographic scoring system have been preliminarily validated and its future is deserving of being anticipated.

Resveratrol inhibits oxidative damage in lungs of heat-stressed broilers by activating Nrf2 signaling pathway and autophagy.

The purpose of this study was to investigate the effects of resveratrol on heat stress-induced lung injury in broilers and the mechanism underlying this process. Sixty two-week-old SPF BWEL broilers were randomly divided into the heat stress group (HS), resveratrol group (heat stress + 400 mg/kg resveratrol), and the control group after one week of feeding, with 20 chickens in each group. Broilers in the control group were reared at 23 ± 2 â„ƒ. Those in the HS and resveratrol group were reared under heat stress (35 â„ƒ ± 2 â„ƒ) for 8 h/day for seven days. Broilers in the resveratrol group were fed a diet supplemented with 400 mg/kg resveratrol two days before the start of the experiment. The feeding was continued for nine days. The results showed that HS decreased body weight (BW), average daily feed intake (ADFI), average daily gain (ADG), and lung weight. It, however, increased the lung index, induced lung congestion, and promoted infiltration of inflammatory cells to the lung. Resveratrol improved growth performance and inhibited heat stress-induced lung damage. Compared with broilers in the control group, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), Beclin-1, LC3 Ⅰ, and LC3 Ⅱ genes in the lung of heat-stressed broilers was significantly lower. The levels of kelch-like ECH-associated protein 1 (Keap1), NQO1, and HO-1 showed a similar trend with gene expressions. Immunofluorescence indicated that HS inhibited the expression of Nrf2 and LC3B proteins. Finally, the ratio of LC3 Ⅱ/LC3 Ⅰ was also significantly lower in the HS group. Further analyses revealed that resveratrol supplements in feeds enhanced antioxidation in the lung by activating the Nrf2 signaling pathway and autophagy. In conclusion, HS causes oxidative damage and inhibits autophagy in broilers. However, resveratrol protects against lung injury by alleviating oxidative stress and enhancing autophagy.

Acetaminophen-induced hepatotoxicity predominantly via inhibiting Nrf2 antioxidative pathway and activating TLR4-NF-κB-MAPK inflammatory response in mice.

To explore the action time and molecular mechanism underlying the effect of acetaminophen (APAP) on liver injury. APAP was used to establish drug-induced liver injury (DILI) model in mice. Mice in the model group were intraperitoneally injected 300 mg/kg APAP for 6, 12, and 24 h respectively, and control group mice were given the same volume of normal saline. The mice were anesthetized through intravenous injection of sodium pentobarbital at 6, 12, and 24 h after APAP poisoning. Analysis of ALT, AST and ALP in serum, liver histopathological observation, oxidative damage and western blot were performed. The livers in APAP exposed mice were pale, smaller, with a rough texture, and poorly arranged cells. Lesions, large areas of hyperemia, inflammation, swelling, poorly cell arrangement, necrosis, and apoptosis of liver cells were obvious in the liver tissue sections. Serum ALT, AST and ALP levels were significantly enhanced at 12 h of APAP adminstration mice than that of in control group mice (P＜0.05). The histopathological alterations and proinflammatory cytokines (IL-1ß, TNF-α and IL-6) levels were most severe at 12 h of APAP-induced hepatotoxicity. APAP treatment induced oxidative stress by decreasing hepatic activities of superoxide dismutase (SOD) and glutathione (GSH) (P＜0.05), and enhancing malondialdehyde (MDA) content (P＜0.05). Moreover, APAP inhibited erythroid 2-related factor 2 (Nrf2) antioxidative pathway with decreased of Nrf2 and HO-1 proteins levels. Furthermore, APAP aggravated the activation of NLRP3 inflammasome by increasing of NLRP3, caspase-1, ASC, IL-1ß and IL-18 proteins levels. Finally, APAP further significantly activated the toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways. This study demonstrated that APAP-induced hepatotoxicity by inhibiting of Nrf2 antioxidative pathway and promoting TLR4-NF-κB-MAPK inflammatory response and NLRP3 inflammasome activation.

Resveratrol relieves chronic heat stress-induced liver oxidative damage in broilers by activating the Nrf2-Keap1 signaling pathway.

Heat stress (HS) affects poultry production and welfare, causing enormous damage to poultry. Resveratrol, an antioxidant and anti-inflammatory natural plant polyphenol, is widely used in agriculture for the prevention of oxidative stress-related diseases. This study aimed to explore the effects and potential mechanism of resveratrol on liver oxidative damage in heat-stressed broilers. Sixty SPF chickens were randomly divided into control, heat stress (HS) and HS+ resveratrol (resveratrol) groups. Broilers were exposed to 35 ± 2 â„ƒ (8 h/d) for 7 consecutive days to induce HS, and the other 16 h/d were kept at 23 ± 2 â„ƒ, similar to the control group. Broilers received 400 mg/kg resveratrol in the basic diet 2 days before exposure to HS and for the following 7 days. The results showed that resveratrol improved growth performance by increasing the average daily gain (ADG) and reducing the feed conversion ratio (FCR), compared with the HS group. Heat stress reduced liver weight and index, increased inflammatory cell infiltration in the liver, enhanced serum AST levels, and decreased TP and ALB II levels, which resulted in liver injury in broilers, and resveratrol effectively alleviated liver injury. Moreover, supplementation with resveratrol enhanced the activities of liver antioxidant enzymes resulting in higher GPX and SOD levels than those in the heat-stressed broilers, and decreased MDA levels. Furthermore, resveratrol alleviated liver oxidative stress by activating the gene and protein levels of Nrf2 and HO-1, enhancing NQO1 and SOD1 gene levels, and decreasing protein levels of HSP70, p62, and Keap1, and thereby alleviated the liver injury of heat-stressed broilers. Compared with the HS group, Nrf2 immunofluorescence was significantly up-regulated in the livers of resveratrol group. These results suggest that resveratrol can enhance the liver antioxidant function by activating the Nrf2-Keap1 signaling pathway to promote growth performance in broilers under HS.

J-shaped association between serum albumin levels and long-term mortality of cardiovascular disease: Experience in National Health and Nutrition Examination Survey (2011-2014).

Background: Cardiovascular disease (CVD) is a constellation of heart, brain, and peripheral vascular diseases with common soil hypothesis of etiology, and its subtypes have been well-established in terms of the albumin-mortality association. However, the association between albumin and the mortality of CVD as a whole remains poorly understood, especially the non-linear association. We aimed to investigate the association of albumin levels with long-term mortality of CVD as a whole. Materials and methods: This study included all CVD patients who participated in the National Health and Nutrition Examination Survey (NHANES 2011-2014). CVD was defined as coronary heart disease, stroke, heart failure, or any combination of these two or three diseases. Serum albumin was tertile partitioned: tertile 1, <4.1; tertile 2, 4.1-4.3; and tertile 3, >4.3 g/dl. COX proportional hazards model was used to assess the association between the serum albumin levels and CVD mortality. Restricted cubic spline (RCS) curves were used to explore the non-linear relationship. Results: A total of 1,070 patients with CVD were included in the analysis, of which 156 deaths occurred during a median 34 months of follow-up. On a continuous scale, per 1 g/dl albumin decrease was associated with an adjusted HR (95% CI) of 3.85 (2.38-6.25). On a categorical scale, as compared with tertile 3, the multivariable adjusted hazard ratio (95% CI) was 1.42 (0.74-2.71) for the tertile 2, and 2.24 (1.20-4.16) for the tertile 1, respectively, with respect to mortality. RCS curve analysis revealed a J-shaped association between albumin and CVD mortality. Conclusion: A J-shaped association between low serum albumin levels and increased long-term mortality of CVD has been revealed. This J-shaped association's implications for CVD prevention and treatment are deserving of being further studied.

Association between remnant cholesterol and verbal learning and memory function in the elderly in the US.

BACKGROUND: The relationship between remnant cholesterol (RC) and atherosclerotic cardiovascular risk has been given increasing attention in recent years. However, its association with verbal learning and memory performance has not been reported. METHODS: Data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 database. Participants aged ≥60 years with available fasting lipid data were included. Verbal learning and memory performance were evaluated using the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Task (CERAD-WL) subtest. The CERAD total score was calculated as the mean of three immediate recalls and a delayed recall. RC was calculated as total cholesterol (TC) minus the sum of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Multivariate ordinal logistic regression was performed to evaluate the association between RC, as well as its derived marker, the TC/RC ratio, and age-stratified quartiles of the CERAD total score. RESULTS: A total of 1377 participants were analysed. On a continuous scale, per 1 mmol/L increase in RC and per 1 unit increase in the TC/RC ratio were associated with multivariable adjusted odds ratios (95% CI) of 0.74 (0.58-0.94) and 1.45 (1.13-1.87), respectively, for having a CERAD total score in a higher quartile. On a categorical scale, higher RC quartiles were associated with a CERAD total score in a lower quartile; in contrast, the higher TC/RC quartile was associated with a CERAD total score in a higher quartile (all P for trend < 0.05). CONCLUSIONS: The current study suggests that lower RC levels and a higher TC/RC ratio are associated with better verbal learning and memory function, which indicates that lowering RC levels could be beneficial for preventing cognitive impairment in elderly individuals. Further research is needed to validate the causal roles of RC and the TC/RC ratio in cognition.

The predictive value of CatLet© angiographic scoring system for long-term prognosis in patients with acute myocardial infarction presenting > 12 h after symptom onset.

Background: We have recently developed the C oronary A rtery T ree description and L esion E valua T ion (CatLet©) angiographic scoring system, which is capable of accounting for the variability in coronary anatomy, and risk-stratifying patients with coronary artery disease. This study aimed to clarify whether the CatLet score had a predictive value for long-term prognosis in patients with acute myocardial infarction (AMI) presenting > 12 h after symptom onset. Materials and methods: The CatLet score was calculated for 1,018 consecutively enrolled AMI patients, who were divided into 3 groups according to the CatLet score tertiles. The primary endpoint was major adverse cardiac events (MACEs), defined as a composite of myocardial infarction, cardiac death, and ischemia-driven revascularization; secondary endpoints were all-cause death, cardiac death, myocardial infarction, and ischemia-driven revascularization. Results: The CatLet score was capable of predicting long-term prognosis at a median 4.9-year follow-up alone or after adjustment for risk factors. Multivariable-adjusted hazard ratios (95% CI)/unit higher score were 1.06 (1.05-1.08) for MACEs, 1.05 (1.03-1.07) for all-cause death, 1.06 (1.04-1.09) for cardiac death, 1.06 (1.04-1.08) for myocardial infarction, and 1.06 (1.04-1.08) for revascularization. The univariate model showed good calibration (χ2 = 8.25, P = 0.4091) and good discrimination (area under ROC curve = 0.7086) for MACEs. Conclusion: The CatLet score is an independent predictor of long-term clinical outcomes of patients with AMI presenting > 12 h after symptom onset (http://www.chictr.org.cn; Registry Number: ChiCTR2000033730).

Association between Serum Uric Acid and Hypertension in a Large Cross-Section Study in a Chinese Population.

Background: The association of serum uric acid (SUA) with hypertension has been well established in Caucasian populations. However, its association with hypertension in Chinese remained to be clarified. Methods: Consecutive patients, homogeneous in Chinese Han ethnicity, aged ≥18 years, abstracted from the database, admitted from 1 January 2010 to 31 December 2013, were included for potential analysis. The patients were grouped according to the presence or absence of hypertension. Unconditional logistic regression was performed to estimate the association between SUA and hypertension. Its possible interactions with risk factors on hypertension were also explored. Results: A total of 9587 patients were finally analyzed in the current study, where 5692 were with hypertension and 3895 were without hypertension. Per 100 µmol/L higher SUA concentration was associated with multivariable-adjusted odds ratios (95% CI) of 1.25 (1.08−1.22) in males, 1.10 (1.01−1.20) in females, and 1.19 (1.13−1.24) in total. On a categorical scale, when compared with the first quintile, the multivariable-adjusted odds ratios (95% CI) were 1.40 (1.20−1.64) for the 2nd quintile, 1.48 (1.27−1.74) for the 3rd quintile, 1.55 (1.32−1.82) for the 4th quintile, and 1.92 (1.63−2.26) for the 5th quintile, with a p for trend < 0.01. Conclusions: SUA is associated with hypertension in a dose-response manner among the Chinese hospitalized population. Management of SUA could help to the prevention and control of hypertension.

Yinhuang oral liquid protects acetaminophen-induced acute liver injury by regulating the activation of autophagy and Nrf2 signaling.

This study aimed to investigate the protective effect and potential mechanism of Yinhuang oral liquid (YOL) against acetaminophen (APAP) induced liver injury in mice. C57BL/6 mice were randomly divided into control group, model group (300 mg/kg APAP), NAC group and YOL group. Mice were treated intragastrical with YOL (8 g/kg) and N-Acetylcysteine (NAC, 300 mg/kg) 6 h before and 6 h after the APAP (300 mg/kg) intraperitoneal injection. 12 h after APAP exposure, blood and liver samples were collected for subsequent testing. The results showed that APAP decreased liver index, induced liver pathological injury with hepatocytes swelling, necrosis and apoptosis and inflammatory cell infiltration. APAP exposure significantly increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels to 35 and 6 multiples than their original levels. YOL alleviated liver pathological damage, decreased the serum levels of ALT and AST in APAP exposure mice, and it worked better than NAC. Moreover, APAP promoted oxidative stress by increasing lipid peroxidation (MDA) and decreasing anti-oxidant enzyme activities of SOD and GSH, inhibited the mRNA levels of Nrf2, HO-1, Gclc and Gclm, and decreased the protein levels of Nrf2, HO-1 and Keap1, compared to control group. Furthermore, APAP exposure significantly down-regulated the mRNA and protein levels of autophagy related genes (Beclin-1, LC3-II, LC3-I, Atg4B, Atg5, Atg16L1 and Atg7). However, the gene levels of mTOR and p-mTOR increased, and p-ULK1 protein level decreased in liver of APAP treated mice. Additionally, YOL alleviated the oxidative injury by up-regulating Nrf2 pathway. The gene and protein levels of autophagy-related genes Beclin-1, LC3-II, LC3-I, Atg4B, Atg5, Atg16L1 and Atg7 reached the basal levels after YOL treatment. In conclusion, YOL had a protective and therapeutic role in APAP-induced liver injury in mice by activating Nrf2 signaling pathway and autophagy.

Heat stress in broilers of liver injury effects of heat stress on oxidative stress and autophagy in liver of broilers.

This study aimed to investigate the effect of chronic heat stress on oxidative stress in liver of broilers. In our study, chickens were randomly allocated to control 1 group (control 7 d), heat stress 1 group (HS1, 7 d), control 2 group (control 14 d) and heat stress 2 group (HS2, 14 d), with 30 replicates in each group. Broilers in heat stress groups exposed 8 h/day heat stress (35 ± 2°C) for 7 or 14 consecutive days, and the rest of time per day were kept at 23 ± 2℃ the same as control group broilers. Growth performance and the liver tissues were collected for histological observation and detection of organ index and liver redox status. The serum indicators (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) related to liver injury were determined. Moreover, Nrf2-related genes and protein expression levels in liver were measured. The results showed that in heat stress group broilers the body weight gain, feed conversion ratio, liver weight, and liver index were decreased, inflammatory cells infiltration in liver, and serum AST level was enhanced, compared with control group broilers. Moreover, the hepatic malondialdehyde (MDA) and superoxide dismutase (SOD) level were increased after 1 wk of heat stress. Nrf2, Sqstm1/p62, HO-1, and NQO1 mRNA expressions in the liver of broilers were decreased by heat stress. P62 and p-p62 protein expressions were significantly up-regulated, but Nrf2 and keap1 protein level was decreased in heat stress group broilers as compared to control group. The mRNA expression levels of Beclin1, LC3-I, LC3-II were down-regulated significantly with heat stress for 1 wk. The mRNA expression level of mTOR up-regulated after 2 wk of heat stress. In conclusion, heat stress induced liver injury of broilers by down-regulating Nrf2-keap1 signaling pathway and autophagy.

Chronic heat stress promotes liver inflammation in broilers via enhancing NF-κB and NLRP3 signaling pathway.

BACKGROUND: This study investigated the effects of chronic heat stress on liver inflammatory injury and its potential mechanisms in broilers. Chickens were randomly assigned to the 1-week control group (Control 1), 1-week heat stress group (HS1), 2-week control group (Control 2), and a 2-week heat stress group (HS2) with 15 replicates per group. Broilers in the heat stress groups were exposed to heat stress (35 ± 2 °C) for 8 h/d for 7 or 14 consecutive days, and the rest of 26 hours/day were kept at 23 ± 2 °C like control group broilers. Growth performance and liver inflammatory injury were examined for the analysis of liver injury. RESULTS: The results showed that heat stress for 2 weeks decreased the growth performance, reduced the liver weight (P < 0.05) and liver index (P < 0.05), induced obvious bleeding and necrosis points. Liver histological changes found that the heat stress induced the liver infiltration of neutrophils and lymphocytes in broilers. Serum levels of AST and SOD were enhanced in HS1 (P < 0.01, P < 0.05) and HS2 (P < 0.01, P < 0.05) group, compared with control 1 and 2 group broilers. The MDA content in HS1 group was higher than that of in control 1 group broilers (P < 0.05). Both the gene and protein expression levels of HSP70, TLR4 and NF-κB in the liver were significantly enhanced by heat stress. Furthermore, heat stress obviously enhanced the expression of IL-6, TNF-α, NF-κB P65, IκB and their phosphorylated proteins in the livers of broilers. In addition, heat stress promoted the activation of NLRP3 with increased NLRP3, caspase-1 and IL-1ß levels. CONCLUSIONS: These results suggested that heat stress can cause liver inflammation via activation of the TLR4-NF-κB and NLRP3 signaling pathways in broilers. With the extension of heat stress time, the effect of heat stress on the increase of NF-κB and NLRP3 signaling pathways tended to slow down.